ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

BackgroundThe distressingly high prevalence of depressive symptoms among adolescents exerts profound impacts on their physical and psychological development， urgently necessitating effective preventive interventions. Existing studies， however， have predominantly focused on isolated risk factors， neglecting to construct an integrated model that systematically disentangles the intricate relationships linking parenting styles， learning burnout， and childhood trauma to adolescent depressive symptoms. Moreover， the potential protective roles of social support and psychological resilience in this context remain insufficiently elucidated. ObjectiveTo construct a structural equation model encompassing multiple pathways to unravel the comprehensive mechanisms through which negative parenting styles， childhood trauma， learning burnout， psychological resilience， and social support collectively influence adolescent depressive symptoms， thereby providing evidence-based intervention strategies. MethodsA stratified sampling technique was utilized to recruit 5 865 students from 12 middle schools in Chengdu City， Sichuan Province from March to May 2022. Participants were assessed using the following validated instruments： the Short-form Egna Minnen av Barndoms Uppfostran （s-EMBU）， the Childhood Trauma Questionnaire-Short Form （CTQ-SF）， the Adolescent Student Burnout Inventory， the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， the Social Support Rating Scale （SSRS），and the Connor-Davidson Resilience Scale （CD-RISC）. A partial least squares structural equation modeling （PLS-SEM） approach was employed to construct a predictive framework examining the complex network of pathways through which negative parenting styles， childhood trauma， learning burnout， psychological resilience，and social support collectively influence depressive symptoms in adolescents. ResultsThe PHQ-9 scores demonstrated significant positive correlations with the scores on s-EMBU overprotection subscale （r=0.272， P<0.01）， s-EMBU rejection subscale （r=0.368， P<0.01）， CTQ-SF （r=0.288， P<0.01） and Adolescent Student Burnout Inventory （r=0.587， P<0.01）. Conversely， significant negative correlations were observed between PHQ-9 scores and both SSRS （r=-0.532， P<0.01） and CD-RISC scores （r=-0.418， P<0.01）. Negative parenting styles （β=0.113， 95% CI： 0.087-0.138） and learning burnout （β=0.339， 95% CI： 0.315-0.364） emerged as significant positive predictors of depressive symptoms， with childhood trauma mediating the relationship between negative parenting styles and depressive symptoms （effect size=0.018， 95% CI： 0.013-0.024）. Social support servesed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.080， 95% CI： 0.069-0.092）， as well as between negative parenting styles and childhood trauma （β=0.041， 95% CI： 0.032-0.050）. It also functioned as an intermediary pathway linking learning burnout to depressive symptoms （β=0.092， 95% CI： 0.081-0.104） and connecting learning burnout with childhood trauma （β=0.048， 95% CI： 0.037-0.058）. Additionally， psychological resilience serveed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.004， 95% CI： 0.002-0.007）， between learning burnout and depressive symptoms （β=0.037， 95% CI： 0.023-0.052）， and between childhood trauma and depressive symptoms （β=0.003， 95% CI： 0.001-0.006）. ConclusionLearning burnout exerts a direct effect on adolescent depressive symptoms. Negative parenting styles influence depressive symptoms both directly and indirectly through childhood trauma. Furthermore， social support and psychological resilience serve as mediator linking negative parenting styles and learning burnout to depressive symptoms in adolescents. ［Funded by Science and Technology Project of the Health Commission of Sichuan Province （number， 24LCYJPT18）］

Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths,posing a serious threat to women′s health worldwide.At present,although the prognosis of some patients with breast cancer has improved,the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis.CD36 is a multiligand transmembrane glycoprotein expressed on various cell types.In recent years,studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells;promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues;regulate the function of Treg cells,CD8+T cells,DCs,and other immune cells,and thus promote tumor development.In addition,CD36 is also associated with breast cancer stem cells,metastasis-initiating cells,and breast drug resistant cells.Therefore,CD36 could be an important potential therapeutic target for breast cancer.

Pleural mesothelioma （PM） is a rare malignant tumor originating from the pleura. Most patients are already in the advanced stage at the time of diagnosis， resulting in a low overall survival rate. MicroRNA （miRNA）， as key regulators of tumor epigenetic modification， have an intertwined interactive network with PM drug resistance. The mechanisms of drug resistance in PM to chemotherapeutic drugs include increasing drug efflux， reducing drug intake， enhancing DNA repair， and altering drug targets. The mechanisms of resistance to targeted therapy drugs include activating alternative signaling pathways， establishing a favorable tumor microenvironment， and triggering epithelial-mesenchymal transition. MiRNA plays a key part in the aforementioned resistance mechanisms， with some miRNAs promoting the drug sensitivity of cancer cells， while others contribute to increased drug resistance. In light of these key regulatory functions， targeting the dysregulated expression of endogenous miRNAs in the process of resistance formation using miRNA antagonists or miRNA mimics may be an effective therapeutic strategy to reverse drug resistance in PM.

italic>Polygonum capitatum is a characteristic Miao medicine in Guizhou, commonly used in clinical practice to treat gastrointestinal and urinary tract infections. Research has found that it has good antibacterial and anti-inflammatory effects, and its main active ingredient is flavonoids. Lavonoid O-methyltransferase (FOMT) is a key enzyme for oxymethylation modification of flavonoid compounds. In order to understand the function and properties of FOMT protein in Polygonum capitatum, the transcriptome was sequenced by Illumina HiSeq 4000 high throughput sequencing technology. Then, the obtained transcripts were annotated and analyzed, and the whole genome of the FOMT gene family in Polygon capitalis was mined and identified. A total of 99 298 Unigenes were obtained, of which 71 514 were successfully annotated by the public database. In the genome of Polygonum capitatum, a total of 50 FOMT genes were identified. The phylogenetic tree showed that FOMT genes were divided into two subfamilies: caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT). Gene sequence analysis showed that the number of FOMT encoded amino acids ranged from 99 to 1 053 aa, the molecular weight ranged from 11 224.91 to 86 687.42 Da, and the isoelectric point ranged from 4.79 to 9.45. The 50 FOMT family members were hydrophobic proteins. Subcellular localization results showed that 54% of FOMT subfamily CCoAOMT and COMT members were located in cytoplasm and 28% were located in chloroplasts. The FOMT gene was tissue specific and highly expressed in the flowers of Polygonum capitatum, followed by the stems, and the least expressed in the roots. In this study, the FOMT gene family of Polygonum capitatum was identified and analyzed to provide theoretical basis for further study of FOMT function and biosynthesis of methylated flavonoids.

Objective: To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera japonica Thunb. (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure. Methods: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues. Results: CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4. Conclusion CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway. This process alleviates ferroptosis in cardiomyocytes. These results provide new insights into the clinical use of CGA and the management of heart failure.