BackgroundThe middle school stage represents a crucial period for the development of borderline personality features. Negative parenting styles and emotional regulation strategies are associated with the formation of borderline personality features. However， the moderating role of emotional regulation strategies between negative parenting styles and borderline personality features among middle school students remains unclear. ObjectiveTo explore the moderating influence of emotional regulation strategies in the relationship between negative parenting styles and borderline personality features among middle school students， and to provide references for the intervention of borderline personality features. MethodsIn October 2023， a total of 5 965 middle school students from three middle schools in Nanning， Guangxi Zhuang Autonomous Region were selected by cluster sampling， and assessed by the Borderline Personality Features Scale for Children （BPFS-C）， the Egna Minnen Barndoms Uppfostran （EMBU）， and the Emotion Regulation Questionnaire-Chinese Revised Version （ERQ-CRV）. Pearson correlation analysis was used to test the correlation between the scores of each scale， and the model 1 of the Process macro program was used to conduct the moderating effect test. ResultsA total of 5 572 middle school students （93.41%） completed this study， and 1 388 of them （24.91%） were identified as having high borderline personality features. The BPFS-C score of middle school students was positively correlated with the score of the negative parenting style dimension of EMBU （r=0.367， P<0.01）， negatively correlated with the score of the cognitive reappraisal dimension of ERQ-CRV （r=-0.168， P<0.01）， and positively correlated with the score of the expression inhibition dimension of ERQ-CRV （r=0.344， P<0.01）. Cognitive reappraisal played a negative moderating effect between negative parenting styles and borderline personality features （β=-0.072， 95% CI： -0.104–-0.041， P<0.01）， while expressive suppression played a positive moderating effect （β=0.076， 95% CI： 0.055–0.097， P<0.01）. ConclusionCognitive reappraisal strategy may help mitigate the negative influence of negative parenting styles on middle school students' borderline personality features， while expressive suppression may exacerbate the harm of negative parenting styles to the borderline personality features of middle school students.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

Objective To investigate the mechanism by which Biejiajian Pill(BJJP)regulates ferroptosis in hepatocellular carcinoma(HCC)cells through the p62/Keap1/NRF2 pathway and to provide an experimental basis for its application in the prevention and treatment of HCC.Methods Huh7 HCC cells were divided into a normal control group,a BJJP drug serum group,an erastin(a ferroptosis inducer)group,a BJJP drug serum+erastin group,and BJJP drug serum+ferrostatin-1(Fer-1)(a ferroptosis inhibitor)group.BJJP drug serum was prepared with animals treated with BJJP and CCK-8 assay was performed to determine the optimal concentration and duration of BJJP intervention.The levels of intracellular iron(Fe),reduced glutathione(GSH),lipid peroxides(MDA),and reactive oxygen species(ROS)were measured.Western blot was performed to determine the expression levels of FTH1,GPX4,xCT,SLC40A1,Keapl,p62,and NRF2.JC-1 staining was performed to measure mitochondrial membrane potential,and cell immunofluorescence was performed to determine the expression of p62 and Keap1.Results According to the CCK-8 assay results,the cell inhibition rate was highest when BJJP was administered at a high dose of 2.2 g/kg(P＜0.001).Furthermore,the inhibition rate of Huh7 cells was highest when Huh7 cells were treated with high-dose BJJP drug serum for 48 h.Therefore,the serum concentration of high-dose BJJP and 48 h were selected as the treatment dose and duration for the subsequent experiment.Compared with the control group,the BJJP drug serum group,the erastin group,and the BJJP drug serum+erastin group showed increased iron content,decreased GSH content,increased MDA levels,increased ROS aggregation,decreased FTH1,GPX4,xCT,SLC40A1,p62,and NRF2 contents,increased Keap1 content,and decreased mitochondrial membrane potential(P＜0.05).Conclusion BJJP regulates ferroptosis in Huh7 HCC cells by inhibiting the p62/Keap1/NRF2 pathway,demonstrating potentials as a therapeutic agent for HCC.

Objective To investigate the effects of circular RNA APLP2(circAPLP2)on the proliferation,migra-tion,and invasion of human colorectal cancer(CRC)cell lines by regulating microRNA-455-3p(miR-455-3p)/Stathmin1(STMN1)axis.Methods RT-qPCR was used to detect the expression of circAPLP2,miR-455-3p and STMN1 in CRC and normal colorectal cell lines and the optimal cell line was screened.Proliferation,migra-tion and invasion were detected by MTT assay,scratch assay and Transwell assay,respectively.The relationship between circAPLP2 and miR-455-3p,between miR-455-3p and STMN1 was confirmed by dual Lucifer's reporter gene assay.Results CircAPLP2 and STMN1 were highly expressed in CRC cells,miR-455-3p showed a low ex-pression.Knocking down circAPLP2 resulted in a decrease in rate of survival and of scratch healing rate and in-vasion of SW620 cells,An up regulation of miR-455-3p expression,a down regulation of STMN1,cyclin D1,N-cadherin protein expression and an up regulation of E-cadherin protein expression were also found(P<0.05).Inhibition of miR-455-3p expression reversed inhibitory effect of knocking down circAPLP2 on SW620 cell prolif-eration,migration,and invasion,up-regulated the STMN1,cyclin D1 and N-cadherin protein expression,and down-regulation of E-cadherin protein expression(P<0.05).Dual luciferase reporter gene assay showed that circAPLP2 targeted at negative regulation of miR-455-3p expression,while miR-455-3p targeted at negative reg-ulation of STMN1 expression.Nude mouse transplantation experiment found that knocking down circAPLP2 affect-ed the growth of transplanted tumors,while miR-455-3p expression was up-regulated and STMN1 expression was down-regulated(P<0.05).Conclusions CircAPLP2 inhibits the proliferation,migration and invasion of colorectal cancer cell lines by regulating the miR-455-3p/STMN1 axis.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*