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Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M.tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4+ T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M.tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.

Core fucosylation, catalyzed by α1,6-fucosyltransferase (FUT8), is an important N-glycosylation modification process that attaches a fucose residue via an α1,6-linkage to the core N-acetylglucosamine of N-glycans in mammals. Research over the past three decades has revealed the critical role of FUT8-mediated core fucosylation modification in various physiological and pathological processes, including cell growth, adhesion, receptor activation, antibody-dependent cellular cytotoxicity (ADCC), tumor metastasis and infections. This review discusses the immune system function involving FUT8 and the mechanisms by which core fucosylation regulates immunity and contributes to disease. A deeper understanding of these mechanisms can provide insights into cellular biology and suggest new therapeutic approaches and targets for related diseases.

Abstract Background Pancreaticoduodenectomy (PD) is a complex procedure and easily accompanied by healthcare-associated infections (HAIs). This study aimed to assess the impact of PBD on postoperative infections and clinical outcomes in PD patients. Methods The retrospective cohort study were conducted in a tertiary hospital from January 2013 to December 2022. Clinical and epidemiological data were collected from HAIs surveillance system and analyzed. Results Among 2842 patients who underwent PD, 247 (8.7%) were diagnosed with HAIs, with surgical site infection being the most frequent type (n = 177, 71.7%). A total of 369 pathogenic strains were detected, with Klebsiella pneumoniae having the highest proportion, followed by Enterococcu and Escherichia coli. Although no significant association were observed generally between PBD and postoperative HAIs, subgroup analysis revealed that PBD was associated with postoperative HAIs in patients undergoing robotic PD (aRR = 2.174; 95% CI:1.011–4.674; P = 0.047). Prolonging the interval between PBD and PD could reduce postoperative HAIs in patients with cholangiocarcinoma (≥4 week: aRR = 0.292, 95% CI 0.100–0.853; P = 0.024) and robotic PD (≤2 week: aRR = 3.058, 95% CI 1.178–7.940; P = 0.022). PBD was also found to increase transfer of patients to ICU (aRR = 1.351; 95% CI 1.119–1.632; P = 0.002), extended length of stay (P

Abstract With the growth of the global population and the development of the economy, the demand for delicious and nutritious meat is increasing. However, the pursuit of high productivity and a high lean meat rate in pig breeding has led to a serious decline in meat quality. How to moderately improve the quality and flavor of pork through nutritional supplementation is of great significance in meeting consumers' demand for high‐quality and delicious pork. Recent studies have shown that fermented feed using probiotics can not only improve the nutritional quality and utilization rate of agricultural by‐products, but also play an important role in improving meat color, increasing intramuscular fat content, regulating the flavor of pork, leading to a sustainable development of agriculture and husbandry. In this paper, we will review the current situation of the probiotics used in fermented feed, the effects of fermentation on the improvement of feed quality, the influence and mechanism of fermented feed on the growth performance, meat quality, and flavor of pigs, and so forth, aiming to provide theoretical basis and technical support for the research and development of fermented feed and its application in the production of high‐quality pork.

The nuclear shell model has been very successful in describing various properties of nuclei, especially in the neighborhood of the closed shells, where the configuration space is usually small but good enough for the construction of the nuclear wave function. However, in the heavy deformed nuclear region, the configuration space is extremely huge. This makes it almost impossible to perform full shell model calculations. To avoid such difficulty, various approximated shell model methods have been developed. Among them, the variation after projection (VAP) method is an important one, in which the nuclear wave functions with good quantum numbers are sufficiently optimized. However, when the VAP method is applied to heavy deformed nuclei, the computational burden is still quite heavy. This is because there are a large number of matrix elements involving the angular momentum projection. All these projected matrix elements should be calculated by integrating the corresponding rotational matrix elements over the three Euler angles. Hence, accelerating the VAP calculation is crucial in extending the VAP application to heavy deformed nuclei, which is the purpose of the present paper. By analyzing the VAP code, it turns out that most of the computational cost is spent on evaluating the projected matrix elements. When the configuration space is huge, such computational cost for the projected matrix elements becomes extremely heavy. Fortunately, all the rotational matrix elements are independent of one another. This makes it very convenient in parallelizing the calculation of these rotational matrix elements. In general, the VAP calculations were accelerated on the traditional CPU platforms. But in recent years, with the rapid developments of the graphics processing unit (GPU), GPU becomes the first choice of modern high-performance computing. Here, by adopting the OpenACC parallel programming directives, the VAP code from the traditional CPU platform to the high-performance GPU platform has been successfully migrated. The calculations of a large amount of the independent rotation matrix elements at each mesh point in the integration of the angular momentum projection were parallelized on a GPU card. It is confirmed that the results calculated by the migrated VAP code are exactly the same as the ones calculated by the original OpenMP parallelized VAP code. Most important of all, the speed of the GPU accelerated VAP code can be several times faster than that of the original OpenMP parallelized VAP code, when they run in the same machine. Using the GPU accelerated VAP code, spectrum of the ground state band of the heavy nucleus 178Hf have been calculated for the first time. This opens the door of the VAP application to the heavy deformed rare-earth nuclei.

Abstract Aberrant N-glycosylation has been implicated in viral diseases. Alpha-(1,6)-fucosyltransferase (FUT8) is the sole enzyme responsible for core fucosylation of N-glycans during glycoprotein biosynthesis. Here we find that multiple viral envelope proteins, including Hepatitis C Virus (HCV)-E2, Vesicular stomatitis virus (VSV)-G, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-Spike and human immunodeficiency virus (HIV)-gp120, enhance FUT8 expression and core fucosylation. HCV-E2 manipulates host transcription factor SNAIL to induce FUT8 expression through EGFR-AKT-SNAIL activation. The aberrant increased-FUT8 expression promotes TRIM40-mediated RIG-I K48-ubiquitination and suppresses the antiviral interferon (IFN)-I response through core fucosylated-EGFR-JAK1-STAT3-RIG-I signaling. FUT8 inhibitor 2FF, N-glycosylation site-specific mutation (Q352AT) of EGFR, and tissue-targeted Fut8 silencing significantly increase antiviral IFN-I responses and suppress RNA viral replication, suggesting that core fucosylation mediated by FUT8 is critical for antiviral innate immunity. These findings reveal an immune evasion mechanism in which virus-induced FUT8 suppresses endogenous RIG-I-mediated antiviral defenses by enhancing core fucosylated EGFR-mediated activation.

Abstract Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES‐based wound dressings. In this study, a novel sandwich‐structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro–electro–mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode–tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

PurposeThis study aimed to investigate the associations between hemoglobin (HGB) levels and bone mineral density (BMD) and fracture risk in type 2 diabetes mellitus(T2DM) population of different ages. MethodThis cross-sectional study included 641 patients with T2DM (57.9% males). BMD of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured using dual-energy X-ray absorptiometry. The 10-year probability of fracture was assessed using a fracture risk assessment tool (FRAX). HGB and other biochemical indices were measured in a certified laboratory at our hospital. Statistical analysis was performed using SPSS 26.0 and R language (R version 4.1.0). Generalized additive models (GAMs) were used to identify the associations between HGB and BMD and fracture risk.ResultsPatients with osteoporosis have lower HGB levels than the non-osteoporotic population and lower FN BMD in patients with anemia than in the non-anemic population. In patients with T2DM, there was sex- and age-related variability in the correlation between HGB levels and BMDs and fracture risk. In older men, HGB level was an independent determinant of BMD and was positively correlated with FN and TH BMD. In non-older women, HGB level was an independent determinant of BMD and fracture risk, positively associated with BMDs and negatively associated with 10-year probability of fracture risk. GAMs revealed a positive linear association between HGB level and BMDs in non-older female patients but not in older male patients.ConclusionOur study provides a new perspective on the association of HGB level and BMDs with fracture risk. Relatively high HGB levels are a protective factor for bone quality in patients with T2DM. However, the bone-protective effect of HGB is influenced by age and sex and persists only in older men and non-older women with T2DM.

Background As population ageing accelerates and life expectancy increases, multimorbidity and disability pose challenges to health and social care systems worldwide. Although multimorbidity is closely related to disability, there is still a lack of research on the impact of multimorbidity on disability in rural middle-aged and elderly people. Objective To evaluate the influence of multimorbidity on disability in rural middle-aged and elderly people using the propensity-score matching (PSM) , providing a reference for formulating strategies for the management of multimorbidity and disability in this population. Methods The data of 11 088 rural middle-aged and elderly people (≥45 years old) were collected from the 2018 China Health and Retirement Longitudinal Study in March 2022, including demographics, chronic disease prevalence, and disability measured by activities of daily living (ADLs) , and instrumental activities of daily living (IADLs) . Participants were divided into multimorbidity and non-multimorbidity groups by the prevalence of multimorbidity (defined as having ≥2 chronic conditions) , and then matched using PSM with a 1∶1 ratio. Conditional Logistic regression model for paired binary data was used to assess the impact of multimorbidity on ADL disability and IADL disability. Results Of 11 088 ural middle-aged and elderly people with chronic diseases, 2 711 (24.45%) had ADL disability, 4 216 (38.02%) had IADL disability, and 7 673 (69.20%) were multimorbidity patients. The prevalence of ADL disability or IADL disability differed significantly by gender, age, marital status, education level, sleep duration, smoking, drinking, disability status, participation in social activities, and prevalence of multimorbidity (P

Abstract Despite great advance has been made in multi‐modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti‐tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune‐related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD‐L1/PD‐1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg‐modulating agents and PD‐L1/PD‐1 inhibitors.

This study aimed to investigate the effects of dietary Eucommia ulmoides leaf extract (ELE) on meat quality, antioxidant capacity, and lipid metabolism in finishing pigs. A total of 240 “Duroc × Landrace × Yorkshire” crossbred pigs with an initial weight of 74.70 ± 0.77 kg were randomly assigned to two groups: control group and 0.2% ELE group, with each group containing 10 replicates of 12 pigs per pen (half barrows and half gilts). The data showed dietary 0.2% ELE supplementation did not affect growth performance but tended to reduce the backfat thickness of the finishing pigs (p = 0.07). ELE diets increased pH value (p < 0.05) and meat color score (p = 0.01) and decreased 45 min L* value (p < 0.05), 24 h L* value (p = 0.01), pressurization loss (p = 0.01), and 24 h drip loss (p < 0.05) in longissimus dorsi (LD) muscle, accompanied by an increased (p < 0.05) proportion of monounsaturated fatty acids (MUFA) and decreased polyunsaturated fatty acids (PUFA) (p = 0.06) and n-6/n-3 PUFA ratio (p = 0.05) compared to controls. In addition, ELE supplementation increased inosine monophosphate (IMP) (p = 0.01), sweet amino acids (AAs) (p < 0.05), and total free AA content (p = 0.05) in LD. Meanwhile, increased activity of glutathione peroxidase (p < 0.05) and superoxide dismutase (p < 0.01) in both serum and LD muscle and decreased malondialdehyde content (p < 0.01) in LD muscle were detected with ELE treatment. Moreover, pigs fed ELE had a higher total protein (p < 0.01), albumin (p < 0.05), and high-density lipoprotein cholesterol (p < 0.05) and a lower total cholesterol (p < 0.01) and triacylglycerols (p = 0.06) in serum. Consistently, significant effects of dietary ELE were observed on the relative mRNA expression of lipid metabolism in the backfat and the LD muscle, respectively. ELE attenuated lipogenic processes in backfat, decreasing the relative expression of acetyl-CoA carboxylase and upregulating the relative expression of adipose triacyl glyceride lipase, carnitine palmitoyl transferase 1B, and fatty acid-binding protein 4 (p < 0.05). ELE also decreased the relative expression of CCAAT/enhancer-binding protein α (p < 0.05), fatty acid translocase (p < 0.05), carnitine palmitoyl transferase 1B (p < 0.01), and adipose triacyl glyceride lipase (p < 0.05) in LD muscle (p < 0.05). More specifically, lipogenesis appeared to be inhibited in both LD muscle and backfat, with the difference being that lipolysis was enhanced in backfat and inhibited in LD muscle. In conclusion, dietary ELE supplementation can potentially enhance carcass traits, sensory quality, and nutritional value of pork without negatively affecting intramuscular fat content. The underlying mechanism for these positive effects may be linked to the alterations in lipid metabolism and increased antioxidant capacity induced by ELE.

Unconventional feed, which is abundant in China, contains anti-nutritional factors and toxins; however, these can be greatly reduced with microbial fermentation, thus improving the nutrient content of the feed, enhancing animal appetites, and ultimately significantly improving the intestinal health and growth performance of animals. When oxidative stress occurs, fermented feed can effectively reduce the damage caused by stress to the gastrointestinal tract, accelerate the removal of gastrointestinal abnormalities, improve the ability to resist intestinal stress, and ensure the efficient production of animals. This review introduces the application of unconventional fermented feed in animal production, and expounds upon the function of unconventional fermented feed in animals with oxidative stress symptoms, so as to provide a theoretical reference for the development and application of unconventional fermented feed in antioxidative stress reduction.

The stability of the output speed of a hydraulic system has a great influence on the working performance of hydraulic equipment. It changes with the system working conditions. The increase in leakage caused by the wear of the hydraulic kinematic pair and the slip of the motor lead to the instability of the output speed. Although the hydraulic system can satisfy the output requirements of the active control scheme with ex ante decision making or the passive feedback control strategy with ex post compensation, it also causes an increase in system complexity and manufacturing cost. The speed stiffness as a basic characteristic of the output of the hydraulic system has not been sufficiently investigated and evaluated. In this paper, the IFMDH (inverter-fed, motor-driven hydraulic) system is taken as the object, and the coupling relationship of each link of the system is revealed by mathematical modelling. The reliability of the model is verified under a wide range of speed and load variations in combination with experiments. By redefining the speed stiffness quantification method, the effects of load conditions, motor stiffness, and speed ratio at the output end on the speed stability of the system are discussed in conjunction with the system coupling mechanism model. The conclusions show that the motor stiffness and the addition of a speed reducer have a significant effect on the system speed stiffness, where changing the output speed ratio has a significant effect on the speed stiffness. The conclusions of the study provide technical support for the rapid design, selection, and system optimisation of hydraulic systems in common scenarios.

BackgroundThe prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown.MethodsTwo IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces.ResultsThe diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of Alistipes and Rikenellaceae strains compared to the other groups.ConclusionIn an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis.