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PubMed2026

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584 mM (OXD) and 0.1498 mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10 ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines↗

PubMed2026

Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.

Hematopoietic stem cell (HSCs) aging is a complex biological process driven by both cell-intrinsic alterations and extrinsic cues from the bone marrow niche. Understanding these mechanisms is critical for developing therapies against aging-related hematopoietic disorders. This review synthesizes recent advances in the molecular mechanisms underlying HSCs aging, including microenvironmental aging, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, and aberrant nuclear mechanotransduction. We summarize that the functional decline of HSCs during aging drives a compensatory expansion of the phenotypically defined stem cell pool, leading to an aberrant increase in cell number. We also highlight aging-associated HSCs heterogeneity, including CD150high and P-selectin-positive subsets that enrich for myeloid-biased or functionally compromised HSCs states while emphasizing that surface phenotype alone may not fully indicate functional rejuvenation. Finally, we discuss emerging rejuvenation strategies-including targeting myeloid-biased HSCs, modulating inflammatory pathways, and implementing epigenetic or metabolic interventions-supported by cutting-edge technologies such as single-cell multi-omics, gene editing, and computational modeling. These approaches hold promise for counteracting age-related hematopoietic decline and restoring immune competence.

Humans↗

PubMed2026

Estrone disrupts early reproductive development in juvenile male Siniperca chuatsi and is associated with brain and gonadal responses.

Whether estrone (E1)-associated disruption of early reproductive development in fish is accompanied by brain responses in addition to direct gonadal effects remains unclear. Here, juvenile Siniperca chuatsi, a non-model but economically important freshwater species, were exposed for 60 d to 0, 0.01, 0.1, and 1.0 μg/L E1, spanning environmentally reported and elevated concentrations. By integrating waterborne concentration monitoring, histopathology, transcriptomics, and quantitative real-time PCR (qPCR) validation, we evaluated E1-associated changes in brain and gonadal tissues during early reproductive development. Waterborne E1 concentrations remained generally stable throughout the exposure period. At the highest tested concentration (1.0 μg/L), E1 caused neuronal vacuolation and pyknosis in the hypothalamic region and induced distinct ovarian-like structures in the gonads of genetic males. In the brain, cyp19a1, crhr1, and adcy2a were significantly upregulated, whereas egr1 was significantly downregulated, indicating transcriptional changes in genes associated with local estrogen conversion, stress-response/cAMP signaling, and neuronal activity-related regulation within a broader injury/stress-response background. In the gonad, RNA-seq analysis showed significant downregulation of star2, hsd3b1, cyp17a1, and cyp11b and significant upregulation of hsd17b1, suggesting alterations in steroidogenesis-related gene expression at the transcriptomic level. qPCR analysis of selected gonadal candidate genes showed expression directions generally consistent with the RNA-seq results, and these molecular patterns were consistent with the feminized histological phenotype. Together, these results indicate that E1 can disrupt early reproductive development in juvenile S. chuatsi and support a cautious working model in which E1 exposure is accompanied by concurrent brain and gonadal responses. This study provides new evidence for understanding the toxic effects and ecological risk implications of natural estrogen E1 during early fish development.

Animals↗

PubMed2026

Functional role and regulatory network of miR-22-3p in chicken hepatic lipid metabolism.

Although microRNA-22-3p (miR-22-3p) is abundantly expressed in the avian liver, its epigenetic role in lipid homeostasis remains largely uncharacterized. To elucidate its in vivo function, 14-day-old female Qingyuan Partridge chickens were intravenously injected with lentiviral vectors to establish miR-22-3p overexpression and knockdown models. Phenotypic analysis demonstrated that miR-22-3p knockdown significantly elevated hepatic triglyceride (TG) levels (p < 0.05) and drove marked steatosis, whereas its overexpression reduced TG content. Transcriptome sequencing (RNA-Seq) revealed profound metabolic remodeling, identifying 23 core lipid-associated genes (e.g., ELOVL6, FADS2, ACSBG2, and PTGIS) heavily enriched in steroid biosynthesis, fatty acid metabolism, and elongation pathways. In conclusion, miR-22-3p functions as a bidirectional epigenetic rheostat that negatively regulates hepatic lipid deposition by orchestrating a multilayered polygenic network, providing novel molecular targets for mitigating avian metabolic disorders and optimizing production traits in indigenous poultry breeds.

Animals↗

PubMed2026

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals↗

PubMed2026

Gastrointestinal digestion governs insect protein hydrolysis and predicted bioactive peptide release: Species-dependent implications for functional food applications.

This study investigates the digestion of insect proteins and the release of predicted bioactive peptides during human gastrointestinal digestion. Using the Infogest in vitro model, mealworm, cricket, and black soldier fly larvae (BSFL) proteins were digested and analyzed through discovery proteomics and bioinformatics to identify predicted bioactive peptides. Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) quantified insect proteins including predicted bioactive peptide precursor proteins, the precursors of predicted bioactive peptides. Results indicated that gastrointestinal digestion strongly influences peptide release, with the gastric phase exhibiting a richer predicted bioactive peptide profile than the small intestinal phase. Many predicted bioactive peptides were rapidly hydrolysed under small intestine conditions, which may lead to reduced stability or diminished activity in vivo, potentially explaining why certain peptides show strong bioactivity in vitro but limited effects in vivo. Additionally, predicted bioactive peptide release varied by insect species, influenced by genetic factors and peptide abundance. These findings highlight the importance of species selection and consideration of proteolytic digestion patterns in optimizing insect-derived bioactive peptides for functional foods and nutraceutical applications.

Animals↗

PubMed2026

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2025

Elucidation of the immunotoxicity of PEDOT: PSS on RAW264.7 macrophages by oxidative stress, inflammatory response, and NF-κB pathway activation.

Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) nanoparticles, widely used conductive polymers, pose environmental and health risks due to their nanoscale dispersion. However, the characteristics of PEDOT: PSS in aquatic systems and the underlying mechanisms of its toxicity in animal and cell models remain poorly understood. This study aimed to investigate the toxicological effects of PEDOT: PSS nanoparticles on macrophages, with a focus on RAW 264.7 cells. After an acute exposure to PEDOT: PSS nanoparticles at different concentrations (5, 10, 20 μg/mL), we observed significant impairments in cell viability, proliferation, migration, adhesion, and phagocytosis, as well as morphological alterations. Concurrently, there was a marked upregulation of inflammatory markers, including reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), indicating the induction of oxidative stress and inflammation. Mechanistically, PEDOT: PSS nanoparticles activated the nuclear factor kappa B (NF-κB) signaling pathway, a key regulator of inflammatory responses, suggesting that they may mediate inflammatory responses and cell damage via activation of the NF-κB signaling pathway. These findings reveal the toxic mechanism of PEDOT: PSS nanoparticles in macrophages and provide new insights into their biological safety implications.

Animals↗

PubMed2026

Genotype II Live-Attenuated ASFV Vaccine Bearing 24 Genes Deletion in 3 Independent Regions Is Able to Provide Complete Protection Against Homologous Lethal Challenge.

African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live-attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV-Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV-Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV-Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF-compatible clinical signs in vaccinated pigs. The ASFV-Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV-Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.

Animals↗

PubMed2026

Predictive Models for Hypoglycemia Risk in Haemodialysis Patients With Diabetic Kidney Disease: Systematic Review and Meta-Analysis.

AIM: To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. DESIGN: Review. METHODS: Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. DATA SOURCES: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. RESULTS: Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). CONCLUSION: Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. IMPACT: This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. REPORTING METHOD: This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL REGISTRATION: PROSPERO: CRD420251243352.

Humans↗

PubMed2026

Exploratory identification and cellular functional characterization of ppiabl as a candidate gene associated with growth traits in Paralichthys olivaceus.

The Japanese flounder (Paralichthys olivaceus) is an important mariculture species. However, the genetic mechanisms underlying its growth traits remain poorly understood. To explore the genetic basis of growth variation, whole-genome resequencing was performed in a cultured cohort of 60 individuals, followed by exploratory genome-wide association analysis and candidate-gene prioritization. The results revealed heritability estimates of 0.40 for body weight and 0.24 for body length, with substantial overlap in associated loci between the two traits. Exploratory association and variant-annotation analyses prioritized ppiabl, which carries a nonconservative missense variant, as a candidate gene for further investigation. Tissue expression analysis showed that ppiabl was highly expressed in muscle tissue. This gene encodes a protein belonging to the conserved peptidyl-prolyl cis-trans isomerase family. In Japanese flounder primary muscle cells, ppiabl knockdown was associated with altered expression of growth-related genes and an increased G1-phase fraction, whereas overexpression produced changes in the opposite direction. In line with this, fast-growing individuals were found to have significantly larger muscle fiber areas than slow-growing ones. These findings suggest that ppiabl may be involved in muscle-related cellular processes associated with growth variation in Japanese flounder, although its contribution to whole-animal growth requires further validation. Overall, this exploratory study prioritizes ppiabl as a candidate gene potentially associated with growth-related cellular processes in Japanese flounder, although validation in larger independent populations and in vivo models is required.

Animals↗

PubMed2026

A systematic review of macaque brain stimulation: Trends and future directions.

Neurostimulation techniques can powerfully modulate neural circuit activity and provide causal insights into the relationship between brain function and behavior. Macaque monkeys have long been a key animal model for brain stimulation studies. While stimulating the macaque brain with one or a few electrodes has already taught us much about brain function and dysfunction, recent technological advances promise a future with more precise stimulation using many more electrodes. However, such possibilities also increase the number of choices an experimenter has when designing their study. We can learn from a rich past, but a comprehensive overview of which brain regions have been studied and with what stimulation parameters is lacking. Here, we present a PRISMA-compliant systematic review of 734 macaque brain stimulation studies using electrical and/or optogenetic stimulation. We find a striking bias in which brain areas have traditionally been stimulated: a mere 10 brain regions account for half of all studies, with the remainder of studies investigating approximately 150 other areas. Across studies, stimulation frequency robustly predicted direct behavioral effects independent of brain region, while amplitude did not. Future studies could more systematically explore less studied regions through lower stimulation frequencies (e.g., 20-50 Hz) alongside established ranges (∼200 Hz). Tools such as fMRI or optical imaging can capture neural circuit engagement evoked by these frequencies, even when behavioral effects are absent or remain subtle. Our synthesis offers a guide towards the next steps in high-channel-count, high-precision stimulation approaches.

Animals↗

PubMed2026

Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impaired cerebellar development.

Genome-wide association studies (GWAS) have identified numerous loci for insomnia, yet functional validation of effector genes remains limited because most risk variants lie in noncoding regions, and the true causal gene is not known. Here, we use prior human cell-based variant-to-gene mapping to nominate six insomnia effector genes and test them in zebrafish, a tractable diurnal vertebrate model well suited for sleep phenotyping. Our CRISPR-based behavioral screening identifies the MEIS1 ortholog, meis1b, as a regulator of sleep maintenance, with crispants displaying impaired nighttime-specific sleep maintenance and increased sleep latency. Comparative chromatin analyses reveal conserved regulatory architecture spanning the human insomnia-associated locus and selectively implicate meis1b, whereas the duplicated ohnolog meis1a was dispensable. Developmental profiling further shows that meis1b is expressed in cerebellar granule progenitors, paralleling human MEIS1 expression, and that its disruption impairs cerebellar development. Together, these findings establish zebrafish as an efficient vertebrate platform for functional interrogation of GWAS candidates and support an evolutionarily conserved cerebellar role for MEIS1 in sleep maintenance.

Animals↗

PubMed2026

Transcriptomic analysis provides molecular insights into the innate immune defense of Mactra veneriformis against Vibrio alginolyticus infection.

Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.

Animals↗

PubMed2026

Seed-derived mucilage polysaccharides as biomaterials for in vivo tissue regeneration: A systematic review.

Chronic wounds, bone defects, and cartilage injuries represent persistent clinical challenges requiring biomaterial platforms that actively regulate inflammation, oxidative stress, angiogenesis, and extracellular matrix remodeling. Conventional synthetic dressings often provide limited biological activity in these contexts. Seed-derived mucilages - polysaccharide-rich hydrocolloids obtained from chia (Salvia hispanica), flaxseed (Linum usitatissimum), fenugreek (Trigonella foenum-graecum), psyllium (Plantago ovata), guar (Cyamopsis tetragonoloba), quince (Cydonia oblonga) etc. - have emerged as biocompatible, biodegradable, and chemically versatile platforms for tissue engineering. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized in vivo evidence on seed-derived mucilage-based biomaterials across wound healing, bone repair, cartilage regeneration, and related applications. PubMed, Scopus, and Web of Science Core Collection were searched for original in vivo experimental studies published in English between 2020 and 2026. Eligible studies reported at least one measurable regenerative outcome. Data were extracted independently by two reviewers, and methodological quality was assessed using the SYRCLE Risk of Bias tool. Forty-three studies were included. Hydrogels were the dominant biomaterial format, followed by films, scaffolds, sponges, nanoparticle systems, and bilayer or Janus composites. Included systems generally improved wound closure, re-epithelialization, collagen deposition, angiogenesis, antioxidant defense, and inflammatory regulation. However, most studies used small animals with short follow-up periods, and many incorporated nanoparticles or bioactive agents, limiting attribution of efficacy to the mucilage matrix alone. Risk of bias was predominantly unclear due to insufficient reporting of randomization and blinding. Blank mucilage controls, standardized characterization, long-term biosafety data, and clinically relevant models are essential prerequisites for translational progress.

Humans↗

PubMed2026

An Update on Inborn Errors of V(D)J Recombination.

V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte-specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical nonhomologous end joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEIs), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase [RAG1, RAG2, and the recently identified RAG cochaperone NudC domain-containing 3 (NUDCD3)], end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development.

Humans↗

PubMed2026

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

Humans↗