Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice.

The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress in gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. Firstly, the characteristics of Mettl3 expression in IBD patients were examined. Afterwards we generated the mice line with IECs-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc. between the two groups. Subsequently, we took advantage of staining assays to analyze mucosal damage and immune infiltration of Mettl3WT and Mettl3KO primary IECs. Bulk RNA sequencing was used to pursuit the differential expression of genes (DEGs) and associated signaling pathways after losing Mettl3. Pyroptosis-related proteins were to determine whether cell death was caused by pyroptosis. Eventually, CyTOF was performed to probe the difference of CD45+ cells, especially CD3e+ T cells clusters after losing Mettl3. In IBD patients, Mettl3 was highly expressed in the inner-nucleus of IECs while significantly decreased upon acute intestinal inflammation. IECs-specific deletion of Mettl3 KO mice triggered a wasting phenotype and developed spontaneous colitis. The survival rate, body weight and intestinal length observed from 2 to 8-week of Mettl3KO mice was significantly lower than Mettl3WT mice. The degree of mucosal damage and immune infiltration in Mettl3KO were even more serious than their WT littermate. Bulk RNA sequencing demonstrated that DEGs were dramatically enriched in NOD-signaling pathways due to the loss of Mettl3. The colonic epithelium were more prone to pyroptosis after losing Mettl3. Subsequently, CyTOF revealed that T cells have altered significantly in Mettl3KO. Furthermore, there were abnormal proliferation of CD4+ T and markedly exhaustion of CD8+ T in Mettl3KO mice. In severe IBD patients, Mettl3 located in the inner-nucleus of IECs and declined when intestinal inflammation occurred. Subsequently, Mettl3 prevented mice from developing colitis.

Synthesis of dimpled polymer-silica nanocomposite particles by interfacial swelling-based seeded polymerization.

Dimpled polymer-silica nanocomposite particles have the combined advantages of dimpled particles and polymer-silica nanocomposite particles. This study presents a novel approach to prepare these particles by interfacial swelling-based seeded polymerization. Polystyrene-silica (PS-SiO2) nanocomposite particles are first prepared by emulsion polymerization of styrene in the presence of glycerol-functionalized silica sols and then dimpled polymer-SiO2 particles are fabricated by interfacial swelling of butyl acrylate (BA)/toluene and subsequent seeded polymerization of BA with the PS-SiO2 particles as seeds. The effects of different parameters, such as the amount of surfactant used in the PS-SiO2/H2O dispersion, BA/toluene mass ratio, PS-SiO2/H2O mass ratio and stirring rate, on the formation of the dimpled particles are investigated. Optimization of the seeded polymerization conditions allows a relatively high percentage of dimpled particles to be achieved.

The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation.

Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ß production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-ß signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme UBC9 and MAVS. Increased MAVS-UBC9 interaction leads to enhanced SUMOylation of MAVS, inhibiting its ubiquitination, resulting in the inhibition of phosphorylation events involving IKKα, TBK1, and IRF3, thus disrupting IFN-ß signaling. This study highlights the role of the N protein of SARS-CoV-2 in modulating the innate immune response by affecting the MAVS SUMOylation and ubiquitination processes, leading to inhibition of the IFN-ß signaling pathway. These findings shed light on the complex mechanisms utilized by SARS-CoV-2 to manipulate the host's antiviral defenses and provide potential insights for developing targeted therapeutic strategies against severe COVID-19.

Genotypic characterization of a Proteus mirabilis strain harboring blaKPC-2 on the IncN plasmid isolated from a patient with bloodstream infection in China.

BACKGROUND: Carbapenemase is the predominant enzyme in the mechanism leading to Enterobacterales resistance to carbapenems, and the rapid spread of the blaKPC gene is a major public health concern. Here, we describe a carbapenem-resistant Proteus mirabilis strain XH983, which harbored a blaKPC-2-producing IncN plasmid, isolated from a bloodstream infection. METHODS: Whole-genome sequencing and bioinformatics analysis were performed to assess the genetic environment of P. mirabilis XH983. Conjugation and transfer experiments were performed and the corresponding strains were confirmed by antimicrobial susceptibility testing. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant P. mirabilis isolates worldwide. RESULTS: P. mirabilis XH983 was isolated from the blood of a patient in Hangzhou, China. The genome of XH983 contained one 4128,916 bp circular chromosome and one 24,225 bp IncN plasmid harboring blaKPC-2. P. mirabilis XH983 had multiple resistance genes, conferring resistance to aminoglycosides [aph(3')-Ia, aph(3'')-Ib, aph(6)-Id, aac(3)-IId, aadA5, aadA1], ß-lactams (blaKPC-2, blaTEM-1B), phenicol (cat, catA1), sulphonamide/trimethoprim (drfA1, drfA17, sul1, sul2) and tetracycline [tet(J)]. The phylogenetic tree showed that XH983 was present in a cluster of 30 isolates, all of which carried blaKPC-2 and most of them came from the same hospital as XH983, indicating the clonal spread of the cluster. CONCLUSION: We characterized carbapenem-resistant P. mirabilis clinical isolate XH983. The genome sequence of P. mirabilis XH983 provides information about resistance mechanisms of P. mirabilis carrying the blaKPC-2 plasmid and the potential spread of blaKPC-2.

Association between emphysema and other pulmonary computed tomography patterns in COVID-19 pneumonia.

To evaluate the chest computed tomography (CT) findings of patients with Corona Virus Disease 2019 (COVID-19) on admission to hospital. And then correlate CT pulmonary infiltrates involvement with the findings of emphysema. We analyzed the different infiltrates of COVID-19 pneumonia using emphysema as the grade of pneumonia. We applied open-source assisted software (3D Slicer) to model the lungs and lesions of 66 patients with COVID-19, which were retrospectively included. we divided the 66 COVID-19 patients into the following two groups: (A) 12 patients with less than 10% emphysema in the low-attenuation area less than -950 Hounsfield units (%LAA-950), (B) 54 patients with greater than or equal to 10% emphysema in %LAA-950. Imaging findings were assessed retrospectively by two authors and then pulmonary infiltrates and emphysema volumes were measured on CT using 3D Slicer software. Differences between pulmonary infiltrates, emphysema, Collapsed, affected of patients with CT findings were assessed by Kruskal-Wallis and Wilcoxon test, respectively. Statistical significance was set at p < 0.05. The left lung (A) affected left lung 20.00/affected right lung 18.50, (B) affected left lung 13.00/affected right lung 11.50 was most frequently involved region in COVID-19. In addition, collapsed left lung, (A) collapsed left lung 4.95/collapsed right lung 4.65, (B) collapsed left lung 3.65/collapsed right lung 3.15 was also more severe than the right one. There were significant differences between the Group A and Group B in terms of the percentage of CT involvement in each lung region (p < 0.05), except for the inflated affected total lung (p = 0.152). The median percentage of collapsed left lung in the Group A was 20.00 (14.00-30.00), right lung was 18.50 (13.00-30.25) and the total was 19.00 (13.00-30.00), while the median percentage of collapsed left lung in the Group B was 13.00 (10.00-14.75), right lung was 11.50 (10.00-15.00) and the total was 12.50 (10.00-15.00). The percentage of affected left lung is an independent predictor of emphysema in COVID-19 patients. We need to focus on the left lung of the patient as it is more affected. The people with lower levels of emphysema may have more collapsed segments. The more collapsed segments may lead to more serious clinical feature.

Transmission and microevolution of methicillin-resistant Staphylococcus aureus ST88 strain among patients, healthcare workers, and household contacts at a trauma and orthopedic ward.

Background: Surgical sites infections (SSIs) caused by Methicillin-resistant Staphylococcus aureus (MRSA) constitute a major clinical problem. Understanding the transmission mode of MRSA is important for its prevention and control. Aim: We investigated the transmission mode of a MRSA outbreak in a trauma and orthopedic hospital ward. Methods: Clinical data were collected from patients (n = 9) with MRSA infection in a trauma and orthopedic ward from January 1, 2015 to December 31, 2019. The wards (n = 18), patients (n = 48), medical staff (n = 23), and their households (n = 5) were screened for MRSA. The transmission mode of MRSA isolates was investigated using next-generation sequencing and phylogenetic analyses. The resistance genes, plasmids, and single-nucleotide variants of the isolates were analyzed to evaluate microevolution of MRSA isolates causing SSIs. The MRSA colonization-positive doctor was asked to suspend his medical activities to stop MRSA spread. Findings: Nine MRSA infected patients were investigated, of which three patients were diagnosed with SSI and had prolonged hospitalization due to the persistent MRSA infection. After screening, MRSA isolates were not detected in environmental samples. The surgeon in charge of the patients with SSI caused by MRSA and his son were positive for MRSA colonization. The MRSA from the son was closely related to the isolates detected in MRSA-induced SSIs patients with 8-9 single-nucleotide variants, while ST88-MRSA isolates with three different spa types were detected in the surgeon's nasal cavity. Comparative genomic analysis showed that ST88-MRSA isolates acquired mutations in genes related to cell wall synthesis, colonization, metabolism, and virulence during their transmission. Suspending the medical activity of this surgeon interrupted the spread of MRSA infection in this ward. Conclusion: Community-associated MRSA clones can invade hospitals and cause severe postoperative nosocomial infections. Further MRSA surveillance in the households of health workers may prevent the transition of MRSA from colonization to infection.

Comparison of Clinical, Laboratory and Radiological Characteristics Between COVID-19 and Adenovirus Pneumonia: A Retrospective Study.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has become a global public health problem. It is important for clinical physicians to differentiate COVID-19 from other respiratory infectious diseases caused by viruses, such as human adenovirus. SUBJECTS AND METHODS: This was a retrospective observational study. We analyzed and compared the clinical manifestations, laboratory findings and radiological features of two independent cohorts of patients diagnosed with either COVID-19 (n=36) or adenovirus pneumonia (n=18). RESULTS: COVID-19 did not show a preference in males or females, whereas 94.4% of patients with adenovirus pneumonia were males. Fever and cough were common in both COVID-19 and adenovirus pneumonia. But the median maximal body temperature of the adenovirus pneumonia cohort was significantly higher than in COVID-19 (P<0.001). Furthermore, 77.8% of patients with adenovirus pneumonia had a productive cough versus only 13.9% of COVID-19 patients (P<0.001). Compared with adenovirus pneumonia, constitutional symptoms were less common in COVID-19, including headache (16.7% vs 38.9%, P=0.072), sore throat (8.3% vs 27.8%, P=0.058), myalgia (8.3% vs 61.1%, P<0.001) and diarrhea (8.3% vs 44.4%, P=0.002). Furthermore, patients with COVID-19 were less likely to develop respiratory failure (8.3% vs 83.3%, P<0.001) and showed less prominent laboratory abnormalities, including lymphocytopenia (61.1% vs 88.9%, P=0.035), thrombocytopenia (2.8% vs 61.1%, P<0.001), elevated procalcitonin (2.8% vs 77.8%, P<0.001) and elevated C-reactive protein (36.1% vs 100%, P<0.001). Besides, a higher percentage of patients with adenovirus pneumonia showed elevated transaminase, myocardial enzymes, creatinine and D-dimer compared with COVID-19 patients. On chest CT, the COVID-19 cohort was characterized by peripherally distributed ground-glass opacity and patchy shadowing, while the adenovirus pneumonia cohort frequently presented with consolidation and pleural effusion. CONCLUSION: There were many differences between patients diagnosed with COVID-19 and those with adenovirus pneumonia in their clinical, laboratory and radiological characteristics. Compared with adenovirus pneumonia, COVID-19 patients tended to show a lower severity of illness.

Analysis of clinical features and outcomes of 161 patients with severe and critical COVID-19: A multicenter descriptive study.

BACKGROUND: This study aimed to investigate clinical characteristics, laboratory indexes, treatment regimens, and short-term outcomes of severe and critical coronavirus disease 2019 (COVID-19) patients. METHODS: One hundred and sixty one consecutive severe and critical COVID-19 patients admitted in intensive care unit (ICU) were retrospectively reviewed in this multicenter study. Demographic features, medical histories, clinical symptoms, lung computerized tomography (CT) findings, and laboratory indexes on admission were collected. Post-admission complications, treatment regimens, and clinical outcomes were also documented. RESULTS: The mean age was 59.38 ± 16.54 years, with 104 (64.60%) males and 57 (35.40%) females. Hypertension (44 [27.33%]) and diabetes were the most common medical histories. Fever (127 [78.88%]) and dry cough (111 [68.94%]) were the most common symptoms. Blood routine indexes, hepatic and renal function indexes, and inflammation indexes were commonly abnormal. Acute respiratory distress syndrome (ARDS) was the most common post-admission complication (69 [42.86%]), followed by electrolyte disorders (48 [29.81%]), multiple organ dysfunction (MODS) (37 [22.98%]), and hypoproteinemia (36 [22.36%]). The most commonly used antiviral drug was lopinavir/ritonavir tablet. 50 (31.06%) patients died, while 78 (48.45%) patients healed and discharged, and the last 33 (20.50%) patients remained in hospital. Besides, the mean hospital stay of deaths was 21.66 ± 11.18 days, while the mean hospital stay of discharged patients was 18.42 ± 12.77 days. Furthermore, ARDS (P < .001) and MODS (P = .008) correlated with increased mortality rate. CONCLUSION: Severe and critical COVID-19 presents with high mortality rate, and occurrence of ARDS or MODS greatly increases its mortality risk.

Facilitators and Barriers Associated with Uptake of HIV Self-Testing among Men Who Have Sex with Men in Chongqing, China: A Cross-Sectional Survey.

While studies on human immunodeficiency virus self-testing (HIVST) continue to accumulate after the World Health Organization's recommendation of HIVST as an additional approach to HIV testing services in 2016, few studies have focused on men who have sex with men (MSM) in Chinese cities. A cross-sectional study was conducted to describe the HIVST status of MSM in Chongqing, China. MSM participants were recruited by random sampling, and qualified interviewers collected data, using confidential self-administered questionnaires. Blood specimens were collected for HIV antibody detection. The survey evaluated the uptake and accuracy of HIVST kits and identified factors that may be associated with HIVST. The proportion of HIVST uptake was 15.6%. The sensitivity and specificity of HIVST were 74.2% (95% confidence interval [CI] 66.6%-80.7%) and 99.0% (95% CI 96.9%-99.7%), respectively. The consistency between the HIVST kit and antibody detection results was 90.5% (95% CI 87.5%-93.0%), and the Kappa value was 0.777 (p < 0.001). The positive predictive value of self-testing kits is 80.9% and the negative predictive value is 17.7%. Having been tested ≥2 times in the last year, higher educational levels, and higher scores of basic HIV/AIDS knowledge facilitated higher uptake of HIVST. Self-reported existing barriers for HIVST uptake included older age, marital status, and having resided in Chongqing for more than two years.

Katanin P80 correlates with larger tumor size, lymph node metastasis, and advanced TNM stage and predicts poor prognosis in non-small-cell lung cancer patients.

OBJECTIVE: The present study aimed to investigate the correlation of katanin P80 expression with clinicopathological features and survival profile in non-small-cell lung cancer (NSCLC) patients. METHODS: Totally, 398 NSCLC patients treated by pulmonary resection were enrolled and their tumor specimens were collected to determine katanin P80 expression by immunohistochemistry (IHC) assay. Clinical data were collected at diagnosis, and survival data including disease-free survival (DFS) and overall survival (OS) were assessed after treatment. RESULTS: There were 195 (49.0%) patients with katanin P80 high expression and 203 (51.0%) patients with katanin P80 low expression, respectively. Meanwhile, katanin P80 high expression was associated with larger tumor size (P = .001), lymph node (LYN) metastasis (P = .005), and advanced TNM stage (P = .001). As for survival data, katanin P80 high expression was correlated with reduced DFS (P < .001) and OS (P < .001). And forward stepwise multivariate Cox's regression revealed that katanin P80 high expression was an independent predictor for decreased DFS (P < .001) and OS (P < .001). Besides, further analysis indicated that DFS (P < .001) and OS (P < .001) were the shortest in patients with katanin P80 high+++ expression, followed by patients with katanin P80 high++ expression and then those with katanin P80 high + expression and katanin P80 low expression. CONCLUSION: Katanin P80 correlates with larger tumor size, LYN metastasis, and advanced TNM stage, and serves as a potential biomarker for predicting poor survival in NSCLC patients.