1.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
2.Research progress on key amino acid sites of 5-HT2A receptor
Lu-Lu XIE ; Xiao-Qian LIU ; Rui-Bin SU ; Yu-Ting LI ; Bo TAN
Chinese Pharmacological Bulletin 2024;40(11):2001-2004
As the target of many psychoactive drugs such as hal-lucinogens,antidepressants,anxiolytics and atypical antipsychot-ics,5-HT2A receptor has been a research hotspot in the field of neuropsychopharmacology.Some key amino acid sites of 5-HT2A receptor play an important role in maintaining the specific con-formation of receptor,coupling different G proteins,and exerci-sing corresponding specific functions.Further studies have shown that mutations of these specific amino acid sites can cause changes in the affinity and potency of the corresponding ligands.Moreover,5-HT2A receptor is a typical G-protein-coupled recep-tor,and different amino acid sites in its structural domain can in-teract with different ligands,causing corresponding dynamic structural changes of the receptor,thus affecting the receptor function.Therefore,studying the relationship between the struc-ture and function of 5-HT2A receptor and key amino acid sites is of great significance for the treatment of related psychiatric dis-eases and the design of new drugs with high efficiency and low toxicity.
3.Establishment and evaluation of non-obese polycystic ovary syndrome rat model
Shiqing QIAO ; Ting WANG ; Yonghuang YAN ; Jiusi YANG ; Yuling YU ; Yanmin WANG ; Yateng SUN ; Yujie WU ; Peixuan ZHU ; Min LI ; Cong CHEN ; Zeqi SU ; Cai ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):965-975
Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P<0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P<0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P<0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.
4.Multidimensional supportive psychological intervention in clinical practice teaching of andrological nursing
Li-Hong LI ; Ya-Ting SUN ; De-Yu KONG ; Shan-Na SU ; Xue ZHANG ; Liang ZHANG ; Hong-En XIANG ; Xuan LUO ; Xu-Qiang WANG
National Journal of Andrology 2024;30(3):229-232
Objective:To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention(MSPI)in the clinical practice teaching of andrological nursing care.Methods:Using the Hamilton Depression Scale(HAMD),we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from De-cember 2021 to December 2022.We equally randomized the subjects into an experimental and a control group,the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention.Results:Compared with the baseline,the HAMD scores were significantly decreased in the experimental group after intervention(12.4±2.1 vs 8.9±2.4,P<0.01),but increased in the controls(13.1±1.8 vs 14.7±1.9,P<0.01);the skill scores dramatically increased in the experimental group(82.6±4.7 vs 91.2±2.4,P<0.01),but decreased in the control group after intervention(81.0±3.5 vs 80.4±2.7,P=0.28).Conclusion:MSPI can significantly enhance the learning enthusiasm of nursing students in a short period,re-duce their psychological stress and improve teaching outcomes.This approach,combining psychology with teaching,can also strength-en the mental resilience of nursing students and better confront them with future professional challenges.
5.Analysis of clinical characteristics of food allergy in children
Guihua YU ; Ning YANG ; Mingyue GU ; Xiaojuan SHI ; Jing ZHAO ; Ran SU ; Mengli CHEN ; Youning XU ; Meiyan WANG ; Ting ZHOU
China Modern Doctor 2024;62(27):70-74
Objective To investigate the food allergy situation of children in Changping District of Beijing,and to explore the influence of allergic family history,gender and mode of delivery on food allergy in children,the distribution of food allergy in different age groups,the types of food allergy that are easy to cause in this area,and the comorbidities of food allergy.Methods A total of 515 children aged 0 to 14 years who were admitted to the general pediatric outpatient and emergency department and inpatient of Beijing Changping Hospital from April to November 2023.Using immunoblotting to detect specific immunoglobulin E in the serum of pediatric patients,and using SPSS 26.0 statistical software to perform binomial tests on gender and delivery mode non parameters;Using custom Excel functions to statistically analyze the family history of allergies,the number of people in different age groups,and the frequency of allergic foods in each group;Use a self-made mini program to statistically analyze the combination of comorbid allergic diseases.Results ① The number of male children with food allergies(306 cases)was higher than that of female children(209 cases),and the difference was statistically significant(P<0.05).(2)There were 109 cases of pediatric patients with parents who had no history of allergic diseases,accounting for 21.17%of the total cases;There were a total of 406 cases where at least one parent had a family history of allergies,accounting for 78.83%of the total cases.Among them,228 cases(44.27%)had one parent with a history of allergies,and 178 cases(34.56%)had both parents with a history of allergies.③ Among 515 children with positive food allergens,there were 10 cases(1.94%)in infancy,37 cases(7.19%)in early childhood,235 cases(45.63%)in preschool,192 cases(37.28%)in school age,and 41 cases(7.96%)in adolescence.The highest positivity rate for food allergens is in milk(444 times),followed by egg white(70 times),cashew nuts(57 times),crab(37 times),beef(26 times),mango(24 times),shrimp(21 times),pineapple(6 times),and shellfish(1 time).Milk protein is the most common allergen in all age groups.(4)Among 515 children with food allergies,399 cases were single food allergies,accounting for 77.47%;116 cases of multiple food allergies(2 or more types of food allergies),accounting for 22.53%.⑤ The most common comorbidity of food allergies is food allergy related gastrointestinal diseases combined with allergic rhinitis,with a total of 267 cases;Secondly,there were 192 cases of allergic rhinitis combined with chronic cough,and 124 cases of food allergy related gastrointestinal diseases combined with chronic cough.Conclusion Milk is the main allergen of food allergy in people of age 14 and under,and gastrointestinal symptoms are the most common in children with food allergy.
6.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
7.Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans
Jinfeng ZHANG ; Yuliang TONG ; Jiapeng WANG ; Ting SU ; Deping ZHAO ; Hao YU ; Kun ZUO ; Ziyue ZHU ; Meiling JIN ; Ning ZHANG ; Xia LEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):18-25
ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan (LW) on mitochondrial damage in the Alzheimer's disease (AD) model of Caenorhabditis elegans (C. elegans). MethodC. elegans transfected with human β-amyloid protein (Aβ) 1-42 gene was used as an AD model. The rats were divided into blank group, model group, metformin group (50 mmol·L-1), and low, medium, and high dose (1.04, 2.08, 4.16 g·kg-1) LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine (5-HT) in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate (ATP) kit, and mitochondrial membrane potential was detected by the JC-1 method. In addition, the mRNA expression of Aβ expression gene (Amy-1), superoxide dismutase-1 (SOD-1), mitochondrial transcription factor A homologous gene-5 (HMG-5), mitochondrial power-associated protein 1 (DRP1), and mitochondrial mitoprotein 1 (FIS1) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT (P<0.05) and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group, in the model group, the mRNA expression of Aβ protein and Amy-1 increased (P<0.01), and the mRNA expression of SOD-1 and HMG-5 decreased (P<0.01). The mRNA expression of DRP1 and FIS1 increased (P<0.01), and the level of mitochondrial membrane potential decreased (P<0.05). The content of ATP decreased (P<0.01). Compared with the model group, in the positive medicine group and medium and high dose LW groups, the mRNA expression of Aβ protein and Amy-1 decreased (P<0.05,P<0.01), and the mRNA expression of SOD-1 and HMG-5 increased (P<0.01). The mRNA expression of DRP1 decreased (P<0.05,P<0.01), and that of FIS1 decreased (P<0.01). The level of mitochondrial membrane potential increased (P<0.01), and the content of ATP increased (P<0.05,P<0.01). ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria, protect mitochondrial DNA, reduce the fragmentation of mitochondrial division, repair the damaged mitochondria, adjust the mitochondrial membrane potential, restore the level of neuronal ATP, and reduce the neuronal damage caused by Aβ deposition.
8.Physical performance evaluated by the timed up and go test and its correlation with sleep in the elderly in China
Yu DU ; Xinxin MA ; Jingjing DUAN ; Jianhong XIAO ; Jian LIN ; Xiong'ang HUANG ; Chao LIU ; Binbin WANG ; Ting DENG ; Tao CHEN ; Wen SU
Chinese Journal of Geriatrics 2024;43(1):29-33
Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.
9.The glutamate-serine-glycine index as a biomarker to monitor the effects of bariatric surgery on non-alcoholic fatty liver disease
Nichole Yue Ting Tan ; Elizabeth Shumbayawonda ; Lionel Tim-Ee Cheng ; Albert Su Chong Low ; Chin Hong Lim ; Alvin Kim Hock Eng ; Weng Hoong Chan ; Phong Ching Lee ; Mei Fang Tay ; Jason Pik Eu Chang ; Yong Mong Bee ; George Boon Bee Goh ; Jianhong Ching ; Kee Voon Chua ; Sharon Hong Yu Han ; Jean-Paul Kovalik ; Hong Chang Tan
Journal of the ASEAN Federation of Endocrine Societies 2024;39(2):54-60
Objective:
Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery.
Methodology:
Ten NAFLD participants were studied at baseline and 6 months post-bariatric surgery. Blood samples were collected for serum biomarkers and metabolomic profiling. Hepatic steatosis [proton density fat fraction (PDFF)] and fibroinflammation (cT1) were quantified with multiparametric magnetic resonance imaging (mpMRI), and hepatic stiffness with magnetic resonance elastography (MRE). Amino acids and acylcarnitines were measured with mass spectrometry. Statistical analyses included paired Student’s t-test, Wilcoxon-signed rank test, and Pearson’s correlation.
Results:
Eight participants provided complete data. At baseline, all had hepatic steatosis (BMI 39.3 ± 5.6 kg/m2, PDFF ≥ 5%). Post-surgery reductions in PDFF (from 12.4 ± 6.7% to 6.2 ± 2.8%, p = 0.013) and cT1 (from 823.3 ± 85.4ms to 757.5 ± 41.6ms, p = 0.039) were significant, along with the GSG index (from 0.272 ± 0.03 to 0.157 ± 0.05, p = 0.001).
Conclusion
The GSG index can potentially be developed as a marker for monitoring the response of patients with NAFLD to bariatric surgery.
Non-alcoholic Fatty Liver Disease
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Amino Acids
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Metabolomics
10.Cloning and functional characterization of α 7 nicotinic acetylcholine receptor molecular chaperone Tmem35a
Zi-han WANG ; Jin-peng YU ; Dong-ting ZHANGSUN ; Xiao-peng ZHU ; Su-lan LUO
Acta Pharmaceutica Sinica 2024;59(7):1993-2001
Nicotinic acetylcholine receptors (nAChRs) belong to ligand-gated ion channel receptors, of which


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