This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.

ObjectiveTo address the key challenges in breast electrical impedance tomography (EIT) reconstruction including the severe ill‑posedness of the inverse problem, limited measurement information from the electrodes, low contrast of small lesions, as well as the common drawbacks of traditional reconstruction methods such as boundary blurring, low spatial resolution, and weak small-target detection capability, and to overcome the limitations of existing deep learning approaches namely low training efficiency, insufficient physical consistency, and substantial information loss during the low‑to‑high dimensional mapping process, this study proposes a multi‑scale attention and dynamic sparse mask fusion network (MADS‑Net). The proposed method aims to enhance high‑resolution reconstruction accuracy, small-lesion detectability, noise robustness, and computational efficiency in breast‑screening-oriented EIT, thereby providing a feasible solution for the application of EIT in breast functional imaging. MethodsThe proposed network adopts a strategy of “locate first, reconstruct later”. It realizes adaptive allocation of computational resources through a dynamic mask module, alleviates information loss in the low-to-high dimensional mapping process via a multi-scale attention mechanism, and embeds physical constraints to improve the physical rationality of reconstruction results. The performance of the proposed method was validated through systematic numerical simulations, agar phantom experiments, and porcine tissue experiments. Comparisons were made with mainstream methods including the Gauss-Newton algorithm, convolutional neural networks, U-Net, and Deep D-Bar. The image correlation coefficient (ICC), root mean square error (RMSE), and peak signal-to-noise ratio (PSNR) were adopted as quantitative evaluation metrics. Furthermore, lesion‑level evaluation metrics were introduced to assess the capability of different methods in reconstructing abnormal target boundaries and small‑sized target regions. ResultsExperimental results demonstrate that MADS-Net outperforms all comparison methods across all test scenarios. In numerical simulations, it achieves higher accuracy in target morphology and spatial location recovery as well as better background suppression. In agar phantom experiments, its detection and imaging reliability for small targets is significantly superior to the comparison methods. In porcine tissue experiments, the model maintains good generalization performance and can adapt to complex biological tissue imaging scenarios. Quantitative results show that MADS-Net achieves an average ICC of 0.917 6±0.048 8, an RMSE as low as0.060 6±0.031 6, and a PSNR of (23.893 9±2.685 3) dB. It successfully detects tiny targets as small as 5 mm within a 100 mm diameter sensing field, reduces the total training duration by 23.5% compared with the baseline method, and maintains stable reconstruction performance even under strong noise interference. ConclusionThe results demonstrate that MADS-Net achieves favorable EIT reconstruction performance in numerical simulations, agar phantom experiments, and porcine tissue experiments, even under common practical imaging challenges including low signal-to-noise ratio and blurred tissue boundaries. This study provides a methodological reference for further research on EIT in breast-screening-related scenarios and other medical functional imaging tasks, and also offers a low-cost, radiation-free alternative for breast lesion screening that aligns with the clinical demand for non-invasive diagnostic tools. It should be noted that real clinical breast data have not yet been used for validation in this study, and the clinical applicability of the proposed method requires further investigation. Future work will prioritize collecting multi-center real clinical breast datasets, and further optimize the model’s generalization ability to adapt to individual differences in breast tissue composition to promote its clinical application.

ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

Background Long working hours, as a common risk factor for occupational stress, is closely related to the occurrence of depressive symptoms. Understanding how long working hours affect occupational stress and depressive symptoms will inform occupational health interventions. Objective To quantify the impact of long working hours exposure on occupational stress and depressive symptoms among Internet industry employees, translate black-box outputs into actionable insights, and demonstrate the value of interpretable machine learning for early-warning occupational-health surveillance. Methods A dataset was derived from a cross-sectional survey involving 2866 internet industry employees in China. This survey was part of the project Risk Assessment Of Long Working Hour Exposure And Its Adverse Health Effects, conducted by the National Institute for Occupational Health and Poisoning Control, Chinese Center for Disease Control and Prevention, from 2021 to 2023. Working hours, occupational stress and depressive symptoms were quantified with a set of structured questionnaires including the Core Occupational Stress Scale and the Patient Health Questionnaire. Pairwise associations were screened by Mantel tests and variance-inflation factors. Key predictors identified through feature selection were fed into six machine-learning risk-prediction models. Visual interpretation was provided by feature importance, Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME), while directed causal effects and intervention impacts of prolonged working hours exposure on occupational stress and depressive symptoms were dissected with causal explanation of features techniques. Results The positive rates of occupational stress and depressive symptoms among internet employees were 12.9% and 77.8% respectively. Twelve core features for occupational stress and nine for depressive symptoms were retained after selection. After these features were supplied to six predictive algorithms and evaluated on five metrics, the Light Gradient Boosting Machine (LGBM) achieved the highest accuracy—0.89 for occupational stress and 0.79 for depressive symptoms on the hold-out test set. The feature-importance rankings converged on fatigue accumulation and life satisfaction as dominant drivers for both outcomes, whereas weekly working hours and daily overtime emerged as the principal exposure-related predictors. The SHAP summary plots revealed that longer weekly hours and daily overtime systematically elevated the probability of occupational stress. The causal feature explanation further quantified that ascending one category in weekly working hours increased the probability of occupational stress by 7.04%. Conclusion Exposure to long working hours is associated with both occupational stress and depressive symptoms among internet industry employees. Interpretable machine-learning frameworks translate these associations into transparent, defensible drivers, enabling precise identification of the pivotal factors and their interplay. This evidence base equips occupational-health practitioners with actionable insights for designing targeted prevention and intervention strategies.

ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the therapeutic effects and mechanisms of Yishen Shengyang formula in allergic rhinitis(AR)by regulating the transcription factor BTB and CNC homology 2(Bach2)to promote regulatory T cell(Treg cell)differentiation.Methods AR mouse models were established via ovalbumin(OVA)sensitization and randomly divided into control group,AR model group(AR group),Yishen Shengyang formula group and dexamethasone group.Nasal symptoms were evaluated using behavioral scores;Histopathological changes in nasal mucosa were observed via hematoxylin-eosin and periodic acid Schiff stain;Serum levels of OVA-specific immunoglobulin E(sIgE),interleukin-4(IL-4),and transforming growth factor-β(TGF-β)were measured by enzyme linked immunosorbent assay;Splenic Treg proportions were analyzed via flow cytometry;Bach2 protein expression was assessed by Western blot.Results Compared with control group,AR group mice showed significantly increased behavioral scores(P<0.05),goblet cell hyperplasia,inflammatory infiltration,elevated OVA-sIgE and IL-4 levels(P<0.05),reduced TGF-β(P<0.05),and decreased splenic Treg proportions and Bach2 expression(P<0.05).Yishen Shengyang formula treatment alleviated nasal symptoms(P<0.05),mitigated mucosal damage,decreased OVA-sIgE and IL-4,increased TGF-β(P<0.05),and upregulated Treg proportions and Bach2 expression(P<0.05),with efficacy comparable to dexamethasone.Conclusion Yishen Shengyang formula demonstrates potential therapeutic effects on allergic rhinitis by upregulating Bach2 expression and promoting Treg cell differentiation.This study provides a novel strategy and experimental basis for the traditional Chinese medicine treatment of AR.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

OBJECTIVES: To investigate the potential circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) immune regulatory network in childhood allergic asthma by analyzing microarray datasets. METHODS: GEO database was used to obtain the datasets of circRNA, miRNA, and mRNA from children with allergic asthma and healthy controls. The Limma package was used to identify differentially expressed circRNA (DEcircRNA), miRNA (DEmiRNA), and mRNA (DEmRNA). ENCORI and other tools were used to predict and construct the regulatory network of endogenous RNA. The DAVID database was used to perform GO and KEGG enrichment analyses, and CIBERSORT and Pearson were used to identify genes associated with immune cell infiltration. RESULTS: A total of 130 DEcircRNAs, 40 DEmiRNAs, and 802 DEmRNAs were identified between the asthma and control groups, and a regulatory network consisting of 12 circRNAs, 7 miRNAs, and 75 mRNAs was established. The GO analysis showed that the differentially expressed genes were mainly involved in the regulation of growth and development, and the KEGG analysis showed that they were mainly involved in the mTOR signaling pathway. The CIBERSORT analysis showed that compared with the control group, the asthma group had higher percentages of CD8⁺ T cells and resting NK cells and lower percentages of resting CD4⁺ memory T cells and activated mast cells. In addition, the Pearson correlation analysis identified six key mRNAs that were positively correlated with immune cell infiltration. CONCLUSIONS The ceRNA immune regulatory network constructed in this study provides a basis for research on the mechanism of childhood allergic asthma and potential therapeutic targets.
Humans ; Asthma/genetics* ; RNA, Circular/physiology* ; MicroRNAs/physiology* ; Child ; Gene Regulatory Networks ; RNA, Messenger/physiology* ; RNA/physiology* ; Male ; Female ; Child, Preschool