Search

ABSTRACT Objectives Intramedullary nailing is preferred for treating elderly proximal humeral fractures, but secondary reductions are common, particularly in elderly and osteoporotic patients. This occurs due to the intramedullary nail fixation's insufficient anti‐varus and anti‐rotational capacities and high stress at the bone–implant interface. We aim to enhance the anti‐varus and anti‐rotational stability of the fixation structure while reducing the stresses on the bone and internal fixation through structural design. Materials and Methods We developed a novel endosteal anatomical support nail (EASN) that integrates an endosteal torus construct into the proximal portion of the angle‐stable proximal humerus nail. The endosteal torus construct includes endosteal anatomical support (EAS) with a flat plane that allows direct fixation of the humeral head fragments and is shaped to conform to the medial side of the medullary cavity of the proximal humerus. We conducted finite element analysis to assess the biomechanical stability of four constructs: EAS with a calcar screw (CS), EAS without CS, non‐EAS with CS, and non‐EAS without CS. This analysis determined the contribution of the EAS to the mechanical stability of the proximal humerus in two‐part PHF with medial column disruption. Specimens were subjected to loads simulating partial‐weight‐bearing (as in rising from a chair or using crutches) and full‐weight‐bearing (as in rising from bed). We evaluated the stiffness of the construct, displacement at the fracture site, von Mises stress, and stress distribution. Results Under compressive or rotational loads, the EAS construct, with or without CS, was significantly stiffer than the non‐EAS construct. Displacement at the fracture site was significantly less with the EAS fixation than with the non‐EAS fixation. However, the stiffness and displacement at the fracture site of the EAS fixation without CS were comparable to those of the non‐EAS construct with CS. The EAS construct reduced the load on the nail and decreased the risk of implant failure. Both von Mises stress and stress distribution were significantly lower following fixation with the EAS constructs. Conclusions This study introduces a novel EAS concept to enhance the anti‐varus and anti‐rotational capabilities of the humeral head and distribute stress at the bone–implant interface in treating elderly PHFs. This strategy shows promise based on our limited analysis.

Abstract We aimed to explore the role of circular RNA 0043256 (circ_0043256) in gastric cancer (GC) and its underlying mechanisms. The impact of circ_0043256 silencing on the proliferation, migration, apoptosis, and aerobic glycolysis of MKN-45 and AGS cells induced by CoCl2 was assessed through the utilization of CCK-8, wound healing assay, flow cytometry, and metabolic analysis. The interaction between circ_0043256 and miR-593-5p, as well as the involvement of the miR-593-5p/RRM2 axis in gastric cancer, were confirmed via luciferase assay, Western blot, and bioinformatics analysis. We found that circ_0043256 was up-regulated in GC tissues and CoCl2-treated MKN-45 and AGS cells. Silencing of circ_0043256 reversed CoCl2-induced proliferation, migration, and aerobic glycolysis in MKN-45 and AGS cells. Additionally, circ_0043256 silencing enhanced cell apoptosis and G2/M phase cell cycle arrest in response to CoCl2 treatment. Furthermore, the miR-593-5p/RRM2 axis was identified as a regulatory mechanism for circ_0043256 function in GC. Silencing of circ_0043256 and miR-593-5p mimic co-transfection significantly inhibited CoCl2-induced cellular responses in MKN-45 and AGS cells. A glycolysis inhibitor 2-DG further enhanced the inhibitory effect of circ_0043256 silencing on aerobic glycolysis of CoCl2-induced MKN-45 and AGS cells. Additionally, the inhibition of circ_0043256 resulted in a reduction in tumor volume and the expression of proliferation marker proteins in nude mice. Moreover, the suppression of circ_0043256 led to an increase in miR-593-5p expression and a decrease in RRM2 expression, ultimately causing a decrease in glycolytic-related proteins associated with the glycolytic pathway. Targeting this axis may offer a novel therapeutic approach for treating GC.

Abstract An increasing number of treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) after the diagnosis of human immunodeficiency virus (HIV) infection. However, data on the association between rapid ART initiation and alterations in brain structure and function remain limited in people with HIV (PWH). A cross-sectional analysis was conducted on HIV-positive men who have sex with men (MSM) undergoing ART. Fifty-four participants who started ART within 30 days of confirmed HIV diagnosis (rapid ART group) and 20 participants who started ART more than 6 months of confirmed HIV diagnosis (non-rapid ART group) completed clinical assessments and multimodal magnetic resonance imaging scans to obtain both anatomical and resting-state functional images. Compared to PWH in the non-rapid ART group, those in the rapid ART group exhibited a greater total gray matter volume (P = 0.001) and functional changes, including a lower amplitude of low-frequency fluctuations in the left angular gyrus (P

Abstract Background Although many people received the COVID-19 vaccine, shortly after the Chinese government announced that the three-year COVID-19 restrictions were being eased, the first large number of Omicron infections appeared in Beijing. We describe epidemiological characteristics, clinical severity, and time-to-event distribution of patients infected with SARS-CoV-2 in Beijing Omicron outbreak, comparing those who received the booster vaccine with cases of full-course/partial-course vaccines. Methods We collected epidemiological, clinical, laboratory, and clinical management data from the hospital information system (HIS) for 1495 cases during Dec 2022-Jan 2023. We also collected illness onset time, diagnosis time, hospital admission time, and start and end times of each treatment. In addition, we collected the time of vaccination, inoculation times, and type of COVID-19 vaccination thorough the vaccination system. We described the epidemiological characteristics across vaccine inoculation doses, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital. We used the Kaplan–Meier method to estimate the survival rate and plot the survival curve, and the Cox proportional hazards model to assess the effect of covariates on survival time. Results Of the 1495 cases, 58.1% were male. The median ages in the non-vaccinated and vaccinated groups were 80 and 47 years. Elderly with underlying medical conditions and lower BMI less willing to vaccinate(p

Abstract. Background:. Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure–response relationship of ANV among people living with HIV. Methods:. Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure–response analysis for virologic responses and safety responses. Results:. ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure–response model revealed no significant correlation between the virologic response (HIV-RNA

BackgroundNumerous studies have reported that dysregulation of fatty acid metabolic pathways is associated with the pathogenesis of vitiligo, in which arachidonic acid metabolism (AAM) plays an important role. However, the molecular mechanisms of AAM in the pathogenesis of vitiligo have not been clarified. Therefore, we aimed to identify the biomarkers and molecular mechanisms associated with AAM in vitiligo using bioinformatics methods.MethodsThe GSE75819 and GSE65127 datasets were used in this study as the training and validation sets, respectively, along with 58 AAM-related genes (AAM-RGs). The differentially expressed genes (DEGs) between the lesional and control groups in the training set were identified through differential expression analysis. A biomarker-based nomogram was constructed to predict the risk of vitiligo.Results15 overlapping candidate genes were obtained between the DEGs and AAM-RGs. Machine-learning algorithms were used to identify six key genes as PTGDS, PNPLA8, FAAH, ABHD12, PTGS1, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL were regarded as biomarkers. A nomogram based on these biomarkers showed potential for predicting the risk of vitiligo. Functional enrichment, immune cell infiltration, and regulatory network analyses were used to elucidate the molecular mechanisms.ConclusionIn conclusion, PTGDS, PNPLA8, and MGLL were implicated in AAM to influence the pathogenesis of vitiligo. These findings offer insights into vitiligo treatment, although further research is needed for a comprehensive understanding.

IntroductionPneumocystis pneumonia (PCP) is a common and serious complication of HIV/AIDS, with a higher prevalence in patients not receiving antiretroviral therapy. Due to the high mortality rate of PCP, accurate prediction of its case fatality rate is very important for clinical treatment. We aimed to develop a risk model for the near-term prognosis of people with HIV/AIDS and PCP and verify its effectiveness.MethodsThis single-center, retrospective observational study was conducted at Beijing Youan Hospital from January 2012 to October 2022. 972 AIDS patients with Pneumocystis pneumonia met our criteria were recruited. The patients were divided into death group and survival group according to clinical outcome during hospitalization. Data of the two groups were collected including general information and laboratory test results. 53 medical characteristics of the two groups were collected. Prediction variables were screened with Multivariate logistic regression analysis and Lasso regression model. We used ROC curve to identify the discrimination of training and testing data sets. The Shapley Additive exPlanation (SHAP) method was applied to explain the final model and the weights of features.ResultsThe overall mortality rate among hospitalized patients was 17.8%. We found that the best prediction effect can be obtained when ALB, PO2, TBIL, LDH, CD4+ T lymphocyte counts are incorporated into the PCP risk prediction model. The model had a perfect discrimination with AUC of 0.994 and 0.947 in training and validation cohorts. The prognosis risk grade was divided into three grades: low-risk group (0-25 points with mortality of 5.9%), moderate-risk group (25-50 points with mortality of 45.1%) and high-risk group (above 50 points with mortality of 80%). There is a statistically significant difference in mortality among these three grades (χ2 = 419.271, P

ObjectiveAlthough research on psychological interventions in generalized anxiety disorder (GAD) has provided evidence of their effectiveness regarding self-reported outcomes, few studies have examined their psychophysiological effects. Heart rate is emerging as a potential biomarker of efficacy in anxiety disorders. This study aimed to investigate the effects of a self-compassion intervention versus a mindfulness intervention on physiological arousal in response to induced stress.MethodsForty-seven patients with GAD had heart rate data collected during a stress task before and after a 2-week pharmacological treatment (known as treatment as usual, TAU), a self-compassion intervention + TAU or a mindfulness intervention + TAU. They also reported state anxiety, positive affect, and negative affect at pre- and post- intervention before the stress task. ANOVAs were conducted to analyze the effects on electrocardiogram data self-reported measurements.ResultsSelf-compassion intervention uniquely decreased heart rate response to a stressor whereas mindfulness intervention did not. Both treatments decreased state anxiety and negative affect to a stressor, while increased positive affect in this context. We also demonstrated a significant correlation between decreased heart rate response and less negative emotions.ConclusionThe Findings provides novel physiological evidence that self-compassion interventions buffer stress reactivity in individuals with GAD. Attention shall be paid to the limitations in small and unequal sample size and a non-randomized study design.

Abstract Background The regulator of calcineurin 1 (RCAN1) is expressed in multiple organs, including the heart, liver, brain, and kidney, and is closely linked to the pathogenesis of cardiovascular diseases, Down syndrome, and Alzheimer’s disease. It is also implicated in the development of various organ tumors; however, its potential role in hepatocellular carcinoma (HCC) remains poorly understood. Therefore, the objective of this study was to investigate the potential mechanisms of RCAN1 in HCC through bioinformatics analysis. Methods We conducted a joint analysis based on the NCBI and TCGA databases, integrating both bulk transcriptome and single-cell analyses to examine the principal biological functions of RCAN1 in HCC, as well as its roles related to phenotype, metabolism, and cell communication. Subsequently, an RCAN1-overexpressing cell line was established, and the effects of RCAN1 on tumor cells were validated through in vitro experiments. Moreover, we endeavored to identify potential related drugs using molecular docking and molecular dynamics simulations. Results The expression of RCAN1 was found to be downregulated in 19 types of cancer tissues and upregulated in 11 types of cancer tissues. Higher levels of RCAN1 expression were associated with improved patient survival. RCAN1 was predominantly expressed in hepatocytes, macrophages, endothelial cells, and monocytes, and its high expression not only closely correlated with the distribution of cells related to the HCC phenotype but also with the distribution of HCC cells themselves. Additionally, Rcan1 may directly or indirectly participate in metabolic pathways such as alanine, aspartate, and glutamate metabolism, as well as butanoate metabolism, thereby influencing tumor cell proliferation and migration. In vitro experiments confirmed that RCAN1 overexpression promoted apoptosis while inhibiting proliferation and invasion of HCC cells. Through molecular docking of 1615 drugs, we screened brompheniramine as a potential target drug and verified our results by molecular dynamics. Conclusion In this study, we revealed the relationship between RCAN1 and HCC through bioinformatics methods, verified that RCAN1 can affect the progress of the disease through experiments, and finally identified potential therapeutic drugs through drug molecular docking and molecular dynamics.

Abstract BackgroundThere is limited literature available regarding the knowledge and use of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) with sexually transmitted infections (STIs). ObjectiveThis study’s objective was to explore the HIV PrEP cascade stages (knowledge, willingness to use, and use) among MSM with STIs in China, in order to promote the implementation of PrEP in this population. MethodsA cross-sectional study was conducted using a respondent-driven sampling method in 19 cities in China, from January to August 2022. The study collected data on demographics, behaviors, and PrEP cascade stages from participants who were not infected with HIV and who self-reported being recently infected with STIs. After using ResultsBy August 2022, following screening and exclusion, a total of 1329 MSM were included in the study. Among them, 85.55% (n=1137) had heard of PrEP, 81.57% (n=1084) expressed their willingness to use PrEP if engaging in high-risk HIV behaviors, 70.58% (n=938) had consulted a health care professional about PrEP, 62.98% (n=837) reported having used PrEP, and 46.35% (n=616) possessed a basic understanding of PrEP. The results of multivariate logistic regression analyses showed that the same factors significantly influenced both knowledge of PrEP and willingness to take PrEP, including age, education, marital status, income, condom usage, participation in group sex, HIV status of the most recent male sexual partner, and postexposure prophylaxis (PEP) usage. The factors significantly related to the PrEP use included income, engagement in commercial sex, participation in group sex, HIV status of the most recent male sexual partner, new drug usage, and PEP usage. ConclusionsMSM with STIs were engaged with the PrEP cascade stages at a relatively high rate, but they lacked an understanding of PrEP and underestimated HIV risk. The prevalence of having a basic understanding of PrEP was lower than PrEP usage, and this suboptimal awareness could impede PrEP efficacy and lead to risk compensation.

Drying technology plays a pivotal role in tea processing. Herein, the differences in color, non-volatile, and volatile components of green tea under various drying methods were investigated. The results indicated that vacuum freeze-microwave increased the L* and b* values, and decreased the a* values of tea leaves. Moreover, vacuum freeze-microwave drying resulted in higher polyphenol content than the other three drying methods although there was no significant difference. A total of 43 volatile compounds were identified. Of these, 2-propanone, ethanol(D), ethanol(M), ethyl acetate(M), 2-methyl-1-butanol, and 2-methylthiophene were found to play an important role in the above discrimination (VIP >1.5). Dry extraction showed a higher content of volatile components than wet extraction. Regardless of the extraction conditions, vacuum freeze-microwave drying exhibited a stronger signal intensity and more volatile components than other drying methods. This study provides a reference for analyzing the quality differences of green tea by different drying methods.

ABSTRACTBackground Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.Method C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics.Result In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice.Conclusion Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

Zeolite foamed asphalt - warm mix mixture (ZFA-WMM) has been applied in large quantities in asphalt pavement, however, a lower construction temperature, residual zeolite water and zeolite minerals have different effects on the cohesion and adhesion properties of zeolite foamed asphalt (ZFA), which indirectly affects the water stability of its mixture. This study analyzed the interface behavior in ZFA-WMM using molecular dynamics simulation. First, the molecular model of ZFA was constructed, and its thermodynamic properties were calculated and compared with experimental values and related simulated values to validated the reasonable of model. Then, the interface models of ZFA-aggregate (quartz and calcite) and ZFA-ZFA were established, simulating the effects of the zeolite mineral dosage, temperature, and interface moisture (residual zeolite water) content on the cohesion and adhesion of ZFA. Furthermore, the occurrence mode of cohesion or adhesion failures in ZFA-WMM were predicted by comparing the ZFA-aggregate adhesion work with ZFA cohesion work. The simulation results indicated that as the zeolite mineral dosage increased, the ZFA cohesion and ZFA-calcite adhesion increased, while ZFA-quartz adhesion first grew and then dropped, reaching its maximum at 9.4 % zeolite mineral dosage. Under the pavement operating temperature range (-15°C∼65°C), higher pavement temperatures are beneficial to ZFA-aggregate adhesion; the cohesion of ZFA first increases and then decrease as temperature rises, reaching its maximum at 25℃. The larger the interface moisture content, the higher the possibility of water separating ZFA from the aggregate surface and the water sensitivity of ZFA-WMM. The ZFA-WMM is prone to adhesion failure, especially at higher zeolite dosages.

Abstract Inhibitors of α‐amylase have been developed to regulate postprandial blood glucose fluctuation. The enzyme inhibition arises from direct or indirect inhibitor‐enzyme interactions, depending on inhibitor structures. However, an ignored factor, substrate, may also influence or even decide the enzyme inhibition. In this work, it is innovatively found that the difference in substrate enzymolysis modes, i.e., structural composition and concentration of α‐1,4‐glucosidic bonds, triggers the diversity in inhibitor‐enzyme aggregating behaviors and α‐amylase inhibition. For competitive inhibition, there exists an equilibrium between α‐amylase‐substrate catalytic affinity and inhibitor‐α‐amylase binding affinity; therefore, a higher enzymolysis affinity and concentration of α‐1,4‐glucosidic structures interferes the balance, unfavoring inhibitor‐enzyme aggregate formation and thus weakening α‐amylase inhibition. For uncompetitive inhibition, the presence of macromolecular starch is necessary instead of micromolecular GalG2CNP, which not only binds with active site but with an assistant flexible loop (involving Gly304‐Gly309) near the site. Hence, the refined enzyme structure due to the molecular flexibility more likely favors the inhibitor binding with the non‐active loop, forming an inhibitor‐enzyme‐starch ternary aggregate. Conclusively, this study provides a novel insight into the evaluation of α‐amylase inhibition regarding the participating role of substrate in inhibitor‐enzyme aggregating interactions, emphasizing the selection of appropriate substrates in the development and screening of α‐amylase inhibitors.

Abstract Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients.

Abstract. Background:. Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48. Methods:. A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C. Results:. A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P 0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥105 copies/mL (compared with

Abstract As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.

Abstract Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4 iKO ) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4 iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4 iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

This paper introduces an almost disturbance decoupling approach to address the disturbance problem for a class of underactuated nonlinear systems. First, a residual system is constructed using a virtual controller and partial differential equations. Next, the unknown disturbances are addressed using an almost disturbance decoupling approach, where Young’s inequality is applied to handle the disturbance terms in the residual system. An almost disturbance decoupling controller is designed for the residual system. The locally asymptotic stability of the closed-loop system is rigorously proven using Lyapunov’s theorem. Finally, simulation results on an IWP system with unknown disturbances and experimental results on an overhead crane are presented to validate the effectiveness of the proposed almost disturbance decoupling control method.

Lutjanus erythropterus protein (Lep) exhibits anti-inflammatory effects, but its antidepressant activity is unknown. This study used a 44-day chronic unpredictable mild stress (CUMS) model to determine whether Lep has a beneficial effect through the gut–brain axis in 3-week-old male C57BL/6 mice. Gavaging with Lep solution alleviated the depression-like behavior and anxiety symptoms in CUMS growing mice. Administration of Lep decreased serum IL-1β, IL-2, IL-6, and TNF-α levels and restored colonic mucosal damage. In addition, Lep improved the disturbance of 5-hydroxytryptamine (5-HT) secretion in the gut–brain axis. Pearson analysis revealed that gut short-chain fatty acid (SCFAs) concentration significantly (p < 0.05) correlated with mucosal damage scores and the depression-like behavior index. Lep was able to prevent the gut SCFA enrichment. Lep upregulated gut Muribaculaceae and downregulated SCFA-producing bacteria by replenishing deficient amino acid (AA) (tryptophan, alanine, aspartate, glutamate) and decreased (p < 0.01) the gene abundance of the AA metabolism pathway of SCFA-producing bacteria, thereby preventing gut SCFA enrichment and alleviating associated depression-like behavior. These findings indicate that Lep could attenuate depression in CUMS juvenile mice via the gut microbiota-SCFA–brain axis.

In this study activated carbon powder (ACP) was incorporated into asphalt to substitute a portion of the conventional filler (mineral powder, MP). The dynamic modulus at elevated temperatures, temperature-dependent viscosity sensitivity, low-temperature creep, and the interaction between asphalt and ACP were examined through dynamic shear rheometer testing, viscosity testing, and bending beam rheometer testing. Moreover, statistical methodologies such as the entropy weight method (EWM) and the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) were employed to optimize the proportion of ACP by evaluating the comprehensive rheological behavior of asphalt mastic (including high temperature performance, low temperature performance, flowability, and asphalt-ACP interaction). The findings demonstrate that ACP can enhance the resistance of asphalt mastic to high-temperature deformation to a certain degree. The ratio of creep rate to stiffness (m/S) decreases with the addition of ACP, indicating that ACP may exacerbate the occurrence of low-temperature thermal cracking in asphalt mastic. The interaction ability of asphalt mastic is significantly enhanced when a portion of the filler is replaced with ACP. The loss factor shows significant impact on the comprehensive evaluation. According to TOPSIS analysis, asphalt mastic with a blending proportion of 40% ACP and 60% MP performs better in terms of comprehensive rheological properties.

Asphalt mixtures are multiphase heterogeneous composites, the random distribution of the components leads to variability in the internal mechanical parameters of the material, but this variability has a certain degree of spatial correlation. In this study, the spatial variability and correlation of mechanical parameters of asphalt mixture materials are studied. Firstly, the viscoelastic and fracture parameters of asphalt mixtures were obtained by uniaxial compression test and semicircular bending (SCB) test. Then, the covariance decomposition method and Latin hypercubic sampling method were used to build the parameter random fields of long-term equilibrium modulus, flexural tensile strength and fracture energy of asphalt mixtures. Finally, using the extended finite element method to simulate the SCB test in ABAQUS. The results show that the application of the random field technique and the consideration of the spatial variability correlation of asphalt mixture material parameters can well simulate the randomness of the mechanical response of asphalt mixture materials caused by the randomness of the internal mechanical parameters in the laboratory test. The spatial variability of different parameters has different effects on the fracture response of semicircular specimens: the long-term equilibrium modulus and flexural and tensile strength mainly affect the loading stage of the load-displacement curve, while the fracture energy has a greater effect on the unloading stage.

For randomly degraded products undergoing a two-stage degradation process, traditional random effects models assume that the degradation rate follows a symmetrically normal distribution. However, certain products exhibit asymmetric degradation rates. In light of this, this paper proposes an approach for reliability analysis based on the inverse Gaussian (IG) degeneration process, which considers both asymmetric random effects and the two-stage nature simultaneously. To begin with, we establish a two-stage IG degradation process model that incorporates a skew normal random effect. Subsequently, we determine the location of change points using the Schwarz Information Criterion (SIC). The estimation of parameters is then conducted by combining Maximum Likelihood Estimations (MLEs) with the Genetic Algorithm (GA). Finally, we validate and demonstrate the practicality for the proposed model through Monte Carlo (MC) simulation and examples involving lithium batteries.

Flax is a crucial fiber crop that exhibits excellent textile properties and serves as a model plant for investigating phloem fiber development. The regulation of multiple genes significantly influences fiber development, notably involving NAC (NAM, ATAF1/2, CUC2) transcription factors in forming the fiber secondary cell wall (SCW). Overexpression of LuNAC61 in flax resulted in sparse top meristematic zone leaves and significantly reduced stem cellulose content. Scanning electron microscopy and staining observations revealed a significant reduction in fiber bundles. β-Glucuronidase (GUS) staining analysis demonstrated high activity of the LuNAC61 promoter in the bast fibers of the flax stem. Additionally, several members of the LuPLATZ and LuCesA families exhibited significant coexpression with LuNAC61. Subcellular localization indicated the presence of LuPLATZ24 protein in the nucleus and cytoplasm, LuNAC61 protein exclusively in the nucleus, and LuCesA10 in the nucleus and endoplasmic reticulum. LuPLATZ24 positively regulates LuNAC61, whereas LuNAC61 negatively affects LuCesA10, suggesting the involvement of a metabolic network in regulating flax fiber development. In conclusion, this study provides a critical opportunity for a comprehensive and in-depth analysis of the mechanisms governing flax fiber development and the potential use of biotechnology to enhance flax fiber yield.

Abstract Shear failure often occurs in engineering rock mass (such as inclined pillar) in gently inclined strata. Prediction and characterization the orientation of shear failure plane is the foundation of rock mass engineering reinforcement. In this paper, sandstone samples are used to perform uniaxial and shear tests to obtain the basic mechanical parameters. Then, by employing the numerical method, the combined compression–shear loading tests were carried out for inclined specimens varied from 0° to 25° at an interval of 5°, to obtain the dip effect on the orientation of rock failure plane. The results show that the failure plane of rock changes with the change of dip angle of rock sample. Based on the Mohr–Coulomb criterion, the ultimate stress state of rock was characterized under combined compression–shear loading. The ultimate strength of rock is equal to the ratio of the stress circle radius of rock under combined compression–shear condition to the stress circle radius of rock under uniaxial compression condition, multiplied by the uniaxial compressive strength. The fracture angle of rock was defined under combined compression–shear loading. A theoretical model was developed for predicting the fracture angle. The developed model could be characterized by internal friction angle, dip angle of rock sample and Poisson's ratio. Finally, the numerical results of the fracture angle were analyzed, which are consistent with the predicted results of the model. The investigation shows that the rock fracture angle has a dip effect, which decreases with the increase of the inclination angle of the sample. The research results provide a new means to identify the potential failure plane of engineering rock mass, and lay a theoretical foundation for calculating the orientation of rock fracture plane.

Abstract Background Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal–fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. Methods This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24–28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. Results In our cohort, 14.0% had an IPI

System-level fault diagnosis model, namely, the PMC model, detects fault nodes only through the mutual testing of nodes in the system without physical equipment. In order to achieve server nodes fault diagnosis in large-scale data center networks (DCNs), the traditional algorithm based on the PMC model cannot meet the characteristics of high diagnosability, high accuracy and high efficiency due to its inability to ensure that the test nodes are fault-free. This paper first proposed a fault-tolerant Hamiltonian cycle fault diagnosis (FHFD) algorithm, which tests nodes in the order of the Hamiltonian cycle to ensure that the test nodes are faultless. In order to improve testing efficiency, a hierarchical diagnosis mechanism was further proposed, which recursively divides high scale structures into a large number of low scale structures based on the recursive structure characteristics of DCNs. Additionally, we proved that $ 2(n-2){n^{k-1}} $ and $ (n-2){t_{n, k}}/{t_{n, 1}} $ faulty nodes could be detected for $ BCub{e_{n, k}} $ and $ DCel{l_{n, k}} $ within a limited time for the proposed diagnosis strategy. Simulation experiments have also shown that our proposed strategy has improved the diagnosability and test efficiency dramatically.

Coverage control is a fundamental and critical issue in plentiful wireless sensor network (WSN) applications. Aiming at the high-dimensional optimization problem of sensor node deployment and the complexity of the monitoring area, an orthogonal learning multi-strategy bald eagle search (OLMBES) algorithm is proposed to optimize the location deployment of sensor nodes. This paper incorporates three kinds of strategies into the bald eagle search (BES) algorithm, including Lévy flight, quasi-reflection-based learning, and quadratic interpolation, which enhances the global exploration ability of the algorithm and accelerates the convergence speed. Furthermore, orthogonal learning is integrated into BES to improve the algorithm’s robustness and premature convergence problem. By this way, population search information is fully utilized to generate a more superior position guidance vector, which helps the algorithm jump out of the local optimal solution. Simulation results on CEC2014 benchmark functions reveal that the optimization performance of the proposed approach is better than that of the existing method. On the WSN coverage optimization problem, the proposed method has greater network coverage ratio, node uniformity, and stronger optimization stability when compared to other state-of-the-art algorithms.

Abstract The α‐amylase inhibition and binding behaviors of shikimic acid and its structural analogues were studied. Uncompetitive inhibition characteristic of shikimic acid was identified through several linear transformation equations of enzymatic data considering the good linearity. Interestingly, the change in concentrations of starch would not decrease the inhibitory effects of shikimic acid with various concentrations used in present study. The inhibitory effect reduced greatly after the ethyl esterification of shikimic acid. Gallic acid was distinguished from shikimic acid by a benzene ring and exhibited lower inhibition than shikimic acid. Shikimic acid affected the α‐amylase structure by binding to the non‐active site but did not quench the α‐amylase fluorescent intensity. However, gallic acid anchored with a subsite containing some fluorescent residues at the entrance of active pocket, quenching the fluorescence intensity of α‐amylase strongly. The difference in shikimic acid and gallic acid made the changes in their binding sites as well as the binding behavior. Conclusively, the carboxyl and hexatomic ring with one double‐bond played an important role in binding of shikimic acid with the non‐active sites of α‐amylase. Shikimic acid has potentials as a functional‐factor in α‐amylase inhibition for controlling the postprandial blood sugar level.

Background: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved. Methods: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot analysis. Results: In response to tumor necrosis factor alpha (TNF-α) treatment and diabetes, the endothelium-dependent vasodilatation to Ach was significantly impaired in aorta from Nur77 KO as compared with those from the wild-type (WT) mice. Endothelial specific overexpression of Nur77 markedly prevented both TNF-α- and high glucose-induced endothelial dysfunction. Compared with WT mice, after TNF-α and high glucose treatment, ROS production in aorta was significantly increased in Nur77 KO mice, but it was inhibited in Nur77-Tg mice, as determined by dihydroethidium (DHE) staining. Furthermore, we demonstrated that Nur77 overexpression substantially increased the expression of several key enzymes involved in nitric oxide (NO) production and ROS scavenging, including endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GCH-1), glutathione peroxidase-1 (GPx-1), and superoxide dismutases (SODs). Mechanistically, we found that Nur77 increased GCH1 mRNA stability by inhibiting the expression of microRNA-133a, while Nur77 upregulated SOD1 expression through directly binding to the human SOD1 promoter in vascular endothelial cells. Conclusion: Our results suggest that Nur77 plays an essential role in attenuating endothelial dysfunction through activating NO production and anti-oxidant pathways in vascular endothelium. Targeted activation of Nur77 may provide a novel therapeutic approach for the treatment of cardiovascular diseases associated with endothelial dysfunction.