PubMed Trending Research Digest — July 02, 2026

Automated digest · 96 articles · 15 research areas · July 02, 2026

Overview

Across this week’s set, a dominant thread is the move from “single-target” approaches toward mechanism-informed combinations and stratification. In oncology, multiple studies connect therapy response or resistance to specific molecular programs—such as lactate–STING immune evasion, lactate-driven PANoptosis suppression, ferroptosis susceptibility shaped by genetic context, and epigenetic/splice-variant switches driving EGFR-TKI resistance. Parallel advances in immunotherapy engineering (e.g., dual tumor–myeloid CAR-T for glioblastoma, GPNMB-directed CAR-T for fusion-driven cancers, and T cell engager frameworks for autoimmunity) emphasize tailoring immune attack to tumor microenvironment constraints and antigen-state dynamics.

A second major theme is the growing integration of systems biology with clinical decision-making. Proteogenomics and multi-omics approaches (HCM molecular subtypes, extramedullary myeloma spatial microenvironments, and lineage tracing roadmaps) are increasingly used to define actionable subgroups and predict outcomes. In parallel, AI tools are being deployed to reduce access inequities and operational barriers—such as locally deployable, case-grounded decision support for hematology tumor boards—while computational platforms (digital twins and “virtual yeast”) aim to make mechanistic prediction more scalable.

Finally, several studies highlight how metabolism and inflammation intersect with disease progression and therapeutic opportunity beyond classic boundaries. Obesity/GLP-1 work spans safety monitoring (micronutrient risk) and next-generation combination strategies; metabolic conditions like liver steatosis reshape metastatic phenotypes; and inflammatory signaling pathways (inflammasome spatial control, hypoxia-driven fibrosis circuits, and oxidative-stress/ferroptosis in SLE-related fertility decline) reveal new intervention points. Infectious disease research continues to strengthen both mechanistic and public-health foundations, from TB permeability and RNAP inhibitor dynamics to malaria epitope discovery and updated TB burden estimates.

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Obesity, GLP-1 Therapies, and Metabolic Combinations

Heat-triggered phospholipid flipping stabilizes plasma membrane fluidity.

The study investigated how cells rapidly protect plasma membranes during heat stress in rice (Oryza sativa), focusing on the P4-ATPase OsALA5 and its β-subunit OsALIS2. It showed that heat exposure triggers a minute-timescale increase in OsALA5 transport activity that selectively enriches saturated phosphatidylcholines in the cytoplasmic plasma membrane leaflet via leaflet-resolved lipidomics and transport assays. This identifies a specific heat-responsive lipid flipping mechanism that stabilizes membrane fluidity and prevents heat-induced membrane damage.

Fan S, Gao P, Huang K et al. · Nature · (2026) · View on PubMed ↗

Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity: Mechanistic pathways, clinical signals, and a monitoring framework.

This narrative clinical review synthesizes evidence on micronutrient risk mechanisms and clinical signals associated with GLP-1 receptor agonists and dual incretin (GIP/GLP-1) agonists used for obesity. It proposes a mechanistic and monitoring framework linking incretin-driven appetite/energy intake changes and gastrointestinal physiology to potential micronutrient disturbances during long-term therapy. Clinically, the review supports proactive micronutrient surveillance to reduce deficiency risk as incretin-based obesity treatments become more widely used.

Simancas-Racines D, Campuzano-Donoso M, Rossetti G et al. · Obesity pillars · (2026) · View on PubMed ↗ · Free PDF ↗

GLP-1-Based Therapies in Type 1 Diabetes: Emerging Evidence on Cardiovascular, Renal, and Safety Outcomes.

This review studied evidence for GLP-1–based therapies in adults with type 1 diabetes (T1D), focusing on cardiovascular, renal, and safety outcomes. It identified three observational real-world studies and reported that GLP-1–based therapies were associated with clinical benefits while also summarizing safety findings and gaps in evidence. The review highlights emerging cardiorenal risk-reduction potential in T1D but underscores the need for more definitive trials to establish causality and long-term safety.

Tentolouris A, Popovic DS, Liarakos AL et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

GLP-1-based combination strategies for weight loss: Multi-target agents and combination therapies.

This review studied GLP-1 receptor agonist (GLP-1RA)–based weight-loss combination strategies, focusing on two development directions: single-agent multi-target agonists and multi-drug combination therapies. It concluded that combination approaches are a frontier to overcome limitations of single-target GLP-1RA mechanisms by engaging multiple metabolic pathways. The significance is that it frames how next-generation anti-obesity regimens may improve efficacy and durability by targeting broader physiology than GLP-1 alone.

Wang X, Lin R, Sun Q et al. · Pharmacological research · (2026) · View on PubMed ↗

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Obstructive Sleep Apnea and Related Pharmacologic Alternatives

Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial.

ATTAIN-OSA is a phase 3 trial evaluating once-daily oral orforglipron in adults with obesity or overweight and moderate-to-severe obstructive sleep apnea (OSA). The study is designed to assess efficacy and safety as an alternative to positive airway pressure (PAP) and injectable GLP-1–based therapies that may have adherence/access barriers. If effective, oral orforglipron could expand feasible long-term pharmacologic options for OSA by improving adherence compared with PAP and injections.

Malhotra A, Gottlieb DJ, Kundel V et al. · Contemporary clinical trials communications · (2026) · View on PubMed ↗

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Inflammatory Bowel Disease (Ulcerative Colitis/Crohn’s) and Surgical/Immunotherapy Strategies

Real-world effectiveness of guselkumab for induction of remission in Crohn’s disease: a prospective multicenter cohort study with propensity score-matched comparison to risankizumab.

In a prospective multicenter cohort in adults with moderate-to-severe Crohn’s disease (CD) in the United Arab Emirates, the study assessed real-world induction of remission with the IL-23 inhibitor guselkumab and compared outcomes with risankizumab using propensity score matching. Clinical remission at Week 12 (Harvey-Bradshaw Index <5) was the primary endpoint after matching on 12 covariates including baseline disease phenotype. The findings provide comparative effectiveness evidence to help clinicians choose between selective IL-23 inhibitors in routine practice where head-to-head trials are lacking.

Al Hosani M, Al Hosani N, Alzaabi MN et al. · Crohn’s & colitis 360 · (2026) · View on PubMed ↗

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

The ECCO Guidelines article provides evidence-based consensus recommendations for surgical treatment of medically refractory ulcerative colitis (UC) in adults, including perioperative optimization, surgical strategies/techniques, and recommended center expertise. It synthesizes guidance intended to support shared decision-making between clinicians and patients when medical therapy fails. Clinically, it standardizes surgical care pathways to improve outcomes and ensure appropriate specialization for complex UC surgery.

Adamina M, Kienle P, Chaparro M et al. · Journal of Crohn’s & colitis · (2026) · View on PubMed ↗

Engineering immune cell therapies for inflammatory bowel disease: from stem cells to CAR T cells.

This Perspective reviewed how engineered immune cell therapies for inflammatory bowel disease (IBD) are being developed, spanning stem cell approaches, regulatory T cell (Treg) and type 1 regulatory T cell (Tr1) therapies, and CAR T cell platforms (CAR T and CAR Treg). It found that early-stage studies using hematopoietic and mesenchymal stem cell–based strategies show promising clinical signals, while CAR T and regulatory-cell approaches are advancing with ongoing attention to safety and efficacy validation. Scientifically and clinically, the article frames engineered cellular immunotherapy as a rapidly evolving path for IBD treatment beyond current small-molecule and cytokine-targeted options.

Neurath MF, Atreya R, Colombel JF et al. · Nature reviews. Gastroenterology & hepatology · (2026) · View on PubMed ↗

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Cancer Immunotherapy (Checkpoint, CAR-T/Cell Therapies, T Cell Engagers)

GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.

The study developed and tested a GPNMB-directed CAR T cell product (GCAR1) against MiT/TFE-family fusion-driven solid tumors in preclinical models and in a first-in-human trial for relapsed/refractory metastatic alveolar soft-part sarcoma (ASPS). GCAR1 showed potent activity against patient-matched cells, organoids, and xenograft models, and interim clinical analysis reported meaningful antitumor activity in a participant from NCT07104682. This identifies GPNMB as a broadly and stably expressed target in ASPS and translocation renal cell carcinoma and supports GCAR1 as a candidate therapy for these fusion-driven cancers.

Zemp FJ, Breckenridge Z, Song H et al. · Nature cancer · (2026) · View on PubMed ↗

Dual tumour-myeloid targeting of glioblastoma with GPNMB CAR-T cells.

The study developed dual tumor–myeloid targeting glioblastoma CAR-T cells using GPNMB as a target to address limitations of conventional tumor-only CAR-T approaches in a microenvironment dominated by tumor-associated macrophages. It aimed to overcome barriers including intratumoral heterogeneity, antigen loss, and immunosuppressive myeloid signaling by engaging both tumor and myeloid components. This provides a strategy to treat glioblastoma as a coupled tumor–immune system and may improve the durability of CAR-T responses.

Savage N, Grewal S, Shaikh MV et al. · Nature · (2026) · View on PubMed ↗

CAR T cell therapy selectively depletes disease-driving mutant calreticulin cells in xenotransplants and human organoid models of myelofibrosis.

This study investigated a CAR T cell therapy targeting mutant calreticulin (mutCALR) in myelofibrosis by testing selective depletion of mutCALR+ disease-driving cells in xenotransplants and human organoid models. The therapy specifically recognized and eliminated mutCALR+ cells, demonstrating feasibility of a targeted immunotherapy approach in a myeloid malignancy with an immunologically hostile tumor microenvironment. The clinical significance is that it provides preclinical proof-of-concept for a precision CAR T strategy for calreticulin-driven myelofibrosis.

Rampotas A, Wong ZC, Gannon I et al. · Science translational medicine · (2026) · View on PubMed ↗

IL-17-driven tumor cell-intrinsic inflammatory programming creates an immunotherapy-permissive microenvironment.

The study examined how IL-17 drives tumor cell-intrinsic inflammatory programming that shapes an immunotherapy-permissive microenvironment in ovarian clear cell carcinoma (OCCC). Using immunohistochemistry and transcriptomic analyses of human OCCC cohorts plus functional experiments in an immunocompetent syngeneic OCCC mouse model, it tested IL-17’s effects on tumor signaling, immune microenvironment remodeling, and responsiveness to immune checkpoint blockade. These findings could help define an immunologically responsive OCCC subset and inform IL-17–linked biomarkers or combination strategies for immunotherapy.

Murakami K, Takamura S, Miyagawa C et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

T cell engagers in autoimmune diseases.

This review studied the therapeutic use of T cell engagers (TCEs)—including antibody-based bispecific and multispecific constructs—in autoimmune diseases. It found that TCEs can reprogram T cells to eliminate cells expressing defined surface antigens and that early clinical results in autoimmunity are promising, with mechanisms and design considerations summarized across targets and formats. Clinically, the article positions TCEs as potentially off-the-shelf, potent alternatives to cellular therapies, while highlighting the need for careful safety and mechanistic optimization.

Grieshaber-Bouyer R, Wu L, Schett G et al. · Nature reviews. Immunology · (2026) · View on PubMed ↗

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

This review examined emerging cancer cell-therapy platforms spanning T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), γδ T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), dendritic cell (DC)-, B cell–, and stem cell–based strategies, building on the clinical success of CAR-T in hematologic malignancies. It highlights a rapidly expanding translational landscape and discusses key engineering and development directions beyond conventional CAR-T. These advances are significant because they broaden the therapeutic toolkit for solid and hematologic cancers by targeting diverse immune-cell biology and tumor microenvironment constraints.

Zi G, Zhang L, Zhou L et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Tailored HER2 ECD mRNA-LNP vaccines boost CD8+ T cell-mediated antitumor immunity for HER2-positive tumor suppression.

The study developed lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines encoding modified extracellular domain (ECD) sequences from rat HER2 (rHER2 ECD) or human HER2 (hHER2 ECD) and evaluated their ability to induce CD8+ T cell-mediated antitumor immunity in vivo. Both vaccines inhibited tumors, but the hHER2 ECD mRNA-LNP showed superior prophylactic and therapeutic efficacy, associated with stronger CD8+ T cell responses. This supports species-tailored HER2 ECD mRNA-LNP design as a strategy to enhance immunogenicity for HER2-positive tumor control.

Li K, Ma Z, Li X et al. · Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · (2026) · View on PubMed ↗

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Cancer Target Discovery & Biomarkers (including antigen/epitope and state markers)

TROP2 targeting reveals therapy-driven cell state dynamics in colorectal cancer.

The study investigated TROP2 as a marker and therapeutic target of poor-prognosis colorectal cancer (CRC) cell states, focusing on WNTlow, fetal-like tumor states linked to metastasis and therapy resistance. It found that TROP2+ cells display context-dependent stem-like capacity and can initiate metastatic outgrowth, and it explored clinically relevant TROP2-directed targeting to disrupt these therapy-driven dynamics. This supports TROP2 as a convergent surface antigen for metastatic/therapy-resistant CRC states and provides a rationale for TROP2-targeted interventions to prevent dissemination.

Vaquero-Siguero N, Georgakopoulos N, Puschhof MC et al. · Nature · (2026) · View on PubMed ↗

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Cancer Genomics, Epigenetics, and Genome Architecture

Replication-stress-induced chromatin loops protect fork stability.

The study analyzed how replication stress affects higher-order chromatin organization to protect stalled replication forks, focusing on CTCF-dependent loop formation and heterochromatin deposition. It showed that replication stress induces transient chromatin loops that enclose de novo heterochromatin-enriched stalled forks, with fork stalling at convergent CTCF motifs leading to stress-dependent CTCF enrichment that constrains loop extrusion. Loop stabilization required both CTCF anchoring and G9a-dependent H3K9me3 deposition on nascent DNA, revealing a mechanistic chromatin-based strategy for fork protection.

Gaggioli V, Sengupta K, Choudhury A et al. · Nature · (2026) · View on PubMed ↗

Proteogenomics of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy.

This proteogenomics study analyzed myocardial samples from 132 patients with hypertrophic cardiomyopathy (HCM) using whole-exome sequencing, RNA sequencing, and proteomics to define molecular subtypes. Unsupervised clustering identified HCM subtypes that were validated in heart tissue and in human induced pluripotent stem cell-derived cardiomyocytes. By revealing subtype-specific biology, the work supports more precise risk stratification and the development of subtype-targeted therapeutic strategies for HCM.

Ma K, Yang J, Guo H et al. · Circulation research · (2026) · View on PubMed ↗

Coordinated DNA 5-mC and RNA m5C methylation epigenetically regulates MZF1 splice variants to drive EGFR-TKI resistance.

The study examined how coordinated DNA 5-methylcytosine (5-mC) and RNA N4-methylcytosine (m5C) methylation regulate MZF1 splice variants in the context of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients and models. It found that the MZF1S splice variant is upregulated in resistant patients and has reduced Zn2+-binding due to C2H2 domain deletion, whereas MZF1L predominates in treatment-sensitive cohorts. These epigenetic and splice-variant mechanisms identify MZF1S/MZF1L regulation as a potential lever to resensitize tumors to EGFR-TKIs.

Zhang H, Pang Y, Liu B et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗

Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.

The study investigated how cohesin complexes containing STAG1 versus STAG2 regulate post-mitotic genome refolding, focusing on stage- and chromatin-context-dependent roles after mitotic exit. It found STAG2 is the predominant paralog and primary orchestrator: STAG1 depletion had negligible effects, while STAG2 promoted early-G1 small euchromatic loops, enhancer–promoter contacts, and transcriptional refiring, and suppressed late-G1 large loops. This clarifies which cohesin subunit is the key driver of genome reorganization after mitosis, informing models of transcriptional recovery.

Wang M, Zhang Y, Shan F et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Rheumatoid factor production is genetically and molecularly distinct from rheumatoid arthritis.

This study investigated the genetic and molecular determinants of rheumatoid factor (RF) autoantibody production and its relationship to progression to rheumatoid arthritis (RA) using UK Biobank and ALTRA cohorts. Using phenome-wide association, genome-wide association, proteome-wide association, and single-cell RNA-seq–based pseudobulk analyses, it found that RF development and progression to RA have distinct genetic, phenotypic, and molecular architectures rather than representing a single continuum. Clinically, this supports RF as a separable immunologic entity from RA and can refine risk stratification and biomarker strategies.

Hocaoglu M, Sawalha AH · The Journal of clinical investigation · (2026) · View on PubMed ↗

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Cancer Cell Biology & Mechanistic Pathways (autophagy, condensates, replication stress, ferroptosis, lactylation, etc.)

Steatosis shapes prognosis-defining liver metastasis heterogeneity in CRC.

The study examined how liver steatosis influences the heterogeneity of colorectal cancer liver metastases, particularly the occurrence of “replacement” versus “encapsulated” metastases, in treatment-naive patients. It found that patients with CRC and liver steatosis have increased occurrence of replacement metastases and identified a steatosis-promoted fatty-acid oxidation mechanism driving this shift. This links a modifiable metabolic condition (steatosis) to clinically prognostic metastasis subtype and suggests metabolic targeting may be needed for replacement liver metastases.

Peng-Winkler Y, Liu XZ, Verheul SML et al. · Nature · (2026) · View on PubMed ↗

AARS2-mediated lactylation of ULK1 promotes autophagy-dependent progression of clear cell renal cell carcinoma.

The study investigated how AARS2-mediated lactylation of the autophagy-initiating kinase ULK1 regulates autophagy-dependent progression of clear cell renal cell carcinoma (ccRCC). It found that AARS2 catalyzes ULK1 lactylation at lysine 46 in response to autophagic stimuli, enhancing ULK1 kinase activity and promoting selective autophagy programs that drive tumor progression. These mechanistic insights identify the AARS2–ULK1 lactylation axis as a potential therapeutic target to modulate autophagy in ccRCC.

Zeng X, Zhu Y, Xiao Y et al. · Autophagy · (2026) · View on PubMed ↗

Reconsidering Cancer Therapy through the Lens of Biomolecular Condensates.

This Cancer Discovery commentary discusses cancer therapy opportunities by targeting biomolecular condensates formed through phase separation. It argues that defining the composition and physicochemical properties of oncogenic condensates could enable new pharmacologic or genetic strategies for chemotherapy and immunotherapy. Scientifically, it reframes therapeutic design around condensate biology, potentially expanding actionable targets beyond conventional signaling pathways.

You K, Yin Q, Feng J et al. · Cancer discovery · (2026) · View on PubMed ↗

AURORA A interacts with DICER and SETD2 to promote S-phase progression.

This study examined how the oncogenic kinase AURORA A regulates S-phase progression and interacts with RNA-processing factors in human cells. Degradation- and interactome-based experiments showed that AURORA A forms an abundant nuclear complex with the ribonuclease DICER (and also engages SETD2), and that RNA degradation shifts these proteins across gradient fractions, linking AURORA A scaffolding to S-phase defects. These findings expand AURORA A biology beyond mitosis and suggest that targeting AURORA A–DICER/RNA-associated functions could be a strategy to exploit S-phase vulnerabilities in cancer.

Müller J, Daunke T, Berner N et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Therapeutic inhibition of telomeric DNA damage response rescues hematopoietic dysfunction driven by telomere shortening and aging.

This study examined whether therapeutic inhibition of the telomeric DNA damage response (tDDR) can rescue hematopoietic dysfunction caused by telomere shortening and aging in telomerase-deficient Terc-/- mice. Targeting telomeric noncoding RNAs with telomeric antisense oligonucleotides (tASOs) suppressed tDDR in hematopoietic organs, reduced senescence and inflammation, and improved hematopoietic function. The findings provide causal evidence that telomeric noncoding RNA–driven tDDR contributes to age-related hematopoietic decline and suggest an antisense-based therapeutic approach.

Oppezzo A, Sepe S, Cicio G et al. · Nature aging · (2026) · View on PubMed ↗

Distinct ATRX functions cooperate with 9-1-1 and CST complexes to safeguard replication and telomere integrity.

This study investigated how the ATRX chromatin remodeler safeguards replication and telomere integrity by cooperating with the 9-1-1 clamp and CST (CTC1-STN1-TEN1) complexes in ATRX-deficient cells. It found that ATRX-CST synthetic lethality arises from telomeric G-rich ssDNA accumulation leading to telomere loss and death, whereas ATRX-9-1-1 synthetic lethality is driven by genome-wide ssDNA lesions that impair DNA replication. These mechanistic dependencies identify specific DNA damage/replication contexts where ATRX pathway disruption becomes therapeutically exploitable.

Segura-Bayona S, Maric M, Takaki T et al. · Nature structural & molecular biology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis.

The study examined genetic determinants of ferroptosis susceptibility in prostate cancer by comparing effects of SPOP mutations and CHD1 deletions in genetically engineered human and murine models. It found that SPOP mutations enhance, whereas CHD1 deletion impairs, the efficacy of ferroptosis inducers targeting GPX4. This defines context-dependent vulnerabilities that could guide patient stratification for ferroptosis-based therapies.

Chen F, Li Q, Gu Q et al. · Nature communications · (2026) · View on PubMed ↗

FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.

The study tested how PARP1/2–PARG signaling and PARylation influence replication fork reversal by combining iPOND with quantitative proteomics and functional assays after acute PARG inhibition. It found that FET family proteins (FUS, EWS, and TAF15) are recruited to replication forks in a PAR-dependent manner to form condensates that slow fork progression and promote fork reversal. This links PARylation-dependent condensate formation to replication stress responses, suggesting potential targets in replication-associated genome instability.

Giansanti C, Schultz JC, Jackson J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Adaptable centriole biogenesis via the intrinsically disordered protein ALMS1.

The study analyzed centriole biogenesis and cartwheel dynamics to determine how the intrinsically disordered protein ALMS1 functions as an external cofactor. It found ALMS1 triggers formation of a cartwheel seed composed of CEP152/CEP63 complexes during interphase without incorporating into the seed, and that cartwheel seed disassembly during mitotic entry correlates with ALMS1 involvement. This provides a mechanistic model for how cartwheel scaffolds assemble and disassemble to drive centriole formation.

Ozaki K, Chang TB, Yang WQ et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

SIRT7-mediated ACSL3 delactylation suppresses colorectal cancer progression by orchestrating tumor-associated macrophage ferroptosis and polarization.

This study investigated how SIRT7 regulates ACSL3 lactylation in tumor-associated macrophages (TAMs) to control colorectal cancer (CRC) progression. It found that ACSL3 is highly expressed in TAMs, and that ACSL3 depletion induces TAM ferroptosis while reprogramming TAMs toward an M1-like phenotype, with SIRT7 identified as the delactylase of lactylated ACSL3. The results are clinically relevant because targeting the SIRT7–ACSL3 axis could therapeutically promote anti-tumor TAM ferroptosis and improve CRC outcomes.

Jiang L, Li C, Teng P et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic inhibition of glutamate-cysteine ligase increases dendritic cell-mediated antitumor immunity in melanoma.

This preclinical study used the transgenic melanoma mouse model tg(Grm1)EPv (ectopic metabotropic glutamate receptor 1, Grm1, expression in melanocytes) to test whether metabolic inhibition of glutamate-cysteine ligase (GCL) enhances dendritic cell–mediated antitumor immunity. It performed LC-MS/MS metabolomics and RNA sequencing to characterize tumor-associated metabolic alterations and reported that inhibiting GCL increases dendritic cell–driven antitumor immune responses in melanoma. The findings are significant because they suggest a metabolic vulnerability that could be exploited to boost dendritic cell function and improve immunotherapy effectiveness.

Dieckmann SM, Tripp CH, Strandt H et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

AARS1 promotes tumor progression and immune evasion via ATF6 lactylation-mediated tryptophan metabolism in hepatocellular carcinoma.

This study examined how alanyl-tRNA synthetase 1 (AARS1) promotes hepatocellular carcinoma progression and immune evasion through ATF6 lactylation–mediated tryptophan metabolism. Using integrated single-cell and spatial transcriptomics stratified by glycolytic activity, it identified AARS1 upregulation associated with higher 18F-FDG PET/CT glycolytic flux, poor prognosis, and immunotherapy resistance, and showed that hepatocyte-specific AARS1 knockout suppressed tumor growth in murine models. The work is significant because it links glycolysis, lactylation, and tryptophan metabolism to immune escape, suggesting AARS1/ATF6 lactylation as a potential therapeutic target in HCC.

Wang Y, Li F, Li J et al. · Cell metabolism · (2026) · View on PubMed ↗

Lactate binds and inhibits the innate immune sensor STING to promote tumor immune evasion.

The study investigated how metabolic lactate in cancer cells affects innate immune sensing in the tumor microenvironment, focusing on STING activation and the molecular interaction between lactate and STING. Lactate directly bound the cGAMP-binding domain of STING, inhibiting cGAMP binding, STING activation, and IRF3-dependent cytokine expression, with upstream signaling involving EGFR-driven phosphorylation of LDHA by PKM2. This identifies lactate–STING blockade as a mechanism of tumor immune evasion and suggests metabolic targeting as a strategy to restore innate immune responsiveness.

Guo D, Meng Y, Yang Q et al. · Immunity · (2026) · View on PubMed ↗

Inhibiting PPM1D Perturbs Mitochondrial Integrity to Stimulate cGAS-STING Signaling and Antitumor Immunity.

The study examined how inhibiting protein phosphatase magnesium-dependent 1δ (PPM1D) affects hepatocellular carcinoma (HCC) immunotherapy resistance in tumor cells and CD8+ T cells, focusing on TNFα–NF-κB regulation and mitochondrial DNA leakage. Genetic or pharmacological PPM1D inhibition enhanced CD8+ T-cell cytotoxicity by perturbing mitochondrial integrity, thereby stimulating cGAS–STING signaling. These findings suggest PPM1D is a mechanistic driver of ICB resistance in HCC and a potential therapeutic target to boost antitumor immunity.

Zhang L, Zheng X, Fu H et al. · Cancer research · (2026) · View on PubMed ↗

Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.

The study investigated whether covalent inhibition of serine hydroxymethyltransferase 2 (SHMT2) by gambogic acid induces ferroptosis in triple-negative breast cancer (TNBC) cells, implicating mitochondrial collapse and mitochondrial metabolism. Gambogic acid covalently inhibited SHMT2 and triggered ferroptosis characterized by mitochondrial dysfunction/collapse. This supports SHMT2 as a druggable metabolic vulnerability in TNBC and positions gambogic acid–like SHMT2 inhibition as a ferroptosis-based therapeutic strategy.

Yang T, Qiu C, Li Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Lactate-Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo-Immunotherapy by Suppressing Tumor PANoptosis.

The study examined how lactate-driven metabolic changes regulate mitochondrial permeability transition and PANoptosis in triple-negative breast cancer (TNBC) under chemo-immunotherapy stress, using single-cell transcriptomics and quantitative lactylome profiling. Elevated tumor lactate promoted resistance by suppressing PANoptosis through KAT8-mediated lactylation of ANT2 at K92, which enabled PGAM5 recruitment to dephosphorylate CypD and restrain mitochondrial permeability transition. This identifies a lactate–KAT8–ANT2–PGAM5–CypD axis as a targetable mechanism of chemo-immunotherapy resistance.

Zhong S, Chen W, Liu F et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Phosphatidylinositol diphosphate binding by ESCRT-III filaments.

This study analyzed how ESCRT-III filaments bind phosphatidylinositol diphosphate (PIP2) and how PIP recognition integrates with earlier ESCRT-I/II recruitment to drive membrane remodeling. The key finding is that ESCRT-III filament subunits directly engage PIP2 through defined binding interactions, providing a molecular basis for how ESCRT machinery is addressed to specific membrane sites and then executes constriction/fission. This advances the mechanistic understanding of endosomal membrane trafficking and offers targets for modulating ESCRT-dependent processes.

Alian A, McCullough J, Moss FR et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming.

This study examined whether post-translational modification of DEK sustains leukemia stem cells (LSCs) in acute myeloid leukemia (AML) by enabling PBX3-driven transcriptional reprogramming, using phosphoproteomics and functional validation in mouse models and patient-derived xenografts. It found that DEK phosphorylation is a critical leukemogenesis-associated event, and that DEK deletion impairs LSC maintenance and AML progression while enhancing LSC chemosensitivity to azacitidine-based standard-of-care therapy. These results identify DEK phosphorylation as a potential therapeutic vulnerability and suggest targeting the DEK–PBX3 transcriptional axis to improve AML treatment responses.

Lei Y, Lai Y, Li Y et al. · Blood · (2026) · View on PubMed ↗

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Solid Tumor Clinical Trials & Treatment Optimization (non-immunotherapy focus)

Casdatifan shows durable response linked to HIF-2α biology in kidney cancer.

The study evaluated casdatifan, an orally bioavailable selective HIF-2α inhibitor, in individuals with refractory metastatic clear cell renal cell carcinoma (ccRCC) in the ARC-20 dose-expansion trial (NCT05536141). It reported meaningful, durable antitumor activity with manageable safety, including low rates of discontinuation due to adverse events and class-effect toxicities such as anemia and hypoxia. This links clinical response durability to HIF-2α pathway biology and supports casdatifan as a therapeutic option for advanced ccRCC.

Choueiri TK, Merchan J, Patnaik A et al. · Nature · (2026) · View on PubMed ↗

Trastuzumab rezetecan versus pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer (HORIZON-Breast01): interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial.

This interim analysis of the multicentre, open-label, randomized phase 3 HORIZON-Breast01 trial compared trastuzumab rezetecan versus pyrotinib plus capecitabine in adults (18–75 years) with histologically confirmed HER2-positive unresectable or metastatic breast cancer previously treated with taxanes and/or anthracyclines. Trastuzumab rezetecan demonstrated clinically meaningful antitumor efficacy with a safety profile consistent with its mechanism, supporting its potential to improve outcomes versus the current standard regimen of pyrotinib plus capecitabine. These results are significant because they provide head-to-head phase 3 evidence for a next-generation HER2-targeted antibody-drug conjugate in a defined post–taxane/anthracycline metastatic population in China.

Yao H, Zhang Q, Li H et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma.

This phase 3, double-blind trial evaluated adjuvant pembrolizumab plus belzutifan versus pembrolizumab plus placebo in participants with resected clear-cell renal-cell carcinoma at increased risk of recurrence. The combination strategy was designed to improve disease outcomes by pairing PD-1 blockade (pembrolizumab) with HIF-2α inhibition (belzutifan), and the study reports efficacy and safety results consistent with the hypothesis that adding belzutifan enhances benefit beyond pembrolizumab alone. This is significant because it tests a rational hypoxia-pathway intensification approach in the adjuvant setting for a high-risk RCC population.

Choueiri TK, Motzer RJ, Karam JA et al. · The New England journal of medicine · (2026) · View on PubMed ↗

First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma.

This retrospective cohort study used the TriNetX database to compare real-world outcomes of first-line enfortumab vedotin plus pembrolizumab (EV/P) versus gemcitabine plus cisplatin (G/C) in adults with metastatic urothelial carcinoma. Patients initiating EV/P were propensity score matched to G/C users by demographics, comorbidities, kidney function, and metastatic location, and the analysis assessed comparative effectiveness endpoints. The clinical significance is that it provides outside-trial evidence on whether the EV/P regimen translates into improved outcomes in routine practice for mUC patients.

Velasquez EL, Titus RS, Nguyen DD et al. · JAMA network open · (2026) · View on PubMed ↗

Long-term outcomes of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma: a randomized, controlled, multicenter, phase 3 study.

This randomized phase 3 trial studied whether adjuvant metronomic capecitabine improves outcomes after definitive chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (n=406). The trial reported long-term results showing the study met its primary endpoint of failure-free survival, with efficacy and safety assessed over a median follow-up of 71.3 months. These data support metronomic capecitabine as a clinically meaningful adjuvant option to reduce recurrence risk in this population.

Tao YL, Wu DH, Zhou Q et al. · Nature cancer · (2026) · View on PubMed ↗

Improving neoadjuvant and perioperative therapy in non-small-cell lung cancer.

This review studied how to improve neoadjuvant and perioperative therapy for non-small-cell lung cancer (NSCLC), focusing on regimens that combine anti–PD-(L)1 antibodies with platinum-doublet chemotherapy. It found that neoadjuvant chemoimmunotherapy, with or without perioperative continuation of anti–PD-(L)1 therapy, has become standard for early-stage resectable, non-oncogene-driven NSCLC and improves pathological response rates and long-term outcomes including overall survival. Clinically, the article emphasizes the next challenge—moving from uniform treatment to biologically tailored perioperative strategies.

Garitaonaindia Y, Wakelee HA, Reck M et al. · Nature reviews. Clinical oncology · (2026) · View on PubMed ↗

Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation/Loss in Eyes With Geographic Atrophy.

This post hoc analysis of pooled phase 2/3 GATHER1 and phase 3 GATHER2 trial data studied patients ≥50 years with non–center point involving geographic atrophy (GA) to determine how baseline ellipsoid zone (EZ) measures relate to GA progression and how avacincaptad pegol (ACP), a complement inhibitor, affects EZ integrity over the first year. It found that ACP treatment slowed progressive ellipsoid zone degradation/loss compared with control during the early treatment period (full quantitative details truncated). This is significant because EZ integrity on SD-OCT is a photoreceptor health biomarker, and ACP’s effect supports complement inhibition as a strategy to preserve retinal structure in GA.

Ehlers JP, Cetin H, Amine R et al. · Ophthalmology · (2026) · View on PubMed ↗

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Hematology & Myeloma/Malignancies (including MRD and tumor microenvironment)

MRD in multiple myeloma: Moving from “minimal” to “measurable”.

This narrative review studied how minimal residual disease (MRD) assessment in multiple myeloma (MM) has evolved from morphology-based “minimal” disease to quantitative “measurable” residual disease. It concluded that next-generation flow cytometry and next-generation sequencing can detect residual disease at sensitivities down to 10^-6 to 10^-7, strengthening the clinical meaning of MRD negativity while emphasizing ongoing issues in assay standardization and interpretation. This is important for clinical decision-making because MRD status increasingly guides prognosis and treatment intensity in MM.

Cassano RC, Banerjee R, Afrough A et al. · Blood reviews · (2026) · View on PubMed ↗

Spatial transcriptomics identifies a suppressive, T-cell excluded tumor microenvironment in extramedullary myeloma.

This study used spatial transcriptomics on extramedullary myeloma tumor biopsies to characterize the tumor microenvironment in comparison with bone marrow–restricted multiple myeloma. It found a suppressive, T-cell–excluded microenvironment dominated by macrophages with an M2 phenotype and plasma-cell transcriptome features with substantial inter-patient heterogeneity. The results are significant because they suggest immune-evasion mechanisms in extramedullary disease that could be targeted to improve outcomes.

Bingham NE, Boiko JR, Jones DC et al. · Blood advances · (2026) · View on PubMed ↗

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Cardiovascular, Metabolic Syndrome, and Musculoskeletal Aging Risks

Gut commensal Bacteroides-derived pantothenic acid alleviates metabolic syndrome.

The study investigated whether gut microbiota-derived pantothenic acid (vitamin B5) protects against metabolic syndrome, focusing on Bacteroides fragilis and its panC-dependent PA biosynthesis in human samples and MetS mouse models. Microbial PA supply was reduced in individuals with metabolic syndrome, and isotope tracing plus germ-free colonization showed that B. fragilis panC is required to restore PA, preserve gut barrier integrity, reduce endotoxemia, and improve metabolic dysfunction. This is clinically significant because it identifies a specific commensal metabolic pathway (panC→PA) as a mechanistic target to potentially prevent or treat metabolic syndrome via microbiome modulation.

Luo Z, Xiao Z, Yuan T et al. · Cell host & microbe · (2026) · View on PubMed ↗

Imaging-Derived Sarcopenic Obesity and Cardiovascular Outcomes: Insights Into Heart Failure Risk and Muscle Biology.

This study developed a deep learning pipeline to quantify sarcopenic obesity from cardiovascular imaging (pectoralis major muscle mass and fat measures) and tested its association with long-term cardiovascular outcomes and heart failure risk. Using long-term follow-up plus genomic and transcriptomic data, the authors aimed to clarify how the coexistence of excess adiposity and low muscle mass relates to heart failure biology beyond BMI-based metrics. The significance is that it offers a more translatable, imaging-derived risk stratification method that may better capture muscle–fat biology relevant to heart failure.

Sanghvi MM, Nicholls HL, Kaplan TM et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Insulin resistance surrogate indices and incident cardiovascular disease across cardiovascular-kidney-metabolic stages 0-3: a prospective cohort study.

This prospective cohort study evaluated associations between multiple insulin resistance (IR) surrogate indices and incident cardiovascular disease across cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3, using machine learning to compare predictive performance. It aimed to determine which IR markers best predict future cardiovascular events within CKM stage strata. The results could refine risk prediction and monitoring strategies for CKM syndrome by identifying the most informative IR surrogate measures.

Xue N, Ma L, Zhou Z et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Bidirectional Relationship and Shared Mechanisms Between Sarcopenia and Osteoporosis: An Observational Study Integrating Genomic, Proteomic, and Metabolomic Data.

This observational study used multi-omics integration (genomic, proteomic, and metabolomic data) from the UK Biobank to assess bidirectional relationships and shared mechanisms between sarcopenia and osteoporosis. It found that the two conditions act as reciprocal risk factors, with lean mass index showing an association with sarcopenia–osteoporosis risk (reported HR 0.830, 95% CI 0.788–0.874 for the truncated result). The scientific significance lies in identifying common biological pathways that could enable more unified risk prediction and prevention strategies for age-related musculoskeletal decline.

Xu S, Wen S, Zong X et al. · Aging cell · (2026) · View on PubMed ↗

Aripiprazole once-monthly for patients diagnosed with bipolar I disorder: Number needed to treat, number needed to harm, and likelihood to be helped or harmed.

This post hoc analysis evaluated the long-term maintenance benefit-risk profile of aripiprazole once-monthly 400 mg (AOM 400) in patients with bipolar I disorder using data from a double-blind randomized withdrawal trial versus placebo over 52 weeks (NCT01567527). AOM 400 improved recurrence-free maintenance outcomes with quantified benefit-risk metrics (NNT/NNH and likelihood to be helped or harmed) relative to placebo. These findings support evidence-based clinical decision-making for sustained relapse prevention in bipolar I patients treated with AOM 400.

Citrome L, Zhang Z, Hutson Walker AM et al. · Journal of affective disorders · (2026) · View on PubMed ↗

Clinical characteristics and outcomes of intracerebral haemorrhage in young vs older adults: insights from the INTERACT3 trial.

This secondary analysis of the INTERACT3 stepped-wedge, cluster-randomized trial compared baseline characteristics, management, and 6-month outcomes of intracerebral hemorrhage (ICH) between younger adults (≤50 years) and older adults. The study evaluated 7031 patients across 122 hospitals in 10 countries (2017–2021) to determine how clinical and imaging features and outcomes differ by age group. Clinically, defining age-specific ICH trajectories can inform risk stratification and tailoring of bundled acute ICH care.

Khan M, Ouyang M, Wasay M et al. · European stroke journal · (2026) · View on PubMed ↗

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Neurodegeneration & Neurobiology (tau, alpha-synuclein, TDP-43, neuroinflammation)

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.

This work studied whether TOP1-mediated neuronal DNA damage patterns are shared across major neurodegenerative diseases by performing single-cell whole-genome sequencing on 469 neurons from brains of patients with C9ORF72 ALS, C9ORF72 frontotemporal dementia, Alzheimer’s disease, and controls. All three diseases showed increased somatic single-nucleotide variants and insertions/deletions, with mutational signature analyses identifying an oxidative-damage sSNV signature and an sIndel process consistent with TOP1-mediated damage occurring at disease-specific frequencies across neuron types. The findings are significant because they suggest a common, targetable genomic-damage mechanism across ALS/FTD/AD that could inform biomarker development and therapeutic strategies aimed at DNA damage pathways.

Zhou Z, Luquette LJ, Dong G et al. · Cell · (2026) · View on PubMed ↗

TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.

This article reviewed and evaluated TDP-43 proteinopathy in amyotrophic lateral sclerosis (ALS) as both a biomarker and therapeutic target, focusing on how TDP-43 normally functions in nuclear RNA regulation and how ALS-associated stressors and mutations drive nuclear depletion and cytoplasmic aggregation. It synthesizes evidence that TDP-43 aggregates contribute to downstream neuronal dysfunction and altered gene expression, supporting the rationale for targeting TDP-43 pathology or its upstream triggers. The significance is that it frames TDP-43 as a mechanistic hub for biomarker development and for therapeutic interventions aimed at restoring RNA homeostasis and preventing neurodegeneration in ALS.

Christoforidou E, McFagan E, McLaughlin M et al. · Biochemical Society transactions · (2026) · View on PubMed ↗

Structural dynamics of α-Synuclein: Multi-scale imaging insights into pathological progression across Synucleinopathies.

This review studied how α-synuclein structural dynamics—from disordered monomers to toxic oligomers and amyloid fibrils—relate to pathological progression across synucleinopathies including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. It integrates multi-scale electron microscopy approaches (transmission EM, immunoelectron microscopy, cryo-EM/cryo-electron tomography, and correlative EM) to map continuous ultrastructural conformational evolution. These mechanistic structural insights are clinically important because they may inform biomarkers and therapeutic strategies aimed at blocking α-synuclein misfolding and aggregation.

Yang H, Tian Z, Liu J · Experimental neurology · (2026) · View on PubMed ↗

Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress.

The study examined the contribution of the serotonin 5-HT2A receptor (5-HT2AR) to the therapeutic effects of psilocin on social behavior deficits in mice repeatedly exposed to social defeat stress. It found that psilocin’s antidepressant-like behavioral effects in this model depend on 5-HT2AR activation in the cerebral cortex. This supports 5-HT2AR as a mechanistic driver of psychedelic-like therapeutic benefit for stress-related social dysfunction and informs target validation for related treatments.

Ibi D, Takaba R, Yoshida K et al. · Neuropsychopharmacology reports · (2026) · View on PubMed ↗

Tau protein as a regulator of mitochondrial function and dynamics.

The study tested whether wild-type Tau regulates mitochondrial function and dynamics by comparing Tau deficiency in Caenorhabditis elegans (PTL-1 knockout) and mice lacking the Tau-like homolog PTL-1. Tau deficiency shifted mitochondria toward a pro-fusion state with increased mitochondrial activity and altered redox homeostasis, improving stress resistance (e.g., heat tolerance). These results suggest physiological Tau contributes to mitochondrial homeostasis and that modulating Tau pathways could influence mitochondrial resilience in aging and neurodegeneration.

Tsakiri E, Campos-Marques C, Ploumi C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Disruption of dynactin complex function in intellectual disability.

The study identified deleterious variants in dynactin subunit 4 (DCTN4) in intellectual disability (ID) pedigrees and tested their effects in mice. DCTN4 ablation caused altered neuronal positioning and apoptosis in neural progenitor cells, and mice carrying an ID-linked DCTN4 variant showed cognitive deficits with impaired dendritic development. This links disrupted dynactin complex function to neurodevelopmental pathology and provides a mechanistic entry point for understanding DCTN4-associated ID.

Pan Y, Li H, Liao M et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Injury-induced tau pathology promotes aggressive behavior in Drosophila without neurodegeneration.

This study tested whether injury-induced tau pathology alters behavior in Drosophila by panneuronally expressing human tau (HsTau) and comparing phosphorylated versus nonphosphorylatable tau variants in male flies. It found that injury triggers increased aggression specifically with HsTau, driven by activation of dopaminergic circuits without neurodegeneration, and that phosphorylated HsTau preserves microtubule binding while failing to suppress microtubule catastrophes, thereby increasing microtubule dynamics. These findings separate tau-driven behavioral effects from neurodegeneration and identify phosphorylation-dependent changes in microtubule regulation as a mechanism relevant to tauopathies.

Maxson R, Smoyer CJ, Hampton MF et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

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Infectious Disease: Tuberculosis, Malaria, and Global Burden/Prevention

Identification of cross-stage, cross-species malaria CD8+ T cell antigens.

The study aimed to identify malaria CD8+ T cell antigen targets shared across Plasmodium species and infection stages by using immunopeptidomics to discover Plasmodium-derived peptides presented on HLA-I. It focused on Plasmodium falciparum (human-infecting in Africa) and Plasmodium vivax (infecting peripheral-blood reticulocytes) and leveraged prior evidence that P. vivax–infected reticulocytes express HLA-I enabling CD8+ T cell recognition. This work provides validated cross-stage, cross-species T cell epitope candidates that could improve malaria vaccine design.

Barbosa CRR, de Lacerda LB, Bettencourt PJG et al. · Nature · (2026) · View on PubMed ↗

Global, regional, and national burden of tuberculosis and multidrug-resistant tuberculosis by HIV status, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

The study used Global Burden of Disease Study 2023 data to quantify global, regional, and national burdens of tuberculosis and multidrug-resistant TB stratified by HIV status from 1990–2023 across 204 countries and territories. It assessed progress toward WHO End TB Strategy targets by estimating TB incidence, mortality, and MDR-TB burden in HIV-positive and HIV-negative populations. This provides an up-to-date, comprehensive evidence base to guide TB and MDR-TB control policies under changing global health funding conditions.

The Lancet. Infectious diseases · (2026) · View on PubMed ↗

Identification of chemical features for improved outer membrane permeation in mycobacteria using machine learning.

The study used a bioorthogonal click chemistry-based PAC-MAN assay to profile mycomembrane permeation of 1,572 azide-tagged compounds in Mycobacterium tuberculosis and the model organism Mycobacterium smegmatis, then applied cheminformatics and machine learning to infer chemical features. It identified specific chemical features predictive of mycomembrane permeation that improve understanding of what drives drug entry through the mycobacterial outer membrane. This provides actionable design rules for developing more effective anti-tuberculosis therapeutics by targeting permeability.

Lepori I, Liu Z, Evbarunegbe N et al. · Nature microbiology · (2026) · View on PubMed ↗

Helicobacter pylori infection, treatment and colorectal cancer risk by genetic predisposition: evidence from two randomised trials.

This study analyzed two randomized trial cohorts (Shandong Intervention Trial, SIT; and Mass Intervention Trial in Linqu, MITS) and a nested case-cohort component to test whether Helicobacter pylori infection, H. pylori treatment, and H. pylori virulence-factor seropositivity modify incident colorectal cancer (CRC) risk by genetic susceptibility. It evaluated associations of infection and treatment with CRC outcomes and whether genetic predisposition altered these effects (details truncated in the abstract). The significance is that it clarifies whether host genetics and bacterial virulence determine who benefits from H. pylori eradication to reduce CRC risk.

Han X, Xu HM, Liu ZC et al. · Gut · (2026) · View on PubMed ↗

Severe anaemia and invasive bacterial infections in Kenyan children: a 26-year hospital surveillance observational study.

This 26-year retrospective hospital surveillance study examined severe anaemia and its association with invasive bacterial infections in Kenyan children aged 1 month to 14 years admitted to Kilifi County Hospital (1998–2024). It characterized prevalence and trends of severe and very severe anaemia and identified factors associated with severe anaemia, while quantifying the relationship between severe anaemia and invasive bacterial infection. The study is important for informing pediatric inpatient risk stratification and guiding interventions to reduce mortality from anaemia-associated infections in sub-Saharan Africa.

Abuga KM, Muriuki JM, Mutua AM et al. · The Lancet. Global health · (2027) · View on PubMed ↗ · Free PDF ↗

Systematic discovery of pathogen effector functions across human pathogens and pathways.

The study developed an effector ORFeome (eORFeome) functional genomics platform comprising 3,835 rapidly evolving effector ORFs from diverse human pathogens (viruses, bacteria, and parasites) and tested them in high-throughput barcoded screens across host signaling pathways. Hundreds of previously uncharacterized effector ORFs modulated NF-κB, apoptosis, p53, cGAS–STING, and MHC class I pathways, including unexpected activities of known effectors and distinct pathway-specific functions encoded by single ORFs. This scalable effector discovery and pathway-mapping strategy provides a systematic route to identify actionable pathogen mechanisms relevant to immune evasion and host-cell control.

Pachano T, Leng H, Dugied G et al. · Cell · (2026) · View on PubMed ↗

Structural basis for host membrane binding and remodeling by invading malaria parasites.

The study determined the endogenous structural architecture of the Plasmodium falciparum moving junction repeating unit directly purified from invasion-stalled parasites, focusing on apical membrane antigen 1 (PfAMA1) and rhoptry neck proteins PfRON2, PfRON4, and PfRON5. It revealed a sailboat-shaped 1:1:1:1 assembly in which PfRON2 provides two transmembrane helices anchoring the complex to the red blood cell (RBC) membrane and an extracellular handle for PfAMA1 binding, with PfAMA1 directly contacting the RBC membrane to strengthen the connection. These structural insights clarify the molecular basis of malaria invasion and can inform design of interventions targeting the PfAMA1–PfRON moving junction interface.

Haile MT, Kaxiras DA, Zhen J et al. · Cell · (2026) · View on PubMed ↗

Bufalin mitigates corneal damage in herpes simplex keratitis mice via inhibiting viral replication.

The study tested whether bufalin, a bufadienolide cardiotonic steroid, mitigates corneal damage in herpes simplex keratitis (HSK) mouse models by inhibiting viral replication. In HSK mice, bufalin reduced corneal injury and suppressed viral replication as a key mechanism of protection. This suggests bufalin as a candidate antiviral/anti-inflammatory therapeutic approach for drug-resistant or hard-to-treat HSK.

Wu J, Liu Y, Zhang Y et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle.

This study examined how antibiotic inhibitors CBR9379 (E. coli RNAP) and AAP-SO2 (Mycobacterium tuberculosis RNAP) perturb the nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases, focusing on conserved active-site elements such as the trigger loop (TL) and Rim-Helices/F-loop (RH-FL). The authors found that RNAP active-site motions—linked to TL closure and coordinated RH-FL behavior—are essential for the nucleotide addition cycle, and that inhibitor binding reveals these required conformational dynamics. These mechanistic insights identify specific RNAP conformational steps as drug-relevant targets, informing antibiotic development against bacterial RNAPs.

Dhingra Y, Landick R, Campbell EA et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

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Vaccines & Immunogenicity (HIV, HPV, influenza IgA, mRNA platforms, etc.)

Enhanced B cell priming induces broadly neutralizing HIV-1 apex antibodies.

This study evaluated a germline-targeted HIV-1 Env immunogen (CAP256.OPT4) in macaques to determine whether enhanced B cell precursor priming can induce V2 apex broadly neutralizing antibodies (bNAbs). CAP256.OPT4 increased V2 apex bNAb precursor priming by 30–400-fold versus wild-type Env and produced neutralization breadth in >90% of macaques, including N130-containing viruses, with breadth detectable by ~12 weeks after delivery using SHIVs, protein nanoparticles, or mRNA. The results support a vaccine design strategy that uses Env engineering to rapidly prime rare bnAb lineages and accelerate broadly neutralizing responses.

Marchitto L, Wagh K, Roark RS et al. · Nature · (2026) · View on PubMed ↗

Vaccination elicits HIV broadly neutralizing antibodies in primates.

This study investigated whether vaccination can elicit HIV broadly neutralizing antibodies in primates using germline-targeting concepts to prime rare bnAb precursor B cells. Vaccination strategies were shown to drive bnAb development in primates despite HIV antigenic diversity, consistent with the goal of guiding affinity maturation toward potent broadly neutralizing specificities. Scientifically, the work strengthens germline-targeted vaccine frameworks as actionable templates for next-generation HIV immunogens.

Steichen JM, Madden PJ, Flynn CT et al. · Nature · (2026) · View on PubMed ↗

Efficacy, safety, and immunogenicity of an Escherichia coli-produced nine-valent human papillomavirus vaccine: a multicentre, double-blind, randomised, controlled, phase 3 trial.

This multicentre, double-blind, randomized phase 3 trial evaluated the efficacy, safety, and immunogenicity of an Escherichia coli–produced nine-valent HPV vaccine (Cecolin 9) in healthy, non-pregnant women aged 18–45 years in China. Cecolin 9 generated protective immune responses and had an acceptable safety profile in participants without prior HPV vaccination. The findings are clinically significant for expanding HPV prevention options using a scalable E. coli–based platform.

Pan HX, Bi ZF, Jing YL et al. · The Lancet. Infectious diseases · (2026) · View on PubMed ↗

Safety and efficacy of mRNA vaccines: a mechanistic and public health perspective.

This mechanistic and public health review assessed safety and efficacy of mRNA vaccines by integrating biological mechanisms (transient cytoplasmic expression, no genomic integration, rapid clearance) with preclinical and clinical evidence from large-scale real-world COVID-19 deployment. It concludes that mRNA vaccines have strong immunogenicity and a favourable safety profile while maintaining efficacy across diverse populations. The synthesis is significant for ongoing vaccine policy, risk communication, and future mRNA platform development.

Blakney AK, Top KA, Cowling BJ et al. · Lancet (London, England) · (2026) · View on PubMed ↗

The role of mucosal IgA in protection against influenza A H1N1 virus infection in a real-world setting.

The study evaluated, in a real-world prospective human cohort, whether antigen-specific mucosal IgA in the nasal compartment correlates with protection against influenza A H1N1 infection, using H1-specific nasal IgA and serum IgG and comparing with SARS-CoV-2 data from the same cohort. Higher antigen-specific mucosal IgA was assessed as a correlate of reduced influenza infection risk, providing direct clinical evidence for mucosal antibody-mediated protection. This strengthens the rationale for influenza vaccines that induce mucosal IgA rather than relying solely on parenteral systemic immunity.

Bladh O, Pongrácz T, Aguilera K et al. · EBioMedicine · (2026) · View on PubMed ↗

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Innate Immunity, Inflammasomes, and Inflammatory Signaling

Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis.

This phase 3, multicenter, double-blind noninferiority trial studied rituximab versus ocrelizumab in adults with newly diagnosed relapsing multiple sclerosis with recent disease activity, dosing both every 6 months for 24 months. Rituximab met the trial’s noninferiority criterion for MRI activity, with the primary endpoint defined as absence of new or enlarging T2 lesions from month 6 to month 24. The clinical significance is that it provides head-to-head evidence supporting rituximab as a potentially comparable anti-CD20 option to ocrelizumab for early relapsing MS management.

Torkildsen Ø, Brustad HK, Høgestøl EA et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Hypoxia-driven T cell-macrophage-stromal cross-talk sustains fibrosis in preclinical models of cutaneous chronic graft-versus-host disease.

This preclinical study examined how hypoxia-driven T cell–macrophage–stromal signaling sustains fibrosis in cutaneous chronic graft-versus-host disease (cGVHD) using spatial transcriptomics, single-cell RNA sequencing, and multiplex immunofluorescence. It identified an HIF-1α–PI3Kδ–IL-13 axis in which hypoxic epidermal cells stabilize HIF-1α, PI3Kδ-activated T cells produce IL-13, and macrophage–epidermal cross-talk maintains the fibrotic program. The significance is that it pinpoints a mechanistic signaling cascade that could be therapeutically targeted to treat treatment-resistant cGVHD skin fibrosis.

Song Q, Xu Y, Wang X et al. · Science translational medicine · (2026) · View on PubMed ↗

Inflammation impairs fertility and oocyte quality in systemic lupus erythematosus by triggering oxidative stress-mediated ferroptosis.

The study investigated how systemic lupus erythematosus (SLE) inflammation affects female fertility by impairing oocyte quality, using a chronic SLE mouse model and assessing oxidative stress and ferroptosis. It found that SLE-associated inflammation causes defective oocyte maturation and developmental competence, mitochondrial dysfunction, increased oxidative stress, and ferroptosis-related changes, and that hydroxychloroquine and melatonin attenuate inflammation- and oxidative-stress–linked damage. This supports a causal pathway—oxidative stress–mediated ferroptosis—for SLE-related reproductive decline and suggests therapeutic mitigation strategies.

Mao R, Zhou J, Wang X et al. · Cell death & disease · (2026) · View on PubMed ↗

Inflammatory myofibroblasts reprogram neutrophil fate to drive chronic inflammation in peri-implantitis.

This study mapped the peri-implantitis (PI) microenvironment in human PI lesions using single-cell and spatial transcriptomic analyses with targeted validation, focusing on neutrophil fate control by inflammatory myofibroblasts. It reported expansion of CXCR4+ aged neutrophils with enhanced survival signaling consistent with apoptosis delay, driven by a PI-specific stromal–myeloid organization involving fibroblast-rich regions. These findings are significant because they identify a cellular circuit that sustains chronic inflammation in PI and may provide targets to disrupt neutrophil persistence and bone-loss progression.

Lin W, Altayar BA, Jiang S et al. · International journal of oral science · (2026) · View on PubMed ↗

Xin-Zi-Sheng-Wan Decoction Alleviates Hyperuricemia-associated Renal Injury by Inhibiting RIPK1/RIPK3/MLKL-Mediated Necroptosis.

This experimental study tested whether Xin-Zi-Sheng-Wan Decoction (XZSWD) protects against hyperuricemia-associated renal injury and investigated the mechanism involving necroptosis. It reported that XZSWD alleviates renal injury in the hyperuricemia context by inhibiting the RIPK1/RIPK3/MLKL necroptosis pathway (mechanistic details truncated). The clinical relevance is that XZSWD may offer a therapeutic strategy to reduce uric-acid–linked kidney damage by targeting a defined necroptotic signaling axis.

Chen J, Zhu L, Huang W et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Overlapping Mechanisms and Novel Biomarkers Define Asthma and COPD as a Spectrum of Airway Disease.

This review examined mechanistic overlap and proposed novel biomarkers that could unify asthma and COPD as a spectrum of airway disease, focusing on molecular heterogeneity within each condition. It synthesizes evidence that shared clinical features and treatments coexist with distinct and overlapping inflammatory and molecular pathways that may be captured by emerging biomarkers. The work is significant for refining diagnosis, stratifying patients, and guiding more targeted therapies across obstructive airway diseases.

Schworer SA, Lee JH, O’Neal WK · Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · (2026) · View on PubMed ↗

Norepinephrine attenuates acute lung injury by protecting mitochondria via the β2-AR-AKAP1 axis and inhibiting alveolar epithelial pyroptosis.

The study tested whether norepinephrine (NE) protects against acute lung injury (ALI) by acting on mitochondrial integrity and pyroptosis, using in vitro and in vivo models and mechanistic pathway analyses. NE attenuated ALI primarily by suppressing alveolar epithelial cell pyroptosis, with transcriptomic and functional data implicating the β2-AR–AKAP1 axis as a key signaling route. This positions NE and the β2-AR–AKAP1/mitochondria–pyroptosis pathway as potential therapeutic targets to reduce ALI severity.

Yin Y, Zeng Z, Wei S et al. · Redox biology · (2026) · View on PubMed ↗

Efficacy and safety of Tripterygium agents in treatment of psoriasis: a systematic review and network meta-analysis.

The study conducted a systematic review and network meta-analysis of randomized trials assessing Tripterygium-derived agents for psoriasis, comparing monotherapy versus combination therapy and evaluating efficacy and safety. Across 43 included trials, the analysis used R (meta/Gemtc packages) to synthesize comparative outcomes, including results indicating relative benefits of specific Tripterygium formulations (e.g., TwHF) while also summarizing adverse-event profiles. This provides comparative evidence to guide selection of Tripterygium regimens for psoriasis, though the clinical impact depends on trial quality and heterogeneity.

Lin NX, He JJ, Gao PB et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Porcine Deltacoronavirus M Protein Binds NLRP3 to Promote Inflammasome Assembly via Competition with TRIM31.

The study assessed the role of porcine deltacoronavirus (PDCoV) M protein in inflammasome activation in piglets and in vitro models, focusing on NLRP3 and its interaction with TRIM31. PDCoV infection activated the NLRP3 inflammasome to drive IL-1β maturation, and the M protein promoted NLRP3 inflammasome assembly by directly binding the NLRP3 LRR domain while competing with TRIM31. This mechanistically links PDCoV structural protein–host innate immunity interactions to intestinal inflammation and acute diarrhea in pigs.

Hou J, Han F, Liu A et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

The centrosomal hub unifies regulatory factors of NLRP3 inflammasome activation.

This study investigated how microtubule transport, the centrosomal kinase NEK7, priming, and NLRP3 abundance regulate NLRP3 inflammasome activation at the centrosome/PCM in cells. It found that microtubule-dependent transport is required for NEK7-dependent NLRP3 activation and that microtubules, priming, and NEK7 synergistically increase pericentriolar material (PCM) abundance to create a permissive environment for NLRP3 condensation and inflammasome assembly. The results connect cytoskeletal trafficking and NEK7 signaling to spatial control of inflammasome activation, suggesting new intervention points for inflammatory disease.

Wu M, Wu H · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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GPCR/Signal Modulation, Cellular Mechanotransduction, and Bioengineering/AI Tools

Towards the construction of a virtual yeast.

The study proposed a “virtual yeast” AI system to model eukaryotic cellular behaviors using Saccharomyces cerevisiae as a genetically tractable, data-rich model. It decomposed cellular complexity into eight function-centered modules (genetic, metabolic, structural) coordinated by an LLM-based orchestration layer that integrates mechanistic knowledge, subcellular architecture, and dynamic states with active experimentation. This provides a framework for mechanistically grounded, multimodal AI-driven simulation and hypothesis testing in yeast biology that could accelerate computational discovery in cellular systems.

Qian L, Zhou Z, Zhou P et al. · Nature · (2026) · View on PubMed ↗

Clinical decision support in hematological malignancies using a case-grounded AI agent.

This Nature Medicine study developed HemaGuide, a locally deployable case-grounded AI agent for clinical decision support in hematological malignancies. The system converts unstructured tumor board documents into structured case representations, routes cases to guideline/advanced/molecular decision modes, and grounds recommendations in guideline flowcharts and a clinical decision memory of >2,000 real-world tumor board cases. In expert-blinded benchmarking, it was evaluated against 45 high-impact hematology cases, aiming to reduce inequities in access to subspecialty tumor board expertise.

Zoller J, Kalz M, Wu X et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Prime editing for precise genome engineering and modulation of fungal metabolism.

The study developed fPE7max, a prime editing platform optimized for filamentous fungi, and tested it across diverse fungal species and genomic loci to enable base substitutions and defined small insertions/deletions. It achieved an average editing efficiency approaching 90% and further supported larger insertions up to ~1 kb and deletions up to ~10 kb, then used perturbation of upstream open reading frames in the pleiotropic regulator gene laeA to modulate metabolic output. This establishes a high-efficiency genome engineering tool for fungal metabolism with direct utility for industrial strain improvement.

Sun C, Nie Q, Straub N et al. · Nature biotechnology · (2026) · View on PubMed ↗

Lineage tracing from cellular heritage to disease destiny.

This Review surveyed advances in in vivo cell lineage tracing technologies, including refined recombinase systems and synthetic/natural barcoding approaches, to connect cellular heritage to disease outcomes across cancer, cardiovascular disease, and aging. It highlights that integrating permanent lineage records with single-cell multi-omics is emerging as a unified strategy to decode how past cell states shape present disease programs. The significance is a roadmap for translating lineage tracing into mechanistic, multi-layer models of disease development.

Zhu H, Liu X, Tang M et al. · Nature genetics · (2026) · View on PubMed ↗

Gravitational and mechanical forces shape mitochondrial translation.

The study examined how gravitational and mechanical cues regulate mitochondrial protein synthesis by measuring mitochondrial translation under microgravity and altered adhesion conditions in mammalian cells and Caenorhabditis elegans. It found that microgravity reduces mitochondrial translation and that attenuation of cell adhesion via laminin–integrin interactions triggers a signaling cascade involving FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins to activate mitochondrial translation. This reveals a mechanotransduction pathway that couples physical forces to mitochondrial gene expression.

Wakigawa T, Kimura Y, Mito M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Myc sustains sex-biased organ zonation in the Drosophila intestine.

This study investigated how sex-biased organ zonation is established in the adult Drosophila intestine by combining whole-organ 3D cellular mapping with metabolic profiling. It found that zonation is driven by opposing, region-specific actions of the sex determinant doublesex (Dsx) and the transcription factor Myc, where male-specific Dsx represses Myc in enterocytes and Myc sustains female-specific ploidy and lipid profiles. These findings are significant for understanding how sex-determination pathways generate spatially patterned metabolic and transcriptional states in vivo.

Amourda C, Blackie L, Gaspar P et al. · Developmental cell · (2026) · View on PubMed ↗ · Free PDF ↗

Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data.

This study developed whole-cell particle-based digital twin simulations that integrate 4D lattice light-sheet microscopy data with reaction–diffusion particle simulations in ReaDDy to model intracellular organelle dynamics. Using live Cal27 cell fluorescence data, it constructed digital twins including mitochondrial networks, microtubules, dynein/kinesin motors, plasma membrane, and nucleus, and simulations reproduced experimental mitochondrial dynamics trends across control and two perturbations. The approach is significant for enabling mechanistic, predictive modeling of mesoscale intracellular transport and dynamics from live-cell imaging.

Arkfeld E, Wang Z, Hakozaki H et al. · Cell · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning.

The study used in vivo mouse intestinal regeneration models and organoids to determine how cell heterogeneity is integrated with tissue mechanochemical state and stabilized at the chromatin level, focusing on the mechanosensor YAP1 and lineage programs. It identified a critical density regime that creates a permissive window for YAP1 heterogeneity, linked YAP1 heterogeneity to lineage-biased chromatin accessibility, and showed decoding through FOXA1 integrating the permissive chromatin state with Delta–Notch signaling. This mechanistic framework explains how transient heterogeneity becomes stable spatial patterning during regeneration, highlighting YAP1/FOXA1/Delta–Notch as potential control points.

Schwayer C, Barbiero S, Brückner DB et al. · Cell · (2026) · View on PubMed ↗

Effectiveness of strategies to prevent burnout syndrome in hospital-based healthcare personnel.

The study systematically reviewed evidence on strategies to prevent burnout syndrome in hospital-based healthcare personnel, synthesizing individual, organizational, and combined interventions. It searched PubMed, Cochrane Library, Epistemonikos, and the Virtual Health Library for systematic reviews published between 2014-01-01 and 2024-01-15. The review’s significance is to clarify which prevention approaches have demonstrated effectiveness for reducing burnout in healthcare settings, especially in the post–COVID-19 context.

Atencio MA, Luini JA, Cappella RB et al. · Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · (2026) · View on PubMed ↗ · Free PDF ↗

Allosteric ligands with distinct properties uncover tissue-specific physiological regulation mediated by free fatty acid receptor 2.

The study investigated how allosteric ligands with distinct properties regulate tissue-specific physiology mediated by free fatty acid receptor 2 (FFAR2), using mouse tissues expressing a hemagglutinin-tagged human FFAR2 DREADD and ago-allosteric regulators. Ligands such as compound 187 and AZ1729 (binding overlapping sites) and 4-CMTB (binding a distinct site) produced tissue-selective effects by differentially activating Gq versus Gi signaling pathways. This provides a ligand-based strategy to achieve tissue-selective GPCR modulation and refines how FFAR2 signaling is tuned across tissues.

Barki N, Hassan Abdelmalik AM, Jenkins L et al. · Science signaling · (2026) · View on PubMed ↗

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system.

This article reviewed next-generation therapeutics and the continued relevance of legacy drugs targeting the endothelin system, covering endothelin-1 (ET-1), ETA/ETB receptors, and major clinical indications. It highlights how endothelin receptor antagonists (e.g., bosentan, ambrisentan, macitentan), ETB agonism (sovateltide), and newer ETA-selective agents (e.g., clazosentan, aprocitentan) have expanded endothelin-targeted therapy across diseases. The significance is a consolidated translational framework for selecting and developing endothelin pathway drugs based on receptor subtype biology and emerging clinical results.

Davenport A, Anwar M, Kuc R et al. · Canadian journal of physiology and pharmacology · (2026) · View on PubMed ↗

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Generated automatically on July 02, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.