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Abstract Background Currently, serum PSA is the most commonly used screening tool in clinical practice. However, PSA levels in the range of 4–10 ng/ml are considered the ‘grey zone’ of prostate cancer screening. Patients within this range need to be further evaluated using additional parameters such as PSA ratio, PSA density, and other indices to determine the necessity of prostate biopsy (PBx). Despite this, patients in the ‘grey zone’ still have a low rate of positive biopsy results. Neutrophils have been found to be associated with tumor development and inflammation. Based on this, we combined PSA and absolute neutrophil counts to calculate the total PSA to absolute neutrophil ratio (PNR), which is higher in patients with prostate cancer and lower in those with benign conditions. PNR is elevated in prostate cancer patients compared to those with prostate enlargement. Therefore, the aim of this study is to explore the diagnostic efficacy of PNR for prostate cancer across different PSA intervals and to provide new insights into the diagnosis, treatment, and screening strategies for prostate cancer. Objective In this study, we explored the predictive value of prostate-specific antigen-to-neutrophil ratio (PNR) for the diagnosis of prostate cancer, with a view to further improving the diagnostic accuracy of prostate cancer. Methods Patients were grouped in three different divisions of PSA 4–10 ng/ml, 10–20 ng/ml, > 20 ng/ml, We grouped the patients and compared the test data such as age, PSA, PSA-density (PSAD), and prostate-specific antigen-to-neutrophil ratio (PNR) between the two groups of patients who had puncture results of prostate cancer and non-prostate cancer at the same time using Log regression test to verify the diagnostic value of PNR. Results When PSA levels are in the range of 4–10 ng/ml, an elevated PNR is an independent risk factor for prostate cancer. In this range, the diagnostic value of f/t PSA and PSAD for prostate cancer is limited. However, the use of PNR can significantly enhance the diagnostic efficacy for prostate cancer and thereby effectively reduce the incidence of unnecessary prostate biopsies.

Abstract The realization of room-temperature-operated, high-performance, miniaturized, low-power-consumption and Complementary Metal-Oxide-Semiconductor (CMOS)-compatible mid-infrared photodetectors is highly desirable for next-generation optoelectronic applications, but has thus far remained an outstanding challenge using conventional materials. Two-dimensional (2D) heterostructures provide an alternative path toward this goal, yet despite continued efforts, their performance has not matched that of low-temperature HgCdTe photodetectors. Here, we push the detectivity and response speed of a 2D heterostructure-based mid-infrared photodetector to be comparable to, and even superior to, commercial cooled HgCdTe photodetectors by utilizing a vertical transport channel (graphene/black phosphorus/molybdenum disulfide/graphene). The minimized carrier transit path of tens of nanometers facilitates efficient and fast carrier transport, leading to significantly improved performance, with a mid-infrared detectivity reaching 2.38 × 1011 cmHz1/2W−1 (approaching the theoretical limit), a fast response time of 10.4 ns at 1550 nm, and an ultrabroadband detection range spanning from the ultraviolet to mid-infrared wavelengths. Our study provides design guidelines for next-generation high-performance room-temperature-operated mid-infrared photodetectors.

Repair of osteoporotic bone defects (OBD) remains a clinical challenge due to dysregulated bone homeostasis, characterized by impaired osteogenesis and excessive osteoclast activity. While drug-loaded 3D-printed scaffolds hold great potential in the restoration of bone homeostasis for enhanced OBD repair, achieving the controlled release and targeted delivery of drugs in a 3D-printed scaffold is still unmet. Herein, we developed an electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds (APS@P) with bone-targeting liposome formulation of salvianolic acid B (SAB-BTL). Benefiting from this strategy, SAB, an unstable and untargetable plant-derived osteogenic compound, was effectively encapsulated in APS@P, demonstrating stable and precise delivery with improved therapeutic efficacy. Owing to SAB-mediated bone homeostasis, APS@P significantly promoted angiogenesis and new bone formation while suppressing bone resorption, resulting in a significant 146 % increase in bone mass and improved microstructure compared to the OBD group. It was confirmed that the encapsulation of SAB into APS@P could promote the osteogenic differentiation of MSCs by stimulating Tph2/Wnt/β-catenin signaling axis, coupled with the stimulation of type H angiogenesis and the suppression of RANKL-mediate bone resorption, thereby enhance OBD repair. This study provides a universal platform for enhancing the bioactivity of tissue-engineered scaffolds, offering an effective solution for the efficient regeneration of osteoporotic bone.

Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.

Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of tumor globally and the leading cause of cancer-related deaths. Although treatment strategies such as immune checkpoint inhibitors and chemotherapy have advanced, the heterogeneity among NSCLC patients results in significant variability in treatment outcomes. Studies have shown that certain patients respond poorly to immune checkpoint inhibitors, indicating that treatment response is closely related to multiple factors. Therefore, it is necessary to develop predictive models to stratify patients based on gene expression and clinical characteristics, aiming for precision therapy. Objective This study aims to construct a stratified prognostic model for NSCLC patients based on lysosome-dependent cell death (LDCD) scoring by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. By analyzing the immune-related characteristics of high-risk and low-risk groups, we further explored the impact of cell death patterns on lung cancer and identified potential therapeutic targets. Methods This study obtained single-cell RNA sequencing data and gene expression data of NSCLC patients and normal lung tissues from the GEO and TCGA databases. We used R packages such as Seurat and CellChat for data preprocessing and analysis, and performed dimensionality reduction and visualization through Principal Component Analysis (PCA) and UMAP algorithms. LASSO regression analysis was used to construct the predictive model, followed by cross-validation and ROC curve analysis. The model’s effectiveness was validated through survival analysis and immune microenvironment analysis. Results The study showed a significant increase in the proportion of monocytes in NSCLC tissues, suggesting their important role in cancer progression. Cell communication analysis indicated that macrophages, smooth muscle cells, and myeloid cells exhibit strong intercellular communication during cancer progression. Using the constructed prognostic model based on 12 LDCD-related genes, we found significant differences in overall survival and immune microenvironment between the high-risk and low-risk groups.

Background: Osteoarthritis (OA) presents a formidable challenge, characterized by as-yet-unclear mechanical intricacies within cartilage and the dysregulation of bone homeostasis. Our preliminary data revealed the encouraging potential of a Sargassum polysaccharide (SP), in promoting chondrogenesis. The aim of our study is to comprehensively assess the therapeutic effects of SP on OA models and further elucidate its potential mechanism. Methods: The protective effects of SP were initially evaluated in an inflammation-induced human chondrocyte (C28) cell model. CCK-8 assays, Alcian blue staining, RT-qPCR and Western blotting were used to verify the chondrogenesis of SP in vitro. To assess the efficacy of SP in vivo, surgically induced medial meniscus destabilization (DMM) OA rats underwent an 8-week SP treatment. The therapeutic effects of SP in OA rats were comprehensively evaluated using X-ray imaging, micro-computed tomography (μ-CT), histopathological analysis, as well as immunohistochemical and immunofluorescent staining. Following these assessments, we delved into the potential signaling pathways of SP in inflammatory chondrocytes utilizing RNA-seq analysis. Validation of these findings was conducted through RT-qPCR and western blotting techniques. Results: SP significantly enhance the viability of C28 chondrocytes, and increased the secretion of acidic glycoproteins. Moreover, SP stimulated the expression of chondrogenic genes (Aggrecan, Sox9, Col2a1) and facilitated the synthesis of Collagen II protein in C28 inflammatory chondrocytes. In vivo experiments revealed that SP markedly ameliorated knee joint stenosis, alleviated bone and cartilage injuries, and reduced the histopathological scores in the OA rats. μ-CT analysis confirmed that SP lessened bone impairments in the medial femoral condyle and the subchondral bone of the tibial plateau, significantly improving the microarchitectural parameters of the subchondral bone. Histopathological analyses indicated that SP notably enhanced cartilage quality on the surface of the tibial plateau, leading to increased cartilage thickness and area. Immunohistochemistry staining and immunofluorescence staining corroborated these findings by showing a significant promotion of Collagen II expression in OA joints treated with SP. RNA-seq analysis suggest that SP's effects were mediated through the regulation of the ITGβ1-PI3K-AKT signaling axis, thereby stimulating chondrogenesis. Verification through RT-qPCR and Western blot analyses confirmed that SP significantly upregulated the expression of ITGβ1, p110δ, AKT1, ACAN, and Col2a1. Notably, knock-down of ITGβ1 using siRNA in C28 chondrocytes inhibited the expression of ITGβ1, p110δ, AKT1, and ACAN. However, these inhibitory effects were not completely reversed by supplemental SP intervention. Conclusions: In summary, our findings reveal that SP significantly enhances chondrogenesis both in vitro and in vivo, alleviating OA progression both in bone and cartilage. The observed beneficial effects are intricately linked to the activation of the ITGβ1-PI3K-AKT signaling axis. The translational potential of this article: Our research marks the first instance unveiling the advantageous effects and underlying mechanisms of SP in OA treatment. With its clinical prospects, SP presents compelling new evidence for the advancement of a next-generation polysaccharide drug for OA therapy.

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM.

A physically feasible, reliable, and safe motion is essential for robot operation. A parameterization-based trajectory planning approach is proposed for an 8-DOF manipulator with multiple constraints. The inverse kinematic solution is obtained through an analytical method, and the trajectory is planned in joint space. As such, the trajectory planning of the 8-DOF manipulator is transformed into a parameterization-based trajectory optimization problem within its physical, obstacle and task constraints, and the optimization variables are significantly reduced. Then teaching–learning-based optimization (TLBO) algorithm is employed to search for the redundant parameters to generate an optimal trajectory. Simulation and physical experiment results demonstrate that this approach can effectively solve the trajectory planning problem of the manipulator. Moreover, the planned trajectory has no theoretical end-effector deviation for the task constraint. This approach can provide a reference for the motion planning of other redundant manipulators.

In this article, we propose an autonomous exploration system based on transfer learning for target point exploration in unknown environments. The system generates a series of clustering points based on the local perceptual information and selects suitable local exploration points through a heuristic method to guide the robot towards the global target direction. This approach alleviates the problem of local optima to a significant extent. To reduce the time cost of deep reinforcement learning in the initial stages, we employ transfer learning by training a model capable of avoiding static obstacles in a simulated environment to accomplish local dynamic navigation tasks. By combining the locally learned dynamic navigation policy with global motion planning, we achieve autonomous exploration for the robot. During the fully autonomous navigation process, we record the robot’s movement trajectory and the generated map. Experimental results demonstrate that compared to similar exploration methods, this approach exhibits advantages in complex dynamic environments, even with the sole use of two-dimensional laser, without the need for maps or excessive information.

Lonicera japonica Thunb. is widely used in Asian countries as a food ingredient to make healthy drinks, with lonicerin, a flavone O-glycoside, as a predominant bioactive compound. This study investigated lonicerin’s effects on high-fat diet-induced hepatic steatosis in mice, compared to its aglycone luteolin. Results showed that lonicerin significantly reduced diet-induced body weight gain and hepatic lipid accumulation in mice, demonstrating greater efficacy than luteolin. This lipid-lowering effect was due to inhibited hepatic fatty acid (FA) biosynthesis and promoted fecal lipid excretion. Moreover, lonicerin favorably modulated gut microbiota by increasing Dubosiella, Eubacterium_brachy_group, and Bilophila, while reducing the pathogenic Desulfovibrionaceae. These changes led to elevated short-chain fatty acid production and altered fecal bile acid (BA) profiles, likely activating the intestinal FXR-FGF15 pathway to inhibit hepatic FA synthesis. In conclusion, lonicerin alleviated diet-induced hepatic steatosis by promoting fecal lipid excretion and inhibiting hepatic FA biosynthesis through modulating the gut microbiota-BA-intestinal FXR axis.

Butylparaben (BuP) is a ubiquitous preservative in cosmetics, foods, and medicine. As an emerging pollutant, it has gained wide attention in recent years. Because amphibians have both aquatic and terrestrial life stages and high skin permeability, they are sensitive to environmental changes. To assess the toxic effects of BuP on amphibians, the present study was conducted on the spot-legged tree frog (Polypedates megacephalus) tadpoles. In the present study, LC50 of BuP for 96 h exposures was 3509 µg/L. Then, the tadpoles were exposed to 0, 350 and 2100 µg/L BuP (hereafter named as CK, B1 and B2) for 12, 24 and 48 h, the oxidative stress and apoptosis in the liver were analyzed. The results showed that the content of MDA and activity of SOD and GSH-PX were increased with an increase in BuP exposure. BuP stress significantly altered the expression of Nrf2-Keap1 signal pathway genes. An increase in the expression of JAK-STAT signal pathway genes was observed with an increase in the exposure to BuP concentration at 24 and 48 h. In contrast, the expression of negative regulators of JAK-STAT signal pathway were significantly increased at 12 h and decreased at 24 and 48 h. A significant decrease in pro-apoptosis genes expression (Bax and Caspase3) were observed at 12 h but increased at 24 and 48 h, while the expression of anti-apoptosis gene (Bcl-2) decreased at 24 and 48 h. These results provide a valuable reference point for assessing the ecological and health risks associated with BuP in the environment.

[Introduction] This study aims to develop an efficient and reliable pulse power supply system based on supercapacitors (SC) for toroidal field (TF) coils in nuclear fusion magnet power systems to address high power demands while improving energy storage efficiency and system stability. [Method] A pioneering pulse power supply structure was devised employing Modular Multilevel Converter (MMC) technology, leveraging the high power density and swift charging-discharging capabilities of SC as primary energy storage units. This design targeted the high-frequency pulse operation requirements of TF coils. Additionally, the benefits of integrating supercapacitors with MMC technology, including system flexibility and scalability, were explored. [Result] The study demonstrates that the developed power supply system effectively meets the pulse operation requirements of nuclear fusion reactors, guaranteeing efficient energy delivery and conversion. [Conclusion] The supercapacitor-based pulse power supply system offers an efficient energy solution for nuclear fusion devices, enhancing energy conversion efficiency, operational stability and device reliability. Subsequent research will focus on optimizing the power structure and performance for diverse applications.

In recent years, one of the most prevalent matters in population ecology has been the study of predator-prey relationships. In this context, this paper investigated the dynamic behavior of a delayed predator-prey model considering square root type functional response and stage structure for predators. First, we obtained positivity and boundedness of the solutions and existence of equilibrium points. Second, by applying the stability theory of delay differential equations and the Hopf bifurcation theorem, we discussed the system's local stability and the existence of a Hopf bifurcation at the positive equilibrium point. Moreover, the properties of the Hopf bifurcation were deduced by using the central manifold theorem and normal form method. Analytical results showed that when the time delay was less than the critical value, the two populations will coexist, otherwise the ecological balance will be disrupted. Finally, some numerical simulations were also included to verify the theoretical results.

Abstract While the role of crystal facets is well known in traditional heterogeneous catalysis, this effect has not yet been thoroughly studied in plasmon-assisted catalysis, where attention has primarily focused on plasmon-derived mechanisms. Here, we investigate plasmon-assisted electrocatalytic CO2 reduction using different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD), and octahedron (OC) - exposing {100}, {110}, and {111} facets, respectively. Upon plasmon excitation, Au OCs doubled CO Faradaic efficiency (FECO) and tripled CO partial current density (jCO) compared to a dark condition, with NCs also improving under illumination. In contrast, Au RDs maintained consistent performance irrespective of light exposure, suggesting minimal influence of light on the reaction. Temperature experiments ruled out heat as the main factor to explain such differences. Atomistic simulations and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs than RDs. These effects now dominate the reaction landscape over the crystal facets, thus shifting the reaction sites when comparing dark and plasmon-activated processes. Plasmon-assisted H2 evolution reaction experiments also support these findings. The dominance of low-coordinated sites over facets in plasmonic catalysis suggests key insights for designing efficient photocatalysts for energy conversion and carbon neutralization.

BackgroundUpper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) both originate from uroepithelial tissue, sharing remarkably similar clinical manifestations and therapeutic modalities. However, emerging evidence suggests that identical treatment regimens may lead to less favorable outcomes in UTUC compared to BLCA. Therefore, it is imperative to explore molecular processes of UTUC and identify biological differences between UTUC and BLCA.MethodsIn this study, we performed a comprehensive analysis using single-cell RNA sequencing (scRNA-seq) on three UTUC cases and four normal ureteral tissues. These data were combined with publicly available datasets from previous BLCA studies and RNA sequencing (RNA-seq) data for both cancer types. This pooled analysis allowed us to delineate the transcriptional differences among distinct cell subsets within the microenvironment, thus identifying critical factors contributing to UTUC progression and phenotypic differences between UTUC and BLCA.ResultsscRNA-seq analysis revealed seemingly similar but transcriptionally distinct cellular identities within the UTUC and BLCA ecosystems. Notably, we observed striking differences in acquired immunological landscapes and varied cellular functional phenotypes between these two cancers. In addition, we uncovered the immunomodulatory functions of vein endothelial cells (ECs) in UTUC, and intercellular network analysis demonstrated that fibroblasts play important roles in the microenvironment. Further intersection analysis showed that MARCKS promote UTUC progression, and immunohistochemistry (IHC) staining revealed that the diverse expression patterns of MARCKS in UTUC, BLCA and normal ureter tissues.ConclusionThis study expands our multidimensional understanding of the similarities and distinctions between UTUC and BLCA. Our findings lay the foundation for further investigations to develop diagnostic and therapeutic targets for UTUC.

Abstract The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, μ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and μ-LEDs’ blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye’s axial length by ~1217 μm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.

Abstract Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc−/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract

Semantic segmentation of urban remote sensing images is a highly challenging task. Due to the complex background, occlusion overlap, and small-scale targets in urban remote sensing images, the semantic segmentation results suffer from deficiencies such as similar target confusion, blurred target boundaries, and small-scale target omission. To solve the above problems, a local-global feature capture and boundary information refinement Swin Transformer segmentor (LGBSwin) is proposed. First, the dual linear attention module (DLAM) utilizes spatial linear attention and channel linear attention mechanisms for strengthening global modeling capabilities to improve the segmentation ability of similar targets. Second, boundary-aware enhancement (BAE) adaptively mines the boundary semantic information through the effective integration of high-level and low-level features to alleviate blurred boundaries. Finally, feature refinement aggregation (FRA) establishes information relationships between different layers, reduces the loss of local information, and enhances local-global dependence, thus significantly improving the recognition ability of small targets. Experimental results demonstrate the effectiveness of LGBSwin, with an F1 of 91.02% on the ISPRS Vaihingen dataset and 93.35% on the ISPRS Potsdam dataset.

ABSTRACTObjectives Despite their use, differences in human papillomavirus (HPV) vaccine efficacies remain uncertain. This study assesses efficacy differences among bivalent, quadrivalent, and nine-valent HPV (2vHPV, 4vHPV, and 9vHPV) vaccines.Methods PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials comparing HPV vaccine efficacy against persistent infection (≥6 months) and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Network meta-analysis yielded direct and indirect comparisons. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were reported, and robustness was evaluated via sensitivity analysis.Results In 11 randomized controlled trials with 58,881 healthy women, for persistent infection with HPV 16, 9vHPV was most effective at 97% (RR = 0.03, 95% CI: 0.01–0.08); for HPV 18, 2vHPV (Cecolin) was most effective at 98% (RR = 0.02, 95% CI: 0.00–0.29); for CIN2+ associated with HPV 16 and 18, 4vHPV was most effective at 99% (RR = 0.01, 95% CI: 0.00–0.10) and 97% (RR = 0.03, 95% CI: 0.00–0.45), respectively; for persistent infection with HPV 31, 33, 45, 52, and 58, 9vHPV was ≥ 95% effective; both 2vHPV vaccines were cross-effective against HPV 31, 33, and 45; and 4vHPV was cross-effective against HPV 31.Conclusions HPV vaccine efficacies differ for different HPV types. Additional data are needed to determine the cross-efficacy of 2vHPV (Cecolin).

AbstractContext Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear.Objective To elucidate styrax’s anti-ischemic stroke protective effects and underlying mechanisms.Materials and methods An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax’s cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify.Results The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1β, and increase SOD and GSH-Px in ischemic-stroke rats (p

Ship piping arrangement is a nondeterministic polynomial problem. Based on the advantages of the grey wolf optimization (GWO) algorithm, which is simple, easy to implement, and has few adjustment parameters and fast convergence speed, the study adopts the grey wolf optimization (GWO) algorithm to solve the ship piping arrangement problem. First, a spatial model of ship piping arrangement is established. The grid cell model and the simplified piping arrangement environment model are established using the raster method. Considering the piping arrangement constraint rules, the mathematical optimization model of piping arrangement is constructed. Secondly, the grey wolf optimization algorithm was optimized and designed. A nonlinear convergence factor adjustment strategy is adopted for its convergence factor. Powell’s algorithm is introduced to improve its local search capability, which solves the problem that the grey wolf algorithm easily falls into the local optimum during the solving process. Simulation experiments show that compared with the standard grey wolf algorithm, the improved algorithm can improve the path layout effect by 38.03% and the convergence speed by 36.78%. The improved algorithm has better global search ability, higher solution stability, and faster convergence speed than the standard grey wolf optimization algorithm. At the same time, the algorithm is applied to the actual ship design, and the results meet the design expectations. The improved algorithm can be used for other path-planning problems.

New computing applications present new challenges to communication networks, for example, traditional network cannot meet the demands of flexible deployment, customized services, security and trustworthiness of new services.As a development paradigm that separated network technology and supported environment, polymorphic network provided new solutions to support the differentiated demands of various new applications.A type of computation-oriented network modality namely computing power network modality was discussed, for the computation-oriented business requirements based on the development trend of computing power network.Firstly, the design of computing power network modality was investigated, then the key technologies of computing power network modality were analyzed.Finally, the application scenarios of computing power network were prospected.It is hoped that the discussion can provide a reference for the future research and development on application of computation-oriented polymorphic network.

Abstract Objective Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. Subjects and Methods This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). Results The median follow-up was 5.2 years. Compared with instillation for 1–2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3–6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27–12.41;0.26–9.28;0.07–0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. Conclusions In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

ABSTRACT: Objectives: The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs. Methods: We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association. Results: A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes. Conclusion: The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.

Abstract Dravet syndrome (DS) is a monogenic, often refractory, epilepsy resultant from SCN1A haploinsufficiency in humans. A novel therapeutic target in DS that can be engaged in isolation or as adjunctive therapy is highly desirable. Here, we demonstrate reduced expression of the rodent glutamate transporter type 1 (GLT‐1) in a DS mouse model, and in wild type mouse strains where Scn1a haploinsufficiency is most likely to cause epilepsy, indicating that GLT‐1 depression may play a role in DS seizures. As GLT‐1 can be upregulated by common and safe FDA‐approved medications, this strategy may be an attractive, viable, and novel avenue for DS treatment.

Primary Sjögren’s Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Abstract Introduction This study aimed to examine the performance of binocular chromatic pupillometry for the objective and rapid detection of primary open-angle glaucoma (POAG), and to explore the association between pupillary light response (PLR) features and structural glaucomatous macular damage. Methods Forty-six patients (mean age 41.00 ± 13.03 years) with POAG and 23 healthy controls (mean age 42.00 ± 11.08 years) were enrolled. All participants underwent sequenced PLR tests of full-field, superior/inferior quadrant-field chromatic stimuli using a binocular head-mounted pupillometer. The constricting amplitude, velocity, and time to max constriction/dilation, and the post-illumination pupil response (PIPR) were analyzed. The inner retina thickness and volume measurements were determined by spectral domain optical coherence tomography. Results In the full-field stimulus experiment, time to pupil dilation was inversely correlated with perifoveal thickness (r = − 0.429, P

Objective: “Metabolism affects function” is the consensus of researchers at present. It has potential clinical application value to study the effects of regulating glutamine (Gln) metabolism on diabetes physiology or pathology. Our research aimed to summarize the latest research progress, frontier hot topics and future development trends in this field from the perspective of scientometrics. Methods: Relevant literatures and reviews were obtained from the Web of Science (WoS) between January 1, 2001 and May 31, 2022. An online analysis platform of bibliometrics, CiteSpace, and VOS viewer software were used to generate visual knowledge network graphs, including publication countries, institutions and authors partnership analysis, co-occurrence analysis, co-citation analysis, as well as citations and keywords burst detection to acquire research trends and hotspots. Results: Our results showed that a total of 945 publications in the WoS database met the analysis requirements, with articles being the main type. The overall characteristics showed an increasing trend in the number of publications and citations. The United States was leading the way in this research and was a hub for aggregating collaborations across countries. Vanderbilt University delivered high-quality impact with the most published articles. DeBerardinis, RJ in this field was the most representative author and his main research contents were Gln metabolism and mitochondrial glutaminolysis. Significantly, there was a relative lack of collaboration between institutions and authors. In addition, “type 2 diabetes”, “glutamine”, “metabolism”, “gene expression” and “metabolomics” were the keywords categories with high frequency in co-citation references and co-occurrence cluster keywords. Analysis of popular keywords burst detection showed that “branched chain”, “oxidative phosphorylation”, “kinase”, “insulin sensitivity”, “tca cycle”, “magnetic resonance spectroscopy” and “flux analysis” were new research directions and emerging methods to explore the link between Gln metabolism and diabetes. Overall, exploring Gln metabolism showed a gradual upward trend in the field of diabetes. Conclusion: This comprehensive scientometric study identified the general outlook for the field and provided valuable guidance for ongoing research. Strategies to regulate Gln metabolism hold promise as a novel target to treat diabetes, as well as integration and intersection of multidisciplinary provides cooperation strategies and technical guarantees for the development of this field.

In this paper, a delayed predator–prey model with a square root functional response is structured and analyzed. Through a discussion of the time delay and an analysis of the characteristic equations, the local stability of the boundary equilibrium and the positive equilibrium and the existence of Hopf bifurcation are investigated. On this basis, the critical value of the Hopf bifurcation is derived. According to the central manifold theorem and normal form theory, the nature of the Hopf bifurcation is obtained. Finally, by conducting numerical simulations, it is observed that incorporating a time delay can influence the stability of the predator and prey populations, causing periodic oscillations in the number of two populations.

ABSTRACT Innate lymphoid cells (ILCs) play a crucial role in mucosal protection and tissue homeostasis. However, the early mucosal defense mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have not been fully understood to date. This knowledge gap has motivated us to develop a coronavirus disease 2019-like mouse model to investigate the interactions between the virus, its receptor, and ILCs. In our study, we conducted intranasal challenges using pseudovirus expressing Spike (PSV-S) to examine the expression patterns of humanized ACE2 (chiACE2) and the transduction of PSV-S in lung and ileum tissues over a specified time period. Within a span of 72 hours, we observed an intense viral transduction induced by the spike protein, which was detected from the central bronchus to the bronchiole and alveolus in the lung (levels 3 to 8). Similarly, we observed the transduction of PSV-S in the villi and crypts of the ileum. Interestingly, our precise three-dimensional colocalization analysis revealed that only 73.74% ± 1.76% of the PSV-S transduction depended on chiACE2. Furthermore, type 2 innate lymphoid cells (ILC2s) exhibited the most pronounced activation in the gut mucosa. This finding indicates the significant role of ILC2s as contributors to the mucosal defense against viral infections. Our data shed light on the critical involvement of ILC2s and their intricate three-dimensional regulatory network in combating SARS-CoV-2 within the mucosa. IMPORTANCE Our study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019.

Abstract The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis‐resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self‐powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.

Background: Osteopenia and fragile fractures are diabetes-associated complications. Many hypoglycemic drugs have effects on bone metabolism. Metformin, as is a prescribed medication for type 2 diabetes mellitus (T2DM), had been reported to have osteoprotective effects beyond its hypoglycemic effect, however the potential mechanism behind these effects remains unclear. In this study, we aimed to investigate the comprehensive effects of metformin on bone metabolism in T2DM rat model and elucidate the potential mechanism. Methods: Goto-Kakizaki spontaneous T2DM rats with significant hyperglycemia were treated with/without metformin for 20 weeks. Glucose tolerance was tested and all rats were weighed every two weeks. The osteoprotective effects of metformin in diabetic rats were determined by quantifying serum bone biomarkers, μ-CT imaging, histological staining, bone histomorphometry, and biomechanical properties analyses. Potential targets of metformin in the treatment of T2DM and osteoporosis were predicted using network pharmacology. The effects of metformin on mesenchymal stem cells (C3H10) cultured in high glucose medium were evaluated by CCK-8 assay, alkaline phosphatase (ALP) staining, qPCR and western blotting. Results: This study demonstrated that metformin significantly attenuated osteopenia, decreased serum glucose and glycated serum protein (GSP) levels, improved bone microarchitecture, and biomechanical properties in GK rats with T2DM. Metformin significantly increased biomarkers of bone formation, and significantly decreased muscle ubiquitin C (Ubc) expression. Network pharmacology analysis found that signal transducer and activator of transcription1 (STAT1) would be a potential target of metformin for regulating bone metabolism. Metformin increased C3H10 ​cell viability in vitro, alleviated ALP inhibition caused by hyperglycemia, increased the osteogenic gene expression of runt-related transcription factor 2 (RUNX2), collagen type I alpha 1 (Col1a1), osteocalcin (OCN), and ALP, while suppressing RAGE and STAT1 expression. Metformin also increased the protein expression of Osterix and decreased that of RAGE, p-JAK2, and p-STAT1. Conclusions: Our results demonstrate that metformin attenuated osteopenia and improved bone microarchitecture in GK rats with T2DM and significantly promoted stem cell osteogenic differentiation under high glucose condition. The effects of metformin on bone metabolism are closely associated with the suppression of RAGE-JAK2-STAT1 signaling axis. The translational potential of this article: Our research provides experiment evidence and potential mechanistic rationale for the use of metformin as an effective candidate for diabetes-induced osteopenia treatment.

The build-up of lactate in solid tumors stands as a crucial and early occurrence in malignancy development, and the concentration of lactate in the tumor microenvironment may be a more sensitive indicator for analyzing primary tumors. In this study, we designed a self-powered lactate sensor for the rapid analysis of tumor samples, utilizing the coupling between the piezoelectric effect and enzymatic reaction. This lactate sensor is fabricated using a ZnO nanowire array modified with lactate oxidase (LOx). The sensing process does not require an external power source or batteries. The device can directly output electric signals containing lactate concentration information when subjected to external forces. The lactate concentration detection upper limit of the sensor is at least 27 mM, with a limit of detection (LOD) of approximately 1.3 mM and a response time of around 10 s. This study innovatively applied self-powered technology to the in situ detection of the tumor microenvironment and used the results to estimate the growth period of the primary tumor. The availability of this application has been confirmed through biological experiments. Furthermore, the sensor data generated by the device offer valuable insights for evaluating the likelihood of remote tumor metastasis. This study may expand the research scope of self-powered technology in the field of medical diagnosis and offer a novel perspective on cancer diagnosis.

Memory augmented neural network for lifelong on-device learning is bottlenecked by limited bandwidth in conventional hardware. Here, the authors demonstrate its efficient in-memristor realization with a close-software accuracy, supported by hashing and similarity search in crossbars.

Stromal antigen 1 (STAG1), a component of cohesion, is overexpressed in various cancers, but it is unclear whether it has a role in the transcriptional regulation of hepatocellular carcinoma (HCC). To test this hypothesis, here, we screened global HCC datasets and performed multiscale embedded gene co‐expression network analysis to identify the potential functional modules of differentially expressed STAG1 co‐expressed genes. The putative transcriptional targets of STAG1 were identified using chromatin immunoprecipitation followed by high‐throughput DNA sequencing. The cohesin‐associated gene score (CAGS) was quantified using the The Cancer Genome Atlas HCC cohort and single‐sample gene set enrichment analysis. Distinct cohesin‐associated gene patterns were identified by calculating the euclidean distance of each patient. We assessed the potential ability of the CAGS in predicting immune checkpoint blockade (ICB) treatment response using IMvigor210 and GSE78220 cohorts. STAG1 was upregulated in 3313 HCC tissue samples compared with 2692 normal liver tissue samples (standard mean difference = 0.54). A total of three cohesin‐associated gene patterns were identified, where cluster 2 had a high TP53 mutated rate and a poor survival outcome. Low CAGS predicted a significant survival advantage but presaged poor immunotherapy response. Differentially expressed STAG1 co‐expression genes were enriched in the mitotic cell cycle, lymphocyte activation, and blood vessel development. PDS5A and PDGFRA were predicted as the downstream transcriptional targets of STAG1. In summary, STAG1 is significantly upregulated in global HCC tissue samples and may participate in blood vessel development and the mitotic cell cycle. A cohesin‐associated gene scoring system may have potential to predict the ICB response.

Abstract Introduction Sjögren's disease (SjD) is a chronic autoimmune disease characterized by the loss of the secretory function of the exocrine glands. At present, drugs that can both correct the immune imbalance and improve exocrine gland function are needed. Meanwhile, vasoactive intestinal peptide (VIP) has been reported as a candidate with anti‐inflammatory and immunoregulatory properties for treating autoimmune diseases. Methods Nonobese diabetic (NOD) mice and the primary splenic lymphocyte cells (SPLCs) were used to construct the SS model. The therapeutic effects of VIP for SjD by evaluating water consumption, histopathology, T cell subsets, and related cytokines. RT‐qPCR and Western blot analysis were used to identify the expression of the PTEN/PI3K/AKT pathway. Results We found that VIP therapy in NOD mice could increase the expression of PTEN and VIP/VPAC1 receptor, as well as decrease the PI3K/AKT pathway. In vitro, the results showed that the PTEN knockdown decreased the Treg/Th17 ratio and enhanced the phosphorylated PI3K/AKT pathway, which were reversed with VIP treatment. Conclusions VIP exerts potential therapeutic action in SjD by upregulating PTEN through the PI3K/AKT pathway and Treg/Th17 cell balance.

AimThe aim of this study is to evaluate the utility of binocular chromatic pupillometry in detecting impaired pupillary light response (PLR) in patients with primary open-angle glaucoma (POAG) and to assess the feasibility of using binocular chromatic pupillometer in opportunistic POAG diagnosis in community-based or telemedicine-based services.MethodsIn this prospective, cross-sectional study, 74 patients with POAG and 23 healthy controls were enrolled. All participants underwent comprehensive ophthalmologic examinations including optical coherence tomography (OCT) and standard automated perimetry (SAP). The PLR tests included sequential tests of full-field chromatic stimuli weighted by rods, intrinsically photosensitive retinal ganglion cells (ipRGCs), and cones (Experiment 1), as well as alternating chromatic light flash-induced relative afferent pupillary defect (RAPD) test (Experiment 2). In Experiment 1, the constricting amplitude, velocity, and time to maximum constriction/dilation were calculated in three cell type-weighted responses, and the post-illumination response of ipRGC-weighted response was evaluated. In Experiment 2, infrared pupillary asymmetry (IPA) amplitude and anisocoria duration induced by intermittent blue or red light flashes were calculated.ResultsIn Experiment 1, the PLR of POAG patients was significantly reduced in all conditions, reflecting the defect in photoreception through rods, cones, and ipRGCs. The variable with the highest area under the receiver operating characteristic curve (AUC) was time to max dilation under ipRGC-weighted stimulus, followed by the constriction amplitude under cone-weighted stimulus and the constriction amplitude response to ipRGC-weighted stimuli. The impaired PLR features were associated with greater visual field loss, thinner retinal nerve fiber layer (RNFL) thickness, and cupping of the optic disk. In Experiment 2, IPA and anisocoria duration induced by intermittent blue or red light flashes were significantly greater in participants with POAG than in controls. IPA and anisocoria duration had good diagnostic value, correlating with the inter-eye asymmetry of visual field loss.ConclusionWe demonstrate that binocular chromatic pupillometry could potentially serve as an objective clinical tool for opportunistic glaucoma diagnosis in community-based or telemedicine-based services. Binocular chromatic pupillometry allows an accurate, objective, and rapid assessment of retinal structural impairment and functional loss in glaucomatous eyes of different severity levels.

A large quantity of scrap aircraft aluminum alloys in retired aircraft was used to produce cast aluminum alloys as raw material, resulting in a decrease of the value. In this work, the mixture of scrap aircraft aluminum alloys has been grade-maintaining recycled into 7075 aluminum alloy to maximize its recovery value. After melting, composition adjusting, refining and casting, the composition of recycled AA7075 ingots meet the requirements of GB/T 3190-2008, and the final melt is of great cleanliness. Four kinds of recycled AA7075 profiles were prepared by extrusion and T6/T73 heat treatment. The mechanical properties of all recycled profiles are superior to ASTM B209-14 and B221M-13 requirements. The T6-treated bars have the highest tensile strength (591 MPa), yield strength (534 MPa), elongation (10.0%), and stress-corrosion susceptibility factor (44.8). Nevertheless, the stress corrosion cracking, exfoliation corrosion and inter-granular corrosion resistance of the T6-treated bars still meet the requirements of aviation aluminum alloys. Scrap aircraft aluminum alloys can be regarded as master alloys for containing Zn, Mg, Cu, etc., and they have low melting point, fast melting speed, and uniform microstructure. Thus, high-quality 7075 aluminum alloys can be obtained by recycling the scrap aircraft aluminum alloys. Furthermore, the recycling process can provide some guidance for the industrial application of recycling scrap aircraft aluminum alloys.

Abstract Background As Traditional Chinese Medicine (TCM) drugs, Huangqi and Danshen are always applied in combination for spinal cord injury (SCI) treatment based on the compatibility theory of TCM. Astragalus Polysaccharidesis (APS) and Tanshinone IIA (TSIIA) are the main active ingredients of Huangqi and Danshen, and they both possess neuroprotective effects through antioxidant activities. However, low solubility and poor bioavailability have greatly limited their application. In recent years, selenium nanoparticles (SeNPs) have drawn enormous attention as potential delivery carrier for antioxidant drugs. Results In this study, TCM active ingredients-based SeNPs surface decorated with APS and loaded with TSIIA (TSIIA@SeNPs-APS) were successfully synthesized under the guidance of the compatibility theory of TCM. Such design improved the bioavailability of APS and TSIIA with the benefits of high stability, efficient delivery and highly therapeutic efficacy for SCI treatment illustrated by an improvement of the antioxidant protective effects of APS and TSIIA. The in vivo experiments indicated that TSIIA@SeNPs-APS displayed high efficiency of cellular uptake and long retention time in PC12 cells. Furthermore, TSIIA@SeNPs-APS had a satisfactory protective effect against oxidative stress-induced cytotoxicity in PC12 cells by inhibiting excessive reactive oxygen species (ROS) production, so as to alleviate mitochondrial dysfunction to reduce cell apoptosis and S phase cell cycle arrest, and finally promote cell survival. The in vivo experiments indicated that TSIIA@SeNPs-APS can protect spinal cord neurons of SCI rats by enhancing GSH-Px activity and decreasing MDA content, which was possibly via the metabolism of TSIIA@SeNPs-APS to SeCys2 and regulating antioxidant selenoproteins to resist oxidative stress-induced damage. Conclusions TSIIA@SeNPs-APS exhibited promising therapeutic effects in the anti-oxidation therapy of SCI, which paved the way for developing the synergistic effect of TCM active ingredients by nanotechnology to improve the efficacy as well as establishing novel treatments for oxidative stress-related diseases associated with Se metabolism and selenoproteins regulation.

Background: In view of the increasing human life and the aging of the population, the search for safe anti-aging drugs has become a hot topic. Agaricus blazei Murrill is a rare edible fungus, with a variety of biological activities. The purpose of this study was to clarify the anti-aging effect and mechanism of ABM-A on the aging induced by D-Galactose in mice. Results: The result showed that ABM-A contained 87.2% of glucose, 3.3% of galactose, 3.8% mannose and 5.7% gluconic acid. The behavior of mice in the treatment group was significantly improved after administration of ABM-A. And the activity of SOD and CAT and the level of T-AOC were increased (p

Abstract Realizing environmental compatibility and high power conversion efficiency (PCE) are crucial in the research of organic photovoltaics towards practical application. Applying environmentally friendly bio‐materials into the modification of cathode interlayer (CIL) is a feasible approach to move towards both targets. In this research, three edible bio‐acids, ursolic acid, citric acid, and malic acid, are employed to modify the PDIN CIL of the organic solar cells (OSCs) with non‐fullerene acceptors. Among these edible bio‐acid modifiers, ursolic acid shows its excellent performance in improving interfacial contact and suppressing charge recombination. It helps to obtain a good interfacial contact and facilitates the electron extraction. As a result, the photovoltaic performance is significantly improved. The average PCE are increased from 17.58% of the control devices to 18.35% of the PDIN + Ursolic Acid based devices, with a maximum PCE of 18.54%. It is the champion efficiency among the reported applications of bio‐derived materials for the CILs. This study demonstrates the successful application of edible bio‐acid, which offers an effective and green approach for the CIL modification to realize highly efficient OSCs.

In the article, a global localization algorithm based on improved ultra-wide-band-based adaptive Monte Carlo localization is proposed for quick and robust kidnap recovery of mobile robot. First, two ultra-wide-band modules, the tag installed inside the mobile robot and the anchor installed inside charging station, are used to obtain the relative distance between the mobile robot and the charging station. Second, the global grid map is converted into a map with obstacle noise given the ranging accuracy of the ultra-wide-band modules with different obstacles. Third, while the robot is kidnapped, matching grids are screened based on the range information of ultra-wide-band modules and the obstacle noise of the grids. Finally, global localization algorithm is performed based on ultra-wide-band-based adaptive Monte Carlo localization to convert randomly generated particles from the whole map into randomly generated particles in the local map. Experimental results based on gazebo simulation and a real scenario showed that our global localization algorithm based on improved ultra-wide-band-based adaptive Monte Carlo localization not only significantly helped to improve the chances of the robot global pose recovery from lost or kidnapped state but also enabled the robot kidnap recovery with a smaller number of randomly generated particles, thus reducing the time to recover its accurate global localization. The algorithm was also more effective especially for kidnap recovery in a similar and large scenario.

In order to solve the problems of high computational complexity, low recognition accuracy of low signal to noise ratio (SNR) environment and low fidelity of simulation data in radar signal modulation recognition, a low complexity radar signal classification algorithm based on spectrum shape was proposed.Signal spectrum was normalized, feature parameters were extracted by spectrum sampling method, and then machine learning classification model was trained.The test results of the data generated by the radar signal source show that the classification accuracy of Barker code, Frank code, LFM code, BPSK, QPSK modulation and conventional radar signals is more than 90% (SNR≥3 dB).The algorithm has low computational complexity, can adapt to the change of signal parameters, and has good generalization.

AimsIncreasing evidence suggests that metformin can affect bone metabolism beyond its hypoglycemic effects in diabetic patients. However, the effects of metformin on fracture risk in type 2 diabetes mellitus (T2DM) patients remain unclear. A systematic review and meta-analysis were performed in this study to evaluate the association between metformin application and fracture risk in T2DM patients based on previous studies published until June 2021.MethodsA systematic search was performed to collect publications on metformin application in T2DM patients based on PubMed, Embase, Cochran, and Web of Science databases. Meta-analysis was performed by using a random-effects model to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). Subgroup analyses based on cohort/case-control and ethnicity and sensitivity analyses were also performed.ResultsEleven studies were included in the meta-analysis. Results demonstrated metformin use was not significantly associated with a decreased risk of fracture (RR, 0.91; 95% CI, 0.81–1.02; I2 = 96.8%). Moreover, metformin use also demonstrated similar results in subgroup analyses of seven cohort studies and four case-control studies, respectively (RR, 0.90; 95% CI, 0.76–1.07; I2 = 98.0%; RR, 0.96; 96% CI, 0.89–1.03; I2 = 53.7%). Sensitivity analysis revealed that there was no publication bias.ConclusionThere was no significant correlation between fracture risk and metformin application in T2DM patients. Due to a limited number of existing studies, further research is needed to make a definite conclusion for clinical consensus.

BackgroundWith the increasing interest of academics in the application of artificial intelligence to sepsis, thousands of papers on this field had been published in the past few decades. It is difficult for researchers to understand the themes and latest research frontiers in this field from a multi-dimensional perspective. Consequently, the purpose of this study is to analyze the relevant literature in the application of artificial intelligence to sepsis through bibliometrics software, so as to better understand the development status, study the core hotspots and future development trends of this field.MethodsWe collected relevant publications in the application of artificial intelligence to sepsis from the Web of Science Core Collection in 2000 to 2021. The type of publication was limited to articles and reviews, and language was limited to English. Research cooperation network, journals, cited references, keywords in this field were visually analyzed by using CiteSpace, VOSviewer, and COOC software.ResultsA total of 8,481 publications in the application of artificial intelligence to sepsis between 2000 and 2021 were included, involving 8,132 articles and 349 reviews. Over the past 22 years, the annual number of publications had gradually increased exponentially. The USA was the most productive country, followed by China. Harvard University, Schuetz, Philipp, and Intensive Care Medicine were the most productive institution, author, and journal, respectively. Vincent, Jl and Critical Care Medicine were the most cited author and cited journal, respectively. Several conclusions can be drawn from the analysis of the cited references, including the following: screening and identification of sepsis biomarkers, treatment and related complications of sepsis, and precise treatment of sepsis. Moreover, there were a spike in searches relating to machine learning, antibiotic resistance and accuracy based on burst detection analysis.ConclusionThis study conducted a comprehensive and objective analysis of the publications on the application of artificial intelligence in sepsis. It can be predicted that precise treatment of sepsis through machine learning technology is still research hotspot in this field.

Probabilistic dual hesitant fuzzy set (PDHFS) is a more powerful and important tool to describe uncertain information regarded as generalization of hesitant fuzzy set (HFS) and dual HFS (DHFS), not only reflects the hesitant attitude of decision-makers (DMs), but also reflects the probability information of DMs. Score function of fuzzy number and weighting method are very important in multi-attribute group decision-making (MAGDM) issues. In many fuzzy environments, the score function and entropy measure have been proposed one after another. Firstly, based on the detailed analysis of the existed score function of PDHF element (PDHFE) and with the help of previous references, we build a novel score function for PDHFE. Secondly, a combined weighting method is built based on the minimum identification information principle by fusing PDHF entropy and Criteria Importance Through Intercriteria Correlation (CRITIC) method. Thirdly, a novel PDHF MAGDM approach (PDHF-EDAS) is built by extending evaluation based on distance from average solution (EDAS) approach to the PDHF environment to solve the issue that the decision attribute information is PDHFE. Finally, the practicability and effectiveness of the PDHF MAGDM technique is verified by suppliers selection (SS) and comparing analysis with existing methods. First published online 23 January 2023

Background: Gastric cancer (GC) is one of the most common cancers of the digestive tract, with the fifth-highest incidence and third highest mortality rate in the world. Methods: In this study, the Kaplan-Meier Plotter database was used to analyze the correlation between the expression of the glutathione peroxidase (GPX) family and the clinical prognosis of gastric cancer (GC). The prognostic value of increased GPX family mRNA expression in GC patients in different clinical stages, with different differentiation degrees, in different genders and human epidermal growth factor receptor-2 (HER2) status, and treated with different therapeutic regimens was also studied. Results: The results showed that with the increase of GPX1 and GPX2 mRNA low expression levels, the overall survival (OS) of gastric cancer patients was longer. However, when the high expression levels of GPX3, GPX5 and GPX6 mRNA increased, gastric cancer patients presented good OS, while the increase of GPX4 mRNA expression level had no significant correlation with OS in gastric cancer patients. Conclusion: The results of this study are expected to provide a reliable basis for the clinical treatment of GC and lay a foundation for the development of a novel GC treatment approach.