ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective:To understand the current status of occupational exposure to dust or harmful gases and occupational protection in people aged ≥40 years in China, and provide data support for the prevention and control of occupational dust or harmful gas exposure.Methods:The data were obtained from the surveillance for chronic obstructive pulmonary disease (COPD) in adults aged ≥40 years selected by multi-stage stratified cluster sampling from 125 surveillance points in 31 provinces (autonomous regions and municipalities) during 2014-2015 and 2019-2020, and relevant information about occupational dust or harmful gas exposure and protection measures were collected through face-to-face interviews. Occupational dust or harmful gas exposure rate and occupational protection rate were estimated by using weighting complex sampling methods, and then the results were compared.Results:From 2014 to 2015 and from 2019 to 2020, a total of 71 061 and 71 023 individuals aged ≥40 years were surveyed, respectively. The rate of occupational exposure to dust or hazardous gas was 33.8% (95% CI: 29.9%-37.7%) during 2019-2020. The occupational exposure rate was higher in men than in women and in rural residents than in urban residents. With the increase of education level, the rate of occupational exposure to dust or harmful gas showed a downward trend. The protection rate against occupational dust or hazardous gas exposure was 47.9% (95% CI: 43.2%-52.6%) during 2019-2020. Compared with 2014-2015, the rate of occupational exposure to dust or hazardous gas decreased by 10.7 percentage points in different gender, area and occupational groups and the occupational protection rate increased by 21.9 percentage points during 2019-2020. The decrease in occupational exposure rate was higher in western China than in eastern and central China, and the increase in occupational protection rate was higher in western China than in eastern and central China. Conclusions:The rate of occupational exposure to dust or harmful gas decreased and the rate of occupational protection against dust or harmful gas exposure increased in China during 2019-2020. However, about one-third of the population still suffer from the occupational exposure, and less than half of them take protection measures. It is necessary to pay more attention to the key populations, such as workers with lower cultural level and rural migrant workers, in occupational health practice.

Objective:To understand the passive smoking exposure status in adults aged ≥40 years in China.Methods:Local residents aged ≥40 years were enrolled as study subjects from 125 areas of chronic obstructive pulmonary disease (COPD) surveillance during 2014-2015 and 2019-2020 in 31 provinces of China. A total of 74 559 adults aged ≥40 years were selected through multi-stage stratified cluster sampling for a face to face questionnaire survey and the data from 64 142 study subjects were used for the analysis. The passive smoking exposure rate, the proportions of the adults reporting passive smoking exposure at four types of places and the proportion of the adults living with daily smokers were described by using complicated sampling weighting method, the related factors were analyzed and the results were compared with the data of COPD surveillance during 2014-2015.Results:The passive smoking exposure rate in the adults aged ≥40 years was 46.4% (95% CI: 44.1%-48.8%) in China during 2019-2020, and the rate was higher in women (47.2%, 95% CI:44.8%-49.7%) than in men (44.8%, 95% CI:42.0%-47.6%) and lower in the older people. The office workers had the highest passive smoking exposure rate. The proportions of those reporting passive smoking exposure at homes, workplaces, restaurants, and public transports were 24.3% (95% CI:22.2%-26.4%)、23.3% (95% CI:21.1%-25.5%)、6.6% (95% CI:5.3%-7.9%) and 2.2% (95% CI:1.6%-2.7%). The higher education level the adults had, the less passive smoking exposure at home they reported. The proportions of those living with daily smokers before 14 years old and since 14 years old were 56.4% and 59.2%. Compared with the data during 2014-2015, the overall passive smoking exposure rate in the adults aged ≥40 years during 2019-2020 showed an increase, and the difference was not significant ( P=0.356); The passive smoking exposure rate at homes declined, but the exposure rate at workplaces increased, with the biggest increase found in those being engaged in farming, forestry, husbandry, fishery and water conservancy. Multivariate analysis indicated that the factors influencing the passive smoking exposure and the exposure proportions at different places included gender, age, occupation, and education level. Conclusions:The passive smoking exposure rate in China is still high, especially in those being engaged in farming, forestry, husbandry, fishery and water conservancy. It is necessary to strengthen supervision of the enforcement of current smoking bans in public places and promote the legislation of ban smoking in public places. More attention should be paid to smoking ban and protection against passive smoking exposure in women, people with lower education level and people being engaged in in farming, forestry, husbandry, fishery and water conservancy.

Objective:To analyze the exposure level and changes in severe respiratory infection among Chinese residents aged ≥40 years in China and to provide essential data for preventing and controlling chronic respiratory diseases.Methods:The data came from chronic obstructive pulmonary disease surveillance of Chinese residents in 2014-2015 and 2019-2020. The surveillance covers 31 provinces (autonomous regions and municipalities) in China. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥40 years. Relevant information about exposure to severe respiratory infections during childhood was collected through investigation. Rigorous complex sampling and weighted analysis were applied to estimate the exposure rate of severe respiratory infections among children with different characteristics among residents aged ≥40 years in China from 2019 to 2020. Additionally, changes in severe respiratory infections during childhood were analyzed over 2014-2015 and 2019-2020.Results:In 2019-2020, the exposure rate of severe respiratory infection before 18 for residents aged ≥40 years in China was 21.58‰ (95% CI: 17.57‰-25.59‰). The exposure rate of severe respiratory infection before the age of 14 was 19.40‰ (95% CI:15.25‰-23.55‰), the difference in the exposure rate between men and women was not statistically significant (both P>0.05), and the exposure rate of urban residents is higher than that of rural residents. The results of multivariate logistic regression analysis showed that in western rural areas, factors including being born by cesarean section, exposure to secondhand smoke before age 14 years old, and a family history of chronic respiratory diseases were associated with severe respiratory infections in childhood. Compared with 2014-2015, the proportion of residents aged 40 and older in China hospitalized for pneumonia or bronchitis before 14 from 2019 to 2020 was slightly lower than five years prior. Conclusions:Among residents in China aged ≥40 years, 21.58‰ experienced severe respiratory infection exposure during childhood, varying exposure levels across different demographic groups. The burden of chronic respiratory diseases in adulthood cannot be ignored. Efforts should be made to expand the coverage of planned immunization and to focus on early-life interventions during childhood to reduce the incidence of severe respiratory infections.