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.

ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P＜0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P＜0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P＜0.05)and negatively correlated with the expression of FBXL5 and FTH1(P＜0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P＜0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P＜0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P＜0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P＜0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P＜0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective:Elucidating causal links between gut microbiota and breast malignancies using mendelian randomization(MR)to Identify specific causal microbial taxa.Methods:Genome-wide association studies(GWAS)summary statistics on gut microbiota and breast malignancies,MiBioGen studied GWAS(N=18473)as exposure samples,and GWAS(N=123579)of breast malignancies in the IEU Open GWAS database as outcome samples.The in-verse variance weighted(IVW),weighted median and MR-Egger methods were used to analyze the MR statistical re-suits.Results:Increased abundance of Pasteurellales increased the risk of breast malignancy(IVW PFDR＜0.05,OR=1.21,95％Cl:1.07～1.36),heterogeneity test and pleiotropy test showed no effect on causality,and the"leave-one-out"method showed that the identified causal association was not driven by any single instrumental variable.The causal relationship is positive.Conclusion:Elevated abundance of pasteurellales in the gut microbiota is associated with an increased risk of breast malignancies

Objective This study aimed to explore the ability of ultrasonographic radiomics in predicting the occurrence of in-stent restenosis(ISR)after carotid artery stenting(CAS)by analyzing the correlation between radiomic features of responsible plaques in carotid artery stenosis and the incidence of ISR.Methods A retrospective collection was conducted on 206 cases that underwent CAS treatment at our hospital.The enrolled patients were randomly split into a training set(144 cases)and a test set(62 cases)at a 7∶3 ratio.We utilized the Darwin Intelligent Research Platform to extract radiomic features from each region of interest,and then screened 1125 ultrasonographic radiomic features.Different machine learning algorithms were employed to construct diagnostic models,and the best-performing classifier was selected.Various prediction models were established,including a clinical-ultrasonographic feature model,a radiomic model,and a combined clinical-ultrasonographic-radiomic model.Results Multivariate logistic regression analysis in the training set revealed that hypertension,hyperuricemia,triglycerides,and plaque location were independent risk factors for ISR after CAS.For the clinical-ultrasonographic model,the area under the curve(AUC)values for the training and validation sets were 0.896 and 0.644,respectively.The corresponding AUC values for the radiomic model were 0.961 and 0.715,while those for the combined model were 0.947 and 0.727.Conclusion The radiomic model demonstrates superior performance in predicting ISR compared to the traditional clinical-ultrasonographic model.The combined model exhibited an enhanced ability to predict ISR occurrence,thereby improving the diagnostic performance of traditional assessments.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

Objective:Elucidating causal links between gut microbiota and breast malignancies using mendelian randomization(MR)to Identify specific causal microbial taxa.Methods:Genome-wide association studies(GWAS)summary statistics on gut microbiota and breast malignancies,MiBioGen studied GWAS(N=18473)as exposure samples,and GWAS(N=123579)of breast malignancies in the IEU Open GWAS database as outcome samples.The in-verse variance weighted(IVW),weighted median and MR-Egger methods were used to analyze the MR statistical re-suits.Results:Increased abundance of Pasteurellales increased the risk of breast malignancy(IVW PFDR＜0.05,OR=1.21,95％Cl:1.07～1.36),heterogeneity test and pleiotropy test showed no effect on causality,and the"leave-one-out"method showed that the identified causal association was not driven by any single instrumental variable.The causal relationship is positive.Conclusion:Elevated abundance of pasteurellales in the gut microbiota is associated with an increased risk of breast malignancies