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.

Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

Objective To externally validate a prediction model based on clinical and CT imaging features for the preoperative identification of high-grade patterns (HGP), such as micropapillary and solid subtypes, in early-stage lung adenocarcinoma, in order to guide clinical treatment decisions. Methods This study conducted an external validation of a previously developed prediction model using a cohort of patients with clinical stage ⅠA lung adenocarcinoma from the Fourth Hospital of Hebei Medical University. The model, which incorporated factors including tumor size, density, and lobulation, was assessed for its discrimination, calibration performance, and clinical impact. Results A total of 650 patients (293 males, 357 females; age range: 30-82 years) were included. The validation showed that the model demonstrated good performance in discriminating HGP (area under the curve>0.7). After recalibration, the model's calibration performance was improved. Decision curve analysis (DCA) indicated that at a threshold probability>0.6, the number of HGP patients predicted by the model closely approximated the actual number of cases. Conclusion This study confirms the effectiveness of a clinical and imaging feature-based prediction model for identifying HGP in stage ⅠA lung adenocarcinoma in a clinical setting. Successful application of this model may be significant for determining surgical strategies and improving patients' prognosis. Despite certain limitations, these findings provide new directions for future research.

OBJECTIVE To prepare polyethylene glycol （PEG）-modified flower lactose （FL） loaded Curcumin （Cur） solid lipid nanoparticle （SLN） inhalable micropowder （referred to as “PEG-Cur-FL”）. METHODS PEG-Cur-FL was prepared by the solvent emulsification diffusion low-temperature solidification method， and its encapsulation efficiency， drug loading capacity， powder properties， aerodynamic particle size， in vitro deposition properties， and in vitro release characteristics were characterized. The mice were divided into Cur-SLN-FL （unmodified with PEG） group and PEG-Cur-FL group， with 55 mice in each group. Both groups of mice were given a single inhalation of 5 mg/kg （calculated as Cur） of the corresponding drug micropowder through an air tube. At 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24， 48 and 72 hours after administration， eyeballs were removed to collect blood and tracheal， lung， liver and kidney tissues were separated. The mass concentration of Cur in mouse plasma and various tissue samples was measured， and the tissue distribution and retention of the drug were analyzed. RESULTS The encapsulation efficiency and drug loading capacity of PEG-Cur-FL were （86.2±1.8）% and （4.2±0.2）%， respectively； the bulk density and tap density were （0.24±0.01） g/cm3 and （0.30±0.01） g/cm3， respectively； the aerodynamic particle size was （2.74±0.64） μm； the in vitro effective site deposition rate （secondary drug deposition rate） was （45.07±2.79）%. Compared with Cur raw materials， Cur-SLN- FL and PEG-Cur-FL had sustained release effects under both leakage and non-leakage conditions， and PEG-Cur-FL had a smoother sustained release in artificial lung fluid， with release characteristics consistent with the Weibull model. The results of in vivo distribution showed that the drug concentration in the lung tissue of PEG-Cur-FL group was significantly lower than that of Cur- SLN-FL group during the same period after 1 hour of administration， while the drug concentration in the lung tissue at 4 to 48 hours was significantly higher than that of Cur-SLN-FL group during the same period （P＜0.05）； the plasma drug concentrations of the PEG-Cur-FL group at all time points from 0.25 to 12 hours were significantly lower than those of the Cur-SLN-FL group during the same period （P＜0.05）， and the drug concentrations in liver and kidney tissues were also lower than those of the Cur-SLN-FL group during the same period （P＜0.05）. CONCLUSIONS PEG-Cur-FL is prepared successfully； the inhalable micropowder has good inhalability and release performance； after administration through the trachea， the effective concentration of Cur in lung tissue can be increased， while reducing its plasma drug concentration and drug distribution concentration in non-target organs.

Objective: To analyze the drug resistance of multidrug-resistant organism (MDRO) among hospitalized children in a children's hospital in Hebei Province from 2019 to 2023, so as to provide the basis for the rational clinical application of antibacterial drugs. Methods: Specimens including sputum, blood, urine, pus, bronchoalveolar lavage fluid, secretions, pleural fluid, and peritoneal fluid of hospitalized children from January 2019 to December 2023 were collected. Pathogen identification and drug susceptibility tests were performed on methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Escherichia coli (ESBLs-EC), extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBLs-KP), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Escherichia coli (CREC). The department distribution, specimen distribution, and drug resistance of MDROs were analyzed. Results: A total of 279 086 samples were submitted for testing, with 3 512 MDROs detected. Among these, MRSA and ESBLs-EC had relatively high detection rates of 35.76% and 41.50%, respectively. In the internal medicine pediatric patients, 1 869 MDROs were detected, accounting for 53.22%. The main departments were respiratory medicine, neonatology, and intensive care. In the surgical department, 1 643 MDROs were detected, accounting for 46.78%, with the main sources being general surgery and cardiac surgery. The highest numbers of MDROs were detected in sputum, pus, and urine samples, with 1 372, 527, and 494 isolates, representing 39.07%, 15.01%, and 14.07%, respectively. The resistance rates of MRSA to penicillin, oxacillin, and erythromycin were between 81.76% and 100.00%. ESBLs-EC and ESBLs-KP had a resistance rate of 100.00% to ceftriaxone. CRKP had a resistance rate of 100.00% to ampicillin/sulbactam and imipenem. CRAB had a resistance rate of 100.00% to cefoxitin, imipenem, and meropenem. CRPA had a resistance rate of 100.00% to ampicillin/sulbactam, ceftriaxone, cefoxitin, and imipenem. CREC had a resistance rate of 100.00% to imipenem. Conclusions In a children's hospital in Hebei Province, infections with MDROs among hospitalized pediatric patients are primarily caused by MRSA and ESBLs-EC. These infections are mainly distributed in the departments of respiratory medicine, neonatology, intensive care, general surgery, and cardiac surgery, with the highest detection rates in sputum, pus, and urine samples. Additionally, MRSA, ESBLs-EC, ESBLs-KP, CRKP, CRAB, CRPA, and CREC show high resistance rate to most antimicrobial agents.

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds.Search Genecards,OMIM,Drugbank,TTD,and PharmGKB databases to obtain targets for gastric cancer.The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer.The String database was utilized construct a protein-protein interaction(PPI)network.Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the shared targets.This process revealed significant regulatory pathways crucial for jolkinolide B's efficacy in treating gastric cancer.Cytoscape 3.7.1 software was utilized create the core network of"Potential Targets of Triptolide B in Gastric Cancer Treatment",and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.Results Jolkinolide B may target multiple proteins,including MAPK1,glycogen synthase kinae-3β(GSK-3β),and JUN,impacting the proliferation,invasion,and metastasis of gastric cancer,ultimately inhibiting its growth.Conclusion We predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Malonylation is an important post-translational modification of proteins.In this work,a comprehensive malonylation proteomics study on hepatocellular carcinoma(HCC)tumorous and non-tumorous tissues using antibody enrichment combined with high performance liquid chromatography-mass spectrometry for discovery of early diagnostic biomarkers or potential new drug targets of HCC was performed.A total of 1299 malonylated peptides containing 1064 malonylated sites were identified from HCC tissues,corresponding to 511 malonylated proteins.Quantitative results showed that 56 and 80 malonylated proteins were up-regulated and down-regulated in HCC tissues,including 60 and 101 malonylated sites,respectively.Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis showed that these differentially modified proteins were involved in various important pathways such as metabolic pathways,fatty acid degradation,and glycolysis/gluconeogenesis.As a key enzyme in glycolysis/gluconeogenesis,phosphoenolpyruvate carboxykinase 1(PCK1)was malonylated at lysine 244(K244)and the malonylation was only detected in HCC tumorous tissues.More importantly,the K244 site served as a binding site for Mn2+and highly conserved across different species.Therefore,it could speculate that the malonylation of K244 would affect its activity and played a role in liver cancer by affecting its binding with Mn2+,which requied further verification through site mutation experiments.Western blot analysis by malonylation pan antibody showed that the malonylation level reduced markedly in HCC tumorous tissues compared with adjacent non-tumorous tissues,which was consistent with mass spectrometry data.In addition,the proliferation and invasion of PLC/PRF/5 cell was significantly inhibited and protein malonylation level was increased obviously when treated with sodium malonate.All the evidence indicated that protein malonylation played an important role in HCC pathogenesis,and its molecular mechanism deserved further investigation.Furthermore,the 136 differentially malonylated proteins provided rich source of candidate targets for further research on HCC pathogenesis.

In recent years,micro photoionization detectors(μPID),with their rapid response speed and excellent sensitivity,have attracted widespread attention in both scientific research and industry.This study developed a portable gas chromatograph based on μPID technology(GC-μPID),and examined its key performance characteristics such as reproducibility,sensitivity,and online analytical capability.The results showed that the method's relative standard deviation(RSD)was controlled within 2.7%,demonstrating good reproducibility;for the standard curves of 27 kinds of volatile organic compounds(VOCs),the linearity was excellent(R2≥0.99),with detection limits of≤10 μg/m3 and benzene series compounds reaching detection limits as low as 0.5 μg/m3.In field applications at an industrial park,this method successfully identified and quantified 17 kinds of VOCs,accurately capturing their diurnal concentration variations.The results above validated that the method developed here had the capability of onsite real-time monitoring and provided an effective tool for in situ monitoring atmospheric pollutants.

By using a strategy of leveraging the ability of metal-organic frameworks(MOFs)materials to precisely regulate the spatial orientation of cyclodextrins(CD),a polystyrene-modified γ-cyclodextrin metal-organic frameworks(PS-CD-MOFs)capillary coating was established and applied to the chiral separation of amino acids in open-tubular capillary electrochromatography(OT-CEC)based on the excellent film-forming property of polystyrene(PS).Characterization results by Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)indicated that PS was successfully grafted onto the surface of CD-MOFs.The modification significantly improved the structural stability and thermal stability of CD-MOFs while maintaining the integrity of the MOFs.The PS-CD-MOFs coated capillary electrophoresis system exhibited excellent performance in separating dansylated amino acid enantiomers(Dns-D,L-AAs).Specifically,under the optimal separation conditions(Sodium dodecyl sulfate/boric acid buffer system,20 cm capillary,and 10 kV effective voltage),good separation was achieved for D,L-methionine(D,L-Met)and D,L-serine(D,L-Ser).Further quantitative analysis showed that Dns-D,L-Met presented a good linear relationship in the concentration range of 10.0-1500.0 μmol/L,with a correlation coefficient close to 0.998,demonstrating high sensitivity and repeatability.Not only did it overcome the problem that traditional CD(used as additives in capillary electrophoresis)could not precisely control the spatial orientation of chiral resolvents,but also it solved the issues of insufficient stability and bonding amount of CD-MOFs coatings by utilizing the excellent film-forming property of polymers on the inner wall of capillaries.This study provided an efficient and controllable new strategy for construction of chiral separation stationary phases.

Objective:To explore the expression of 7-dehydrocholesterol reductase (DHCR7) in gastric cancer using bioinformatics methods and its relationship with clinical pathological characteristics and prognosis of gastric cancer patients.Methods:DHCR7 expression in gastric cancer was analyzed using the UALCAN database; DHCR7 mRNA expression and its relationship with the prognosis of gastric cancer patients were analyzed using the Kaplan-Meier plotter database; The expression of DHCR7 and its correlation with tumor immune infiltration level were analyzed using Sangerbox 3.0 and TIMER database; Real-time fluorescence quantitative PCR was used to detect the expression of DHCR7 mRNA in gastric cancer tissues and adjacent tissues; immunohistochemical staining was conducted to detect the DHCR7 expression in gastric cancer tissues and adjacent tissues and its correlation with clinical pathological parameters; Receiver operator characteristic (ROC) curve was used to evaluate the efficacy of DHCR7 expression in the diagnosis of gastric cancer.Results:The analysis results of the UALCAN database showed that there were statistically significant differences in DHCR7 mRNA expression among gastric cancer patients of different genders ( χ2=18.15, P<0.001), grades ( χ2=16.32, P<0.001), and TP53 mutation status ( χ2=20.12, P<0.001). Survival analysis showed that the 10-year overall survival (OS) rate ( HR=1.55, 95% CI: 1.31-1.84, P<0.001), 10-year progression free survival (PFS) rate ( HR=1.67, 95% CI: 1.36-2.05, P<0.001), and 10-year post progression survival (PPS) rate ( HR=1.81, 95% CI: 1.43-2.28, P<0.001) of gastric cancer patients with high DHCR7 expression were significantly lower than those with low DHCR7 expression. Immune infiltration analysis showed the expression of DHCR7 was negatively correlated with the comprehensive score ( r=-0.51, P<0.001), stromal cell score ( r=-0.48, P<0.001), immune cell score ( r=-0.45, P<0.001), CD4 + T cells ( r=-3.01, P<0.001), macrophages ( r=-0.40, P<0.001), neutrophils ( r=-0.32, P<0.001), and dendritic cells ( r=-0.37, P<0.001) infiltration levels in gastric cancer, and positively correlated with the purity of gastric cancer cells ( r=0.15, P<0.001). The qRT-PCR results showed that compared with adjacent tissues (1.86±0.51), the expression of DHCR7 in gastric cancer tissues (3.43±0.13) was significantly upregulated, with a statistically significant difference ( t=42.89, P<0.001). The relative expression level of DHCR7 in normal gastric mucosal cells GES-1 was 1.06±0.19, and the relative expression levels in four types of gastric cancer cells (HGC-27, AGS, SNU-1, and SGC-7901) were 2.40±0.26, 1.88±0.11, 1.51±0.04, and 2.63±0.20, respectively, there were statistically significant differences in the expression of DHCR7 among the five types of cells ( F=38.34, P<0.001), and the relative expression level of DHCR7 in normal gastric mucosal cells was statistically significant different compared to the four types of gastric cancer cells mentioned above ( P=0.002; P=0.003; P=0.017; P<0.001) ; The immunohistochemical results showed that the high expression rate of DHCR7 in gastric cancer tissues was 80.0% (96/120), which was significantly higher than that in adjacent tissues (68.3%) (82/120) ( χ2=56.84, P<0.001). There were statistically significant differences in tumor maximum diameter ( χ2=40.17, P<0.001), histological grade ( χ2=16.20, P<0.001) and pTNM stage ( χ2=16.99, P<0.001) between patients with high and low DHCR7 expression. The ROC curve results showed that the area under the curve (AUC) of DHCR7 expression level for diagnosing gastric cancer were 0.76 (based on TCGA database, 95% CI: 0.68-0.83, P<0.001) and 0.97 (120 clinical samples of gastric cancer, 95% CI: 0.95-0.99, P<0.001), respectively. Conclusions:DHCR7 is highly expressed in gastric cancer and closely associated with poor prognosis in patients, which may be a novel biomarker for the diagnosis and prognosis of gastric cancer.