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.

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.

BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To develop a Self-Report Scale of Symptoms for Post Intensive Care Syndrome-Family(PICS-F)and validate its reliability and validity,providing a scientific tool for healthcare professionals to comprehensively assess post intensive care syndrome-family.Methods Based on the symptom experience dimension of Symptom Management Theory,a preliminary version of the scale was developed through literature analysis,semi-structured interviews,expert consultations,and a pilot survey.A convenience sampling method was used to conduct the pre-trial version of the scale questionnaire survey on 442 family members of ICU patients at a tertiary A comprehensive hospital in Wuhan from June to September 2024.The test of the validity and reliability was conducted.Results The developed scale consists of 4 dimensions and 20 items.Exploratory factor analysis identified 4 factors,with a cumulative variance contribution rate of 70.921％.The content validity index at the scale level was 0.941,and the content validity indices for individual items ranged from 0.809 to 1.000.Confirmatory factor analysis indicated that the model fit indices were within acceptable ranges.The overall Cronbach's αcoefficient for the scale was 0.941,and the split-half reliability was 0.832.Conclusion The Self-Report Scale of Symptoms for PICS-F demonstrates good reliability and validity.It can comprehensively reflect the primary symptoms of PICS-F,and can serve as an effective measurement tool for clinicians to assess PICS-F in family members of ICU patients.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

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.