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.

Objective To investigate the protective effect of β-glucan(BG)against intestinal ischemia reperfusion(II/R)injury by regulating the secretion of glucagon-like peptide-1(GLP-1).Methods Male C57BL/6 mice(6～8 weeks old)were subjected,and finally,the experiments had sham group,II/R group,II/R+BG group(0.1 mg/mL BG in drinking water for 2 weeks before modeling),II/R+liraglutide(LLT,GLP-1 analogue)group(0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling),and II/R+BG+Ex9-39(GLP-1 R antagonist)group(intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling).After modeling,HE staining was used to observe intestinal morphological changes,and RT-qPCR and Western blotting were employed to evaluate the molecules(Occludin,ZO-1 and Claudin-1)related to intestinal barrier damage.The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay,respectively,and RT-PCR for the molecules related to GLP-1 expression(Gcg,Pcsk1/2,GIP and Foxa2).The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules.Results II/R induced significant decreases in the mRNA levels of Occludin,ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice(P＜0.05).While,the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group(P＜0.05).BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice,and improved the mRNA expression of GLP-1-related molecules(P＜0.05).The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score,with statistical difference in comparison with the II/R group(P＜0.05).GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage,with notably differences in the expression of Occludin,ZO-1 and Claudin-1 and Chiu's score(P＜0.05).Conclusion BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.

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.

This study analyzed the epidemiological characteristics of imported malaria in Yunnan Province from 2020 to 2023,to provide scientific evidence for formulating measures to decrease imported malaria and prevent re-establishment of malaria transmission.Malaria data reported by the China Disease Prevention and Control Information System were analyzed to determine parasite species;sources of infection;temporal,spatial,and population distributions;and importation routes.A total of 828 malaria cases were reported in the province.Plasmodium vivax and Plasmodium falciparum accounted for 89.98％and 8.33％of cases,respectively.A total of 47.58％of cases were imported from Myanmar,and all P.falciparum malaria ca-ses were from Africa.Thirteen(81.25％)prefectures or municipalities reported malaria,among which Dehong,Baoshan,Kunming,and Lincang reported 94.32％of cases.A total of 52.54％of cases were in young men.The proportion of cross-bor-der personnel flow,land input,and aircraft input were 88.89％and 11.11％respectively.A total of 98.19％of patients sought medical care within 7 days after fever onset,and 82.85％initiated diagnosis for malaria,and 84.90％of diagnoses were con-firmed by health facilities at or below the county level.Imported malaria is a major challenge in preventing re-establishment of transmission in Yunnan.Most imported cases involved cross-border malaria transmission of mainly Plasmodium vivax between China and Myanmar.To achieve malaria elimination,vigilance of health staff in malaria diagnosis and treatment should be pro-moted,and intensive malaria health education should be provided to people traveling to malaria endemic territories,to enable individual protection,and timely diagnosis and treatment after return from endemic countries.

Aim To investigate the effects of hydroxyl-safflor yellow A(HSYA)on the regenerative and re-pair functions of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods hUC-MSCs were mechanically isolated,and their morphology was ob-served.Cell surface marker expression was analyzed u-sing flow cytometry.Osteogenic differentiation was used to confirm the multipotency of the cells.The cells were treated with various concentrations of HSYA(0,100,200,400,600 μmol·L-1),and the optimal con-centration and duration of treatment were determined u-sing the CCK-8 assay.Cells were divided into four groups:control,100,200,and 400 μmol·L-1.The proliferative capacity of hUC-MSCs was assessed by EdU incorporation.Vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BD-NF)levels in the culture supernatant were measured u-sing enzyme-linked immunosorbent assays.Cell migra-tion ability was evaluated by Scratch assays.The ex-pression levels of VEGF,BDNF,and fibroblast growth factor 2(FGF2)were detected by Western blotting.Results The isolated cells exhibited characteristics consistent with stem cell surface markers and demon-strated osteogenic and adipogenic differentiation poten-tial.After 48 hours of treatment,no cytotoxicity was observed at concentrations of 100,200,and 400 μmol·L-1compared to the control group.HSYA signifi-cantly increased the number of EdU-positive cells and cell migration rate,with the most pronounced effect was achieved at 200 μmol·L-1(P＜0.01).VEGF and BDNF levels in the supernatant were elevated,with the highest expression observed at 200 μmol·L-1(P＜0.01).Similarly,the expression levels of BDNF,VEGF,and FGF2 were significantly upregulated in the HSYA groups,with the highest levels at 200 μmol·L-1(P＜0.01).Conclusion HSYA promotes the proliferation,migration and angiogenesis of hUC-MSCs,with an optimal concentration of 200 μmol·L-1.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Diabetes-related cognitive impairment(DCI)is a major complication of type 2 diabetes melli-tus(T2DM).Although exercise is essential in alleviating DCI,the underlying mechanisms remain un-clear.The aim of this study is to investigate the role and mechanism of exosomal miR-126a-5p induced by exercise in ameliorating DCI.Twenty-four 16-week-old male db/db mice were randomly divided into dia-betes group(n=12;DM)and exercise intervention group(n=12;DE).The control group consisted of male m/m mice of the same age group(n=12;CON).The DE group underwent 8 weeks of moderate in-tensity treadmill training(10 m/min,5 days a week).In the MWM experiment,compared to the CON group,the DM group exhibited prolonged escape latency(P<0.01),reduced swimming speed and target quadrant time(P<0.001),and decreased expression of miR-126a-5p and EX-miR-126a-5p in hipp-ocampal tissue(P<0.001).After exercise intervention,the DE group showed improved performance with decreased escape latency(P<0.05),increased swimming speed and target quadrant time(P<0.05),and elevated levels of exosomal miR-126a-5p(P<0.001).Morphological staining revealed a de-crease in the expression and proportion of NeuN in hippocampal neurons and an increase in the expression and proportion of glial cells in the CA1 and CA3 regions of DM group mice compared to CON group mice(P<0.05),while DE group mice showed increased fluorescence intensity and proportion of neurons(P<0.05).Western blotting analysis revealed that the DM group also showed significant upregulation of amy-loid β(Aβ),high mobility group box 1(Hmgb1),and NF-κB in the hippocampus(P<0.05),which were reduced after exercise(P<0.05).Moreover,exosomal miR-126a-5p overexpression greatly de-creased the levels of Hmgb1,NF-κB,and amyloid precursor protein(APP)in HT22 cells and TNF-α,IL-1β in supernatant exposed to HG(P<0.05),while inhibition of miR-126a-5p led to increased levels of these proteins(P<0.05).In conclusion,eight weeks of treadmill exercise improved cognitive function in db/db mice,likely through the EXs-miR-126/HMGB1/NF-κB pathway to reduce inflammation in hip-pocampal tissue.

In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70％.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.

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.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China