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.

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Objective Gallstone disease(GSD)is one of the common digestive tract diseases with a high worldwide prevalence.The effects of GSD on patients include but are not limited to the symptoms of nausea,vomiting,and biliary colic directly caused by GSD.In addition,there is mounting evidence from cohort studies connecting GSD to other conditions,such as cardiovascular diseases,biliary tract cancer,and colorectal cancer.Early identification of patients at a high risk of GSD may help improve the prevention and control of the disease.A series of studies have attempted to establish prediction models for GSD,but these models could not be fully applied in the general population due to incomplete prediction factors,small sample sizes,and limitations in external validation.It is crucial to design a universally applicable GSD risk prediction model for the general population and to take individualized intervention measures to prevent the occurrence of GSD.This study aims to conduct a multicenter investigation involving more than 90 000 people to construct and validate a complete and simplified GSD risk prediction model.Methods A total of 123 634 participants were included in the study between January 2015 and December 2020,of whom 43 929 were from the First Affiliated Hospital of Chongqing Medical University(Chongqing,China),11 907 were from the First People's Hospital of Jining City(Shandong,China),1 538 were from the Tianjin Medical University Cancer Institute and Hospital(Tianjin,China),and 66 260 were from the People's Hospital of Kaizhou District(Chongqing,China).After excluding patients with incomplete clinical medical data,35 976 patients from the First Affiliated Hospital of Chongqing Medical University were divided into a training data set(n=28 781,80% )and a validation data set(n=7 195,20% ).Logistic regression analyses were performed to investigate the relevant risk factors of GSD,and a complete risk prediction model was constructed.Factors with high scores,mainly according to the nomograms of the complete model,were retained to simplify the model.In the validation data set,the diagnostic accuracy and clinical performance of these models were validated using the calibration curve,area under the curve(AUC)of the receiver operating characteristic curve,and decision curve analysis(DCA).Moreover,the diagnostic accuracy of these two models was validated in three other hospitals.Finally,we established an online website for using the prediction model(The complete model is accessible at https://wenqianyu.shinyapps.io/Completemodel/,while the simplified model is accessible at https://wenqianyu.shinyapps.io/Simplified/).Results After excluding patients with incomplete clinical medical data,a total of 96 426 participants were finally included in this study(35 876 from the First Affiliated Hospital of the Chongqing Medical University,9 289 from the First People's Hospital of Jining City,1 522 from the Tianjin Medical University Cancer Institute,and 49 639 from the People's Hospital of Kaizhou District).Female sex,advanced age,higher body mass index,fasting plasma glucose,uric acid,total bilirubin,gamma-glutamyl transpeptidase,and fatty liver disease were positively associated with risks for GSD.Furthermore,gallbladder polyps,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,and aspartate aminotransferase were negatively correlated to risks for GSD.According to the nomograms of the complete model,a simplified model including sex,age,body mass index,gallbladder polyps,and fatty liver disease was constructed.All the calibration curves exhibited good consistency between the predicted and observed probabilities.In addition,DCA indicated that both the complete model and the simplified model showed better net benefits than treat-all and treat-none.Based on the calibration plots,DCA,and AUCs of the complete model(AUC in the internal validation data set=74.1%[95% CI:72.9%-75.3%],AUC in Shandong=71.7%[95% CI:70.6%-72.8%],AUC in Tianjin=75.3%[95% CI:72.7%-77.9%],and AUC in Kaizhou=72.9%[95% CI:72.5%-73.3%])and the simplified model(AUC in the internal validation data set=73.7%[95% CI:72.5%-75.0%],AUC in Shandong=71.5%[95% CI:70.4%-72.5%],AUC in Tianjin=75.4%[95% CI:72.9%-78.0%],and AUC in Kaizhou=72.4%[95% CI:72.0%-72.8%]),we concluded that the complete and simplified risk prediction models for GSD exhibited excellent performance.Moreover,we detected no significant differences between the performance of the two models(P>0.05).We also established two online websites based on the results of this study for GSD risk prediction.Conclusions This study innovatively used the data from 96 426 patients from four hospitals to establish a GSD risk prediction model and to perform risk prediction analyses of internal and external validation data sets in four cohorts.A simplified model of GSD risk prediction,which included the variables of sex,age,body mass index,gallbladder polyps,and fatty liver disease,also exhibited good discrimination and clinical performance.Nonetheless,further studies are needed to explore the role of low-density lipoprotein cholesterol and aspartate aminotransferase in gallstone formation.Although the validation results of the complete model were better than those of the simplified model to a certain extent,the difference was not significant even in large samples.Compared with the complete model,the simplified model uses fewer variables and yields similar prediction and clinical impact.Hence,we recommend the application of the simplified model to improve the efficiency of screening high-risk groups in practice.The use of the simplified model is conducive to enhancing the self-awareness of prevention and control in the general population and early intervention for GSD.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthe-sized and then accumulated at high levels in Saccharina japonica (Sja);however, the underlying con-trol mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive tran-scriptomic data from different tissues, generations, and sexes as well as under different stress con-ditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposalineand hyperthermia conditions. Our results indicate that the ecophysiological significance of such dif-ferentially expressed genes may be attributable to the evolution of heteromorphic generations (fil-amentous and thallus) and environmental adaptation of Laminariales.