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PubMed2026

Antennal transcriptome analysis of chemosensory proteins in the raspberry weevil, Aegorhinus superciliosus (Coleoptera: Curculionidae).

Aegorhinus superciliosus (Coleoptera: Curculionidae) is a polyphagous pest of economic importance in southern Chile, the chemical ecology of which remains poorly characterized. Across insect species, chemosensory proteins, including odorant receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), odorant-binding proteins (OBPs), chemosensory proteins (CSPs), and sensory neuron membrane proteins (SNMPs), mediate the detection of chemical cues involved in host selection, reproduction, and other ecologically relevant behaviors. In this study, the antennal transcriptome of adult A. superciliosus was sequenced and analyzed using a de novo RNA-seq approach. Three independent biological replicates per sex were used for RNA-seq, and the same number of independent biological replicates was used for RT-qPCR validation; sequencing yielded 147,409,936 high-quality reads after quality filtering. A total of 112 candidate chemosensory genes were identified, comprising 43 ORs, 34 OBPs, 10 CSPs, 18 IRs, 5 GRs, and 2 SNMPs. Phylogenetic analyses assigned these candidate proteins to established clades, providing a comparative framework for functional inference for ORs and OBPs. Sex- and tissue-biased expression analyses revealed that several ORs, including AsupOR4, AsupOR19, and AsupOBP13, exhibit antennal enrichment and sex-specific expression patterns. Notably, AsupOR19 and AsupOBP13 displayed strong female-biased expression. In addition, transcripts of selected ORs and OBPs were detected in non-antennal tissues, such as the rostrum and legs, suggesting potential functional versatility beyond canonical olfaction. Together, these findings represent the first molecular identification of the chemosensory repertoire of A. superciliosus. This study establishes a foundation for reverse chemical ecology approaches aimed at identifying behaviorally active volatile organic compounds (VOCs) toward environmentally sustainable strategies for integrated pest management.

Animals↗

PubMed2026

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P < 0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P = 0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P < 0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans↗

PubMed2026

Pathogenic properties of myasthenia gravis AChR autoantibodies associate with clinical response to efgartigimod.

BACKGROUND: Efgartigimod, a neonatal Fc receptor (FcRn) blocker, effectively reduces total IgG, including pathogenic acetylcholine receptor (AChR) autoantibodies in myasthenia gravis (MG); however, clinical responses vary. To investigate this variability, we studied how efgartigimod impacts AChR-specific autoantibody profiles and associated pathogenic mechanisms, including complement activation, AChR internalisation and ACh-binding site blockade. METHODS: Serum samples (N=150) were sourced from 50 AChR autoantibody-positive generalised MG patients participating in the phase 3 ADAPT study, randomised to receive efgartigimod (N=40) or placebo (N=10) in cycles of 4-weekly infusions. Samples were collected at baseline, day 29 and day 57 during the first cycle. Live cell-based assays quantified AChR-specific IgG subclasses and isotypes and assessed their capacity to mediate pathomechanisms. RESULTS: Efgartigimod decreased all detectable AChR-specific IgG subclasses. At baseline, AChR autoantibody-mediated C3b deposition, AChR internalisation and ACh-binding site blockade were detected in 42 (84%), 41 (82%) and 10 (20%) patients, respectively. After 4-weekly infusions of efgartigimod, the magnitude of all three pathomechanisms was significantly decreased. However, the extent of this reduction varied across individuals. Double responders on both MG-activities of daily living and quantitative MG scores demonstrated a greater reduction in complement activity and AChR internalisation compared with patients who responded on only one score or were double non-responders. In addition, efgartigimod reduced IgG-dependent IgM binding to AChR. CONCLUSIONS: These findings suggest that clinical efficacy may be more closely associated with functional modulation of the AChR-specific autoantibodies than with their absolute quantity alone. These results support the evaluation of mechanistic pathway monitoring as a potential strategy to predict or guide efgartigimod treatment response.

Humans↗

PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Chemical Complementarities of Neuroblastoma Tumor-Resident TCR CDR3s and CMV Antigens are Associated with a Better Outcome.

A likely immune response to a virus can be detected via the presence of TCR CDR3s that (a) exactly match CDR3s known to bind viral antigens or (b) represent chemical complementarity to viral antigens. Previous studies, based on genomics approaches to characterizing anti-CMV TCR CDR3s in patient blood samples, have indicated the possibility that a systemic CMV infection is associated with worse outcomes for NBL, as well as for breast cancer. Thus, the association of NBL tumor-resident anti-CMV TCR CDR3s and patient outcomes was evaluated here, with results indicating that high levels of chemical complementarity between tumor-resident TCR CDR3s and CMV antigens represented a better outcome. This is in apparent contrast to results obtained via the previous study of blood sourced, anti-CMV TCR CDR3s representing a worse outcome. This study identified gene expression values associated with the tumor-specific anti-CMV TCR CDR3s, representing exact matches to known anti-CMV TCR CDR3s, which may assist in identifying a potential underlying mechanism effecting the better outcomes associated with the tumor-resident, anti-CMV TCR CDR3s. Overall, results here raise the question of whether an anti-CMV response directly against the tumor, or within the tumor microenvironment, is involved in reductions in tumor progression or responsiveness to treatment?

Humans↗

PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗

PubMed2026

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved ∼80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans↗

PubMed2026

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans↗

PubMed2026

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased μ-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety‑four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5 mg, PCIA 0.55 mg/kg) or sufentanil group (loading dose 10 μg, PCIA 3 μg/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9 ± 3.1 versus 177.5 ± 3.9, p < 0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3 days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p > 0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p = 0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans↗

PubMed2026

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans↗

PubMed2026

Mapping antibody sequences and effector functions across spatial niches.

Antibodies are fundamental to human health but can also drive pathology. Each antibody has a molecular specificity, encoded by their clonally heritable B cell receptor (BCR). Recent advances in spatial transcriptomics coupled with repertoire sequencing have enabled capturing antibody-secreting cells (ASCs) and their clonal BCR within their tissue microenvironment. However, our understanding of antibody production niches remains limited. Furthermore, where antibodies are produced can be distinct from where antibodies exert their effector function. Here, we propose a conceptual spatial framework to distinguish between 'antibody production niches', defined by the ASC, BCR, and niche composition, versus 'antibody functional niches', composed of the antibody, antigen, and effector landscape. We then examine the possibilities and challenges to map and link antibody-encoding sequences and antibody effector functions using current and emerging technologies. Combined, we argue that integrating spatial sequence data with the antibody functional context is essential to decode the architecture of antibody-mediated immunity.

Humans↗

PubMed2026

Exercise-associated epigenetic remodeling and TCR repertoire dynamics in Lynch syndrome carriers.

Lynch syndrome (LS) carriers are at elevated cancer risk. Emerging evidence suggests that exercise may serve as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers undergoing a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Integrative transcriptomic analysis highlights ISL1 as a key exercise-repressed, epigenetically regulated gene, and identifies FLCN as a colorectal cancer (CRC)-associated methylation target. TCR analysis reveals an exercise-associated increase in systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. Collectively, these findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.

Lynch syndrome↗

PubMed2026

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate > 81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r = 0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, αVβ3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals↗

PubMed2026

A conserved distal-tail helical extension defines a tailspike attachment architecture in Gram-negative siphophages.

Rapid growth of bacteriophage genome collections has outpaced functional annotation of tail-tip proteins, limiting comparative analysis of host-recognition structures. Starting from a shared distal-tail gene organization in the Salmonella phages 9NA and Jersey, I developed a morphogenetic bioinformatic framework integrating gene synteny, sequence comparison, profile hidden Markov model (HMM) screening, structural evidence, structure-aware searching, and AlphaFold modeling. Comparison with the experimentally characterized lambda and Sf11 tail assemblies identified a predominantly alpha-helical C-terminal extension of the distal-tail (DT) protein associated with tailspike attachment, termed the distal-tail helical extension (DT-helix). Screening 541,986 proteins from 5167 complete NCBI RefSeq tailed-phage genomes, followed by evidence-based evaluation of sequence, genomic context, and structural architecture, identified 165 curated DT-helical-extension-associated phages. Their DT proteins segregated into six sequence groups. In the four principal multi-member groups, cognate tailspikes showed group-specific conservation in proximal N-terminal regions but substantially greater downstream diversity, consistent with sequence constraint at the DT-tailspike attachment boundary. A complementary ProstT5/Foldseek search supported the established groups but revealed no convincing additional highly divergent family. Together with the experimentally characterized Sf11 attachment interface, these findings define a recurrent morphogenetic architecture linking conserved distal-tail scaffolds to more variable receptor-binding proteins across siphophages infecting Gram-negative bacteria. Although universal exchangeability is not established, the identified scaffold-receptor-binding boundaries provide a framework for molecular characterization and rational phage engineering. Accession-level information for the 165 curated phages is available through PhageTailDB.

Viral Tail Proteins↗

PubMed2026

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

Humans↗

PubMed2026

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male↗

PubMed2026

Maternal vitamin B12 deprivation exacerbates offspring obesity by reducing early-life colonization with Bifidobacterium pseudolongum.

Vitamin B12 deficiency during pregnancy and lactation is common, yet its mechanistic impact on reproductive outcomes and offspring health remains poorly understood. Here, we show that maternal dietary vitamin B12 deprivation not only impairs maternal glucose metabolism and reproductive outcomes but also exacerbates high-fat-diet-induced obesity in offspring. These effects are mediated by gut microbiota and associated with a marked reduction of Bifidobacterium pseudolongum (B. pseudolongum) in both dams and their offspring. Maternal vitamin B12 deprivation limits early-life acquisition of B. pseudolongum in offspring during lactation, subsequently intensifying obesity and metabolic dysregulation. Early-life restoration of B. pseudolongum or its key metabolite, acetate, effectively ameliorates this aggravated obesity. Mechanistically, acetate acts through the Ffar2 receptor to upregulate Ehhadh expression. Together, these data establish that perinatal nutrition imprints long-term metabolic phenotypes in offspring via early-life acquisition of the gut microbiota, with a critical window during lactation.

Animals↗

PubMed2026

Safety, Pharmacokinetics, and Pharmacodynamics of Single-Dose Programmed Cell Death Protein 1 Inhibitor, Budigalimab, in People With HIV-1 With Antiretroviral Therapy-Suppressed Viral Load.

BACKGROUND: Blockade of inhibitory immune checkpoint receptor programmed cell death protein 1 (PD-1) on target immune cells is associated with improved HIV-specific immune function and activation of latent HIV. This randomized, placebo-controlled, Phase 1b study assessed low doses of investigational anti-PD-1 monoclonal antibody, budigalimab, for safety, tolerability, pharmacokinetics, and pharmacodynamics in people with HIV (PWH) on antiretroviral therapy. METHODS: Participants received single doses of budigalimab 10 mg subcutaneous (SC), 20 mg SC, 10 mg intravenous (IV), or placebo (n = 8 per arm) and were followed for 24 weeks. RESULTS: Of 32 randomized participants, 22 reported adverse event(s) (AE); most (n = 19) were grade ≤2 and no grade ≥4 AE or treatment-related serious AE. Two participants reported a non-treatment-related grade 3 AE (placebo, n = 1 pneumonia; 10 mg IV, n = 1 elevated aspartate aminotransferase). One reversible immune-related AE (grade 2 lichenoid keratosis) was reported (20 mg SC). Geometric mean maximum serum concentrations were 0.37, 1.57, and 3.2 µg/mL with 10 mg SC, 20 mg SC, and 10 mg IV, respectively. Drug exposure with 20 versus 10 mg SC dosing was more than dose proportional and less variable. Subcutaneous bioavailability was approximately 53%-62%. The PD-1 receptor saturation was ≥95% in most participants (median duration: 20 mg SC, 42 days; 10 mg SC, 14 days; 10 mg IV, 35 days). CONCLUSIONS: Findings suggest an acceptable safety profile for single-dose budigalimab in PWH, with a favorable pharmacokinetic profile for 20 mg SC and 10 mg IV. Further evaluation as a potential component of an HIV treatment is underway.

Humans↗