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.

This study aims to explore the impact of host plants on the quality of Taxilli Herba and provide a theoretical basis for the quality control of Taxilli Herba. The components of Taxilli Herba from three different host plants(Morus alba, Salix babylonica, and Cinnamomum cassia) and its 3 hosts(mulberry branch, willow branch, and cinnamon branch) were detected by widely targeted metabolomics based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). Principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and Venn diagram were employed for analysis. A total of 717 metabolites were detected in Taxilli Herba from the three host plants and the branches of these host plants by UPLC-MS/MS. The results of PCA and OPLS-DA of Taxilli Herba from the three different host plants showed an obvious separation trend due to the different effects of host plants. The Venn diagram showed that there were 32, 8, and 26 characteristic metabolites in samples of Taxilli Herba from M. alba host, S. babylonica host, and C. cassia host, respectively. It was found by comparing the characteristic metabolites of Taxilli Herba and its hosts that each host transmits its characteristic components to Taxilli Herba, so that the Taxilli Herba contains the characteristic components of the host. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the differential metabolites of Taxilli Herba from the three hosts were mainly enriched in flavonoid biosynthesis, arginine and proline metabolism, and glycolysis/gluconeogenesis pathways. Furthermore, the differential metabolites enriching pathways of Taxilli Herba from the three hosts were different depending on the host. In a word, host plants have a significant impact on the metabolites of Taxilli Herba, and it may be an important factor for the quality of Taxilli Herba.
Metabolomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Quality Control ; Salix/chemistry* ; Cinnamomum aromaticum/metabolism* ; Principal Component Analysis

Traditional Chinese medicine(TCM), a treasure of the Chinese nation, contains abundant chemical components and demonstrates unique pharmacological activities, showing important values in clinical applications. With profound connotations and broad application prospects, TCM urgently needs us to further explore and conduct systematic research. Puerarin is a small-molecule natural isoflavonoid carbon glycoside extracted from plants of Pueraria. It is also the main active ingredient of Puerariae Lobata Radix, a Chinese herbal medicine with both medicinal and edible values. Puerarin has a variety of pharmacological effects such as blood pressure-lowering, anti-atherosclerosis, anti-ischemia-reperfusion injury, antithrombotic, anti-tumor, anti-inflammatory, liver-protecting, nerve cell-protecting, and intestinal microbiota-regulating effects. It is also an active ingredient that has been widely studied. This article comprehensively reviews the research progress in the pharmacological effects and molecular mechanisms of puerarin over the years, aiming to provide references and theoretical support for the in-depth research and development as well as clinical application of puerarin.
Isoflavones/chemistry* ; Humans ; Animals ; Drugs, Chinese Herbal/chemistry* ; Pueraria/chemistry*

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.