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Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus’s entry into host cells and membrane fusion of the virus. However, the functions and relationship between host ppGalNAc-Ts and O-glycosylation on the S protein remain unclear. Herein, we identify 15 O-glycosites and 10 distinct O-glycan structures on the S protein using an HCD-product-dependent triggered ETD mass spectrometric analysis. We observe that the isoenzyme T6 of ppGalNAc-Ts (ppGalNAc-T6) exhibits high O-glycosylation activity for the S protein, as demonstrated by an on-chip catalytic assay. Overexpression of ppGalNAc-T6 in HEK293 cells significantly enhances the O-glycosylation level of the S protein, not only by adding new O-glycosites but also by increasing O-glycan heterogeneity. Molecular dynamics simulations reveal that O-glycosylation on the protomer-interface regions, modified by ppGalNAc-T6, potentially stabilizes the trimeric S protein structure by establishing hydrogen bonds and non-polar interactions between adjacent protomers. Furthermore, mutation frequency analysis indicates that most O-glycosites of the S protein are conserved during the evolution of SARS-CoV-2 variants. Taken together, our finding demonstrate that host O-glycosyltransferases dynamically regulate the O-glycosylation of the S protein, which may influence the trimeric structural stability of the protein. This work provides structural insights into the functional role of specific host O-glycosyltransferases in regulating the O-glycosylation of viral envelope proteins.

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By deploying computation and storage resources at the network edge that is close to the data source,and scheduling tasks offloaded by users efficiently,edge computing can greatly improve the quality of experience (QoE) of users.However,due to the lack of the reliable infrastructure support,the failure of edge servers or communication links could easily fail the edge computing service.To handle this problem,we establish the failure models of the computing nodes and communication links in edge computing,and then propose the rescheduling algorithm DaGTR (Dependency-aware Greedy Task Rescheduling) for the scheduling of dependent user tasks in resource failure scenarios.DaGTR includes two sub-algorithms,DaGTR-N and DaGTR-L,which are responsible for handling the node and link failure events respectively.DaGTR can sense the data dependency of tasks,and reschedule the tasks affected by failure events based on greedy method to ensure the successful execution of each task.Simulation results show that the algorithm can effectively avoid the task failure caused by failure events and improve the success rate of tasks in the case of resource failure.

Background To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. Methods and findings In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I.sup.2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I.sup.2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I.sup.2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I.sup.2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I.sup.2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I.sup.2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). Conclusions Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity., Author(s): Gifty Marley 1,2, Xia Zou 3, Juan Nie 4, Weibin Cheng 5,6, Yewei Xie 2, Huipeng Liao 2, Yehua Wang 2, Yusha Tao 2, Joseph D. Tucker 2,7, Sean [...]

Abstract Background Morbidity and mortality in transplant patients is increased by infection caused mainly by rare opportunistic pathogens. The present study reports a case where Hongkongmyces snookiorum caused subcutaneous phaeohyphomycosis in a kidney transplant patient. Case presentation A 47-year old Chinese woman with chronic kidney disease 5 underwent kidney transplantation 3 years ago. Her regular medications included Tacrolimus (1 mg, two times daily), Mycophenolate Mofetil (two times 250 mg, twice daily) and Prednisone acetate tablets (5 mg daily). Eighteen months ago, her proximal right index finger was red, painful and swollen. After admission, a hard and fluctuating 1 cm × 1 cm abscess was found on the dorsal side of the right index finger. Gram and fluorescence staining of a direct smear of a syringe extraction from the abscess revealed presence of filamentous fungi. White velvet colonies (2–3 mm) were found on blood plate and Sabouraud glucose agar (SGA) after 1 week, and grey aerial hyphae were observed. After 15 days, a 26 mm gray colony was also observed on SGA. The homology between this filamentous fungus and Hongkongmyces snookiorum ILLS00125755 (Genbank Sequence ID: MH161189.1) was 99.66%. An in vitro antifungal susceptibility test showed that this filamentous fungus was sensitive to azoles such as itraconazole and voriconazole. Conclusions We report an opportunistic fungus infection caused by Hongkongmyces snookiorum in a transplant patient. Our finding shows that prevention of subcutaneous fungal infection is necessary for kidney transplantation patients.

Microbial fermentation has been widely used to preserve or improve the nutritional properties of food. Liquid feeding can increase feed intake and reduce the morbidity of piglets. The objective of this study was to evaluate the effects of a diet fermented with bacteria and enzymes and liquid feeding on growth performance, nutrient digestibility, digestive enzyme activity, microflora, and expressions of intestinal development-related genes in weaning pigs. A total of 198 piglets (Duroc × Landrace × Yorkshire) with body weights of 8.70 ± 0.45 kg were assigned to three groups with six replicates per treatment, and 11 weaned piglets per replicate according to the initial body weight and sex. The three dietary treatments (all nonpelleted diets) were a standard dry feed as the control (CON), a control diet supplemented with antibiotics (AB), and a liquid feeding with a fermented diet (LFD). The liquid feeding diet, having the same composition and proportion of each ingredient as the control diet, was prepared by storing the dietary cereals (corn, soybeans, etc.) and water (1:0.5, wt/wt) in a closed tank at 26–30 °C with enzymes and bacteria, and then adding the remaining dietary ingredients immediately before feeding. The whole trial lasted 42 days. On days 11 to 14 and 39 to 42, fresh faecal samples were collected to evaluate the apparent total tract digestibility of nutrients. Performance, digestibility, serum physiochemical parameters, intestinal barrier function, microbiota, and microbial metabolites were measured. The experimental data were subjected to analysis of variance using the GLM procedure of SAS for a complete randomized block design, with a “pen” as the experimental unit. The results showed that the AB increased (p < 0.05) average daily gain and reduced (p < 0.05) feed conversion (F/G) over the course of 1–14 days compared to the control. The liquid feeding group significantly increased (p < 0.05) average daily gain, average daily feed intake, and final body weight compared to the other two dietary groups. The digestibility of crude protein, ether extract, ash, gross energy, Ca, and P also improved in the liquid feeding group. Moreover, the liquid feeding group significantly decreased (p < 0.05) serum urea nitrogen and D-lactate concentrations, as well as the activity of diamine oxidase, and increased (p < 0.05) serum total protein and glucose concentrations on day 14. Furthermore, the liquid feeding group significantly increased (p < 0.05) mRNA expressions of zonula occludens-2 (ZO-2) in the jejunum and zonula occludens-1 (ZO-1), ZO-2, occludin, and claudin-1 in the ileum. In addition, microbiota measurement suggested an increase in Lactobacillus content and a decrease in Escherichia coli with higher (p < 0.05) concentrations of acetic acid, propionic acid, butyric acid, and total volatile fatty acids in the caecal and colonic digesta of piglets in the liquid feeding group. In conclusion, the diet in the liquid feeding group was able to increase palatability, improve nutrient digestibility, and modulate metabolism, which resulted in higher feed efficiency and better growth performance in the piglets.

This study, inspired by the Risk Information Seeking and Processing (RISP) model, examines the mechanisms by which perceived hazard characteristics and the informational subjective norms of Chinese youth, aged from 14 to 44 years old, become associated with their intentions to seek cancer risk information online. A sample of 684 Chinese youths was collected from four cities in Mainland China with results revealing that perceived hazard characteristics and informational subjective norms motivate their online cancer risk information seeking intentions. Specifically, perceived probability, perceived severity, and institutional trust are positively related to negative affect, however the relationship between personal control and negative affect is not significant. Institutional trust and personal control are positively related to positive affect while perceived probability and perceived severity have no significant effect on positive affect. Negative affect and informational subjective norms are positively related to perceived information insufficiency, while the relationship between positive affect and perceived information insufficiency is not significant. Negative affect, positive affect, informational subjective norms, and perceived information insufficiency are all positively related to the online cancer risk information seeking intentions of Chinese youth. [ABSTRACT FROM AUTHOR]

Background: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E‐FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. Methods: An Attention U‐net and a U‐net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. Results: In 10 random tests, the Attention U‐net and U‐net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U‐net performed better at identifying negative images than the U‐net, which had an average specificity of 91% compared to 86% for the U‐net. Additionally, the Attention U‐net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U‐net's average dice coefficient of 0.82. Conclusions: The Attention U‐net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E‐FAST in clinical work. [ABSTRACT FROM AUTHOR]