Objective To assess the stability of the molluscicidal activity of the fermentation broth supernatant of Bacillus indicus F19, so as to provide insights into development of novel molluscicides derived from this isolate. Methods Healthy Oncomelania hupensis snails free from Schistosoma japonicum infections and acclimated in the laboratory for 7 days were selected. The fermentation broth supernatant of B. indicus F19 was prepared. For each treatment condition, four experimental groups and one control group were established, with 10 mL of the fermentation broth supernatant each group. O. hupensis snails were exposed to different pH values (3, 6, 9 and 12), temperatures (40, 60, 80 °C and 100 °C), and ultraviolet (UV) exposure durations (1, 2, 3 h and 4 h). Then, the supernatant was diluted with dechlorinated water to concentrations of 50%, 10%, and 5% (v/v), and 10 mL of each dilution solution was added to three separate tubes, with an equal volume of dechlorinated water as a blank control. Twenty O. hupensis snails were transferred to each tube, immersed for 48 h and 72 h, and collected for viability assessment using the shell-tapping method. The mortality of O. hupensis snails was calculated and compared among dilution groups and the blank control group to evaluate the molluscicidal activity of the fermentation broth supernatant of B. indicus F19. Results There was a significant difference in the mortality of O. hupensis snails immersed in 5% fermentation broth supernatants of B. indicus F19 for 48 h at various pH levels (χ² = 11.556, P < 0.05), and the mortality reduced to 13.33% (8/60) in the experimental groups at a pH value of 12, which was significantly lower than in the blank control group [33.33% (20/60)] (χ² = 6.708, P < 0.05). There was a significant difference in the mortality of O. hupensis snails immersed in 10% fermentation broth supernatants of B. indicus F19 for 72 h at various pH levels (χ² = 31.691, P < 0.001), and the mortality reduced to 71.67% (43/60) and 65.00% (39/60) in the experimental group at pH values of 9 and 12, which was significantly lower than in the blank control group [100.00% (60/60)] (χ² = 8.571 and 12.110, both P values < 0.01). The mortality of O. hupensis snails both reduced to 23.33% (14/60) following immersion in 5% fermentation broth supernatants of B. indicus F19 heated in a water bath at 80 °C and 100 °C for 48 h, which was lower than that of unheated O. hupensis snails [33.33% (20/60)] and snails heated in a water bath at 40 °C [35.00% (21/60)] and 60 °C [33.33% (20/60)], and there was no significant difference in the mortality of O. hupensis snails among groups (χ² = 3.898, P > 0.05). The mortality of O. hupensis snails was 68.33% (41/60), 66.67% (40/60), 65.00% (39/60), and 68.33% (41/60) following immersion in fermentation broth supernatants heated in a water bath at 40, 60, 80 °C and 100 °C for 72 h, which was all lower than that of snails in the control group [71.70% (43/60)]; however, there was no significant difference seen in the snail mortality among groups (χ² = 0.674, P > 0.05). The mortality of O. hupensis snails was 73.33% (44/60), 71.67% (43/60), 71.67% (43/60), and 75.00% (45/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, 33.33% (20/60), 31.67% (19/60), 35.00% (21/60), and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) and 33.33% (20/60) following 48 h immersion in 10% fermentation broth supernatants of B. indicus F19 without UV irradiation, and no significant differences were found among groups (χ² = 0.229 and 0.150, both P values > 0.05). In addition, the mortality of O. hupensis snails was 76.67% (46/60), 71.67% (43/60), 70.00% (42/60), and 76.67% (46/60) following 72 h immersion in 5% fermentation broth supernatants of B. indicus F19 irradiated by UV for 1, 2, 3 h and 4 h, and 71.67% (43/60) in the control group, and there was no significant difference in the snail mortality among groups (χ² = 1.193, P > 0.05). Conclusion The molluscicidal action of the fermentation broth supernatants of B. indicus F19 is tolerant to high temperature and UV irradiation; however, the activity is attenuated under alkaline conditions.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.

Objective:To investigate the value of transabdominal bowel ultrasonography (TBUS) in evaluating the active phase of Crohn′s disease (CD) and its complications, and to compare the diagnostic efficacy of the international bowel ultrasound segmental activity score (IBUS-SAS) and the multidetector computed tomography enterography (MDCTE) score in the active phase.Methods:A totle of 103 CD patients who were admitted to the Nanjing Drum Tower Hospital from March 2021 to May 2023 were retrospectively analyzed. All patients underwent TBUS and MDCTE examinations. TBU parameters such as bowel wall thickness (BWT), color Doppler imaging signal (CDS), inflammatory fat (i-fat), and bowel wall stratification (BWS) were recorded. The patients were divided into the remission group and the active group based on the Crohn′s disease activity index. The latter group was further divided into the mild active group and the moderate-to-severe active group.Receiver operating characteristic curves (ROC) were plotted, and the diagnostic efficacy of TBUS parameters and two scoring systems in assessment of the active phase of CD was evaluated by sensitivity, specificity, area under the curve (AUC), and optimal cut-off values. Endoscopic or histopathological results were served as the gold standard for the diagnosis of intestinal strictures. The diagnostic efficacy of TBUS and MDCTE in CD complicated with intestinal stenosis were evaluated by ROC analysis. Spearman correlation analysis was performed to analyze the correlation between TBUS parameters, imaging scores, and clinical laboratory indicators such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and faecal calprotectin (FC).Results:In distinguishing the active phase and the remission phase of CD, BWT (a sensitivity of 85.7%, specificity of 90.9%, and cut-off value of 4.4 mm), CDS (a sensitivity of 95.7%, and specificity of 63.6%), IBUS-SAS (a sensitivity of 91.4%, specificity of 84.8%, and cut-off value of 23.8), and MDCTE score (a sensitivity of 77.1%, specificity of 75.8%, and cut-off value of 6.5) had high diagnostic efficacies. In distinguishing mild and moderate-severe active phases of CD, BWT, CDS and i-fat demonstrated high sensitivity (81.4%, 69.8% and 62.8%) and specificity (81.5%, 77.8% and 100.0%); IBUS-SAS (a sensitivity of 83.7%, specificity of 88.9%, and cut-off value of 40.0) and MDCTE score (a sensitivity of 83.7%, specificity of 85.2%, and cut-off value of8.5) had high diagnostic efficacy. In the diagnosis of CD complicated with intestinal stenosis, the AUC, sensitivity, specificity, and accuracy of MDCTE was 0.942, 94.0%, 94.3%, and 94.2%, respectively. The AUC, sensitivity, specificity, and accuracy of TBUS in the diagnosis of CD complicated with intestinal stenosis was 0.952, 96.0%, 94.3%, and 95.1%, respectively. The results of Spearman correlation analysis revealed that BWT, CDS, and i-fat have positively correlated with ESR, CRP, and FC ( r value: 0.252 to 0.451, all P<0.05). Conclusions:TBUS demonstrates good application value in evaluating the activity of CD and intestinal stenosis. IBUS-SAS has the potential application for precise assessment of CD activity.

Objective To distinguish Cremastra appendiculata(D.Don)Makino,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and its easily confusing products Oreorchis patens and Iphigenia indica Kunth using the ITS sequence in DNA barcodes;To explore the genetic diversity of Cremastra appendiculata germplasm resources.Methods Three different original Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and their easily confusing products Cremastrae Pseudobulbus of Oreorchis patens and Iphigenia indica Kunth were selected as the research objects,and the genomic DNA of the above samples were extracted by the modified CTAB method,and then the ITS sequences were amplified,sequenced and spliced by PCR technology.The Kimura 2-Parameter(K2P)model was used to calculate the genetic distance,and the phylogenetic tree was constructed with the help of neighbour joining method(NJ)for genetic relationship analysis.Results Except for the Iphigenia indica Kunth species that were not found during the BLAST search,the BLAST comparison results of the other samples were higher than 95%.At the same time,the results of phylogenetic tree showed that Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides were clustered into one branch,respectively,and the easily confusing products were also respectively clustered into one branch.Conclusion The ITS sequence in DNA barcodes can be used to accurately distinguish Cremastra appendiculata,Pleione yunnanensis Rolfe and Pleione bulbocodioides,and its easily confusing products Oreorchis patens and Iphigenia indica Kunth.

Implementation Science is an interdisciplinary field dedicated to systematically studying how to effectively translate evidence-based research findings into practical application and implementation. In the health-related context, it focuses on enhancing the efficiency and quality of healthcare services, thereby facilitating the transition from scientific evidence to real-world practice. This article elaborates on Theories, Models, and Frameworks (TMF) within health-related Implementation Science, clarifying their basic concepts and classifications, and discussing their roles in guiding implementation processes. Furthermore, it reviews and prospects current research from three aspects: the constituent elements of TMF, their practical applications, and future directions. Five representative frameworks are emphasized, including the Consolidated Framework for Implementation Research (CFIR), the Practical Robust Implementation and Sustainability Model (PRISM), the Exploration, Preparation, Implementation, Sustainment (EPIS)framework, the Behavior Change Wheel (BCW), and the Normalization Process Theory (NPT). Additionally, resources such as the Dissemination & Implementation Models Webtool and the T-CaST tool are introduced to assist researchers in selecting appropriate TMFs based on project-specific needs.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*