Donkeys (Equus asinus africanus) play a critical role in rural and peri-urban livelihoods in Kenya, supporting transportation, agriculture, and income generation. Despite their economic and social importance, donkeys remain underrepresented in national policies and development strategies. Limited data exist on the governance structures, operational challenges, and opportunities for upgrading the donkey value chain. This study aimed to map the donkey value chain, assess governance frameworks, identify constraints, and explore upgrading opportunities across diverse Kenyan production systems. A cross-sectional study was conducted in seven purposively selected counties-Bungoma, Kitui, Nairobi, Kiambu, Narok, Turkana, and Nakuru-to capture variation across agro-ecological zones and rural-urban divides. Data were collected through Key Informant Interviews and Focus Group Discussions with government officials, donkey owners, transporters, and other value chain actors. Thematic analysis was performed using Taguette software, while quantitative data were summarised to show key value chain nodes and trends. Findings revealed that the donkey value chain is largely informal, with minimal regulatory oversight and fragmented markets. Inputs such as, veterinary services, and feed were accessed primarily through informal networks, with market dynamics influenced by seasonal labour demands. Donkeys were predominantly used for transporting farm produce, firewood, water, and waste, while their manure was used for agricultural fertilization and pest control. Donkey milk, though not widely consumed, was used in some communities for treating respiratory ailments such as asthma and tuberculosis. In Turkana County, donkey meat consumption persisted as a cultural practice, contrasting with other regions where donkeys were primarily working animals. Weak governance structures facilitated illegal donkey trade and theft, contributing to a rapid decline in donkey populations, particularly following the establishment and subsequent closure of donkey abattoirs that fuelled demand for skin. Sustaining the donkey sector requires strengthening regulatory frameworks to enhance animal welfare, control illegal trade, and improve service delivery. Formal integration of donkeys into national livestock policies is crucial for unlocking investment in donkey-related research, improving access to veterinary care and quality inputs, and scaling up the productive and medicinal use of donkey-derived outputs such as milk and manure.
To study biochemical mechanisms underlying the development of autism spectrum disorders (ASD), an experimental model based on early postnatal administration of valproic acid (VPA) to Wistar rats was used. Social behavior impairments characteristic of ASD was accompanied by cognitive impairments and were associated with the increased neutrophil elastase (NE) activity in the serum and cerebellum of the rats treated with VPA. Increased NE activity in the cerebellum may indicate development of neuroinflammation. Impaired antioxidant defense under the influence of VPA was manifested by the increased glutathione S-transferase (GST) activity in the serum and cerebellum of rats. Correlation analysis revealed a link between the NE activity and formation of social behavior in animals. Enzymes of glutamate metabolism (glutamate dehydrogenase and glutamine synthetase) and antioxidant defense enzymes that regulate oxidative stress (OS) levels correlated with formation and maintenance of the acquired skills in both control and experimental animals.
The study evaluated the knowledge and practices of small-scale dairy farmers regarding trace mineral supplementation in Malawi, including the socio-economic challenges they face and the implications for cow nutrition, productivity, and welfare. Interviews with 172 farmers across two agro-ecological zones revealed that most farmers rely on imported supplements from agro-veterinary shops, with only a small minority formulating their own mixes. Although the majority reported increased milk production following supplementation, very few tailored mineral delivery to specific animal requirements, such as growth stage or lactation phase. Interestingly, ordinary salt and mineral blocks were the most common forms of supplementation. Unconventional sources like crushed eggshells were used by about one‑third of farmers, reflecting adaptive responses to high cost and limited availability. Notably, neither formal education nor years of dairy experience was associated with effective supplementation practices. Key challenges to supplementation included high ingredient cost, poor availability of quality supplements, and limited technical knowledge. The study highlighted that small-scale dairy farmers frequently rely on generalized recommendations for trace mineral supplementation amid unreliable supply chains. This practice may exacerbate trace mineral deficiencies or overfeeding, with negative consequences for animal health and productivity, underscoring the need for developing region‑specific guidelines, enhanced farmer capacity building, and strengthened local supply chains.
Dystocia in dairy cattle presents significant challenges to productivity and animal welfare, leading to increased stillbirths, calf mortality, and reduced fertility. This study employs Fuzzy Decision-Making Trial and Evaluation Laboratory-Analytic Network Process (FDANP) and Fuzzy Analytic Hierarchy Process (FAHP) methodologies to analyze and prioritize the multifactorial causes of dystocia, integrating expert judgments and addressing uncertainties through fuzzy logic. Following the collection of data from experts through a questionnaire, the findings indicated that the FDANP identified calf weight, the body condition score of the dam, and the calving interval as the most significant factors influencing dystocia. In contrast, parity, calf sex, and multiple births were determined to have the least impact on this condition. Furthermore, the FAHP method, which does not measure the criteria of influence and susceptibility, highlighted milk period, calf weight, and gender status as the most important factors. This divergence is expected, as FDANP captures the systemic causal structure-where factors like body condition score and calving interval have broad influence-while FAHP reflects direct, hierarchical judgments of importance, often placing greater weight on intrinsic attributes like parity. The study introduces a novel approach by combining breeder expertise with advanced analytical methods, providing a comprehensive framework for understanding and managing dystocia in dairy cattle. The integration of fuzzy logic accommodates the inherent uncertainties and variabilities in expert opinions, enhancing the robustness of the analysis. This research underscores the importance of expert ideas and comprehensive management strategies in mitigating dystocia risks, ultimately aiming to improve animal welfare and economic outcomes in dairy operations. Also, this comparative study represents a significant advancement in the field of dairy cattle production as, to the best of our knowledge, it provides the first framework for conducting more effective strategies within this domain using a comparative fuzzy multi-criteria decision making (MCDM), approach. Furthermore, the study outlines recommendations for future research, aimed at enhancing the applicability of these methods in dairy cattle production systems.
While the therapeutic potential of hypothermia for treating tissue damage has been investigated for over 90 years, its effectiveness is still debated. This review introduces the history of hypothermia in medicine first, followed by a description of cellular mechanisms behind its neuroprotective effects observed in animal studies and some clinical studies. The next section focuses on current cooling approaches/devices, as well as cooling parameters recommended by researchers and clinicians to maximize the benefits of hypothermia. Animal and clinical studies of implementing hypothermia for spinal cord and brain tissue injury are presented next. The outcomes in treating conditions like traumatic brain injury (TBI), spinal cord injury (SCI), stroke, and cardiopulmonary issues will be discussed in detail. The review also examines the risks and benefits of hypothermia, supported or disputed by clinical studies. Contributions from bioengineers in the research field are presented in the last section, with details of cooling device design and theoretical simulations. Ultimately, the review highlights that successful hypothermia treatment hinges on achieving targeted tissue cooling quickly after injury, with mild hypothermia often being proven as effective as deeper cooling, provided a slow rewarming rate is implemented.
Hot flashes are a common vasomotor symptom (VMS) experienced by postmenopausal women. In rodents, VMS-like symptoms can be assessed by monitoring tail skin temperature (TST), which reflects thermoregulatory changes. However, because the TST is highly sensitive to handling and environmental stresses, a reliable assessment requires continuous monitoring under low-stress and unrestrained conditions. In this study, we established a monitoring system for aged Wistar rats and evaluated hot flash-like symptoms using a within-subjects design across four physiological states: intact, ovariectomized (OVX), 17β-estradiol (E2) treatment, and E2 withdrawal. E2 treatment significantly decreased dark-phase TST (26.63 ± 0.26°C) compared with OVX (29.39 ± 0.18°C), and this effect was reversed upon pellet removal. We also quantified ΔTST, defined as the difference between light- and dark-phase TST, and found that E2 treatment markedly increased ΔTST, indicating an estrogen-dependent restoration of circadian TST amplitude. Because aged rats exhibit irregular estrous cycles and reduced ovarian steroidogenesis, yet remain underutilized in VMS research, this model provides a physiologically relevant platform for studying menopausal vasomotor dysfunction. By repeatedly monitoring the same individuals, inter-individual variability is minimized and reliable detection of within-subject changes is achieved with a small number of animals. These findings demonstrate that our method enables reliable long-term TST monitoring under unrestrained conditions and offers a practical and validated approach for investigating the pathophysiology of menopausal vasomotor dysfunction and for screening candidate compounds targeting hot flash-like symptoms in rodents.
Tumor cell metastasis through blood circulation is a complex process and is one of the great challenges in cancer research as metastatic spread is responsible for ∼90% of cancer-related mortality. Tumor cell intravasation into, arrest and adhesion at, and extravasation from the microvessel walls are critical steps in metastatic spread. Understanding these steps may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to and regulators of the material exchange between circulating blood and body tissues. The cleft between adjacent endothelial cells is the principal pathway for water and solute transport through the microvessel wall in health. This cleft has been found to be the location for tumor cell adhesion and extravasation. The blood flow-induced hydrodynamic factors such as shear rates and stresses, shear rate, and stress gradients, as well as vorticities, especially at the branches and turns of microvasculatures, also play important roles in tumor cell arrest and adhesion. This chapter first reports the current advances from in vivo animal studies and in vitro culture cell studies to demonstrate how the endothelial integrity or microvascular permeability, hydrodynamic factors, microvascular geometry, cell adhesion molecules, and surrounding extracellular matrix affect critical steps of tumor metastasis in the microcirculation. One addition of this updated chapter shows the role of glycocalyx at tumor cells in tumor cell metastasis. Another addition describes a new in vitro 3D-microchannel model for tumor metastasis in the microcirculation.
Rathi cattle, an indigenous Bos indicus breed of north-western India, represent a valuable genetic resource due to their adaptation to arid environments, heat tolerance and dairy potential. However, genomic information on this breed remains limited. This study provides the first double-digest restriction-site associated DNA sequencing (ddRAD) based genome-wide assessment of Rathi cattle using a large sample size. A total of 96 animals were genotyped, generating 78,193 high-quality SNPs with 96.52% alignment to the Bos taurus (ARS-UCD2.0) reference genome, guaranteeing dependable variant identification. The population exhibited moderate genetic diversity with nucleotide diversity (π = 0.33 ± 0.09) and heterozygosity (Ho = 0.291 ± 0.084; He = 0.329 ± 0.104). Runs of homozygosity (ROH) made up 5.43% of the genome, and most of them were short segments (< 2 Mb), which shows that there hasn't been much inbreeding lately (FROH = 0.0512). Effective population size (Ne) declined from 1454 (150 generations ago) to 94 at present, highlighting the impact of demographic bottlenecks and genetic drift. The declining Ne suggests a risk of future genetic erosion, highlighting the need for effective conservation and breeding strategies. Population structure analyses (PCA, ADMIXTURE and STRUCTURE) revealed clear genetic distinctness of Rathi from other indigenous dairy breeds, despite its composite origin. Selection signature analyses (Tajima's D, CLR, ROH islands and iHS) identified candidate regions harboring genes associated with immunity (IL2RB, USP18), reproduction (INHBA, MEI4, HBA), lactation (LRRC8D, TRERF1, CCND3) and stress adaptation (CARHSP1, ITGAV). These findings are highlighting the valuable insights about diversity, demographic history and adaptive potential of rathi and offering genomic resources for conservation, sustainable utilization and genetic improvement programs.
The α-ketoglutarate dehydrogenase complex (KGDHC) serves as a master regulator of cell's molecular machinery. Beyond its classical role as a rate-limiting enzyme in the tricarboxylic acid (TCA) cycle, KGDHC has emerged as a critical redox sensor that can act as both a source and a target of reactive oxygen species (ROS), thereby regulating cellular redox homeostasis. This review summarizes evidence from genetically modified animal models and cell culture studies demonstrating that compromised KGDHC activity affects neuronal metabolism, redox homeostasis, and cellular signaling. KGDHC dysfunction causes mitochondrial failure, resulting in reduced ATP synthesis and activation of AMP-activated protein kinase (AMPK). Although inhibition of KGDHC reduces mitochondrial ROS formation, it also disrupts physiological ROS-dependent signaling mechanisms. In KGDHC-deficient mice, impaired ROS signaling and energy deficit decrease brain adaptability, increase susceptibility to neurotoxins, and disrupt crucial pathways by downregulating PGC-1α and Nrf2. These alterations result in suppression of antioxidant defences and lead to neuronal death in the hippocampus and memory impairment. Moreover, KGDHC dysfunction induces mitochondrial fragmentation and is strongly linked to excitotoxicity, further accelerating neuronal dysfunction. As observed in heterozygous models, even partial KGDHC deficiency can exacerbate persisting cellular and mitochondrial defects, leading to the development of more severe pathological conditions.
Sex-specific interactions between neurosignaling systems, which generate, propagate, and terminate signals in nervous tissue, and metabolic pathways that support these processes may underlie sex differences in adaptation and therapeutic efficacy. This study aimed to characterize these interactions as systemic indicators of sex-specific adaptive responses in a rat model of metabolic stress induced by the inhibition of pyruvate dehydrogenase complex (PDC), which catalyzes the key reaction linking anaerobic glycolysis to aerobic glucose oxidation. To inhibit brain PDC, we used a single intranasal administration of methyl acetylphosphinate (MeAcP), a phosphinate analog of pyruvate, or dimethyl acetylphosphonate (AcPMe2), a membrane-permeable precursor of phosphonate pyruvate analogs. Effects were assessed 24 h post-administration by measuring biochemical and physiological parameters in the cerebral cortex, including glutamate levels, glutamine synthetase (GS) activity, and activities of enzymes in the tricarboxylic acid (TCA) cycle and affiliated pathways. Neurosignaling was evaluated using surrogate indicators: ECG (electrocardiogram) parameters and spontaneous behavior in the open field test. Relationships between measured parameters were analyzed using Spearman's rank correlation coefficients, with the correlation strength classified according to the Chaddock's scale. In control animals, no sex differences were observed in the mean values of biochemical or ECG parameters. However, behavioral parameters (e.g., grooming and locomotion) and the overall structure of correlations between the studied parameters exhibited marked sex dependence. In control females, strong correlations were detected between ECG parameters and GS activity, whereas in males, ECG parameters were strongly associated with malic enzyme (ME) activity. Male controls also showed strong correlations between locomotor/exploratory behavior and activities of ME, PDC, and 2-oxoglutarate dehydrogenase complex (OGDC). Administration of PDC inhibitors induced a sex-specific reorganization of relationships between neurosignaling indicators and glutamate metabolism, which eliminated pronounced sex differences in locomotor activity observed in controls, while revealing new sex-related differences in glutamate levels, glutamate dehydrogenase (GDH) and ME activities, grooming bout duration, and freezing time. The reduction in glutamate levels observed in females following PDC inhibition was consistent with the established decrease in de novo glutamate synthesis from glucose under conditions of impaired substrate flux through the TCA cycle. Overall, these findings demonstrate that the relationships among metabolic, behavioral, and ECG parameters are inherently sex-specific. Moreover, the homeostatic response of the cerebral cortex to PDC inhibition reshapes these relationships, thereby modifying sex-dependent biochemical and behavioral characteristics observed under control conditions.
We present a new set of English property norms for 260 object concepts based on the standardized Snodgrass and Vanderwart (1980) picture set. For each object, 100 participants provided a basic-level label (dog), a superordinate category (animal), and three features (bark, tail, fur), yielding a dataset of 78,000 features. Our norms differ from other datasets in four important ways: they (1) probe basic-level information, (2) separate taxonomic and feature information, (3) use open-ended responses for natural descriptions, and (4) include a larger number of responses per object (100 vs. ~ 30 participants in other norms). We analyzed feature statistics such as frequency, distinctiveness, and co-occurrence, and contrasted our norms with those of McRae et al. (2005), CSLB (Devereux et al., 2014), and Hovhannisyan et al. (2021). Compared to picture-based norms, our data-derived from black-and-white line drawings-elicited more diverse features and aligned more closely with language-based norms, particularly CSLB. We assessed the generalizability of our norms using an object-property congruency task, where 144 participants judged whether properties (basic level, superordinate, and features) were related to objects. Objects were shown in three picture formats with increasing ecological validity: (1) colored line drawings, (2) realistic photographs, and (3) realistic photographs of objects in scenes. We then contrasted these data with those of Antal & de Almeida (2024) employing the original line-drawing set. Agreement rates for object-property pairs remained high across picture formats and property types. Bayesian inference revealed minimal variability in congruency judgments across picture formats, with responses tightly clustered around zero. Results show that our norms are generalizable to realistic visual stimuli. Norms are available at https://osf.io/c6brw/overview .
Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is characterized by neuroinflammation and neurodegeneration. Both the innate and adaptive immune systems, with effector cells such as B and T lymphocytes, are critically involved in the pathogenesis of MS. Existing disease-modifying therapies have limited efficacy against progressive MS, and there is a strong need to identify new drug targets. Investigating how peripheral organs influence lymphocyte dynamics in the pathogenesis of MS may provide new insights for identifying novel therapeutic targets. The spleen is the largest secondary lymphoid organ with several immunological roles, including the activation of naïve CD4+ T cells. In this study, we investigated the contribution of the spleen to experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, in splenectomized (SPX) mice. SPX mice exhibited more severe EAE symptoms and larger demyelinated areas than sham-operated controls. SPX mice showed enhanced T-helper type 1 (Th1) differentiation at the onset of the disease and increased activation of ionized calcium-binding adapter molecule 1 (Iba1)-immunopositive myeloid cells at the peak of the disease. Thus, we inferred that the spleen plays an important role in the pathology of EAE by regulating microglial activation and macrophage infiltration during the disease's acute phase.
Biofilm-associated oral infections, including dental caries, periodontitis, and peri-implantitis, remain fundamentally challenging to manage due to the highly dynamic oral microenvironment and the intrinsic tolerance of multispecies biofilms to conventional antimicrobial strategies. In this context, stimuli-responsive metal-organic frameworks (MOFs) have emerged not merely as drug carriers, but as programmable platforms capable of integrating environmental sensing, on-demand activation, and multimodal antibacterial action. This review critically re-examines smart MOF-based antibacterial systems through the lens of the oral microenvironment, highlighting how pH fluctuations, enzymatic activity, inflammatory redox stress, and biomechanical forces collectively govern MOF stability, activation, and therapeutic performance. We establish oral-specific design principles for stimuli-responsive MOFs, systematically analyze representative MOF families-including ZIFs, Zr-based frameworks, porphyrinic MOFs, and MIL-series materials-and delineate key activation mechanisms driven by pH, enzymes, redox cues, and light. Particular emphasis is placed on the integration of photodynamic therapy (PDT) with controlled antibiotic release, where MOFs enable spatially confined, synergistic disruption of biofilms while mitigating off-target toxicity and antimicrobial resistance. Beyond mechanistic insights, we critically evaluate preclinical evidence across in vitro, ex vivo, and animal models, and identify translational bottlenecks related to biosafety, ion release control, material reproducibility, and clinical deployment in the oral cavity. By bridging oral pathophysiology with materials engineering, this review provides a conceptual and practical framework for the rational design of next-generation, adaptive MOF systems, and offers guidance for prioritizing research directions with the greatest potential for clinical impact in precision antibacterial dentistry.
Metastatic castration-resistant prostate cancer (CRPC) remains a clinical challenge, and epithelial-mesenchymal transition (EMT) contributes to metastatic progression and reduced response to therapy. However, the upstream epigenetic mechanisms that sustain EMT programs in advanced prostate cancer (PCa) are not fully defined. We identify the histone H3 lysine 9 (H3K9) methyltransferase SET domain bifurcated 1 (SETDB1) as a key regulator of EMT and metastasis through direct repression of RhoB, the small GTPase. SETDB1 is genomically amplified and transcriptionally upregulated in metastatic CRPC, and SETDB1 depletion reduces cell migration, invasion, and metastatic dissemination. Integrated chromatin profiling and transcriptomic analyses demonstrate that SETDB1 occupies the RhoB promoter and mediates its transcriptional silencing through H3K9 methylation. Restoration of RhoB reverses EMT gene expression and suppresses invasive behavior, whereas RhoB knockdown rescues the effects of SETDB1 depletion, establishing RhoB as a critical downstream effector of SETDB1 function. Androgen signaling inhibitor-resistant PCa models exhibit RhoB loss and EMT activation, linking this axis to therapy-resistant phenotypes. Finally, antisense oligonucleotide-mediated SETDB1 silencing restores RhoB expression and suppresses EMT and invasion in CRPC cell models. Together, these findings define a SETDB1-RhoB epigenetic pathway that promotes EMT and metastatic progression in PCa and may be therapeutically targeted in advanced disease. Prostate cancer is a leading cause of cancer-related death in men. Although many patients initially respond to hormone therapies that block androgen receptor signaling, advanced prostate cancer often becomes resistant to treatment and spreads to other organs. One process that helps cancer spread is called epithelial–mesenchymal transition (EMT), in which tumor cells become more mobile and invasive. In this study, we investigated how the protein SETDB1 contributes to prostate cancer progression. We found that SETDB1 suppresses the tumor suppressor gene RHOB, which normally helps prevent EMT and cancer cell migration. Using genomic, molecular, and animal models, we showed that increased SETDB1 activity promotes EMT, invasion, and metastasis in prostate cancer. Importantly, restoring RhoB reversed many of these aggressive features. These findings identify the SETDB1–RhoB pathway as a potential therapeutic target for advanced prostate cancer.
Globally, the pathogen-driven enteric diseases remain a leading cause of morbidity and mortality, disproportionately affecting populations in low-income regions. While significant strides have been made in vaccine research, challenges such as high production costs, complex manufacturing processes, and inefficient distribution continue to hinder global vaccine accessibility. To overcome these challenges, plant-based edible vaccines have emerged as a promising and innovative alternative, offering advantages such as affordability, ease of administration, and reduced reliance on cold-chain infrastructure. This study presents a comprehensive overview of recent advances in the development of edible plant-derived vaccines, highlighting the strategic evolution from conventional genetic engineering to more refined and scalable biotechnological methods. In the work, various applications targeting diseases such as measles, hepatitis B, rabies, dengue, and norovirus, are discussed as well as veterinary vaccines for livestock and aquaculture. The significant progress in creating vaccines targeting prevalent human pathogens is examined and the discussion is extended to include edible vaccines developed for livestock, underscoring their role in both public and veterinary health. Furthermore, the review emphasizes the transformative potential of 'omics' technologies, such as genomics, proteomics, and metabolomics, as well as artificial intelligence in streamlining vaccine design, improving antigen expression, and accelerating development timelines. This assessment review was conducted by performing a comprehensive literature survey of peer-reviewed articles. By integrating multidisciplinary insights, the work underscores the feasibility and future prospects of edible plant vaccines as a sustainable solution to global immunization challenges, with practical applications in improving vaccine accessibility, enhancing outbreak preparedness, and supporting immunization efforts in resource-limited settings. It aims to inform and inspire continued research and collaborative innovation in this emerging field with significant implications for global public health.
This network meta-analysis involved nine randomized controlled trials, comprising 595 participants (average age = 37.8 years, 55.3% female, 83.9% schizophrenia spectrum disorders), evaluating the comparative risk-benefit profiles of glucagon-like peptide-1 receptor agonists in individuals with obesity comorbid with mental illness. Outcomes included body weight (primary); body mass index (BMI); waist circumference; blood-based measures, including fasting plasma glucose, hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; systolic and diastolic blood pressure; death; all-cause discontinuation; adverse event-related discontinuation; serious adverse events (SAEs), injection site-related adverse events, headache, dizziness, nausea, vomiting, constipation, and diarrhea; psychiatric hospitalization; and changes in overall schizophrenia symptoms. Treatment arms comprised subcutaneous exenatide (S-EXE)(twice-daily [BID]/once-weekly [QW]), subcutaneous liraglutide (S-LIR)(once-daily [QD]), and subcutaneous semaglutide (S-SEM)(QW), alongside a control group (placebo, k = 8; non-placebo, k = 1). S-LIR(QD) and S-SEM(QW) were significantly associated with reduced body weight compared with control, with standardized mean differences (95% confidence intervals) of -0.945 ( - 1.784 to -0.106) and -2.101 ( - 2.978 to -1.224), respectively. S-LIR(QD) was associated with waist circumference and HbA1c level reductions, lower SAE incidences, and higher nausea, vomiting, and constipation incidences compared with the control. S-SEM(QW) was associated with reduced BMI, waist circumference, fasting plasma glucose, and HbA1c levels, and higher nausea, vomiting, and constipation compared with the control. Each drug did not differ from control regarding other outcomes. S-SEM(QW) may be the preferred treatment option, given its largest estimated effects versus control on body weight; however, its comparative ranking is uncertain due to sparse networks, substantial heterogeneity, and predominant indirect evidence.
Adipogenesis, a crucial physiological process, serves to safely sequester lipids, thereby preventing lipotoxicity in peripheral organs and preserving metabolic health during obesity. While insulin signaling plays a pivotal role in adipogenesis, regulating factors, especially the braking mechanism governing this process, warrant further investigation. Our study identified proteasome-dependent degradation of the insulin receptor (IR) during the early stages of adipogenesis as a critical event for the mitotic clonal expansion phase of the adipocyte differentiation program. A series of studies confirmed that the ubiquitinated modification of IR is regulated by E3 ligase FBXO2, and this is based on IR phosphorylation. We further elucidated that the FBD domain of FBXO2 is indispensable for its function in catalyzing p-IR ubiquitination. Gain or loss of function of Fbxo2 inhibited or promoted SVF or 3T3L1 cells proliferation and adipogenesis both in vitro and in vivo, which regulated adipose hyperplasia and plasticity of adipose tissue. Moreover, FBXO2 played an important role in regulating the metabolic health of mice when subjected to caloric excess. Collectively, our findings unveil FBXO2 as a negative regulator of adipogenesis by impairing the insulin signaling pathway.
A simultaneous rapid test method for pesticide residues in livestock products by LC-MS/MS was developed and validation tests were conducted. For the extraction method, the QuEChERS method was applied, and samples were extracted with acetonitrile, followed by salting out and dehydration. For purification, C18 and PSA columns were used instead of GPC. Based on the validity guidelines of the Ministry of Health, Labor and Welfare, 48 pesticide residues were evaluated at 0.01 μg/g and 0.1 μg/g for cattle muscle, swine muscle and milk. The trueness of the method for 43 pesticides in all three types of food samples was 70-120%, with satisfactory repeatability and within-laboratory reproducibility. Thus, this method demonstrated the usefulness of simultaneous rapid testing for pesticide residues in livestock products.
Thymic epithelial tumors (TETs) are heterogeneous neoplasms. While most early-stage cases are curable after resection, advanced or aggressive subtypes have limited treatment options and poor outcomes. The molecular mechanisms underlying their metabolic reprogramming remain poorly understood. Proline-rich Coiled-coil 2a (PRRC2A), a N6-methyladenosine (m6A) reader protein, is significantly upregulated in TET tissues and is associated with poor clinical outcomes. Multi-omics analyses and molecular experiments revealed that PRRC2A binds to m6A-modified sites within the NCOA4 mRNA, thereby stabilizing NCOA4 transcripts and enhancing its protein expression. Elevated NCOA4 interacts with PKM2, a rate-limiting glycolytic enzyme, resulting in increased glycolysis and promoting TETs progression. In vivo experiments showed that inhibition of PRRC2A suppressed tumor growth and metastasis in TETs, while combined treatment with the PKM2 inhibitor C599 and PRRC2A knockdown produced enhanced antitumor effects. These findings provide novel insights into the glycolytic metabolic regulation of TETs and suggest that the PRRC2A-NCOA4-PKM2 axis represents a promising therapeutic target.