Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The correct working posture of dentists is not only the premise of clinical diagnosis, treatment quality and safety but also an important guarantee for the occupational health of dentists. Presently, research on the working posture of dental professionals and related influencing factors is relatively mature internationally. Still, the dental curriculums in our country have not systematically introduced theoretical knowledge and standards related to working posture. This review analyzes and summarizes previous literature on the importance of dental working posture, criteria, assessment methods, and influencing factors, in hopes of providing references and theoretical supports for future guidelines and standards.

Objective:The present study was designed to strengthen the education of research integrity, and to improve the awareness of academic misconduct and academic literacy of medical post-graduate students.Methods:A questionnaire survey was conducted with master post-graduate students of a university affiliated hospital, and statistical analysis on the education of research integrity and the perception of academic misconduct among the survey respondents was performed.Results:Academic master post-graduate students′ cognitions of the misconduct in scientific research process and overall academic misconduct were better than that of professional master post-graduate students, and there were significant differences ( P<0.05). The more times of participation in research integrity training, the better cognition of misconduct of scientific research process, research results publication process, and overall academic misconduct, with significant differences ( P<0.05). Conclusions:The education on scientific research integrity of medical post-graduates should be carried out systematically, while the content should be improved and the form should be enriched for scientific research integrity education, so that the medical post-graduates can have a deeper understanding of the code of academic practices, and an education model of scientific research integrity for medical post-graduate which is suitable for China′s national conditions can be gradually developed.

Objective:To analyze the research hotspots and frontiers of hospital research management research from 1981 to 2022.Methods:The relevant literature in the field of hospital scientific research management was retrieved from the CNKI database to explore the trends of publications in this research field. A scientific knowledge graph was drawn and a visualization analysis of the information of authors, issuing units, and research institutions were conducted by Cite Space.5.8.R3.Research hotspots were discussed based on keyword emergence, cluster analysis, and keyword time zone graph.Results:The publication trend in this field was generally policy-oriented, but the cooperation among authors and institutions was relatively loose, and the research hotspots were gradually shifting from scientific research funding management to discipline construction, talent training, translational medicine, and informatization. Cluster analysis found that the main content of hospital scientific research management was scientific research funding and clinical scientific research management and the main management objects were the medical and nursing staff.Conclusions:Hospital scientific research managers must adhere to the policy-oriented approach, strengthen the cooperation and exchanges in scientific research management, innovate the scientific research management mode around the research hotspots and development trends, and promote the quality and efficiency of scientific research management.

Based on the characteristics of medical specialty, this research group has developed the virtual simulation experiment teaching project of Chinese revolutionary morality (red medicine spirit). This project uses 3D simulation technology and OpenGL technology to build a virtual experimental learning environment based on WebGL, learn general Fu Lianzhang's glorious deeds and immersive experience of the inheritance and development of the spirit of red medicine by contemporary "heroes in harms way" in the fight against the COVID-19 epidemic in the form of 3D animation interaction. Through research, it is found that virtual simulation teaching is conducive to promoting students' understanding and mastery of medical humanities and improving students' satisfaction with teaching, with good popularization value.

Objective:By analyzing the biomedical papers retracted due to the reason that " original data not provided" , to discuss the necessity of preventing scientific data misconduct and the feasible solutions for its management.Methods:Data of the international papers that were published from Jan 2011 to Dec 2021 and retracted due to " original data not provided" were retrieved from Retraction Watch Database. The data of time distribution, institution, journal sources, reasons for retraction, and disciplinary distribution were statistically analyzed and visually processed by using software packages of Excel, Python 3.7, Gephi 0.92.Results:A total number of 529 papers published in the biomedical field were retracted due to " original data not provided" , and the time of publication and retraction occurred mainly in 2019 (27.41%) and 2021 (41.97%). In addition to the reason " original data not provided" used as search term, the reasons for withdrawal were mainly data and image problems caused by scientific data misconduct, and reasons related to the discovery and investigation process of the paper, and these reasons had a strong co-linear relationship. Besides, the 4 disciplinary of biology-cellular, biology-cancer, genetics, medicine-oncology also had a strong co-linear relationship.Conclusions:It is necessary to incorporating scientific research data management into the scientific research code of conduct, strengthen the training on the code of conduct for original scientific research records keeping, establish the scientific research data review mechanism, and promote the prevention and governance of scientific research data misconduct in the biomedical field.

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca²⁺ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca²⁺ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca²⁺ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca²⁺ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca²⁺ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.
Animals ; Astrocytes ; Hippocampus/physiology* ; Humans ; Memory, Short-Term/physiology* ; Mice ; Neurons/physiology* ; Population Dynamics

Voluntary service spirit is highly coupled with medical humanistic spirit. Participating in voluntary service is an important channel for medical students to grow up. There are deficiencies in medical students' voluntary service at the social, school and personal levels. It is of great significance to strengthen the top-level design of all staff, whole process and all-round volunteer service, build a volunteer service platform with distinctive characteristics, normal development and multi benefits, create a "school local co construction" volunteer service brand, select advanced figures in voluntary service for medical students, and establish and improve long-term mechanisms for the operation, incentive and guarantee of voluntary services, thus improving the medical students' awareness of voluntary service, protecting their legitimate rights and interests in the service process, expanding the influence of voluntary service and enhancing the effectiveness of voluntary service.

Objective:To analyze the main related factors for undertaking the NSFC project among the in-service master and doctor in a third-grade First-class hospital in 2020.Methods:By collecting and comparing the age of the target population, the type of education and degree, SCI papers publication and experience as principal investigator of scientific research projects and other variables, the factors affecting the commitment of the NSFC project were analyzed.Results:A total of 743 feedbacks from the people with master′s degree and doctor′s degree in this survey, 69 of whom had undertaken the NSFC project (accounting for 9.3% of the total number). By the univariate analysis, age, education, age more than 55 years old, professional Dr. and academic Dr., published SCI paper publication, JCR1/JCR2/JCR3/JCR4 publication and experience as principal investigator of scientific research project should significantly improve the opportunity of undertaking the NSFC project. The multivariate analysis results show that the main factors influencing the commitment of the NSFC project are the professional Dr., the academic Dr. and having hosted projects.Conclusions:Professional or academic doctors and experience as principal investigator of scientific research projects have significant advantages in undertaking the NSFC project. Medical institutions should fully consider the advantages of different types of scientific research personnel and make clear their differences in professional fields, in order to develop more targeted programs to improve the capacity for scientific research.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.