Objective: To explore the mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide the basis for alleviating social isolation in this population. Methods: From July to November 2024, elderly patients with T2DM aged ≥65 years were selected by using the convenience sampling method from the endocrinology and geriatrics departments of a tertiary hospital in Shanxi Province. Demographic and clinical data were collected using structured questionnaires. Frailty was assessed using the FRAIL Scale, psychological flexibility was measured with the Acceptance and Action Questionnaire-II (AAQ-II), exercise self-efficacy was evaluated via the Chinese version of the Exercise Self-Efficacy Scale, and social isolation was quantified employing the General Alienation Scale. The mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation were analyzed using the Process macro program. Results: A total of 300 elderly patients with T2DM were included, with a mean age of (71.16±4.88) years. There are 167 males (55.67%) and 133 females (44.33%). The mean scores for frailty, psychological flexibility, exercise self-efficacy, and social isolation were (2.82±1.59), (28.32±6.95), (5.69±1.20), and (39.27±9.24). Mediation analysis revealed that frailty positively affected social isolation (β=0.227, 95%CI: 0.132-0.323). It also indirectly positively influenced social isolation through psychological flexibility (β=0.165, 95%CI: 0.105-0.234) and exercise self-efficacy (β=0.150, 95%CI: 0.093-0.217), and the chained mediating effect of psychological flexibility and exercise self-efficacy (β=0.066, 95%CI: 0.038-0.100). Conclusion Frailty exacerbates social isolation by diminishing psychological flexibility and exercise self-efficacy among elderly patients with T2DM.

Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

This paper summarized professor XUE Boshou's clinical experience of using Fangfeng （Radix Saposhnikoviae）. Firstly， Fangfeng is used to scatter wind and release the exterior， disseminate and penetrate the pathogens， and can treat the early-staged externally contracted heat diseases with exterior qi constraint and blocking， and serious internal heat through Xiaodu Xijiao Beverage （消毒犀角饮） from Beneficial Formulas from the Taiping Imperial Pharmacy （《太平惠民和剂局方》）combined with Yinqiao Powder （银翘散）， Shengjiang Powder （升降散） and Zhizichi Decoction （栀子豉汤） in their modifications. Secondly， it eliminates wind and dispels dampness， relieves itching， and heals sores， with self-made Xue's Guomin Decoction （薛氏过敏煎） in modification being formulated to treat allergic skin diseases caused by pathogenic wind attacking the exterior. Thirdly， it disperses liver qi and soothes the spleen， lifts yang and stops diarrhea， and can be used in modified Tong Xie Yao Formula （痛泻要方） from Teachings of ZHU Danxi （《丹溪心法》） when treating diarrhea caused by liver constraint and spleen deficiency. Fourthly， it can disperse stagnated qi throughout the body and unblock the meridians of the five zang （脏） organs， commonly in formulation of modified Huangqi Chifeng Decoction （黄芪赤风汤） from Correction of Errors in Medical Works （《医林改错》） to treat patients with qi deficiency and blood stasis after radiotherapy and chemotherapy of tumors， as well as alopecia areata or even alopecia universalis， chronic rhinitis and others.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective To explore the application of the TST-IGRA two-step method in the screening of close contacts of active tuberculosis patients among three high schools in Jinshan District in 2020-2021，and to provide evidence for improving the prevention and control of tuberculosis in schools. Methods Three school tuberculosis outbreaks in Jingshan District from 2020 to 2021 were included in the present study. After excluding active tuberculosis, tuberculin skin test and γ-interferon release assay (IGRA) were conducted to screen latent infection of Mycobacterium tuberculosis in close contacts, and the necessity of the two-step method was analyzed. Results A total of 362 close contacts were screened in the three outbreaks, and 350 people were tested by TST. Comparing the results of TST and IGRA among different types of close contacts, it was found that the positive rate of TST in teachers was higher than that in students（54.84% vs 20.38%，P<0.05）. The positive rate of TST among students from high-burden areas of pulmonary tuberculosis in Shanghai was higher than that of local students（24.71% vs 18.80%，P<0.05). IGRA detection was performed on those with moderate and strong positive TST results, and the results showed that the positive rate of IGRA in those with strong positive TST results was only 17.7%, with Kappa value of 0.3. Conclusion The prevention and control of tuberculosis in school should strengthen the annual health examination of teachers and staff, promote timely medical treatment for suspected tuberculosis symptoms, reasonably increase the screening frequency of students in high-burden areas of tuberculosis in Shanghai, and collect students’ previous history of tuberculosis exposure. When screening close contacts, after excluding active tuberculosis, it is recommended that TST and IGRA should be combined to determine latent Mycobacterium tuberculosis infection and achieve accurate intervention.

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*

How to discover the valuable knowledge from the large amount of prescription data accumulated in the long-term medical practice of traditional Chinese medicine (TCM) is one of the important contents of TCM modernization.Based on the prescription data of Xue' s clinical practice of many years,this paper explored the method of combining TCM network and prescription network to find out Xue' s common core drug combination.Based on 9,584 prescriptions in the Hospital Information System of Guang'anmen Hospital of China Academy of Chinese Medical Sciences,prescription network and drug network were constructed according to the similarity of prescription composition and drug co-occurrence relationship.Using the complex network analysis methods,such as community analysis method,to analyze the prescription and drug compatibility,the results were evaluated and analyzed by Xue and his successors.As a result,through complex network analysis,126 modular prescriptions and 4 TCM modules were obtained.One of the core components of the prescription module included Xiao Chai Hu decoction,Yin Qiao powder,and Sheng Jiang powder compound addition and subtraction.It was in consistent with the drug composition of exogenous febrile prescriptions excavated earlier.In conclusion,using the complex network methods,we can get some core drug combinations prescribed by Prof.Xue,and achieve the common compound core drug combination for treating diseases with certain vantages,laying a foundation for further inheriting and excavating Xue' s effective experience.