Search

Background Methods Results Conclusion ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values.520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi‐square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan–Meier method and log‐rank test.Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non‐tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast‐like cells but absent in tumor‐infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast‐like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial‐mesenchymal transformation (EMT), TGF‐beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC.ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway. [ABSTRACT FROM AUTHOR]

Critics of quality-adjusted life-years argue that it discriminates against older individuals. However, little empirical evidence has been produced to inform this debate. This study aimed to compare published cost-effectiveness analyses (CEAs) on patients aged ≥65 years and those aged <65 years. We used the Tufts Cost-Effectiveness Analysis Registry to identify CEAs published in MEDLINE between 1976 and 2021. Eligible CEAs were categorized according to age (≥65 years vs <65 years). The distributions of incremental cost-effectiveness ratios (ICERs) were compared between the age groups. We used logistic regression to assess the association between age groups and the cost-effectiveness conclusion adjusted for confounding factors. We conducted sensitivity analyses to explore the impact of mixed age and age-unknown groups and all ICERs from the same CEAs. Subgroup analyses were also conducted. A total of 4445 CEAs categorized according to age <65 years (n = 3784) and age ≥65 years (n = 661) were included in the primary analysis. The distributions of ICERs and the likelihood of concluding that the intervention was cost-effective were similar between the 2 age groups. Adjusted odds ratios ranged from 1.132 (95% CI 0.930-1.377) to 1.248 (95% CI 0.970-1.606) (odds ratio >1 indicating that CEAs for age ≥65 years were more likely to conclude the intervention was cost-effective than those for age <65 years). Sensitivity and subgroup analyses found similar results. Our analysis found no systematic differences in published ICERs using quality-adjusted life-years between CEAs for individuals aged ≥65 years and those for individuals aged <65 years. • Critics argue that quality-adjusted life-years discriminate against older people and those with disabilities or receiving palliative care. • Analyses of published cost-effectiveness analyses found no systematic differences in cost-effectiveness conclusions between cost-effectiveness analyses focused on individuals aged ≥65 years and those for individuals aged <65 years. • This empirical evidence can be used to inform debates about the use of quality-adjusted life-years in drug price negotiations, reimbursement, and coverage policy making. [ABSTRACT FROM AUTHOR]

The lightweight designs of automobiles and space shuttles have raised the bar for aluminum (Al) and its alloys. Graphene (GP) has found widespread application in aluminum matrix composites due to its exceptional mechanical, electrical, and thermal properties. In this study, a successful preparation of 6061Al reinforced with GP was achieved through a powder metallurgy method. This involved mixing GP with 6061Al alloy powders via ball milling, followed by hot-pressing sintering to produce the final GP-reinforced Al alloy nanocomposite. The effect of the pH value of the plating solution on the electroless plating of GP has been studied for the first time. The results show that the strength of the aluminum-matrix composites with copper plating has been significantly improved compared with that of the composites without copper plating. When the pH value of the plating solution is 12, the tensile strength of the composites obtained has been increased by 60.41%. Compared with the matrix material, the conductivity of the composite material has also increased. This work shows that the mechanical behavior of graphene-reinforced metal matrix composites (MMCs) can be improved by adjusting the distribution of graphene coatings, which is of great benefit for the preparation of high strength and lightweight composites with good electrical conductivity. [ABSTRACT FROM AUTHOR]

Inland water bodies, being the most active biogeochemical cycle reactors, play a pivotal role in the global carbon cycle and CO2 budget. This study integrates existing observation dataset of CO2 flux (fCO2) in rivers, lakes and reservoirs in China, to elucidate their spatial-temporal patterns and key influencing factors and to reappraise the significance for regional carbon balance. It showed that, the fCO2 in rivers, lakes and reservoirs in China presented significant variability with large range of −379.3–4947.6, −160.1–785.0 and −74.0–1603.1 mg CO2 m−2 h−1, respectively. The median of the fCO2 in rivers was of 228.5 mg CO2 m−2 h−1, observably higher than these in lakes and reservoirs (26.0 and 28.3 mg CO2 m−2 h−1, respectively). The fCO2 in rivers and reservoirs exhibited similar decreasing trend from south to north as a result of universal climate restraint, the averaged fCO2 in Pearl River and Yangtze River basins showed much higher than that in Northeastern rivers. While, the averaged fCO2 in the Mongolia-Xinjiang lake district and the Northeast lake district were higher than other lake districts, followed by the Qinghai-Xizang lake district, and the Eastern and Yungui lake district were generally low, contradicting the climatic restriction. The water primary production enhancement resulting from human activities was the main driver of spatial variation in the fCO2 in lakes. Meanwhile, the fCO2 in rivers presented seasonal pattern with higher wet season than dry season, while opposite patterns were found in lakes and reservoirs. Seasonal temperature, precipitation and water primary production were main factors. Furthermore, it showed pH was a key factor indicating the variability of the fCO2 levels either in rivers, lakes or in reservoirs. In lakes, the fCO2 is closely linked to chlorophyll a (Chl-a) and dissolved oxygen (DO), whereas, the fCO2 in rivers is primarily associated with organic carbon (OC) and total nitrogen (TN), highlighting the diverse controlling mechanisms of fCO2 in various inland water types. In addition, we found that water body sizes play an important role in regulating the fCO2 levels, and small waters act as hotspots of CO2 flux. Additionally, widespread urbanization and agricultural activities may enhance CO2 emissions from rivers but potentially mitigating that from lakes. Nevertheless, the comprehensive impact of these factors on CO2 emissions in inland water requires further evaluation. Based on the extrapolation method, we re-estimated that the total CO2 emission of inland waters in China is approximately 117.3 Tg yr−1, which could offset 4.6%–12.8% of the total land carbon sink in China. [ABSTRACT FROM AUTHOR]

Background: Ionizing radiation can induce bystander effects (RIBE), and Astragalus polysaccharides (APS) have a protective effect against RIBE. It has been proved that RIBE occurred and APS played the inhibitory effects on the RIBE when radiation was carried out only one time. However, whether RIBE happened by multiple irradiations and the effects of APS on the RIBE are unclear. This study aimed to investigate whether APS suppress RIBE damage induced by multiple irradiations. Materials and Methods: A549 cells were irradiated with 2 Gy X-rays to obtain a conditioned medium. Bone mesenchymal stem cells (BMSCs) was incubated with the conditioned medium 5 times every 3 days or APS. Cell proliferation was detected by CCK-8 and colony formation assay, and genomic instability and DNA damages were detected by the micronucleus and immunofluorescence assay. The protein associated with methylation and cancer-associated proteins in BMSCs were detected by western blot. Results: After five stimulations with a conditioned medium, the proliferative capacity of BMSCs decreased; APS pre-intervention promoted the proliferation of BMSCs. And conditional medium intervention increased the micronucleus rate and a number of 53BP1 foci; APS pre-intervention reduced the micronucleus rate and number of 53BP1 foci. In addition, the conditional medium intervention reduced the expression of methylation-related proteins and increased the expression of cancer-related proteins, while APS pre-intervention reversed this trend. Conclusion: Irradiated A549 conditioned medium can induce RIBE of BMSCs, which might be related to methylation and cancer-associated proteins and APS may block RIBE by multiple irradiations in BMSCs. [ABSTRACT FROM AUTHOR]

Background: The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. Methods: A model of bleomycin-induced pulmonary fibrosis was established, followed by treatment with bortezomib. Tissue samples were collected for analysis of immune cell subsets and functional assessment by flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors, as well as the characteristics of cell populations. Results: Here, we observed that the expression of CXCL16 and CXCR6 was elevated in the lung tissue of a pulmonary fibrosis model. In the context of pulmonary fibrosis or TGF-β1 stimulation in vitro, macrophages exhibited an M2-polarized phenotype and secreted more CXCL16 than those of the control group. Moreover, flow cytometry revealed increased expression levels of CD69 and CXCR6 in pulmonary CD4 T cells during fibrosis progression. The administration of bortezomib alleviated bleomycin-induced pulmonary fibrosis, accompanied by reduced ratio of M2-polarized macrophages and decreased accumulation of CD4 T cells expressing CXCR6. Conclusions: Our findings provide insights into the key immune players involved in bleomycin-induced pulmonary fibrosis and offer preclinical evidence supporting the repurposing strategy and combination approaches to reduce lung fibrosis. [ABSTRACT FROM AUTHOR]

An ultrahigh-performance magnesium/sodium hybrid-ion battery (MNHB) is developed using ternary CoSe/NiSe2/CuSe2 (CNCS) "micro-flowers" as cathode materials, working with a coordinative [Mg2Cl2][AlCl4]2 and bis(trifluoroethylsulfonyl)imide anionic sodium salt in triglyme electrolyte. After 2000 cycles at 2.0 A g−1, the MNHB shows a stable capacity of 115.5 mA h g−1 and a high Coulombic efficiency exceeding 99.8%. The battery shows very rapid charging, and good stability in extreme environments, providing new opportunities to develop other hybrid-ion systems. [ABSTRACT FROM AUTHOR]

Let G be a simple connected graph. The eccentric distance sum (EDS) of G is defined as ξ d (G) = ∑ v ∈ V (G) ɛ G (v) D G (v) , where ɛ G (v) is the eccentricity of the vertex v and D G (v) = ∑ u ∈ V (G) d G (u , v) is the sum of all distances from the vertex v. We denote the set of trees with order n and maximum degree Δ by T n , Δ. In 2015, the tree having the maximal EDS among all trees in T n , Δ was determined (Miao, 2015). In this paper, the tree having the second maximal EDS among all trees in T n , Δ is characterized. [ABSTRACT FROM AUTHOR]

Background: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8+T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. Methods: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used. Chimeric mice-deficient of PGRN (Grn−/−) in bone marrow (BM) compartment was also generated. Association of PGRN expression with chemokine production or BCa development was investigated by histological and immunological assays. Results: We found PGRN was involved in exhaustion of cytotoxic CD8+T cell in BCa with the increasing expressions of M2 markers and intercellular cell adhesion molecule-1 (ICAM-1) on macrophages. Specifically, ablation of PGRN in PY8119 cells reduced tumor burden, accompanied by the infiltrating of cytotoxic CD8+T cells into tumor nests. Moreover, our result revealed that blockade of PD-1 in PGRN-depleted tumors exhibited better antitumor effect in vivo and significantly decreased tumor burden. Conclusion: These findings suggest that inhibition of PGRN may act as a potential immune-therapeutic strategy by recovering infiltration of CD8+T cell in BCa tissue and thereby enhancing the response to anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the leading cause of premature death. The death of cardiomyocytes (CMs) and the dysfunction of the remaining viable CMs are the main pathological factors contributing to heart failure (HF) following MI. This study aims to determine the transcriptional profile of CMs and investigate the heterogeneity among CMs under hypoxic conditions. Single-cell atlases of the heart in both the sham and MI groups were developed using single-cell data (GSE214611) downloaded from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The heterogeneity among CMs was explored through various analyses including enrichment, pseudo time, and intercellular communication analysis. The marker gene of C5 was identified using differential expression analysis (DEA). Real-time polymerase chain reaction (RT-PCR), bulk RNA-sequencing dataset analysis, western blotting, immunohistochemical and immunofluorescence staining, Mito-Tracker staining, TUNEL staining, and flow cytometry analysis were conducted to validate the impact of the marker gene on mitochondrial function and cell apoptosis of CMs under hypoxic conditions. We identified a cell subcluster named C5 that exhibited a close association with mitochondrial malfunction and cellular apoptosis characteristics, and identified Slc25a4 as a significant biomarker of C5. Furthermore, our findings indicated that the expression of Slc25a4 was increased in failing hearts, and the downregulation of Slc25a4 improved mitochondrial function and reduced cell apoptosis. Our study significantly identified a distinct subcluster of CMs that exhibited strong associations with ventricular remodeling following MI. Slc25a4 served as the hub gene for C5, highlighting its significant potential as a novel therapeutic target for MI. [ABSTRACT FROM AUTHOR]

Prenylated stilbenoids possess a range of biological activities, including anti-inflammatory, antioxidant, antidiabetic, anticancer, neuroprotective and vasorelaxant properties. However, their potential is limited by the scarcity of these compounds in nature. In this study, we present an eco-friendly biosynthetic method for producing prenylated resveratrol in Escherichia coli. By co-expressing the MVA pathway for DMAPP synthesis with a prenyltransferase, we successfully achieved in vivo prenylation of resveratrol. We then reconstructed a novel biosynthetic pathway for 2-C-prenyl resveratrol by integrating the resveratrol pathway. Through careful metabolic flux engineering to accumulate acetyl-CoA and malonyl-CoA, we created a high-yield strain that produced 2-C-prenyl resveratrol, achieving a significant titer of 68.4 mg L−1 in flask cultures. This research marks the first microbial production of prenylated stilbenoids, providing a foundation for sustainable green production of these compounds. [ABSTRACT FROM AUTHOR]

Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis. The tumor immune microenvironment was analyzed using the CIBERSORT algorithm, followed by functional analysis and immunotherapy efficacy prediction by gene set variation analysis. The role of model genes in regulating endometrial cancer in vitro was verified by CCK‐8, colony formation, wound healing, and transabdominal invasion assays, and verified in vivo by subcutaneous tumor transplantation in nude mice. A prognostic model containing 14 genes was constructed and validated in 3 cohorts and clinical samples. The results showed differences in the infiltration of immune cells between the high‐risk and low‐risk groups, and that the high‐risk group may respond better to immunotherapy. Experiments in vitro confirmed that knockdown of epoxide hydrolase 2 (EPHX2) and acyl‐CoA oxidase like (ACOXL) had an inhibitory effect on EC cells, as did overexpression of hematopoietic prostaglandin D synthase (HPGDS). The same results were obtained in experiments in vivo. Prognostic models related to fatty acid metabolism can be used for the risk assessment of endometrial cancer patients. Experiments in vitro and in vivo confirmed that the key genes HPGDS, EPHX2, and ACOXL in the prognostic model may affect the development of endometrial cancer. [ABSTRACT FROM AUTHOR]

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level. [ABSTRACT FROM AUTHOR]

Accurate modeling and parameter identification of photovoltaic (PV) cells is a difficult task due to the nonlinear characteristics of PV cells. The goal of this paper is to propose a multi strategy sine–cosine algorithm (SCA), named enhanced sine–cosine algorithm (ESCA), to evaluate nondirectly measurable parameters of PV cells. The ESCA introduces the concept of population average position to increase the population exploration ability, and at the same time introduces the personal destination agent mutation mechanism and competitive selection mechanism into SCA to provide more search directions for ESCA while ensuring the search accuracy and diversity maintenance. To prove that the proposed ESCA is the best choice for extracting nondirectly measurable parameters of PV cells, ESCA is evaluated by the single‐diode model, the double‐diode model, the three‐diode model, and the photovoltaic module model (PVM), and compared with eight existing popular methods. Experimental results show that ESCA outperforms similar methods in terms of diversity maintenance, high efficiency, and stability. In particular, the proposed ESCA method is less than the SCA by 0.081, 0.144, and 0.578 in the standard deviation statistics metrics of the three PVM models (PV‐PWP201, STM6‐40/36, and STP6‐120/36), respectively. Therefore, the proposed ESCA is an accurate and reliable method for parameter identification of PV cells. [ABSTRACT FROM AUTHOR]

Neuromorphic ferroelectric transistors integrating sensing and memory capabilities for photoelectric stimuli have provided a remarkable platform for multifunctional bionic vision. However, most hardware demonstrations utilizing ferroelectric transistors cannot implement multiple bio‐visual functions simultaneously under a small operating voltage with scalable material systems, which reduces the compatibility with complementary metal‐oxide‐semiconductor (CMOS) technology and blocks further bio‐visual applications. Herein, an optoelectronic transistor gated is constructed with ferroelectric LiNbO3, which exhibits sensing‐memory‐processing functions and logic integration simultaneously under a low operating voltage (≈1.5 V). Benefiting from the programmable photoinduction and strong ferroelectric polarization, the reliable and highly controllable synaptic characteristics and the bio‐visual selective learning behavior are successfully demonstrated. A high recognition accuracy (≈94.5%) in simulations is also achieved due to the unique linear synaptic plasticity. Furthermore, based on dual‐wavelength modulation, the full‐optical logics “AND” and “OR” are established within the same device. This work provides novel opportunities for the complex multifunctional bionic vision and toward large‐scale integration compatible with silicon‐based CMOS processes. [ABSTRACT FROM AUTHOR]

Key message: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes. [ABSTRACT FROM AUTHOR]

This study explored the effect of parental emotion socialization behavior (ESB) on depressive symptoms with a focus on the mediating effect of emotion regulation and the moderating role of family cohesion. A total of 236 Chinese adolescents were surveyed and reported on parental ESB, family cohesion, emotion dysregulation, and depressive symptoms. The results indicated that parental ESB toward negative emotions was associated with adolescents' depressive symptoms, as mediated by emotion dysregulation. Moreover, higher levels of family cohesion both enhanced the negative relationships between supportive ESB toward anger/sadness and emotion dysregulation and strengthened the positive relationship between non-supportive parental ESB toward sadness and emotion dysregulation. These findings clarify the interactive effects of multiple components of emotional parenting, reveal the double-edged effects of family cohesion in the association between parental ESB and depressive symptoms in adolescents, and highlight the importance of evaluating the family emotional context in research and clinical interventions. [ABSTRACT FROM AUTHOR]

Background: Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. Methods: Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. Results: We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. Conclusions: Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype. [ABSTRACT FROM AUTHOR]

Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet. To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV. High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques. MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells. Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV. • MiR-1469 derived from plasma exosomes of patients with non-segmental vitiligo is significantly elevated. • MiR-1469 is negatively correlated with the frequency of IFN-γ+ natural killer cells in non-segmental vitiligo. • MiR-1469 downregulates proliferation viability and IFN-γ secretion of natural killer cells by inhibiting CD122. [ABSTRACT FROM AUTHOR]

Purpose: Metaheuristic algorithms based on biology, evolutionary theory and physical principles, have been widely developed for complex global optimization. This paper aims to present a new hybrid optimization algorithm that combines the characteristics of biogeography-based optimization (BBO), invasive weed optimization (IWO) and genetic algorithms (GAs). Design/methodology/approach: The significant difference between the new algorithm and original optimizers is a periodic selection scheme for offspring. The selection criterion is a function of cyclic discharge and the fitness of populations. It differs from traditional optimization methods where the elite always gains advantages. With this method, fitter populations may still be rejected, while poorer ones might be likely retained. The selection scheme is applied to help escape from local optima and maintain solution diversity. Findings: The efficiency of the proposed method is tested on 13 high-dimensional, nonlinear benchmark functions and a homogenous slope stability problem. The results of the benchmark function show that the new method performs well in terms of accuracy and solution diversity. The algorithm converges with a magnitude of 10-4, compared to 102 in BBO and 10-2 in IWO. In the slope stability problem, the safety factor acquired by the analogy of slope erosion (ASE) is closer to the recommended value. Originality/value: This paper introduces a periodic selection strategy and constructs a hybrid optimizer, which enhances the global exploration capacity of metaheuristic algorithms. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) is one of the most toxic mycotoxins widely found in agricultural products. In this study, a sensitive enzyme-linked immunosorbent assay (ELISA) integrated with immunoaffinity column extraction for the detection of ZEN in food and feed samples was developed. A ZEN derivative containing a carboxylic group was first synthesized and then linked to bovine serum albumin (BSA). The formed ZEN–BSA conjugate was used as the immunogen for the production of the monoclonal antibody (mAb) against ZEN. The hybridoma clones (1G5) capable of secreting antibodies against ZEN were successfully selected. Based on this mAb, the IC50 and LOD of the ELISA for ZEN were 0.37 ng mL−1 and 0.04 ng mL−1, respectively, which were 1.6–308.1 times lower than those in the published ELISAs, indicating the high sensitivity of our assay. There was no cross-reactivity of the mAb with other four mycotoxins (patulin, AFB1, DON, and OTA). Due to the high similarity in molecular structures among ZEN and its homologs (α-zearalanol, β-zearalanol, zearalanone, α-zearalenol, β-zearalenol), the CR values of the mAb with the homologs were within 3.59%–105.71%. Taking advantage of plenty of mAb, the immunoaffinity column was prepared by immobilizing the mAb on Sepharose-4B gel and filling it into an SPE column. ZEN spiked samples (corn, wheat, feed) were extracted using an immunoaffinity column and measured by ELISA and HPLC-FLD simultaneously. The recoveries of the ELISA for ZEN in the spiked samples were 92.46–105.48% with RSDs of 4.87–10.11%. A good correlation between ELISA (x) and HPLC-FLD (y) with the linear regression equation y = 1.0589x + 1.43815 (R2 = 0.998, n = 6) was obtained. To verify the applicability, the proposed ELISA was also applied to some real samples randomly collected from a local market. It was proven that the newly produced mAb-based ELISA was a feasible and sensitive method for the detection of ZEN in food and feed samples. [ABSTRACT FROM AUTHOR]

Parents and adolescents often hold discrepant perceptions of parental emotion socialization, which reflect misunderstandings in parent-adolescent communication on emotions and have potential detrimental effects on mental health of adolescents. The present study investigated the associations between parent-adolescent congruence and discrepancy in parental emotion socialization perception to two specific negative emotions (anger and sadness) and depressive symptoms in Chinese adolescents. A total of 372 adolescents (48.4% female, Mage = 13.43, SDage = 0.49) and their parents (79.6% mother, Mage = 41.15, SDage = 5.46) participated in this study. Both parents and adolescents reported perceived parental emotion socialization to anger and sadness, and adolescents reported depressive symptoms. Data were analyzed using polynomial regression and response surface analyses. Both congruence and discrepancy in parent and adolescent's reports were associated with adolescent depressive symptoms. A higher level of adolescent depressive symptoms was associated with higher parent-adolescent congruence in supportive responses to anger, sadness, and nonsupportive responses to anger. A higher level of depressive symptoms was associated with inconsistent reporting of supportive responses to sadness and nonsupportive responses to anger (only when parents had a more positive view than adolescents). This study highlights the significance of evaluating parent-child communication process by assessing perceived emotion socialization from both parents and adolescents and analyzing the reporting congruence and discrepancy. It also suggests that enhancing effective communication regarding parental emotion socialization could be a promising target for adolescent mental health promotion programs. [ABSTRACT FROM AUTHOR]

In the transfer learning paradigm, models that are pre-trained on large datasets are used as the foundation models for various downstream tasks. However, this paradigm exposes downstream practitioners to data poisoning threats, as attackers can inject malicious samples into the re-training datasets to manipulate the behavior of models in downstream tasks. In this work, we propose a defense strategy that significantly reduces the success rate of various data poisoning attacks in downstream tasks. Our defense aims to pre-train a robust foundation model by reducing adversarial feature distance and increasing inter-class feature distance. Experiments demonstrate the excellent defense performance of the proposed strategy towards state-of-the-art clean-label poisoning attacks in the transfer learning scenario. [ABSTRACT FROM AUTHOR]

Aims: Cross-sectional studies have demonstrated the association of skeletal muscle mass with metabolic-associated fatty liver disease (MAFLD), while longitudinal data are scarce. We aimed to explore the impact of changes in relative skeletal muscle mass on the MAFLD treatment response. Methods: MAFLD patients undergoing magnetic resonance imaging-based proton density fat fraction for liver fat content (LFC) assessments and bioelectrical impedance analysis before and after treatment (orlistat, meal replacement, lifestyle modifications) were enrolled. Appendicular muscle mass (ASM) was adjusted by weight (ASM/W). Results: Overall, 256 participants were recruited and divided into two groups: with an ASM/W increase (n=166) and without an ASM/W increase (n=90). There was a great reduction in LFC in the group with an ASM/W increase (16.9% versus 8.2%, P < 0.001). However, the change in LFC in the group without an ASM/W increase showed no significant difference (12.5% versus 15.0%, P > 0.05). △ASM/W Follow-up-Baseline [odds ratio (OR)=1.48, 95% confidence interval (CI) 1.05-2.07, P = 0.024] and △total fat mass (OR=1.45, 95% CI 1.12-1.87, P = 0.004) were independent predictors for steatosis improvement (relative reduction of LFC ≥ 30%). The subgroup analysis showed that, despite without weight loss, decrease in HOMA-IR (OR=6.21, 95% CI 1.28-30.13, P=0.023), △total fat mass Baseline -Follow-up (OR=3.48, 95% CI 1.95-6.21, P <0.001 and △ASM/W Follow-up-Baseline (OR=2.13, 95% CI 1.12-4.05, P=0.022) independently predicted steatosis improvement. Conclusions: ASM/W increase and loss of total fat mass benefit the resolution of liver steatosis, independent of weight loss for MAFLD. [ABSTRACT FROM AUTHOR]

The aim of the work described here was to investigate the efficacy and potential mechanisms of low-intensity pulsed ultrasound (LIPUS) for the treatment of arthrogenic contracture induced by immobilization in rabbits. The left knee joint of rabbits was immobilized for 6 wk to establish the model of extending knee joint contracture. The rabbits were divided into a control group (C), a group immobilized for 6 wk (IM-6w), a group remobilized for 1 wk (RM-1w), a group subjected to LIPUS intervention for 1 wk (LIPUS-1w), a group remobilized for 2 wk (RM-2w) and a group subjected to LIPUS intervention for 2 wk (LIPUS-2w). The degrees of arthrogenic contracture and joint capsule fibrosis were assessed, as were the levels of reactive oxygen species (ROS) and the activation status of the TGF-β1/Smad signaling pathway in the joint capsule. After immobilization for 6 wk, the degrees of arthrogenic contracture and joint capsule fibrosis increased. The ROS level increased, as evidenced by an increase in malondialdehyde content and a decrease in superoxide dismutase content. In addition, the TGF-β1/Smad signaling pathway was significantly activated. The degrees of knee joint contracture increased in the first week after remobilization and decreased in the second week. Furthermore, joint capsule fibrosis continued to develop during the 2 wk of remobilization, and the ROS level increased, while the TGF-β1/Smad signaling pathway was significantly activated. LIPUS effectively reduced the level of ROS in the joint capsule, which further inhibited activation of the TGF-β1/Smad signaling pathway, thereby improving joint capsule fibrosis and reducing arthrogenic contracture. The high ROS levels and overactivation of the TGF-β1/Smad signaling pathway may be reasons why immobilization induces knee joint capsule fibrosis. LIPUS can alleviate the degree of knee joint capsule fibrosis induced by immobilization by inhibiting the production of ROS and the activation of the TGF-β1/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

The integration of the roles of caregivers and interventionists is important in parenting a child with autism spectrum disorder (ASD). However, an instrument to measure dual‐role behaviors is unavailable. This study developed and validated the Dual Role Behaviors Scale for parents of autistic children (DRBS‐A). Initial items were generated using the interview transcripts of a previous qualitative study. The initial scale was administered to 422 parents. Data were randomly halved to generate Samples 1 and 2. Exploratory factor analysis conducted using Sample 1 (autism spectrum disorder = 216) screened items based on factor loadings and explored the scale's structure. Confirmatory factor analysis (CFA) conducted with Sample 2 (N = 206) examined structural validity. Among the participants, 121 (Sample 3) derived from the two samples were followed up after 1 month to examine the test–retest reliability. Convergent validity was examined with another sample of 105 parents (Sample 4). The formal version of the DRBS‐A comprised 20 items across four dimensions: parental acceptance, parental disengagement, persistence in interventions, and punishment in interventions. The four‐factor structure with two higher order factors was supported by the CFA results (χ2 = 290.90, df = 165, CFI = 0.94, TLI = 0.93, RMSEA = 0.061, SRMR = 0.063). The subscales' test–retest reliabilities ranged from 0.61 to 0.78. The internal consistencies were satisfactory (Cronbach's αs: 0.67–0.93). Convergent validity was supported by correlations of the DRBS‐A dimensions with parental involvement and positive parenting practice. Other factors related to dual‐role behaviors were also explored. The DRBS‐A has good validity and reliability and can be used to explore the effects of role integration. [ABSTRACT FROM AUTHOR]

Depression is one of the most common psychological problems in adolescence. Familial and school-related factors are closely related to adolescents' depression, but their combined effects need further examination. The purpose of this study was to explore the combined effects of risk/protective factors of depression in family and school domains using a sample of Chinese adolescents differing in gender, age group and left-behind status. A total of 2455 Chinese students in primary and secondary school participated in the cross-sectional survey and reported multiple risk/protective factors in family and school environments and depressive symptoms. Association rule mining, a machine learning method, was used in the data analyses to identify the correlation between risk/protective factor combinations and depression. We found that (1) Family cohesion, family conflict, peer support, and teacher support emerged as the strongest factors associated with adolescent depression; (2) The combination of these aforementioned factors further strengthened their association with depression; (3) Female gender, middle school students, and family socioeconomic disadvantages attenuated the protective effects of positive relational factors while exacerbating the deleterious effects of negative relational factors; (4) For individuals at risk, lack of mental health education resources at school intensified the negative impact; (5) The risk and protective factors of depression varied according to gender, age stage and left-behind status. In conclusion, the findings shed light on the identification of high-risk adolescents for depression and underscore the importance of tailored programs targeting specific subgroups based on gender, age, or left-behind status. [ABSTRACT FROM AUTHOR]

Phase separation of polymer blends has attracted much interest in designing high-performance materials with specific mechanical and dielectric properties. To this end, three types of poly(methacrylic ester)s, including poly(methyl methacrylate) (PMMA), poly(butyl methacrylate) (PBMA), and poly(isobutyl methacrylate) [P(iBMA)], have been incorporated in the poly(vinylidene fluoride-co-hexafluoropropylene) [P(VDF-HFP)] matrix, respectively. As exemplified in P(VDF-HFP)/P(iBMA) blended films, a conspicuous phase separation is experimentally observed and the blended film presents an enhanced Young's modulus and a one-fold increment in the elongation over the pristine P(VDF-HFP). The excellent plasticity is benefited from the interfacial regions between the two phases, which could effectively pin the cracks and retard the slippage under deformation. Simultaneously, an ultra-high Weibull breakdown strength (∼774 MV/m) is obtained in the blends, benefiting from the improved Young's modulus and excellent plasticity. The blends are endowed with an excellent energy storage density (∼21 J/cm3 at 830 MV/m), along with an impressive cycling stability. In contrary, P(VDF-HFP)/PMMA and P(VDF-HFP)/PBMA blended films sacrifice the plasticity due to the scarcity of phase separation; therefore, even though Young's moduli have been improved, there is no remarkable improvement for breakdown strengths and energy storage performances. The experimental results are augmented by molecular dynamics simulations. This contribution provides a facile approach to develop high-performance polymer dielectric materials through a phase separation design and emphasize the importance of plasticity for breakdown strength. [ABSTRACT FROM AUTHOR]

Objective: The goal of this research was to determine whether or not there is a saturation effect and whether or not the visceral adiposity index (VAI) correlates with bone mineral density (BMD) in adult Americans. Methods: This study used multivariate logistic regression models to examine the association between VAI and total femur BMD, drawing on the most up-to-date data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. Saturation levels and non-linear connections were calculated using a smooth curve-fitting algorithm and an investigation of saturation effects. Subgroup analyses and interaction tests were also conducted. Results: This study ultimately recruited 6257 individuals aged 20 years or older. According to multivariate regression analysis, those with high VAI scores exhibited higher total femur BMD. Total femur BMD was greater in the highest VAI quartile (Q4: 0.060 g/cm2) after adjustment than in the lowest VAI quartile (Q1) (P < 0.05). After controlling for variables, subgroup analysis failed to reveal any significant interaction effects. Furthermore, the study determined that VAI and BMD exhibited a specific saturation effect through the investigation of the saturation effect and the fitting of smooth curves. Saturation effect investigation of total femur BMD using VAI revealed a saturation value of 3.3. Conclusion: The present study uncovered a non-linear relationship between VAI and total femur BMD, which exhibited a saturation effect. [ABSTRACT FROM AUTHOR]

The current study aimed to examine the role of cognitive emotion regulation as a mediator in the association between pandemic-related job stressors and the psychological symptoms of healthcare professionals in the late stage of the COVID-19 pandemic, and the role of reflective functioning as a resilience factor moderating both the associations of pandemic-related job stressors and cognitive emotion regulation, as well as psychological symptoms.Methods: This cross-sectional survey conducted in October 2020 included 2393 healthcare professionals working in departments with a high risk of exposure to COVID-19 from 22 hospitals in Beijing, China. Participants were asked to complete questionnaires measuring pandemic-related job stressors, anxiety, depression, reflective functioning, and cognitive emotion regulation strategies. Path analyses were performed to examine the hypothesized model.Results: Epidemic-related job stressors had significant direct effects on depression (β=0.31, p< 0.001) and anxiety symptoms (β=0.29, p< 0.001) and the indirect effects through mediation of maladaptive cognitive regulation were also significant (for depression, indirect effect=0.06, SE=0.01, CI=[0.04, 0.07]; for anxiety, indirect effect=0.06, SE=0.01, CI=[0.04, 0.08]). The dimension of certainty about mental states in the reflective functioning questionnaire (RFQc) moderated the direct effect of pandemic-related job stressors on depression (β=− 0.05, p< 0.001) and moderated the effect of job stressors on maladaptive cognitive regulation (β=0.06, p< 0.001).Conclusion: The results shed light on the roles of cognitive emotion regulation and reflective functioning in coping with pandemic-related job stressors in frontline healthcare workers in periods of dealing with major infectious diseases. The findings have implications for developing interventions for healthcare workers in need. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. There is no cure currently. The discovery that mutations in the gene SOD1 are a cause of ALS marks a breakthrough in the search for effective treatments for ALS. SOD1 is an antioxidant that is highly expressed in motor neurons. Human SOD1 is prone to aberrant modifications. Familial ALS-linked SOD1 variants are particularly susceptible to aberrant modifications. Once modified, SOD1 undergoes conformational changes and becomes misfolded. This study aims to determine the effect of selective removal of misfolded SOD1 on the pathogenesis of ALS. Methods: Based on the chaperone-mediated protein degradation pathway, we designed a fusion peptide named CT4 and tested its efficiency in knocking down intracellularly misfolded SOD1 and its efficacy in modifying the pathogenesis of ALS. Results: Expression of the plasmid carrying the CT4 sequence in human HEK cells resulted in robust removal of misfolded SOD1 induced by serum deprivation. Co-transfection of the CT4 and the G93A-hSOD1 plasmids at various ratios demonstrated a dose-dependent knockdown efficiency on G93A-hSOD1, which could be further increased when misfolding of SOD1 was enhanced by serum deprivation. Application of the full-length CT4 peptide to primary cultures of neurons expressing the G93A variant of human SOD1 revealed a time course of the degradation of misfolded SOD1; misfolded SOD1 started to decrease by 2 h after the application of CT4 and disappeared by 7 h. Intravenous administration of the CT4 peptide at 10 mg/kg to the G93A-hSOD1 reduced human SOD1 in spinal cord tissue by 68% in 24 h and 54% in 48 h in presymptomatic ALS mice. Intraperitoneal administration of the CT4 peptide starting from 60 days of age significantly delayed the onset of ALS and prolonged the lifespan of the G93A-hSOD1 mice. Conclusions: The CT4 peptide directs the degradation of misfolded SOD1 in high efficiency and specificity. Selective removal of misfolded SOD1 significantly delays the onset of ALS, demonstrating that misfolded SOD1 is the toxic form of SOD1 that causes motor neuron death. The study proves that selective removal of misfolded SOD1 is a promising treatment for ALS. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicles (UAVs) providing additional on-demand communication and computing services have become a promising technology. However, the limited energy supply of UAVs, which constrains their service duration, has emerged as an obstacle in UAV-enabled networks. In this context, a novel task offloading framework is proposed in UAV-enabled mobile edge computing (MEC) networks. Specifically, heterogeneous UAVs with different communication and computing capabilities are considered and the energy consumption of UAVs is minimized via jointly optimizing user association and UAV deployment. The optimal transport theory is introduced to analyze the user association sub-problem, and the UAV deployment for each sub-region is determined by a dragonfly algorithm (DA). Simulation results show that the energy consumption performance is significantly improved by the proposed algorithm. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that immobilization enhances reactive oxygen species (ROS) production and mitophagy activity in atrophic skeletal muscle. However, there are relatively few studies examining the biological changes and underlying mechanisms of skeletal muscle during remobilization. In this study, we aimed to investigate the effects of remobilization on skeletal muscle and explore the role of BNIP3-dependent mitophagy in this process. Methods: Thirty rats were randomly divided into six groups based on immobilization and remobilization time: control (C), immobilization for two weeks (I-2w), and remobilization for one day (R-1d), three days (R-3d), seven days (R-7d), and two weeks (R-2w). At the end of the experimental period, the rectus femoris muscles were removed and weighed, and the measurements were expressed as the ratio of muscle wet weight to body weight (MWW/BW). Sirius Red staining was performed to calculate the values of cross-sectional area (CSA) of rectus femoris. Oxidative fluorescent dihydroethidium was used to evaluate the production of ROS, and the levels of superoxide dismutase (SOD) were also detected. The morphological changes of mitochondria and the formation of mitophagosomes in rectus femoris were examined and evaluated by transmission electron microscope. Immunofluorescence was employed to detect the co-localization of BNIP3 and LC3B, while Western blot analysis was performed to quantify the levels of proteins associated with mitophagy and mitochondrial biogenesis. The total ATP content of the rectus femoris was determined to assess mitochondrial function. Results: Within the first three days of remobilization, the rats demonstrated decreased MWW/BW, CSA, and ATP concentration, along with increased ROS production and HIF-1α protein levels in the rectus femoris. Results also indicated that remobilization triggered BNIP3-dependent mitophagy, supported by the accumulation of mitophagosomes, the degradation of mitochondrial proteins (including HSP60 and COX IV), the elevation of BNIP3-dependent mitophagy protein markers (including BNIP3, LC3B-II/LC3B-I, and Beclin-1), and the accumulation of puncta representing co-localization of BNIP3 with LC3B. Additionally, PGC-1α, which is involved in the regulation of mitochondrial biogenesis, was upregulated within the first seven days of remobilization to counteract this adverse effect. Conclusion: Our findings suggested that BNIP3-denpendent mitophagy was sustained activated at the early stages of remobilization, and it might contribute to the worsening of skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

Objectives: To provide clinical guidance for early diagnosis and effective management of primary cesarean scar choriocarcinoma, which is an extremely rare but highly malignant trophoblastic tumor. Methods: This retrospective case series summarized the clinical courses of seven patients diagnosed with cesarean scar choriocarcinoma. Results: We identified two patients in our institution with cesarean scar choriocarcinoma. In addition, details of the previous five patients were extracted from databases and analyzed to provide more clinical information. The seven patients had an average age of 31.14 years, their tumor sizes ranged from 2.0 to 6.5 cm, and their pretreatment serum β‐human chorionic gonadotropin (β‐hCG) levels ranged from 3664 to 312 468 mIU/mL. All the patients were categorized as having FIGO Stage I disease, with four patients at low risk and three at high risk. Six of the seven were misdiagnosed with ectopic pregnancy before pathologic examination. Conclusions: Clinicians should pay attention to masses in cesarean scar and to continuous elevation of serum β‐hCG levels after treatment. When cesarean scar choriocarcinoma is suspected, diagnostic surgery can be chosen for tentative treatment and pathologic sampling. Salvage EMA‐CO chemotherapy (etoposide, actinomycin D, methotrexate, cyclophosphamide and vincristine) should be performed as early as possible to prevent metastasis and recurrence after pathologic diagnosis. Synopsis: Clinical courses of seven patients diagnosed with primary cesarean scar choriocarcinoma are summarized to provide clinical references for early diagnosis and effective management. [ABSTRACT FROM AUTHOR]

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein–Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Background: Recent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options. Methods: We constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009–2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars. Results: In Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%. Interpretation: For patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China. [ABSTRACT FROM AUTHOR]

• Brain hypoxia–ischemia (HI) induces brain structural and functional injury. • Desflurane post-treatment reduces HI-induced brain injury. • Transient receptor potential ankyrin 1 contributes to HI-induced brain injury. Perinatal hypoxic-ischemic (HI) brain injury leads to mortality and morbidity in neonates and children. There are no effective and practical methods to attenuate this brain injury. This study determined whether desflurane, a volatile anesthetic with limited effect on the cardiovascular system, protected against HI-induced brain damage and the role of transient receptor potential ankyrin 1 (TRPA1), a mediator for simulated ischemia-induced myelin damage, in this protection. Seven-day-old male and female Sprague-Dawley rats had brain HI. They were exposed to 4.8%, 7.6% or 11.4% desflurane immediately or 4.8% desflurane at 0.5, 1 or 2 h after the HI. Brain tissue loss was evaluated 7 days later. Neurological functions and brain structures of rats with HI and 4.8% desflurane post-treatment were evaluated 4 weeks after the HI. TRPA1 expression was determined by Western blotting. HC-030031, a TRPA1 inhibitor, was used to determine the role of TRPA1 in the HI-induced brain injury. HI induced brain tissue and neuronal loss, which was attenuated by all tested concentrations of desflurane. Desflurane post-treatment also improved motor function, learning and memory in rats with brain HI. Brain HI increased the expression of TRPA1 and this increase was inhibited by desflurane. TRPA1 inhibition reduced HI-induced brain tissue loss and impairment of learning and memory. However, the combination of TRPA1 inhibition and desflurane post-treatment did not preserve brain tissues, learning and memory better than TRPA1 inhibition or desflurane post-treatment alone. Our results suggest that desflurane post-treatment induces neuroprotection against neonatal HI. This effect may be mediated by inhibiting TRPA1. [ABSTRACT FROM AUTHOR]

In order to improve the dispersibility and uneven distribution of carbon nanotubes (CNTs) in the copper matrix, the surface of CNTs were modified to enhance their dispersibility in the copper matrix. In this paper, different concentrations (7.5%, 15%, 30%) of HNO3 were used to functionalize the surface of CNTs to improve the chemical inertness of CNTs, and surface modification was performed on the purified and de-hybridized CNTs to make the CNTs better dispersed in the metal matrix. At the same time, the mechanical properties and electrical conductivity of the carbon nanotube-reinforced copper-based composites were analyzed. According to research result, 15% HNO3 combined with subsequent surface treatment have the best effect on surface modification of CNTs, significantly improving the dispersibility of CNTs and better exerting the excellent coordination effect of CNTs in copper-based composite. In addition, it is confirmed that the obtained Cu-CNTs/Cu composites have excellent comprehensive properties, which provide a new idea to improve the characteristics of copper-based composites doped with CNTs. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Splenic tissue outside the normal anatomical site can be collectively referred to as ectopic spleen. Clinically, the commonest causes of ectopic spleen include accessory spleen, splenic tissue implantation, and splenogonadal fusion (SGF). Accessory spleen is mostly caused by congenital dysplasia, is mostly located near the spleen, and may be supplied by the splenic artery. Splenic implantation is mostly caused by autologous spleen tissue transplantation caused by trauma or surgery. SGF is the abnormal fusion of the spleen with the gonad or with the mesonephric derivatives. As a rare developmental malformation, it is difficult to make a correct diagnosis preoperatively, and easily misdiagnosed as a testicular tumor cause lifelong harm to patients. An 18‐year‐old male student who developed left testicular pain without obvious cause that radiated to the perineum 4 months prior to presentation. He was diagnosed with cryptorchidism 12 years ago and underwent orchiopexy without intraoperative frozen section examination. An ultrasound was performed, identifying hypoechoic nodules in the left testis, suggestive of seminoma. During surgery, the testicular tumor revealed a dark red tissue and the diagnosis of a pathological ectopic splenic tissue was made. Because the clinical manifestations of SGF are not specific, misdiagnosis and unnecessary orchiectomy may occur. If a complete preoperative examination which includes biopsy or intraoperative frozen section is performed, unnecessary orchiectomy can be effectively avoided and bilateral fertility can be preserved. [ABSTRACT FROM AUTHOR]

The entanglements on various dual properties, such as the wave–particle duality, spin-up and spin-down, and so on, have attracted enormous attention, but how to obtain their entanglement states easily was not clear until now for the particle system. Herein, a method is found for constructing entanglement states on various dual properties of the N-particle system by using the basis vectors of the wave function before the entanglement for the N particles, where the N particles are independent of each other before forming the N-particle system. Moreover, the wave function on the dual property of any one of the mutually independent N particles can be written as a linear combination of the same basis vectors before forming the N-particle system. Notably, the wave–particle entanglement state of two photons in the previous experimental work (Rab et al, Nat. Commun.8, 915 (2017)) and the entanglement state on the spin of two electrons have been obtained using the method. [ABSTRACT FROM AUTHOR]

This paper studies the environmentally sustainable investment of an agricultural supply chain composed of a farmer and a company, under three subsidy policies which are the non-subsidy policy, the fixed subsidy policy, and the Agriculture Risk Coverage (ARC) subsidy policy. Then, we analyse the impact of different subsidy policy and adverse weather on the costs of the government and profits of the farmer and the company. By comparing with the non-subsidy policy, we find that both the fixed subsidy policy and the ARC policy encourage the farmer to improve the environmentally sustainable investment level and increase the profit of the farmer and the company. We also find that both the fixed subsidy policy and the ARC subsidy policy lead to an increase in government spending. Our results show that the ARC subsidy policy has a significate advantage in encouraging the farmer's environmentally sustainable investment if the adverse weather is relatively serious, comparing with the fixed subsidy policy. In turn, our results also show that the ARC subsidy policy is more beneficial for both the farmer and the company than the fixed subsidy policy if the adverse weather is relatively serious, which then leads to a higher expenditure of the government. Therefore, our conclusion serves as a theoretical basis for governments to formulate agricultural subsidy policies and promote sustainable development of the agricultural environment. [ABSTRACT FROM AUTHOR]

Objectives: The use of intravenous analgesics during emergency cesarean section may lead to adverse neonatal outcomes. In our study, we investigated whether a single intravenous (i.v.) dose of 25 mg esketamine administered to parturients with inadequate analgesia during epidural anesthesia for cesarean section would affect the neonate. Design: We reviewed the records of parturients who were transferred from labor analgesia to epidural anesthesia for emergency cesarean section from January 2021 to April 2022. Parturients were grouped by whether they received esketamine infusions during the incision–delivery interval. Neonatal outcomes, including umbilical arterial-blood gas analysis (UABGA), Apgar score, and total days spent by the neonate in the hospital, were compared between the two groups. The secondary outcomes of this study included BP, heart rate (HR), SPO2 and the incidence of adverse effects in parturients during operation. Setting: China. Results: After propensity score matching, 31 patients remained in each of the non-esketamine and esketamine groups. There were no significant differences in neonatal outcomes, including UABGA, Apgar score, and total days in the hospital, between the two groups. Additionally, our study showed a similar hemodynamic performance in parturients between the two groups during operation. Conclusions: Intravenous esketamine (25 mg) is safe for neonates when it is given to parturients transferred from labor analgesia to emergency cesarean section. [ABSTRACT FROM AUTHOR]

Skeletal muscle wasting and atrophy is highly prevalent in chronic renal failure (CRF) and increases the risk of mortality. According to our previous study, we speculate that urotensin II (UII) can induce skeletal muscle atrophy by upregulating ubiquitin–proteasome system(UPS) in CRF. C2C12 mouse myoblast cells were differentiated into myotubes, and myotubes were exposed to different concentrations of UII. Myotube diameters, myosin heavy chain(MHC), p-Fxo03A, skeletal muscle-specific E3 ubiquitin ligases such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1) were detected. Three animal models (the sham operation mice as normal control (NC) group, wild-type C57BL/6 mice with 5/6 nephrectomy (WT CRF) group, UII receptor gene knock out (UT KO) mice with 5/6 nephrectomy (UT KO CRF) group) were designed. Cross-sectional area (CSA) of skeletal muscle tissues in three animal models were measured, and western blot detected protein of UII, p-Fxo03A, MAFbx and MuRF1, and immunofluorescence assays explored the satellite cell marker of Myod1 and Pax7, and PCR arrays detected the muscle protein degradation genes, protein synthesis genes and the genes which were involved in muscle components. UII could decrease mouse myotube diameters, and upregulate dephosphorylated Fxo03A protein. MAFbx and MuRF1 were higher in WT CRF group than that in NC group, but after UII receptor gene was knocked out (UT KO CRF), their expressions were downregulated. UII could inhibit the expression of Myod1 but not Pax7 in animal study. We first demonstrate that skeletal muscle atrophy induced by UII associated with upregulating ubiquitin–proteasome system and inhibiting the differentiation of satellite cells in CRF mice. [ABSTRACT FROM AUTHOR]

As we have previously discussed,[[2]] the term "plasmablasts" has been widely used in the literature to describe the KSHV-infected B-lineage cells in the lymph nodes of KSHV-MCD, although it may be debatable whether these cells truly represent plasmablasts. Abbreviations DLBCL diffuse large B-cell lymphoma FITC fluorescein isothiocyanate FMO Fluorescence Minus One FSC forward scatter H&E haematoxylin and eosin HHV8 human herpesvirus 8 Ig immunoglobulin KSHV Kaposi sarcoma-associated herpesvirus LANA-1 latency associated nuclear antigen-1 LRP lambda-restricted plasmablastic population MCD multicentric Castleman disease PEL primary effusion lymphoma SSC side scatter We appreciate the insightful comments by Vanjak et al. regarding our recent publication 'A novel approach for characterization of KSHV-associated multicentric Castleman disease from effusions'.[1] In our report, we used a broad definition of "plasmablasts" to describe the Kaposi sarcoma-associated herpesvirus (KSHV)-infected, lambda-restricted B-lineage cells in KSHV-associated multicentric Castleman disease (KSHV-MCD), referred to as the lambda-restricted plasmablastic population (LRP) in the publication. The normal B cells were negative for LANA-1 and served as an internal negative control. gl Vanjak et al. raised an important point regarding the specificity of the flow cytometry-based analysis in differentiating between KSHV-MCD and other KSHV-associated lymphoproliferations, including PEL and KSHV/human herpesvirus 8 (HHV8)-positive diffuse large B-cell lymphoma (KSHV/HHV8 SP + sp DLBCL). [Extracted from the article]

Port site metastasis (PSM) is considered an uncommon and rare complication in gynecologic malignancies with unclear treatment recommendations or guidelines. Thus, we report the treatment strategies and outcomes of two cases of PSMs following gynecologic malignancies and a review of the literature to provide much information about the most frequent sites of PSMs and the incidence of PSMs in different gynecological tumors. A 57-year-old woman underwent laparoscopic radical surgery for right ovarian serous carcinoma in June 2016 followed by postoperative chemotherapy. Because PSMs were present near the port site of the bilateral iliac fossa, the tumors were completely removed on August 4, 2020, and the patient received chemotherapy. She has shown no signs of relapse. During the same period, a 39-year-old woman underwent laparoscopic type II radical hysterectomy for endometrial adenocarcinoma involving the endometrium and cervix on May 4, 2014, without adjuvant treatment. In July 2020, a subcutaneous mass under her abdominal incision was removed, and chemotherapy plus radiotherapy was administered. Metastasis was found in the left lung in September 2022, but there was no abnormality in the abdominal incision. We showed the two cases of PSMs, reviewed articles to provide some new insights about the incidences of PSMs in the gynecologic tumors, and discussed the proper preventive strategies. [ABSTRACT FROM AUTHOR]

A prediction interval (PI) method is developed to quantify the model uncertainty of embankment settlement prediction. Traditional PIs are constructed based on specific past period information and remain unchanged; hence, they neglect discrepancies between previous calculations and new monitoring data. In this paper, a real-time prediction interval correction method is proposed. Time-varying PIs are built by continuously incorporating new measurements into model uncertainty calculations. The method consists of trend identification, PI construction, and real-time correction. Primarily, trend identification is carried out by wavelet analysis to eliminate early unstable noise and determine the settlement trend. Then, the Delta method is applied to construct PIs based on the characterized trend, and a comprehensive evaluation index is introduced. The model output and the upper and lower bounds of the PIs are updated by the unscented Kalman filter (UKF). The effect of the UKF is compared with that of the Kalman filter (KF) and extended Kalman filter (EKF). The method was demonstrated in the Qingyuan power station dam. The results show that the time-varying PIs based on trend data are smoother than those based on original data with better evaluation index scores. Also, the PIs are not affected by local anomalies. The proposed PIs are consistent with the actual measurements, and the UKF performs better than the KF and EKF. The approach has the potential to provide more reliable embankment safety assessments. [ABSTRACT FROM AUTHOR]

Summary: A biopsy of lymphoid tissue is currently required to diagnose Kaposi sarcoma‐associated herpesvirus (KSHV)‐associated multicentric Castleman disease (KSHV–MCD). Patients showing clinical manifestations of KSHV–MCD but no pathological changes of KSHV–MCD are diagnosed as KSHV inflammatory cytokine syndrome. However, a lymph node biopsy is not always feasible to make the distinction. A pathognomonic feature of lymph nodes in KSHV–MCD is the expansion of KSHV‐infected, lambda‐restricted but polyclonal plasmablasts. To investigate whether these cells also reside in extra‐nodal sites, effusion from 11 patients with KSHV–MCD and 19 with KSHV inflammatory cytokine syndrome was analysed by multiparametric flow cytometry. A distinct, lambda‐restricted plasmablastic population (LRP) with highly consistent immunophenotype was detected in effusions in 8/11 patients with KSHV–MCD. The same population was also observed in 7/19 patients with KSHV inflammatory cytokine syndrome. The detection of LRP stratified KSHV inflammatory cytokine syndrome into two clinically distinct subgroups; those with detectable LRP closely resembled KSHV–MCD, showing similar KSHV viral load, comparable severity of thrombocytopenia and hypoalbuminaemia, and similar incidences of hepatosplenomegaly. Collectively, the detection of LRP by flow cytometry can serve as a valuable tool in diagnosing KSHV–MCD. KSHV inflammatory cytokine syndrome with LRP in effusions may represent a liquid‐form of KSHV–MCD. [ABSTRACT FROM AUTHOR]

The Internet-of-Things (IoT) massive access is a significant scenario for sixth-generation (6G) communications. However, low-power IoT devices easily suffer from remote interference caused by the atmospheric duct under the 6G time-division duplex (TDD) mode. It causes distant downlink wireless signals to propagate beyond the designed protection distance and interfere with local uplink signals, leading to a large outage probability. In this paper, a remote interference discrimination testbed is originally proposed to detect interference, which supports the comparison of different types of algorithms on the testbed. Specifically, 5,520,000 TDD network-side data collected by real sensors are used to validate the interference discrimination capabilities of nine promising AI algorithms. Moreover, a consistent comparison of the testbed shows that the ensemble algorithm achieves an average accuracy of 12% higher than the single model algorithm. [ABSTRACT FROM AUTHOR]

Fritillariae cirrhosae bulbus (FCB) is one of the most important traditional Chinese medicines (TCM) for the treatment of cough and phlegm. Due to increasing demand and the complexity of FCB's botanical origin, various substitutes have appeared in the market, resulting in a major challenge to distinguish FCB and its substitutes (F. pallidiflorae bulbus, FPB). Therefore, discriminating FCB from FPB has becoming an urgent necessity. In this study, an ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous quantification of nine steroidal alkaloids (imperialine-3-β-D-glucoside, imperialine, verticine, verticinone, peimisine, yibeinoside A, delavine, delavinone, ebeidinone) within 8 min. According to the composition and content of the above nine compounds, multivariate chemometric analyses were applied for the classification of FCB and FPB. The quantitative results showed that there were both similarities and differences in the content of nine steroidal alkaloids between FCB and FPB, and it was difficult to directly distinguish these two species. Fortunately, with the aid of chemometric analyses, FCB and FPB were successfully differentiated by partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA) models based on the nine alkaloids' content. Moreover, four compounds (yibeinoside A, ebeiedinone, delavinone and imperialine) were discovered as potential markers for the identification and differentiation of FCB and FPB. Additionally, compared to other studies, this work collected a large number of samples (49 batches of FCB and 17 batches of FPB) to ensure the reliability of the results. In conclusion, this work established a new approach for the authentication of FCB based on its active components, which provides a good reference for the quality control of FCB and will help us to understand the chemical composition differences between FCB and its adulterants further. [ABSTRACT FROM AUTHOR]