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Abstract Background The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. Objectives To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. Methods A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. Results Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34–68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). Conclusions A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.

Abstract Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed a high-fat diet (HFD) supplemented with L-NAME for 12 weeks and subsequently intraperitoneally injected with EMPA for another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes in the failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. HFpEF group) and 173 DEPs (HFpEF vs. EMPA group). The regulation of immune system processes was enriched in all groups and the interferon response genes (STAT1, Ifit1, Ifi35 and Ifi47) were upregulated in HFpEF mice but downregulated after EMPA administration. In addition, EMPA treatment suppressed the increase in the levels of aging markers (p16 and p21) in HFpEF hearts. Further bioinformatics analysis verified STAT1 as the hub transcription factor during pathological changes in HFpEF mice. We next treated H9C2 cells with IFN-γ, a primary agonist of STAT1 phosphorylation, to investigate whether EMPA plays a beneficial role by blocking STAT1 activation. Our results showed that IFN-γ treatment caused cardiomyocyte senescence and STAT1 activation, which were inhibited by EMPA administration. Notably, STAT1 inhibition significantly reduced cellular senescence possibly by regulating STING expression. Our findings revealed that EMPA mitigates cardiac inflammation and aging in HFpEF mice by inhibiting STAT1 activation. The STAT1–STING axis may act as a pivotal mechanism in the pathogenesis of HFpEF, especially under inflammatory and aging conditions. Graphical abstract The schematic figure depicts a mechanism model of the STAT1–STING axis in HFpEF (this figure was drawn using FigDraw software).

Fungi have been identified as a prolific source of structurally unique secondary metabolites, many of which display promising biological and pharmacological properties. This review provides an overview of the structures of new natural products derived from fungi and their biological activities along with the research strategies, which focuses on literature published in the representative journals in 2023. In this review, a total of 553 natural products including 219 polyketides, 145 terpenoids, 35 steroids, 106 alkaloids, and 48 peptides are presented. By summarising the latest findings, this review aims to provide a guide and inspire further innovation in the fields of the discovery of fungal natural products and pharmaceutical development.

In this study, the effects of different drying methods on the polyphenol content and antioxidant activity of noni fruit were compared. The total phenol content and the content of seven phenolic compounds in noni samples after natural sun-drying, vacuum freeze-drying, and hot-air drying were determined using the forint-phenol colorimetric method and high-performance liquid chromatography (HPLC). The antioxidant capacity of each sample was assessed using the free radical scavenging ability and iron ion reducing ability experiment. The results showed that the total phenolic content of noni fruit after natural sun-drying, vacuum freeze-drying and hot air-drying were 7.78, 12.42 and 6.38 mg/g, respectively. The scavenging ability against DPPH radicals were 17.57, 35.98 and 13.63 μmol Trolox/g, and the scavenging ability against ABTS+· were 17.57, 36.09, 13.63 μmol Trolox/g. The FRAP antioxidant values were 43.12, 73.49, 39.12 μmol Trolox/g, respectively. There was no significant difference (P>0.05) in total polyphenol content and antioxidant properties between the noni fruits after naturally sun-drying and hot air-drying. However, these properties were significantly different (P

Abstract Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes’ biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted. Graphical Abstract

Abstract Gastrointestinal stromal tumors (GISTs) are a rare type of tumor that can develop liver metastasis (LIM), significantly impacting the patient's prognosis. This study aimed to predict LIM in GIST patients by constructing machine learning (ML) algorithms to assist clinicians in the decision-making process for treatment. Retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database, and cases from 2010 to 2015 were assigned to the developing sets, while cases from 2016 to 2017 were assigned to the testing set. Missing values were addressed using the multiple imputation technique. Four algorithms were utilized to construct the models, comprising traditional logistic regression (LR) and automated machine learning (AutoML) analysis such as gradient boost machine (GBM), deep neural net (DL), and generalized linear model (GLM). We evaluated the models' performance using LR-based metrics, including the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), as well as AutoML-based metrics, such as feature importance, SHapley Additive exPlanation (SHAP) Plots, and Local Interpretable Model Agnostic Explanation (LIME). A total of 6207 patients were included in this study, with 2683, 1780, and 1744 patients allocated to the training, validation, and test sets, respectively. Among the different models evaluated, the GBM model demonstrated the highest performance in the training, validation, and test cohorts, with respective AUC values of 0.805, 0.780, and 0.795. Furthermore, the GBM model outperformed other AutoML models in terms of accuracy, achieving 0.747, 0.700, and 0.706 in the training, validation, and test cohorts, respectively. Additionally, the study revealed that tumor size and tumor location were the most significant predictors influencing the AutoML model's ability to accurately predict LIM. The AutoML model utilizing the GBM algorithm for GIST patients can effectively predict the risk of LIM and provide clinicians with a reference for developing individualized treatment plans.

Immune checkpoint inhibitors (ICIs) are used to relieve and refuel anti-tumor immunity by blocking the interaction, transcription, and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints. Thousands of small molecule drugs or biological materials, especially antibody-based ICIs, are actively being studied and antibodies are currently widely used. Limitations, such as anti-tumor efficacy, poor membrane permeability, and unneglected tolerance issues of antibody-based ICIs, remain evident but are thought to be overcome by small molecule drugs. Recent structural studies have broadened the scope of candidate immune checkpoint molecules, as well as innovative chemical inhibitors. By way of comparison, small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features. Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions, including immune regulation, anti-angiogenesis, and cell cycle regulation. In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins, which will lay the foundation for further exploration.

Abstract Background Widespread exposure to phthalates may raise the probability of various diseases. However, the association of phthalate metabolites with periodontitis remains unclear. Methods Totally 3402 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 cycles were enrolled in the cross-sectional investigation. We utilized weighted logistic regression to evaluate the association of ten phthalate metabolites with periodontitis. Restricted cubic spline analysis was applied to investigate potential nonlinear relationships. Results The weighted prevalence of periodontitis in the study was 42.37%. A one standard deviation (SD) rise in log-transformed levels of mono-2-ethyl-5-carboxypenty phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-isobutyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP) was associated with higher odds of periodontitis, with odds ratios (95% confidence intervals) of 1.08 (1.02-1.14), 1.07 (1.02-1.11), 1.10 (1.05-1.15), 1.05 (1.01-1.09), 1.09 (1.04-1.14), and 1.08 (1.03-1.13), respectively. Individuals with the highest quartile concentrations of MECPP, MnBP, MEHHP, MEOHP, and MBzP were associated with 32%, 20%, 30%, 25%, and 26% increased odds of periodontitis, respectively, compared to those with the lowest quartile. Additionally, mono-(3-carboxypropyl) phthalate (MCPP) demonstrated an interesting inverted J-shaped relationship with periodontitis. Conclusions The findings indicate an association of certain phthalate metabolites with periodontitis among US adults.

Abstract The increasing penetration of renewable energy and the further coupling of the electricity and carbon markets have hindered the realization of efficient and low‐carbon transformation processes in new power systems. This study addresses the optimization problems of joint peer‐to‐peer (P2P) electricity and carbon trading in multi‐energy microgrids (MEMGs), taking into account the risks associated with renewable generation in a distributed manner. First, a coordinated operation model is developed to describe the joint P2P electricity and carbon trading issues among MEMGs, aiming to minimize operating costs, mitigate potential risk losses, and reduce renewable energy wastage. Second, the conditional value‐at‐risk technique, paired with stochastic programming, is employed to quantify potential risk losses arising from uncertainties. Finally, a distributed optimization approach is developed based on the alternating direction method of multipliers to maintain the privacy and independence of decision‐making in individual MEMGs. During the trading processes, the Lagrangian multipliers are used as price signals to ensure fairness in optimal trading schemes among MEMGs. Moreover, a parallel solution mechanism is implemented to improve overall operational efficiency with minimal calculation expenditure. The simulation results demonstrate that the proposed method can reduce operation costs and carbon emissions while also preventing a significant amount of renewable energy abandonment.

Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient’s lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.

Lithium in coal, as a new type of associated mineral resource, has considerable potential for exploration. Exploration of high-lithium coal seams is essential for developing and using the associated lithium resources. To explore the distribution of lithium resources in the early stages of development in coal seams, the relationship between coal seam logging data and lithium content was analyzed by taking Guojiadi Coal Mine (China) as example. By analyzing the correlation between the different logging curves and the lithium content in coal and combining the K-means algorithm to identify the logging characteristics of different lithium-containing coal seams, we finally obtained the logging identification characteristics of high-lithium coal seams. The results reveal differences in the logging curves of coal seams with different lithium contents. The natural gamma and lateral resistivity of high-lithium coal seams are approximately 80 API and 100 Ω.M, respectively. Our study shows that the early identification of high-lithium coal seams can be evaluated from a logging perspective. We propose a preliminary identification method of high-lithium coal seam based on logging curve parameters by clustering analysis of borehole logging data to achieve accurate prediction.

IntroductionMycoplasma pneumoniae (MP) is the major cause of respiratory infections that threaten the health of children and adolescents worldwide. Therefore, an early, simple, and accurate detection approach for MP is critical to prevent outbreaks of MP-induced community-acquired pneumonia.MethodsHere, we explored a simple and accurate method for MP identification that combines loop-mediated isothermal amplification (LAMP) with the CRISPR/Cas12b assay in a one-pot reaction.ResultsIn the current study, the whole reaction was completed within 1 h at a constant temperature of 57°C. The limit of detection of this assay was 33.7 copies per reaction. The specificity of the LAMP-CRISPR/Cas12b method was 100%, without any cross-reactivity with other pathogens. Overall, 272 clinical samples were used to evaluate the clinical performance of LAMP-CRISPR/Cas12b. Compared with the gold standard results from real-time PCR, the present method provided a sensitivity of 88.11% (126/143), specificity of 100% (129/129), and consistency of 93.75% (255/272).DiscussionTaken together, our preliminary results illustrate that the LAMP-CRISPR/Cas12b method is a simple and reliable tool for MP diagnosis that can be performed in resource-limited regions.

Existing feeder block division methods fail to consider the complementary characteristics and uncertainty between power sources and loads, which result in excessive feeder blocks, low inter-block balance, and significant disparity in net load peak-valley difference. To address these issues, a medium-voltage feeder block division method that considers the uncertainty and complementary characteristics of sources and loads is proposed. Firstly, based on the probability density characteristics of sources and loads, an uncertainty model of DG output and load demand is established. Secondly, considering the constraints of block maximum load rate and feeder non-crossing, a feeder block division model is established. Additionally, a set of center circles is defined, and based on this, an improved K-means clustering algorithm is proposed. The initial clustering centers based on the center circles is set, and the clustering centers based on the arcs of the center circles corrected. And the weighted distances between power sources and clustering centers are calculated. An algorithm flow for improved K-means clustering feeder block division is designed accordingly. Finally, the case studies show that the result of block division is improved.

Tumors present a formidable health risk with limited curability and high mortality; existing treatments face challenges in addressing the unique tumor microenvironment (hypoxia, low pH, and high permeability), necessitating the development of new therapeutic approaches. Under certain circumstances, certain bacteria, especially anaerobes or parthenogenetic anaerobes, accumulate and proliferate in the tumor environment. This phenomenon activates a series of responses in the body that ultimately produce anti-tumor effects. These bacteria can target and colonize the tumor microenvironment, promoting responses aimed at targeting and fighting tumor cells. Understanding and exploiting such interactions holds promise for innovative therapeutic strategies, potentially augmenting existing treatments and contributing to the development of more effective and targeted approaches to fighting tumors. This paper reviews the tumor-promoting mechanisms and anti-tumor effects of the digestive tract microbiome and describes bacterial therapeutic strategies for tumors, including natural and engineered anti-tumor strategies.

Background Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD.Objectives To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients.Design A retrospective cohort study.Setting This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan.Participants A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded.Outcome measures We identified PHD according to the patient’s discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs.Results In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively.Conclusion Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.

Obesity is affecting global health with multiple complications, including cardiac dysfunction. Currently, it is uncertain whether drug therapy should be applied in the early stages of obesity-induced cardiac dysfunction, with weight reduction as the first choice. Sleeve gastrectomy (SG) has been widely used to treat obesity and its complications, showing promising results. However, it remains unclear whether SG can alleviate obesity-induced cardiac dysfunction. A sudden decline in body weight and food intake was observed in both the obese and obese + SG groups, with a higher rate of increase observed in the Obese group. Elevated levels of plasma glucose, serum insulin, and glycated haemoglobin in obese rats were significantly reduced by SG. Markedly increased levels of alanine transaminase, aspartate transaminase, alkaline phosphatase albumin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, elevated values of heart rate, left ventricular end-systolic pressure, left ventricular end-diastolic pressure, systolic pressure, and end diastolic pressure, and decreased value of stroke volume were observed in obese rats, which were sharply reversed by SG. Furthermore, enhanced pathological changes, including inflammatory cell infiltration and loss of cytoplasm striations, enhanced oil red O staining, increased TUNEL-positive cells, upregulated Bax and cleaved-caspase-3, and downregulated Bcl-2, were observed in obese rats, which were notably alleviated by SG. Lastly, the increased levels of relative proteins observed in obese rats were significantly reduced by SG. In conclusion, SG improved cardiac function and glucose-lipid metabolism disorders in obese rats induced by a high-fat and high-sugar diet.

Abstract Background The link between low grip strength, diminished physical performance, and adverse health outcomes in older adults has been well-established. However, the impact of older adults who cannot complete these tests on disability and mortality rates remains unexplored without longitudinal study. Methods We collected data from the China Health and Retirement Longitudinal Study (CHARLS). Participants aged 60–101 were enrolled at baseline. We analyzed the prevalence of populations unable to complete handgrip strength (HGS), gait speed (GS), and five times chair stand test (FTCST). Completing risk models were used to estimate the risk of mortality and disability over seven years. Results A total of 3,768 participants were included in the analysis. The percentage of older adults unable to complete the GS and FTCST tests increased notably with age, from 2.68 to 8.90% and 2.60–20.42%, respectively. The proportion of older people unable to perform the HGS was relatively stable, ranging from 1.40 to 3.66%. Compared to older adults who can complete these tests, those who cannot perform FTCST face a significantly higher risk of mortality, with 49.1% higher risk [hazard ratio (HR) = 1.491, 95% CI = 1.156, 1.922; subdistribution hazard ratio (SHR) = 1.491, 95%CI = 1.135,1.958)]. Participants who were unable to complete the GS test had a higher risk of developing ADL disability, regardless of whether they were compared to the lowest-performing group (HR = 1.411, 95%CI = 1.037,1.920; SHR = 1.356, 95%CI = 1.030,1.785) or those who can complete the GS (HR = 1.727, 95%CI = 1.302,2.292; SHR = 1.541, 95%CI = 1.196,1.986). No statistically significant difference in the risk of developing ADL disability among older adults who were unable to complete the HGS test compared with either the poorest performing group (HR = 0.982, 95% CI = 0.578, 1.666; SHR = 1.025, 95% CI = 0.639, 1.642) or those who were able to complete the HGS test (HR = 1.008, 95% CI = 0.601, 1.688; SHR = 0.981, 95% CI = 0.619, 1.553). The risk of all-cause mortality was not significantly different for older adults who were unable to complete the HGS test compared to those with the worst performance (HR = 1.196, 95%CI = 0.709–2.020; SHR = 1.196, 95%CI = 0.674, 2.124) or those who were able to complete the test (HR = 1.462, 95%CI = 0.872–2.450; SHR = 1.462, 95%CI = 0.821,2.605). Conclusion The risks of adverse events faced by older adults unable to complete the tests vary, indicating the necessity for future research to conduct separate analyses on this high-risk population.

Abstract Background For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. Methods 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People’s Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. Results NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA

Protein post-translational modifications (PTMs) are at the heart status of cellular signaling events and broadly involved in tumor progression. CD147 is a tumor biomarker with various PTMs, promoting tumor metastasis and metabolism reprogramming. Nevertheless, the relationship between the PTMs of CD147 and apoptosis has not been reported. In our study, we produced a specific anti-CD147-K71 di-methylation (CD147-K71me2) antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer (NSCLC) tissues were lower than that in NSCLC adjacent tissues. SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2. RNA-seq showed that FOSB was the most significant differentially expressed gene (DEG) between wild-type CD147 (CD147-WT) and K71-mutant CD147 (CD147-K71R) groups. Subsequently, we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38, leading to tumor cell apoptosis. In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis. Taken together, our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification, which is distinct from the pro-cancer function of CD147 itself, broadening our perspective on tumor-associated antigen CD147.

Zeolite P1, a significant conversion product of fly ash, is predominantly utilized for the removal of metal ions, adsorption of carbon dioxide, and capture of aromatic compounds. Despite its diverse applications, its role as a catalyst remains underexplored in the scientific community. Traditionally, mordenite (MOR) zeolites are considered typical dimethyl ether (DME) carbonylation catalysts, whose Brønsted acid sites located on the 8-membered rings (8-MR) are the key active sites for this reaction. This conventional approach underscores the importance of specific zeolite structures in facilitating catalytic processes. H–P1 zeolite was synthesized through a template-free approach in this paper. When applied to DME carbonylation, this zeolite exhibited an impressive selectivity of up to 93% for methyl acetate (MA), suggesting its potential as a highly effective catalyst. This promising outcome hints at a new frontier for the application of the P1 zeolite, potentially revolutionizing its role in catalysis and expanding its utility beyond traditional adsorption processes. The findings suggest that the P1 zeolite could be a versatile material in the realm of catalytic chemistry, offering new pathways and methodologies for various chemical reactions.

Abstract Background Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. Methods This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. Results A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: −14.0 to − 10.5; P

Abstract Background About 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to predict miscarriage in threatened miscarriage, yet its performance is still debated. Aim To evaluate the performance of single serum progesterone predicting miscarriage in early pregnant patients with threatened miscarriage. Method The online database was searched to yield the literature using the terms of ‘Abortion’, ‘Miscarriage’, and ‘serum Progesterone’, including PubMed, Scopus, Embase, Cochrane library, and China national knowledge infrastructure. Receiver operating characteristic (ROC) curve, likelihood ratio (LLR) and diagnostic odds ratio (DOR) and 95% confidence interval (CI) were computed. Publication bias was assessed by the deeks funnel plot asymmetry test. Subgroup analyses were conducted according to the progesterone level (

Accurate face recognition technology is of great significance for face anti-counterfeiting. Due to illumination, posture, angle, and other reasons, the existing face liveness detection technology is difficult to adapt the environmental changes, resulting in low detection accuracy. To address this issue, this paper presents a novel high-performance face anti-spoofing detection method named RGCS_ConvNeXt. The data-enhanced face images are fed into the ConvNext network, which group convolution is added to extract the correlation between different features, and the coordinate attention mechanism is used to enhance the facial feature extraction capability both spatially and directionally. Then SPPF is used to extract the features at different scales to enhance the representation of the feature map. Finally, the facial key point detection technique is utilized to calculate the eye EAR value to achieve accurate face anti-counterfeiting recognition. The proposed algorithm shows an average classification error rate of 0.3%, 1.7%, 1.9%±1.5% and 2.8%±3.4%, respectively, on the four protocols of the OULU-NPU public dataset. On the Siw dataset, the average classification error rate is 0.69%, a reduction of 0.02% compared to the MA-Net network. The half-error rate on the MSU-MFSD dataset is 2.39%, a 0.21% reduction compared to the DPCNN network. The algorithm shows good accuracy on the OULU-NPU, MSU-MFSD and Siw datasets, reaching 99.64%, 98.40% and 99.25% respectively, 0.26% higher than the SE-FeatherNet network’s average accuracy.

The feature selection for interval-valued data (IVD) aims to identify representative features from a large set of features, which can reduce the model complexity, minimize the training time, and enhance the generalization ability of the model. Addressing the inter-feature correlations in IVD, we propose a feature selection method called the maximum information coefficient for interval-valued data (IVD_MIC). First, the method balances the relationship between the midpoint and radius of IVD with an adjustment factor, constructing the interval-valued data unified representation frame (URF). Based on the URF, the method measures the degree of correlation between two features by calculating the maximum information coefficient, and obtains the maximum information coefficient matrix for IVD. Then the features with strong correlation are progressively removed from three perspectives(row, column, and both row and column), generating a series of corresponding candidate feature subsets. Finally, IVD_MIC is validated on candidate feature subsets to obtain the final classification accuracy and optimal feature subset. The experiment results on synthetic and real-world datasets with different classifiers demonstrate that the overall performance of IVD_MIC surpasses other methods. The average accuracy of IVD_MIC is higher, improving by 0.23%, 0.53% and 0.45% compared to the second-best method on LIBSVM, CART Tree and KNN, respectively.

Abstract The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.

Expressions serve as intuitive reflections of a person’s psychological state, making the extraction of effective features for accurate facial expression recognition a crucial research problem. However, when facial information is incomplete, the existing convolutional neural networks face some challenges in extracting features. To address this issue, this paper introduces a pyramidal convolutional attention residual network(PCARNet) based on the ResNet18. PCARNet combines the pyramidal convolution module and an improved convolutional attention mechanism to effectively extract expression features and achieve high-precision facial expression recognition. The proposed model utilizes pyramidal convolution to extract facial expression features at multiple scales, capturing both global and local information of the face. Grouped convolution is employed to reduce the computational complexity and the number of parameters. Additionally, to avoid the adverse effects of channel dimensionality reduction on the attention mechanism and enhance the capacity for information exchange across channels, the Share MLP module within the convolutional attention mechanism was replaced by a one-dimensional convolution with adaptive kernel size. The improved convolutional attention mechanism assigns weights to the extracted multiscale features based on both channel and spatial dimensions, enhancing the representation of crucial facial features. Experimental results demonstrate the high recognition accuracy of the proposed method on public datasets such as Fer2013, RAF-DB, and CK+. The accuracies achieved are 73.725%, 87.516%, and 95.455%, respectively. Compared to other methods, the proposed approach shows improvements of at least 1.4%, 2.4%, and 0.25% on the respective datasets, confirming its high reliability and performance.

Background Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known.Methods The Cochrane Library, PubMed and Web of Science databases were searched from the date of inception of the database to June 2022 for literature exploring the impact of haemostasis methods during ovarian cystectomy on ovarian reserve. A traditional meta-analysis was performed using Review Manager software. A network meta-analysis (NMA) was performed using Stata and GemTC software.Results The direct meta-analysis comparison indicated that the mean postoperative reduction of anti-Müllerian hormone (AMH) level was significantly higher in the electrocoagulation (bipolar) group than suture and haemostatic sealant group, both in the overall group and subgroup of women with ovarian endometrioma. In NMA, the reduction of postoperative AMH levels in the electrocoagulation (bipolar) group was higher than the suture group at 6 months with a statistical significance, and at 1, 3 and 12 months without a significant difference. The difference in the postoperative decrease of AMH level did not reach statistical significance between suture and sealant, coagulation and haemostatic sealant. The comprehensive ranking results revealed that suture treatment was, with the highest probability, beneficial to the protection of the ovarian reserve.Conclusions There was insufficient research to detect the optimal haemostasis method for ovarian reserve preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.

Potatoes (Solanum tuberosum L.) are the third largest food crop globally and are pivotal for global food security. Widespread N fertilizer waste in potato cultivation has caused diverse environmental issues. This study employed microbial metagenomic sequencing to analyze the causes behind the declining N use efficiency (NUE) and escalating greenhouse gas emissions resulting from excessive N fertilizer application. Addressing N fertilizer inefficiency through breeding has emerged as a viable solution for mitigating overuse in potato cultivation. In this study, transcriptome and metabolome analyses were applied to identify N fertilizer-responsive genes. Metagenomic sequencing revealed that excessive N fertilizer application triggered alterations in the population dynamics of 11 major bacterial phyla, consequently affecting soil microbial functions, particularly N metabolism pathways and bacterial secretion systems. Notably, the enzyme levels associated with NO3- increased, and those associated with NO and N2O increased. Furthermore, excessive N fertilizer application enhanced soil virulence factors and increased potato susceptibility to diseases. Transcriptome and metabolome sequencing revealed significant impacts of excessive N fertilizer use on lipid and amino acid metabolism pathways. Weighted gene co‑expression network analysis (WGCNA) was adopted to identify two genes associated with N fertilizer response: PGSC0003DMG400021157 and PGSC0003DMG400009544.

Listeria monocytogenes is one of the leading causative agents of foodborne disease outbreaks worldwide. Herein, the antibiofilm effect and mechanism of Mannosylerythritol Lipid-A against L. monocytogenes EGD-e is reported for the first time. MEL-A effectively attenuated biofilm formation while reducing the viability and motility of bacteria within the biofilm in the early stage, and influenced bacterial adhesion by affecting the secretion of extracellular polysaccharides and eDNA. RT-qPCR revealed that MEL-A significantly suppressed the expression of genes involved in flagellar movement and virulence. Untargeted LC-MS metabolomics indicated that MEL-A affected the fluidity and permeability of cell membranes by significantly upregulating unsaturated fatty acids, lipids and glycoside metabolites, and affected protein biosynthesis, nucleotide metabolism and DNA synthesis and repair by significantly downregulating amino acid metabolism and nucleic acid metabolism. These pathways may constitute the key targets of biofilm formation inhibition by MEL-A. Furthermore, MEL-A showed good removal effects on mature biofilms under different temperatures, different materials and milk. Our data indicated that MEL-A could be used as a novel antibiofilm agent to improve food safety. Our study provides new insights into the possible inhibitory mechanism of MEL-A and the response of L. monocytogenes EGD-e to MEL-A.

In this work, the polysaccharide profile of different grapes and red wines in China was studied and the influences of two common winemaking techniques on the components of wine were analyzed. The soluble polysaccharide content in the skins of native grape species in China (non-Vitis vinifera grapes) was significantly higher than that of Vitis vinifera species, while the terroir effect on V. vinifera varieties was limited. The combination of the enzyme preparation and the addition of mannoproteins (MPs) at the beginning of alcoholic fermentation (MP1 + E) could increase the contents of MPs and acid polysaccharides (APS) compared to the control wines. Meanwhile, better color characteristics and higher level of anthocyanin derivatives were observed. However, MP1 + E treatment reduced the content of polysaccharides rich in arabinose and galactose (PRAGs) due to enzymatic hydrolysis. The study will provide useful information for winemakers to regulate the wine polysaccharide profile.

Abstract Aim Metastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis‐associated immune signature in HCC is worth exploring. Methods Bioinformatic analysis was conducted based on the single‐cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell–cell interaction were further analyzed and verified. Results Generally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion‐specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis. Conclusions HCC with metastasis exhibited upregulation of exhaustion‐specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.

IntroductionSwine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza.MethodsHere, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated.ResultsOur results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets.ConclusionTaken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

Abstract Background Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT’s anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine. Methods In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected. Results MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area. Conclusions MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.

Abstract. Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell–cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.

AIM:To observe the clinical efficacy of modified Buyang Huanwu Decoction in treating non-proliferative diabetic retinopathy(NPDR)of qi and yin deficiency and stagnation of collaterals, and to quantitatively analyze the changes in peripapillary vessel density before and after treatment using optical coherence tomography angiography(OCTA).METHODS:A randomized controlled trial was used to collect a total of 58 patients(99 eyes)with qi and yin deficiency and stagnation of collaterals NPDR who visited our hospital from June 2022 to November 2022, and patients were randomly divided into an observation group(n=29, 51 eyes)and a control group(n=29, 48 eyes). The control group received basic treatment according to the recommendations for DR published by the American Academy of Ophthalmology in 2019(blood glucose control, diabetes health education, and regular follow-up for patients with mild NPDR; and add local/grid-like laser photocoagulation if necessary for patients with moderate NPDR), while the observation group received modified Buyang Huanwu Decoction in addition to the basic treatment for 1mo. The best-corrected visual acuity(BCVA), traditional Chinese medicine(TCM)efficacy, peripapillary telangiectasia vessel density(ppVD), and changes in peripapillary retinal nerve fiber layer(pRNFL)thickness were compared between the two groups before and after treatment.RESULTS:The BCVA(LogMAR)of the observation group was 0.20(0.10, 0.30)after 1mo of treatment, which was significantly improved compared with that of the control group of 0.30(0.20, 0.40; P

BackgroundDicamba is widely used in agricultural production in China, but it is extremely soluble in water and can be harmful to human health when it enters the body via water drinking. It is necessary to establish an accurate, sensitive, and rapid detection method to determine the residues of dicamba in domestic drinking water. ObjectiveTo establish two methods for the determination of dicamba residues in drinking water by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) respectively. MethodsThe conditions of the proposed method using HPLC-MS/MS included CAPCELL PAK ST chromatographic column, ammonium formate water solution and methanol as the mobile phase, and isocratic elution. The system was operated under multiple reaction monitoring mode and electrospray negative ionization mode. Trimethylsilylated diazomethane was used as a derivatizing agent for GC-MS/MS, and an external standard curve was used to evaluate the system. The residues of dicamba in seven water samples of tap water or secondary water supply from six regions in Chengdu were detected by the established systems to evaluate their applicability and to understand the status quo of dicamba residues in drinking water. ResultsFor the HPLC-MS/MS, the linear range of dicamba was 1.00-100 μg·L−1, the regression equation was \begin{document}$\hat Y $\end{document}=1250.9X+2681.5, the correlation coefficient was 0.9988, the relative standard deviations were 1.23%-26.3%, the limit of detection was 0.95 μg·L−1, and the spiked recoveries were 91.8%-111%. For the GC-MS/MS, the linear range of dicamba was 0.200-10.0 μg·L−1, the regression equation was \begin{document}$\hat Y $\end{document}=190597X+40911, the correlation coefficient was 0.9993, the relative standard deviations were 0.64%-3.90%, the limit of detection was 0.18 μg·L−1, and the spiked recoveries were 97.3%-105%. No dicamba residue was identified in the seven water samples of tap water or secondary water supply from six regions in Chengdu by the proposed methods. ConclusionThe two detection methods established in this study are sensitive and rapid, meet the requirements from the detection of dicamba residues in drinking water, and provide an experimental basis for subsequent research on the detection of dicamba residues. In the future, it is necessary to continue to pay attention to the pollution of dicamba in drinking water in Chengdu.

In this study, a novel adaptive nonsingular terminal sliding mode (ANTSM) control frame combined with a modified extended state observer (MESO) is presented to enhance the anti-interference performance of the permanent magnet synchronous motor (PMSM) system. In the face of time-varying disturbances with unknown upper bounds, traditional nonsingular terminal sliding mode (NTSM) controllers typically utilize the large control gain to counteract the total disturbance, which will cause unsatisfactory control performances. To address this tough issue, an ANTSM control technique was constructed for the PMSM system by tuning the control gain automatically without overestimation. On this basis, the MESO was adopted to estimate the unknown total disturbance, whose estimation was offset to the ANTSM control input. By applying finite-time techniques, the estimation error will finite-time converge to zero. The proposed MESO has a more rapid estimation speed than the traditional extended state observer (ESO). Finally, the validity of the ANTSM + ESO composite control algorithm is confirmed by comprehensive experiments.

Abstract Background We aimed to investigate the interaction between serum uric acid (SUA) levels with estimated glomerular filtration rate (eGFR) to low muscle strength (LMS) among older people in China. Methods Cohort data were obtained from China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015. A total of 2,822 community-dwelling adults aged 60 and above were enrolled for the follow-up. Serum uric acid was collected after 8 h of fasting, and handgrip strength was measured with a dynamometer. eGFR was calculated with an equation based on the Chinese population. A generalized additive model was employed for interaction analysis and progressively adjusted confounders. Results During the follow-up, a total of 659 individuals were excluded due to the lack of grip strength data, leaving 2,163 participants for analysis. Despite the protective effect of high uric acid against low muscle strength, especially in older females, it is not statistically significant (OR = 0.69, 95%CI = 0.45–1.04, P = 0.075). Following the progressive adjustment of covariates, the association between higher eGFR and elevated SUA levels remained statistically significant in females, showing a reduced odds ratio with low muscle strength (OR = 0.82, 95%CI = 0.70–0.97, P = 0.021). However, this trend was not observed in male participants. Conclusions This Chinese population-based cohort study suggests that among older females, a higher serum uric acid level combined with a higher estimated glomerular filtration rate is linked to a reduced risk of low muscle strength. This implies that the relationship between high serum uric acid levels and the risk of low grip strength might differ by gender.

This study was conducted with the primary objective of assessing the performance of cfDNA methylation in the detection of colorectal cancer (CRC). Five tumor tissue, 20 peripheral blood leucocyte, and 169 cfDNA samples were collected for whole-genome bisulfite sequencing (WGBS) analysis. Bioinformatic analysis was conducted to identify differentially methylated regions (DMRs) and their functional characteristics. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation levels of DMRs in the tissues and leucocytes. cfDNA samples from CRC patients and healthy controls were used to evaluate the performance of the DMR analysis. WGBS analysis revealed a decrease in DNA methylation levels in the CpG context in CRC tumor tissues compared with adjacent normal tissues. A total of 132 DMRs in cfDNA were identified as potential markers for diagnosing CRC. In a cohort of 95 CRC patients and 74 healthy controls, a combination of the three DMRs (DAB1, PPP2R5C, and FAM19A5) yielded an AUC of 0.763, achieving 64.21% sensitivity and 78.38% specificity in discriminating CRC patients from healthy controls. This study provides insights into DNA methylation patterns in CRC and identifies a set of DMRs in cfDNA with potential diagnostic value for CRC. These DMRs hold promise as biomarkers for CRC detection, offering promise for non-invasive CRC diagnosis. Further research is warranted to validate these findings in larger cohorts.

Bioactive compounds (BACs) have attracted much attention due to their potential health benefits. However, such substances have problems such as difficulty dissolving in water, poor stability, and low intestinal absorption, leading to serious limitations in practical applications. Nowadays, food colloidal delivery carriers have become a highly promising solution due to their safety, controllability, and efficiency. The use of natural macromolecules to construct delivery carriers can not only regulate the solubility, stability, and intestinal absorption of BACs but also effectively enhance the nutritional added value of functional foods, improve sensory properties, and extend shelf life. Moreover, smart-responsive colloidal delivery carriers can control the release characteristics of BACs, thus improving their absorption rate in the human body. This review describes the characteristics of several typical food colloid delivery carriers, focuses on their physical properties from static structure to dynamic release, summarizes their applications in delivery systems, and provides an outlook on the future development of food colloid delivery carriers. The different compositions and structures of food colloids tend to affect their stability and release behaviors, and the different surface properties and rheological characteristics of the carriers predestine their different application scenarios. The control of in vivo release properties and the effect on food media should be emphasized in the future exploration of safer and more controllable carrier systems.

Proanthocyanidins (PAs) and anthocyanins are flavonoids that contribute to the quality and health benefits of grapes and wine. Salinity affects their biosynthesis, but the underlying mechanism is still unclear. We studied the effects of NaCl stress on PA and anthocyanin biosynthesis in grape suspension cells derived from berry skins of Vitis vinifera L. Cabernet Sauvignon using metabolite profiling and transcriptome analysis. We treated the cells with low (75 mM NaCl) and high (150 mM NaCl) salinity for 4 and 7 days. High salinity inhibited cell growth and enhanced PA and anthocyanin accumulation more than low salinity. The salinity-induced PAs and anthocyanins lacked C5’-hydroxylation modification, suggesting the biological significance of delphinidin- and epigallocatechin-derivatives in coping with stress. The genes up-regulated by salinity stress indicated that the anthocyanin pathway was more sensitive to salt concentration than the PA pathway, and WGCNA analysis revealed the coordination between flavonoid biosynthesis and cell wall metabolism under salinity stress. We identified transcription factors potentially involved in regulating NaCl dose- and time-dependent PA and anthocyanin accumulation, showing the dynamic remodeling of flavonoid regulation network under different salinity levels and durations. Our study provides new insights into regulator candidates for tailoring flavonoid composition and molecular indicators of salt stress in grape cells.

Exploring the coupling coordinated development of carbon emission reduction and sequestration (CERS) and food security in agriculture is conducive to mitigating climate change and achieving sustainable development goals. However, there is little research on the coupling coordinated development of these two systems. Based on panel data of 31 Chinese provinces from 2001 to 2021, this study used the dynamic fuzzy set qualitative comparative analysis (fsQCA) method to analyze the levels and driving paths of coupling coordinated development between agricultural CERS and food security. The results revealed that (1) the coupling coordination degree increased from 0.443 in 2001 to 0.489 in 2021, showing an upward trend. (2) We identified three driving paths of coupling coordination development: technology-driven, finance-driven and urban-development-driven. (3) The grain sown area and unit yield are core variables, serving as fundamental pillars, and their combination with technology or financial expenditure enhances this coordinated development. Notably, the grain sown area and unit yield exhibit a complementary relationship, while agricultural technology and financial expenditure demonstrate a substitution relationship. (4) Temporal analysis showed a consistent trend in the technology-driven and finance-driven paths. Regional analysis revealed marked heterogeneity: the technology-finance synergy path predominates in the remote west, the technology-driven path lies in the mountainous southwest, the finance-driven path clusters in the north, and the urban-development-driven path is located in economically advanced regions. Policymakers should formulate policies according to these different driving paths to promote coupling coordinated development.

Influenza A virus (IAV) non-structural protein 1 (NS1) is a virulence factor that allows the virus to replicate efficiently by suppressing host innate immune responses. Previously, we demonstrated that the serine (S) at position 42 of NS1 in H1N1 swine influenza virus (SIV) is a critical residue in interferon (IFN) resistance, thus facilitating viral infections. Here, by lncRNA-seq, a total of 153 differentially expressed lncRNAs were identified, and the lncRNA HCG4 was selected due to its significantly higher expression after infection with the NS1 S42P mutant virus. Overexpression of HCG4 enhanced IFN-β production and suppressed SIV infection, highlighting the potential antiviral activity of HCG4 against SIV. Further investigation suggested that HCG4 served as a positive feedback mediator for RIG-I signaling. It alleviated the inhibitory effect on RIG-I K63-linked ubiquitination by NS1 protein, thereby resulting in an increase in RIG-I-mediated IFN production. Taken together, our findings demonstrate that HCG4 modulates the innate immune response to SIV infection through K63-linked RIG-I ubiquitination, providing insights into the role of lncRNAs in controlling viral infections.

This paper studies the recycling and remanufacturing mode and sales channel issues in the closed-loop supply chain. Specifically, this study establishes an e-commerce closed-loop supply chain consisting of a manufacturer and an e-commerce platform, and divides the recycling model into recycling by the manufacturer or recycling by the platform. Considering two common sales models in e-commerce platforms: the resale model and agency model, combined with the recycling model, four different research scenarios are formed. We use backward induction to solve the Stackelberg game problem and explore the remanufacturing and channel strategies of the manufacturer and the e-commerce platform. The research results show that for the manufacturer, under the same recycling model, when consumers' preference for remanufactured products and the sensitivity of recycling volume to recycling prices are low, he will prefer the resale model. Under the same sales model, the manufacturer always prefers the recycling model in which he is responsible for recycling. However, the choice of platform is contrary to that of the manufacturer. In the resale model, both the manufacturer and the platform will choose to recycle by themselves, which cannot achieve a win-win situation. Under the agency model, when consumers' preference for remanufactured products is high and the sensitivity coefficient of recycling volume to recycling price is low, supply chain members can achieve a win-win situation, and the scope of the win-win situation decreases as the unit production cost of new products increases. In addition, rising consumer preference for remanufactured products will lead to lower consumer surplus.

BackgroundRadiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear.MethodIn this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. ResultsWe observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. ConclusionIn recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells.