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The effects of covering technology and the combined membrane covering with biochar on nutritional elements content during the aerobic composting process of agricultural waste were studied. The results showed that the concentration effect of organic matter degradation during composting increased the nitrogen, phosphorus, and potassium contents in all treatment groups. The proportion of available phosphorus and available potassium also increased to varying degrees. Compared with composting without an expanded poly(tetrafluoroethylene) (PTFE) covering with 0.2 to 0.4 µm pores, the covered composting increased the total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium contents by 13.1%, 12.6%, 7.4%, 21.5%, and 16.6%, respectively, while the addition of biochar to polymer membrane-covered composting increased the total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium contents by 19.7%, 13.7%, 8.3%, 18.0%, and 20.2%, respectively. This study indicated that membrane covering technology can effectively increase the nutrient element contents in compost products and the availability of phosphorus and potassium and that the addition of biochar enhances these effects.

Abstract Anaplastic thyroid carcinoma (ATC) is a highly aggressive human malignancy without effective treatment. Yes-associated protein (YAP) is a critical effector of the Hippo pathway, which is essential in thyroid carcinogenesis. However, the underlying mechanisms of aberrant YAP expression in ATC are not completely understood. Ubiquitylation-related enzyme siRNA screening identified the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) as a stabilizer of YAP in ATC cells. UBR1 deficiency reduced YAP protein levels and its target gene expression. UBR1 directly interacted with YAP and promoted its monoubiquitylation, competitively suppressing its polyubiquitylation and resulting in extended protein half-life. UBR1 depletion reduced ATC cell proliferation and migration in vitro. Xenograft tumor studies also suggested that UBR1 knockdown suppressed ATC cell growth in vivo. Furthermore, exogenous YAP expression partially reversed the inhibitive effects of UBR1 depletion on ATC cell proliferation and migration. Our studies demonstrated that UBR1 directly interacts with YAP and stabilized it in a monoubiquitylation-dependent manner, consequently promoting ATC tumorigenesis, suggesting that UBR1 might be a potentially therapeutic target for ATC treatment.

Abstract This study constructed a comprehensive analysis of cell death modules in eliminating aberrant cells and remodeling tumor microenvironment (TME). Consensus analysis was performed in 490 lung adenocarcinoma (LUAD) patients based on 4 types of cell death prognostic genes. Intersection method divided these LUAD samples into 5 cell death risk (CDR) clusters, and COX regression analysis were used to construct the CDR signature (CDRSig) with risk scores. Significant differences of TME phenotypes, clinical factors, genome variations, radiosensitivity and immunotherapy sensitivity were observed in different CDR clusters. Patients with higher risk scores in the CDRSig tended to be immune-excluded or immune-desert, and those with lower risk scores were more sensitive to radiotherapy and immunotherapy. The results from mouse model showed that intense expression of the high-risk gene PFKP was associated with low CD8+ T cell infiltration upon radiotherapy and anti-PD-L1 treatment. Deficient assays in vitro confirmed that PFKP downregulation enhanced cGAS/STING pathway activation and radiosensitivity in LUAD cells. In conclusion, our studies originally performed a comprehensive cell death analysis, suggesting the importance of CDR patterns in reprogramming TME and providing novel clues for LUAD personalized therapies.

Coal gasification technology is an effective way to the clean and efficient utilization of coal, the entrained-flow gasification process with radiant syngas cooler (RSC) can effectively recover the sensible heat from high temperature syngas and improve energy utilization rate. The radiation screen adopted inside the RSC is not only keeping the overall structure compact, but improving the heat transfer area greatly. In order to study the thermal deformation of the radiation screen in the RSC under gasification operating conditions, a three-dimensional radiation screen model is established by using the fluid-structure coupling principle to simulation analysis. The simulation results show that under normal operating conditions, the temperature of the whole water-cooling pipe reaches the maximum value at 5.30 m from the top. In the circumferential direction, the surface temperature of the pipe 1 closest to the center of the RSC is parabola distribution. Temperature in the middle of the fire-facing side is the highest, and the maximum temperature difference between the fire-facing side and its back side reaches 60 K. Due to the cooling action of adjacent water-cooling pipe, the surface temperature of pipe 2−5 becomes bimodal distribution. The spatial arrangement has direct effect on the surface temperature distribution of water-cooling pipe. The local deformation of pipe 1 closest to the center of the RSC in water-cooling pipe without fixed is the largest, which is 5.20 cm. Maximum offset in π direction is 4.58 cm, far exceeding the pitch of water-cooling pipes, and the collision between water-cooling pipes is prone to occur. The overall deformation arises after water-cooling pipe is fixed. Maximum thermal deformation of water-cooling pipe with fixed is 3.28 cm, which is 36.9% lower than that of water-cooling pipe without fixed. The relative shift in the π direction basically disappears. Local deformation between the water-cooling pipe is smaller than the distance between the pipes. The occurrence of collision between water-cooling pipes is disappeared for the fixed action of the fixture. The changes of inlet syngas temperature and surface deposition affect the surface temperature gradient and deformation of water-cooling pipe with varying degrees, the offset direction is π/2 side of the water-cooling pipe.

Abstract Background The zero-profile implant system (Zero-P) and conventional plates have been widely used in anterior cervical discectomy and fusion (ACDF) to treat cervical spondylosis. The purpose of this study was to compare the effects of the application of Zero-P and new conventional plates (ZEVO, Skyline) in ACDF on the sagittal imaging parameters of cervical spondylosis patients and to analyze their clinical efficacy. Methods We conducted a retrospective study on 119 cervical spondylosis patients from January 2018 to December 2021, comparing outcomes between those receiving the Zero-P device (n = 63) and those receiving a novel conventional plate (n = 56, including 46 ZEVO and 10 Skyline plates) through ACDF. Cervical sagittal alignment was assessed pre- and postoperatively via lateral radiographs. The Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and visual analog scale (VAS) scores were recorded at baseline, after surgery, and at the 2-year follow-up to evaluate patient recovery and intervention success. Results There were significant differences in the postoperative C0-C2 Cobb angle and postoperative sagittal segmental angle (SSA) between patients in the novel conventional plate group and those in the Zero-P group (P

Abstract Osteoporosis (OP) is a bone metabolism disease that is associated with inflammatory pathological mechanism. Nonetheless, rare studies have investigated the diagnostic effectiveness of immune-inflammation index in the male population. Therefore, it is interesting to achieve early diagnosis of OP in male population based on the inflammatory makers from blood routine examination. We developed a prediction model based on a training dataset of 826 Chinese male patients through a retrospective study, and the data was collected from January 2022 to May 2023. All participants underwent the dual-energy X-ray absorptiometry (DXEA) and blood routine examination. Inflammatory markers such as systemic immune-inflammation index (SII) and platelet-to-lymphocyte ratio (PLR) was calculated and recorded. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Multivariable logistic regression analysis was applied to construct a predicting model incorporating the feature selected in the LASSO model. This predictive model was displayed as a nomogram. Receiver operating characteristic (ROC) curve, C-index, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance. Internal validation was test by the bootstrapping method. This study was approved by the Ethic Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Ethic No. JY2023012) and conducted in accordance with the relevant guidelines and regulations. The predictive factors included in the prediction model were age, BMI, cardiovascular diseases, cerebrovascular diseases, neuropathy, thyroid diseases, fracture history, SII, PLR, C-reactive protein (CRP). The model displayed well discrimination with a C-index of 0.822 (95% confidence interval: 0.798–0.846) and good calibration. Internal validation showed a high C-index value of 0.805. Decision curve analysis (DCA) showed that when the threshold probability was between 3 and 76%, the nomogram had a good clinical value. This nomogram can effectively predict the incidence of OP in male population based on SII and PLR, which would help clinicians rapidly and conveniently diagnose OP with men in the future.

Meat and its derivatives serve as crucial sources of protein, vitamins, minerals, and other essential nutrients for humans. Pork stands as China’s primary animal-derived food product consumed widely across diverse dietary structures; evaluating intramuscular fat content becomes pivotal in assessing its quality standards. Nonetheless, the intricate molecular mechanisms governing intramuscular fat deposition remain elusive. Our study utilized sequencing technology to scrutinize longitudinal development stages within Ningxiang pig’s longest dorsal muscles aiming to unravel these underlying mechanisms. In three distinct comparisons (30d vs. 90d, 90d vs. 150d and 150d vs. 210d) there were 578, 1,000 and 3,238 differentially expressed mRNA, along with 16, 158 and 85 lncRNAs were identified. STEM analysis unveiled six enriched model profiles for lncRNAs while seven such profiles emerged for mRNAs; notably, multiple shared model profiles existed between both RNA types. Enriched analysis highlighted numerous genes from mRNA profile8 and lncRNA profile7 significantly associated with pathways linked to fat deposition. Weight Gene Co-Expression Network Analysis (WGCNA) revealed that differential expression modules (DMEs) & differential expression lncRNAs primarily clustered within cyan, dark slate blue and pale turquoise modules. Furthermore, target genes PKD2 (MSTRG21592.MTRSG8859 and MTRSG18175), COL5A1 (MTRSG9969 and MTRSG180) and SOX13 (MTRSG21592 and MTRSG9088) as core components all intricately tied into processes related to fat deposition. This study lays the groundwork for deeper exploration into the molecular mechanisms underlying LDM fat deposition traits, and it also presents candidate genes for future molecular marker-assisted breeding.

ObjectivesTo explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on motor function and cortical excitability in stroke patients with different motor evoked potential (MEP) status.MethodsA total of 80 stroke patients were enrolled in this randomized controlled trial and divided into two groups according to MEP status (− or +) of lesioned hemisphere. Then, each group was randomly assigned to receive either active or sham LF-rTMS. In addition to conventional rehabilitation, all participants received 20 sessions of rTMS at 1 Hz frequency through the active or the sham coil over 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Shoulder Abduction Finger Extension (SAFE) and Barthel Index (BI), bilateral resting motor threshold (rMT), amplitude of Motor evoked potential (MEP) and Central Motor Conduction Time (CMCT), and Interhemispheric asymmetry (IHA) were blindly assessed at baseline, 4 weeks and 8 weeks after treatment, respectively.ResultsAt 4 weeks after intervention, FMA and NIHSS changed scores in 1 Hz MEP(+) group were significantly higher than those in the other three groups (p

Lead (Pb) is an environmentally widespread bone toxic pollutant, contributes to the development of osteoporosis. Butyric acid, mainly produced by the fermentation of indigestible dietary fiber by gut microbiota, plays a pivotal role in the maintenance of bone homeostasis. However, the effects of butyric acids on the Pb induced osteoporosis have not yet been elucidated. In this study, our results showed that Pb exposure was negatively related to the abundance of butyric acid, in the Pb-exposed population and Pb-exposed mice. Pb exposure caused gut microbiota disorders, resulting in the decline of butyric acid-producing bacteria, such as Butyrivibrio_crossotus, Clostridium_sp._JN9, and the butyrate-producing enzymes through the acetyl-CoA pathway. Moreover, results from the NHANES data suggested that dietary intake of butyrate was associated with a reduced risk of osteoporosis in lead-burdened populations, particularly among men or participants aged 18–60 years. In addition, butyrate supplementation in mice with chronic Pb exposure improved the bone microarchitectures, repaired intestinal damage, upregulated the proportion of Treg cells. Taken together, these results demonstrated that chronic Pb exposure disturbs the gut-bone axis, which can be restored by butyric acid supplement. Our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced bone toxicity.

Abstract The incomplete combustion of biomass and fossil fuels results in the formation of not only black carbon (BC) but also black nitrogen (BN), the dissolved fractions of which (i.e., DBC and DBN) are important components of dissolved organic matter pool. Relative to DBC, the activity and reactivity of DBN are much less understood. Here, we investigated the catalytic effect of DBN derived from N-enriched biomass in the abiotic transformation of chlorophenols by sulfides. The medium-temperature DBN (450 °C) exhibited 13–144% higher catalytic efficiency than other DBN samples and 9.3 times higher than its DBC counterpart. Both electron paramagnetic resonance spectra and fluorescent probe technique indicated that the attached sulfides contributed to the formation of reactive oxygen species (ROS) as the “primary” radicals by favoring electron transfer from DBN to chemisorbed oxygen, and then the generated ROS reacted with N-oxides in DBN to form reactive nitrogen species (RNS) as the “secondary” radicals. The contribution of RNS to the decay of 2-chlorophenol by DBN450 was up to 72%, much higher than that of ROS and non-radical mechanism. These findings suggest that the catalytic effect of DBN is distinct but no less significant than that of DBC to the abiotic transformation of micropollutants in water/soil systems. Graphical Abstract

Abstract. Background. Human immunodeficiency virus type 1 (HIV-1) remains a persistent global health challenge. Therefore, a continuous exploration of novel therapeutic strategies is essential. A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic approaches. Methods. In this study, we performed a flux balance analysis using a genome-scale metabolic model (GEM) integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 interventions. We generated a GEM by integrating an HIV-1 production reaction into CD4+ T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion production. Differential analysis was used to predict biochemical reactions altered optimal for HIV-1 production. In addition, we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets, which were subsequently validated by human phytohemagglutinin (PHA) blasts infected with HIV-1. Results. Differential analysis identified several altered biochemical reactions, including increased lysine uptake and oxidative phosphorylation (OXPHOS) activities in the virus optima compared with the host optima. In silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis, and OXPHOS could serve as potential anti–HIV-1 metabolic targets. In vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6% (385.4 ± 67.5 pg/mL in the metformin-treated group vs. 888.4 ± 32.3 pg/mL in the control group, P < 0.001). Conclusion. Our integrated host-virus genome-scale metabolic study provides insights on potential targets (OXPHOS) for anti-HIV therapies.

Abstract Background This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS). Methods A total of 421 women aged 20–37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS. Results The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS. Conclusion AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.

Abstract Background Weight management is an effective prevention and treatment strategy for diabetes mellitus. This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic patients towards weight management. Methods Diabetic patients treated at Qidong City, Jiangsu Province, between January 2023 and June 2023 were included in this cross-sectional study. A self-designed questionnaire was used to collect their demographic characteristics and KAP toward weight management. Structural equation modeling (SEM) was employed to examine the inter-relationships among KAP scores. Results Among a total of 503 valid questionnaires that were collected, 55.07% were filled out by men and 54.67% by those aged

Timely and accurate mapping of paddy rice cultivation based on remote sensing technology is crucial and valuable for ensuring food security and sustainable environmental management. In most relevant studies, rice mapping was conducted using time-series images, but conventional rice mapping methods are not specifically designed for time-series data, making it difficult to extract the deep information contained in these data. To address these problems, in this paper, an automatic rice mapping method based on an integrated time-series gradient boosting tree (Auto-ITSGBT) is proposed using GF-6 WFV and Sentinel-2 MSI data. This method accounts for the local and overall shape features of time-series curves, and fully exploits the information related to phenological characteristics between time-series data. The proposed rice mapping method is tested and validated in three typical rice-producing areas, which are located in different provinces of China characterized by diverse climate conditions, planting times or topographies. The results show that the overall accuracy and Kappa coefficient of the method exceeded 95% and 0.93, respectively, at all study sites, respectively. Our method performs better than the existing competing methods, with an overall accuracy improvement of 2% to 4%. To identify the rice planting areas as early as possible, rice mapping was conducted by reducing the number of images one by one. The rice distribution map was obtained in mid-July with an overall accuracy of at least 90%, thus obtaining a spatial distribution map of rice with high accuracy before harvesting.

Abstract Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no‐function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no‐function allele carriers. However, the influence of patient‐specific demographic, clinical, and other genetic factors on outcomes with genotype‐guided DAPT has not been defined. In addition, the impact of genotype‐guided de‐escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no‐function allele has not been investigated in a diverse, real‐world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient‐specific factors on clinical outcomes with CYP2C19‐guided DAPT, evaluate the safety and effectiveness of CYP2C19‐guided DAPT de‐escalation following PCI in a real‐world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real‐world population.

BackgroundTranscranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research.Material and methodsThe database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references.ResultsA total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford’s law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends.ConclusiontACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.

Abstract The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel‐based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non‐hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient‐reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel‐based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.

BackgroundParkinson’s disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients’ quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses.MethodsThe data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions.ResultsA total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments.ConclusionThis bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10−5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P

The canopy radiative transfer model enables quantitative inversion of vegetation biophysical parameters by rapidly simulating spectral information. However, structural input parameters, such as the leaf inclination angle distribution (LAD), are often set to empirical values in classic models, leading to simulation errors. Laser point cloud technology has developed rapidly in recent years, and the 3D structure of vegetation can be detailed using laser sensors and processing software, providing the necessary conditions for accurate solutions of radiative transfer models of the canopy. However, the mechanisms for improving existing models of canopy radiative transfer by introducing laser point clouds have not yet been theoretically analyzed in detail. In this study, a precise solution was proposed by incorporating the accurate LAD obtained from laser point clouds into the intermediate function of the traditional Scattering by Arbitrarily Inclined Leaves (SAIL) model, which is a widely used multiangle radiative transfer model. The calculation of the leaf inclination angle and the derivation of the improved model were detailed in this paper. Experiments from different observation angles and bands compared the similarity between the actual measured spectra and the simulated spectra for both the traditional SAIL model and the proposed model with accurate structural parameters. The overall similarity of the proposed model with respect to the conventional SAIL model was improved, indicating that introducing laser point clouds improved the simulation accuracy. The proposed model achieved more significant improvements in the blue 450 nm and red 670 nm bands. Moreover, the similarity improvements differed between different angles. Finally, we analyzed the sensitivity of the structural parameters of the SAIL model and the proposed model using local and global sensitivity analysis methods.

Abstract The implementation of primary tumor resection (PTR) in the treatment of kidney cancer patients (KC) with bone metastases (BM) has been controversial. This study aims to construct the first tool that can accurately predict the likelihood of PTR benefit in KC patients with BM (KCBM) and select the optimal surgical candidates. This study acquired data on all patients diagnosed with KCBM during 2010–2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was utilized to achieve balanced matching of PTR and non-PTR groups to eliminate selection bias and confounding factors. The median overall survival (OS) of the non-PTR group was used as the threshold to categorize the PTR group into PTR-beneficial and PTR-Nonbeneficial subgroups. Kaplan–Meier (K–M) survival analysis was used for comparison of survival differences and median OS between groups. Risk factors associated with PTR-beneficial were identified using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to validate the predictive performance and clinical utility of the nomogram. Ultimately, 1963 KCBM patients meeting screening criteria were recruited. Of these, 962 patients received PTR and the remaining 1061 patients did not receive PTR. After 1:1 PSM, there were 308 patients in both PTR and non-PTR groups. The K–M survival analysis results showed noteworthy survival disparities between PTR and non-PTR groups, both before and after PSM (p

Ascorbic acid (AA) plays an important role in many physiological and biochemical processes. Adequate quantification of AA is required for controlling the intake of AA for health management. In this study, a portable probe was fabricated based on the assembled FePO4@GO nanozyme by homogeneous precipitation. FePO4@GO exhibits excellent peroxidase (POD) activity. As an efficient free radical scavenger, ascorbic acid scavenges 1O2 free radicals produced by hydrogen peroxide catalyzed by peroxidase enzymes and then inhibits the color reaction of 3,3′,5,5′-tetramethylbenzidine (TMB). A good linear relationship between the color of the reaction system and the concentration of AA in the range of 2.5–75 μM was presented, and the detection limit is 1.25 μM. Furthermore, a visual colorimetric detection platform was constructed using a smartphone. The AA content is accurately reflected by intelligent recognition of color changes in the reaction system. It provides an alternative approach for portable and visual rapid detection of Vitamin C (VC) in medicine. Meanwhile, it also provides a reference for the assembly of an intelligent detection platform based on nanozymes.

Although phase change materials (PCMs) exhibit effective performance in the thermal management of lithium-ion batteries (LIBs), their development is limited by low thermal conductivity and susceptibility to leakage during the solid–liquid phase transition. To address these challenges and enhance thermal management capabilities, this study introduces a novel composite phase change material (CPCM) synthesized by physically mixing paraffin (PA), expanded graphite (EG), and bacterial cellulose (BC). The thermal performance of CPCMs with varying BC proportions is evaluated, and their impact on temperature control in battery thermal management systems (BTMS) is assessed. The results show that the addition of EG and BC significantly improves the thermal conductivity of the CPCM, reaching a value of 1.39 W·m−1·K−1. This also enhances the uniformity of temperature distribution within the battery module and reduces CPCM leakage. By comparing temperature variations within the battery module under different operating conditions, it was found that the intricate network structure of the CPCM promotes uniform temperature distribution, effectively mitigating temperature rise. Consequently, the maximum temperature and maximum temperature difference within the battery module were maintained below 47 °C and 4 °C, respectively. Compared to a system without phase change material at a 3C discharge rate, the maximum cell temperature, maximum module temperature, and maximum temperature difference were reduced by 32.38%, 26.92%, and 34.94%, respectively. These findings provide valuable insights for the design and optimization of BTMS.

Rapid localization of ROI (Region of Interest) for tomographic medical images (TMIs) is an important foundation for efficient image reading, computer-aided education, and well-informed rights of patients. However, due to the multimodality of clinical TMIs, the complexity of anatomy, and the deformation of organs caused by diseases, it is difficult to have a universal and low-cost method for ROI organ localization. This article focuses on actual concerns of TMIs from medical students, engineers, interdisciplinary researchers, and patients, exploring a universal registration method between the clinical CT/MRI dataset and CVH (Chinese Visible Human) to locate the organ ROI in a low-cost and lightweight way. The proposed method is called Two-step Progressive Registration (TSPR), where the first registration adopts “eye–nose triangle” features to determine the spatial orientation, and the second registration adopts the circular contour to determine the spatial scale, ultimately achieving CVH anatomical knowledge automated mapping. Through experimentation with representative clinical TMIs, the registration results are capable of labeling the ROI in the images well and can adapt to the deformation problem of ROI, as well as local extremum problems that are prone to occur in inter-subject registration. Unlike the ideal requirements for TMIs’ data quality in laboratory research, TSPR has good adaptability to incomplete and non-thin-layer quality in real clinical data in a low-cost and lightweight way. This helps medical students, engineers, and interdisciplinary researchers independently browse images, receive computer-aided education, and provide patients with better access to well-informed services, highlighting the potential of digital public health and medical education.

Structural diversity guided steroidal thiazolidin-4-one conjugates were designed and synthesized based on six steroid skeletons mainly including androst-4-ene-3,17-dione, dehydroepiandrosterone, epiandrosterone, androst-1,4-diene-3,17-dione, dienedione and 9α-hydroxy-androst-4-ene-3,17-dione. Their in vitro inhibition activities against cell proliferation were fully investigated, and some of which exhibited good antiproliferative activities as potential CDK1 inhibitor. The detailed analysis of structure–activity relationships (SARs) based on the inhibition activities, kinase assay, and molecular docking model demonstrated that the structure of different steroidal core ring skeleton as well as the N substituents of the thiazolidin-4-one ring influenced the inhibitory activity on cancer cell lines. Especially, compounds 15c and 16c have certain inhibitory effects on the tyrosine protein kinases CDK1/CyclinA2, ALK, CDK6/CyclinD1, FGFR1 and PIM2. Compounds 16c displayed highest inhibitory effect on the kinases of CDK1/CyclinA2 with inhibition rate 56.38 % at the concentration of 10 μM, which induced cell death in A875 cells at least partly (initially), by apoptosis.

Abstract Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β‐blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP‐lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR‐2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA

Abstract As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib‐CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post‐baseline plasma samples of 60 MM patients treated with carfilzomib‐based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post‐baseline/baseline metabolite ratios that differ between the CVAE and no‐CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T‐UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21–0.94, p = 0.044) compared with the no‐CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver‐operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31–0.87, p = 0.023) was significantly lower in post‐baseline/baseline ratios of CVAE patients compared with no‐CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib‐CVAE and potential cardioprotective strategies.

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. A genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly disruption of two nuclear receptors, Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

The Ningxiang pig, a distinguished local breed in China, is recognized for its good meat quality traits. This study examines the proteomics of Ningxiang pigs at three developmental stages and delves into the upstream transcriptomics of these proteomics. Such an analysis facilitates a deeper understanding of the molecular interplay between proteins and transcriptomes in the Ningxiang pig muscle, influencing muscle growth and development. In this research, we analyzed the muscles of Ningxiang pigs at three developmental stages: 30 days in weaned piglets, 90 days in nursery pigs, and 210 days in late fattening pigs. There a total of 16 differentially co-expressed miRNAs (ssc-miRNA-1, ssc-miRNA-378, ssc-miRNA-143, ssc-miRNA-30e, etc.), 74 differentially co-expressed mRNA (PLIN3, CPT2, IGF2 and HSP90AB1, etc.) have been identified in the three stages. 572 differentially abundant proteins (DAPs) (APOC3, NDUFA2, HSPD1, ATP5E, PDHA1, etc.) were readily identified by comparing different time periods. According to the KEGG enrich pathway results that DAPs most enriched in growth and development pathways, immune mechanism pathways and maintaining functions of physical. Through short time-series expression miner (STEM) association analysis, a total of 571 negative miRNA-mRNA interaction pairs and 2 negative miRNA-mRNA-protein (Chr05_11955-Pig.17268.1-ATP5F1B, ssc-miR-194a-3p-Pig.15802.1-ACY1) interaction pairs were found. Our study provides a theoretical basis on molecular mechanism for the study of IMF deposition, muscle growth and immunity in Ningxiang pig breed.

AimConventional approaches to diagnosing common eye diseases using B-mode ultrasonography are labor-intensive and time-consuming, must requiring expert intervention for accuracy. This study aims to address these challenges by proposing an intelligence-assisted analysis five-classification model for diagnosing common eye diseases using B-mode ultrasound images.MethodsThis research utilizes 2064 B-mode ultrasound images of the eye to train a novel model integrating artificial intelligence technology.ResultsThe ConvNeXt-L model achieved outstanding performance with an accuracy rate of 84.3% and a Kappa value of 80.3%. Across five classifications (no obvious abnormality, vitreous opacity, posterior vitreous detachment, retinal detachment, and choroidal detachment), the model demonstrated sensitivity values of 93.2%, 67.6%, 86.1%, 89.4%, and 81.4%, respectively, and specificity values ranging from 94.6% to 98.1%. F1 scores ranged from 71% to 92%, while AUC values ranged from 89.7% to 97.8%.ConclusionAmong various models compared, the ConvNeXt-L model exhibited superior performance. It effectively categorizes and visualizes pathological changes, providing essential assisted information for ophthalmologists and enhancing diagnostic accuracy and efficiency.

Flexible high-density microelectrode arrays (HDMEAs) are emerging as a key component in closed-loop brain–machine interfaces (BMIs), providing high-resolution functionality for recording, stimulation, or both. The flexibility of these arrays provides advantages over rigid ones, such as reduced mismatch between interface and tissue, resilience to micromotion, and sustained long-term performance. This review summarizes the recent developments and applications of flexible HDMEAs in closed-loop BMI systems. It delves into the various challenges encountered in the development of ideal flexible HDMEAs for closed-loop BMI systems and highlights the latest methodologies and breakthroughs to address these challenges. These insights could be instrumental in guiding the creation of future generations of flexible HDMEAs, specifically tailored for use in closed-loop BMIs. The review thoroughly explores both the current state and prospects of these advanced arrays, emphasizing their potential in enhancing BMI technology.

Structured illumination microscopy (SIM) is a popular and powerful super-resolution (SR) technique in biomedical research. However, the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio (SNR) of raw images. To obtain high-quality SR images, several raw images need to be captured under high fluorescence level, which further restricts SIM’s temporal resolution and its applications. Deep learning (DL) is a data-driven technology that has been used to expand the limits of optical microscopy. In this study, we propose a deep neural network based on multi-level wavelet and attention mechanism (MWAM) for SIM. Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image, resulting in superior SR images compared to those generated using wide-field images as input data. We also demonstrate that the number of SIM raw images can be reduced to three, with one image in each illumination orientation, to achieve the optimal tradeoff between temporal and spatial resolution. Furthermore, our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms. We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.

Abstract Background Through bioinformatics analysis to identify the hub genes of Intervertebral disc degeneration (IVDD) associated with basement membranes (BMs) and find out the potential molecular targets and drugs for BMs-related annulus fibrosus (AF) degeneration based on bioinformatic analysis and molecular approach. Methods Intervertebral disc degeneration (IVDD) related targets were obtained from GeneCards, DisGenet and OMIM databases. BMs related genes were obtained from Basement membraneBASE database. The intersection targets were identified and subjected to protein-to-protein interaction (PPI) construction via STRING. Hub genes were identified and conducted Gene ontology (GO) and pathway enrichment analysis through MCODE and Clue GO in Cytospace respectively. DSigDB database was retrieved to predict therapeutic drugs and molecular docking was performed through PyMOL, AutoDock 1.5.6 to verify the binding energy between the drug and the different expressed hub genes. Finally, GSE70362 from GEO database was obtained to verify the different expression and correlation of each hub gene for AF degeneration. Results We identified 41 intersection genes between 3 disease targets databases and Basement membraneBASE database. PPI network revealed 25 hub genes and they were mainly enriched in GO terms relating to glycosaminoglycan catabolic process, the TGF-β signaling pathway. 4 core targets were found to be significant via comparison of microarray samples and they showed strong correlation. The molecular docking results showed that the core targets have strong binding energy with predicting drugs including chitosamine and retinoic acid. Conclusions In this study, we identified hub genes, pathways, potential targets, and drugs for treatment in BMs-related AF degeneration and IVDD.

Sub-synchronous oscillations (SSO) caused by large-scale wind farm integrated systems have become an important issue threatening the security and stability of power systems. Some practical cases have shown that SSO can propagate through multiple voltage levels to more than hundreds kilometers. Many studies have focused on this problem, but there is a lack of research on the power propagation characteristics of SSO. In this paper, a measurement-based method for sub synchronous oscillation (SSO) propagation path criterion in SSO events is proposed. The method is based on the concept of sub synchronous power (SSP). By monitoring the sign of SSP generated by different wind farms or turbines, the propagation path can be identified. The method gives an effective way to quantitatively analyze the power propagation path of sub synchronous oscillations from the power perspective. Experimental cases demonstrate the practicality of the method.

The modern power system exhibits typical “double-high” characteristics as a result of the extensive use of new energy sources like wind and photovoltaics that are connected to the electrical grid, and as a result of this development, sub-synchronous oscillations are becoming an increasingly significant issue. There is an urgent need to research the main influencing factors and propagation mechanism of SSO in complex AC–DC grid since they have a wide range of propagation properties. In this article, the propagation mechanism based on the sub-synchronous power propagation divider coefficient is proposed, and a quantitative analysis approach based on the maximal information coefficient (MIC) of the influencing factors of sub-synchronous oscillation propagation is clarified. The results demonstrate that the power flow on AC transmission is the key factor affecting the propagation of the SSO power’s AC component, the AC transmission resistance characteristics at the frequency of the sub-synchronous oscillation is the main factor affecting the propagation of SSO power’s DC component, and the sub-synchronous power propagates in the complex system according to the diversion coefficient of circuit branch. The efficiency of the method and mechanism proposed in this paper is confirmed by the simulation results.

Effectively evaluating the effectiveness of bridge strengthening is a necessary means to ensure the normal operation of existing strengthened bridges, especially when evaluating the effectiveness of bridge strengthening without interrupting normal traffic. Based on a distributed long-gauge Fiber Bragg Grating (FBG) sensor, this paper derived the macro-strain influence line (MSIL) formula for a simply supported beam bridge under a moving vehicle load, studied the changes in the MSIL at the bottom of the beam under the vehicle load before and after the prestressed CFRP plate strengthening, and proposed a rapid evaluation method for the strengthening effect based on the amplitude of the MSIL as the evaluation index for the strengthening effect. Finally, the prestressed CFRP-strengthened steel beam was tested under the moving vehicle load. The theoretical analysis and the experimental results confirm that under the load of moving vehicles, the macro-strain–time history amplitude of the strengthened steel beams under different prestressed tensioning conditions is different. The amplitude of the macro-strain time history of the strengthened bridge is reduced compared to before strengthening, and the local strengthening effect of the bridge can be monitored by the amplitude change in a single sensor. The change in global stiffness can be evaluated by monitoring the MSIL obtained from multiple long-gauge strain sensors.

(1) Background: Atopic dermatitis (AD) is characterized as a chronic inflammatory skin disease with a significant incidence rate. The pathophysiological mechanisms underlying AD remain incompletely understood. However, extensive research demonstrates that a complex interplay among genetic, immune, and environmental factors contributes to the disruption of skin barrier function. Inflammation is identified as one of the pathological mechanisms in AD. Recombined mussel adhesive protein exhibits anti-inflammatory properties. However, recombinant mussel adhesive protein has been used less frequently for AD, so we explored the therapeutic effect of recombinant mussel adhesive protein for AD and the potential mechanism. (2) Methods: We established a mice model of AD in vivo and an LPS-induced inflammation model in HaCaT cells in vitro. Through assessment of skin lesion scores, itch frequency, transepidermal water loss, skin microcirculation, HE staining, Elisa assays for IL-6, IL-12, IL-13, IL-4, IL-5, IFN-γ, IgE, and TNF-α, immunohistochemical staining for filaggrin and CK14, Masson staining, and Western blot analysis of NF-κB p65, P-P65, Keap1, and Nrf2, the effects of recombined mussel adhesive protein on AD symptoms, pathology, inflammation, and its mechanisms are investigated. (3) Results: The recombined mussel adhesive protein significantly improved the compromised skin barrier, reduced scratching frequency in mice, decreased transepidermal water loss, and lowered the expression of inflammatory factors, thus ameliorating skin inflammation damage. Mechanistically, recombined mussel adhesive protein downregulated the expression of P-p65/p65 and Keap1 while upregulating the level of Nrf2. (4) Conclusions: Overall, our results demonstrate the effectiveness of recombined mussel adhesive protein in attenuating DNFB-induced AD by inhibiting NF-κB and activating the Keap1/Nrf2 signaling pathway. Thus, recombined mussel adhesive protein is a promising therapeutic candidate for the treatment of AD.

Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 min. The proposed detection platform offers portability, ease of use, and high sensitivity, which facilitates the monitoring of exercise-induced muscle injuries at the point of care. This feature is particularly advantageous for end users, enabling timely detection of sports-related injuries and ultimately enhancing prognosis and sports life.

China’s small-arched shed-building machinery mostly adopts manual pole casting and mechanical planting, which have low building efficiency and mechanization. Therefore, we designed an automatic feeding device for shed poles to realize automatic single separation, orderly conveyance and timely dropping of poles. Considering shed pole-pitching pass rate as the evaluation index for the regression model, we adopted a three-factor, three-level experimental design and established the speed of the reclaiming ring, height of the falling shed poles and reclaiming ring spacing as the main influencing factors, obtaining 23.94 r/min, 408.799 mm and 1350 mm, respectively in experiments with a trellis qualification rate of 95.36%. Design-Expert 13 was used to perform analysis of variance and determine the optimal parameter combinations. The average measured trellis qualification rate in tests with the bench adjusted and the optimal parameter combination was 94.23%, with 1.13% relative error between test and theoretical optimization values. This confirmed the optimal parameter combination’s dependability. In field verification test results, pick-up card ring speed was 24 r/min; height of trellis pole drop, 410 mm; pick-up card ring spacing, 1350 mm; and pitching rate, 95.37%, obtaining 0.01% error compared with theoretically optimized values. The prototype operational performance was stable and satisfied design requirements.

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.

Abstract Background Large-scale genotype–phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments. Results We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection. Conclusion Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.

Abstract Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil's high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood–brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs (“oil + hairs”), ultrasound gel with hair shaving (“ultrasound gel + no hair”), and ultrasound gel with hairs (“ultrasound gel + hairs”). The quality of the coupling was evaluated by $${\mathrm{T}}_{2}$$ T 2 -weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The outcome of FUS-BBBO was assessed by MRI contrast agent extravasation using in vivo $${\mathrm{T}}_{1}$$ T 1 -weighted contrast-enhanced MRI. It was also evaluated by ex vivo fluorescence imaging of the mouse brain after intravenous injection of a model drug, Evans blue. The results showed that “oil + hairs” consistently achieved high-quality acoustic coupling without trapping air bubbles. The FUS-BBBO outcome was not significantly different between the “oil + hairs” and the “ultrasound gel + no hair” groups. These two groups had significantly higher levels of BBB opening than the “ultrasound gel + hairs” group. This study demonstrated that oil could be a coupling medium for transcranial FUS procedures without shaving hairs.

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P

Background: Pancreatic cancer is a malignancy with high mortality due to the difficulties in early detection. We investigated and compared the diagnostic and prognostic performance of several blood biomarkers, including microRNA-25 (miR-25), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125). Methods: A retrospective study was conducted at the Chinese People’s Liberation Army General Hospital from May 2014 to September 2018. Serum specimens were collected, and miR-25 expression levels were measured using real-time quantitative polymerase chain reaction. Serum CA19-9, CEA, and CA125 levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses including nonparametric test, receiver operator characteristic (ROC) curves, Kaplan-Meier analysis, and subsequent log-rank test were performed with PRISM 5.0 software. Univariate and multivariate analyses were performed with the R software. P

Abstract Background Many people were found with pulmonary nodules during physical examinations. It is of great practical significance to discriminate benign and malignant nodules by using data mining technology. Methods The subjects' demographic data, baseline examination results, and annual follow‐up low‐dose spiral computerized tomography (LDCT) results were recorded. The findings from annual physical examinations of positive nodules, including highly suspicious nodules and clinically tentative benign nodules, was analyzed. The extreme gradient boosting (XGBoost) model was constructed and the Grid Search CV method was used to select the super parameters. External unit data were used as an external validation set to evaluate the generalization performance of the model. Results A total of 135,503 physical examinees were enrolled. Baseline testing found that 27,636 (20.40%) participants had clinically tentative benign nodules and 611 (0.45%) participants had highly suspicious nodules. The proportion of highly suspicious nodules in participants with negative baseline was about 0.12%–0.46%, which was lower than the baseline level except the follow‐up of >5 years. In the 27,636 participants with clinically tentative benign nodules, only in the first year of LDCT re‐examination was the proportion of highly suspicious nodules (1.40%) significantly greater than that of baseline screening (0.45%) (p 0.05). Furthermore, 322 cases with benign nodules and 196 patients with malignant nodules confirmed by surgery and pathology were compared. A model and the top 15 most important clinical variables were determined by XGBoost algorithm. The area under the curve (AUC) of the model was 0.76 [95% CI: 0.67–0.84], and the accuracy was 0.75. The sensitivity and specificity of the model under this threshold were 0.78 and 0.73, respectively. In the validation of model using external data, the AUC was 0.87 and the accuracy was 0.80. The sensitivity and specificity were 0.83 and 0.77, respectively. Conclusions It is important that pulmonary nodules could be more accurately identified at the first LDCT examination. A model with 15 variables which are routinely measured in the clinic could be helpful to distinguish benign and malignant nodules. It could help the radiological team issue a more accurate report; and it may guide the clinical team regarding LDCT follow‐up.

Diabetes mellitus, an epidemic with a rapidly increasing number of patients, always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization, decreased angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Herein, a poly (lactic-co-glycolic acid) (PLGA)-based microneedle patch loaded with magnesium hydride (MgH2) (MN-MgH2) is manufactured for defeating diabetic wounds. The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH2 that can generate hydrogen (H2) and magnesium ions (Mg2+) after reaction with body fluids. The released H2 reduces the production of ROS, transforming the pathological microenvironment induced by diabetes mellitus. Meanwhile, the released Mg2+ promotes the polarization of pro-healing M2 macrophages. Consequently, cell proliferation and migration are improved, and angiogenesis and tissue regeneration are enhanced. Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H2 and Mg2+ locally and sustainably.

Summary: The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis.

The Bacillus velezensis strain NBNZ-0060 was isolated from the bottom sediment samples of the lake Jin in Wuhan, China. This strain is an aerobic denitrifying bacterium and able to promote growth of submerged macrophytes. The 3,929,784 bp entire genome contains 3,781 coding sequences (CDS), 27 rRNAs, 85 tRNAs, 5 ncRNAs, with an average G + C content of 46.5%. The average nucleotide identity and digital DNA-DNA values between strain NBNZ-0060 and Bacillus velezensis NRRL B-41580T were 98.28% and 84.5%, respectively. The genome data have been deposited in NCBI with the accession number CP133277.1.