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.

Ultrasound-stimulated microbubble cavitation(USMC)is a cavitation phenomenon triggered by oscillating microbubbles in ultrasound field,and this effect has led to breakthroughs in improving the permeability of cell membranes,enhancing the sensitivity of tumor cells to chemotherapy or immunotherapy,and increasing the penetration of thrombolytic drugs into blood clots and vascular recanalization.In recent years,the cross-fertilization of ultrasound medicine and materials science have given rise to the study of ultrasound-responsive multifunctional nanobubble to enhance USMC treatment.This article reviews the application and research progress of USMC in improving tissue perfusion in ischemic diseases,tumor chemotherapy and immunotherapy,ultrasonic thrombolysis,and other treatments.

Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.
Yeasts/genetics* ; Yarrowia/metabolism* ; Gene Editing ; Metabolic Engineering

Objective:To identify the risk factors of postoperative atrial fibrillation (POAF) in critically ill lung surgery patients and establish a nomogram.Methods:213 critically ill lung surgery patients were collected in Beijing Chaoyang Hospital from January 2018 to December 2021. Logistic analysis was used to analyze the risk factors of POAF. A nomogram was developed based on the verified risk factors. Results:The independent risk factors associated with POAF was mitral regurgitation ( OR=4.270, 95% CI: 1.380-13.213, P=0.012), cedilanid ( OR=14.619, 95% CI: 2.913-73.373, P=0.001), catecholamine ( OR=3.244, 95% CI: 1.144-9.203, P=0.027), pericardiotomy( OR=6.079, 95% CI: 1.362-27.128, P=0.009), systematic lymph node dissection( OR=5.460, 95% CI: 1.770-16.846, P=0.003). Nomogram model showed the ROC was 0.801(95% CI: 0.721-0.881, P<0.001). Conclusion:The risk factors of POAF in critically ill lung surgery patients are mitral regurgitation, cedilanid, catecholamine, pericardiotomy and systematic lymph node dissection. The nomogram predicted POAF better than other scoring systems.

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.

Topical anesthesia are being widely used in clinical diagnostic or therapeutic fields such as ophthalmology, ENT, dermatology, urology. It is defined as superficial loss of sensation in mucous membranes or skin, produced by direct application of penetrating local anesthetics. Topical anesthesia has the advantages of simple performance, high safety, quick recovery, which can effectively improve patient's satisfaction. In recent years, more and more attention has been paid to the concept of comfortable diagnosis and treatment. The new drugs and application methods of topical anesthesia are emerging constantly, special attention must be paid to their pharmacological characteristics and possible adverse reactions when using them. This article reviews the research progress of topical anesthesia in clinical application in order to provide reference for clinical practice.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging tech-nologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.
Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome ; Humans ; Medicine, Chinese Traditional ; Precancerous Conditions/pathology* ; Stomach Neoplasms/pathology*

Vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. Traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Vascular Endothelial Growth Factor A