搜索结果：Translational animal science

Pulmonary fibrosis remains a major unresolved challenge in clinical practice. In 2025, pulmonary fibrosis research achieved a series of important advances. This article reviews the progress in basic and translational research of pulmonary fibrosis in 2025. To retrieve literature related to basic and translational research in pulmonary fibrosis, a keyword search was performed, which covered PubMed and Web of Science databases for publications from January 1, 2025 to December 31, 2025. Advances in experimental models of pulmonary fibrosis-including animal models, lung-on-a-chip models, and biomaterial-based models-have enabled better recapitulation of pathological characteristics of the disease. At the mechanistic level, deeper insights regarding core pathological processes have been gained, including small-airway dysfunction, aberrant alveolar epithelial repair, profibrotic macrophage activation, adaptive immune niches, and pathological fibroblast transitions. At the translational level, approval of nerandomilast represented an important milestone, while artificial intelligence (AI)-derived compounds, niche-targeted intervention strategies, and combination therapies have broadened the landscape of anti-fibrotic drug development. In 2025, significant progress has been made in experimental models, mechanistic study, and drug development for pulmonary fibrosis. These advances are shifting the field from a focus on signaling pathways toward an integrative perspective, laying the foundation for in-depth understanding of complex pathological mechanisms of pulmonary fibrosis.

Few conditions in reproductive medicine rival polycystic ovary syndrome (PCOS) in terms of clinical breadth and global impact. Affecting roughly 6-21% of women of childbearing age depending on which diagnostic criteria are applied PCOS sits at the intersection of endocrinology, metabolism, and gynecology, making it difficult to capture within any single disciplinary lens. Its hallmarks are well rehearsed: excess androgens, disrupted ovulation, and the characteristic follicular architecture seen on pelvic ultrasound. Yet what makes PCOS genuinely challenging is the degree to which these reproductive features overlap with far-reaching metabolic consequences, including insulin resistance, type 2 diabetes, lipid abnormalities, and a meaningfully elevated cardiovascular risk profile that persists well beyond the fertile years. Despite several decades of sustained investigation, the origins of PCOS remain imperfectly understood. Genetic susceptibility, epigenetic programming, environmental chemical exposures, and modern dietary habits all appear to play contributory roles, though no single culprit has emerged. The molecular picture is equally layered: aberrant insulin signaling feeds androgen overproduction, gonadotropin secretion goes out of balance, inflammatory cytokines accumulate, oxidative injury mounts, and more recently the gut microbial community has been implicated as an additional participant in this cascade. Diagnosis is further complicated by the phenotypic variability of the syndrome, with different criteria yielding meaningfully different patient populations. Treatment, in turn, requires individualization; lifestyle change, hormonal therapies, insulin sensitizers, and an expanding repertoire of repurposed drugs and plant-based agents each address different facets of a fundamentally heterogeneous disorder. This review provides a comprehensive and integrated account of PCOS across its full biological and clinical spectrum. It covers epidemiology, clinical presentation, risk factors, and current diagnostic frameworks. Pathophysiological mechanisms are examined in depth. A central and distinctive focus of this review is the experimental preclinical landscape. Established animal induction models, letrozole, dehydroepiandrosterone (DHEA), testosterone/dihydrotestosterone propionate, and high-fat diet protocols are critically evaluated for their translational relevance. Drawing on these models, we comprehensively catalogue protective agents across four systematic tables, encompassing both repurposed pharmaceuticals (metformin, GLP-1 receptor agonists, SGLT-2 inhibitors, statins, melatonin) and bioactive natural compounds (curcumin, berberine, quercetin, fisetin, myricetin, apigenin, and others), detailing their induction models, mechanistic pathways, and therapeutic outcomes. Together, this review aims to serve as a single, authoritative reference bridging basic science, translational pharmacology, and clinical practice in PCOS, while identifying the most promising avenues for future research and personalized therapeutic development.

Kyasanur Forest Disease (KFD) is a tick-borne viral haemorrhagic fever endemic to forested regions of South India, with case fatality rates ranging from 3% to 10% and seasonal outbreaks causing recurrent illness among at-risk populations such as forest workers and villagers. The historically used formalin-inactivated KFD vaccine showed limited effectiveness in field studies, providing only about 62% protection. This moderate level of protection highlights the need for improved vaccines that offer higher efficacy and longer-lasting immunity for populations living in endemic areas. A major challenge in vaccine development is the limited understanding of immune responses that protect against KFD, along with the lack of preclinical models that fully reflect the disease as it occurs in humans. Existing animal models-including murine systems and limited non-human primate studies -have contributed to understanding viral replication, lethality, viraemia kinetics, and basic immunological responses. However, murine models often fail to reproduce the full spectrum of human immunopathology, particularly haemorrhagic manifestations and complex host immune responses, while non-human primate models remain limited by cost, accessibility, and incomplete characterisation. Furthermore, variability in experimental endpoints and the absence of standardized immunogenicity and neutralisation assays restrict cross-study comparability and hinder identification of immune correlates of protection. This review critically synthesises current knowledge on KFD animal models and host immune responses, identifying key gaps in translational relevance. We propose a prioritised roadmap that includes: (i) development and validation of advanced preclinical models that better mimic human disease progression and immune dysregulation; (ii) systematic identification of serological and cellular correlates of protection; and (iii) standardisation of virological, serological, and immunological assays to support regulatory evaluation and vaccine benchmarking. Addressing these challenges through coordinated interdisciplinary efforts will accelerate the development of next-generation KFD vaccines and therapeutics tailored to endemic populations.

Hypothermia and hypometabolism are important for hibernating animals to survive harsh environmental conditions. Induction of a hypothermic and hypometabolic state is considered an avenue to treat severe diseases, such as ischemic stroke. However, noninvasive and safe methods to achieve a long-lasting hypothermic and hypometabolic state remain limited. Here, we present data from preclinical and clinical studies to explore the feasibility and safety of drug-induced hypothermia by administration of chlorpromazine and promethazine (C+P). In mice, C+P treatment induced hypothermia and suppressed glucose metabolism in the brain. C+P treatment reduced infarct volumes and improved neurological deficit in a mouse middle cerebral artery occlusion model induced by suture insertion. Furthermore, C+P treatment reduced body temperature, suppressed metabolism, and exerted cerebroprotective effects in a rhesus monkey model of stroke. In a double-blind, phase 1 clinical trial (NCT06663631), a total of 32 patients diagnosed with acute ischemic stroke were enrolled, receiving either placebo or increasing doses of C+P treatment: 10, 20, 50, or 100 milligrams. All doses were safe and well tolerated. Only 100 milligrams of C+P resulted in a modest and transient reduction in body temperature. Plasma proteomic profiling revealed a down-regulation of markers associated with aerobic respiration and glucose metabolism. These findings highlight the translational potential of C+P treatment and warrant a larger trial to further investigate safety and efficacy of C+P.

Lactate is increasingly recognized not only as a metabolic end product of glycolysis but also as a signaling metabolite that links metabolic reprogramming to epigenetic and transcriptional regulation through protein lactylation. Emerging evidence suggests that the lactate-lactylation axis contributes to the pathogenesis of female reproductive diseases, including endometriosis, endometrial cancer, polycystic ovary syndrome, and ovarian cancer. This review summarizes current evidence on lactate production, lactate transport, and histone/non-histone lactylation in female reproductive diseases. Available studies indicate that aberrant lactate accumulation and lactylation may influence chromatin accessibility, transcription factor activity, immune remodeling, ferroptosis resistance, steroidogenic dysfunction, and DNA damage repair. These processes may contribute to disease progression and may provide candidate biomarkers or therapeutic targets, including lactylation-related enzymes, lactate transporters, glycolytic regulators, and lactate-depleting strategies. However, the current evidence base remains dominated by cell and animal studies, and major barriers persist, including incomplete identification of bona fide reader proteins, insufficient standardization of site-specific lactylation detection, limited validation in human cohorts, and uncertainty regarding disease specificity. The lactate-lactylation axis provides a useful framework for understanding metabolic-epigenetic coupling in female reproductive diseases and may inform future biomarker development, patient stratification, and mechanism-based therapeutic strategies.

The brain-wide burden of MR-visible perivascular spaces (PVS) is age-dependent in rhesus macaques. Automated quantification in 94 male and female animals ranging 5-28 years of age demonstrated a robust association of age with PVS count and volume, and an anatomical distribution paralleling that of humans. Preliminary ex vivo microscopy confirmed that an MRI-detected tubular structure corresponded to a perivascular space. These findings begin to establish the rhesus macaque as a tractable model for understanding the role of perivascular function in age-related brain vulnerability.

Neonatal respiratory distress syndrome (RDS) is among the most prevalent morbidities in late preterm and term infants. Although the gut-lung axis has been implicated in neonatal respiratory disease, the relationship between RDS and early gut microbiome composition remains poorly characterized. This study aimed to characterize gut microbiome alterations associated with RDS and surfactant replacement therapy (SRT), and to evaluate the biological plausibility of a disease-specific probiotic intervention. Two complementary cohorts were prospectively enrolled. In the clinical observational cohort (n = 45), fecal samples collected within 48 h of birth were analyzed by Nanopore 16S rRNA sequencing across three groups: infants without RDS (control group, n = 25), infants with RDS who did not receive SRT (RDS(S-) group, n = 7), and infants with RDS who received SRT (RDS(S+) group, n = 13). In the probiotic discovery cohort (n = 40), gut microbiota of infants without RDS (CON group, n = 17) and infants with RDS (RDS group, n = 23) were characterized by metagenomic sequencing and culturomics. Candidate probiotic strains were evaluated in a fermenter for intestinal microbiota model (FIMM) and a fecal microbiota transplantation (FMT) mouse model. The RDS(S-) group exhibited depletion of beneficial taxa including Bifidobacterium and Lacticaseibacillus and enrichment of opportunistic pathogens including Enterococcus and Staphylococcus. Following SRT, gut microbial profiles partially shifted toward those of the control group. Limosilactobacillus fermentum SLAM_LAF05 and Bifidobacterium longum SLAM_BIL02 were identified as CON-enriched candidate probiotic strains through direct microbiome comparison and selected based on superior acid and bile tolerance and adhesion capacity. In the FIMM model, probiotic supplementation increased microbial diversity and suppressed opportunistic pathogens. In the FMT mouse model, probiotic supplementation was associated with upregulation of ZO-1, MUC2, and Reg3g, reduction of fecal calprotectin, and restoration of serum IgG levels. This study provides an early translational characterization of RDS-associated gut dysbiosis and its partial resolution following SRT, and establishes proof-of-concept for a disease-specific probiotic approach. These findings offer a new perspective on the interplay between gut microbial dynamics and the early postnatal respiratory course, and provide a basis for future investigations into microbiota-targeted strategies in neonates with RDS.

The RAW264.7/THP1 cells have been extensively employed as macrophage models in inflammation research. However, comprehensive comparisons of their expression profiles remain largely unexplored. In this study, we conducted a systematic bioinformatics analysis to characterize the whole-cell proteome, phosphoproteome, acetylome, and ubiquitinome profiles of lipopolysaccharide-stimulated RAW264.7/THP1 cells. Through comparative temporal analysis of differentially regulated proteins (classified as rapid, persistent, or slow dysregulation patterns), we identified IGF2, COPZ1, and GTF2B, exhibiting persistent downregulation in both cell models. Additionally, we observed that nearly all dysregulated proteins within each modification type exhibited significant enrichment in the other two modification types, forming a highly interconnected protein-protein interaction network. Notably, VIMENTIN demonstrated significant downregulation across three modification types (phosphorylation at Ser56/214, acetylation at Lys235, and ubiquitination at Lys139), with coordinated downregulation observed in both cell lines. It was also shown that VIMENTIN mutation at Ser56, Lys235, and Lys139 dramatically reduces the expression of CDK1, which may help the inflammation response by averting mitotic catastrophe and changing the macrophage cell cycle. These findings provide valuable molecular insights into species-specific macrophage responses and establish an important reference data set for discovering novel inflammatory proteins and investigating macrophage-associated diseases using these experimental models. Notably, our work delineates vimentin-centered regulatory networks that may offer novel diagnostic biomarkers and therapeutic targets for inflammatory diseases.

Neurovascular uncoupling (NVU) contributes to neurological disorders like Alzheimer's disease. While a mouse NVU model exists, a reliable rat model critical for cognitive research remains underdeveloped. To address this methodological gap, we investigated a pharmacological approach in rats using the same drugs (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH), L-NG-nitroarginine methyl ester (L-NAME), indomethacin) that proved to be efficacious in mice. The compounds were formulated as a cocktail solution and administered intraperitoneally for 13 days to aged, cognitively experienced Long-Evans rats. Our goal was to induce NVU while minimizing adverse systemic effects seen previously (e.g., hypertension, intestinal ulceration). The treatment induced only a modest (28%, non-significant) reduction in cerebral hyperaemia, with decreased prostaglandin E2 levels but unchanged 11,12-epoxyeicosatrienoic acid concentration in the brain. Cognitive effects were limited-transient impairment in the 5-choice task but no changes in spontaneous alternation, visual discrimination, cooperation, or motor learning. Significant adverse effects emerged: reduced food intake, weight loss, gastrointestinal malaise, and moderate renal toxicity. Our findings specifically highlight the challenges of achieving sufficient and symptomatically apparent NVU while minimizing systemic toxicity. While partial NVU occurred, this polypharmacy approach had major limitations. A reliable, industrially applicable rat NVU model remains urgently needed to accelerate antidementia drug development.

Synthetic modification of dansylcadaverine (1) and our previously identified dynamin I and clathrin-mediated endocytosis inhibitor S1-47 gave rise to new members of the sulfonadyns class of GTP-competitive dynamin inhibitors. Analogues in this class displayed high dynamin I, dynamin II, and clathrin-mediated endocytosis inhibition (inhibition of Tfn-A594 uptake in U2OS cells). Dynamin activity was typically low micromolar with modest to no dynamin I versus dynamin II selectivity. For all analogues excepting those with bulky biaryl-terminal substituents, CME inhibition was within 1 order of magnitude of the dynamin I/II inhibition values. Michaelis-Menten kinetic analysis confirmed the GTP-competitive nature of these compounds. Closer examination of one analogue, 13 (we call S1-178B2), showed no dose-limited off-target effects in a CEREP ExpresS profile panel (55 binding assays) screen at 10 &#x3bc;M. Moreover, S1-178B2 showed no protein kinase activity when examined against PKA, PKC2&#x3b2;, AurA/Aur2 kinase, and CaMK2&#x3b1;. Preliminary pharmacokinetic evaluation reveals that a 100 mg/kg IP injection gave a 17 &#x3bc;M blood and 32 &#x3bc;M brain concentration after 15 and 30 min, respectively. A pull-down bead based on S1-178B2 allowed the identification of both dynamin I and dynamin II, supporting on-target activity in cells. Examination of S1-178B2 in the 6 Hz psychomotor seizure test revealed a significant increase in seizure threshold at doses of 30 (p = 0.003) and 100 mg/kg ip (p < 0.0001), with the higher dose proving to be similarly effective as the first-line antiseizure medication, sodium valproate. Finally, S1-178B2 was examined in the rat kindling model of epilepsy, demonstrating a clear dose-dependent reduction in seizure duration (p = 0.012) and a reduction in severity (p = 0.09) at 100 and 300 mg/kg, comparable to another first-line antiseizure medication, carbamazepine. These results indicate that the sulfonadyns show promise as a novel class of antiseizure medication with a mechanism of action targeting CME.

The striatum plays a central role in motor control, cognition, reward processing, and habit formation, and its dysfunction is implicated in a broad spectrum of neurological and psychiatric disorders. Although animal models have provided important insights into striatal development and disease mechanisms, species-specific differences in cellular composition, developmental timing, and circuit organization limit their translational relevance to the human brain. In this context, human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, have emerged as valuable platforms for modeling human striatal development and pathology in vitro. In this review, we summarize current approaches for generating striatal cell types from PSCs, with a particular focus on medium spiny neurons (MSNs), the principal projection neurons of the striatum. We discuss key developmental principles underlying dorsal and ventral striatal specification and highlight the protracted maturation of human MSNs, which may contribute to human-specific disease vulnerability. Advances in differentiation strategies, including small molecule-based patterning, transcription factor-driven induction, and three-dimensional organoid and assembloid systems, have progressively improved the efficiency, reproducibility, and cellular complexity of PSC-derived striatal models. We further review applications of PSC-derived striatal systems in disease modeling, noting that most studies to date have focused on Huntington's disease, where these models have revealed early developmental, transcriptional, synaptic, and network-level abnormalities. More recent studies have begun to extend these approaches to other neurological conditions and to incorporate circuit-level analyses using cortico-striatal assembloids. In parallel, the growing availability of single-cell and single-nucleus transcriptomic datasets from the human striatum provides powerful reference frameworks for benchmarking the identity and maturation state of PSC-derived striatal cells. Finally, we discuss current challenges and limitations of PSC-based striatal models, including incomplete maturation, limited representation of non-neuronal cell types, and restricted applicability to psychiatric disorders. We propose that continued integration of developmental biology, public multi-omics resources, and advanced in vitro modeling strategies will be essential for advancing human striatal models and expanding their utility in translational neuroscience.

Getah virus (GetV) is an arthropod-borne alphavirus historically recognized as an emerging zoonotic pathogen of veterinary significance, particularly in livestock and equine populations across Asia and parts of the Western Pacific. Over the past several decades, its expanding ecological range, broad mosquito vector competence, and increasing frequency of animal outbreaks have positioned GetV as a growing concern for animal health surveillance, diagnostics, and vaccine development. However, beyond its established role in veterinary virology, a critical and underexplored dimension of GetV biology is its emerging potential in oncolytic virotherapy. Recent discoveries, particularly involving the M1 strain, reveal a striking capacity for tumor-selective replication driven by defects in antiviral innate immune signaling within malignant cells. This property positions GetV-derived platforms as promising candidates for next-generation oncolytic virus development, capable of direct tumor lysis and secondary activation of antitumor immunity. These findings signal a paradigm shift in how traditionally zoonotic alphaviruses may be repurposed for precision oncology. We therefore hypothesize that whilst broad cellular tropism enables Getah virus entry into different kinds of cells, the oncolytic efficacy requires another layer of intracellular permissiveness characterized by tumor-specific innate immune defects. This Perspective synthesizes the current state of knowledge on GetV from both veterinary and translational oncology viewpoints and outlines the dual-use trajectory of the virus from agricultural pathogen to therapeutic bioplatform. We further highlight unresolved questions surrounding mechanisms of tumor selectivity, biosafety and host restriction, genetic stability, immune modulation, and regulatory translational barriers. Addressing these gaps will be essential for advancing GetV-based oncolytic platforms toward clinical applicability. Collectively, GetV represents a compelling example of how emerging zoonotic viruses may be strategically repositioned at the interface of infectious disease surveillance and cancer therapy innovation.

To catalogue the ossification mechanisms operating along the proximal-distal axis of the human mandible and integrate them into a unified regional framework. Narrative review of embryological, molecular, transcriptomic, and clinical genetics evidence identified through structured searches of PubMed, Scopus, and Web of Science. The type of evidence (human, animal, in vitro, or combined) underpinning each major finding was tracked. Five non-overlapping mechanisms operate across ten mandibular regions: (i) intramembranous ossification of the body, ramus, and coronoid process; (ii) parachondral ossification, defined as intramembranous bone formation in mesenchyme adjacent to Meckel's cartilage (MC) under MC-derived paracrine guidance (BMP5, BMP7, FGF7, SEMA3A from the intermediate MC) and used as the operative descriptor for mandibular body formation; (iii) endochondral ossification of primary cartilage at the symphysis and anterior MC midsegment, via chondrocyte-to-osteoblast transdifferentiation; (iv) endochondral ossification of secondary cartilage at the condylar and angular processes, with viable hypertrophic chondrocytes and chondroid bone; and (v) perichondral ossification at the MC surface. Transdifferentiation executes mechanism (iii) and is not a separate mode. Posterior MC degradation proceeds via autophagy, apoptosis, and chondroclastic resorption, with independent chondral centres near dental primordia contributing further. Treacher Collins syndrome, cleidocranial dysplasia, and Pierre Robin sequence reflect disruptions at different mechanistic levels. The mandible is a composite structure employing multiple ossification modes in a region-specific manner; parachondral ossification most accurately characterises mandibular body formation. The framework carries translational implications for tissue engineering, distraction osteogenesis, and prenatal molecular rescue, evidenced only preclinically in a Treacher Collins mouse model.

Aberrant regulation of autophagy and persistent activation of the phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) signaling axis are recognized hallmarks of cancer progression, therapeutic resistance, and disease relapse. Coumarins, a chemically diverse class of natural and synthetic benzopyranone derivatives, have recently emerged as promising modulators of both autophagy and PI3K/mTOR signaling, positioning them as attractive candidates for next-generation anticancer strategies. This review critically examines current evidence on the ability of coumarin derivatives to regulate autophagy and PI3K/mTOR signaling in cancer, with emphasis on their mechanistic intersections, therapeutic implications, and translational potential. A structured and integrative analysis of preclinical studies was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles were identified using combinations of keywords such as "coumarins", "autophagy", "PI3K/mTOR", and "cancer". Only peer-reviewed studies written in English and reporting data from cellular or animal cancer models were included. Mechanistic evidence related to autophagy induction or inhibition, modulation of the PI3K/mTOR pathway, pharmacokinetic properties, safety considerations, and combination therapy strategies was systematically evaluated. Accumulating evidence demonstrates that coumarins can either induce or inhibit autophagic flux in a context-dependent manner, often through direct or indirect modulation of PI3K/mTOR signaling. These dual actions influence cancer cell survival, apoptosis, senescence, and sensitivity to chemotherapy. Several coumarins exhibit multitarget activity, addressing therapy resistance while maintaining favorable safety profiles. Emerging data further support their use in rational combination strategies and patient-stratified therapeutic approaches. Coumarins represent versatile molecular scaffolds capable of fine-tuning autophagy and PI3K/mTOR signaling in cancer. A deeper mechanistic understanding, alongside optimization of pharmacokinetics and patient stratification, will be essential for translating coumarin-based modulators into clinically effective anticancer therapies.

The purpose of this study was to systematically evaluate neuroprotective interventions for photoreceptor preservation in rodent models of retinal detachment (RD). A systematic search of PubMed, Embase, Web of Science, and Google Scholar identified studies evaluating neuroprotective agents in rodent RD models. The primary outcome was a reduction in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells quantified on retinal tissue sections (histology-based); secondary outcomes included preservation of the outer nuclear layer (ONL) and electroretinography (ERG). Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Thirty-six studies (2007-2025) met inclusion criteria: 19 rat, 12 mouse, and 5 combined-species. Interventions included small molecules and recombinant proteins (n = 30), monoclonal antibodies (n = 3), peptides (n = 2), and extracellular vesicle therapy (n = 1). Eight (22.2%) evaluated US Food and Drug Administration (FDA)-approved agents for non-retinal indications. Anti-inflammatory interventions achieved the highest median TUNEL reduction (84.5%, interquartile range [IQR] = 62.3%-88.1%), followed by anti-inflammatory/antioxidant approaches (70.8%, IQR = 54.3%-76.0%), metabolic modulators (59.6%, IQR = 42.9%-64.8%), and anti-apoptotic agents (59.0%, IQR = 56.6%-69.3%). Between-group differences were not statistically significant (Kruskal-Wallis P = 0.32). Quantitative ERG data were available in only six studies (16.7%). The risk of bias was largely unclear across selection and performance domains, with assessor blinding most reported (63.9% low risk). Ten studies additionally evaluated genetically modified backgrounds as complementary mechanistic strata (n = 11 experiments). Inflammation-targeted therapies showed the most consistent numerical photoreceptor rescue across rodent RD studies. With eight studies evaluating FDA-approved agents, the field has clear repurposing opportunities; closing the translational gap will require rigorously designed, functionally oriented preclinical trials that reflect clinically realistic treatment delays.

As a new generation of biomaterials, biodegradable zinc (Zn)-based implants hold substantial promise for clinical use due to their favorable biocompatibility and controllable degradation behavior. This review summarizes recent progress in Zn-based implants, focusing on the physiological roles of Zn, current Zn-based implant systems, and relevant applicable standards. To address the critical challenges faced in practical applications, such as optimizing corrosion rate, antibacterial performance, and biocompatibility, researchers have employed innovative strategies, including alloying (e.g., Zn-Mg, Zn-Mn, Zn-Li), surface modifications, and functional coatings. Meanwhile, a detailed overview is provided of in vitro and in vivo degradation evaluation systems, advances in preclinical animal studies, and the status of clinical trials, together with regulatory requirements for biodegradable metals set by domestic and international authorities. Key mechanistic and translational bottlenecks that currently limit clinical adoption are identified, together with critical directions for the rational design and standardized evaluation of next-generation Zn-based implants.

Cartilage is an avascular and aneural connective tissue vital for joint function, yet its limited intrinsic regenerative capacity poses significant challenges for treating injuries and degenerative diseases such as osteoarthritis (OA). Conventional models-including animal studies, cell lines, and primary chondrocyte cultures-exhibit considerable limitations in accurately replicating the native cartilage microenvironment, species-specific relevance, and differentiation potential. Recently, cartilage organoids have emerged as transformative tools that closely emulate the architecture, cellular heterogeneity, and extracellular matrix (ECM) properties of native cartilage, thereby offering a physiologically relevant platform for investigation. This review systematically examines the mechanisms governing chondrogenesis, including chondrocyte differentiation and matrix synthesis, as well as the construction of cartilage disease models. We focus on recent advances in cartilage organoid research, covering cultivation techniques, structural and functional characteristics, and diverse characterization methodologies. Furthermore, we highlight their applications in simulating pathological features of cartilage diseases, drug screening, toxicity testing, and gene therapy exploration. Current technological limitations-such as challenges in vascularization and mechanical strength-are discussed, together with future directions for developing multifunctional organoids and associated ethical and clinical considerations. This review aims to provide insights into the translational potential of cartilage organoids in regenerative medicine and disease modeling.

We updated WHO estimates of the global, regional, and national foodborne disease burden caused by chemical hazards. We estimated incidence, mortality, and disability-adjusted life-years (DALYs) of aflatoxins B1 and M1, inorganic arsenic, lead, methylmercury, cadmium, dioxin, peanut allergy, and cassava cyanide for 2000-21. We used data from systematic reviews, established dose-response relationships, the Global Burden of Disease Study 2021, and, where applicable, a structured expert judgment study. We used disease-specific models and a hierarchical meta-regression model with geographical clustering and global linear time trend with uncertainty propagation. In 2021, the nine foodborne chemicals caused 6&#xb7;26 million (95% uncertainty interval [UI] 3&#xb7;36-10&#xb7;30) cases, 1&#xb7;12 million (0&#xb7;40-2&#xb7;10) deaths, and 29&#xb7;8 million (12&#xb7;9-53&#xb7;1) DALYs globally. Inorganic arsenic and lead caused the highest burden. Cardiovascular diseases due to inorganic arsenic and lead caused 88&#xb7;9% of foodborne chemical deaths and 76&#xb7;5% of foodborne chemical DALYs. The greatest DALY rate was estimated for the South-East Asia region, with 789 DALYs (272-1660) per 100&#x2009;000 people mostly due to inorganic arsenic and lead (94&#xb7;2%). The region of the Americas carried the highest foodborne chemical DALY rate in children younger than 5 years, with 749 DALYs (435-1260) per 100&#x2009;000 children, mainly due to the effect of methylmercury on intellectual disability (91&#xb7;0%). DALY rates from dioxin showed the steepest decrease from 2000 to 2021. Dietary exposure to chemicals causes a substantial global disease burden. An integrated response with ongoing non-communicable disease prevention efforts is key. Granular assessment including subnational exposure contexts is essential to ensure equity. WHO.

Enterotoxigenic Escherichia coli (ETEC) is the main pathogen causing bacterial diarrhea in piglets. Ningxiang piglets (native Chinese breed) has the characteristics of stress resistance and low diarrhea rate, which is closely related to the intestinal microbial structure shaped by its high fiber feed. Our study found that Parabacteroides distasonis (P. distasonis), a representative intestinal bacterial species in Ningxiang piglets, had a positive correlation with fecal secretory immunoglobulin A (sIgA). P. distasonis strain was isolated from Ningxiang piglets and verified the regulation on intestinal injury induced by ETEC in piglets. Results showed P. distasonis could alleviate the weight loss of piglets caused by ETEC infection. P. distasonis significantly decreased the diarrhea rate and inhibited the colonization of ETEC in intestinal mucosa, while decreased the ileal mucosal IL-1&#x3b2;, IL-6 and TNF-&#x3b1; levels after ETEC infection (P&#x2009;<&#x2009;0.05). P. distasonis decreased the serum DAO activity, D-lactate and Endotoxin and upregulating the expression of small intestine mucosal sIgA. P. distasonis enhanced the expression of tight junction proteins, including claudin-1, claudin-3, occludin, and zonula occludens-1 (ZO-1), at both the transcriptional and translational levels (P&#x2009;<&#x2009;0.05). It also upregulates the expression of intestinal epithelial proliferation markers including PCNA, &#x3b2;-catenin, CHGA, Lgr5 and LYZ (P&#x2009;<&#x2009;0.05). Furthermore, P. distasonis affected the microbial structure and increased the relative abundances of beneficial genera, as well as increased the SCFAs contents in ileum of ETEC-challenged piglets. Taken together, P. distasonis could maintain the integrity of intestinal epithelial barrier, alleviate intestinal inflammation and repair intestinal barrier damage caused by ETEC, which provides theoretical basis for nutritional intervention of diarrhea in piglets.