ObjectiveTo investigate the value of predictive models established based on machine learning methods in predicting the risk of metabolic associated fatty liver disease （MAFLD）， and to analyze its key risk factors. MethodsA retrospective analysis was performed for the 50 variables of 2 168 healthy individuals who underwent physical examination in Department of Health Assessment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， from January 2021 to December 2024， including body composition， past history， and laboratory tests， and according to whether they were diagnosed with MAFLD or not， they were divided into MAFLD group with 265 individuals and non-MAFLD group with 1 903 individuals. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Randomly split the research data into a training set and a validation set in a 70% to 30% ratio. Predictive factors were screened from the training set data using univariate analysis， LASSO regression， and multivariate Logistic regression analysis. Predictive models were then constructed using seven machine learning methods： Logistic regression， decision tree， random forest （RF）， eXtreme gradient boosting， light gradient boosting machine， support vector machine， and artificial neural network. Model performance was evaluated by plotting receiver operating characteristic curve for the validation set and calculating the area under the curve （AUC）， sensitivity， specificity， and Youden index for each model. Furthermore， the SHapley Additive exPlanation （SHAP） method was used to analyze the contribution of variables in the optimal model. ResultsThe prevalence rate of MAFLD among the 2 168 subjects was 12.22% （265/2 168）. Smoking， diastolic blood pressure， phase angle， visceral fat area， muscle fat ratio， waist-to-hip ratio， aspartate aminotransferase， non-HDL-C/HDL-C ratio， triglyceride-glucose index， and gallstones were independent risk factors for MAFLD （all P<0.05）. The seven predictive models of support vector machine， eXtreme gradient boosting， decision tree， light gradient boosting machine， artificial neural network， RF， and Logistic regression had an AUC of 0.738， 0.754， 0.757， 0.786， 0.795， 0.796， and 0.815， respectively， in the validation set， among which the RF model had the best discriminatory ability （AUC=0.796， 95% confidence interval： 0.754 — 0.839）， with a sensitivity of 81.01%， a specificity of 63.16%， and a Youden index of 44.17%. The SHAP analysis showed that visceral fat area， waist-to-hip ratio， and diastolic blood pressure were the top three predictive factors in terms of importance. ConclusionThe RF model， constructed based on body composition and clinical indicators， has a good performance in predicting the risk of MAFLD， and its interpretability can help to identify high-risk individuals in the early stage in clinical practice.

Inteins are unique protein insertion sequences capable of self-excision, enabling the covalent ligation of flanking extein peptides via amide bond formation. This process proceeds spontaneously without requiring external enzymes, cofactors, or chemical reagents, granting inteins exceptional biocompatibility and traceless performance in protein engineering applications. Split inteins represent a specialized and versatile subclass whose splicing domains are encoded by two separate gene fragments rather than a single continuous open reading frame. These fragments, known as the N-terminal (IntN) and C-terminal (IntC) split inteins, associate through non-covalent interactions including hydrophobic forces, hydrogen bonds, and van der Waals forces to assemble into an active three-dimensional structure, which then drives efficient extein ligation and enables protein trans-splicing. Protein trans-splicing mediated by split inteins has become a cornerstone for traceless protein ligation owing to its high specificity and irreversibility, fundamentally reshaping strategies for protein modification, assembly, and functional regulation. Compared with traditional chemical ligation methods, split intein systems require no complex chemical derivatization of peptide fragments and can operate efficiently at micromolar concentrations under physiological conditions, thus avoiding structural and functional damage caused by organic reagents. In contrast to enzymatic ligation tools such as sortase, split inteins eliminate the need for additional enzymes or cofactors, simplifying reaction systems, reducing costs, and minimizing non-specific side products. These distinctive advantages render split inteins highly promising for applications in chemical biology, synthetic biology, and biopharmaceutical development. In recent years, deepened mechanistic understanding has established structure-guided rational design as the primary approach to overcoming key limitations of split inteins, including intrinsic aggregation propensity, strict extein sequence dependence, and limited splicing efficiency. Bioinformatic tools have been used to identify aggregation-prone regions in the IntN fragment, and site-directed mutagenesis of hydrophobic residues, relocation of split sites, or removal of misfolding-prone sequences has substantially reduced in vitro aggregation and improved soluble expression and assembly activity. Rational engineering of catalytic residues and adjacent flexible loops has relaxed strict amino acid preferences at extein junctions, enhancing sequence tolerance and reducing the risk of functional impairment in target proteins. Consensus design based on multiple sequence alignments has yielded ultra-fast splicing variants such as Cfa DnaE and Cat-TerL, which exhibit significantly accelerated kinetics and improved tolerance to denaturing conditions. Meanwhile, advances in structural biology have further clarified the conformational dynamics and catalytic mechanisms of splicing, supporting the precise design of high-performance intein modules. On this basis, electrostatic interaction tuning and metagenomic screening have yielded multiple mutually orthogonal split intein pairs, enabling selective multi-fragment protein ligation and providing new routes for the efficient synthesis of large multi-domain functional proteins. With these engineered split inteins offering continuously improved performance and expanded applicability, protein trans-splicing has been widely applied in numerous cutting-edge areas of protein research and biomedicine. In gene delivery, split intein-based systems overcome the packaging limit of adeno-associated viral vectors, enabling the accurate reconstitution of large therapeutic proteins and base editors in target cells, thereby enhancing the efficacy and scope of gene therapy for genetic diseases. In internal protein sequence editing, split inteins mediate precise sequence replacement and modification in flexible regions or loops of target proteins, without the need for complex multi-step ligation and protein refolding involved in traditional protein semisynthesis. In protein-protein interaction studies, intein-mediated splicing covalently captures transient and weak intracellular complexes, enabling sensitive, high-throughput interaction detection and drug screening. In synthetic biology, conditionally controllable splicing systems support the construction of diverse intracellular and cell-surface biological logic gates for the precise regulation of cellular behavior. In mechanistic biochemical research, split inteins enable photocatalytic proximity labeling and site-specific tagging, allowing the preparation of homogeneous protein samples carrying precise post-translational modifications such as ubiquitination and polyglutamylation for chromatin interactome analysis and epigenetic studies. Moreover, covalent trapping strategies using split inteins stabilize transient enzymatic intermediates, providing unprecedented insights into molecular mechanisms such as nucleosome ubiquitination that are difficult to elucidate using conventional methods. This review systematically summarizes key technological advances in split inteins over the past decade, highlighting engineering strategies, mechanistic insights, and the development of orthogonal components. It comprehensively surveys emerging applications at the frontiers of protein research, analyzes current core challenges, and proposes future directions, particularly emphasizing artificial intelligence-driven de novo design and novel splicing pathways to break existing technical bottlenecks. By enabling traceless, efficient, and versatile protein manipulation, split inteins continue to serve as indispensable tools that drive innovation in protein engineering and fundamental life science research.

Obesity is a chronic low-grade inflammation and a risk factor for diseases such as diabetes， hypertension， dyslipidemia， and malignant tumors， demonstrating an increasingly grim development situation. The nuclear factor-kappa B （NF-κB） signaling pathway is a key signaling pathway involved in the immune response and inflammatory response. In obese individuals， the expression of NF-κB is overactivated， which leads to abnormal inflammatory responses in the body. Therefore， it is expected to alleviate inflammation and treat obesity by regulating the NF-κB signaling pathway， which has been proven effective by a large number of studies. The available studies on the NF-κB signaling pathway mostly focus on tumors， and there is no systematic review of the mechanism of this pathway in mediating obesity and the traditional Chinese medicine （TCM） treatment. We reviewed the research progress in the pathological and physiological processes of obesity mediated by NF-κB signaling pathway and TCM treatment， aiming to give insights into the clinical treatment of obesity with TCM and provide reference targets and research directions for exploring the biological foundations and the development of new TCM preparations.

Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.

Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*