Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited. Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults. Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models. Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL⁻¹, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities. Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

Perilipin 2(PLIN2)is located on the surface of lipid droplets,acting as an important marker pro-tein of liver lipid droplets.Several studies have shown the crucial role of PLIN2 in regulating liver lipid metabolism by modulating the formation and stability of lipid droplets.Additionally,it is also directly or indirectly involved in many physio-logical and disease processes related to nonalcoholic fatty liver disease(NAFLD),thereby playing an important role in the development of NAFLD.This paper reviews the distribution,structure,function and role of PLIN2 in NAFLD to provide insights into the development of PLIN2-targeted drugs for the prevention and treatment of NAFLD.

Perilipin 2(PLIN2)is located on the surface of lipid droplets,acting as an important marker pro-tein of liver lipid droplets.Several studies have shown the crucial role of PLIN2 in regulating liver lipid metabolism by modulating the formation and stability of lipid droplets.Additionally,it is also directly or indirectly involved in many physio-logical and disease processes related to nonalcoholic fatty liver disease(NAFLD),thereby playing an important role in the development of NAFLD.This paper reviews the distribution,structure,function and role of PLIN2 in NAFLD to provide insights into the development of PLIN2-targeted drugs for the prevention and treatment of NAFLD.

ObjectiveTo evaluate the supportive policies for caregivers issued in China, and analyze the structures and contents. MethodsThe national supportive policies for family caregivers in China within the past decade were text-mined using ROSTCM 6.0. Secondary indicators were established according to the Policy Modeling Consistency (PMC) index model combining with World Health Organization six blocks of health services. ResultsThe average PMC score was 7.38. There were seven good policies and three accepted policies. The policies covered well in publicity, recipients and functions, and needed to improve in incentive and restraint. ConclusionChina's policies have played a positive role in supporting family caregivers. It is needed to reduce the burden on family caregivers and improve their welfare.

Background Previous studies have shown that bisphenol A exposure is associated with the risk of hypertension; however, most of them are cross-sectional and the conclusions are not consistent. Objective To evaluate the association between bisphenol A exposure and the incident risk of hypertension. Methods Based on a nested case-control design involving 1990 subjects derived from the Dongfeng-Tongji cohort, a total of 1080 subjects were included in this study after excluding 887 hypertensive cases at baseline and 23 subjects with missing blood pressure data in follow-up visits. Epidemiological information was collected through questionnaire survey, and serum bisphenol A concentration was detected by high performance liquid chromatography tandem mass spectrometry. Logistic regression model was used to analyze the potential association between serum bisphenol A level and the risk of hypertension incidence, and linear regression model was used to analyze the association between serum bisphenol A level and blood pressure changes between baseline and follow-up. Results The average age of the 1 080 participants was (62.03±7.45) years, of which 41.1% were male. During the follow-up period, a total of 477 (44.2%) developed hypertension. The median serum concentration of bisphenol A in the total population was 3.15 μg·L⁻¹, and the baseline bisphenol A concentration in the new case group (3.24 μg·L⁻¹) was higher than that in the control group (2.98 μg·L⁻¹) (P<0.05). After adjustment for selected covariates, the risk of hypertension increased by 12% (OR=1.12, 95%CI: 1.02, 1.22) for each unit increase in naturally log-transformed bisphenol A; the systolic blood pressure and diastolic blood pressure increased by 1.88 (95%CI: 1.08, 2.69) mmHg and 1.14 (95%CI: 0.68, 1.61) mmHg, respectively. Compared with the low bisphenol A tertile group, the risk of hypertension in the middle tertile and high tertile groups increased by 39% (OR=1.39, 95%CI: 1.01, 1.91) and 40% (OR=1.40, 95%CI: 1.02, 1.93) respectively; the systolic blood pressure increased by 5.91 (95%CI: 3.06, 8.76) mmHg and 5.71 (95%CI: 2.82, 8.59) mmHg, and the diastolic blood pressure increased by 3.09 (95%CI: 3.06, 8.59) mmHg and 2.89 (95%CI: 1.22, 4.57) mmHg, respectively (P_trend<0.001). A positive association between serum bisphenol A level and hypertension was found among those who were female, never/former smokers, never/former drinkers, without family history of hypertension, with physical exercise, and with prehypertension at baseline (P_trend<0.05). There was no interaction between selected stratified variables and bisphenol A levels on hypertension (P_interaction>0.05). Conclusion Bisphenol A exposure is positively associated with the risk of hypertension.

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of →4)-α-D-GalAp-(1 → and →6)-β-D-Galp-(1 → and the branched structure of →5)-α-L-Araf-(1 →.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akker-mania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type Ⅲ phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.

Objective:To explore a method to obtain more mouse bone marrow cells more quickly.Methods:Take both lower limbs of the same mouse,the bone marrow cells were obtained by either the tube-nesting EP method or the traditional syringe irrigation method,recorded the time and quantity of bone marrow cells,to analyze the proportion of viable cells by flow cytometry,and to detect the proliferation of these bone marrow cells used CCK-8 method.Results:Compared with the traditional syringe irrigation method,the time of obtaining mouse bone marrow cells by tube-nesting EP method was shorter(P<0.000 1).Compared with the traditional syringe irrigation method,the number of bone marrow cells obtained by tube-nesting EP method was more(P<0.05).The proportion of live cells and proliferation ability of bone marrow cells obtained by the two methods were identical.Conclusion:Tube-nesting EP method is a new faster method to get more mouse bone marrow cells.

Objective:To identify the morphological alterations in the Golgi apparatus of skin fibroblasts in spinocerebellar ataxia type 3 (SCA3) patients.Methods:In this study, 3 SCA3 patients and 3 healthy volunteers were obtained in the First Affiliated Hospital of Zhengzhou University from 2016 to 2020. The cytosine, adenine, and guanine repeats of 3 SCA3 patients were 14/76, 20/80 and 21/82, respectively. Tissue mass culture was used to amplify skin fibroblasts derived from SCA3 patients and healthy volunteers. Cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry, respectively. Western blotting and immunofluorescence assay were used to detect the protein expression of ataxin-3, Golgi reassembly stacking protein 2 (GORASP2), and Golgi matrix protein 130 (GM130) in the skin fibroblasts. The morphology of the Golgi apparatus in skin fibroblasts was detected using transmission electron microscopy.Results:Tissue culture of skin fibroblasts of both SCA3 patients and healthy volunteers was successfully established. The patient-derived dermal fibroblasts expressing mutant ataxin-3 protein exhibited reduced cell viability ( t=5.06,P=0.007), increased apoptosis ( t=3.77, P=0.020), fragmentation of the Golgi apparatus, increased expression of GM130 ( t=5.23, P=0.006), and decreased expression of GORASP2 ( t=4.35, P=0.012). Transmission electron microscopy revealed that the Golgi apparatus was disorganized in skin fibroblasts. Conclusion:Fragmentation of the Golgi apparatus occurs in the skin fibroblasts of SCA3 patients, and abnormal morphology and structure of the Golgi apparatus may be involved in the pathogenesis of SCA3.

Objective To investigate the real-time regulatory effects of IFN-γ, programed death ligand 2(PDL2) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway on the adherence, proliferation and migration of human placenta-derived mesenchymal stem cells(hPMSCs) based on a finding that IFN-γ could enhance the expression of PDL2 in hPMSCs through JAK/STAT signaling pathway.Methods hPMSCs were isolated by using enzyme digestion method and then co-cultured with IFN-γ, anti-PDL2 monoclonal antibody (anti-PDL2 McAb) and JAK inhibitor, respectively.Real-time cell analysis (RTCA) was used to detect the dynamic changes in the adherence, proliferation and migration of hPMSCs following various interventions.Results IFN-γ remarkably suppressed hPMSCs proliferation during the period from 40 hours to 80 hours after intervention and also inhibited the non-targeted migration of hPMSCs.However, hPMSCs adherence was not affected by IFN-γ.Co-culturing hPMSCs with anti-PDL2 McAb significantly enhanced hPMSCs adhesion and inhibited their non-targeted migration, but had no significant effect on hPMSCs proliferation.Furthermore, the proliferation of hPMSCs co-cultured with IFN-γ and anti-PDL2 McAb was significantly inhibited as compared with that of anti-PDL2McAb treatment group.The adhesion, migration and proliferation of hPMSCs were significantly inhibited after co-culturing them with JAK inhibitor.Conclusion IFN-γ can remarkably suppress the proliferation and migration of hPMSCs.PDL2 can enhance the migration and inhibit the adhesion of hPMSCs.JAK/STAT signaling pathway is involved in regulating the adhesion, migration and proliferation of hPMSCs.