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Abstract Idiopathic inflammatory myopathy (IIM) with autoantibodies recognizing the signal recognition particle (SRP) is characterized by prominent proximal weakness, infrequent extramuscular involvement, dramatically elevated creatine kinase levels, and myofiber necrosis with few inflammatory cell infiltrates in muscle tissue. To enhance understanding of the clinically used diagnosis and treatment of this disease, this study presents a single-center experience and analysis of a Chinese cohort with anti-SRP IIM. The most recent European Neuromuscular Center criteria were used to include Anti-SRP IIM patients from September 2016 to November 2019. Prior to treatment initiation, all sera were collected for the detection of anti-SRP autoantibodies and other myositis-related autoantibodies. Muscle strength, concurrent autoimmune conditions, comorbidities like interstitial lung disease (ILD), treatment outcomes, and follow-up results were also documented. Univariate logistic regression was employed to determine factors affecting prognosis. Among 271 patients with IIM, we identified 23 (8.5%) patients with anti-SRP IIM. Lower limb muscle weakness was frequently more severe. Interstitial lung disease (ILD) was observed in 50% of anti-SRP IIM patients. The presence of ILD may serve as a predictor of a poor prognosis, as revealed by univariate logistic regression analysis (odds ratio, 3.8, 95% CI: 1.0-6.8, p = 0.05).This Chinese Anti-SRP IIM cohort from Hunan province seems to have higher incidences of ILD, and associated ILD may be a risk factor for a poor prognosis. To fully understand the specific role of the anti-SRP autoantibody in this unique subset with ILD, further research is necessary.

Abstract Cervical cancer is a kind of tumor related to chronic HPV infection. Currently, the treatment of cervical cancer is guided mainly by clinicopathological factors. The role of tumor microenvironment in the prognosis and treatment of cervical cancer has been ignored. We aimed to use bioinformatics to identify the molecular subtypes in cervical cancer and construct a predictive nomogram combining a matrix-immune signature (MIS) and clinicopathological factors to support treatment decisions. Two cervical cancer subtypes with different prognoses were identified based on matrix- and immune-genes in TCGA-CESC. The MIS was developed using Cox regression and Lasso algorithm and verified in the Cancer Genome Characterization Initiative (CGCI) using time-dependent receiver operating characteristic (ROC) curve analysis. Multivariable analysis identified lymph node metastases, lymphovascular space invasion, and the MIS as independent prognostic factors, which were used to construct the predictive nomogram. The areas under the ROC curve of the model were 0.872, 0.879, and 0.803 for the 1-, 3-, and 5-year periods, respectively. The C-index was 0.845. Calibration curves confirmed the excellent prognosis prediction of the nomogram. The nomogram indicted a 3-year survival rate of > 90% in patients with a total score > 110.1. The constructed predictive nomogram has significant implications for prognostic assessment and treatment selection in cervical cancer.

WHO classified Helicobacter pylori as a Group I carcinogen for gastric cancer as early as 1994. However, despite the high prevalence of H. pylori infection, only about 3 % of infected individuals eventually develop gastric cancer, with the highly virulent H. pylori strains expressing cytotoxin-associated protein (CagA) and vacuolating cytotoxin (VacA) being critical factors in gastric carcinogenesis. It is well known that H. pylori infection is divided into two types in terms of the presence and absence of CagA and VacA toxins in serum, that is, carcinogenic Type I infection (CagA+/VacA+, CagA+/VacA-, CagA-/VacA+) and non-carcinogenic Type II infection (CagA-/VacA-). Currently, detecting the two carcinogenic toxins in active modes is mainly done by diagnosing their serological antibodies. However, the method is restricted by expensive reagents and intricate procedures. Therefore, establishing a rapid, accurate, and cost-effective way for serological profiling of carcinogenic H. pylori infection holds significant implications for effectively guiding H. pylori eradication and gastric cancer prevention. In this study, we developed a novel method by combining surface-enhanced Raman spectroscopy with the deep learning algorithm convolutional neural network to create a model for distinguishing between serum samples with Type I and Type II H. pylori infections. This method holds the potential to facilitate rapid screening of H. pylori infections with high risks of carcinogenesis at the population level, which can have long-term benefits in reducing gastric cancer incidence when used for guiding the eradication of H. pylori infections.

Due to the high dispersion of solid powder, it is very easy to form a powder/gas hybrid system, which greatly increases the probability and severity of explosion accidents. The researchers both domestically and internationally have conducted extensive research on the hybrids explosion systems. This paper reviews the combustion characteristics, explosion mechanisms, and explosion prevention experiments of hybrids. Current research results on explosion prevention technology are organized, and the current challenges in experimental studies of hybrids explosions are summarized, providing references for future experimental studies.

Abstract Objectives Serum/glucocorticoid-inducible kinase 1 (SGK1) gene encodes a serine/threonine protein kinase that plays an essential role in cellular stress response and regulation of multiple metabolic processes. However, its role in bovine adipogenesis remains unknown. In this study, we aimed to clarify the role of SGK1 in bovine lipid accumulation and improvement of meat quality. Methods Preadipocytes were induced to differentiation to detect the temporal expression pattern of SGK1. Heart, liver, lung, spleen, kidney, muscle and fat tissues were collected to detect its tissue expression profile. Recombinant adenovirus and the lentivirus were packaged for overexpression and knockdown. Oil Red O staining, quantitative real-time PCR, Western blot analysis, Yeast two-hybrid assay, luciferase assay and RNA-seq were performed to study the regulatory mechanism of SGK1. Results SGK1 showed significantly higher expression in adipose and significantly induced expression in differentiated adipocytes. Furthermore, overexpression of SGK1 greatly promoted adipogenesis and inhibited proliferation, which could be shown by the remarkable increasement of lipid droplet, and the expression levels of adipogenic marker genes and cell cycle-related genes. Inversely, its knockdown inhibited adipogenesis and facilitated proliferation. Mechanistically, SGK1 regulates the phosphorylation and expression of two critical proteins of FoxO family, FOXO1/FOXO3. Importantly, SGK1 attenuates the transcriptional repression role of FOXO1 for PPARγ via phosphorylating the site S256, then promoting the bovine fat deposition. Conclusions SGK1 is a required epigenetic regulatory factor for bovine preadipocyte proliferation and differentiation, which contributes to a better understanding of fat deposition and meat quality improvement in cattle.

Abstract Objective The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS). Methods A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters. Results The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05). Conclusion Vitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance.

Introduction Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI- ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear. Therefore, this study aimed to evaluate the protective effect of ondansetron, a 5-HT3 inhibitor, on TBI-ALI, and to explore whether the underlying mechanism is related to the regulation of TREM-1. Material and methods A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed. Results TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue. Conclusions Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

Resveratrol (RSV) has been shown to prevent epithelial-mesenchymal transition (EMT) in different diseases by modulating several signaling pathways, and RSV can prevent EMT by modulating the signaling of the TGF-β/Smad axis. In the development of renal ischemia‒reperfusion injury (RIRI), RSV and MSC-derived exosomes could ameliorate RIRI via different signaling pathways. In this study, we aimed to investigate the effect of RSV plus MSC-derived exosomes on the prognosis of RIRI. Quantitative real-time polymerase chain reaction (PCR) was performed to measure the expression of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA in TCMK-1 cells and mice under various conditions. HE and Masson staining were used to evaluate kidney injury and fibrosis in mice under various conditions. RSV effectively maintained the TGF-β- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Moreover, MSC-derived exosomes effectively reinforced the effect of RSV on reducing the TGF-β- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Furthermore, MSC-derived exosomes enhanced the capability of RSV to maintain the RIRI-induced increases in Cr and BUN, as well as the upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in mice. In addition, MSC-derived exosomes enhanced the capability of RSV to decrease RIRI-induced kidney injury and fibrosis in mice. Our findings showed that the administration of MSC-derived exosomes and RSV could suppress the TGF-β-induced epithelial-mesenchymal transition. This suppressive effect was promoted by the coadministration of MSC-derived exosomes and RSV.

Abstract Background Toxoplasma gondii and Neospora caninum are closely related protozoan parasites that are considered important causes of abortion in livestock, causing huge economic losses. Hunan Province ranks 12th in the production of beef and mutton in China. However, limited data are available on the seroprevalence, risk factors and molecular characterization of T. gondii and N. caninum in beef cattle and goats in Hunan province, China. Methods Sera of 985 beef cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using indirect hemagglutination test (IHAT) and anti-N. caninum IgG using competitive-inhibition enzyme-linked immunoassay assay (cELISA). Statistical analysis of possible risk factors was performed using PASW Statistics. Muscle samples of 160 beef cattle and 160 goats were examined for the presence of T. gondii DNA (B1 gene) and N. caninum DNA (Nc-5 gene) by nested PCR. The B1 gene-positive samples were genotyped at 10 genetic markers using the multilocus nested PCR-RFLP (Mn-PCR-RFLP). Results Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) and against N. caninum in 2.1% (21/985) and 2.0% (23/1147) of the beef cattle and goats, respectively. Based on statistical analysis, the presence of cats, semi-intensive management mode and gender were identified as significant risk factors for T. gondii infection in beef cattle. Age was a significant risk factor for T. gondii infection in goats (P 3 years was a significant risk factor for N. caninum infection in beef cattle (P

IntroductionPrevious studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms.MethodsIn this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms.ResultsCompared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson–Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset.ConclusionSleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.

Abstract Background Breast cancer (BC) is one of the malignant diseases threatening the life and health of women worldwide. The CYP4B1 gene was abnormally expressed in BC and was associated with the prognosis of BC patients. This study aimed to explore the relationship between CYP4B1 single nucleotide polymorphisms (SNPs) and BC risk in Chinese women. Methods A case-control study of 1,143 women (571 patients and 572 healthy individuals) was conducted. Rs2297813 G/T, rs12142787 G/A, and rs3766197 C/T in CYP4B1 were selected and genotyped by MassARRAY system. The relationships between these SNPs and the risk of BC were assessed by logistic regression analysis. In addition, multi-factor dimensionality reduction (MDR) was used to analyze SNP-SNP interactions. Results CYP4B1 rs2297813 had a risk-increasing effect on BC in women with body mass index (BMI) ≤ 24 kg/m2 (OR = 1.72, p = 0.026). CYP4B1 rs12142787 was associated with an increased BC risk in smokers (AA: OR = 1.32, p = 0.045). Among non-drinkers, rs2297813 (OR = 1.69, p = 0.009) and rs12142787 (OR = 1.51, p = 0.020) were related to an increased incidence of BC. CYP4B1 rs3766197 (OR = 1.61p = 0.031) was associated with a higher risk of advanced stages (III/IV stage) of BC. Besides, the contributions of CYP4B1 rs2297813 (OR = 1.55, p = 0.021) and rs12142787 (OR = 1.53, p = 0.033) to BC risk might be associated with more than one birth in patients with BC. The three-locus model consisting of rs2297813, rs12142787, and rs3766197 was regarded as the best predictive model for BC risk. Conclusion CYP4B1 SNPs were associated with BC risk in Chinese women, especially in patients with BMI ≤ 24 kg/m2, smokers, non-drinkers, patients in advanced stages (III/IV stage), and patients who reproduced once. These findings shed light on the relationship between CYP4B1 SNPs and BC risk in Chinese women.

Abstract To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including “Takayasu Arteritis”, “Tuberculosis”, and “Mycobacterium tuberculosis”, the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48–43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71–28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70–87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25–68.77%) and active TB at 14.40% (95% CI 9.03–20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population.

In offshore pile engineering, the installation of jacked piles generates compaction effects within soil, thus further affecting previously installed adjacent piles. This study proposes a three-dimensional numerical model for pile group installation, soil consolidation, and loading analysis. Subsequently, the effect of pile spacing and pile length-to-diameter ratio on the deformation, internal forces, and vertical bearing capacity of adjacent piles are investigated. The results indicate that with an increase in pile center distance, the peak lateral displacement of the adjacent piles decreases, whereas the peak vertical displacement increases. As the pile length-to-diameter ratio increases, the peak vertical and lateral displacements of the adjacent piles are enhanced. In addition, the peak axial force of the adjacent piles initially decreases and then increases with the penetration depth of the subsequent pile, whereas the peak bending moment initially increases and then decreases. The vertical bearing capacity of the subsequent pile is significantly superior to that of the adjacent piles. Therefore, the effects of pile installation on adjacent piles should be included in pile engineering. The impact of the subsequent pile installation on the bearing capacity of adjacent piles can be significantly reduced by increasing the pile center distance and pile length-to-diameter ratio. The findings provide useful guidance for pile group engineering.

ObjectiveTo analyse whether the accumulation of early adverse experiences among individuals of different generations has an impact on disabilities and evaluate the cumulative effects of disadvantages in rural older adults in China.MethodsA Binary Logit Model was used to analyse the life course effects of the disability dilemma among rural older adults.ResultsRegarding Activities of Daily Life (ADLs), there was no significant difference between older adults that experienced 1 adverse events and the control group. The probability of older adults experiencing difficulties in 2, 3, 4, or more types of ADLs was 1.486 times, 2.173 times, and 3.048 times higher than that of the control group, respectively. Regarding Instrumental Activities of Daily Life (IADLs), there was no significant difference between the population that experienced 1 or 2 adverse events and the control group. The probability of experiencing difficulties in 3, 4, or more types of IADLs was 1.527 times and 1.937 times higher than that of the control group, respectively. Early adverse events had a cumulative disadvantageous effect on disability in older adults. The longer the duration of adverse experiences, the higher the risk of disability in old age. Education had a significant mitigating effect on health risks.ConclusionPay attention to early factors in the life course, strengthen the promotion of health prevention concepts, and pay attention to the moderating and relieving effects of education on health. We should also gradually improve the rural disability care system and family health security capabilities in China’s rural areas.

Purposes Diseases such as hypertension and malaria infection often raise the rigidity of red blood cells (RBCs). Consequently, the morphology and rheological characteristics of RBCs change, which means understanding the deformability and flow characteristics of sick RBCs is of great significance for clinical diagnosis and drug treatment. Methods In this work, RBCs were treated with a series of fixatives to mimic sick RBCs. Devices such as microfluidic chip, injection pump, fluorescence inverted microscope, and high-speed camera were used to study the flow characteristics of treated RBCs flowing in microchannel in vitro. The relationships between the deformability of RBCs and Cell free Layer (CFL) thickness, flow velocity, and other parameters were explored. Findings The results show that, after treating with fixative solution, the diameter of RBCs increases, the width of CFL becomes thinner, and the velocity of RBCs becomes lower. After the disease, the rigidity of RBCs is enhanced, the deformability is reduced, and the flow characteristics of red blood cells are obviously changed.

Background: The rapid and reliable detection of pathogenic bacteria at an early stage is a highly significant research field for public health. However, most traditional approaches for pathogen identification are time-consuming and labour-intensive, which may cause physicians making inappropriate treatment decisions based on an incomplete diagnosis of patients with unknown infections, leading to increased morbidity and mortality. Therefore, novel methods are constantly required to face the emerging challenges of bacterial detection and identification. In particular, Raman spectroscopy (RS) is becoming an attractive method for rapid and accurate detection of bacterial pathogens in recent years, among which the newly developed surface-enhanced Raman spectroscopy (SERS) shows the most promising potential. Aim of Review: Recent advances in pathogen detection and diagnosis of bacterial infections were discussed with focuses on the development of the SERS approaches and its applications in complex clinical settings. Key Scientific Concepts of Review: The current review describes bacterial classification using surface enhanced Raman spectroscopy (SERS) for developing a rapid and more accurate method for the identification of bacterial pathogens in clinical diagnosis. The initial part of this review gives a brief overview of the mechanism of SERS technology and development of the SERS approach to detect bacterial pathogens in complex samples. The development of the label-based and label-free SERS strategies and several novel SERS-compatible technologies in clinical applications, as well as the analytical procedures and examples of chemometric methods for SERS, are introduced. The computational challenges of pre-processing spectra and the highlights of the limitations and perspectives of the SERS technique are also discussed. Taken together, this systematic review provides an overall summary of the SERS technique and its application potential for direct bacterial diagnosis in clinical samples such as blood, urine and sputum, etc.

Abstract Estimating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -specific immunoglobulin G (IgG) immunoglobulin M (IgM) antibodies are increasingly important for tracking the spread of infection and defining herd immunity barrier and individual immunization levels in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Therefore, we conducted the present systematic review and meta-analysis to evaluate the seroprevalence of SARS-CoV-2 IgM and IgG antibodies of recovered COVID-19 patients in long-term follow-up studies. A systematic search of the MEDLINE, Embase, COVID-19 Primer, PubMed, CNKI, and the Public Health England library databases was conducted. Twenty-fourth eligible studies were included. Meta-analysis showed that 27% (95%CI: 0.04–0.49) and 66% (95%CI:0.47–0.85) were seropositive for SARS-CoV-2 IgM and IgG, respectively, while in long-term 12 months following up studies, the seroprevalences of IgM antibody (17%) decreased and IgG antibody (75%) was higher than 6 months follow-up patients. However, due to the limited number of relevant studies, the high level of heterogeneity, and the large gap in studies conducted, the findings of our study may not accurately reflect the true seroprevalence status of SARS-CoV-2 infection. Nevertheless, sequential vaccination or booster immunization is considered to be a necessary long-term strategy to sustain the fight against the pandemic.

Abstract Background Although there are concerns about the association between dermatomyositis (DM) and malignancy, the clinical features in elderly DM patients with lung cancer are largely unknown. Here, we elucidated the clinical features and risk factors of lung cancer in elderly DM patients. Methods The data of elderly DM patients (≥65 years old) with or without lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2016 to November 2022 were retrospectively analyzed. Results Male patients with elderly onset DM (EODM) symptoms were found to be prone to lung cancer (p

Abstract Aim The aim of this study was to examine hope level and its influencing factors in patients with decompensated liver cirrhosis. Design A prospective observational study. Methods We selected 93 patients with decompensated liver cirrhosis from a Chinese university hospital based on the inclusion and exclusion criteria. A general information questionnaire and Herth Hope Index were used, and multiple linear regression identified factors associated with the patients' hope level. Results The participants' average hope level was 32.01 ± 6.14 (moderate). The hope score's highest and lowest dimensions were “interconnectedness” (11.29 ± 2.17) and “temporality and future” (10.12 ± 2.28), respectively. Multiple linear regression showed that education level and monthly per capita income were independent influencing factors (p

Abstract Background N 6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC. Methods We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP. Results METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A “reader” YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2. Conclusions In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.

$30~\mu $ m ultra-thin Mo-Re sheet had been joined by micro resistance spot welding (MRSW) and successfully applied to the low heating power cathode of traveling wave tube (TWT). The effects of different welding parameters, surface state and protection conditions on the joint’s appearance, micro-structure and lap shear strength (LSS) were analyzed in this paper. The results showed that a 63.5 N LSS of the MRSW joint was obtained under the following conditions: electrode force $F=9.0$ N, welding current $I=1000\text{A}$ , ramping time $t_{1}=5$ ms, welding time $t_{2}=2$ ms and dip in the alcohol for protection. The fracture occurs in the heat affected zone (HAZ). Using metallurgical microscopy observed the nugget, metallurgical fusion could be found, the diameter of nugget was about $\Phi 0.3$ mm, without gas pores. Scanning electron microscopy (SEM) was used to observe the fracture surface. It could be found some “whisker” shape diverged from the joint center to the surroundings in HAZ. The electrode tip was observed by energy dispersive spectroscopy (EDS) and optical profiler. It was found that the tip was uneven and adhered the base metal obviously after spark. Additional work about electrode sticking will be required. The thermal test data showed that the use of ultra-thin Mo-Re sheet can reduce a space TWT cathode heating power (CHP) by 0.57 W, which will effectively save satellite energy and improve the expected working life of vacuum electronic devices.

Background: Oxidative stress could seriously affect the growth performance of piglets. As natural extracts of Alfalfa (Medicago sativa), alfalfa saponins have been shown to function as antioxidants in piglets in vivo. However, few studies have investigated the effects and mechanism of alfalfa saponins against oxidative stress in piglet cells in vitro. In the current study, piglets’ small intestinal epithelial cell line (IPEC-J2) was explored to investigate the protective effects of alfalfa saponins on injured cells induced by H2O2. Methods: To investigate the effects and mechanism of alfalfa saponins against oxidative stress in piglet cells, the cell viability, activity of antioxidant enzymes, LDH and the amount of MDA were detected in H2O2-treated cells after the cells were pre-incubated with alfalfa saponins. The mechanism of alfalfa saponins against H2O2-induced oxidative cell damage was explored by detecting the expression of mitochondrial apoptosis-related proteins. Furthermore, the signaling pathway of alfalfa saponins in IPEC-J2 cells under oxidative stress was also investigated. Results: The results indicated that alfalfa saponins could rescue cell viability, elevate the activity of antioxidant enzymes and down-regulate the activity of LDH and the amount of MDA in H2O2-induced cells. Conclusion: Alfalfa saponins could inhibit oxidative stress-induced cell mitochondrial apoptosis through the MAPK signaling pathway, thereby providing a new method for improving antioxidant stress ability by means of nutritional regulation.

Abstract Background Heterotaxy syndrome (HTX) is caused by aberrant left–right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. Methods Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. Results Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. Conclusion Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Abstract Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects multiple systems and increases the risk of mental disorders such as depression and anxiety. We conducted an observational, single-center, cross-sectional study to investigate the relationship between depression, anxiety, and SLE disease activity. Methods The Patient Health Questionnaire 9 (PHQ-9) was used to assess depression, and the 7-item Generalized Anxiety Disorders Scale was used to assess anxiety (GAD-7). Using the chi-square/exact Fisher's tests, socio-demographic data, clinical and other characteristics of SLE patients were compared between depression or anxiety and non-depression/non-anxiety groups. To identify optimal levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) for predicting depression or anxiety, receiver-operator curves (ROC) were drawn. Results Among the 325 patients involved in this study, patients with depression or anxiety had significantly higher SLE activity (p

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25–37 °C) and pH (6.5–9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV–visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of α-helix and reducing of β-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification.

Cigarette smoke exposure is an important factor in chronic inflammation in patients with allergic rhinitis (AR); however, the relationship between cigarette smoke and AR-related glucocorticoid resistance requires further study. In mice, calpeptin significantly reduces inflammation of the lower respiratory tract caused by cigarette smoke, but whether it can treat glucocorticoid-resistant AR caused by cigarette smoke requires further research. In this study, we confirmed that cigarette smoke exposure can aggravate the Th2 inflammatory response in AR leading to glucocorticoid resistance. The underlying mechanism may be related to decreased expression of DNA methyltransferase 3a (Dnmt3a), and increased expression of interferon regulatory factor 1 (IRF1). In addition, we found that calpeptin can inhibit the expression of IRF1 and thus treat AR-associated glucocorticoid resistance in rats exposed to cigarette smoke. These data suggest that calpeptin may downregulate IRF1 and therefore treat glucocorticoid resistance in AR-associated with cigarette smoke exposure.

Objectives: We investigated the effects of macrophage migration inhibitory factor (MIF) knockdown or overexpression combined with ultraviolet radiation B (UVB) irradiation on cell proliferation and apoptosis of oral squamous cell carcinoma (OSCC). Methods: MIF expression in OSCC and adjacent tissues was detected by immunohistochemistry. MIF expression in human immortalized oral epithelial cells (HIOEC) and OSCC cells was detected by western blotting. MIF was knocked down or overexpressed in OSCC cell lines (SCC-25 and CAL-27). OSCC cells were set up into control (CON), MIF overexpression/knockdown (oeMIF/shMIF), CON + UVB, and oeMIF + UVB/shMIF + UVB groups based on their exposure to UVB irradiation. Cell line proliferation was studied using a cell counting kit-8 (CCK-8) and colony formation assays. Flow cytometry was applied for determination of apoptosis, cell cycle, reactive oxygen species (ROS) abundance, and mitochondrial membrane potential. Apoptosis-related proteins were assayed by western blotting. Results: The expression of MIF was significantly higher in OSCC tissues and cell lines than in adjacent tissues and HIOEC. MIF knockdown accompanied by UVB irradiation significantly hampered cell viability and proliferation compared to MIF knockdown or UVB irradiation alone. Western blotting and flow cytometry showed that MIF knockdown combined with UVB irradiation not only induced apoptosis via the mitochondrial pathway but also mediated the cell cycle. Flow cytometry showed that ROS and mitochondrial membrane potential depolarization were increased in the combination treatment groups compared with the mono-treatment groups. Additionally, the ROS scavenger N-acetylcysteine significantly attenuated MIF knockdown combined with UVB irradiation-induced apoptosis and reversed MIF knockdown combined with UVB irradiation-induced MAPK activation. Conclusion: MIF knockdown combined with UVB irradiation significantly inhibited the proliferation of OSCC cells. MIF was involved in UVB-induced ROS generation and enhanced UVB irradiation-induced mitochondria-dependent apoptosis of OSCC cells by activating the MAPK pathway. This suggests that MIF-targeted therapy combined with UVB irradiation may be a novel approach for treating OSCC.

Abstract Purpose Asians have a low venous thromboembolism (VTE) incidence following total knee arthroplasty (TKA). This systematic review and network meta-analysis was conducted to evaluate the best prophylaxis against VTE in Asians following total knee arthroplasty in current literature. Materials and Methods A systematic search of PubMed, Embase and CINAHL was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Prophylaxis types were separated into low-molecular-weight heparin (LMWH), novel oral anti-coagulants (NOAC), mechanical-only prophylaxis (MOP) and no prophylaxis (NP). The primary outcome was VTE incidence, grouped according to diagnosis modality (ultrasound, venography, clinical). The secondary outcome was bleeding incidence, grouped into minor and major bleeding. Results Fourteen eligible articles, totalling 4259 patients, were pooled with the following significant results: NOACs had lower venography-diagnosed VTE incidence than LMWH (12.77%, p = 0.02) and NP (20.64, p

Abstract Building photovoltaic (PV) may provide a growing share of electricity for big cities. However, lack of measured radiation data on vertical surface remains a critical problem for building PV deployment. With the development of urbanization and industrialization, high aerosol load is altering the nature of solar radiation in Beijing. Hence, ten in‐plane solar radiation models are reviewed to choose optimal model for calculating solar radiation on vertical surface in such high turbidity area. At the same time, the effect of atmospheric turbidity on the model accuracy is revealed for further understanding on the optimal model. To give general suggestion on model selection, the performance of the ten models for each weather type is tested based on new method of weather type classification. Finally, solar resource on vertical surface and output energy of building PV system are evaluated by the optimal model to guide building PV deployment. The results indicate that Perez model is suitable to calculate solar radiation on vertical surface in high turbidity area. High atmosphere turbidity will cause Perez model inaccurate. Model selection can be made by the status of atmospheric transmittance. It is feasible to apply building PV in Beijing with AC output energy of 630–971 kWh/kWp/year.

Although M2 macrophages are involved in the orchestration of type 2 inflammation in allergic diseases, the mechanisms underlying non-coding RNA (ncRNA)-mediated macrophage polarization in allergic rhinitis (AR) have not been systematically understood. Here, we identified long non-coding RNA (lncRNA) MIR222HG as a key regulator of macrophage polarization and revealed its role in AR. Consistent with our bioinformatic analysis of GSE165934 dataset derived from the Gene Expression Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical samples and animal models of AR, respectively. Mir222hg was upregulated in M1 macrophages and downregulated in M2 macrophages. The allergen-ovalbumin facilitated polarization of RAW264.7 cells to the M2 phenotype, accompanied by the downregulation of mir222hg expression in a dose-dependent manner. Mir222hg facilitates macrophage M1 polarization and reverses M2 polarization caused by ovalbumin. Furthermore, mir222hg attenuates macrophage M2 polarization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway. Collectively, the data highlight the remarkable role of MIR222HG in the modulation of macrophage polarization and allergic inflammation, as well as its potential role as a novel AR biomarker or therapeutic target.

Introduction: Gene expression analysis by reverse transcription quantitative polymerase chain reaction (qRT-PCR) has been widely used in research including insects. The selection of appropriate reference genes is the key to obtaining accurate and reliable results from qRT-PCR. However, studies on the expression stability of reference genes in Megalurothrips usitatus remain lacking.Methods: In this study, qRT-PCR was used to analyze the expression stability of candidate reference genes in M. usitatus. The expression levels of six candidate reference gene transcription of M. usitatus were analyzed. GeNorm, NormFinder, BestKeeper, and ΔCt were used to analyze the expression stability of M. usitatus treated with biological factors (developmental period treatment) and abiotic factors (light, temperature, insecticide treatment, respectively). Comprehensive stability ranking of candidate reference genes was recommended by RefFinder.Results and Discussion: Results showed that ribosomal protein S (RPS) was the most suitable expression in insecticide treatment. Ribosomal protein L (RPL) was the most suitable expression at developmental stage and light treatment, whereas elongation factor was the most suitable expression in temperature treatment. RefFinder was used to comprehensively analyze the above four treatments, and the results showed that RPL and actin (ACT) showed high stability in each treatment. Therefore, this study identified these two genes as reference genes in the qRT-PCR analysis of different treatment conditions of M. usitatus. Ourfindings will be beneficial for improving the accuracy of qRT-PCR analysis for future functional analysis of the target gene expression in M. usitatus.

Objective Lupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus.Methods This is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case–control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed.Results A total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups.Conclusions CLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren’s syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren’s syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Biomimetic nanocomposites are widely used in the biomedical field because they can effectively solve the problems existing in the current cancer treatment by realizing multi-mode collaborative treatment. In this study, we designed and synthesized a multifunctional therapeutic platform (PB/PM/HRP/Apt) with unique working mechanism and good tumor treatment effect. Prussian blue nanoparticles (PBs) with good photothermal conversion efficiency were used as nuclei and coated with platelet membrane (PM). The ability of platelets (PLTs) to specifically target cancer cells and inflammatory sites can effectively enhance PB accumulation at tumor sites. The surface of the synthesized nanocomposites was modified with horseradish peroxidase (HRP) to enhance the deep penetration of the nanocomposites in cancer cells. In addition, PD-L1 aptamer and 4T1 cell aptamer AS1411 were modified on the nanocomposite to achieve immunotherapy and enhance targeting. The particle size, UV absorption spectrum and Zeta potential of the biomimetic nanocomposite were determined by transmission electron microscope (TEM), Ultraviolet-visible (UV-Vis) spectrophotometer and nano-particle size meter, and the successful preparation was proved. In addition, the biomimetic nanocomposites were proved to have good photothermal properties by infrared thermography. The cytotoxicity test showed that it had a good killing ability of cancer cells. Finally, thermal imaging, tumor volume detection, immune factor detection and Haematoxilin-Eosin (HE) staining of mice showed that the biomimetic nanocomposites had good anti-tumor effect and could trigger immune response in vivo. Therefore, this biomimetic nanoplatform as a promising therapeutic strategy provides new inspiration for the current diagnosis and treatment of cancer.

Abstract Background Epidemiological evidence between the sleep disorders and allergy-related outcomes is limited. Objectives The purpose of the present study was to estimate the relationship between sleep disorders and allergy-related outcomes in adults. Methods We built logistic regression models to examine the associations between sleep disorders and allergy-related outcomes in adult participants using the 2005–2006 NHANES database. Allergy-related outcomes included sIgE levels, asthma, hay fever, sneezing, wheezing, and eczema. Sleep disorders included sleep latency, sleep length, sleep problems, OSA symptoms, and daytime sleepiness. A t-test was used for between-group comparisons. Results Participants with OSA symptoms had 2.72 × higher odds of experiencing hay fever and 1.54 × higher odds of having eczema compared to Non-OSA symptoms participants. Participants with insufficient sleep (≤ 6 h/night) had 1.27 × higher odds of developing allergic sensitisation compared to participants with adequate sleep (7–8 h/night). Sneezing was positively associated with sleep problems (OR: 1.706; 95% CI 1.386, 2.099), OSA symptoms (OR: 1.297; 95% CI 1.049, 1.605), and daytime sleepiness (OR: 1.569; 95% CI 1.205, 2.04). Conclusion Our findings suggest a positive association between allergy-related outcomes and sleep disorders. In particular, OSA symptoms, daytime sleepiness, and sleep problems are strongly associated with allergic conditions. Graphical Abstract

The shortage of high-quality coarse feed resources is the main factor that restricts the development of animal husbandry in many developing countries. The present study aimed to investigate the effects of replacing corn silage with daylily silage on the growth performance, slaughter performance, blood biochemical indicators, meat quality, and muscle amino acid composition of Tan sheep. A total of 72 healthy Tan sheep were randomly assigned to four groups. In each group, 0%, 20%, 40%, and 60% of corn silage were replaced with daylily silage (denoted as CON, HC20, HC40, and HC60, respectively). Tan sheep fed with daylily silage showed no significant adverse effects on their growth performance, meat quality, and muscle amino acid composition (p > 0.05). Some increase was observed in the carcass fat content value (GR-value, p < 0.05), thickness of backfat (p < 0.05), and the blood urea level (p < 0.05). These findings indicate that the utilization of daylily silage instead of whole-plant corn silage has no adverse effects on the growth performance and meat quality of Tan sheep, thus indicating that it can partially replace whole-plant corn feed as a feed resource for Tan sheep.

The constant updating of lupus drug treatment guidelines has led to a question. How can the efficacy of treatment be more effectively monitored? Systemic lupus erythematosus (SLE) is a complex autoimmune disease that often presents clinically with multi-organ involvement, and approximately 30% of patients with SLE develop lupus nephritis (LN). Therefore, it is important to better track disease progression and drug efficacy. Now, kidney biopsy is still the gold standard for diagnosing and guiding the treatment of LN, but it is invasive and expensive. If simple, non-invasive and effective biomarkers can be found, drug intervention and prognosis can be better monitored and targeted. In this review, we focus on LN and explore biomarkers related to LN therapeutics, providing clinicians with more possibilities to track the therapeutic effect of drugs, improve treatment options and assess patient outcomes.

Polysaccharides exist as one of the most abundant components in lotus leaves, which attract increasing attention owing to their promising health-promoting benefits. In this study, the digestive and microbial degradation characteristics of lotus leaf polysaccharides (LLP) were studied by using an in vitro gastrointestinal model. The results suggested that LLP was stable in the human upper gastrointestinal tract in vitro according to its digestive stabilities at different simulated digestion stages. Conversely, the indigestible LLP (LLPI) could be remarkably utilized by intestinal microbiota in human feces during in vitro fermentation, and its fermentability was 58.11% after the in vitro fermentation of 48 h. Indeed, the microbial degradation characteristics of LLPI during in vitro fermentation by human fecal inoculum were revealed. The results showed that the content of reducing sugars released from LLPI obviously increased from 0.498 to 2.176 mg/mL at the initial fermentation stage (0–6 h), and its molecular weight sharply decreased from 4.08 × 104 to 2.02 × 104 Da. Notably, the molar ratios of arabinose (Ara), galactose (Gal), and galacturonic acid (GalA) in LLPI decreased from 2.89 to 1.40, from 5.46 to 3.72, and from 21.24 to 18.71, respectively, suggesting that the utilization of arabinose and galactose in LLPI by intestinal microbiota was much faster than that of galacturonic acid at the initial fermentation stage. Additionally, LLPI could remarkably regulate gut microbial composition by increasing the abundances of several beneficial microbes, including Bacteroides, Bifidobacterium, Megamonas, and Collinsella, resulting in the promoted generation of several short-chain fatty acids, especially acetic, propionic, and butyric acids. The findings from the present study are beneficial to better understanding the digestive and microbial degradation characteristics of LLP, which indicate that LLP can be used as a potential prebiotic for the improvement of intestinal health.

Over the past decades, conventional methods and molecular assays have been developed for the detection of tuberculosis (TB). However, these techniques suffer limitations in the identification of Mycobacterium tuberculosis (Mtb), such as long turnaround time and low detection sensitivity, etc., not even mentioning the difficulty in discriminating antibiotics-resistant Mtb strains that cause great challenges in TB treatment and prevention. Thus, techniques with easy implementation for rapid diagnosis of Mtb infection are in high demand for routine TB diagnosis. Due to the label-free, low-cost and non-invasive features, surface enhanced Raman spectroscopy (SERS) has been extensively investigated for its potential in bacterial pathogen identification. However, at current stage, few studies have recruited handheld Raman spectrometer to discriminate sputum samples with or without Mtb, separate pulmonary Mtb strains from extra-pulmonary Mtb strains, or profile Mtb strains with different antibiotic resistance characteristics. In this study, we recruited a set of supervised machine learning algorithms to dissect different SERS spectra generated via a handheld Raman spectrometer with a focus on deep learning algorithms, through which sputum samples with or without Mtb strains were successfully differentiated (5-fold cross-validation accuracy = 94.32%). Meanwhile, Mtb strains isolated from pulmonary and extra-pulmonary samples were effectively separated (5-fold cross-validation accuracy = 99.86%). Moreover, Mtb strains with different drug-resistant profiles were also competently distinguished (5-fold cross-validation accuracy = 99.59%). Taken together, we concluded that, with the assistance of deep learning algorithms, handheld Raman spectrometer has a high application potential for rapid point-of-care diagnosis of Mtb infections in future.

ABSTRACT With increasing demand for high-quality pork, development of green and healthy feed for finishing pigs is urgently needed. In this study, the effects and mechanisms of mulberry and paper mulberry silages on growth performance, meat quality, and intestinal health of finishing pigs were explored. Intestinal microbiota were profiled, and microbially produced short-chain fatty acids (SCFAs) were measured. The average daily gain (ADG) and feed conversion rate (FCR) with mulberry and paper mulberry silages were not significantly different from those of the control. Meat quality as measured by pork marbling and fatty acids in the longissimus dorsi was better with mulberry silage. The highest concentration of SCFAs was also with mulberry silage. According to 16S rRNA sequencing, Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae, which are important in SCFA production, were biomarkers of mulberry silage. PICRUSt functional analysis of intestinal microbes indicated that galactose metabolism, starch and sucrose metabolism, and carbohydrate digestion and absorption decreased significantly in silage treatments but increased in the control. Correlations between intestinal microbes and SCFAs and fatty acids indicated Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA and fatty acid contents. The results indicated that mulberry silage could increase SCFA content through shaping intestinal microbes to affect the deposition of fatty acids, which laid a solid theoretical foundation for improving pork quality. IMPORTANCE To avoid competition between people and animals for food, it is essential to develop nontraditional feeds. In this study, the effects of the silages of the unconventional feed resources mulberry and paper mulberry on meat quality of finishing pigs were examined. With mulberry silage in the diet, meat quality improved as indicated by meat color, marbling score, and beneficial fatty acids in the longissimus dorsi muscle. Pigs fed mulberry silage had the highest concentrations of short-chain fatty acids (SCFAs), and 16S rRNA sequencing identified Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae as biomarkers, which are important in SCFA production. Functions of intestinal microbes in the two silage groups primarily involved amino acid metabolism and SCFA production. Correlations between intestinal microbes and SCFAs and fatty acids indicated that Clostridium_sensu_stricto-1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA contents in the intestine and fatty acids in the longissimus dorsi.

Primary bladder mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare bladder tumor. Only scarce reports have been reported. We hereby report a case of an 81-year-old female patient with bladder tumor presenting with frequent urination and dysuria, whose pelvic magnetic resonance imaging (MRI) considered bladder cancer. She underwent transurethral resection of the bladder tumor (TURBT), and histopathology confirmed the mass to be bladder MALT lymphoma. The patient refused further treatment, and no disease recurrence one year after surgery. The current data are insufficient to draw conclusions about the long-term efficacy of treatment for this tumor, regular follow-up is necessary. To further understand the clinical features, pathology, treatment and prognosis of this tumor, we have searched the literature from 1990 to the present, analyzing a total of 64 cases of primary MALT lymphoma.

The present study deals with the synthesis of zeolite-loaded FeOOH@ZnO by hydrothermal method and investigates the effects of coexisting SO32− and PO43− ions in the aqueous solution on the adsorption performance for S2−. The results showed that the HNO3-modified zeolite loaded with FeOOH@ZnO (FeOOH@ZnO/HZ) resulted in a maximum S2− removal rate of ≈98%. The adsorbent's performance on removing S2− was significantly enhanced, compared with NaOH and ZnCl2-modified zeolites loaded with FeOOH@ZnO, and the adsorption was proved to be a heat-absorbing process. When SO32− and PO43− coexisted with S2−, SO32− and PO43− had a significant influence on the adsorption properties of FeOOH@ZnO/HZ. When three ions of S2−, SO32− and PO43− were present simultaneously, the adsorption performance of FeOOH@ZnO/HZ on S2− was further, and the removal rate dropped to about 80%. Moreover, FeOOH@ZnO/HZ also adsorbed PO43− and SO32− in the system containing multiple ions, but the adsorption rates of PO43− and SO32− were much lower than S2−. This indicated that the adsorption of S2− in the presence of FeOOH@ZnO/HZ dominates under competitive conditions. HIGHLIGHTS Modified zeolite-loaded FeOOH@ZnO is prepared.; The effect of PO43− and SO32− in water on the performance of FeOOH@ZnO/HZ in the adsorption of S2− is studied.; FeOOH@ZnO/HZ has a good adsorption effect on S2− and the adsorption process is a heat-absorbing process.; PO43− and SO32− affect the adsorption of S2− by FeOOH@ZnO/HZ, but S2− still dominates the adsorption competition.;

Abstract Aims The management of heart failure (HF) in young children is challenging. The present study aimed to clarify the effect of left univentricular epicardial pacing on dilated cardiomyopathy with left bundle branch block (LBBB) in children. Methods and results A total of five cases (30.86 ± 16.39 months, three female) of children weighing 5.8–15 kg with dilated cardiomyopathy and LBBB were included in this study. LBBB in one child occurred after device closure of peri‐membranous ventricular septal defects, and the remaining four were idiopathically discovered early after birth. Before implantation, all children suffered from refractory HF and cardiac dilatation; the left ventricular ejection fraction was 33.48 ± 5.84% with Ross Heart Failure Classification III–IV. Electrical and mechanical dyssynchrony were observed in all children with QRS duration >140 ms and prolonged septal‐to‐left posterior wall motion delay. Left univentricular epicardial pacing was successfully implanted via left axillary minithoracotomy in the five children. Sensed atrioventricular delays (83 ± 15 ms) were optimized by velocity time integral of aortic blood flow before discharge. During the follow‐up period (10.8 ± 2.68 months), the dilated failing heart was reversed significantly in terms of decreased left ventricular dimension (55.62 ± 3.46 vs. 38.94 ± 3.69 mm, P = 0.005), while the left ventricular ejection fraction improved to 60.18 ± 8.78% (P = 0.006). Conclusions In young children with low body weight, if HF is caused by or related to LBBB, left ventricular epicardial pacing still has an excellent effect.

Defects in laterality pattern can result in abnormal positioning of the internal organs during the early stages of embryogenesis, as manifested in heterotaxy syndrome and situs inversus, while laterality defects account for 3~7% of all congenital heart defects (CHDs). However, the pathogenic mechanism underlying most laterality defects remains unknown. In this study, we recruited 70 laterality defect patients with CHDs to identify candidate disease genes by exome sequencing. We then evaluated rare, loss-of-function (LOF) variants, identifying candidates by referring to previous literature. We chose TRIP11, DNHD1, CFAP74, and EGR4 as candidates from 776 LOF variants that met the initial screening criteria. After the variants-to-gene mapping, we performed function research on these candidate genes. The expression patterns and functions of these four candidate genes were studied by whole-mount in situ hybridization, gene knockdown, and gene rescue methods in zebrafish models. Among the four genes, trip11, dnhd1, and cfap74 morphant zebrafish displayed abnormalities in both cardiac looping and expression patterns of early signaling molecules, suggesting that these genes play important roles in the establishment of laterality patterns. Furthermore, we performed immunostaining and high-speed cilia video microscopy to investigate Kupffer's vesicle organogenesis and ciliogenesis of morphant zebrafish. Impairments of Kupffer's vesicle organogenesis or ciliogenesis were found in trip11, dnhd1, and cfap74 morphant zebrafish, which revealed the possible pathogenic mechanism of their LOF variants in laterality defects. These results highlight the importance of rare, LOF variants in identifying disease-related genes and identifying new roles for TRIP11, DNHD1, and CFAP74 in left-right patterning. Additionally, these findings are consistent with the complex genetics of laterality defects.

ABSTRACT The rapid and accurate identification of the causing agents during bacterial infections would greatly improve pathogen transmission, prevention, patient care, and medical treatments in clinical settings. Although many conventional and molecular methods have been proven to be efficient and reliable, some of them suffer technical biases and limitations that require the development and application of novel and advanced techniques. Recently, due to its cost affordability, noninvasiveness, and label-free feature, Raman spectroscopy (RS) is emerging as a potential technique for fast bacterial detection. However, the method is still hampered by many technical issues, such as low signal intensity, poor reproducibility, and standard data set insufficiency, among others. Thus, it should be cautiously claimed that Raman spectroscopy could provide practical applications in real-world settings. In order to evaluate the implementation potentials of Raman spectroscopy in the identification of bacterial pathogens, we investigated 30 bacterial species belonging to 9 different bacterial genera that were isolated from clinical samples via surfaced enhanced Raman spectroscopy (SERS). A total of 17,149 SERS spectra were harvested from a Raman spectrometer and were further analyzed via machine learning approaches, which showed that a convolutional neural network (CNN) deep learning algorithm achieved the highest prediction accuracy for recognizing pathogenic bacteria at both the genus and species levels. In summary, the SERS technique holds a promising potential for fast bacterial pathogen identification in clinical laboratories with the integration of machine learning algorithms, which might be further developed and sharpened for the direct identification and prediction of bacterial pathogens from clinical samples. IMPORTANCE In this study, we investigated 30 bacterial species belonging to 9 different bacterial genera that were isolated from clinical samples via surfaced enhanced Raman spectroscopy (SERS). A total of 17,149 SERS spectra were harvested from a Raman spectrometer and were further analyzed via machine learning approaches, the results of which showed that the convolutional neural network (CNN) deep learning algorithm could achieve the highest prediction accuracy for recognizing pathogenic bacteria at both the genus and species levels. Taken together, we concluded that the SERS technique held a promising potential for fast bacterial pathogen diagnosis in clinical laboratories with the integration of deep learning algorithms, which might be further developed and sharpened for the direct identification and prediction of bacterial pathogens from clinical samples.

IntroductionDiet strongly affects gut microbiota composition, and gut bacteria can influence the intestinal barrier functions and systemic inflammation through metabolic endotoxemia. In-house feeding system (IHF, a low dietary fiber source) may cause altered cecal microbiota composition and inflammatory responses in meat geese via increased endotoxemia (lipopolysaccharides) with reduced intestinal alkaline phosphatase (ALP) production. The effects of artificial pasture grazing system (AGF, a high dietary fiber source) on modulating gut microbiota architecture and gut barrier functions have not been investigated in meat geese. Therefore, this study aimed to investigate whether intestinal ALP could play a critical role in attenuating reactive oxygen species (ROS) generation and ROS facilitating NF-κB pathway-induced systemic inflammation in meat geese.MethodsThe impacts of IHF and AGF systems on gut microbial composition via 16 sRNA sequencing were assessed in meat geese. The host markers analysis through protein expression of serum and cecal tissues, hematoxylin and eosin (H&E) staining, localization of NF-қB and Nrf2 by immunofluorescence analysis, western blotting analysis of ALP, and quantitative PCR of cecal tissues was evaluated.Results and DiscussionIn the gut microbiota analysis, meat geese supplemented with pasture showed a significant increase in commensal microbial richness and diversity compared to IHF meat geese demonstrating the antimicrobial, antioxidant, and anti-inflammatory ability of the AGF system. A significant increase in intestinal ALP-induced Nrf2 signaling pathway was confirmed representing LPS dephosphorylation mediated TLR4/MyD88 induced ROS reduction mechanisms in AGF meat geese. Further, the correlation analysis of top 44 host markers with gut microbiota showed that artificial pasture intake protected gut barrier functions via reducing ROS-mediated NF-κB pathway-induced gut permeability, systemic inflammation, and aging phenotypes. In conclusion, the intestinal ALP functions to regulate gut microbial homeostasis and barrier function appear to inhibit pro-inflammatory cytokines by reducing LPS-induced ROS production in AGF meat geese. The AGF system may represent a novel therapy to counteract the chronic inflammatory state leading to low dietary fiber-related diseases in animals.

Objective: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. Methods: This systematic review and meta‐analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. Results: Six randomized controlled trials comprising 516 participants were included.The meta‐analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (−0.66 mmol/L; 95 % CI (confidence intervals) [− 1.28, − 0.04]), plasma glucose 2 h after meal (2-h PG) (−1.18 mmol/L; 95 % CI [−1.94, −0.42]) in six RCTs, body mass index (BMI) (−3.07 mmol/L; 95 % CI [−6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (−0.36 mmol/L; 95 % CI [−1.04, 0.31]) in three RCTs, and triglycerides (TG) (−0.76 mmol/L; 95 % CI [−1.37, −0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (−0.97 mmol/L; 95 % CI [−1.18, −0.76]). Conclusions: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.

Abstract Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19+ B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6–Blimp-1 axis, providing a novel target for SLE treatment.

Mammalian Ste20-like kinase 2 (MST2) is a core component of the Hippo pathway and plays an important role in regulating cell apoptosis, cell proliferation and cell cycle progression, but it has rarely been studied in invertebrates, especially crustaceans. In this study, the MST2 gene in penaeus japonicus shrimp was characterized. A 2111 bp long nucleotide sequence encoding 690 amino acids was obtained. The molecular weight of MST2 protein is 78.47222 kDa. The bioinformatics analysis indicated that the MST2 protein has an S_TK-c (Ser/Thr kinase) domain and a SARAH (Salvador/Ras-association domain family/Hippo) domain, which is consistent with other species. The analysis of subcellular localization showed that MST2 was mainly present in the cytoplasm. Real time PCR and apoptosis analysis indicated that MST2 was involved in the white spot syndrome virus (WSSV) infection process and inhibited viral infection by promoting apoptosis. This study revealed the potential function of MST2 in virus invasion and cell apoptosis, providing a new target for preventing shrimp virus infection.