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 explore the role of resilience and stress in childhood maltreatment and adolescent depression and anxiety symptoms, and to provide a basis for adolescent psychological intervention. Methods From September to October 2022, a total of 11 217 students from four middle schools in Changsha were selected by multistage stratified sampling, and the Childhood Trauma Questionnaire, Depression–Anxiety–Stress Scales and the Resilience Scale for Chinese Adolescents were used to carry out online questionnaire survey. Results The detection rate of depressive symptoms and anxiety symptoms in adolescent was 19.43% (2 179) and 28.7% (3 224). The direct effect of childhood maltreatment on depressive symptoms was significant (β =0.09), Childhood maltreatment is a negative prediction of resilience (β = -0.57) and a positive prediction of pressure (β =0.06); Resilience can negatively predict stress (β = -0.61) and depressive symptoms (β = -0.25) (all P values <0.001); The direct effect of childhood maltreatment on anxiety symptoms was significant (β =0.03), resilience negatively predicts anxiety symptoms (β = -0.08) (all P values <0.01). Resilience and stress have a partially mediating role between childhood maltreatment and depressive symptoms, the mediation effect value was 0.39, accounting for 81.25% of the total effect. The effect values of the three pathways accounted for 29.17%, 8.33% and 43.75% of the total effect, respectively. Resilience and stress have a partial mediating effect between childhood abuse and anxiety symptoms, and the mediating effect was 0.36, accounting for 92.31% of the total effect, and the effect values of the three pathways accounted for 12.82%, 10.26% and 69.23% of the total effect, respectively. Conclusion Childhood maltreatment could affect adolescents’ depression and anxiety through the chain mediating effect of resilience and stress.

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.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.

Hymenoptera venom-sensitized patients may experience systemic reactions,and severe patients may even present life-threatening symptoms such as collapse and syncope.Here we report a case of anaphylaxis triggered by multiple sensitization with Hymenoptera venom.Clinical diagnosis and in vitro allergen testing showed that the patient developed anaphylaxis to wasp and/or fire ant venom.In clinical practice,allergen testing of patients with anaphylaxis to Hymenoptera venom aims to clarify the sensitizing proteins and lay a foundation for future research on immunotherapy for Hymenoptera venom in China.For Hymenoptera-allergic patients,daily outdoor protection is crucial,and an epinephrine syringe can be carried with them if necessary.
Anaphylaxis/etiology* ; Humans ; Animals ; Hymenoptera/immunology* ; Arthropod Venoms/adverse effects* ; Male ; Female ; Middle Aged ; Adult ; Wasp Venoms/adverse effects*