Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway.

Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.

Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

Virgibacillus tibetensis sp. nov., isolated from salt lake on the Tibetan plateau of China.

One bacterial strain, designated as C22-A2T, was isolated from Lake LungmuCo in Tibet. Cells of strain C22-A2T were long rod-shaped, Gram-stain-negative, non-spore-forming, with positive catalase and oxidase activity. Optimal growth occurred at 20-25 °C, pH 8.0 and with 3.0-7.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene and whole genome sequences revealed that strain C22-A2T belonged to the genus Virgibacillus, showing the highest 16S rRNA gene similarity to Virgibacillus halodenitrificans DSM 10037T (97.6%). The average nucleotide identity values between strain C22-A2T and the type strains of related species in the genus Virgibacillus were less than 74.4% and the digital DNA-DNA hybridization values were less than 20.2%, both below the species delineation thresholds of 95 and 70% respectively. The genome analysis revealed that strain C22-A2T harboured genes responsible for osmotic and oxidative stress, enabling it to adapt to its surrounding environment. In terms of biochemical and physiological characteristics, strain C22-A2T shared similar characteristics with the genus Virgibacillus, including the predominant cellular fatty acid anteiso-C15 : 0, the major respiratory quinone MK-7, as well as the polar lipids phosphatidylglycerol and diphosphatidylglycerol. Based on the comprehensive analysis of phylogenetic, phylogenomic, morphological, physiological and biochemical characteristics, strain C22-A2T is proposed to represent a novel species of the genus Virgibacillus, named as Virgibacillus tibetensis sp. nov. (=CGMCC 1.19202T=KCTC 43426T).

Jaw relation recording and transferring: Using digital technology to augment its instruction in predoctoral prosthodontics.

OBJECTIVES: The study compared the learning effectiveness and teaching satisfaction of dental students from three teaching methods (traditional, digital, and combined pedagogy) for instructing jaw relation recording and transferring (JRRT). METHODS: Note that, 276 fourth-year undergraduate students from three classes were randomly divided into three groups to study JRRT in complete dentures using different teaching methods: traditional pedagogy group, digital pedagogy group, and combined digital and traditional pedagogy group. After the course, the learning effectiveness of basic knowledge and satisfaction questionnaire was administered to the three groups of participants using a quick response code for online answering. The questionnaire was customized by the teacher based on the content delivered to each group. RESULTS: The data were analyzed using the Chi-square test with Fisher's exact test. Both the digital and combined pedagogy groups showed a significant increase in basic knowledge test scores and higher satisfaction, compared to the traditional pedagogy group (p < 0.01). Particularly, the participants from combined pedagogy showed better teaching satisfaction than the digital pedagogy group (p < 0.001). CONCLUSIONS: The use of digital technology in JRRT significantly enhanced students' learning effectiveness and teaching satisfaction. CLINICAL SIGNIFICANCE: This educational innovation emphasizes digital technology to visualize vital concepts and operational intricacies related to JRRT. The findings have major implications for improving teaching methods in the field of prosthodontic dentistry.

Correction: Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats.

Correction for 'Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats' by Lu Li et al., Food Funct., 2019, 10, 2560-2572, https://doi.org/10.1039/C9FO00075E.

Effects of postprandial exercise timing on blood glucose and fluctuations in patients with type 2 diabetes mellitus.

BACKGROUND: The aim of this study was to assess how moderate-intensity aerobic exercise performed 45 minutes and 90 minutes after a meal affects blood glucose levels and fluctuations in individuals diagnosed with type 2 diabetes mellitus (T2DM). METHODS: Twenty-two patients with T2DM, who were solely receiving oral hypoglycemic medication, were enrolled and divided randomly into two categories: those exercising 45 minutes after a meal (45-minute postprandial exercise group) and those exercising 90 minutes post-meal (90-minute postprandial exercise group). Both groups engaged in a 30-minute session of moderate-intensity aerobic stationary bike exercise following breakfast. This aerobic exercise regimen consisted of two stages, with the groups switching exercise timings after the initial phase. Continuous glucose monitoring (CGM) was utilized to evaluate the blood glucose levels and fluctuations in the participants. RESULTS: After breakfast, both overall daily blood glucose levels and the area under the curve for blood glucose following breakfast were reduced in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. The 45-minute postprandial exercise group demonstrated greater time spent within the target glucose range and less time above the target range than the 90-minute postprandial exercise group. Additionally, measures such as standard deviation, mean amplitude of glycemic excursions, largest amplitude of glycemic excursions, and postprandial glucose excursion for breakfast, peak postprandial glucose levels, and duration of elevated glucose levels were all lower in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. CONCLUSIONS: Moderate-intensity aerobic exercise lasting 45 minutes after meals was found to be more efficient in decreasing blood glucose levels and minimizing fluctuations compared to exercising 90 minutes after meals in patients with T2DM. Additionally, it notably reduced the peak in blood glucose levels after meals.

Efficient elimination of antibiotics and antibiotic resistance genes in hyperthermophilic sludge composting.

Composting is widely applied in recycling ever-increasing sewage sludge. However, the insufficient elimination of antibiotics and antibiotic resistance genes (ARGs) in conventional compost fertilizer poses considerable threat to agriculture safety and human health. Here we investigated the efficacy and potential mechanisms in the removal of antibiotics and ARGs from sludge in hyperthermophilic composting (HTC) plant. Our results demonstrated that the HTC product was of high maturity. HTC led to complete elimination of antibiotics and potential pathogens, as well as removal of 98.8 % of ARGs and 88.1 % of mobile genetic elements (MGEs). The enrichment of antibiotic-degrading candidates and related metabolic functions during HTC suggested that biodegradation played a crucial role in antibiotic removal. Redundancy analysis (RDA) and structural equation modelling (SEM) revealed that the reduction of ARGs was attributed to the decline of ARG-associated bacteria, mainly due to the high-temperature selection. These findings highlight the feasibility of HTC in sludge recycling and provide a deeper understanding of its mechanism in simultaneous removal of antibiotics and ARGs.

A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria.

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo.

Analysis of prognostic risk factors and development of a predictive model for fetuses with right aortic arch with mirror-image branching: a prognostic evaluation method based on ultrasound parameter features.

Background: Prenatal ultrasound plays a crucial role in the diagnosis and classification of right aortic arch (AO) with mirror-image branching (RAA-MB). The recent research in this area has primarily focused on qualitative diagnosis, neglecting the quantitative analysis of ultrasound factors that impact RAA-MB outcomes. This study used echocardiography to measure prenatal ultrasound parameters for vascular ring and trachea in fetuses with RAA-MB, employing a nomogram model to evaluate factors influencing their prognosis, thereby providing a comprehensive characterization of potential outcomes. Methods: A retrospective case-control study was conducted from March 2019 to March 2023. A systematic gathering of prenatal echocardiograms and clinical data was completed for a cohort comprising 92 cases of fetal RAA-MB at the Ultrasound Medicine Center of Gansu Provincial Maternity and Child Care Hospital. Participant recruitment was executed through random selection from among those receiving outpatient medical care. Within the cohort, 42 cases were categorized as fetuses with isolated RAA-MB, while the remaining 50 cases were characterized as fetuses with RAA-MB and associated anomalies. Measurements were taken of the angle between the right AO and the ductus arteriosus (DA) (AO-DA), the distance between the AO and DA, the diameter of AO and DA, and the distance growth rate (DGR) of the AO-DA distance. Additionally, measurements were taken of the tracheal anterior-posterior diameter, tracheal left-right diameter, and tracheal circumference in the three-vessel tracheal view. In the AO view, measurements were taken of the tracheal cross-sectional area (TA) and the vessel ring cross-sectional area (VRA). The relationship between these parameters and the prognosis of fetuses with RAA-MB was assessed using logistic regression analysis. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of the predictive model based on these factors. Results: The multivariate logistic regression analysis revealed that the independent predictive factors for the prognosis of fetuses with RAA-MB were the AO-DA distance [odds ratio (OR) =0.012], TA (OR =0.401), and VRA (OR =1.103) (all P values <0.001). The area under the ROC curve was 0.891 [95% confidence interval (CI): 0.789-0.914; P<0.001], indicating a high accuracy of the model's predictions. Conclusions: The AO-DA distance, TA, and VRA are factors that influence the prognosis of fetuses with RAA-MB. The column chart model constructed based on these parameters can effectively provide a reference for predicting the risk of adverse outcomes in fetuses with RAA-MB.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

BACKGROUND AND AIM: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. METHODS: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. RESULTS: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. CONCLUSION: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

The imaging manifestations of persistent truncus arteriosus in children.

Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.

[Research Progress in Examination Methods,Influencing Factors, and Drug Treatment of Vigilance].

Vigilance is a sensitive ability to respond to small changes in the environment and it is a major component of various cognitive performance tasks.Professionals in a variety of fields require high physical and vigilance performance during the working process to ensure productivity,workplace safety,and their own safety. This article reviews the research progress in vigilance in terms of the examination methods,influencing factors,and drug treatment in recent years,aiming to improve the understanding of vigilance and provide support for the research on vigilance and clinical treatment of vigilance-related dysfunctions.

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

Construction of a predictive model for gastric cancer neuroaggression and clinical validation analysis: A single-center retrospective study.

BACKGROUND: This study investigated the construction and clinical validation of a predictive model for neuroaggression in patients with gastric cancer. Gastric cancer is one of the most common malignant tumors in the world, and neuroinvasion is the key factor affecting the prognosis of patients. However, there is a lack of systematic analysis on the construction and clinical application of its prediction model. This study adopted a single-center retrospective study method, collected a large amount of clinical data, and applied statistics and machine learning technology to build and verify an effective prediction model for neuroaggression, with a view to providing scientific basis for clinical treatment decisions and improving the treatment effect and survival rate of patients with gastric cancer. AIM: To investigate the value of a model based on clinical data, spectral computed tomography (CT) parameters and image omics characteristics for the preoperative prediction of nerve invasion in patients with gastric cancer. METHODS: A retrospective analysis was performed on 80 gastric cancer patients who underwent preoperative energy spectrum CT at our hospital between January 2022 and August 2023, these patients were divided into a positive group and a negative group according to their pathological results. Clinicopathological data were collected, the energy spectrum parameters of primary gastric cancer lesions were measured, and single factor analysis was performed. A total of 214 image omics features were extracted from two-phase mixed energy images, and the features were screened by single factor analysis and a support vector machine. The variables with statistically significant differences were included in logistic regression analysis to construct a prediction model, and the performance of the model was evaluated using the subject working characteristic curve. RESULTS: There were statistically significant differences in sex, carbohydrate antigen 199 expression, tumor thickness, Lauren classification and Borrmann classification between the two groups (all P < 0.05). Among the energy spectrum parameters, there were statistically significant differences in the single energy values (CT60-CT110 keV) at the arterial stage between the two groups (all P < 0.05) and statistically significant differences in CT values, iodide group values, standardized iodide group values and single energy values except CT80 keV at the portal vein stage between the two groups (all P < 0.05). The support vector machine model with the largest area under the curve was selected by image omics analysis, and its area under the curve, sensitivity, specificity, accuracy, P value and parameters were 0.843, 0.923, 0.714, 0.925, < 0.001, and c:g 2.64:10.56, respectively. Finally, based on the logistic regression algorithm, a clinical model, an energy spectrum CT model, an imaging model, a clinical + energy spectrum model, a clinical + imaging model, an energy spectrum + imaging model, and a clinical + energy spectrum + imaging model were established, among which the clinical + energy spectrum + imaging model had the best efficacy in diagnosing gastric cancer nerve invasion. The area under the curve, optimal threshold, Youden index, sensitivity and specificity were 0.927 (95%CI: 0.850-1.000), 0.879, 0.778, 0.778, and 1.000, respectively. CONCLUSION: The combined model based on clinical features, spectral CT parameters and imaging data has good value for the preoperative prediction of gastric cancer neuroinvasion.

[Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise].

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

A hybrid quantum-classical classification model based on branching multi-scale entanglement renormalization ansatz.

Tensor networks are emerging architectures for implementing quantum classification models. The branching multi-scale entanglement renormalization ansatz (BMERA) is a tensor network known for its enhanced entanglement properties. This paper introduces a hybrid quantum-classical classification model based on BMERA and explores the correlation between circuit layout, expressiveness, and classification accuracy. Additionally, we present an autodifferentiation method for computing the cost function gradient, which serves as a viable option for other hybrid quantum-classical models. Through numerical experiments, we demonstrate the accuracy and robustness of our classification model in tasks such as image recognition and cluster excitation discrimination, offering a novel approach for designing quantum classification models.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy.

BACKGROUND: The intrapapillary capillary loop (IPCL) characteristics, visualized using magnifying endoscopy, are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma (ESCC). Japan Esophageal Society (JES) classification is the most widely used classification. Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor: tortuosity, dilatation, irregular caliber, and different shapes. However, the pathological characteristics of IPCLs have not been thoroughly investigated, especially the microvascular structures corresponding to the deepest parts of the lesions' infiltration. AIM: To investigate differences in pathological microvascular structures of ESCC, which correspond to the deepest parts of the lesions' infiltration. METHODS: Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023. Patients first underwent magnified endoscopic examination, followed by endoscopic submucosal dissection or surgical treatment. Pathological images were scanned using a three-dimensional slice scanner, and the pathological structural differences in different types, according to the JES classification, were analyzed using nonparametric tests and t-tests. RESULTS: The 35 lesions were divided into four groups according to the JES classification: A, B1, B2, and B3. Statistical analyses revealed significant differences (a P < 0.05) in the short and long calibers, area, location, and density between types A and B. Notably, there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3 (P > 0.05). However, significant differences in the short calibers, long calibers, and area of IPCL were observed between types B1 and B3 (a P < 0.05); no significant differences were found in the density or location (P > 0.05). CONCLUSION: Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy, especially between the types A and B.

Prevalence of infection and reinfection among health care workers in a hospital of Northern China between BA.5/BF.7 and XBB.1.5 wave.

BACKGROUND: To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs). METHODS: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions. RESULTS: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs. CONCLUSIONS: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services.

TGM1/3-mediated transamidation of Exo70 promotes tumor metastasis upon LKB1 inactivation.

Exo70, a key exocyst complex component, is crucial for cell motility and extracellular matrix (ECM) remodeling in cancer metastasis. Despite its potential as a drug target, Exo70's post-translational modifications (PTMs) are poorly characterized. Here, we report that Exo70 is transamidated on Gln5 with Lys56 of cystatin A by transglutaminases TGM1 and TGM3, promoting tumor metastasis. This modification enhances Exo70's association with other exocyst subunits, essential for secreting matrix metalloproteinases, forming invadopodia, and delivering integrins to the leading edge. Tumor suppressor liver kinase B1 (LKB1), whose inactivation accelerates metastasis, phosphorylates TGM1 and TGM3 at Thr386 and Thr282, respectively, to inhibit their interaction with Exo70 and the following transamidation. Cantharidin, a US Food and Drug Administration (FDA)-approved drug, inhibits Exo70 transamidation to restrain tumor cell migration and invasion. Together, our findings highlight Exo70 transamidation as a key molecular mechanism and target and propose cantharidin as a therapeutic strategy with direct clinical translational value for metastatic cancers, especially those with LKB1 loss.