Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate ...the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2-C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine.
Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Federated learning (FL) has been facilitating privacy-preserving deep learning in many walks of life such as medical image classification, network intrusion detection, and so forth. Whereas it ...necessitates a central parameter server for model aggregation, which brings about delayed model communication and vulnerability to adversarial attacks. A fully decentralized architecture like Swarm Learning allows peer-to-peer communication among distributed nodes, without the central server. One of the most challenging issues in decentralized deep learning is that data owned by each node are usually non-independent and identically distributed (non-IID), causing time-consuming convergence of model training. To this end, we propose a decentralized learning model called Homogeneous Learning (HL) for tackling non-IID data with a self-attention mechanism. In HL, training performs on each round's selected node, and the trained model of a node is sent to the next selected node at the end of each round. Notably, for the selection, the self-attention mechanism leverages reinforcement learning to observe a node's inner state and its surrounding environment's state, and find out which node should be selected to optimize the training. We evaluate our method with various scenarios for two different image classification tasks. The result suggests that HL can achieve a better performance compared with standalone learning and greatly reduce both the total training rounds by 50.8% and the communication cost by 74.6% for decentralized learning with non-IID data.
Lymphocyte-activation gene 3 (LAG3) is a highly anticipated immune checkpoint in the context of cancer, exerting regulatory control over immune cell proliferation and function to reinforce the ...advancement of cancers. However, the comprehensive functional analysis of LAG3 across various cancer types remains undisclosed; thus, this study aims to investigate the pan-cancer expression profile of LAG3. We have investigated the expression profile, prognostic significance, and genetic alterations of LAG3 in various cancers while elucidating its characteristic in immune response regulation. Our findings demonstrated that elevated LAG3 expression is significantly associated with favorable prognosis in patients with cutaneous melanoma (SKCM), and it may be a potential biomarker for SKCM. Furthermore, multiple immune algorithms have highlighted the important regulatory role of LAG3 for the tumor-infiltrating immune cells including CD8 + T cells, B cells, dendritic cells (DCs), macrophages, and natural killer (NK) cells. We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.
The mechanisms governing electric field and partial discharge (PD) under stress cone dislocation remain unclear. This study employs the finite element method to explore the relationship between the ...electric field, externally applied voltage, and length of dislocation. Subsequently, the correlation between voltage and electric field is determined. The relationship between voltage and PD is established through PD tests conducted under stress cone dislocation conditions. By considering the influence of voltage, the association between the electric field and PD is established, revealing the mechanism of PD initiation by electric field distortion in joints. The findings suggest that the lifetime and reliability were increased by wrapping semi‐conductive self‐adhesive tape around the exposed cross‐linked polyethylene (XLPE) insulation layer. The electric field at a specific location is approximately proportional to the applied voltage. However, the slope is influenced by the composite insulation interface and the radial distance of the copper conductor. When crossing the interface between the XLPE insulation layer and the accessory insulation layer, the slope decreases significantly. The threshold for electric field PD is determined by examining the electric field distribution and the PD inception voltage during testing. When the voltage is sufficiently high, significant electric field distortions can occur at multiple points in the joint, potentially leading to concurrent PDs at several locations.
This study employs the finite element method to explore the relationship between the electric field, externally applied voltage, and length of dislocation. Subsequently, the correlation between voltage and electric field is determined. The relationship between voltage and partial discharge (PD) is established through PD tests conducted under stress cone dislocation conditions. By considering the influence of voltage, the association between the electric field and PD is established, revealing the mechanism of PD initiation by electric field distortion in joints.
Predominant network intrusion detection systems (NIDS) aim to identify malicious traffic patterns based on a handcrafted dataset of rules. Recently, the application of machine learning in NIDS helps ...alleviate the enormous effort of human observation. Federated learning (FL) is a collaborative learning scheme concerning distributed data. Instead of sharing raw data, it allows a participant to share only a trained local model. Despite the success of existing FL solutions, in NIDS, a network's traffic data distribution does not always fit into the single global model of FL; some networks have similarities with each other but other networks do not. We propose Segmented-Federated Learning (Segmented-FL), where by employing periodic local model evaluation and network segmentation, we aim to bring similar network environments to the same group. A comparison between FL and our method was conducted against a range of metrics including the weighted precision, recall, and F1 score, using a collected dataset from 20 massively distributed networks within 60 days. By studying the optimized hyperparameters of Segmented-FL and employing three evaluation methods, it shows that Segmented-FL has better performance in all three types of intrusion detection tasks, achieving validation weighted F1 scores of 0.964, 0.803, and 0.912 with Method A, Method B, and Method C respectively. For each method, this scheme shows a gain of 0.1%, 4.0% and 1.1% in performance compared with FL.
The lack of rapid and effective approaches to determine the health benefits of strains is one of the main challenges affecting the selection of probiotics from large numbers of candidates. In this ...study, the probiotic potential of 44
strains isolated from different Chinese traditional fermented foods was evaluated, including acid and bile salt resistance, adhesion ability, survival in simulated human gastrointestinal transit, antioxidant activity, bile salt hydrolase (BSH) activity, and antibacterial activity. All tested
strains showed high antioxidant capacity, BSH activity, and antibacterial activity. Among the strains, B652, C232, D444, and E932 were identified as the best comprehensive performed strains, which were selected for whole-genome sequencing, in order to provide clear information and identify key genes responsible for functional characteristics
. It demonstrated that the antioxidant activity, adhesion activity, and ability to survive in the simulated gastric environment were found to be closely correlated with antioxidant enzyme encoding genes, cell-surface protein-encoding genes, and stress response genes, respectively. The numbers of functional genes present in strains might decide their performance in probiotic profile evaluation. The outcome of the study could support the development of a novel approach for the screening and identification of probiotics.
Wider coverage and a better solution to a latency reduction in 5G necessitate its combination with multi-access edge computing technology. Decentralized deep learning (DDL), such as federated ...learning and swarm learning, as a promising solution to privacy-preserving data processing for millions of smart edge devices leverages distributed computing of multilayer neural networks within the networking of local clients, without disclosing the original local training data. Notably, in industries such as finance and healthcare, where sensitive data of transactions and personal medical records are cautiously maintained, DDL can facilitate the collaboration among these institutes to improve the performance of trained models while protecting the data privacy of participating clients. In this survey article, we demonstrate the technical fundamentals of DDL that benefit many walks of society through decentralized learning. Furthermore, we offer a comprehensive overview of the current state of the art in the field by outlining the challenges of DDL and the most relevant solutions from novel perspectives of communication efficiency and trustworthiness.
Monitoring creatinine levels is critical for evaluating renal function and muscular health in athletes. Creatinine is a waste product of creatine metabolism in skeletal muscle, and is filtered by the ...kidneys at a relatively constant rate. Elevated serum creatinine can indicate impaired kidney function, rhabdomyolysis, or skeletal muscle trauma. In athletes, creatinine levels increase after intense exertion due to muscle breakdown and myoglobin release. Abnormal creatinine signifies poor training adaptation, overtraining, or trauma. Therefore, close monitoring of creatinine in athletes provides insight into their physical condition. Current laboratory methods for measuring creatinine like Jaffe reaction and high-performance liquid chromatography are accurate but time-consuming, requiring blood sampling. Biosensors offer rapid, painless creatinine detection from small volumes, but current versions suffer from instability, use of mediators, and lack portability. Boron nitride nanotubes (BNNTs) are promising materials for electrochemical biosensing due to their structure, surface chemistry, and biocompatibility. Here, we report BNNT-based electrochemical biosensors for detecting creatinine in blood samples from athletes. BNNTs synthesized by induction thermal plasma technique were used to immobilize creatinine metabolizing enzymes. Creatinine levels were measured by chronoamperometry and compared to isotope dilution mass spectrometry. We demonstrate high sensitivity and selectivity of the BNNT biosensor with facile fabrication method and portable platform, promising for rapid creatinine monitoring in athletes. This can provide insight into muscular damage and renal function during training and competition.
Nitrosative/oxidative stress plays an important role in neuronal death following cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford significant neuroprotection on ...ischemic stroke, however, whether its mechanism is related to attenuating nitrosative/oxidative stress is not clear. In the present study, we investigated the effect of CHR on neuronal injury related to nitric oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO) model. Our results revealed that nitrite plus nitrate (NOx−) and 3-nitrotyrosine (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were subsequently attenuated by CHR treatment. Moreover, 3-NT is colocalized with NeuN and TUNEL, suggesting that neuronal apoptosis following I/R is associated with 3-NT and CHR suppresses NO-associated neuronal cell death. Accordingly, cleaved caspase-3 expression in ischemic brain was decreased by CHR treatment. I/R also decreased the activity of total superoxide dismutase (SOD) and manganese-dependent SOD (MnSOD), whilst increased reactive oxygen species (ROS) production significantly. Interestingly, CHR reversed this decrease in total SOD, and MnSOD activity, and inhibited ROS generation in the ischemic brain. Taken together, our results provide direct evidence suggesting that CHR attenuates nitrosative/oxidative stress injury induced by I/R, providing a novel therapeutic target in the treatment of acute ischemic stroke.
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