BACKGROUND:Naringin has been shown to promote the proliferation and osteogenic differentiation of bone marrow derived mesenchymal stem cells,making it a potential candidate for treating osteoporosis andenhancing fracture healing.However,its clinical application is limited by its low bioavailability.OBJECTIVE:To prepare chitosan/β-tricalcium phosphate scaffolds loaded with naringin and characterize their biological properties.METHODS:Chitosan/β-tricalcium phosphate scaffolds were prepared by freeze-drying and chemical crosslinking.The chitosan/β-tricalcium phosphate scaffolds were immersed in anhydrous ethanol solution containing naringin for 3 hours.After vacuum cold drying,chitosan/β-tricalcium phosphate/naringin scaffolds were obtained.The pore size,porosity,swelling rate,degradation rate,mechanical properties,and in vitro release capacity of naringin of the scaffolds were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of chitosan/β-tricalcium phosphate scaffolds and chitosan/β-tricalcium phosphate/naringin scaffolds,respectively,and cell proliferation,adhesion,activity and alkaline phosphatase activity after osteogenic differentiation were detected.RESULTS AND CONCLUSION:(1)The results of scanning electron microscopy showed that the naringin-chitosan/β-tricalcium phosphate composite scaffold had a porous mesh structure.The average pore diameter was(106.82±25.22)μm;the porosity was(76.26±4.81)％;24-hour swelling rate was(796.17±31.76)％;in vitro degradation rate of 7.71％at 4 weeks,and naringin could be slowly released in vitro for 9 days.There was no significant difference in the average pore size,porosity,24-hour swelling rate,in vitro degradation rate,compression strength and compression modulus at 4 weeks between the chitosan/β-tricalcium phosphate scaffold and the chitosan/β-tricalcium phosphate scaffold(P＞0.05).(2)Rat bone marrow mesenchymal stem cells adhered well to the surfaces of the two scaffolds and had good activity.Compared with the chitosan/β-tricalcium phosphate scaffold,the chitosan/β-tricalcium phosphate/naringin scaffold promoted the proliferation of rat bone marrow mesenchymal stem cells(P＜0.05),and increased the alkaline phosphatase activity of bone marrow mesenchymal stem cells after osteogenic differentiation(P＜0.05).(3)The results show that the chitosan/β-tricalcium phosphate/naringin scaffolds exhibit favorable physical properties and can effectively promote the adhesion,proliferation,and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Naringin has been shown to promote the proliferation and osteogenic differentiation of bone marrow derived mesenchymal stem cells,making it a potential candidate for treating osteoporosis andenhancing fracture healing.However,its clinical application is limited by its low bioavailability.OBJECTIVE:To prepare chitosan/β-tricalcium phosphate scaffolds loaded with naringin and characterize their biological properties.METHODS:Chitosan/β-tricalcium phosphate scaffolds were prepared by freeze-drying and chemical crosslinking.The chitosan/β-tricalcium phosphate scaffolds were immersed in anhydrous ethanol solution containing naringin for 3 hours.After vacuum cold drying,chitosan/β-tricalcium phosphate/naringin scaffolds were obtained.The pore size,porosity,swelling rate,degradation rate,mechanical properties,and in vitro release capacity of naringin of the scaffolds were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of chitosan/β-tricalcium phosphate scaffolds and chitosan/β-tricalcium phosphate/naringin scaffolds,respectively,and cell proliferation,adhesion,activity and alkaline phosphatase activity after osteogenic differentiation were detected.RESULTS AND CONCLUSION:(1)The results of scanning electron microscopy showed that the naringin-chitosan/β-tricalcium phosphate composite scaffold had a porous mesh structure.The average pore diameter was(106.82±25.22)μm;the porosity was(76.26±4.81)％;24-hour swelling rate was(796.17±31.76)％;in vitro degradation rate of 7.71％at 4 weeks,and naringin could be slowly released in vitro for 9 days.There was no significant difference in the average pore size,porosity,24-hour swelling rate,in vitro degradation rate,compression strength and compression modulus at 4 weeks between the chitosan/β-tricalcium phosphate scaffold and the chitosan/β-tricalcium phosphate scaffold(P＞0.05).(2)Rat bone marrow mesenchymal stem cells adhered well to the surfaces of the two scaffolds and had good activity.Compared with the chitosan/β-tricalcium phosphate scaffold,the chitosan/β-tricalcium phosphate/naringin scaffold promoted the proliferation of rat bone marrow mesenchymal stem cells(P＜0.05),and increased the alkaline phosphatase activity of bone marrow mesenchymal stem cells after osteogenic differentiation(P＜0.05).(3)The results show that the chitosan/β-tricalcium phosphate/naringin scaffolds exhibit favorable physical properties and can effectively promote the adhesion,proliferation,and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

Surface proteins play pivotal roles in physiological processes, including cell recognition, signal transduction, substance transport, and immune responses. However, challenges persist in characterizing abnormal surface proteins in disease states and identifying therapeutic targets, due to the low abundance of these proteins within the total proteome and the frequent presence of their complex glycosylation modifications. Recent years have witnessed the vigorous development of chemical proteomics, leading to the successful creation of various chemical probes for the labeling and characterization of cell surface proteins. These techniques have subsequently been applied to the detection of disease surface proteins and the discovery of corresponding targets. Surface protein characterization techniques based on chemical proteomics are discussed herein, focusing on the principles of amino acid-targeted labeling, proximity labeling, and glycoprotein capture. The novelty, advantages, and limitations of techniques such as targeted lysine labeling, peroxidase and photocatalytic proximity labeling, and chemical glycan capture and metabolic glycan labeling are elaborated, and their applications across various biological models and disease types are described, aiming to provide some reference for target discovery and drug development targeting surface proteins.

Autism spectrum disorder （ASD）， also known as autism， is a series of neurodevelopmental disorders characterized by social disorders and repetitive stereotyped behaviors/narrow interests. Its pathogenesis is complex， and there is a lack of effective treatment drugs， with some cases having adverse outcomes. Recent studies have consistently revealed that individuals with autism spectrum disorder （ASD） commonly exhibit characteristics such as gut microbiota dysbiosis （abnormal Bacteroidetes/Firmicutes ratio）， impaired intestinal barrier function （elevated serum levels of zonulin and LPS）， and intestinal immune dysregulation （increased pro-inflammatory cytokines including IL-6 and TNF-α）， suggesting that gastrointestinal abnormalities may influence central nervous system development through neuroendocrine， immunoregulatory， and metabolic pathways. Consequently， growing scholarly attention has focused on dietary interventions as potential approaches to alleviate clinical symptoms in children with ASD. This review systematically summarizes the role of gut microbiota and their metabolite alterations in ASD pathogenesis， along with recent advancements in understanding the microbiota-gut-brain axis mechanisms. Additionally， it elaborates on the therapeutic effects and underlying biological basis of restrictive diet therapy， modified diet therapy， and nutritional supplementation therapy in promoting the health of children with ASD. This systematic review reveals that children with ASD exhibit significant gut microbiota dysbiosis （e.g.， increased Clostridium， decreased Faecalibacterium） and abnormal metabolite profiles （e.g.， altered short-chain fatty acid spectra， elevated 4EPS levels）. These alterations exacerbate neuroinflammation and immune dysregulation through the microbiota-gut-brain axis， thereby impacting nervous system development and function. Furthermore， interventions such as ketogenic diets， camel milk， and specific nutritional supplements can alleviate certain ASD symptoms by modulating gut microbiota， restoring intestinal barrier function， and improving metabolic pathways. Future investigations should aim to create multi-omics evaluation systems for pinpointing potential beneficiaries， devise individualized intervention strategies rooted in microbiome characteristics， and verify their therapeutic value and safety in large-scale randomized controlled trials. These efforts are crucial to transitioning ASD treatment from symptomatic control to address disease etiology， thereby paving the way for improving prognoses.

Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Objective: To investigate the incidence and risk factors of open gingival embrasures (OGEs) in the incisor region after treatment with clear aligners in adult non-extraction patients and provide a reference for preventing the occurrence of an open gingival wedge gap in the incisal area after orthodontic treatment. Methods: This study has been reviewed and approved by the institutional medical ethics committee, and informed consent was obtained from the patients. A total of 125 adult patients with malocclusion who completed clear aligner treatment at Hefei Stomatological Hospital from September 2022 to December 2024 were selected as the study subjects. Based on the presence or absence of OGEs in the incisor region observed in frontal intraoral photographs taken immediately after treatment completion, the patients were divided into a normal group and an OGE group. Clinical data, including intraoral photographs, digital models, and cone-beam computed tomography before and after treatment, were analyzed. Measurements such as incisor overlap and rotation, crown morphology, number of attachments, and interproximal enamel reduction (IPR) were recorded and analyzed. Results: The incidence of OGEs between the maxillary and mandibular central incisors after clear aligner treatment in adult patients was 28.8% and 39.2%, respectively. No statistically significant differences were observed between the normal and OGE groups in terms of sex, Angle's classification, gingival biotype, overbite, overjet, IPR amount, age, treatment duration, tooth axis angulation, or horizontal movement distance of mandibular central incisors before and after treatment (P 0.05). However, significant differences were found in the number of attachments, anteroposterior distance between mesial incisal angles, distance from the interproximal contact point (ICP) to the alveolar bone crest (ABC) (ICP-ABC), horizontal distance between mesial cementoenamel junction (CEJ) of two adjacent central incisors (CEJ-CEJ) and labial alveolar bone thickness (P 0.05). IPR amount and mandibular incisor intrusion were significantly associated with the severity of OGEs (P 0.05). Regression analysis revealed that the number of attachments, anteroposterior distance between mesial incisal angles, ICP-ABC distance, and CEJ-CEJ horizontal distance were significantly correlated with the occurrence of OGEs. Conclusion The incidence of open gingival embrasures in the mandibular central incisor region is relatively high among adult patients treated with clear aligners. The number of attachments (n = 2), the anteroposterior distance between the mesio-incisal angles, the distance from the tooth contact point to the alveolar bone crest, and the horizontal distance between adjacent cementoenamel junctions have been identified as risk factors for the development of open gingival embrasures upon completion of orthodontic treatment.