GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Objective: To assess the awareness and associated factors of wild mushroom poisoning among students in Guizhou Province, so as to provide a scientific foundation for wild mushroom poisoning prevention and control among students. Methods: By a multi stage stratified cluster random sampling method, 1 162 students from Guizhou Province were selected in May 2024. The questionnaire survey was administered to evaluate knowledge regarding wild mushroom poisoning. Data were analyzed employing the χ 2 test and Logistic regression model. Results: Among the nine questions assessing awareness of wild mushroom poisoning, only three had the awareness rate exceeding 70%. Binary Logistic regression analysis revealed that students who "actively learn about the prevention of wild mushroom poisoning" ( OR=0.48, 95%CI =0.26-0.92) and "spread knowledge about wild mushroom poisoning to others" ( OR=0.47, 95%CI =0.33-0.69) scored higher on the wild mushroom poisoning knowledge questions ( P <0.05). Conversely, students with a habit of consuming wild mushrooms ( OR=1.52, 95%CI =1.15-2.02) scored lower ( P < 0.05 ). 42.3% of the students suggested that scientific dissemination and publicity about wild mushrooms should be intensified. Conclusions The awareness rate of wild mushroom poisoning knowledge among students in Guizhou Province requires further attention. Comprehensive knowledge should be disseminated systematically through various channels to further improve students awareness of the prevention and control of wild mushroom poisoning.

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Objective To investigate the role of dynamin-related protein 1(Drp-1)and peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)in the lung tissues of neonatal rats with meconium aspiration syndrome(MAS)and its mechanism.Methods Fifty 2-3-week-old SD neonatal rats were randomly divided into five groups(n=10):control group,model group and SN50 low,medium and high concentration groups.In control group,2 ml/kg of saline was injected into the trachea after tracheal exposure,and 2 ml/kg of meconium suspension was injected into the trachea of the rest of groups;after 24 h,control and model groups were left untreated,and 100 μl of each of SN50 concentrations of 10,30,and 60 μg/ml was injected into SN50 low,medium,and high concentration groups intraperitoneally;the rats of each group were killed after 6 h,and the chest X-rays,the gross views of the lungs,the lung wet/dry weight ratios(W/D),and the lungs of the rats in control group and model group were examined.After 6 h,the rats in each group were executed,and the pathological changes of lung tissue were observed by chest radiographs,lung gross view,lung wet/dry weight ratio(W/D)and HE staining;Western blotting was used to detect the changes of nuclear factor κB(NF-κB)(p65),p-NF-κB p65(p-p65),Drp-1,and PGC-1α proteins expression in neonatal rat lung tissues,and immuno-histochemistry was used to observe the expression of p65,Drp-1,and PGC-1α related proteins expression in neonatal rat lung tissues.Results Compared with control group,model group showed inflammatory infiltration in the chest radiograph and gross view,and the W/D and lung injury pathology scores were significantly higher(P＜0.05);compared with model group,the chest radiograph and gross view of inflammation were slightly reduced in SN50 low,medium and high concentration groups,and the W/D and lung injury pathology scores were significantly lower(P＜0.05).Western blotting showed that,compared with control group,the protein expression levels of p-p65 and Drp-1 in the lung tissues of neonatal rats were significantly higher in model group(P＜0.05),and the protein expression level of PGC-1α was significantly lower(P＜0.05);compared with model group,the protein expression levels of p-p65 and Drp-1 were significantly lower in SN50 low,medium,and high concentration groups(P＜0.05),and the difference in the protein expression level of PGC-1α in SN50 low concentration group was not statistically significant(P＞0.05),whereas the PGC-1α expression levels in SN50 medium and high concentration groups were significantly higher(P＜0.05);the difference in the total p65 protein expression levels in each group was not statistically significant(P＞0.05).Immunohistochemical assay results showed that,compared with control group,p65 and Drp-1 protein expression levels were significantly higher in model group(P＜0.05),and PGC-1α protein expression level was significantly lower(P＜0.05);compared with model group,p65 protein expression level was significantly lower in SN50 low concentration group(P＜0.05),and the difference in Drp-1 and PGC-1α protein expression levels were not statistically significant(P＞0.05),Drp-1 protein expression level was significantly lower(P＜0.05),and PGC-1α protein expression level was significantly higher(P＜0.05)in SN50 middle and high concentration groups.Conclusion Fecal inhalation can induce lung tissue inflammation in neonatal rats,and the mechanism may be related to enhanced oxidative stress,promotion of mitochondrial dysfunction,activation of the Drp-1/NF-κB signaling pathway,and inhibition of PGC-1α protein expression.

Humans ; Myocarditis/diagnostic imaging* ; Magnetic Resonance Imaging ; Myocardium ; Giant Cells

ObjectiveA growing body of research suggests a strong link between metabolic imbalance and Alzheimer’s disease (AD). In recent years, the development of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in AD. Serum levels of tryptophan and tyrosine were associated with mild cognitive impairment (MCI) and AD. The purpose of this study is to further characterize tryptophan and tyrosine levels in MCI and AD. MethodsWe stratified 765 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort into cognitively normal (CN; n=207), stable mild cognitive impairment (sMCI; n=201), progressive mild cognitive impairment (pMCI; n=171), and dementia due to AD (n=186). Serum tryptophan and tyrosine were analyzed for diagnostic value of MCI and AD. To evaluate the relationships between serum tryptophan and tyrosine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (¹⁸F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. ResultsSerum tryptophan was decreased in patients with AD, pMCI or sMCI compared with CN. Serum tyrosine was decreased in patients with AD or pMCI compared with CN. Serum tryptophan has diagnostic value for pMCI and AD. Serum tyrosine has diagnostic value for AD. ConclusionSerum tryptophan and tyrosine contribute to the early diagnosis of AD. The detection of tryptophan and tyrosine can contribute to the pathogenesis of AD. Serum tryptophan and tyrosine were not significantly associated with core AD markers, cognitive function, brain structure and brain metabolism, so serum tryptophan and tyrosine may not be good peripheral AD biomarkers.

Humans ; Myocarditis/diagnostic imaging* ; Magnetic Resonance Imaging ; Myocardium ; Giant Cells

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.