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Abstract Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.

The subgenus Homoneura Wulp, 1891 (Diptera, Lauxaniidae, Homoneurinae) is highly diverse with more than 220 species known from China, representing more than 80% of the Chinese genus Homoneura Wulp, 1891. These species were assigned into 21 species groups in studies mainly focusing on the classification and description of species. The phylogenetic relationships of each subgenus of Homoneura and the phylogenetic relationship of the species groups are still not well understood. We investigated the male morphology to provide the basis to further revise the species groups of this subgenus. In this survey, 230 species were examined and 117 morphological characters obtained, a phylogenetic analysis was conducted using the maximum parsimony analysis with TNT and WinClada. The analyses yielded 45 most parsimonious trees and one strict consensus tree. A phylogenetic hypothesis is proposed dividing the subgenus Homoneura into 12 species groups: H. (H.) nigrifacies, H. (H.) pallida, H. (H.) patella, H. (H.) beckeri, H. (H.) formosae, H. (H.) henanensis, H. (H.) nigra, H. (H.) notostigma, H. (H.) ornatifrons, and H. (H.) trispina, H. (H.) laticosta, and H. (H.) quinquenotata. This research provides valuable contributions towards a better understanding of the phylogenetic relationships within the subgenus Homoneura. However, the monophyly of the genus and subgenus was not supported.

Abstract Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability.

Abstract Objectives STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. Conclusions In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

Abstract Background The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients. Methods Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc. Results To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis. Conclusions We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.

Abstract The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold tumor categorization based on the abundance of intra-tumoral immune cells. By incorporating the spatial immune contexture, the tumor immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, the mechanisms underlying these different immune phenotypes are yet to be comprehensively elucidated. In this review, we discuss how tumor cells and the tumor microenvironment interact collectively to shape the immune landscape from the perspectives of tumor cells, immune cells, the extracellular matrix, and cancer metabolism, and we summarize potential therapeutic options according to distinct immunophenotypes for personalized precision medicine.

AIM: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions. METHODS: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients. Using lentivirus to knock down FBN1 levels, vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay, fluorescein fundus angiography (FFA) and immunofluorescence labeled with tight junction marker in vivo. High glucose-induced monkey retinal vascular endothelial cells (RF/6A) were used to investigate effects of FBN1 on the cells in vitro. The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance (TEER) assay and flow cytometry, respectively. RESULTS: FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients (GSE60436 datasets) using RNA-seq approach. Besides, knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection. Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group, and knocking down of FBN1 increased the tight junction levels. In vitro, 30 mmol/L glucose could significantly inhibit viability of RF/6A cells, and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation. Down-regulation of FBN1 reduced high glucose (HG)-stimulated retinal microvascular endothelial cell permeability, increased TEER, and inhibited RF/6A cell apoptosis in vitro. CONCLUSION: The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions. Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage, reduce vascular leakage, cell apoptosis, and maintain vascular endothelial cell barrier function.

Abstract Purpose Early ambulation is an important step in accelerating post-joint replacement surgery recovery. However, there is limited research on populations who are unable to walk immediately after the operation. The purpose of this study was to determine the factors influencing postoperative ambulation in total knee arthroplasty (TKA) patients. Methods Primary TKA patients were included in this retrospective study. All patients were divided into two groups. Patients who began walking within 24 h were categorized as the early ambulation group, while patients who began walking after 24 h were classified as the late ambulation group. Recorded demographic data included age, gender, body mass index (BMI), clinical diagnosis, and comorbidities. Hematological parameters potentially affecting patients’ preoperative physical condition were also documented. Additionally, intraoperative metrics such as surgical time, surgical side, tourniquet time, intraoperative blood loss, the placement of drains, and prosthetic model were recorded. Results A total of 453 patients (79.0% female, 21.0% male) were included in this study. The average age of all patients was 68.5±7.9 years, ranging from 36 to 87 years, with an average BMI of 27.2±9.9 kg/ $$\mathrm {m^{2}}$$ m 2 . The mean postoperative ambulation time was 1.6 days, with a range of 0–4 days. In univariate group comparisons, an increase in postoperative time to ambulation was significantly associated with a history of heart disease ( $$P

Abstract Background Excessive inflammation is a major cause of implant failure. The surface morphology, hydrophilicity, and loading of biomaterials are major properties modulating anti-inflammatory macrophage activation. This paper investigates the regulatory effects of modifying the surface of Titanium dioxide nanotubes (TNTs) with graphene oxide (GO) on the polarization of mouse monocyte macrophages (RAW264.7). Methods TNT was produced by the anodic oxidation of titanium. GO was subsequently electrodeposited on the TNT to obtain a TNT–GO composite. The samples were characterised through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction. RAW264.7 cells were separately seeded onto the surface of three groups of samples: pure Ti, TNT, and TNT–GO. Under the condition of lipopolysaccharide stimulation, the influence of the sample surfaces on the gene expression profiles was investigated through RNA sequence analysis. In addition, cell spreading was observed through SEM, cell adhesion and proliferation were analysed using the CCK8 assay, and the expression of inflammation-related factors was investigated by ELISA and cellular immunofluorescence staining. The production of reactive oxygen species (ROS) in the RAW264.7 cells on the surface of the three groups was detected via immunofluorescence staining. Results The CCK8 results indicated that the adhesion and proliferation of the RAW264.7 cells were reduced on the TNT and TNT–GO surfaces. ELISA results revealed significant differences in the pro-inflammatory factors tumour necrosis factor-α and interleukin-6 secretion among the three groups at 24 h (p

Poverty threatens human development especially for developing countries, so ending poverty has become one of the most important United Nations Sustainable Development Goals (SDGs). This study aims to explore China’s progress in poverty reduction from 2016 to 2019 through time-series multi-source geospatial data and a deep learning model. The poverty reduction efficiency (PRE) is measured by the difference in the out-of-poverty rates (which measures the probability of being not poor) of 2016 and 2019. The study shows that the probability of poverty in all regions of China has shown an overall decreasing trend (PRE = 0.264), which indicates that the progress in poverty reduction during this period is significant. The Hu Huanyong Line (Hu Line) shows an uneven geographical pattern of out-of-poverty rate between Southeast and Northwest China. From 2016 to 2019, the centroid of China’s out-of-poverty rate moved 105.786 km to the northeast while the standard deviation ellipse of the out-of-poverty rate moved 3 degrees away from the Hu Line, indicating that the regions with high out-of-poverty rates are more concentrated on the east side of the Hu Line from 2016 to 2019. The results imply that the government’s future poverty reduction policies should pay attention to the infrastructure construction in poor areas and appropriately increase the population density in poor areas. This study fills the gap in the research on poverty reduction under multiple scales and provides useful implications for the government’s poverty reduction policy.

Adipose tissue is a highly attractive reservoir of stem cells due to its accessibility and abundance, and the SVF within it holds great promise for stem cell-based therapies. The use of mechanical methods for SVF isolation from adipose tissue is preferred over enzymatic methods, as it can be readily applied in clinical settings without additional processing steps. However, there is a lack of consensus on the optimal approach for mechanically isolating SVF. This comprehensive review aims to present and compare the latest mechanical isolation methods for SVF from adipose tissue, including centrifugation, filtration/washing, emulsification, vibration, and mincing/adiponizing. Each of these methods possesses unique advantages and limitations, and yet, no conclusive evidence has emerged demonstrating the superiority of one approach over the others, primarily due to the dearth of well-controlled prospective studies in this field.

Probability-based methodologies have gained widespread recognition for their pivotal role in steering decision-making in contexts marked by uncertainty or vagueness. In order to guarantee that decisions made in these circumstances are both significant and impactful, various methodologies focused on probability have been devised and utilized. This study seeks to significantly enrich the existing literature by proposing a new probability model termed the weighted sine exponentiated Weibull distribution. Certain characteristics are obtained for the suggested model. Additionally, the parameter estimation method and simulation studies related to the suggested model are also provided. Two distinct data sets, acquired from the disciplines of physical education and reliability, were effectively implemented using the proposed model, resulting in a successful outcome. Through the utilization of the p-value and various tests, it becomes apparent that the weighted sine exponentiated Weibull model consistently surpasses its competitor distributions in terms of statistical significance. The proposed model’s practical illustration highlights its effectiveness and potential for extensive use in both physical education and reliability research and practice.

Abstract Background Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities. Case presentation A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient’s sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient’s sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases. Conclusion This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.

Abstract In recent decades boreal wildfires have occurred frequently over eastern Siberia, leading to increased emissions of carbon dioxide and pollutants. However, it is unclear what factors have contributed to recent increases in these wildfires. Here, using the data we show that background eastern Siberian Arctic warming (BAW) related to summer Russian Arctic sea-ice decline accounts for ~79% of the increase in summer vapor pressure deficit (VPD) that controls wildfires over eastern Siberia over 2004-2021 with the remaining ~21% related to internal atmospheric variability associated with changes in Siberian blocking events. We further demonstrate that Siberian blocking events are occurring at higher latitudes, are more persistent and have larger zonal scales and slower decay due to smaller meridional potential vorticity gradients caused by stronger BAW under lower sea-ice. These changes lead to more persistent, widespread and intense high-latitude warming and VPD, thus contributing to recent increases in eastern Siberian high-latitude wildfires.

Homoneura picta belongs to the Homoneurinae subfamily of Lauxaniidae, and it is widely distributed and common in China. This study reports the newly sequenced mitochondrial genome of H. picta. The sequence is 15,469 bp long and contains 37 genes (13 protein-coding, 22 tRNA, and 2 rRNA genes) and a control region. The overall base composition is 38.4% for A, 37.7% for T, 14.1% for C, and 9.8% for G, with a bias toward A + T (76.1%). Phylogenetic analysis show that Homoneura is a sister genus of Cestrotus. We have successfully sequenced the mitochondrial genome of H. picta, which can be useful in investigating the phylogenetic status of Homoneurinae. Our results provide data for further studies of phylogeny in Diptera.

Abstract Background Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. Methods The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. Results This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P

Precise quantification of the JAK2V617F mutation using highly sensitive assays is crucial for diagnosis, treatment process monitoring, and prognostic prediction in myeloproliferative neoplasms' (MPNs) patients. Digital droplet polymerase chain reaction (ddPCR) enables precise quantification of low-level mutations amidst a high percentage of wild type alleles without the need for external calibrators or endogenous controls. The objective of this study was to optimize a ddPCR assay for detecting the JAK2V617F mutation and establish it as a laboratory-developed ddPCR assay in our center. The optimization process involved fine-tuning five key parameters: primer/probe sequences and concentrations, annealing temperature, template amount, and PCR cycles. Our ddPCR assay demonstrated exceptional sensitivity, and the limit of quantification (LoQ) was 0.01% variant allele frequency with a coefficient of variation of approximately 76%. A comparative analysis with quantitative PCR on 39 samples showed excellent consistency (r = 0.988).

Abstract This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan–Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

Abstract Objective To examine the bi-directorial association between diversified leisure activity participation and cognitive function over a 7-year period. Methods Data analyzed was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a large-scale longitudinal national study. The baseline survey was conducted in 2011 with follow-up every three years. We traced a total of 2718 participants over a period of 7 years. We used adjusted random intercept cross-lagged panel models (RI-CLPMs) to examine the bi-directorial associations between diversified leisure activity participation and cognitive function. Results We observed bi-directorial associations between diversity of leisure activity and cognitive function across waves at the between-person and within-person levels. The adjusted random intercept cross-lagged panel models fitted the data appropriately, and the 3-year cross-lagged effects of prior diversified leisure activity participation on cognitive function (β = 0.058, p

Abstract Background Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. Case presentation A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. Conclusion While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.

Abstract Background Genetically modified (GM) crop plants with transgenic expression of Bacillus thuringiensis (Bt) pesticidal proteins are used to manage feeding damage by pest insects. The durability of this technology is threatened by the selection for resistance in pest populations. The molecular mechanism(s) involved in insect physiological response or evolution of resistance to Bt is not fully understood. Results To investigate the response of a susceptible target insect to Bt, the soybean pod borer, Leguminivora glycinivorella (Lepidoptera: Tortricidae), was exposed to soybean, Glycine max, expressing Cry1Ac pesticidal protein or the non-transgenic parental cultivar. Assessment of larval changes in gene expression was facilitated by a third-generation sequenced and scaffolded chromosome-level assembly of the L. glycinivorella genome (657.4 Mb; 27 autosomes + Z chromosome), and subsequent structural annotation of 18,197 RefSeq gene models encoding 23,735 putative mRNA transcripts. Exposure of L. glycinivorella larvae to transgenic Cry1Ac G. max resulted in prediction of significant differential gene expression for 204 gene models (64 up- and 140 down-regulated) and differential splicing among isoforms for 10 genes compared to unexposed cohorts. Differentially expressed genes (DEGs) included putative peritrophic membrane constituents, orthologs of Bt receptor-encoding genes previously linked or associated with Bt resistance, and those involved in stress responses. Putative functional Gene Ontology (GO) annotations assigned to DEGs were significantly enriched for 36 categories at GO level 2, respectively. Most significantly enriched cellular component (CC), biological process (BP), and molecular function (MF) categories corresponded to vacuolar and microbody, transport and metabolic processes, and binding and reductase activities. The DEGs in enriched GO categories were biased for those that were down-regulated (≥ 0.783), with only MF categories GTPase and iron binding activities were bias for up-regulation genes. Conclusions This study provides insights into pathways and processes involved larval response to Bt intoxication, which may inform future unbiased investigations into mechanisms of resistance that show no evidence of alteration in midgut receptors.

BackgroundTotal hip arthroplasty or total knee arthroplasty (THA/TKA) is often associated with varying degrees of pain. In recent years, transdermal buprenorphine (TDB) patch has shown encouraging results for acute postoperative pain control in orthopedic surgery. The aim of our study was to investigate the efficacy and safety of the combination of TDB patch and nonsteroidal anti-inflammatory drugs (NSAIDs) as a multimodal analgesic regimen after THA/TKA.MethodsPatients who underwent THA and TKA between January 2022 and January 2023 were reviewed. Three postoperative analgesic regimens were selected: Group A (flurbiprofen 50 mg and tramadol 37.5 mg/acetaminophen 325 mg), Group B (flurbiprofen 50 mg and TDB 5 mg), and Group C (Parecoxib 40 mg and TDB 5 mg). The primary outcomes were the Wong-Baker face pain scale revision (FPS-R) scores and the rate of sleep disturbances. Secondary outcomes of the study included the proportion of patients with postoperative pain relief rates categorized as 0%, 0.05).ConclusionThis study suggests that the combination of TDB patch and NSAIDs is safe and effective for postoperative analgesia after THA/TKA.

Background: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio. Methods: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression. Results: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio. Conclusion: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Sorafenib (Sf) is currently the first-line treatment for HCC. However, due to the side effects and unsatisfied efficiency of Sf, it is urgent to combine different therapeutic agents to inhibit HCC progression and increase the therapeutic efficacy. Here, our study constructed a Sf and KIAA1199-siRNA co-loaded liposome Sf-Lp-KIAA, which was prepared by electrostatic interaction of KIAA1199-siRNA and Sf loaded liposome (Sf-Lp). The particle size, zeta potential, the in vitro cumulative release was investigated. The physical and chemical properties were characterized, and the inhibition of HepG2 growth and metastasis in vitro was investigated. The cellular uptake of the co-loaded liposome was significantly higher than that of free siRNA, and the drug/siRNA could be co-delivered to the target cells. Sf-Lp-KIAA could significantly inhibit the growth, migration, invasion and down-regulate KIAA1199 expression of HepG2 cells in vitro than that of single Sf treated group. In addition, the co-delivery liposome accumulated in the HepG2 subcutaneous tumor model and suppress tumor growth after systemic administration without induce obvious toxicity. The present study implied that the co-delivery of Sf and KIAA1199-siRNA through the co-loaded liposomes exerted synergistic antitumor effects on HCC, which would lay a foundation for HCC therapy in the future.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aβ-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.

Background: Evidence linking nitrogen dioxide (NO2) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO2 among elderly individuals in China. Methods: A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005–2018. Residential exposures to NO2 and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO2 exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO2-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO2-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO2-related deaths between 2010 and 2020 into four primary contributing factors. Results: A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO2 exposure with all-cause death across a broad range from 6.6 to 95.7 μg/m3. Every 10-μg/m3 rise in yearly average NO2 concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031–1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023–1.063) for each 10-μg/m3 growth in NO2. Reaching a 10-μg/m3 counterfactual target of NO2 concentration in China could avoid 0.33 (95% empirical CI: 0.19–0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23–0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14–0.36) million deaths and 0.21 (95% empirical CI: 0.12–0.31) years of LLE in 2020. The net fall in NO2-attributable deaths (–26.8%) between 2010 and 2020 was primarily driven by the declines in both NO2 concentration (–41.6%) and mortality rate (–27.1%) under population growth (+41.0%) and age structure transition (+0.9%). Conclusions: Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO2 exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO2-attributable mortality.

Multiple myeloma (MM) is a plasma cell malignancy considered incurable despite the recent therapeutic advances. Effective targeted therapies are therefore needed. Our previous studies proved that inhibiting CDK7 impairs the cell cycle and metabolic programs by disrupting E2F1 and MYC transcriptional activities, making it an appealing therapeutic target for MM. Given that CDK7 and BRD4 operate in two distinct regulatory axes in MM, we hypothesized that targeting these two complementary pathways simultaneously would lead to a deeper and more durable response. Indeed, combination therapy had superior activity against MM cell growth and viability, and induced apoptosis to a greater extent than single-agent therapy in both cell lines and patient cells. This synergistic activity was also observed in Waldenström’s Macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for combination therapy’s potential as a therapeutic strategy in MM and WM.

We extend the translationally invariant quantum East model to an inhomogeneous chain with East/West heterojunction structure. In analogy to the quantum diffusion of particles, we observe a plateaus-shaped entanglement entropy spreading in the heterojunction during time evolution that can be regarded as continuous cycles in a quantum heat engine. In order to figure out the possibility of manipulating the entanglement entropy as a quantum resource, the entropy growth is shown to be determined by the initial occupation and the site-dependent chemical potential, and the former is equivalent to an effective temperature. Through fine adjustment of these parameters, we discover the entanglement flow is simply superposed with those from two sources of the chain. An intriguing relation between our model and the traditional heat engines is subsequently established.

Benzophenone (BP)-type UV filters are commonly added to sunscreens and cosmetics to protect against UV radiation for human skin and hair. As a result, BPs are ubiquitous in the environment and human body, and their endocrine-disrupting characteristics have been a hot topic of discussion. However, our knowledge regarding the detrimental effects of prenatal exposure to BPs on pregnant women and their offspring remains limited. To fill this gap, we determined five BP derivatives in 600 serum samples obtained from pregnant women. All the target analytes, except 2,4-dihydroxybenzophenone (BP-1), have achieved a 100 % detection rate. The most prevalent compound was 2-hydroxy-4-methoxybenzophenone (BP-3), with a median concentration of 0.545 ng/mL. Significant and positive correlations were observed among BP derivatives, indicating both endogenous metabolism and common external sources. Utilizing Bayesian kernel machine regression (BKMR) and quantile-based g-computation (QGC) models, we found relationships between BP exposure and reduced neonatal birth weight (BW) and birth chest circumference (BC) during the third trimester. Notably, the adverse effect of BPs on birth size was sex-specific. Moreover, triglyceride (TG) was identified as a potential mediator of the effect of BPs on blood pressure, and co-exposure to BPs was linked to disruptions in thyroid hormone levels and glucose regulation. Further research is warranted to unravel the toxicity of BPs and their detrimental effects on pregnant women and fetuses.

The pre-stressed flexible cable-supported photovoltaic (PV) systems (FCSPSs) are gradually becoming the preferred PV structure for large-span and mountain photovoltaic power plants. The wind-induced response of FCSPSs under negative wind conditions is more pronounced than under positive wind conditions. In this study, a series of two-way fluid-structure interaction (FSI) coupling numerical simulations are conducted to investigate the effect of ground anchors on the wind-induced vibration response of FCSPSs. Firstly, an analysis approach for wind-induced vibration coefficients of FCSPSs is established, involving model equivalency, coefficient definitions, model creation, and grid and solution settings. Secondly, modal analysis is performed on FCSPSs by varying the stiffness ratio (SR) of the ground anchor. Subsequently, changes in support reaction, ground anchor tension, translational displacement, and rotational displacement, as well as the wind field variation in the fluid domain under wind load, are evaluated for SR values ranging from 0 to 5. Finally, a quantitative evaluation of the wind-induced vibration coefficient in the FCSPS is conducted for different SR values. The results indicate that the configuration of ground anchor cables significantly mitigates the support reaction and displacement response of the FCSPS under negative wind conditions. Moreover, the stiffness ratio of the ground anchor has a relatively minor impact on wind-induced vibration coefficients (reaction force, displacement).

The purpose of this study is to explore the survival strategy of Phoebe bournei seedlings in natural communities under extremely low light environment. Two-year-old seedlings of P. bournei were used as experimental materials. Leaf morphology, anatomical structure and photosynthetic physiological characteristics of P. bournei seedlings were measured by simulating different light environments (100%, 35% and 10% light transmittance), and to explore the internal relationship between seedling morphology, physiological plasticity and light adaptation. The results were as follows: (1) The leaf length, leaf width, leaf area and specific leaf area (SLA) of seedlings increased with the decrease of light intensity. The leaf thickness, palisade tissue thickness, spongy tissue thickness and palisade/spongy (palisade tissue thickness/spongy tissue thickness) of 10% light transmittance were the minimum. (2) The net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), light utilization efficiency (LUE), photochemical quenching coefficient (qp), non photochemical quenching coefficient (NPQ), effective photosynthetic quantum yield (Fv′/Fm′) and potential photochemical efficiency (Fv/Fo) of photosystem Ⅱ of 35% light transmittance were significantly higher than those of 100% and 10% light transmittances. (3) Chlorophyll a, chlorophyll b, carotenoids, total chlorophyll and maximal photochemical efficiency (Fv/Fm) all increased with the decrease of light intensity, but chlorophyll a/b decreased with the decrease of light intensity. (4) The phenotypic plasticity indexes of seedling structure and physiology showed that photosynthetic pigment content characteristics > morphological characteristics > photosynthetic characteristics > anatomical structure characteristics > chlorophyll fluorescence parameter characteristics, among which, the phenotypic plasticity indexes of leaf area, SLA, Pn, Gs, LUE and photosynthetic pigment content ranged from 0.455 to 0.755. To sum up, P. bournei seedlings are not suitable to grow under full light, and perform well under about 35% light transmittance; under extremely low light with 10% light transmittance, P. bournei leaves can improve light energy capture by increasing leaf area, SLA, Pn and photosynthetic pigment content; the seedlings of P. bournei mainly adapt to the low light environment by adjusting the plasticity of photosynthetic pigment content and morphology, coordinating with the changes of anatomical structure, photosynthetic physiology and chlorophyll fluorescence parameter plasticity. This study can provide theoretical reference for the management and selection of light environment of P. bournei for future cultivation.

Abstract Background This study aimed to explore the associations between household air pollution (HAP), measured by cooking fuel use, sensory impairments (SI), and their transitions in Chinese middle-aged and older adults. Methods Participants were recruited from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and were subsequently followed up until 2018. Data on SI were collected by self-reported hearing and vision impairments, which were divided into three categories: non-SI, single SI (hearing or vision impairment), and dual SI (DSI). Cooking fuels, including solid and clean fuels, are proxies for HAP. The transitions of cooking fuels and SI refer to the switching of the fuel type or SI status from baseline to follow-up. Cox proportional hazard regression models were used to explore associations, and hazard ratios (HRs) and 95% confidence intervals (CI) were used to evaluate the strength of the association. Results The prevalence of non-SI, single SI, and DSI was 59.6%, 31.8%, and 8.6%, respectively, among the 15,643 participants at baseline in this study. Over a median follow-up of 7.0 years, 5,223 worsening SI transitions were observed. In the fully adjusted model, solid fuel use for cooking was associated with a higher risk of worsening SI transitions, including from non-SI to single SI (HR = 1.08, 95% CI = 1.01–1.16) and from non-SI to DSI (HR = 1.26, 95% CI = 1.09–1.47), but not from single SI to DSI. In addition, compared to those who always used solid fuels, participants who switched from solid to clean fuel for cooking appeared to have attenuated the risk of worsening SI transitions. The statistical significance of the associations remained in the set of sensitivity analyses. Conclusion Solid fuel use was associated with higher risks of worsening SI transitions, while converting the type of cooking fuel from solid to clean fuels may reduce the risk of worsening SI transitions. Our study suggests that tailored clean fuel interventions, especially in developing countries, should be implemented to prevent sensory impairments and hence reduce the burden of sensory impairment-related disability.

Abstract Background This study aims to identify the risk factors contributing to spinal cord injury (SCI) following a type A acute aortic dissection (TA-AAD). Methods This retrospective study was conducted at a single center and involved 481 patients who received frozen elephant trunk stent implantation for TA-AAD. Additionally, these patients underwent total arch replacement with deep hypothermic circulatory arrest. This study was performed at Fuwai Hospital between September 2016 and April 2020. Results The resulting data of the multivariate logistic regression analysis demonstrated that preoperative platelet count (odds ratio [OR] = 0.774) and D-dimer levels (OR = 2.247) could serve as independent predictors for postoperative SCI in patients with TA-AAD. Conclusion The findings indicate that preoperative platelet count and D-dimer levels are independent risk factors for postoperative SCI in patients with TA-AAD. This study holds significant clinical implications regarding the prognosis and therapeutic responses for patients with TA-AAD.

Abstract In recent decades, winter Arctic sea-ice concentration (SIC) has experienced a most prominent decline over Barents-Kara Seas (BKS). However, what regulates the time scale and spatial structure of the SIC variability over the Eurasian Arctic is unclear. Here, we find that the SIC variability over the Eurasian Arctic exhibits two major modes: decadal dipole mode with antiphase variation between the BKS and East Greenland (EG), and interannual monopole mode with in-phase variation between the BKS and EG. This decadal mode mainly results from interdecadal changes in ocean heat transports (OHTs) through Barents Sea Opening (BSO) and EG, lagging the Atlantic Multidecadal Oscillation by 7–16 years. The positive SIC dipole mode with a decrease over the BKS and an increase over the EG is also tied to the negative Arctic Oscillation comprised of Ural blocking and the negative North Atlantic Oscillation (NAO). However, the SIC loss of the interannual monopole mode mainly stems from the positive Arctic dipole comprised of Ural blocking and positive NAO through interannual changes in the BSO OHT and atmospheric moisture or heat transport. We further highlight that interannual atmospheric transports and BSO OHT associated with the Arctic dipole contribute to ~66% and ~34% of the interannual variability of the Eurasian Arctic SIC during 1960-2017, respectively. On decadal timescales, the relative contributions of atmospheric transports associated with Arctic Oscillation and OHT to the Eurasian Arctic SIC variability are ~19% and ~81%, respectively. Especially, the contribution of decadal atmospheric transports is significantly intensified during 2000–2017.

Abstract The development of stable and efficient ligands is of vital significance to enhance the catalytic performance of carbonylation reactions of alkenes. Herein, an aryldiphosphine ligand (L11) bearing the [Ph2P(ortho-C6H4)]2CH2 skeleton is reported for palladium-catalyzed regioselective carbonylation of alkenes. Compared with the industrially successful Pd/1,2-bis(di-tert-butylphosphinomethyl)benzene catalyst, catalytic efficiency catalyzed by Pd/L11 on methoxycarbonylation of ethylene is obtained, exhibiting better catalytic performance (TON: >2,390,000; TOF: 100,000 h−1; selectivity: >99%) and stronger oxygen-resistance stability. Moreover, a substrate compatibility (122 examples) including chiral and bioactive alkenes or alcohols is achieved with up to 99% yield and 99% regioselectivity. Experimental and computational investigations show that the appropriate bite angle of aryldiphosphine ligand and the favorable interaction of 1,4-dioxane with Pd/L11 synergistically contribute to high activity and selectivity while the electron deficient phosphines originated from electron delocalization endow L11 with excellent oxygen-resistance stability.

Introduction: G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular signaling pathways after interacting with bile acids. TGR5 plays an important role in multiple physiological processes and is considered to be a potential target for the treatment of various metabolic diseases, including type 2 diabetes. Evidence has emerged that genetic deletion of TGR5 results in an increase in basal urine output, suggesting that it may play a critical role in renal water and salt reabsorption. The present study aims to elucidate the effect and mechanism of TGR5 activation on urine concentration. Methods: Mice were treated with TGR5 agonists (LCA and INT-777) for 3 days. The 24-h urine of mice was collected and analyzed for urine biochemical parameters. The mRNA expressions were detected by real-time PCR, and the protein expressions were detected by western blot. Immunohistochemistry and immunofluorescence were performed to examine the cellular location of proteins. The cultured primary medullary collecting duct cells were pretreated with H89 (a PKA inhibitor) for 1 h, followed by 12-h treatment of LCA and INT-777. Luciferase reporter assays were used to detect the effect of CREB on the gene transcription of AQPs. Gel electrophoretic mobility shift assays were used to analyze DNA–protein interactions. Results: Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation. In cultured primary medullary collecting duct cells, LCA and INT-777 dose-dependently upregulated AQP2 and AQP3 expression in a cAMP/PKA-dependent manner. Mechanistically, both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays. Conclusion: Collectively, our findings demonstrate that activation of TGR5 can promote urine concentration by upregulation of AQP2 and AQP3 expression in renal collecting ducts. TGR5 may represent an attractive target for the treatment of patients with urine concentration defect.

Abstract Background Laminin-α5, a major component of the basal lamina, is predominantly synthesized by endothelial and mural cells (pericytes and vascular smooth muscle cells) in the CNS. Loss of laminin-α5 in either population fails to induce any abnormalities due to functional redundancy. Thus, the functional significance of laminin-α5 in neurovascular integrity remains unknown. Here, we hypothesize that ablation of laminin-α5 in both endothelial and mural cells increases neurovascular permeability. Methods The compound knockout mice were generated by crossing laminin-α5 floxed mice with Tie2-Cre and PDGFRβ-Cre, which target endothelial cells and mural cells, respectively. Neurovascular permeability in these mutants was determined with both exogenous and endogenous tracers. Endothelial paracellular and transcellular permeability was assessed by examining the expression of tight junction proteins and transcytosis-associated proteins. In addition, transmission electron microscopy (TEM) was used to visualize tight junction ultrastructure and endothelial caveolae vesicles. Defects in pericytes and astrocytes were investigated by examining pericyte coverage/contact and astrocyte polarity. Results Elevated neurovascular permeability was observed in the mutants. Subsequent studies found increased Caveolin-1 and decreased major facilitator superfamily domain-containing protein 2a (MFSD2A) expression, but unaltered Claudin-5 or zonula occludens-1 (ZO-1) expression. Consistent with these results, mutant mice exhibited increased endothelial caveolae vesicle number with intact tight junction structure under TEM. Additionally, pericyte coverage and contact were also decreased in the mutant mice, while astrocyte polarity was unaffected. Conclusions These results strongly indicate that endothelial and mural cell-derived laminin-α5 actively maintains neurovascular integrity via the transcellular rather than paracellular mechanism.

Abstract Background Chinese National Essential Public Health Service Package (NEPHSP) has mandated primary health care providers to provide falls prevention for community-dwelling older people. But no implementation framework is available to guide better integration of falls prevention for older people within the primary health care system. Methods This is a two-stage online participatory design study consisting of eight workshops with stakeholders from three purposively selected cities. First, two workshops were organised at each study site to jointly develop the framework prototype. Second, to refine, optimise and finalise the prototype via two workshops with all study participants. Data analysis and synthesis occurred concurrently with data collection, supported by Tencent Cloud Meeting software. Results All participants confirmed that the integration of falls prevention for older people within the NEPHSP was weak and reached a consensus on five opportunities to better integrate falls prevention, including workforce training, community health promotion, health check-ups, health education and scheduled follow-up, during the delivery of NEPHSP. Three regional-tailored prototypes were then jointly developed and further synthesised into a generic implementation framework by researchers and end-users. Guided by this framework, 11 implementation strategies were co-developed under five themes. Conclusions The current integration of falls prevention in the NEPHSP is weak. Five opportunities for integrating falls prevention in the NEPHSP and a five-themed implementation framework with strategies are co-identified and developed, using a participatory design approach. These findings may also provide other regions or countries, facing similar challenges, with insights for promoting falls prevention for older people.

Abstract Background Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people. Methods 3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012–2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted. Results During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend 0). Conclusions Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Beijing remain elusive. SARS-CoV-2-positive children admitted to the intensive care unit (ICU) with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis-based multiplex PCR from December 12, 2022, to January 24, 2023. The SARS-CoV-2 sub-variants were identified using next-generation sequencing. Plasma was positive for two (positive; P), one (suspicious; S), or no (negative; N) SARS-CoV-2 genes were classified as plasmatic RNA-positive (RNAemia; P + S) or without RNAemia (N). Clinical and laboratory data of the enrolled cases were then collected and analyzed. The 34 enrolled children included 26 males and 24 younger than three years. All were negative for other respiratory pathogens. BF.7.14 (18/29) was the predominant subvariant. Viral loads in respiratory specimens, hours from symptom onset to the first respiratory specimen collection (time-variable), with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs. N and RNAemia vs. without RNAemia group. Among most cases, the T lymphocyte ratios decreased, while the cytokine level and the B lymphocyte ratio increased. The time variables were 2.22 ± 2.05 and 4.00 ± 2.49 days in BF.7.14 and BA.5.2 infections, respectively. In conclusion, SARS-CoV-2 was more likely to cause severe infections among males aged ≤ 3 years old with comorbidities during the SARS-CoV-2 outbreak in Beijing, while RNAemia is more common in children at the early stage of severe BF.7.14 infections, and most had high cytokine levels and B-cell activation.

Abstract Background Deep vein thrombosis (DVT) is a frequent complication following hip arthroplasty. There still has been a lack of studies analyzing the perioperative risk factors of DVT following hip arthroplasty via direct anterior approach (DAA). Methods Patients who underwent unilateral primary hip arthroplasty via DAA in our hospital from August 2015 to January 2022 were included. Patients’ data, including demographic data, clinical features, past medical history, operative data, and laboratory data, were analyzed and compared between patients with and without DVT. Logistic regression analysis was conducted to identify the independent risk factors. Receiver operating characteristic (ROC) curve analysis was used to assess the best cutoff value of continuous variables with statistical significance. Result A total of 651 patients were included. The incidence of DVT before and after hip arthroplasty was 12.7% and 6.7%, respectively. Logistic regression analysis indicated that age ≥ 65 years (OR 4.594, 95% CI 1.994–10.587), women (OR 2.331, 95% CI 1.285–4.227), and cerebral infarction (OR 1.984, 95% CI 1.138–3.460) were independent risk factors for preoperative DVT. And age ≥ 65 years (OR 4.859, 95% CI 1.062–22.226), tumor (OR 3.622, 95% CI 1.108–11.841), and preoperative D-dimer (OR 1.040, 95% CI 1.004–1.078) were risk factors for postoperative DVT. The ROC curve analysis showed that the best cutoff value of preoperative D-dimer for the diagnosis of postoperative DVT is 1.44 mg/L. Conclusions The incidence of DVT in patients undergoing DAA hip arthroplasty was low and the occurrence of DVT before and after unilateral primary hip arthroplasty performed through DAA was related to multiple factors.

Abstract Thin-walled structures utilizing the release of stored strain energy for self-deployment have gained popularity in deployable space structures. However, the integration of traditional rigid or bulky sensors to monitor their mechanical behavior presents challenges due to large local deformations and strains involved in folding and deployment. Here we introduce a concept of structural electronic skin (e-skin) that is soft, lightweight, and designed for sensing the folding and deployment of tape-spring hinges. The e-skin demonstrates the capability to accommodate significant hinge deformation and enables multimodal sensing, including strain measurements, motion sensing, and dynamics monitoring. The research showcases a promising approach that leverages the design and manufacturing of soft electronics to fulfill the requirements of thin, lightweight, and soft functional devices for multifunctionality in deployable space structures.

Abstract Background Deep vein thrombosis (DVT) has been one of the most dangerous complications in total hip arthroplasty (THA). If a patient’s pre-surgical DVT is overlooked, it can easily be mistaken for a post-operative thrombus and lead to an increased risk of DVT during and after surgery. This retrospective study was to explore the incidence and associated risk factors of deep vein thrombosis (DVT) in non-fracture patients before total hip arthroplasty (THA). Methods From September 2015 to September 2020, 1242 patients admitted for THA were enrolled with 1120 patients (90.2%) for primary THA and 122 patients (9.8%) for revision THA. An experienced sonographer performed a bedside ultrasound to detect DVT in bilateral lower limbs preoperatively. Univariate and logistic regression analysis was performed to identify the independent risk factors. Results 38 patients (3.1%) were detected with preoperative DVT. Univariate analysis showed that age (P

Abstract Background Fine motor skills are closely related to cognitive function. However, there is currently no comprehensive assessment of fine motor movement and how it corresponds with cognitive function. To conduct a complete assessment of fine motor and clarify the relationship between various dimensions of fine motor and cognitive function. Methods We conducted a cross-sectional study with 267 community-based participants aged ≥ 60 years in Beijing, China. We assessed four tests performance and gathered detailed fine motor indicators using Micro-Electro-Mechanical System (MEMS) motion capture technology. The wearable MEMS device provided us with precise fine motion metrics, while Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. We adopted logistic regression to analyze the relationship between fine motor movement and cognitive function. Results 129 (48.3%) of the participants had cognitive impairment. The vast majority of fine motor movements have independent linear correlations with MoCA-BJ scores. According to logistic regression analysis, completion time in the Same-pattern tapping test (OR = 1.033, 95%CI = 1.003–1.063), Completion time of non-dominant hand in the Pieces flipping test (OR = 1.006, 95%CI = 1.000-1.011), and trajectory distance of dominant hand in the Pegboard test (OR = 1.044, 95%CI = 1.010–1.068), which represents dexterity, are related to cognitive impairment. Coordination, represented by lag time between hands in the Same-pattern tapping (OR = 1.663, 95%CI = 1.131–2.444), is correlated with cognitive impairment. Coverage in the Dual-hand drawing test as an important indicator of stability is negatively correlated with cognitive function (OR = 0.709, 95%CI = 0.6501–0.959). Based on the above 5-feature model showed consistently high accuracy and sensitivity at the MoCA-BJ score (ACU = 0.80–0.87). Conclusions The results of a comprehensive fine-motor assessment that integrates dexterity, coordination, and stability are closely related to cognitive functioning. Fine motor movement has the potential to be a reliable predictor of cognitive impairment.

This paper studies the distributed bipartite output formation control problem of heterogeneous discrete-time linear multi-agent systems (MASs) via cooperative output regulation theory. To construct the bipartite formation, under the structurally-balanced augmented directed signed graph, the followers of two antagonistic subgroups are supposed to respectively keep the desired relative positions with the leader, also called as the exosystem, in the same magnitude but the opposite sign. Since the information of exosystem can not be directly obtained by all followers, the distributed exosystem observer based on the discrete-time algebraic Riccati equality (ARE) is presented and the distributed state feedback controller is further designed. Moreover, in the case where the states of followers are not available, the distributed output feedback controller is proposed by introducing the state estimator. Finally, two numerical examples are given to demonstrate the effectiveness of analytic results.

Abstract This research investigates the distribution, progressive changes, and contributing factors of macular choroidal and retinal thickness in Tibetan children utilizing swept-source optical coherence tomography (SS-OCT). The Lhasa childhood study recruited 1632 students from seven primary schools in Lhasa. These participants underwent OCT and ophthalmological evaluations, encompassing retinal and choroidal thickness measurements, refractive error, axial length (AL), and systemic examinations. The median age of the scholars was 8.57 ± 0.50 years with a median spherical equivalent (SE) of 0.19 ± 1.28D. Multivariate regression analysis revealed that thinner macular choroid thickness was correlated with lower value of SE, worse best-corrected visual acuity, higher mean arterial blood pressure (MABP) and boys, while retinal thickness was associated with better image quality and lower value of SE. The choroid and retina were significantly thinner in myopic children. SE was positively related to the thickness of all choroidal and full retinal subregions. In comparison to baseline data from 20 months prior, most regions of the full retina had significantly thinned. Choroidal thickness of Tibetan children is thinner than that of same-age children from other regions. Thinning of retina, the outer-sector GCC and GCIPL may be specified as a follow-up and prognostic indicator for myopia.

Mining latent information from human trajectories for understanding our cities has been persistent endeavors in urban studies and spatial information science. Many previous studies relied on manually crafted features and followed a supervised learning pipeline for a particular task, e.g. land use classification. However, such methods often overlook some types of latent information and the commonalities between varying urban sensing tasks, making the features engineered for one specific task sometimes not useful in other tasks. To tackle the limitations, we propose a multi-view trajectory embedding (MTE) approach to learn the features of urban regions (region representations) in an unsupervised manner, which does not rely on a specific task and thus can be generalized to varying urban sensing tasks. Specifically, MTE incorporates three salient information views carried by human trajectories, i.e. transition, spatial, and temporal views. We utilize skip-gram to model human transition patterns exhibited from massive amounts of human trajectories, where long-range dependency is meaningful. Subsequently, we leverage unsupervised graph representation learning to model spatial adjacency and temporal pattern similarities, where short-range dependency is favorable. We perform extensive experiments on three downstream tasks, i.e. land use classification, population density estimation, and house price prediction. The results indicate that MTE considerably outperforms a series of competitive baselines in all three tasks, and different information views have varying levels of effectiveness in particular downstream tasks, e.g. the temporal view is more effective than the spatial view in land use classification, while it is the opposite in house price prediction.

Background Currently, several studies have explored the association between the modified creatinine index (mCI) and prognosis in patients on hemodialysis (HD). However, some of their results are contradictory. Therefore, this study was conducted to comprehensively assess the role of mCI in predicting prognosis in HD patients through meta-analysis.Methods We searched and screened literature from PubMed, Embase, Web of Science, and Cochrane databases from their establishment until March 2024. Relevant data were extracted. The statistical analysis was performed using Stata 15.0, RevMan 5.4, and Meta DiSc 1.4 software.Results The results showed a positive association between mCI and nutritional status in HD patients (BMI r = 0.19, 95% CI: 0.1–0.28, p = .000; albumin r = 0.36, 95% CI: 0.33–0.39, p = .000; normalized protein catabolic rate (nPCR) r = 0.25, 95% CI: 0.13–0.38, p = .000). In addition, mCI in deceased HD patients was significantly lower than that in HD survivors (SMD = −0.94, 95% CI: −1.46 to −0.42, p = .000). A low mCI was associated with an increased risk of all-cause death in HD patients (HR = 1.95, 95% CI: 1.57–2.42, p = .000). In addition, a low mCI was significantly associated with decreased overall survival (OS) in HD patients (HR = 3.01, 95% CI: 2.44–3.70, p = .000). mCI showed moderate diagnostic accuracy for sarcopenia in both male and female HD patients (male AUC = 0.7891; female AUC = 0.759).Conclusions The mCI can be used as a prognostic marker for HD patients, and monitoring mCI may help to optimize the management of HD and improve overall prognosis in patients.

AbstractIt has been reported that CDK8 plays a key role in acute myeloid leukaemia. Here, a total of 40 compounds were rational designed and synthesised based on the previous SAR. Among them, compound 12 (3-(3-(furan-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide) showed the most potent inhibiting activity against CDK8 with an IC50 value of 39.2 ± 6.3 nM and anti AML cell proliferation activity (molm-13 GC50 = 0.02 ± 0.01 μM, MV4-11 GC50 = 0.03 ± 0.01 μM). Mechanistic studies revealed that this compound 12 could inhibit the phosphorylation of STAT-1 and STAT-5. Importantly, compound 12 showed relative good bioavailability (F = 38.80%) and low toxicity in vivo. This study has great significance for the discovery of more efficient CDK8 inhibitors and the development of drugs for treating AML in the future.