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Contract bridge is a competitive-cooperative multiplayer game. In the bidding phase, the decision-making process is complex, given the extensive range of inaccessible information from the partner and opponents. Inferring partner private information seems to be a viable way to promote cooperation. However, extant research has neglected the reliability and effective utilization of inferred information, consequently limiting adaptability in the face of unpredictable policies and hidden hands of opponents. This paper introduces a novel bidding decision algorithm for contract bridge, utilizing generative adversarial inferring (GAI) and alternate inference-decision reinforcement learning (AID-RL). Specifically, GAI advances the reliability and rationality of partner information inference, factoring in stochastic noises and utilizing adversarial training. Concurrently, AID-RL strengthens the effective and explicit exploitation of inference by integrating a reinforcement objective that increases decision-making payoff into the inference model training alongside the original generative objective. Moreover, a novel self-play approach, augmented by the counterfactual difference reward (CDR) mechanism is proposed to expedite policy updates and ensure robust decision-making against inference biases and unknown opponents. Empirical results demonstrate the superior performance of our algorithm, attaining a noteworthy victory of + 0.359 IMPs against Wbridge5, outperforming EPNN and SiB + 0.596 and + 0.062 IMPs. [ABSTRACT FROM AUTHOR]

Nanoparticles have gained attention as potential antiviral agents, but the effects of graphene oxide nanoparticles (GONPs) on influenza virus remain unclear. In this study, we evaluated the antiviral activity of GONPs against influenza virus strain A/Hunan-Lengshuitan/11197/2013(H9N2). Our results show that GONPs with a diameter of 4 nm exerted an antiviral effect, whereas those with a diameter of 400 nm had no effect. Treatment with 4-nm GONPs reduced viral titers by more than 99% and inhibited viral nucleoprotein expression in a dose-dependent manner. We also confirmed that 4-nm GONPs inhibited the infectivity of H9N2 in MDCK cells. A transmission electron microscopic analysis revealed morphological abnormalities in the GONP-treated virus, including the destruction of the envelope glycoprotein spikes and an irregular shape, suggesting that GONPs cause the destruction of the viral coat proteins. Our results highlight the potential utility of GONPs in the prevention and treatment of viral infections, especially those of emerging and re-emerging viruses. [ABSTRACT FROM AUTHOR]

This paper presents an enhanced non-destructive optical measurement method crucial for 3D IC technology. Utilizing a deep neural network and electromagnetic simulation tool, an inverse model is established to predict the critical dimensions (CD) of micron and sub-micron structures. The forward model accelerates data generation, overcoming limitations of the finite-difference time-domain (FDTD) method. Compared to FDTD simulations of reflectance spectra which take about 50 min, the model's prediction time for reflectance spectra is only 0.01 s. The three key dimensions with better prediction results from the inverse model are top radius (Rtop), height, and bottom radius (Rbot). In the proposed joint training model, by simultaneously training forward and inverse models and adjusting the weights of forward and inverse loss functions, the mean absolute percentage error (MAPE) for Rtop, height, and Rbot is reduced from 0.26 to 0.08%, 0.69 to 0.44%, and 4.01 to 0.6% respectively. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, the impact of CAF subpopulation trajectory differentiation on CRC remains unclear. Methods: In this study, we first explored the trajectory differences of CAFs subpopulations using bulk and integrated single-cell sequencing data, and then performed consensus clustering of CRC samples based on the trajectory differential genes of CAFs subpopulations. Subsequently, we analyzed the heterogeneity of CRC subtypes using bioinformatics. Finally, we constructed relevant prognostic signature using machine learning and validated them using spatial transcriptomic data. Results: Based on the differential genes of CAFs subpopulation trajectory differentiation, we identified two CRC subtypes (C1 and C2) in this study. Compared to C1, C2 exhibited worse prognosis, higher immune evasion microenvironment and high CAF characteristics. C1 was primarily associated with metabolism, while C2 was primarily associated with cell metastasis and immune regulation. By combining 101 combinations of 10 machine learning algorithms, we developed a High-CAF risk signatures (HCAFRS) based on the C2 characteristic gene. HCAFRS was an independent prognostic factor for CRC and, when combined with clinical parameters, significantly predicted the overall survival of CRC patients. HCAFRS was closely associated with epithelial-mesenchymal transition, angiogenesis, and hypoxia. Furthermore, the risk score of HCAFRS was mainly derived from CAFs and was validated in the spatial transcriptomic data. Conclusion: In conclusion, HCAFRS has the potential to serve as a promising prognostic indicator for CRC, improving the quality of life for CRC patients. [ABSTRACT FROM AUTHOR]

Background: Metabolic unhealth (MUH) is closely associated with cardiovascular disease (CVD). Life's Essential 8 (LE8), a recently updated cardiovascular health (CVH) assessment, has some overlapping indicators with MUH but is more comprehensive and complicated than MUH. Given the close relationship between them, it is important to compare these two measurements. Methods: This population-based cross-sectional survey included 20- to 80-year-old individuals from 7 National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Based on the parameters provided by the American Heart Association, the LE8 score (which ranges from 0 to 100) was used to classify CVH into three categories: low (0–49), moderate (50–79), and high (80–100). The MUH status was evaluated by blood glucose, blood pressure, and blood lipids. The associations were assessed by multivariable regression analysis, subgroup analysis, restricted cubic spline models, and sensitivity analysis. Results: A total of 22,582 participants were enrolled (median of age was 45 years old), among them, 11,127 were female (weighted percentage, 49%) and 16,595 were classified as MUH (weighted percentage, 73.5%). The weighted median LE8 scores of metabolic health (MH) and MUH individuals are 73.75 and 59.38, respectively. Higher LE8 scores were linked to lower risks of MUH (odds ratio [OR] for every 10 scores increase, 0.53; 95% CI 0.51–0.55), and a nonlinear dose–response relationship was seen after the adjustment of potential confounders. This negative correlation between LE8 scores, and MUH was strengthened among elderly population. Conclusions: Higher LE8 and its subscales scores were inversely and nonlinearly linked with the lower presence of MUH. MUH is consistent with LE8 scores, which can be considered as an alternative indicator when it is difficult to collect the information of health behaviors. [ABSTRACT FROM AUTHOR]

Because the growth of mangoes is often affected by pests and diseases, the application of object detection technology can effectively solve this problem. However, deploying object detection models on mobile devices is challenging due to resource constraints and high-efficiency requirements. To address this issue, we reduced the parameters in the target detection model, facilitating its deployment on mobile devices to detect mango pests and diseases. This study introduced the improved lightweight target detection model GAS-YOLOv8. The model's performance was improved through the following three modifications. First, the model backbone was replaced with GhostHGNetv2, significantly reducing the model parameters. Second, the lightweight detection head AsDDet was adopted to further decrease the parameters. Finally, to increase the detection accuracy of the lightweight model without significantly increasing parameters, the C2f module was replaced with the C2f-SE module. Validation with a publicly available dataset of mango pests and diseases showed that the accuracy for insect pests increased from 97.1 to 98.6%, the accuracy for diseases increased from 91.4 to 91.7%, and the model parameters decreased by 33%. This demonstrates that the GAS-YOLOv8 model effectively addresses the issues of large computational volume and challenging deployment for the detection of mango pests and diseases. [ABSTRACT FROM AUTHOR]

Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography–tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD. [ABSTRACT FROM AUTHOR]

The present study investigates the efficacy of newly developed Zr-based metal–organic frameworks, specifically MIP-206, and its amine-modified counterpart, MIP-206-NH2, for the re-covery of antimony (Sb) from both synthetic and actual mining wastewater. Batch method studies were employed to examine the effect of waste media pH, Sb concentration, process kinetics, and the performance of the regeneration solution. MIP-206-NH2 exhibited impressive separation capabilities, achieving 102.18 mg/g and 63.23 mg/g for Sb (V) and Sb (III), respectively. In contrast, the pristine MIP-206 reached maximum values of 26.26 mg/g for Sb (V) and 16.95 mg/g for Sb (III). The separation process was well-described by the Langmuir equation, and the kinetics followed the pseudo-second-order model. Although the amine modification resulted in a decrease in the surface area of MIP-206 from 1345.21 to 1169.86 m2/g, SEM and XRD analyses confirmed that the structural integrity of MIP-206-NH2 remained unchanged. In terms of reusability, MIP-206-NH2 maintained up to 90% of its separation performance over 9 cycles, while MIP-206 demonstrated effectiveness for 7 cycles. The regeneration solution exhibited a capacity of approximately 0.63 mol/L for Sb (V) and 0.71 mol/L for Sb (III). Furthermore, MIP-206 and MIP-206-NH2 demonstrated successful application in selectively separating Sb from real mining wastewater. [ABSTRACT FROM AUTHOR]

Debris flows can develop into mega catastrophes in semi-arid regions when the source materials come from landslides, and both snowmelt and precipitation are involved in increasing water discharge. In such environments, the formation of large-scale debris flows exhibits a distinguishable pattern, in which a multi-fold lower triggering rainfall threshold holds compared to humid regions. Previous research mainly focuses on mechanisms in humid environments or neglects variations across aridity classes. In this study, the formation and evolutionary mechanism of a debris flow occurring in a semi-arid context is investigated via field surveys, granularity measurement, terrain and climate analyses, and snow cover change detection. By examining the July 22, 2021, Xiao Dongsuo debris flow at Amidongsuo Park in the Qilian Ranges on the northeastern margin of the Tibetan Plateau, the mechanism of debris flows in semi-arid regions is revealed. The research finds that the large debris flow, whose course erosion scales up the disaster by 0.12 million m3, is primarily supplied by landslide deposits of 1.16 million m3. The debris flow is empowered by the integrated flow of extreme precipitation and extreme heat-stimulated snowmelt. However, the precipitation required to trigger the debris flow is much lower than that of precipitation-dominated ones and those in humid regions. In semi-arid mountains, prolonged extreme heat tends to increase soil moisture in areas covered by snow or permafrost. This reduces slope stability and induces slope failures, amplifying the disaster magnitude and raising disaster risks through extended deterioration. Hence, this study inspects the failure mechanism associated with debris flows in semi-arid regions for a more comprehensive understanding to constitute viable control plans for analogous disasters. [ABSTRACT FROM AUTHOR]

The fifth generation (5G) of mobile networks is emerging as a key enabler of modern factory automation (FA) applications that ensure timely and reliable data exchange between network components. Network slicing (NS), which shares an underlying infrastructure with different applications and ensures application isolation, is the key 5G technology to support the diverse quality of service requirements of modern FA applications. In this article, an end-to-end (E2E) NS solution is proposed for FA applications in a 5G network. Regression approaches are used to construct a performance model for each slice to map the service level agreement to the network attributes. Interference coordination approaches for switched beam systems are proposed to optimize radio access network (RAN) performance models. A case study of a non-public network is used to show the proposed NS solution. Simulation result shows that for services with different QoS requirements, different IC approaches should be used as optimization methods. Design prediction using regression approach has been evaluated and shows that the prediction successful rate increases when more existing data are used. [ABSTRACT FROM AUTHOR]

Advances in AI techniques have fueled research on using EEG data for psychiatric disorder diagnosis. Despite EEG's cost-effectiveness and high temporal resolution, low Signal-to-Noise Ratio (SNR) hampers critical marker extraction and model improvement, while denoising techniques will lead to a loss of effective information in EEG. The aim of this study is to employ AI methods for the processing of raw EEG data. The primary objectives of the processing are twofold: first, to acquire more reliable markers for schizophrenia, and second, to construct a superior automatic classification for schizophrenia. To remove the noises and retain task-related (classification tasks) effective information mostly, we introduce an Effective Information Estimation Framework (EIEF) based on three key principles: the task-centered approach, leveraging 1D-CNNs' test metrics to gauge effective information proportion, and feedback. We address a theoretical foundation by integrating these principles into mathematical derivations to propose the mathematical model of EIEF. In experiments, we established a paradigm pool of 66 denoising paradigms, with EIEF successfully identifying the optimal paradigms (on two datasets) for restoring effective information. Utilizing the processed dataset, we trained a 3D-CNN for automatic schizophrenia diagnosis, achieving outstanding test accuracies of 99.94 % on dataset 1 and 98.02 % on dataset 2 in subject-dependent evaluations, and accuracies of 89.85 % on dataset 1 and 98.02 % on dataset 2 in subject-independent evaluations. Additionally, we extracted 38 features from each channel of both processed and raw datasets, revealing that 20.86 % (dataset 1) of feature distribution differences between the patients and the healthy exhibited significant changes after implementing the optimal paradigm. We enhance model performance and extract more reliable electrobiological markers. These findings have promising implications for advancing the field of the clinical diagnosis and pathological analysis of Schizophrenia. [ABSTRACT FROM AUTHOR]

Global warming has a severe impact on the flowering time and yield of crops. Histone modifications have been well-documented for their roles in enabling plant plasticity in ambient temperature. However, the factor modulating histone modifications and their involvement in habitat adaptation have remained elusive. In this study, through genome-wide pattern analysis and quantitative-trait-locus (QTL) mapping, we reveal that BrJMJ18 is a candidate gene for a QTL regulating thermotolerance in thermotolerant B. rapa subsp. chinensis var. parachinensis (or Caixin, abbreviated to Par). BrJMJ18 encodes an H3K36me2/3 Jumonji demethylase that remodels H3K36 methylation across the genome. We demonstrate that the BrJMJ18 allele from Par (BrJMJ18Par) influences flowering time and plant growth in a temperature-dependent manner via characterizing overexpression and CRISPR/Cas9 mutant plants. We further show that overexpression of BrJMJ18Par can modulate the expression of BrFLC3, one of the five BrFLC orthologs. Furthermore, ChIP-seq and transcriptome data reveal that BrJMJ18Par can regulate chlorophyll biosynthesis under high temperatures. We also demonstrate that three amino acid mutations may account for function differences in BrJMJ18 between subspecies. Based on these findings, we propose a working model in which an H3K36me2/3 demethylase, while not affecting agronomic traits under normal conditions, can enhance resilience under heat stress in Brassica rapa. The study reveals that the BrJMJ18 gene, encoding an H3K36me2/3 Jumonji demethylase, is a candidate gene for a QTL regulating thermotolerance in a thermotolerant Brassica rapa subspecies, and its allele (BrJMJ18Par) can modulate flowering time, plant growth, and chlorophyll biosynthesis in a temperature-dependent manner. [ABSTRACT FROM AUTHOR]

Target detection, as a core issue in the field of computer vision, is widely applied in many key areas such as face recognition, license plate recognition, security protection, and driverless driving. Although its detection speed and accuracy continue to break records, there are still many challenges and difficulties in target detection of remote sensing images, which require further in-depth research and exploration. Remote sensing images can be regarded as a "three-dimensional data cube", with more complex background information, dense and small object targets, and more severe weather interference factors. These factors lead to large positioning errors and low detection accuracy in the target detection process of remote sensing images. An improved YOLOv7 object detection model is proposed to address the problem of high false negative rate for dense and small objects in remote sensing images. Firstly, the GAM attention mechanism is introduced, and a global scheduling mechanism is proposed to improve the performance of deep neural networks by reducing information reduction and expanding global interaction representations, thus enhancing the network's sensitivity to targets. Secondly, the loss function CIoU in the original Yolov7 network model is replaced by SIoU, aiming to optimize the loss function, reduce losses, and improve the generalization of the network. Finally, the model is tested on the public available RSOD remote sensing dataset, and its generalization is verified on the Okahublot FloW-Img sub-dataset. The results showed that the accuracy (MAP@0.5) of detecting objects improved by 1.7 percentage points and 1.5 percentage points respectively for the improved Yolov7 network model compared to the original model, effectively improves the accuracy of detecting small targets in remote sensing images and solves the problem of leakage detection of small targets in remote sensing images. [ABSTRACT FROM AUTHOR]

The steroid hormone 17β-estradiol (E2) has a significant impact on the development and progression of tumors. E2 stimulates tumor cell growth and metabolism, leading to an increase in reactive oxygen species (ROS) production. However, the rise in ROS levels is not sufficient to cause severe harm to cancer cells. and the mechanisms that regulate ROS are not well understood. Since FOXM1 plays a crucial role in the production of ROS, we aimed to investigate the impact of E2 on oxidative stress and the involvement of FOXM1 in the Ishikawa endometrial cancer cell line. Our research revealed that E2 controls the levels of ROS inside cells and safeguards them from apoptosis by promoting the expression of FOXM1. We observed a decrease in the expression of FOXM1 alongside an increase in oxidative damage. Moreover, cells demonstrated elevated levels of FOXM1 and ERα upon E2 treatment. Overall, our findings suggest that E2 prevents apoptosis induced by oxidative stress in endometrial cancer cells by encouraging the expression of FOXM1, potentially affecting ERα. [ABSTRACT FROM AUTHOR]

Mitochondria are dynamic organelles that participate in different cellular process that control metabolism, cell division, and survival, and the kidney is one of the most metabolically active organs that contains abundant mitochondria. Perturbations in mitochondrial homeostasis in the kidney can accelerate kidney aging, and maintaining mitochondrial homeostasis can effectively delay aging in the kidney. Kidney aging is a degenerative process linked to detrimental processes. The significance of aberrant mitochondrial homeostasis in renal aging has received increasing attention. However, the contribution of mitochondrial quality control (MQC) to renal aging has not been reviewed in detail. Here, we generalize the current factors contributing to renal aging, review the alterations in MQC during renal injury and aging, and analyze the relationship between mitochondria and intrinsic renal cells. We also introduce MQC in the context of renal aging, and discuss the study of mitochondria in the intrinsic cells of the kidney, which is the innovation of our paper. In addition, during kidney injury and repair, the specific functions and regulatory mechanisms of MQC systems in resident and circulating cell types remain unclear. Currently, most of the studies we reviewed are based on animal and cellular models, the relationship between renal tissue aging and mitochondria has not been adequately investigated in clinical studies, and there is still a long way to go. [ABSTRACT FROM AUTHOR]

Specific emitter identification (SEI) is a technology that identifies different emitters through their unique characteristics. Research on traditional specific emitter identification systems focuses on general feature extraction. However, its effectiveness significantly decreases when faced with various influencing factors, such as time changes. Existing domain adaptation SEI methods also suffer from limitations such as the single domain scale and the poor performance against unpredictable changing factors. In this paper, we propose a multi-scale iterative domain adaptation (MSIDA) method for SEI based on domain adaptation, targeting the time variation factor specifically. The proposed method collects signals across different domain scales (seconds and days) and uses an improved domain adaptation method to align signals based on their domain characteristics and source properties at different scales, thereby eliminating the influence of the time factor. Given that the impact of certain factors such as time on SEI is unpredictable and irregular, our proposed method continuously tracks the influence of these factors through iterative domain adaptation, thereby improving the model's generalization ability to these influencing factors. Furthermore, considering the difficulty of labeling data, our proposed flexible loss function can effectively mine the available information from both unlabeled and labeled data. Whether compared with traditional SEI methods or existing domain adaptation SEI methods, experimental results show that our proposed MSIDA method achieved at least a 6% increase in recognition accuracy, which have demonstrated that our proposed method is more robust to temporal variation factors. [ABSTRACT FROM AUTHOR]

Summary: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. Introduction: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. Methods: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. Results: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. Conclusion: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic disorder with intricate pathogenic mechanisms. Despite the availability of various oral medications for controlling the condition, reports of poor glycemic control in type 2 diabetes persist, possibly involving unknown pathogenic mechanisms. In recent years, the gut microbiota have emerged as a highly promising target for T2DM treatment, with the metabolites produced by gut microbiota serving as crucial intermediaries connecting gut microbiota and strongly related to T2DM. Increasingly, traditional Chinese medicine is being considered to target the gut microbiota for T2DM treatment, and many of them are edible. In studies conducted on animal models, edible traditional Chinese medicine have been shown to primarily alter three significant gut microbiotal metabolites: short-chain fatty acids, bile acids, and branched-chain amino acids. These metabolites play crucial roles in alleviating T2DM by improving glucose metabolism and reducing inflammation. This review primarily summarizes twelve edible traditional Chinese medicines that improve T2DM by modulating the aforementioned three gut microbiotal metabolites, along with potential underlying molecular mechanisms, and also incorporation of edible traditional Chinese medicines into the diets of T2DM patients and combined use with probiotics for treating T2DM are discussed. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a common diabetic complication. Studies show that mitophagy inhibition induced-ferroptosis plays a crucial role in DN progression. UHRF1 is associated with mitophagy and is highly expression in DN patients, however, the effect of UHRF1 on DN is still unclear. Thus, in this study, we aimed to investigate whether UHRF1 involves DN development by the mitophagy/ferroptosis pathway. We overexpressed UHRF1 using an adeno-associated virus 9 (AAV9) system in high-fat diet/streptozotocin-induced diabetic mice. Renal function index, pathological changes, mitophagy factors, and ferroptosis factors were detected in vivo. High-glucose cultured human renal proximal tubular (HK-2) cells were used as in vitro models to investigate the mechanism of UHRF1 in DN. We found that diabetic mice exhibited kidney damage, which was alleviated by UHRF1 overexpression. UHRF1 overexpression promoted PINK1-mediated mitophagy and inhibited the expression of thioredoxin interacting protein (TXNIP), a factor associated with mitochondrial dysfunction. Additionally, UHRF1 overexpression alleviated lipid peroxidation and free iron accumulation, and upregulated the expression of GPX4 and Slc7a11, indicating the inhibition effect of UHRF1 overexpression on ferroptosis. We further investigated the mechanism of UHRF1 in the mitophagy/ferroptosis pathway in DN. We found that UHRF1 overexpression promoted PINK1-mediated mitophagy via inhibiting TXNIP expression, thus suppressing ferroptosis. These findings confirmed that upregulation of UHRF1 expression alleviates DN, indicating that UHRF1 has a reno-protective effect against DN. [ABSTRACT FROM AUTHOR]

Soybean [Glycine max (L.) Merr.] is an important seed crop with agricultural sustainability that can be used to meet the growing demand for plant-based oil and protein worldwide. Expanding the cultivation of soybean to high-latitude regions could be an effective strategy for enhancing soybean production. Low temperatures in these regions can inhibit seed germination during the planting season. Despite their importance, many cold tolerance-related genes in soybean remain unidentified. Here, we carried out a genome-wide association study (GWAS) in a diverse soybean population with large variations in cold tolerance-related germination traits. The analyses led to the identification of a total of 46 single-nucleotide polymorphisms (SNPs) that were significantly associated with cold tolerance-related traits. We identified a new locus on chromosome 18, qCold-18–3, that was associated with both the low-temperature germination rate and potential. Furthermore, Abscisic Acid-Deficient4 (GmABA4) was prioritized as the most promising candidate gene. In addition, GmABA4 was strongly induced in a cold-tolerant accession by cold stress during germination, and it contains cis-acting elements associated with low temperature in its promoter region. Haplotype analysis revealed that the accessions harboring Hap3 of GmABA4 were more tolerant to low temperature than those harboring the other haplotypes. In this study, a new cold tolerance-related candidate gene, GmABA4, was identified through GWAS, and further study could advance our understanding of the underlying genetic mechanisms and facilitate the breeding of soybean with improved cold tolerance. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic kidney disease (DKD) is one of the prominent microvascular complications of diabetes and the leading cause of end-stage renal disease. Inflammation plays a crucial role in the development and progression of DKD. Currently, only a few studies depict the landscape of infiltrating immune cells and their potential regulatory network in DKD. To gain a better understanding of the role of immune cells in the renal microenvironment, we sought to reveal the profile of infiltrating immune cells and their potential regulatory network in DKD. Methods: We obtained the transcriptomes and the corresponding clinical data of 19 DKD and 25 control samples from the Gene Expression Omnibus and Nephroseq databases, respectively. Thereafter, we conducted an analysis on the infiltrating immune cells and identified immune-related differentially expressed genes through bioinformatics. Finally, correlation analyses among immune cells, immune genes, and clinical manifestations were performed, and differentially infiltrating immune cell subsets were verified through multiplex immunofluorescence staining. Results: We demonstrated the landscape of infiltrating immune cells in patients with DKD and identified the top five hub immune regulatory genes (C3, IL7R, TYROBP, BMP2, and CXCL6). Three of the core genes (C3, BMP2, and CXCL6) were significantly correlated with the estimated glomerular filtration rate. Through multiplex immunofluorescence staining, we verified that macrophage numbers were remarkably elevated, whereas Treg cells were remarkably reduced in diabetic kidney tissues. Th2 cells were scarce in the kidney tissue. Conclusion: Collectively, our findings shed light on new, possible therapeutic strategies for DKD, from an immune microenvironment perspective. [ABSTRACT FROM AUTHOR]

Severe heterogeneity within glioblastoma has spurred the notion that disrupting the interplay between multiple elements on immunosuppression is at the core of meaningful anti-tumor responses. T cell immunoreceptor with Ig and ITIM domains (TIGIT) and its glioblastoma-associated antigen, CD155, form a highly immunosuppressive axis in glioblastoma and other solid tumors, yet targeting of TIGIT, a functionally heterogeneous receptor on tumor-infiltrating immune cells, has largely been ineffective as monotherapy, suggesting that disruption of its inhibitory network might be necessary for measurable responses. It is within this context that we show that the usurpation of the TIGIT − CD155 axis via engineered synNotch-mediated activation of induced pluripotent stem cell-derived natural killer (NK) cells promotes transcription factor-mediated activation of a downstream signaling cascade that results in the controlled, localized blockade of CD73 to disrupt purinergic activity otherwise resulting in the production and accumulation of immunosuppressive extracellular adenosine. Such "decoy" receptor engages CD155 binding to TIGIT, but tilts inhibitory TIGIT/CD155 interactions toward activation via downstream synNotch signaling. Usurping activities of TIGIT and CD73 promotes the function of adoptively transferred NK cells into intracranial patient-derived models of glioblastoma and enhances their natural cytolytic functions against this tumor to result in complete tumor eradication. In addition, targeting both receptors, in turn, reprograms the glioblastoma microenvironment via the recruitment of T cells and the downregulation of M2 macrophages. This study demonstrates that TIGIT/CD155 and CD73 are targetable receptor partners in glioblastoma. Our data show that synNotch-engineered pluripotent stem cell-derived NK cells are not only effective mediators of anti-glioblastoma responses within the setting of CD73 and TIGIT/CD155 co-targeting, but represent a powerful allogeneic treatment option for this tumor. Given its immunosuppressive effect in glioblastoma (GBM), targeting the TIGIT-CD155 axis presents an attractive therapeutic strategy. Here, the authors develop an adoptive natural killer (iNK) cells therapy with anti-CD155 synNotch-inducible CD73 antibody production to reverse the effect of TIGIT-CD155 signaling for the treatment of GBM. [ABSTRACT FROM AUTHOR]

In this study, we propose a generalized pseudoclassical theory for the kicked rotor model in an attempt to discern the footprints of the classical dynamics in the deep quantum regime. Compared with the previous pseudoclassical theory that applies only in the neighborhoods of the lowest two quantum resonances, the proposed theory is applicable in the neighborhoods of all quantum resonances in principle by considering the quantum effect of the free rotation at a quantum resonance. In particular, it is confirmed by simulations that the quantum wavepacket dynamics can be successfully forecasted based on the generalized pseudoclassical dynamics, offering an intriguing example where it is feasible to bridge the dynamics in the deep quantum regime to the classical dynamics. The application of the generalized pseudoclassical theory to the P T -symmetric kicked rotor is also discussed. [ABSTRACT FROM AUTHOR]

Objective: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. Methods: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. Results: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). Conclusions: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis. [ABSTRACT FROM AUTHOR]

Groundwater fluctuations are an important factor in the occurrence of landslides. Rainfall or changes in reservoir levels can cause fluctuations in groundwater within the slope, making the slope susceptible to landslides. This paper proposes a simple method that directly correlates groundwater level and rainfall, enabling the prediction of changes in the three-dimensional (3D) phreatic surface under rainfall infiltration. Based on the solved phreatic surface, we derive the seepage force and the normal stress expression on the sliding surface. A strict overall analysis method is proposed for solving the safety factor of the slope subjected to rainfall. The reliability of the proposed method is established through verification against various scenarios defined by a classic slope model. Furthermore, we investigate the variations in the phreatic surface and the evolution of safety conditions under rainfall infiltration for a project slope located in the Three Gorges Reservoir area. The results demonstrate that the rise in groundwater level due to rainfall infiltration is small and consistent relative to the entire landslide body. The magnitude of groundwater level rise is directly proportional to precipitation volume, while soil porosity above phreatic surface exerts a greater influence on safety factor than permeability coefficient and saturation. [ABSTRACT FROM AUTHOR]

Purpose: Understanding the variations and driving variables of soil ecological stoichiometry in high-altitude alpine ecosystems is crucial for the effective management and regulation of vulnerable environments. In high-altitude alpine ecosystems with limited data availability, the connection between soil nutrient content, particularly soil nutrient stoichiometry and land use types, remains unclear. This study aimed to investigate the characteristics and control of soil nutrient stoichiometric ratios under different land use patterns. Methods: A transect covering farmland (FA), forestland (FO), and grassland (GR) was established in the southeast of Tibet Autonomous Region, and totally, 59 sampling points at an interval of 25–30 km were selected for field survey and sampling. The patterns and drivers of soil nutrient stoichiometry under various land use types were studied by measuring soil properties at different depths (0–10 cm, 10–20 cm, and 20–30 cm). Results: Soil organic carbon (SOC), total nitrogen (TN), C:N, C:P, and N:P ratios in FO and GR were higher than those in FA, while total phosphorus (TP) exhibited the opposite trend. Both SOC content and C:P ratio were significantly influenced by soil depth (p < 0.05), showing a declining tendency with the increasing soil depth. TN, TP, C:N, and N:P were not affected by soil depth (p > 0.05). Redundancy analysis indicated that mean annual rainfall, total porosity, and slope were the key factors affecting soil nutrient stoichiometry in FA and FO, while nutrient stoichiometry in GR was mainly affected by bulk density, altitude, and slope. In the random forest model, soil properties, climate, and topography could jointly explain 60.81⁓84.78% of the total differences in SOC, TN, and TP concentrations and stoichiometric ratios. Conclusion: Our findings showed that SOC, TN, and TP concentrations and their ratios were significantly influenced by land use patterns and that the driving factors of SOC, TN, TP concentrations and their stoichiometric ratios were different. This work provides a basis for understanding ecosystem processes and designing sustainable soil and environmental management decisions in alpine regions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the molecular pathogenesis of Graves' disease (GD). Methods: The gene expression profile in CD4+ T cells from GD patients and healthy controls were analyzed through mRNA-sequencing. The expression of NR4A2 was determined by quantitative real-time PCR and western blot. The levels of Th17 and Treg were determined by flow cytometry. ELISA was employed to detect the levels of IL-10, IL-17A, IL-17F and IL-22. Results: In the CD4+ T cells from GD patients, there were 128 up-regulated and 510 down-regulated genes. Subsequently, we focused on the role of nuclear receptor 4 group A member 2 (NR4A2) in GD. NR4A2 was lowly expressed in the CD4+ T cells from GD patients. Its expression was negatively correlated with free triiodothyronine and tetraiodothyronine, but positively correlated with thyroid stimulating hormone. NR4A2 knockdown decreased the percentage of Treg cells, with a decreased IL-10 level. While its over-expression augmented the Treg differentiation, with an elevated IL-10 level. In addition, knockdown or over-expression of NR4A2 showed no significant influence on Th17 differentiation. Conclusion: These results indicate that the low level of NR4A2 in GD patients may suppress Treg differentiation, but have no influence on Th17 differentiation, leading to the imbalance of Th17/Treg and contributing to the development of GD. Revealing the role of NR4A2 in GD provides a novel insight for the treatment of GD. [ABSTRACT FROM AUTHOR]

Glucose oxidation reaction is kinetically sluggish and demands a highly efficient catalyst. Herein, we report a direct glucose alkaline fuel cell (DGAFC) using physically mixed Ni2Co nanoparticles and reduced graphene oxide (Ni2Co-rGO) supported on nickel foam as an anode to promote glucose oxidation. The DGAFC with the Ni2Co-rGO anode delivered a remarkably enhanced peak power density of 40.44 W/m2 at room temperature, which was 74.91% higher than the control (23.12 W/m2). Different techniques including XPS, SEM, linear sweep voltammetry, and electrochemical impedance spectroscopy were used to explore the physiochemical and electrochemical properties of the catalyst. Our results demonstrate that Ni2Co-rGO exhibits an excellent activity toward glucose oxidation in alkaline medium, leading to a drastic improvement in the anode performance. There should be a synergistic effect between rGO and Ni2Co. In the Ni2Co-rGO nanocomposite, rGO not only acts as a support for the Ni2Co nanoparticles and also promotes the electron transfer during the glucose oxidation process. This study can promote the development of bi-transition metal-based catalysts for DGAFCs. [ABSTRACT FROM AUTHOR]

In this study, an integrated QuEChERS method was developed for the rapid determination of 22 per- and polyfluoroalkyl substances (PFASs) in milk by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The extraction and purification processes were combined into one step with this method. Meanwhile, the solid–liquid separation was carried out by magnetic suction (Fe3O4-SiO2) instead of the centrifugal process. The primary experimental parameters were optimized, including the type of extraction solvent, the amounts of magnetic nanomaterials (Fe3O4-SiO2), and the purification materials (ZrO2 and C18). The developed method exhibits high precision (RSDs < 9.9%), low limits of detection (0.004–0.079 μg/kg) and limits of quantitation (0.01–0.26 μg/kg), and acceptable recovery (71.7–116%) under optimized conditions. The developed integrated QuEChERS method had clear superiority in terms of sample pretreatment time, operating procedures, reagent amount, and recovery. This makes it an excellent alternative analytical technique for PFAS residue measurement at low micrograms-per-kilogram ranges with desirable sensitivity. [ABSTRACT FROM AUTHOR]

Objective: Currently, it is unclear whether serum Cystatin C can be used to evaluate the prognosis of ALS. We aim to study the relationship between serum Cystatin C and survival in ALS. Methods: Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, and the Chinese PLA General Hospital from January 2016 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. According to the levels of serum Cystatin C, the participants were divided into high and low Cystatin C levels groups. The comparison between groups was performed with parametric or non-parametric test. Kaplan–Meier method and Cox regression model were used to calculate survival analysis. Results: Three hundred fifty-six sporadic ALS patients were enrolled in this study, including 203 males and 153 females. Among all ALS patients, 26 cases (7.3%) were lost to follow-up, 226 cases (63.5%) died, and 104 cases (29.2%) were still alive at the last follow-up. The median survival time of all ALS patients was 42.0 months. Patients with high Cystatin C levels had shorter median survival than those with lower Cystatin C levels (38.0 months vs. 48.0 months, P = 2.58 × 10−4). In multivariate Cox regression analysis, onset form, age of onset, diagnostic delay, disease progression rate, creatinine, and serum Cystatin C levels were associated with ALS survival. Conclusions: Our study found that serum Cystatin C was associated with ALS survival, and serum Cystatin C level might be an independent predictor of ALS survival. [ABSTRACT FROM AUTHOR]

Phospholipase D (PLD) with the higher transphosphatidylation activity was screened from Streptomyces sp. LD0501 basing on the protoplast mutagenesis technology. Then, it was successfully bio-imprinted to form a hyperactivated structure and rigidified by the intramolecular cross-linking, which was immobilized on the nonporous nanoscale silica. Characterization techniques were employed to investigate the structure and physicochemical properties of the catalysts, including Fourier transform infrared (FTIR) spectra and scanning electron microscopy (SEM) analysis. Transphosphatidylation activity and selectivity were improved significantly when immobilized PLD was used. The maximum yield for the production of phosphatidylserine (PS) reached 97% and the side reaction, the hydrolysis, was minimized. These results were further confirmed by the nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. The imprint-induced characteristics of PLD was successfully "remembered" even in the present of much water. In addition, this immobilized hyperactivated PLD showed the excellent operational stabilities and environmental tolerances. [ABSTRACT FROM AUTHOR]

Background: Clinical use of dynamic myocardial perfusion imaging (D-MPI) of cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT is growing, showing a higher application value than conventional SPECT. The prognostic value of ischemia in patients with non-obstructive coronary arteries (INOCA) remains an important challenge for investigation. The primary objective of this study was to investigate the prognostic value of myocardial flow reserve (MFR) measured with low-dose D-MPI of CZT cardiac-dedicated SPECT in the assessment of patients with INOCA. Methods: Consecutive screening of patients with INOCA and obstructive coronary artery disease (OCAD) who had coronary angiography (CAG) data was performed within three months before or after D-MPI imaging. The patients who met the inclusion criteria were retrospectively analyzed and follow-up by telephone was performed. The enrolled patients were then divided into the INOCA and OCAD groups. INOCA was defined as signs and/or symptoms of myocardial ischemia but with < 50% epicardial stenosis. OCAD was defined as obstructive stenosis (≥ 50% stenosis) of epicardial coronary arteries or their major branches on the CAG. Medical treatments, Seattle Angina Questionnaire (SAQ) scores, and major adverse cardiac events (MACEs) were studied. The Kaplan–Meier survival curve, Log-rank test, and univariable COX regression analysis were used to evaluate the prognosis of patients and associated predictors, with P < 0.05 being considered statistically significant. Results: A total of 303 patients (159 males and 144 females) were enrolled for the final analysis after excluding 24 patients who were lost to follow-up. The mean age of the included cases was 61.94 ± 8.59 years, of which 203 (67.0%) cases were OCAD and 100 (33.0%) cases were INOCA, respectively. The median follow-up was 16 months (14-21 months). Kaplan–Meier survival curves showed that the incidence of MACE was similar in the INOCA and OCAD groups (log-rank P = 0.2645), while those with reduced MFR showed a higher incidence of MACE than those with normal MFR (log-rank P = 0.0019). The subgroup analysis in the OCAD group revealed that 105 patients with reduced MFR had a higher incidence of MACE than those with normal MFR (log-rank P = 0.0226). The subgroup analysis in the INOCA group showed that 37 patients with reduced MFR had a higher incidence of MACE than those with normal MFR in the INOCA group (log-rank P = 0.0186). Univariable Cox regression analysis showed for every 1 unit increase in MFR, the risk of MACE for INOCA was reduced by 66.1% and that for OCAD by 64.2%. For each 1 mL·g−1·min−1 increase in LV-sMBF, the risk of MACE was reduced by 72.4% in INOCA patients and 63.6% in OCAD patients. Conclusions: MFR measured with low-dose D-MPI CZT SPECT provides incremental prognostic value in patients with INOCA. Patients with reduced MFR show an increased risk of MACE, increased symptom burdens, and impaired quality of life. INOCA patients with reduced MFR experienced higher rate of MACE than OCAD patients with normal MFR. [ABSTRACT FROM AUTHOR]

Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in bladder cancer (BC) remains undefined. This study aimed to elucidate the function of ADRM1 in BC through a combination of bioinformatics analysis and immunohistochemical analysis (IHC). Utilizing R version 3.6.3 and relevant packages, we analyzed online database data. Validation was conducted through IHC data, approved by the Institutional Ethics Committee (Approval No. K20220830). In both paired and unpaired comparisons, ADRM1 expression was significantly elevated in BC tissues compared to adjacent tissues, as evidenced by the results of TCGA dataset and IHC data. Patients with high ADRM1 expression had statistically worse overall survival than those with low ADRM1 expression in TCGA dataset, GSE32548 dataset, GSE32894 dataset, and IHC data. Functional analysis unveiled enrichment in immune-related pathways, and a robust positive correlation emerged between ADRM1 expression and pivotal immune checkpoints, including CD274, PDCD1, and PDCD1LG2. In tumor microenvironment, samples with the high ADRM1 expression contained statistical higher proportion of CD8 + T cells and Macrophage infiltration. Meanwhile, these high ADRM1-expressing samples displayed elevated tumor mutation burden scores and stemness indices, implying potential benefits from immunotherapy. Patients with low ADRM1 expression were sensitive to cisplatin, docetaxel, vinblastine, mitomycin C, and methotrexate. According to the findings from bioinformatics and IHC analyses, ADRM1 demonstrates prognostic significance for BC patients and holds predictive potential for both immunotherapy and chemotherapy responses. This underscores its role as a biomarker and therapeutic target in BC. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan–Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Macrophages (MΦ) play a role in neonatal etiologies of obstructive cholestasis, however, the role for precise MΦ subsets remains poorly defined. We developed a neonatal murine model of bile duct ligation (BDL) to characterize etiology-specific differences in neonatal cholestatic MΦ polarization. Neonatal BDL surgery was performed on female BALB/c mice at 10 days of life (DOL) with sham laparotomy as controls. Comparison was made to the Rhesus Rotavirus (RRV)-induced murine model of biliary atresia (BA). Evaluation of changes at day 7 after surgery (BDL and sham groups) and murine BA (DOL14) included laboratory data, histology (H&E, anti-CD45 and anti-CK19 staining), flow cytometry of MΦ subsets by MHCII and Ly6c expression, and single cell RNA-sequencing (scRNA-seq) analysis. Neonatal BDL achieved a 90% survival rate; mice had elevated bile acids, bilirubin, and alanine aminotransferase (ALT) versus controls (p < 0.05 for all). Histology demonstrated hepatocellular injury, CD45+ portal infiltrate, and CK19+ bile duct proliferation in neonatal BDL. Comparison to murine BA showed increased ALT in neonatal BDL despite no difference in histology Ishak score. Neonatal BDL had significantly lower MHCII-Ly6c+ MΦ versus murine BA, however, scRNA-seq identified greater etiology-specific MΦ heterogeneity with increased endocytosis in neonatal BDL MΦ versus cellular killing in murine BA MΦ. We generated an innovative murine model of neonatal obstructive cholestasis with low mortality. This model enabled comparison to murine BA to define etiology-specific cholestatic MΦ function. Further comparisons to human data may enable development of immune modulatory therapies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, is a major cause of mortality in patients. However, identifying circulatory markers to diagnose DKD requires a thorough understanding of the metabolic mechanisms of DKD. In this study, we performed ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to reveal altered metabolic profiles of amino acids (AAs) in patients with DKD. We found decreased plasma levels of histidine and valine, increased urine levels of proline, decreased urine levels of histidine and valine, and increased saliva levels of arginine in patients with DKD compared with the levels in patients with type 2 diabetes mellitus (T2DM) and in healthy controls. Our analyses of the key metabolites and metabolic enzymes involved in histidine and valine metabolism indicated that the AAs level alterations may be due to enhanced carnosine hydrolysis, decreased degradation of homocarnosine and anserine, enhanced histidine methylation, and systemic enhancement of valine metabolism in patients with DKD. Notably, we generated a distinct diagnostic model with an AUC of 0.957 and an accuracy up to 92.2% on the basis of the AA profiles in plasma, urine and saliva differing in patients with DKD using logistic regression and receiver operating characteristic analyses. In conclusion, our results suggest that altered AA metabolic profiles are associated with the progression of DKD. Our DKD diagnostic model on the basis of AA levels in plasma, urine, and saliva may provide a theoretical basis for innovative strategies to diagnose DKD that may replace cumbersome kidney biopsies. [ABSTRACT FROM AUTHOR]

The CoO-Co3O4/C and CoO-Co3O4/N-C composites were synthesized from β-cyclodextrin (CD)-cobalt acetate and β-CD-Zeolitic imidazolate framework-67 (ZIF-67) via adduct and coordination interactions, respectively. The transformation of the composition and structure of their precursors as well as the composites were studied. The two composites were employed as catalysts for the oxidative degradation of Bisphenol A in the presence of potassium persulfate. The catalytic results confirmed that the CoO-Co3O4/C and CoO-Co3O4/N-C composites demonstrated about 5.2 and 3.7-fold higher degradation rates than that of Co3O4 obtained by cobalt acetate, respectively, and also displayed a robust reusability, which could be due to the unique oxidation-reduction property between CoO and Co3O4 and the small particle size of cobalt oxides with carbonaceous species. The possible degradation mechanism was also investigated by controlled experiments. This work provided new development for the synthesis of functional materials by the assistance of supramolecules as well as their potential applications in the environmental catalysis. Highlights: β-CD–Co(Ac)2 adduct and β-CD-ZIF-67 were synthesized. CoO-Co3O4/C and CoO-Co3O4/N-C composites were obtained by calcination. Efficient catalytic abilities for Bisphenol A degradation were achieved. [ABSTRACT FROM AUTHOR]

Background: Currently, miRNAs are involved in the development of amyotrophic lateral sclerosis (ALS), and identifying circulating miRNAs that are causally associated with ALS risk as biomarkers is imperative. Methods: We performed a two-sample Mendelian randomization study to evaluate the causal relationship between miRNAs and ALS. Our analysis was conducted using summary statistics from miRNA expression quantitative loci (eQTL) data of the Framingham Heart Study and ALS genome-wide association studies data. Another independent miRNA data was used to further validate. Results: We identified eight unique miRNAs that were causally associated with ALS risk. Using expression data of miRNAs from an independent study, we validated three high-confidence miRNAs, namely hsa-miR-27b-3p, hsa-miR-139-5p, and hsa-miR-152-3p, which might have a potential causal effect on ALS risk. Conclusion: We suggested that higher levels of hsa-miR-27b-3p and hsa-miR-139-5p had protective effects on ALS, whereas higher levels of hsa-miR-152-3p might act as a risk factor for ALS. The analytical framework presented in this study helps to understand the role of miRNAs in the development of ALS and to identify the biomarkers for ALS risk. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is a congenital disorder caused by the failure of enteric neural crest cells (ENCCs) to colonize the distal bowel, resulting in absence of enteric nervous system. While a range of molecules and signaling pathways have been found to contribute to HSCR development, the risk factors and pathogenesis of this disease in many patients remain unknown. We previously demonstrated that increased activity of the prostaglandin E2 (PGE2)/PGE2 receptor subtype EP2 pathway can be a risk factor for HSCR. In this study, an Ednrb-deficient mouse model of HSCR was generated and used to investigate if PGE2/EP2 pathway could be a potential therapeutic target for HSCR. We found that downregulation of PGE2/EP2 signaling by siRNA-mediated ablation of a PGE2 synthase or pharmacologic blockage of EP2 enhanced ENCC colonization in the distal bowel of Ednrb−/− mice and alleviated their HSCR-like symptoms. Furthermore, blockage of EP2 was shown to promote ENCC migration through upregulating p38 mitogen-activated protein kinase activity, which was downregulated in the colon of Ednrb−/− mice and in the distal aganglionic bowel of HSCR patients. These data provide evidence that maternal exposure during embryonic development to an environment with dysregulated activation of the PGE2/EP2 pathway may predispose genetically susceptible offspring to HSCR, and avoidance or early disruption of maternal events (e.g. inflammation) that possibly enhance PGE2/EP2 signaling during pregnancy would reduce the occurrence and severity of this disease. Key messages: Knockdown of PTGES alleviates HSCR severity in Ednrb−/− mice. Blockage of EP2-mediated PGE2 signaling alleviates HSCR severity in Ednrb−/− mice. Blockage of EP2-mediated PGE2 signaling promotes ENCC migration via enhancing p38 activity. [ABSTRACT FROM AUTHOR]

Crystallization kinetics serve as the foundation for understanding crystallization behavior and designing crystallizer scale-ups. This study investigates the crystallization kinetics of Potassium Chloride (KCl) during the cooling crystallization process, utilizing the intermittent dynamic method under varying experimental conditions within a continuous mixed-suspension mixed-product-removal (MSMPR) crystallizer. Concurrently, the study explores the functional relationship between particle size and crystal growth rate. Kinetic rates were determined using a least-squares method for multivariate linear regression, and the validity of the kinetic model was confirmed through experimental testing. The findings suggest that the KCl crystallization process is governed by surface reaction, and that coalescence occurs between particles. It was observed that an increase in suspension density, supersaturation ratio, and stirring rate enhances both the nucleation rate and growth rate of KCl. The factors influencing the nucleation rate of KCl crystals, in order of significance, are stirring rate, supersaturation, and suspension density. Additionally, an increase in stirring rate was found to inhibit aggregation. Further investigation revealed that the growth rate of KCl crystals is size-dependent. Consequently, growth rate equations for KCl during the cooling crystallization process were derived using two particle-size-dependent growth rate models. When compared to the CR model, the MJ2 model demonstrated superior relevance and adaptability to experimental results in describing the population density distribution of KCl, with an average relative error of approximately 13.37% between model values and experimental data. This research offers valuable theoretical guidance for optimizing the crystallization process and designing industrial crystallizers. [ABSTRACT FROM AUTHOR]

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Chemical composition, surface morphology characteristics, and mineralogical characteristics of feed coals from six power plants were studied in this paper, as well as alteration behavior of mineral phase, functional groups, and trace elements during combustion. The apparent morphology of feed coals is different in compactness and order, while sharing a similar lamellar shape. Quartz, kaolinite, calcite, and illite are the main minerals in feed coals. There are obvious differences in the calorific value and temperature range in volatiles stages or coke combustion stages for feed coals. Peak positions for the main functional groups in feed coals are similar. After burning at 800 ℃, most organic functional groups in feed coals were lost in products, but the group of -CH2 on the side chain skeleton of n-alkane and the aromatic hydrocarbon bond (Ar–H) still existed in the ash, and the vibration of Si–O-Si bond and Al–OH bond in inorganic functional groups was strengthened. During combustion, Pb and Cr in feed coals will be accumulated in the mineral residues, unburned carbon, and residual ferromanganese minerals, along with the loss of organic matter and sulfide or the decomposition of carbonate. Pb and Cr are more easily adsorbed by the fine-graded coal combustion products. Occasionally, the abnormal phenomenon occurred in a medium-graded ash but with the maximum adsorption of Pb and Cr, which is mainly caused by the collision and agglomeration of the combustion products, or the adsorption capacity of different mineral components. The effects of diameter, coal species and feed coal on the forms of Pb and Cr in combustion products were also analyzed in this study. The study has some guiding significance for understanding the behavior track and alteration mechanism of Pb and Cr during coal combustion. [ABSTRACT FROM AUTHOR]

A green electrochemical biosensor was developed based on metal-organic framework (MOF)-catalyzed atom transfer radical polymerization (ATRP) for quantifying miRNA-21, used as the proof-of-concept analyte. Unlike conventional ATRP, Mn-PCN-222 (PCN, porous coordination network) could be used as an alternative for green catalyst to substitute traditional catalysts. First, poly (diallyldimethylammonium chloride) (PDDA) was fixed on the surface of the indium tin oxide (ITO) electrode, and then the Mn-PCN-222 was linked to ITO electrode via electrostatic binding with PDDA. Next, aminated ssDNA (NH2-DNA) was used to modify the electrode further by amide reaction with Mn-PCN-222. Then, the recognition and hybridization of NH2-DNA with miRNA-21 prompt the generation of DNA−RNA complexes, which further hybridize with Fc-DNA@β-CD-Br15 and permit the initiator to be immobilized on the electrode surface. Accordingly, β-CD-Br15 could initiate the polymerization of ferrocenylmethyl methacrylates (FcMMA) under the catalysis of MOF to complete the ATRP reaction. FcMMA presented a distinct electrochemical signal at ~ 0.33 V. Taking advantage of the unique multi-site properties of β-CD-Br15 and the efficient catalytic reaction induced by Mn-PCN-222, ultrasensitive detection of miRNA-21 was achieved with a detection limit of 0.4 fM. The proposed electrochemical biosensor has been applied to the detection of miRNA-21 in serum samples. Therefore, the proposed strategy exhibited potential in early clinical biomedicine. [ABSTRACT FROM AUTHOR]

Development of effective recycling strategies for cathode materials in spent lithium-ion batteries are highly desirable but remain significant challenges, among which facile separation of Al foil and active material layer of cathode makes up the first important step. Here, we propose a reaction-passivation driven mechanism for facile separation of Al foil and active material layer. Experimentally, >99.9% separation efficiency for Al foil and LiNi0.55Co0.15Mn0.3O2 layer is realized for a 102 Ah spent cell within 5 mins, and ultrathin, dense aluminum-phytic acid complex layer is in-situ formed on Al foil immediately after its contact with phytic acid, which suppresses continuous Al corrosion. Besides, the dissolution of transitional metal from LiNi0.55Co0.15Mn0.3O2 is negligible and good structural integrity of LiNi0.55Co0.15Mn0.3O2 is well-maintained during the processing. This work demonstrates a feasible approach for Al foil-active material layer separation of cathode and can promote the green and energy-saving battery recycling towards practical applications. Separating active cathode materials from current collectors poses a critical challenge in battery recycling. Here, the authors develop a facile strategy that relies on a reaction-passivation mechanism to effectively separate the aluminum foil and cathode active material in spent lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Monascus produces a kind of mycotoxin, citrinin, whose synthetic pathway is still not entirely clear. The function of CtnD, a putative oxidoreductase located upstream of pksCT in the citrinin gene cluster, has not been reported. In this study, the CtnD overexpressed strain and the Cas9 constitutively expressed chassis strain were obtained by genetic transformation mediated by Agrobacterium tumefaciens. The pyrG and CtnD double gene–edited strains were then obtained by transforming the protoplasts of the Cas9 chassis strain with in vitro sgRNAs. The results showed that overexpression of CtnD resulted in significant increases in citrinin content of more than 31.7% and 67.7% in the mycelium and fermented broth, respectively. The edited CtnD caused citrinin levels to be reduced by more than 91% in the mycelium and 98% in the fermented broth, respectively. It was shown that CtnD is a key enzyme involved in citrinin biosynthesis. RNA-Seq and RT-qPCR showed that the overexpression of CtnD had no significant effect on the expression of CtnA, CtnB, CtnE, and CtnF but led to distinct changes in the expression of acyl-CoA thioesterase and two MFS transporters, which may play an unknown role in citrinin metabolism. This study is the first to report the important function of CtnD in M. purpureus through a combination of CRISPR/Cas9 editing and overexpression. [ABSTRACT FROM AUTHOR]

Different sources of factors in environment can affect the spread of COVID-19 by influencing the diffusion of the virus transmission, but the collective influence of which has hardly been considered. This study aimed to utilize a machine learning algorithm to assess the joint effects of meteorological variables, demographic factors, and government response measures on COVID-19 daily cases globally at city level. Random forest regression models showed that population density was the most crucial determinant for COVID-19 transmission, followed by meteorological variables and response measures. Ultraviolet radiation and temperature dominated meteorological factors, but the associations with daily cases varied across different climate zones. Policy response measures have lag effect in containing the epidemic development, and the pandemic was more effectively contained with stricter response measures implemented, but the generalized measures might not be applicable to all climate conditions. This study explored the roles of demographic factors, meteorological variables, and policy response measures in the transmission of COVID-19, and provided evidence for policymakers that the design of appropriate policies for prevention and preparedness of future pandemics should be based on local climate conditions, population characteristics, and social activity characteristics. Future work should focus on discerning the interactions between numerous factors affecting COVID-19 transmission. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has revealed that circular RNAs (circRNAs) are critical regulators for the development of various tumors, containing diffuse large B-cell lymphoma (DLBCL). CircRNA microarray analysis suggested that circ_0000877 was freakishly increased in DLBCL tissues. Objective: This study is designed to explore the role and mechanism of circ_0000877 on DLBCL development. Results: Circ_0000877 and HK2 were increased, and miR-671-5p was reduced in DLBCL tissues and cell lines. Also, circ_0000877 silencing hindered DLBCL cell proliferation and glycolysis, and induced apoptosis in vitro. Mechanically, circ_0000877 functioned as a sponge of miR-671-5p, and circ_0000877 knockdown-mediated DLBCL cell development inhibition was relieved by miR-671-5p downregulation. Moreover, HK2 acted as a direct target gene of miR-671-5p, and enhanced HK2 might abolish the impact of miR-671-5p on DLBCL cell progression. Conclusion: Circ_0000877 silencing mitigated DLBCL cell malignant biological behavior partly via miR-671-5p/HK2 axis, referring to circ_0000877 as an underlying prognostic biomarker. These data provided a promising strategy for treating DLBCL malignancies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of ancillary features (AFs) of Liver Imaging Reporting and Data System (LI-RADS) in the diagnostic performance of small HCC (≤ 20 mm) on gadoxetic acid-enhanced MRI. Methods: A total of 154 patients with 183 hepatic observations were analysed in this retrospective study. Observations were categorized using only major features (MFs) and combined MFs and AFs. Independently significant AFs were identified through logistic regression analysis, and upgraded LR-5 criteria were developed using these as new MFs. The diagnostic performance of the modified LI-RADS (mLI-RADS) was calculated and compared with that of LI-RADS v2018 using McNemar's test. Results: Restricted diffusion, transitional and hepatobiliary phase hypointensity were independently significant AFs. The mLI-RADS a, c, e, g, h and i (upgraded LR-4 lesions that were categorized using only MFs to LR-5 using a certain or any one, two, three of the above AFs as new MFs) yielded a significantly greater sensitivity than that of the LI-RADS v2018 (68.0%, 69.1%, 69.1%, 69.1%, 69.1%, 68.0% vs. 61.9%, all p < 0.05), whereas the specificities were not significantly different (84.9%, 86.0%, 84.9%, 83.7%, 84.9%, 87.2% vs. 88.4% all p > 0.05). When independently significant AFs were used to upgrade the LR-4 nodules categorized by combined MFs and AFs (mLI-RADS b, d and f), the sensitivities were improved, but the specificities were decreased (all p < 0.05). Conclusions: Independently significant AFs may be used to upgrade an observation from LR-4 (categorized only using MFs) to LR-5, which can improve diagnostic performance for small HCC. [ABSTRACT FROM AUTHOR]

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