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 and aims Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide, with no currently effective treatment. ALD is caused by excessive lipid buildup, which eventually triggers inflammation and fibrosis in the liver. Activation of hepatic Kupffer cells (KCs) and macrophages drives liver inflammation, which can worsen alcohol-induced liver injury. The autophagy-lysosome system is crucial for macrophages to support their innate immune functions. Transcription factor EB (TFEB) is a key regulator of autophagy and lysosomal biogenesis, but the role of macrophage TFEB in ALD development is unknown. The aim of this study was to evaluate the effects of Gao-binge alcohol consumption on myeloid cell TFEB and elucidate the role of myeloid TFEB in ALD. Methods Two-to-three-month-old male and female LysM Cre− (WT) and LysM Cre+ Tfeb Flox/Flox (f/f) (myeloid-Tfeb KO) mice were subjected to chronic alcohol feeding plus an acute binge following the Gao-binge model. Serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol content were determined using biochemical assays. Total hepatic protein content and messenger RNA (mRNA) levels of autophagy-related proteins and inflammatory markers were determined using immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). Isolated hepatic infiltrating macrophages and KCs from mice given intragastric ethanol infusions were analyzed by Western blot for TFEB and autophagy-related protein content. Raw 264.7 macrophages were treated with ethanol, lipopolysaccharide (LPS), and LPS plus ethanol to examine nuclear TFEB translocation using immunofluorescence. Results We found that TFEB levels were higher in macrophage/KC cells than in hepatocytes and cholangiocytes. While ethanol feeding increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as hepatic triglyceride levels, no significant differences were observed between WT and myeloid-Tfeb KO mice. The number of F4/80-positive KCs/macrophages was similar in all four experimental groups, but hepatic neutrophil infiltration increased in alcohol-fed myeloid-Tfeb KO mice. LPS or ethanol alone induced nuclear TFEB translocation only moderately in Raw 264.7 macrophages. Conclusions Our findings suggest that myeloid TFEB is dispensable for alcohol-induced liver injury in mice.

Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.

Objective:To investigate the relationship between the morphology of bone marrow plasma cells, the identification of M protein, and the detection of minimal residual disease(MRD)by flow cytometry in elderly patients with multiple myeloma(MM).Additionally, the impact on progression-free survival(PFS)is analyzed.Methods:A total of 60 elderly MM patients with bone marrow morphology reports and corresponding flow MRD detection, collected from February 1, 2017, to January 31, 2022, at Beijing Chaoyang Hospital Affiliated to Capital Medical University, were included in this study.We collected data on plasma cells from morphological examination and flow cytometry-based MRD detection. By combining these findings with M-protein identification results from 35 cases, we analyzed the correlations among these three parameters. Patients were stratified into two groups based on median values of: flow cytometry MRD(0.246% of nucleated cells), morphological plasma cell percentage(3.5%), and M-protein quantification(2.5 g/dl).This stratification enabled evaluation of their prognostic value for PFS.Results:A total of 60 elderly MM patients were enrolled, including 41 males with age of 65.0(63.0, 68.5)years and 19 females with age of 67.0(64.0, 72.0)years The morphology of bone marrow in 60 elderly patients with MM revealed 10 cases of primitive plasma cells(16.67%), 48 cases of immature plasma cells(80.00%), and 2 cases with no plasma cells(3.33%).A positive correlation was observed between the proportion of bone marrow plasma cells and the corresponding flow MRD in terms of both the proportion of nuclear cells and the proportion of plasma cells.Specifically, the proportion of the morphological protoplasma group showed a strong correlation with flow MRD(proportion of plasma cells)( r=0.82, P<0.01), while the proportion of the morphological immature plasma group exhibited moderate correlations with flow MRD(proportion of nuclear cells)( r=0.74, P<0.05)and flow MRD(proportion of plasma cells)( r=0.70, P<0.01).No significant correlation was found between the type and quantity of M protein and flow MRD( P>0.05).The PFS time for the flow MRD ≥0.246%(nucleated cells)group was shorter than that of the<0.246% group( P<0.05).There was no significant difference in PFS between the groups with plasma cell ratios ≥3.5% and<3.5%( P=0.15).Additionally, no significant difference in PFS was observed between patients with M protein quantitation ≥2.5 g/dl and those with M protein quantitation<2.5 g/dl( P=0.94). Conclusions:The proportion of bone marrow plasma cells correlates with flow MRD in elderly patients with MM, and a high MRD load indicates a poor prognosis.However, no significant correlation was found between M protein levels and flow MRD or PFS.Clinical attention should focus on the dynamic monitoring of plasma cell morphology and flow MRD.Nevertheless, the morphological detection of plasma cells remains crucial for auxiliary diagnosis due to its intuitiveness, cost-effectiveness, and broad applicability.

Objective:To analyze the characteristics and influential factors of ischemic stroke in young adults.Methods:This study used a retrospective research design. From May 2021 to April 2022, a total of 80 patients aged 18 to 45 years with acute ischemic stroke, who were hospitalized in the Department of Neurology of Yuncheng Central Hospital, were selected for the patient group. Additionally, 80 healthy individuals in the same age range who underwent outpatient examinations during this period were selected as the control group. The risk factors, imaging characteristics, pathological causes, severity, progression, and prognosis of ischemic stroke were analyzed.Results:The average age of the 80 patients with ischemic stroke was (39.6 ± 5.1) years. These patients included 56 male patients (70.0%) and 24 female patients (30.0%). Univariate analysis revealed statistically significant differences in the prevalence of hypertension ( χ2 = 70.45, P < 0.001), hyperlipidemia ( χ2 = 92.35, P < 0.001), hyperglycemia ( χ2 = 8.73, P < 0.001), smoking ( χ2 = 14.82, P < 0.001), alcohol consumption ( χ2 = 4.81, P < 0.001), and familial inheritance ( χ2 = 3.79, P < 0.001) between the patient and control groups. Multivariate logistic regression analysis indicated that hyperlipidemia ( OR = 6.75, 95% CI: 4.21-10.04, P < 0.001), hypertension ( OR = 5.83, 95% CI: 3.75-9.34, P < 0.001), smoking ( OR = 7.36, 95% CI: 1.37-3.04, P < 0.001), alcohol consumption ( OR = 1.57, 95% CI: 1.03-2.42, P < 0.001), familial inheritance ( OR = 1.66, 95% CI: 1.01-2.49, P < 0.001), and hyperglycemia ( OR = 2.16, 95% CI: 1.22-3.56, P < 0.001) are independent risk factors for ischemic stroke in young adults. Conclusions:Hyperlipidemia, hypertension, smoking, alcohol consumption, family history, and hyperglycemia are risk factors for ischemic stroke in young adults. It is essential to enhance the promotion of healthy living practices and to monitor patients' blood pressure and lipid levels regularly, as this can help reduce the likelihood of stroke occurrence.

Objective:To compare the treatment time stability, inter- and intra-fraction errors, and clinical target volume (CTV) to planning target volume (PTV) margin expansions under different gated window settings in deep inspiration breath hold (DIBH) radiotherapy for breast cancer, and to analyze the correlation between organ at risk (OAR) dose optimization and changes in lung volume.Methods:A retrospective analysis was conducted on 65 patients with left-sided breast cancer who received DIBH radiotherapy after modified radical mastectomy. CT simulation positioning was performed using 2 mm or 3 mm gated window for DIBH, followed by target delineation, treatment planning, and dose verification. During treatment, setup errors guided by cone beam CT (CBCT), intra-fraction monitoring errors, and treatment times were recorded. The coefficient of variation (CV) of treatment time was calculated for both gated window settings. Based on inter- and intra-fraction error distributions, the expansion distance of the CTV were determined using the van Herk formula. Dosimetric differences between DIBH and free-breathing (FB) plans for the left lung, heart, and left anterior descending coronary artery (LAD) were compared. Spearman correlation analysis was performed between the relative increase in left lung volume and the relative reduction in OAR dose. Paired t-tests were used for inter-group comparisons. Results:The mean CV of the 3 mm gated window group was 0.08±0.03, which was lower than that of the 2 mm group (0.10±0.04; t=-3.91, P<0.001). The setup errors of the 2 mm group in the X, Y, and Z directions were (1.27±1.03), (1.68±0.94), (1.90±1.25) mm, respectively-significantly smaller than those of the 3 mm group [(1.81±1.41), (2.07±1.69), (2.93±1.90) mm; t=-5.80, -2.33, -5.33; P<0.001,=0.014,<0.001). Setup errors for both groups were within the 25%-75% range and all below 5 mm. The intra-fraction deviations of the 2 mm group in the X, Y, and Z directions were (0.54±0.33), (0.79±0.44), (0.70±0.53) mm, respectively, significantly smaller than those of the 3 mm group [(0.62±0.43), (0.93±0.66), (0.87±0.67) mm; t=-3.87, -3.46, -2.71,all P<0.001). The mean intra-fraction errors of both groups were within 1 mm, with greater deviations in the Y and Z directions than those in the X direction. The CTV expansion margins for the 2 mm group in the X, Y, and Z directions were 4.21, 5.35, 5.99 mm, respectively, while those for the 3 mm group were 5.81, 6.89, 9.06 mm. Compared with FB, DIBH significantly reduced the doses to the left lung, heart, and LAD (all P<0.01). The increase in left lung volume was moderately negatively correlated with the reduction in left lung D mean ( r=-0.43, P=0.028), and highly negatively correlated with the dose reductions to the heart and LAD (both P<0.001). Conclusions:The variability in respiratory gated window settings can lead to differences in treatment time stability as well as inter- and intra-fraction errors, consequently affecting CTV-to-PTV margins. The DIBH technique demonstrates significant dosimetric benefits in reducing radiation exposure to the left lung, heart, and LAD. Volumetric expansion of the left lung is strongly and inversely correlated with the reduction in radiation dose to both the heart and LAD.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy