Structural optimization of lead compounds is a crucial step in drug discovery. One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules, thereby accelerating the molecular optimization process. Deep molecular diffusion generative models simulate a gradual process that creates novel, chemically feasible molecules from noise. However, the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules, leading to challenges in modifying the scaffold-based molecular structures, and creates limitations in the stability and diversity of the generated molecules. To address these challenges, we propose a deep molecular diffusion generative model, the three-dimensional (3D) equivariant diffusion-driven molecular generation (3D-EDiffMG) model. The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder (dual-SWLEE) is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions. Additionally, a gate multilayer perceptron (gMLP) block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies. The experimental results show that 3D-EDiffMG effectively generates unique, novel, stable, and diverse drug-like molecules, highlighting its potential for lead optimization and accelerating drug discovery.

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Objective To study the inhibitory effect of Huidu Yinhua powder from the Orthodox Manual of External Medicine on methicillin-resistant Staphylococcus aureus(MRSA),virulence factor α-hemolysin(Hla)activity,and biofilm formation,and to explore the optimal ratios of Huidu Yinhua powder and provide experimental support for its use.Methods The inhibitory effects of Huidu Yinhua powder and the herbs in the formula on USA300 were analyzed by the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and disk diffusion assay(K-B method).Hemolysis,neutralization,oligomerization,and Western blot assays were used to verify in which form the drug inhibits the activity of virulence factor α-hemolysin(Hla).A biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua powder on biofilm.Orthogonal experiments were performed to explore the optimal ratio of Huidu Yinhua powder.Results Huidu Yinhua powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL with antibacterial circle diameter of(7.50±0.50)mm.Huidu Yinhua powder inhibited Hla activity by inhibiting Hla secretion.The minimum effective concentration(MEC)was 16 mg/mL,and the MEC of biofilm was 8 mg/mL.In Huidu Yinhua powder,honeysuckle and astragalus only affected the hemolytic activity of MRSA and biofilm formation without inhibiting bacterial growth.The hemolytic activity and biofilm of MEC were both 32 mg/mL.Glycyrrhiza had a strong bacterial inhibitory capacity with a MIC90 of 8 mg/mL and biofilm MEC of 1 mg/mL without showing inhibitory hemolytic activity at subinhibitory concentrations.The orthogonal experiment showed that,at a ratio of honeysuckle,astragalus,and glycyrrhiza in Huidu Yinhua powder of 1∶2∶4,the MIC90 was 16 mg/mL,MEC of hemolytic activity was 8 mg/mL and that of biofilm was 4 mg/mL,both of which were the lowest among the nine groups.Conclusions Huidu Yinhua powder affects the hemolytic activity and biofilm formation of MRSA at subinhibitory concentrations with the optimal ratio of honeysuckle,astragalus,and glycyrrhiza being 1∶2∶4.

Objective To construct an evidence-based practice model for nurses in preventing deep vein thrombosis(DVT)and provide a scientific and targeted theoretical basis for nurses to carry out evidence-based nursing practice in DVT prevention.Methods Based on the previous evidence-based nursing practice project on DVT prevention after hip and knee arthroplasty,the research team used theoretical analysis and brainstorming to develop a draft of the work model.Expert meetings were organized to validate the content of the draft using the Delphi method,leading to the finalization of the evidence-based practice model for nurses in preventing DVT.Results The Knowledge-to-Action(KTA)framework was selected as the basic framework for constructing the evidence-based nursing practice model for preventing DVT.Theoretical Domain Framework,Theory of Planned Behavior,and Social Cognitive Theory were chosen to explore the influencing factors of nurses'behavior change in preventing DVT through evidence-based practice.The authority coefficient of the participating experts was 0.904,indicating high reliability.The final model consisted of 6 key components:knowledge generation,problem identification,localization and adaptation,knowledge application,sustained knowledge use,and conceptual framework for behavior change through evidence-based practice.Conclusion Based on theoretical analysis and clinical practice,this study developed an evidence-based practice model for nurses in preventing DVT using the expert meeting.The research methodology was scientific,and the content was reliable,providing a theoretical basis for nurses to engage in evidence-based nursing practice for DVT prevention.

Purpose To explore the application of contrast-enhanced ultrasound in evaluating the local muscle microcirculation before and after acupuncture at Zusanli point in normal people.Materials and Methods A total of 72 healthy volunteers who visited the Department of Ultrasound,the Second Affiliated Hospital of Fujian Medical University from September 2018 to May 2020 were prospectively collected,all subjects performed ultrasound contrast before acupuncture,acupuncture with strongest deqi,and two hours after acupuncture to observe the blood flow perfusion of the microvessels in the tibialis anterior muscle.The pre-selected areas of interest the small arteries,muscle tissues and venules in the middle were analyzed to obtain the time-intensity curve and contrast transit time(CTTs)perfusion parameters.Needle sensation was evaluated using objective scoring criteria for acupuncture combined with moxibustion recipients.Gastrin,plasma gastrin,cholecystokinin,and secretin were measured in all subjects before acupuncture,when acupuncture had the strongest deqi,and two hours after acupuncture.Results ①CTTs of arterial-muscle,muscle-venous and arterial-venous of the tibialis anterior muscle at acupuncture with strongest deqi were significantly shorter than those at before acupuncture and two hours after acupuncture(all P<0.001),and there was no significant difference in CTTs before and after acupuncture and moxibustion(P>0.05);②when acupuncture deqi was strongest,serum gastrin,plasma prokinetics,cholecystokinin,and secretin were significantly increased compared with those before acupuncture and two hours after acupuncture,with statistically significant difference(all P<0.001),while there was no significant difference in these parameters between before acupuncture and two hours after acupuncture(P>0.05);③when acupuncture had the strongest deqi,there were positive correlations between gastrin,plasma prokinetic hormone,cholecystokinin,and secretin values and CTTs of arterial-muscle,muscle-venous,and arterial-venous(r=0.360-0.702,P<0.001).Conclusion Acupuncture of the Zusanli,when it gains the strongest deqi,can cause changes in the microcirculation around the skeletal muscle,leading to a significant shortening of CTTs,and also promotes the secretory function of the gastrointestinal tract.

Extranodal NK/T cell lymphoma, nasal type（ENKTL） is a highly aggressive malignant tumor derived from NK cells. This article reports a case of ENKTL invading the larynx and digestive tract. The clinical clinical manifestations include hoarseness and intranasal masses.
Humans ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Nose/pathology* ; Nose Neoplasms/pathology* ; Larynx/pathology* ; Gastrointestinal Tract/pathology*

OBJECTIVES: This study aimed to analyze the bacteria in dental caries and establish an optimized dental-ca-ries diagnosis model based on 16S ribosomal RNA (rRNA) data of oral flora. METHODS: We searched the public databa-ses of microbiomes including NCBI, MG-RAST, EMBL-EBI, and QIITA and collected data involved in the relevant research on human oral microbiomes worldwide. The samples in the caries dataset (1 703) were compared with healthy ones (20 540) by using the microbial search engine (MSE) to obtain the microbiome novelty score (MNS) and construct a caries diagnosis model based on this index. Nonparametric multivariate ANOVA was used to analyze and compare the impact of different host factors on the oral flora MNS, and the model was optimized by controlling related factors. Finally, the effect of the model was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: 1) The oral microbiota distribution obviously differed among people with various oral-health statuses, and the species richness and species diversity index decreased. 2) ROC curve was used to evaluate the caries data set, and the area under ROC curve was AUC=0.67. 3) Among the five hosts' factors including caries status, country, age, decayed missing filled tooth (DMFT) indices, and sampling site displayed the strongest effect on MNS of samples (P=0.001). 4) The AUC of the model was 0.87, 0.74, 0.74, and 0.75 in high caries, medium caries, low caries samples in Chinese children, and mixed dental plaque samples after controlling host factors, respectively. CONCLUSIONS The model based on the analysis of 16S rRNA data of oral flora had good diagnostic efficiency.
Humans ; Child ; Bacteria/genetics* ; Dental Caries/microbiology* ; Dental Caries Susceptibility ; Microbiota/genetics* ; RNA, Ribosomal, 16S

Heat shock proteins (HSPs) widely exist in all organisms, the structures of which are usually extraordinarily conservative. They are also well-known stress proteins that are involved in response to physical, chemical and biological stresses. HSP70 is an important member of the HSPs family. In order to study the roles of amphibians HSP70 during infection, the cDNA sequence of Rana amurensis hsp70 family genes were cloned by homologous cloning method. The sequence characteristics, three-dimensional structure and genetic relationship of Ra-hsp70s were analyzed by bioinformatics methods. The expression profiles under bacterial infection were also analyzed by real-time quantitative PCR (qRT-PCR). Expression and localization of HSP70 protein were tested by immunohistochemical techniques. The results showed that three conservative tag sequences of HSP70 family, HSPA5, HSPA8 and HSPA13, were found in HSP70. Phylogenetic tree analysis indicated four members are distributed in four different branches, and members with the same subcellular localization motif are distributed in the same branch. The relative expression levels of the mRNA of four members were all significantly upregulated (P < 0.01) upon infection, but the time for up-regulating the expression levels were diverse in different tissues. The immunohistochemical analysis showed that HSP70 was expressed to different degrees in the cytoplasm of liver, kidney, skin and stomach tissue. The four members of Ra-hsp70 family have ability to respond bacterial infection to varying degrees. Therefore, it was proposed that they are involved in biological processes against pathogen and play different biological functions. The study provides a theoretical basis for functional studies of HSP70 gene in amphibians.
Heat-Shock Proteins/genetics* ; Phylogeny ; Amino Acid Sequence ; HSP70 Heat-Shock Proteins/metabolism* ; Stress, Physiological

Adiponectin receptor 1 (AdipoR1) and Adiponectin receptor 2 (AdipoR2) can bind to adiponectin (AdipoQ) secreted by adipose tissue to participate in various physiological functions of the body. In order to explore the role of AdipoR1 and AdipoR2 in amphibians infected by Aeromonas hydrophila (Ah), the genes adipor1 and adipor2 of Rana dybowskii were cloned by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed by bioinformatics. The tissue expression difference of adipor1 and adipor2 was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and an inflammatory model of R. dybowskii infected by Ah was constructed. The histopathological changes were observed by hematoxylin-eosin staining (HE staining); the expression profiles of adipor1 and adipor2 after infection were dynamically detected by qRT-PCR and Western blotting. The results show that AdipoR1 and AdipoR2 are cell membrane proteins with seven transmembrane domains. Phylogenetic tree also shows that AdipoR1 and AdipoR2 cluster with the amphibians in the same branch. qRT-PCR and Western blotting results show that adipor1 and adipor2 were up-regulated at different levels of transcription and translation upon Ah infection, but the response time and level were different. It is speculated that AdipoR1 and AdipoR2 participate in the process of bacterial immune response, providing a basis for further exploring the biological functions of AdipoR1 and AdipoR2 in amphibians.
Animals ; Receptors, Adiponectin/metabolism* ; Phylogeny ; Adiponectin/metabolism* ; Cloning, Molecular ; Ranidae/genetics*

Objective:To summarize the research status and contents of the needs of breast cancer patients undergoing first operation.Methods:The articles related to the needs of patients undergoing first surgery for breast cancer were searched by computer in PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP and China Biology Medicine disc. The search period was from January 1, 2013 to December 31, 2022.Results:A total of 17 articles were included, and the research design mainly focused on qualitative and observational studies. Breast cancer patients with first operation had a high degree of demand, and the demand content was diverse, mainly including information needs, health guidance needs, emotional needs and social support needs. The needs of breast cancer patients with different ages and different treatment stages were different.Conclusions:It is suggested that a personalized needs intervention plan should be formulated to meet the diversified needs of breast cancer patients.