1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
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.
2.Construction of Tax-PC/SDC/PVP-K30 micelles and their protective effect on alcoholic liver injury
Shi-yu ZHANG ; Jing-meng SUN ; Dong-dong LI ; Xin ZHANG ; Jia-hui ZHANG ; Wei-yu ZHANG
Acta Pharmaceutica Sinica 2025;60(2):488-497
Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by
3.Cryopreservation of small-volume red blood cells: evaluation of blood group antigen reactivity and its application value
Yaling ZHAO ; Yanxia WANG ; Ziye WANG ; Siyu MA ; Wei SHAO ; Yuanyuan ZHANG ; Xin JIANG ; Jia GAN
Chinese Journal of Blood Transfusion 2025;38(3):352-357
[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.
4.Research progress on the mechanism of action of traditional Chinese medicine regulating Nrf2 signaling pathway to improve sepsis-induced lung injury
Yang LI ; Ruifen ZHANG ; Tingting JIA ; Hairong ZHANG ; Jian ZHAO ; Xinsheng HUANG ; Xiao LI ; Xin ZHONG
China Pharmacy 2025;36(12):1530-1535
Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome, whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress, the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine (TCM) to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients (including five types of compounds: flavonoids, terpenes, alkaloids, saponins, phenols) and 6 kinds of compound preparations (including three types of formulas: heat-clearing and detoxifying formulas, purgative formulas for promoting bowel movement, and formulas for reinforcing vital qi and consolidating the constitution) can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1, heme oxygenase-1, antioxidant response element and AMP-activated protein kinase, thereby alleviating sepsis-induced lung injury.
5.Research on the enrollment status of students in Master's Degree Program in Pediatrics in China and the countermeasures
Mingyue WEN ; Xin JIN ; Jinzhong JIA ; Zhisheng LIANG ; Yuexin LI ; Rui ZHU ; Mengquan LIU ; Qi YAN ; Mengting ZHANG ; Zhiqiang WANG
Chinese Journal of Medical Education Research 2024;23(9):1197-1202
Objective:To investigate the enrollment scale and distribution of Master's Degree in Pediatrics programs in China, and to provide a reference for promoting pediatric education and disciplinary development.Methods:Data on colleges and universities authorized to award Master's Degree in Pediatrics in 2023 were collected, sorted, and analyzed for the number, structure, distribution, and enrollment scale and direction of these institutions using descriptive statistics.Results:Among the 117 clinical medicine academic master's degree programs in China, 72 enroll pediatric academic master's degree candidates, with an enrollment of 260 students. Among the 120 master's degree programs in clinical medicine, 104 enroll professional master's degree candidates, enrolling 1 195 students. Enrollment is mainly concentrated in East China, "non-double first-class" colleges and universities, medical colleges and universities with subject level B, and enrollment is carried out in the direction of secondary disciplines.Conclusions:The number of colleges and universities authorized to award Master's Degree in Pediatrics was small, and the distribution of these colleges and universities was unbalanced. The enrollment scale was small and the orientation of Professional Master's Degree was not reasonable. Some colleges and universities were authorized to award Master's Degree in Pediatrics, but did not enroll any students. It is suggested to increase the number of colleges and universities authorized to award Master's Degree in Pediatrics and strengthen the staffing of pediatric departments. The aim is to expand the enrollment scale of candidates for Master's Degree in Pediatrics, improving the differential training of candidates for Academic Master's Degree and Professional Master's Degree, and attach importance to the construction of pediatrics.
6.Research progresses of endogenous vascular calcification inhibitor BMP-7
Xin ZHOU ; Lu XING ; Peng-Quan LI ; Dong ZHAO ; Hai-Qing CHU ; Chun-Xia HE ; Wei QIN ; Hui-Jin LI ; Jia FU ; Ye ZHANG ; Li XIAO ; Hui-Ling CAO
Chinese Pharmacological Bulletin 2024;40(7):1226-1230
Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.
7.Digital study on proximal clavicle anatomical plate based on 3D printing technology
Yi ZHENG ; Xing-Guo ZHENG ; Jia-Kai ZHANG ; Jun-Long WU ; Xin-Hua YUAN
China Journal of Orthopaedics and Traumatology 2024;37(3):278-280
Objective To explore feasibility of 3D metal printing technology combined with virtual design proximal clavicle anatomical plate.Methods A 52-year-old male healthy volunteer was retrospectively selected to design proximal clavicle anatomical plate system by using Mimics15.01,NX12.0 and other software.STL data were input into 3D printer to print 1∶1 clavicle model and proximal clavicle anatomical plate.The fit of the plate was tested in vitro and the accuracy of screw position was evaluated by imaging.Printing time of model,nail path design and fabrication time of the anatomical plate at proximal clavicle were recorded.Results The 3D metal printing proximal clavicle anatomical plate fitted well to clavicle model,orienta-tion of proximal clavicle locking screw was accurate,and X-ray and CT scan showed the screw position was good.Printing time of model,the time of nail path design,and the time of making anatomical plate of proximal clavicle were 120,15 and 300 min respectively.Conclusion The proximal clavicular anatomical plate system based on 3D metal printing technology could achieve good lamination of proximal clavicular fracture plate and precise screw placement,providing a new and accurate surgical method for the treatment of the proximal clavicular fracture.
8.Finite element analysis of anatomic plate fixation for proximal clavicular fractures
Yi ZHENG ; Jia-Kai ZHANG ; Jun-Long WU ; Xin-Hua YUAN
China Journal of Orthopaedics and Traumatology 2024;37(9):917-920
Objective To explore establishment and finite element analysis of personalized proximal clavicular anatomical plate screw fixation model.Methods A 40-year-old male healthy volunteer was selected and the finite element analysis modules of 3D reconstruction software Mimics 15.01,Hypermesh 2019 and Abaqus 2020 were used.The finite element model of anatomic plate at the proximal clavicle was established,and a vertical load of 250 N was applied to the distal end of long axis of clavicle about 15 mm,then the overall structure,plate and screw displacement cloud image,Mises stress distribution were ob-served.Results The displacement distribution of the overall structure shows the maximum displacement was distributed on the distal clavicle.Under the four conditions of normal upper limb weight,longitudinal clavicle fracture,oblique fracture and shoulder impact violence during fall,longitudinal clavicle fracture and oblique fracture,the maximum displacement were 1.04 mm,1.03 mm,1.35 mm and 1.33 mm,respectively.The displacement cloud map of titanium alloy steel plate showed the largest displacement was distributed near the distal clavicular bone,and the maximum displacement were 0.89 mm,0.88 mm,1.10 mm and 1.09 mm,respectively.The displacement cloud map of titanium alloy screw showed the largest displacement was distribut-ed at the root of the distal screw,and the maximum displacement were 0.88 mm,0.87 mm,1.08 mm and 1.06 mm,respectively.Mises stress distribution showed the maximum stress was mainly distributed on titanium alloy plates and screws,and the stress on the clavicle was very small.Mises stress distribution cloud showed the maximum Mises stress was distributed at the second row of screw holes near the clavicle,and the maximum Mises stress were 673.1,678.1,648.5,654.4 MPa,respectively.The maximum stresses of titanium alloy screws were 414.5,417.4,415.8 and 419.7 MPa,respectively.Conclusion The biomechan-ical changes of personalized proximal clavicular anatomical plates are demonstrated by using 3D finite element method to pro-vide biomechanical data for personalized proximal clavicular anatomical plates.
9.Chain of transmission and gene sequence analysis of SARS-CoV-2 Omicron BA.2.3.7 infection caused by a cold chain product
Xin-Xin YANG ; Zhi-Wei CHEN ; Min-Hong CHEN ; Hai-Mei JIA ; Xiao-Yang ZHANG
Chinese Journal of Zoonoses 2024;40(4):384-390
The aim of this study was to trace to origin of SARS-CoV-2 originating from imported cold-chain products re-sponsible for an outbreak that occurred on September 6-9,2022 in Mawei District,Fuzhou City,Fujian Province,China.Sam-ples from all positively infected persons and one positive sample from a swab of a cold-chain product during the outbreak were collected for gene sequencing.Epidemiological investigations were conducted on all positively infected persons to analyze the chain of transmission of the virus.Nucleic acids were detected by real-time fluorescence quantitative PCR,and the outbreak was characterized by a total of eight positive infections,which were asymptomatic.Whole-genome sequencing of three infected per-sons and one cold-chain product sample identified 75 nucleotides and 55 amino acid mutation sites of the BA.2.3.7 variant,with four highly homologous whole-genome sequences.These results confirmed that the outbreak was caused by exposure to impor-ted cold-chain products carrying the SARS-CoV-2 Omicron BA.2.3.7 strain.
10.Molecular epidemiological characteristics of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018
Zhen-Guo GAO ; Muti-Mahe ; Jun ZHAO ; Jia HUANG ; Xuan ZHANG ; Yuan CHEN ; Lina·Turxunbayi ; Quan-Xi LI ; Xin MA
Chinese Journal of Zoonoses 2024;40(8):774-781
This study was aimed at analyzing the molecular epidemiological characteristics of all 14 cases of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018,to provide a scientific basis for prevention,control,and treatment.The genomic sequence was obtained through high-throughput gene sequencing after nucleic acid extraction.Homolo-gy analysis,evolution analysis,mutation locus analysis,and homology modeling were performed in bioinformatics analysis software.The nucleotide homology and amino acid homology of the HA gene in 14 human infected H7N9 viruses were(97.39%-100%)and(98.38%-100%),respectively.The nucleotide homology of the NA gene and the amino acid homology ranged from 97.73%to 100%.All viruses were low pathogenic avian influenza viruses belonging to the Yangtze River Delta lin-eage and were divided into two subclades,which were most similar to the A/Hunan/02650/2016 vaccine strain.All HA pro-teins G186V and T160A were mutated;13 strains of Q226L were mutated;and none of the four key neuraminidase inhibitor resistance sites of NA protein were mutated.All sites of M2 protein S31N and V27A were mutated,all sites of PB1 protein T368V were mutated,and all sites of PA protein K356R were mutated.Xinjiang H7N9 virus exhibited double receptor bind-ing,and was resistant to amantadine drugs and sensitive to neuraminidase inhibitors,which may be used in early disease sta-ges.Strengthened monitoring and timely detection of avian in-fluenza virus genome changes will be critical for prevention and control,and formulation of countermeasures.

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