The presence of microcystin-LR (MC-LR) poses a grave threat to both ecosystems and public health. Some studies have indicated that MC-LR can result in neurotoxicity, yet the specific mechanisms and effects remain unclear. This research used brain organoid models and mouse models to investigate the neurotoxic effects and mechanisms associated with MC-LR exposure. Findings from microelectrode array (MEA) assessments demonstrated a statistically significant reduction in both discharge activity and the number of neurons in the cerebral organoid upon acute exposure to MC-LR (P < 0.05). TUNEL (TdT-mediated dUTP nick end labeling) staining indicated that MC-LR exposure led to neuronal death and reduced neuron numbers in brain organoids. Meanwhile, the exposure of 12-month-old mice to low concentrations of MC-LR (0, 1, 60, and 120 μg/L) was found to lead to a decrease in the number of neurons based on histopathological and biochemical analyses. Moreover, long-term exposure to MC-LR also activated the JNK/NF-κB signaling pathway in the hippocampal region of the mouse brain tissue. The qPCR analysis demonstrated increased expression levels of the inflammatory markers nlrp3, caspase-1, il-18, il-6, and the pyroptosis-related marker gsdmd in hippocampal neuron tissue from groups exposed to 60 μg/L and 120 μg/L of MC-LR in mice. These results are consistent with those of the Western blot analysis. This study elucidated that prolonged exposure to MC-LR triggered activation of the JNK/NF-κB signaling pathway, neuroinflammation, neuronal pyroptosis.

Tri-ortho-cresyl phosphate (TOCP) is a widely used organophosphate ester with established multiple organ toxicity, yet its neurotoxic mechanisms remain incompletely elucidated. This study integrated network toxicology, molecular docking, and animal experiments to investigate the molecular mechanisms underlying TOCP-induced sciatic nerve toxicity. A total of 173 potential targets were identified through public databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these targets are significantly involved in autophagy, apoptosis, glycerolipid metabolism, and multiple neurodegenerative pathways. Focusing on four core targets (BECN1, SQSTM1/p62, SLC7A11, GLUL), molecular docking demonstrated strong binding affinities between TOCP and these proteins (binding energies < -5 kcal/mol). In a hen model, TOCP exposure (750 mg/kg, single oral gavage) induced marked sciatic nerve damage, characterized by myelin disruption and axonal degeneration. Western blot analysis further validated protein expression changes: compared with the control group, TOCP exposure upregulated Beclin-1, SQSTM1/p62, LC3II/Ⅰ, NCOA4, ACSL4, and Fe2+ levels by 1.919-, 2.443-, 1.497-, 1.506-, 1.243-, and 1.669-fold, respectively (P < 0.05), while downregulating SLC7A11, GLUL, FTH1, and GPX4 expression to 0.458-, 0.893-, 0.813-, and 0.573-fold of the control levels (P < 0.05). Collectively, these findings demonstrate that TOCP exerts neurotoxicity primarily by disrupting autophagic balance and impairing the oxidative defense system. This study provides novel insights into the molecular mechanisms of TOCP-induced sciatic neurotoxicity and offers a theoretical foundation for its prevention and treatment.

Background: Persistent exposure to toxic heavy metals through contaminated drinking water is now a critical global environmental and public health issue. Cadmium (Cd), arsenic (As), and mercury (Hg) are elements with high nephrotoxic properties and are able to induce oxidative stress, renal dysfunction, and progressive cellular injury after long-term exposure. Objective: To assess the effect of chronic exposure to waterborne Cd, As, and Hg on renal function parameters and oxidative stress biomarkers in the chronically exposed population. Methods: A cross-sectional analysis was performed from January 2025 to August 2025 involving 160 participants. The exposed group included 100 individuals with long-term consumption of contaminated groundwater, while 60 healthy individuals consuming treated water served as controls. Blood and urine samples were collected to measure serum creatinine, blood urea nitrogen (BUN), serum uric acid, estimated glomerular filtration rate (eGFR), urinary albumin, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx). The heavy metal levels were assessed using atomic absorption spectrophotometry. Results: Cadmium, arsenic, and mercury levels in blood were found to be significantly higher in the exposed individuals as compared to the control (p<0.001). The renal function parameters were significantly elevated serum creatinine, BUN, serum uric acid, and urinary albumin, in addition to significantly decreased eGFR among the exposed participants. The antioxidant enzymes such as SOD, catalase, and GPx were found to be significantly reduced, while MDA levels were found to be significantly increased in both groups (p<0.001). Heavy metal concentrations, renal function markers, and oxidative stress markers showed good correlation. Conclusion: Waterborne toxic elements can be a significant cause of renal dysfunction and nephrotoxicity in chronically exposed populations, likely through oxidative stress.

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of anthropogenic, persistent, and highly toxic PAH contaminants associated with developmental toxicity, 9-fluorenone (9-FLO) is a typical member of the OPAH family. Due to its ketone group, it has higher polarity, which results in increased solubility in water and greater potential for transport via atmospheric particles or water bodies. Polyethylene (PE), an amorphous polymer, is characterized by high diffusivity, high permeability, and a large internal molecular free volume, which confers a strong absorption capacity for organic pollutants. The effects of individual and combined exposures to these two common environmental pollutants on aquatic life remain unclear. In this study, we evaluated the effects of PE and 9-FLO exposure on growth, development, metabolism, and behavior using zebrafish as a model organism. We employed methods and techniques such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking, automated behavior analysis, microscopy imaging, and real-time fluorescence quantification. Zebrafish embryos at 2 h post-fertilization (hpf) were exposed to PE and 9-FLO, both individually and in combination. Our studies showed that exposure to PE or 9-FLO alone increases embryonic mortality and decreases hatchability compared to the control group. The 9-FLO group exhibited delayed hatching and inhibited larval length growth. The exposed groups showed a loose arrangement of telencephalic neurons, partial apoptosis, decreased dopamine (DA) content, increased serotonin (5-HT) content, decreased exercise capacity, reduced rhythmic amplitude, and increased rest time. The combined exposure group showed a slight alleviation of these effects compared to the single exposure groups but still exhibited significant differences from the control group. In summary, early exposure to PE and 9-FLO in zebrafish embryos, whether alone or in combination, affects growth, development, apoptosis, neurotransmitter release, and motor behavior of zebrafish neurons.

This study investigated the protective effects of resveratrol (Res) against tri-o-cresyl phosphate (TOCP)-induced spinal cord neurotoxicity in adult hens, focusing on its modulation of ferroptosis via the p62/Keap1/Nrf2 pathway. Resveratrol is a classical neuroprotective compound with antioxidant properties and the ability to activate Nrf2. Adult hens were assigned to six groups: Control, TOCP, Ferrostatin-1 (Fer-1), Ferrostatin-1 + TOCP, Resveratrol, and Resveratrol + TOCP. Spinal cord tissues were analyzed using behavioral OPIDN scoring, histology (hematoxylin-eosin and Nissl staining), biochemical assays, and Western blotting for ferroptosis- and p62/Keap1/Nrf2-related proteins. TOCP exposure induced severe ultrastructural damage, including myelin sheath disruption and neuronal degeneration, along with increased malondialdehyde (MDA) and Fe2+ levels and decreased glutathione (GSH) and superoxide dismutase (SOD) activity. Western blot analysis demonstrated upregulation of NCOA4, ACSL4, Nrf2, P62, and LC3 II, with downregulation of GPX4, SLC7A11, FTH1, and Keap1. Resveratrol treatment significantly attenuated these molecular, biochemical, and histopathological alterations, mitigating oxidative stress and ferroptotic changes.

Exposure to graphene oxides (GOs) may induce neurotoxic effects, but the mechanisms and extent of these effects remain unclear, partly due to limitations in traditional neurotoxicity models. In this study, we utilized 3D human brain organoids and zebrafish larvae to investigate GO-induced neurodevelopmental toxicity. In 3D human brain organoids, GOs significantly reduced cellular viability in a dose-dependent manner, with bulk RNA-sequencing indicating minimal impact on neuron-related pathways. However, single-cell RNA-sequencing revealed significant alterations in glutamatergic and GABAergic neurons, particularly in gene ontology terms related to synaptic function and neuronal development. Further analysis showed that GO exposure affected the localization, morphology, and electrophysiological activity of GABAergic neurons. Additionally, key genes involved in neurodegeneration (ko05022) and protein processing in endoplasmic reticulum (ko04141) were dysregulated in GABAergic neurons. In vivo studies using zebrafish larvae demonstrated altered locomotor behaviors, including hyperactivity during dark cycles and reduced swimming distances during light cycles, alongside a loss of GABAergic neurons in specific brain regions. These findings highlight the potential neurodevelopmental toxicity of GOs, especially through their impact on GABAergic neurons, and underscore the value of combining 3D human brain organoids and zebrafish models with single-cell resolution techniques to better understand the neurotoxic effects of nanomaterials.

Objective To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods Forty Male C57BL/6J mice were randomly divided to four groups(Control, IR, IR+Rg1, Rg1), IR+Rg1and Rg1group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 d, followed by single-dose irradiation of 5 Gy X-ray irradiation (2 Gy/min) for the IR and IR+Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis. Results Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count(IR: 20.70 ± 1.62 vs. IR+Rg1: 33.93 ± 2.20, t = -13.23, P < 0.05), and reduced sperm malformation rates(IR: 46.33 ± 2.18 vs. IR+Rg1: 39.00 ± 1.67, t = 7.33, P < 0.05). Further TUNEL and ELISA assays demonstrated that Rg1 inhibited testicular apoptosis(IR: 3.21 ± 0.28 vs. IR+Rg1: 1.81 ± 0.18, t = 1.40, P < 0.05)and modulated serum testosterone(IR: 4.47 ± 0.23 vs. IR+Rg1: 6.65 ± 0.09, t = -2.18, P < 0.05), GnRH(IR: 24.37 ± 0.92 vs. IR+Rg1: 32.98 ± 1.33, t = -8.61, P < 0.05), and FSH levels (IR: 1.41 ± 0.11 vs. IR+Rg1: 2.69 ± 0.21, t = -1.28, P < 0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice. Conclusions Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.

Ionizing radiation, as an increasingly serious environmental pollutant, has aroused widespread public concern. Melatonin, as an indole heterocyclic compound, is known to have anti-inflammatory and antioxidant effects. However, few studies have considered the comprehensive impact of melatonin on radiation damage. In this study, we used zebrafish as experimental materials and employed methods such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking for automated behavior analysis, microscope imaging, and real-time fluorescence quantitative analysis. Zebrafish embryos at 2 h post-fertilization (hpf) were treated under four different experimental conditions to assess their growth, development, and metabolic consequences. Our findings indicate that 0.10 Gy gamma radiation significantly augments body length, eye area, spine width, and tail fin length in zebrafish, along with a marked increase in oxidative stress (P < 0.05). Moreover, it enhances cumulative swimming distance, time, and average speed, suggesting elevated activity levels. We observed circadian rhythm phase shifts, peak increases, and cycle shortening, accompanied by abnormal expression of genes pivotal to biological rhythms, exercise, melatonin synthesis, apoptosis/anti-apoptosis, and oxidation/antioxidant balance. The inclusion of melatonin (1 × 10-5 mol/L MLT) ameliorated these radiation-induced anomalies, while its independent effect on zebrafish was negligible. Melatonin can regulate oxidative stress responses, hinders apoptosis responses, and reprogramming the expression of rhythm-related genes in zebrafish embryos after reprogramming radiation stimulation. Overall, our research highlights melatonin's critical role in countering the biological damage inflicted by gamma radiation, proposing its potential as a therapeutic agent in radiation protection.

This study explores the neuroprotective effects of resveratrol (Resv) against tri-o-cresyl phosphate (TOCP)-induced neurotoxicity in the spinal cord of adult hens. It is well documented that TOCP exposure causes significant neurodegeneration via mechanisms that involve endoplasmic reticulum (ER) stress and impaired autophagy. In this experiment, adult hens were assigned to one of four groups: Control, Resv, TOCP, and TOCP + Resv. The spinal cord tissues were examined through transmission electron microscopy, hematoxylin and eosin (HE) staining, Nissl staining, and Western blotting to evaluate key proteins associated with ER stress and autophagy. Additionally, RT-qPCR and immunofluorescence were employed to measure sirtuin1 (SIRT1) expression. The findings revealed that TOCP induced severe ultrastructural damage, including disrupted myelin sheaths, dilated ER, and extensive neurodegeneration, as confirmed by histological evaluations. The expression levels of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, Beclin-1, P62, and LC3-II were also significantly elevated by TOCP. However, Resv treatment markedly attenuated these pathological changes by reducing ER stress, restoring autophagic flux, and upregulating SIRT1 expression, preserving spinal cord integrity. These results indicate that Resv can effectively counteract TOCP-induced neurotoxicity by modulating ER stress and autophagy, underscoring its potential as a therapeutic agent for neuroprotection.

目的 探究钙蛋白酶对三邻甲苯基磷酸酯(TOCP)诱导的人神经母细胞瘤SH-SY5Y细胞自噬的调节作用.方法 不同浓度TOCP处理未分化和分化的SH-SY5Y细胞,用荧光分光光度法检测钙蛋白酶活性.抑制钙蛋白酶活性后,通过Western blotting检测TOCP对自噬相关蛋白的影响;抑制钙通道后,用荧光分光光度法检测胞质钙离子浓度对钙蛋白酶活性的影响.结果 TOCP诱导未分化和分化的SH-SY5Y细胞钙蛋白酶活性上升;钙蛋白酶抑制剂可降低TOCP诱导的自噬相关蛋白LC3-Ⅱ和Beclin1表达.维拉帕米和2-APB阻断钙通道后钙蛋白酶活性降低,维拉帕米而非2-APB可以抑制TOCP诱导的自噬相关蛋白LC3-Ⅱ表达.结论 TOCP在未分化和分化的SH-SY5Y细胞中诱导的自噬受钙蛋白酶活性的调节.

目的 进行人蛋白激酶Cα(PKCα)蛋白结构和功能的生物信息学分析,为人PKCα的调控机制及生物学功能提供理论基础.方法 利用NCBI、TMHMM、ProtComp、ProtParam等数据库和生物信息学分析工具,对人PKCα蛋白的结构、性质、功能域及蛋白质空间结构进行分析.结果 人PKCα属不稳定蛋白,为非跨膜亲水性蛋白,无信号肽属于非分泌性蛋白,具有磷酸化位点.其二级结构主要是无规则卷曲,三级结构主要是蛋白质扭曲.无二硫键,有离子通道活性和钙释放通道活性,参与离子转运并与多种蛋白存在相互作用关系.结论 人PKCα蛋白在参与和调节离子转运、细胞死亡、能量代谢等许多生理过程中起着重要的作用.

Hand-transmitted vibration is one of the most common physical harmful factors in the workplace，and the hand-arm vibration syndrome caused by it lacks effective treatment, and seriously affects the physical and mental health of the involved workers. As an important target for hand-transmitted vibration, the nervous system has attracted increasing attention from scholars, and much progress has been made in recent years in studying the effects of hand-transmitted vibration on nervous system function. Based on related literature at home and abroad, this paper introduced the hand-transmitted vibration-associated damage in peripheral, autonomic, and central nervous systems, and then explored the associated influence factors, like vibration frequency, environment temperature, and individual factors. The potential directions for further research were also proposed.

BackgroundHand-transmitted vibration is one of the most common occupational hazards and is closely related to symptoms of fingertip terminal nerve damage. ObjectiveTo analyze the effects of hand-transmitted vibration on the terminal nerve of fingertips. MethodsWe systematically searched literature about the effects of hand-transmitted vibration on fingertip terminal nerve at home and abroad. The outcome index was the number (rate) of fingertip terminal nerve symptoms reported by the vibration group and the control group, such as finger numbness and finger tingling, and the search period was from database inception to December 2021. The quality of cross-sectional studies was assessed using the criteria recommended by the Agency for Healthcare Research and Quality (AHRQ), and the quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). NoteExpress 3.2 was used for literature management, and Excel 2003 was used for data collection and extraction. RevMan 5.4.1 software was used for statistical analysis, and random effect model was used to calculate the OR value of pooled effects and to draw forest plots. Subgroup analysis was carried out according to the working years with vibration exposure. At the same time, sensitivity analysis was performed after excluding studies with the largest weight and funnel plots were generated to evaluate publication bias. ResultsA total of 3619 articles were retrieved, and 39 articles were finally included, including 29 Chinese articles and 10 English articles; 36 cross-sectional studies and 3 cohort studies. In total, 8399 subjects were studied, including 5673 cases in the vibration exposure group and 2726 cases in the control group. Random effect model was used to merge the included literature. The results of meta-analysis showed that compared with the control group, hand-transmitted vibration was significantly associated with the self-reported occurrence of finger numbness (OR=8.29, 95%CI: 5.43-12.66), finger tingling (OR=7.50, 95%CI: 4.78-11.77), finger swelling (OR=8.25, 95%CI: 4.06-16.76), finger stiffness (OR=10.71, 95%CI: 3.60-31.87), finger trembling (OR=5.11, 95%CI: 2.60-10.04), hand weakness (OR=11.05, 95%CI: 3.98-30.68), hand sweating (OR=2.70, 95%CI: 1.64-4.43), hand coldness (OR=3.54, 95%CI: 2.42-5.18) (P<0.01). The subgroup analysis showed that the odds ratios of both finger numbness and finger tingling increased in the early and middle stages of vibration exposure (<5 years and 5-10 years of exposure duration）(finger numbness: OR=11.11, 19.07; finger tingling: OR=4.70, 16.55, respectively)(P<0.01), and decreased in the late stage of vibration exposure (10-15 years and ≥15 years of exposure duration) (finger numbness: OR=9.57, 2.30; finger tingling: OR=5.71, 6.00, respectively) (P<0.01). The results of sensitivity analysis showed a stable pooled effect (OR=13.96, 95%CI: 4.85-40.13, Z=4.89, P<0.01). The funnel plot results showed positive publication bias. ConclusionOccupational exposure to hand-transmitted vibration can cause finger numbness, finger tingling, finger swelling, finger stiffness, finger trembling, hand weakness, hand sweating, and hand coldness.

随着移动互联时代的到来,医疗卫生领域从传统的服务模式跨越到以移动医疗技术(mHealth)为发展重点的现代化服务模式.在HIV防治工作中,mHealth已被广泛应用,其可及性、便捷性、高效性、经济性的特点非常适用于极其敏感的HIV高危行为人群,特别是善于使用移动互联技术进行社交、寻找性伴和获取信息的MSM,加之也是最易感染HIV的群体.本文综述了在HIV暴露前预防、HIV检测、健康行为干预、服药依从性及护理这几方面针对MSM的移动医疗干预的应用现状,并分析干预效果和局限性,为未来我国制定可推广的移动医疗干预策略提供依据.

Calcium (Ca2+) is an essential signaling molecule in all cells. It is involved in numerous fundamental functions, including cell life and death. Abnormal regulation of Ca2+ homeostasis may cause human diseases. Usually known as a member of the transient receptor potential (TRP) family, TRP ankyrin 1 (TRPA1) is the only member of the ankyrin subfamily identified in mammals so far and widely expressed in cells and tissues. As it is involved in numerous sensory disorders such as pain and pruritus, TRPA1 is a potential target for the treatment of neuropathy. The functions of TRP family members are closely related to Ca2+. TRPA1 has a high permeability to Ca2+, sodium and potassium ions as a non-selective cation channel and the Ca2+ influx mediated by TRPA1 is involved in a variety of biological processes. In the present review, research on the relationship between the TRPA1 channel and Ca2+ ions and their interaction in disease-associated processes was summarised. The therapeutic potential of the TRPA1 channel is highlighted, which is expected to become a novel direction for the prevention and treatment of health conditions such as cancer and neurodegenerative diseases.

The circadian clock is an endogenous timing system that ensures that various physiological processes have nearly 24 h circadian rhythms, including cell metabolism, division, apoptosis, and tumor production. In addition, results from animal models and molecular studies underscore emerging links between the cell cycle and the circadian clock. Mutations in the core genes of the circadian clock' can disrupt the cell cycle, which in turn increases the possibility of tumors. At present, tumor chronotherapy, which relies on a circadian clock mechanism, is developing rapidly for optimizing the time of drug administration in tumor treatment to improve drug efficacy and safety. However, the relationship between the circadian clock and the cell cycle is extremely complicated. This review summarizes the possible connection between the circadian clock and the cell cycle. In addition, the review provides evidence of the influence of the circadian clock on senescence and cancer.

新冠肺炎疫情全球大流行暴露出各国重大疫情防控体制、机制和公共卫生体系存在一些明显的短板.本文专门对我国传染病的监测预警系统进行剖析,分析其存在的不足,并结合当前形势提出相应的对策和建议.

2020年伊始,我国遭遇了疫情肆虐的重大公共卫生事件.文章反思疫情所反映的公共卫生体系建设的不足之处及对策建议,思考如何才能使公共卫生事业得到进一步的长足发展,为公共卫生事业更快更好的发展,为推进"健康中国"贡献自己的力量.

新时期,国家提出并实施了创新驱动发展战略,将创新摆在国家发展全局的核心位置.在"双一流"建设背景下,公共卫生教育迎来了新的机遇和挑战.通过分析当前公共卫生教育存在的不足,提出宏观与微观相结合,建立"三层次"的公共卫生创新人才培养路径.营造培养创新人才的环境,突破人才培养体制机制难点,形成各具特色的创新人才培养模式,为高等学校推进创新人才培养提供参考.