BACKGROUND:The decreased postural control ability due to mild cognitive impairment in elderly people leads to the increased risk of falls.Dual-task is the primary research paradigm for evaluating the relationship between cognition and postural control in the scenes close to real life.The sample entropy of the plantar center of pressure(COP)displacement during standing can represent the complexity of postural control. OBJECTIVE:Based on the COP displacement sample entropy,to analyze the differences in postural stability characteristics and control strategies between older adults with mild cognitive impairment and cognitively normal older adults during the dual-task with postural control and spatial working memory,aiming to explore the impact of cognitive impairment on the postural control ability during standing. METHODS:Sixteen older adults with mild cognitive impairment and 17 cognitively normal older adults were eligible and selected for the study.They completed five test tasks,including spatial working memory,double-feet balance stance,Romberg stance,double-feet balance stance-spatial working memory dual-task,and Romberg stance-spatial working memory dual-task,with three valid completions of each task.The plantar COP data were collected by the Kistler 3D force platform.The indicators included cognitive behavior(cognitive score and reaction time)and kinematic indexes(COP displacement and sample entropy). RESULTS AND CONCLUSION:The older adults with mild cognitive impairment performed the spatial working memory task with the greatest cognitive score and the shortest reaction time,the double-feet balance stance-spatial working memory dual-task with moderate cognitive score and reaction time,and the Romberg stance-spatial working memory dual-task with the smallest cognitive score and the longest reaction time,where the differences were significant among the tasks(P<0.05).In the older adults with mild cognitive impairment,the anterior-posterior and medial-lateral COP displacements were significantly greater,and their sample entropy values were significantly smaller in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task than in the double-feet balance stance and Romberg stance tasks(P<0.05).In the spatial working memory task,there were no significant differences in cognitive score and reaction time between the both groups(P>0.05);however,in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,cognitive scores were significantly smaller and reaction times were longer in the older adults with mild cognitive impairment compared with the cognitively normal older adults(P<0.05).In the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,the older adults with mild cognitive impairment exhibited significantly greater anterior-posterior and medial-lateral COP displacements and significantly smaller sample entropy values compared with the cognitively normal older adults(P<0.05).All findings indicate that compared with cognitively normal older adults,older adults with mild cognitive impairment exhibit smaller complexity,poorer systematic adaption and decreased automatic regulation of the postural control during performing the dual-tasks,who are more susceptible to spatial working memory interference,leading to the increased risk of falls.

Avian coccidiosis, an acute parasitic disease that mainly harms chicks, is widely prevalent across the world, which poses a serious threat to poultry industry. Because of the single prophylactic formulations, veterinary clinical treatment of coccidiosis mainly relies on chemically synthesized agents, polyether ionophores and Chinese herbal medicines. The introduction of novel anticoccidial drugs is slow for a long period of time, and there is an increasing problem of anticoccidial drug resistance following long-term use, which has become an urgent problem to be solved in poultry industry. This review summarizes the levels of anticoccidial drug resistance across China from 2018 to 2023, and analyzes the resistance to various anticoccidial agents in coccidia. It is indicated that the overall prevalence of anticoccidial drug resistance is high in coccidia, and development of novel anticoccidial agents and products with reduced antibiotics use and alternatives of antibiotics is of an urgent need.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.
Hyperuricemia/microbiology* ; Humans ; Gastrointestinal Microbiome/physiology* ; Probiotics/therapeutic use* ; Uric Acid/blood* ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional

With the rapid proliferation of lithium-ion batteries in new energy vehicles and energy storage systems, increasing attention has been drawn to the occupational exposure risks and potential health hazards associated with their key cathode materials—nickel–cobalt–manganese (NCM) ternary compounds—throughout their entire life cycle. This review outlined the full life cycle of NCM materials and the occupational exposure risks that may arise during each stage. Based on the latest epidemiological and toxicological evidence, it summarized the health effects and toxicities associated with occupational exposure to NCM materials. The review further analyzed major challenges in current occupational health management system, including the limitations of existing occupational exposure limits, the lack of dedicated medical surveillance standards for NCM-related hazards, and the misalignment between occupational hygiene practices and the rapid expansion of the new-energy industry. Finally, future research directions were proposed with the aim of providing a scientific foundation for protecting worker health and supporting the sustainable development of lithium-ion battery industry.

ObjectiveTo explore the mechanism of Naoxintong capsules' intervention in cerebral ischemia-reperfusion by building a mouse cerebral ischemia-reperfusion model based on short-chain fatty acids. MethodC57BL/6J male mice were randomly divided into the sham group， model group， Naoxintong group （158.9 mg∙kg^-1）， and Ginaton group （12.1 mg∙kg^-1） according to the random number table method. The model of cerebral ischemia-reperfusion （MCAO/R） was prepared via the filament occlusion method. The effect of Naoxintong capsules on brain injury in MCAO/R mice was evaluated by the neuroethological score， cerebral infarction area determination， Nissl staining， and immunofluorescence staining. Hematoxylin-eosin （HE） staining and Western blot were employed to evaluate the effect of Naoxintong capsules on the intestinal barrier in MCAO/R mice. The content of short-chain fatty acids in mouse feces was detected by LC-MS/MS. ResultCompared to the sham group， the model group exhibited significant increases in the cerebral infarction area， neuroethological score， and cell apoptosis rate （P<0.01）， with a notable decrease in the number of Nissl bodies （P<0.01）. The protein expression levels of Claudin-1 and Occludin were significantly reduced （P<0.05）. Compared with the model group， the intervention of Naoxintong capsules significantly decreased the cerebral infarction area （P<0.05） and improved the neuroethological score （P<0.01） and cell apoptosis rate （P<0.01）， with the number of Nissl bodies （P<0.01） and expression levels of Claudin-1 and Occludin proteins （P<0.01） increased. LC-MS/MS results showed that compared to the sham group， the model group featured a significantly reduced content of acetic acid， propionic acid， and butyric acid in feces （P<0.01）， while valeric acid， isovaleric acid， and isobutyric acid levels were increased （P<0.01）. The intervention of Naoxintong capsules notably lowered the content of valeric acid， isovaleric acid， and isobutyric acid （P<0.01）. ConclusionNaoxintong capsules can improve brain and intestinal barrier damage and play a protective role in cerebral ischemia-reperfusion by regulating the content of short-chain fatty acids.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.