OBJECTIVE: To investigate the susceptibility of venetoclax-resistant acute myeloid leukemia (AML) cell lines to ferroptosis and to uncover the underlying molecular mechanisms using transcriptomic and metabolomic analysis methods. METHODS: Venetoclax-resistant AML cell lines were constructed using a low-dose concentration escalation method. The sensitivity of cells to chemotherapeutic drugs was detected by CCK-8 assay. The susceptibility of drug-resistant cell lines to ferroptosis was assessed using transcriptomic and metabolomic analysis methods. The expression of cellular GPX4 and SLC7A11 protein was detected by Western blot, and cell death and lipid peroxidation levels were measured by flow cytometry. Depmap database and TCGA cohort were applied to explore the effect of ferroptosis-related genes expression on prognosis. RESULTS: Venetoclax-resistant cell lines exhibited sensitivity to ferroptosis inducers RSL3, APR246, and sorafenib. The ferroptosis inhibitor Fer-1 partially inhibited cell death induced by these inducers. Compared with the parental cells, significant changes in metabolites and gene expression levels related to ferroptosis were observed in the resistant cell lines. In particular, deregulated expression of SLC7A11 and GPX4 may play critical role in ferroptosis susceptibility. Besides, GPX4 was identified as more important for AML cell survival and higher GPX4 expression may predict shortened overall survival, NPM1 mutant and IDH1 R132 mutation positive patients may prone to possess higher GPX4 expression. CONCLUSION Venetoclax-resistant AML cell lines remain susceptible to ferroptosis, higher GPX4 expression maybe a critical marker for poor prognosis. Regulating the expression of ferroptosis-related genes and metabolites may enhance the efficacy of venetoclax and provide new treatment options for AML patients.
Humans ; Ferroptosis ; Leukemia, Myeloid, Acute/metabolism* ; Sulfonamides/pharmacology* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Drug Resistance, Neoplasm ; Metabolomics ; Cell Line, Tumor ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Transcriptome

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To analyze the disease burden and trend of osteoporosis in China from 1990 to 2021,and provide theoretical basis for the prevention and control of osteoporosis. Methods:Using the Global Burden of Disease 2021 (GBD 2021) database,the descriptive analysis of the mortality and disease burden of osteoporosis in different sex and age groups in China from 1990 to 2021 was conducted,the annual change percentage and the average annual change percentage were calculated using Joinpoint Software,and the Age-Period-Cohort (APC) model was used to evaluate the impact of age,period and birth cohort factors on disease burden. Results:The mortality and disease burden of Low Bone Mineral Density (LBMD) in male is higher than that of female,and the mortality and disease burden increases with age,and the mortality and disease burden is the highest in people over 80 years old. The gross rate of Disability Adjusted Life Years (DALYs) in female is higher than that in male after the age of 65;falls are the leading cause of LBMD-related deaths. The mortality rate,DALY rate and YLL rate showe a downward trend. The burden of LBMD mortality and disease in China is higher than that in the world. The age effect coefficient shows an upward trend,the period effect coefficient shows a first increasing and then decreasing trend,and the birth cohort effect coefficient shows a downward trend. Conclusion:With the intensification of aging,the burden of osteoporosis-related diseases in China will still be very heavy in the future. It is needed to actively carried out fall prevention and control strategies to reduce the occurrence of osteoporotic fractures and related deaths;take multiple measures to strengthen the monitoring and prevention of osteoporosis.

Objective:To analyze the disease burden and trend of osteoporosis in China from 1990 to 2021,and provide theoretical basis for the prevention and control of osteoporosis. Methods:Using the Global Burden of Disease 2021 (GBD 2021) database,the descriptive analysis of the mortality and disease burden of osteoporosis in different sex and age groups in China from 1990 to 2021 was conducted,the annual change percentage and the average annual change percentage were calculated using Joinpoint Software,and the Age-Period-Cohort (APC) model was used to evaluate the impact of age,period and birth cohort factors on disease burden. Results:The mortality and disease burden of Low Bone Mineral Density (LBMD) in male is higher than that of female,and the mortality and disease burden increases with age,and the mortality and disease burden is the highest in people over 80 years old. The gross rate of Disability Adjusted Life Years (DALYs) in female is higher than that in male after the age of 65;falls are the leading cause of LBMD-related deaths. The mortality rate,DALY rate and YLL rate showe a downward trend. The burden of LBMD mortality and disease in China is higher than that in the world. The age effect coefficient shows an upward trend,the period effect coefficient shows a first increasing and then decreasing trend,and the birth cohort effect coefficient shows a downward trend. Conclusion:With the intensification of aging,the burden of osteoporosis-related diseases in China will still be very heavy in the future. It is needed to actively carried out fall prevention and control strategies to reduce the occurrence of osteoporotic fractures and related deaths;take multiple measures to strengthen the monitoring and prevention of osteoporosis.

This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica. The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) and Masson staining, the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were detected, and transforming growth factor β1 (TGF-β1), Smad family member 3 (Smad3), α-smooth muscle actin (α-SMA) pathway index expression in lung tissue was detected by fluorescence quantitative PCR. UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them. The results showed that compared with the model group, the medium (1.5 g·kg^-1) and high (3.0 g·kg^-1) doses of Amygdalus mongolica total extract could significantly reduce the lung index, significantly increase the activity of SOD in serum and lung tissue, reduce the degree of alveolar inflammation and pulmonary fibrosis, and reduce MDA in serum and lung tissue, and significantly reduce TGF-β1, Smad3, α-SMA mRNA expression in lung tissue. Serum metabolomics profile analysis identified 25 significantly different metabolites, the Amygdalus mongolica total extract can participate in linoleic acid metabolism, glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers: lysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z)), lysoPC(20∶0/0∶0), PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0), 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOME), 9,10-dihydroxy-12-octadecenoic acid (9,10-DHOME) to affect pulmonary fibrosis. This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats, and provided a reference basis for the clinical application of Amygdalus mongolica. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No.20170315).

Carboxyl CoA ligases(CCLs) is an important branch of adenylate synthetase gene family, which mainly has two-step catalytic reactions. Firstly, in the presence of adenosine triphosphate, it can catalyze the pyrophosphorylation of carboxylateswith diffe-rent structures to form corresponding acyl adenosine monophosphate intermediates. Secondly, adenosine monophosphate was replaced by free electrons in the mercaptan group of enzyme A or other acyl receptors by nucleophilic attack to form thioesters. In this study, on the basis of the transcriptome database of Arnebia euchroma, two genes were selected, named AeCCL5(XP_019237476.1) and AeCCL7(XP_019237476.1). Bioinformatics analysis showed that their relative molecular weights were 60.569 kDa and 60.928 kDa, theoretical PI were 8.59 and 8.92, respectively. They both have transmembrane domains but without signal peptide. By multiple sequence alignment and phylogenetic tree analysis, we found that the similarity between AeCCLs and other plant homologous proteins was not high, and the substrate binding sites of AeCCLs were not highly conserved. The reasons might be that the sequence and structure need to adapt to the changes of new substrates in the process of evolution. In this study, the full-length of AeCCL5 and AecCCL7 were cloned into the expression vector pCDFDuet-1. The proteins of AeCCL5 and AeCCL7 with His-tag were expressed in Escherichia coli. The proteins of AeCCL5 and AeCCL7 were purified by nickel column. In vitro enzymatic reactions proved that both AeCCL5 and AeCCL7 can participate in the upstream phenylpropane pathway of shikonin biosynthesisby catalyzing 4-coumaric acid to produce 4-coumarin-CoA, and then to synthesis p-hydroxybenzoic acid, which is an important precursor of shikonin biosynthesis in A. euchroma.
Boraginaceae/genetics* ; Cloning, Molecular ; Coenzyme A ; Coenzyme A Ligases/genetics* ; Ligases ; Phylogeny

This paper summarized the effects of ecological planting on secondary metabolism firstly and pointed out that ecological planting can increase the content of secondary metabolites in plants, especially the content of defensive secondary metabolites. The possible mechanism was analyzed subsequently. Then, we reviewed the induction and utilization of secondary metabolism in the ecological planting of Chinese materia medica from the perspectives of biological control of pests and diseases, promotion of beneficial microorganism accumulation, optimization of mixed planting, regulation of no-tillage and straw cover. In this article, we pointed out that paying close attention to secondary metabolism is the most important feature of ecological planting of Chinese materia medica. Ecological planting can promote the accumulation of secondary metabolites of Chinese materia medica which means can improve the quality of Chinese materia medica, beneficial to the prevention and control of diseases, insects and weeds. Furthermore, lacking of systemic researches,the extensive verifications and systematic in-depth researches on the ecological planting of Chinese materia medica should be carry out urgently.
Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional ; Plants, Medicinal ; Secondary Metabolism

Objective To explore factors influencing the incidence of carotid atherosclerosis in different genders so as to provide reference for the specific prevention of the disease. Methods A nested case-control study was conducted to analyze factors influencing the incidence of carotid atherosclerosis in Jinchang cohort population who were randomly selected through stratified sampling by age and followed up. A risk prediction model was established and the goodness of fit was evaluated by the area under the receiver operator characteristic curve (ROC). Results The standardized incidence of carotid atherosclerosis in this follow-up population was 12.32%, and the incidence rate of males (13.65%) was greater than that of females (11.29%). The difference was statistically significant ( 2=4.267, P<0.001). Age, education, elevated systolic blood pressure, and elevated low-density lipoprotein cholesterol were common risk factors for carotid atherosclerosis in both men and women. Elevated fasting plasma glucose (OR=2.556, 95% CI: 1.618-4.038) and elevated triglyceride (OR=1.535, 95% CI: 1.058-2.227) were only associated with men. Abdominal obesity (OR=1.414, 95% CI: 1.013-1.974) was only associated with women. The area under ROC of male and female prediction models was 0.835 (95% CI: 0.815-0.856) and 0.809 (95% CI: 0.788-0.831), respectively. The sensitivity was 78.0% and 78.9%, the specificity was 78.8% and 73.1%, and the diagnostic coincidence rate was 91.3% and 82.4%, respectively. Conclusions There are different risk factors for carotid atherosclerosis in males and females, and targeted prevention and control measures should be taken according to gender. The risk prediction model established by Logistic regression had certain guiding value.

Objective·To evaluate the impact of one-child on body mass index (BMI), and percentage of body fat in primary school students. Methods·All the sample was recruited from 5 elementary schools in Gaohang Town, Shanghai, China. The baseline data of height, body weight, and percentage of body fat was obtained in 2013, and re-measured in 2014 and 2015, respectively. Birth weight, breast feeding, diet and time for physical activities of each children and the highest education level, height, and body weight of their parents were also collected by a self-completed questionnaire. Logistic regression and Mix model was used to analyze the relationship between one-child and BMI, BMI-Z score, and percentage of body fat. Results·A total number of 2515 (1323 boys and 1192 girls) primary school students completed the study and entered the analysis. The percent of one child in this study population was 72.0％ (1812/2515). BMI-Z score, time for physical activities, parental education level, and maternal BMI were higher, while the rate of breast feeding was lower in one-child group compared to non-one-child group. The results of Logistic regression showed boys (compared to girls), macrosomia ( ≥4000g vs normal birth weight), overweight father and mother (compared to normal BMI) were risk factors for overweight. The factor of one-child didn't increase the risk of overweight (OR=1.119, 95％ CI 0.911-1.374). After potential con-founders adjusted, the annual increase of BMI (β=0.028, 95％ CI -0.045-0.100), BMI-Z score (β=0.002, 95％CI -0.034-0.037) and percentage of body fat (β=0.013, 95％ CI -0.181-0.207) showed no obvious difference between the two groups. Conclusion·One-child factor showed no obvious relationship with BMI, BMI-Z score and percentage of body fat in primary school students.