Lipidomics and metabolomics investigation into the effect of DAG dietary intervention on hyperuricemia in athletes.

The occurrence of hyperuricemia (HUA; elevated serum uric acid) in athletes is relatively high despite that exercise can potentially reduce the risk of developing this condition. Although recent studies have shown the beneficial properties of DAG in improving overall metabolic profiles, a comprehensive understanding of the effect of DAG in modulating HUA in athletes is still lacking. In this study, we leveraged combinatorial lipidomics and metabolomics to investigate the effect of replacing TAG with DAG in the diet of athletes with HUA. A total of 1,074 lipids and metabolites from 94 classes were quantitated in serum from 33 athletes, who were categorized into responders and non-responders based on whether serum uric acid levels returned to healthy levels after the DAG diet intervention. Lipidomics and metabolomics analyses revealed lower levels of xanthine and uric acid in responders, accompanied by elevated plasmalogen phosphatidylcholines and diminished acylcarnitine levels. Our results highlighted the mechanisms behind how the DAG diet circumvented the risk and effects associated with high uric acid via lowered triglycerides at baseline influencing the absorption of DAG resulting in a decline in ROS and uric acid production, increased phospholipid levels associated with reduced p-Cresol metabolism potentially impacting on intestinal excretion of uric acid as well as improved ammonia recycling contributing to decreased serum uric acid levels in responders. These observed alterations might be suggestive that successful implementation of the DAG diet can potentially minimize the likelihood of a potentially vicious cycle occurring in high uric acid, elevated ROS, and impaired mitochondrial metabolism environment.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Micrometer Groove Array Structures Inspired by Desert Grasses on Curved Substrates for Enhanced Surface Condensation Efficiency.

Drawing inspiration from the microstructures on biological surfaces to create highly efficient water-collecting surfaces is an effective way to address water scarcity. Inspired by the role of the convex and concave grooves on the surface of Namib desert grass in promoting condensation, we show that optimizing the curvature radius improves the condensation rate of droplets. This convex-concave geometry, combined with nanoneedle structures on the groove ridges, facilitates droplet merging and self-removal through jumping, refreshing the condensation site and further enhancing condensation efficiency. Meanwhile, reducing the adhesive resistance in the groove valleys accelerates droplet migration and removal. We believe this design strategy can be applied to a wide range of water collection and phase change heat transfer applications.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Best evidence summary for aspiration prevention and management in critically ill patients with nasogastric feeding.

AIM: To evaluate and summarize the available evidence on the prevention and management of nasogastric aspiration in critically ill patients to inform the development of evidence-based clinical practice. DESIGN: This study was an evidence summary according to the evidence summary reporting standard of the Fudan University Center for Evidence-Based Nursing. METHOD: According to the '6S' model of evidence resources, evidence on the prevention and management of aspiration in critically ill patients on nasogastric feeding was retrieved, including clinical decision-making, best practices, guidelines, evidence summaries, expert consensus and systematic evaluations. DATA: UpToDate, BMJ Best Practice, JBI, National Guideline Clearing-house, Guidelines International Network, Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence, Registered Nurses Association of Ontario, Yi Mai tong Guidelines Network, the Cochrane Library, PubMed, Web of Science, Embase, OVID, Sinomed, CNKI, Wan Fang database. The search period was from January 2013 to June 2023. RESULTS: We included a total of 30 high-quality articles and summarized 36 pieces of evidence from them. These pieces of evidence covered 11 dimensions of multidisciplinary management, aspiration risk assessment, tube location, nutritional infusion management, position management, airway management, and oral hygiene. The level of evidence in the study was predominantly level 1 and level 5, with 27 pieces of evidence recommended as 'strong' and 9 pieces of evidence recommended as 'weak'. CONCLUSION: This study summarizes 36 pieces of evidence on preventing and managing aspiration in critically ill patients with nasogastric feeding. But the characteristics of hospitals should be considered in the application of future evidence. IMPACT: Aspiration is the most serious complication during nasogastric feeding, which seriously affects the prognosis of patients. Preventing and managing aspiration in nasogastric patients has proven to be a challenging clinical problem. This study summarized 36 pieces of best evidence in 11 dimensions, including multidisciplinary team, assessment and identification, line position, feeding management, and so on. The implementation of these evidences is conducive to standardizing the operation behaviour of nasogastric feeding in clinical medical staff and reducing the occurrence of aspiration. REPORTING METHOD: This research followed the evidence summary reporting specifications of the Fudan University Center for Evidence-based Nursing. TRIAL REGISTRATION: The registration number is 'ES20221368'.

Systems pharmacology: a combination strategy for improving efficacy of PD-1/PD-L1 blockade.

Targeting tumor microenvironment (TME), such as immune checkpoint blockade (ICB), has achieved increased overall response rates in many advanced cancers, such as non-small cell lung cancer (NSCLC), however, only in a fraction of patients. To improve the overall and durable response rates, combining other therapeutics, such as natural products, with ICB therapy is under investigation. Unfortunately, due to the lack of systematic methods to characterize the relationship between TME and ICB, development of rational immune-combination therapy is a critical challenge. Here, we proposed a systems pharmacology strategy to identify resistance regulators of PD-1/PD-L1 blockade and develop its combinatorial drug by integrating multidimensional omics and pharmacological methods. First, a high-resolution TME cell atlas was inferred from bulk sequencing data by referring to a high-resolution single-cell data and was used to predict potential resistance regulators of PD-1/PD-L1 blockade through TME stratification analysis. Second, to explore the drug targeting the resistance regulator, we carried out the large-scale target fishing and the network analysis between multi-target drug and the resistance regulator. Finally, we predicted and verified that oxymatrine significantly enhances the infiltration of CD8+ T cells into TME and is a powerful combination agent to enhance the therapeutic effect of anti-PD-L1 in a mouse model of lung adenocarcinoma. Overall, the systems pharmacology strategy offers a paradigm to identify combinatorial drugs for ICB therapy with a systems biology perspective of drug-target-pathway-TME phenotype-ICB combination.

Enhanced wide-range gas pressure sensing with an all-solid open Fabry-Pérot interferometer.

The sensors with a wide gas pressure detection range are urgently demanded in many industrial applications. Here, we propose a gas pressure sensor based on an all-solid open Fabry-Pérot interferometer, which is prepared by using optical contact bonding to ensure high structural strength and high-quality factor of 8.8 × 105. The applied pressure induces a change in the refractive index of the air, leading to the shift of the resonant spectrum. The pressure is detected by calibrating this shift. The sensor exhibits a pressure sensitivity of 4.20 ± 0.01 nm/MPa in a pressure range of 0 to 10 MPa and has a minimum pressure resolution of 0.005 MPa. Additionally, it shows a lower temperature cross-sensitivity of -0.25 kPa/°C. These findings affirm that the sensor achieves high-sensitivity pressure sensing across a wide detection range. Moreover, owing to its exceptional mechanical strength, it holds great promise for applications in harsh environments, such as high temperature and high pressure.

High-Content Screening Discovers Microplastics Released by Contact Lenses under Sunlight.

The widespread use of plastic products leads to the ubiquity of microplastics in daily life, while the release of microplastics from long-used contact lenses has not been reported due to the limitations of conventional detection methods. Here, we established a new and rapid method to capture and count microplastics by using a high-content screening system. This method can simultaneously measure the diameter, area, and shape of each plastic particle, and the reliability and applicability of this method were verified with commercial microplastics. It is estimated that 90,698 particles of microplastics could be released from a pair of contact lenses during a year of wearing. The microplastics in the leachates were confirmed to be released from the contact lenses by scanning electron microscopy and Fourier transform infrared spectroscopy fingerprint analysis. Our study reveals an undiscovered pathway of microplastic direct exposure to humans, highlighting the urgent need to assess the potential health risks caused by eye exposure to microplastics.

Comparative Biomechanical Analysis of Anterior Process Locking Plate Alone versus Combined with Percutaneous Cannulated Screw Fixation for Sanders Type II Calcaneal Fractures: A Finite Element Study.

BACKGROUND Calcaneal fractures are the most common tarsal bone fractures, and account for 75% of intra-articular fractures. The purpose of this study was to compare the biomechanical stability of the anterior process locking plate combined with the percutaneous cannulated screw fixation (screw group) versus the anterior process locking plate fixation alone (plate group) for the treatment of Sanders type II calcaneal fractures using finite element analysis to provide a theoretical basis for clinical work. MATERIAL AND METHODS We established a 3D model of Sanders type II calcaneal fracture; assigned material properties to the internal fixation systems; applied loads; set up analysis criteria; analyzed the displacement of the fracture, relative displacement, stress state of bone tissue, and internal fixation; and compared mechanical stability. RESULTS For Sanders type II A, II B, and II C calcaneal fractures, the degree of displacement and relative displacement of the fracture in the screw group was less than that of the plate group. For all subtypes of Sanders type II calcaneal fractures, the screw group had better mechanical stability than the plate group. CONCLUSIONS Both fixation methods (screw and plate group) were within a reasonable range for restoring the levelling effect of the joint surface and maintaining the strength of fixation, and both had good mechanical stability. Finite element analysis is a relatively reliable method, and biomechanics and clinical studies must further verify the experimental results.

Soy lecithin increases the stability and lipolysis of encapsulated algal oil and probiotics complex coacervates.

BACKGROUND: Co-encapsulation of probiotics and omega-3 oil using complex coacervation is an effective method for enhancing the tolerance of probiotics under adverse conditions, whereas complex coacervation of omega-3 oil was found to have low lipid digestibility. In the present study, gelatin (GE, 30 g kg-1 ) and gum arabic (GA, 30 g kg-1 ) were used to encapsulate Lactobacillus plantarum WCFS1 and algal oil by complex coacervation to produce microcapsules containing probiotics (GE-P-GA) and co-microcapsules containing probiotics and algal oil (GE-P-O-GA), and soy lecithin (SL) was added to probiotics-algal oil complex coacervates [GE-P-O(SL)-GA] to enhance its stability and lipolysis. Then, we evaluated the viability of different microencapsulated probiotics exposed to freeze-drying and long-term storage, as well as the survival rate and release performance of encapsulated probiotics and algal oil during in vitro digestion. RESULTS: GE-P-O(SL)-GA had a smaller particle size (51.20 µm), as well as higher freeze-drying survival (90.06%) of probiotics and encapsulation efficiency of algal oil (75.74%). Moreover, GE-P-O(SL)-GA showed a higher algal oil release rate (79.54%), lipolysis degree (74.63%) and docosahexaenoic acid lipolysis efficiency (64.8%) in the in vitro digestion model. The viability of microencapsulated probiotics after simulated digestion and long-term storage at -18,4 and 25 °C was in the order: GE-P-O(SL)-GA > GE-P-O-GA > GE-P-GA. CONCLUSION: As a result of its amphiphilic properties, SL strongly affected the physicochemical properties of probiotics and algal oil complex coacervates, resulting in higher stability and more effective lipolysis. Thus, the GE-P-O(SL)-GA can more effectively deliver probiotics and docosahexaenoic acid to the intestine, which provides a reference for the preparation of high-viability and high-lipolysis probiotics-algal oil microcapsules. © 2022 Society of Chemical Industry.

Integral Reinforcement-Learning-Based Optimal Containment Control for Partially Unknown Nonlinear Multiagent Systems.

This paper focuses on the optimal containment control problem for the nonlinear multiagent systems with partially unknown dynamics via an integral reinforcement learning algorithm. By employing integral reinforcement learning, the requirement of the drift dynamics is relaxed. The integral reinforcement learning method is proved to be equivalent to the model-based policy iteration, which guarantees the convergence of the proposed control algorithm. For each follower, the Hamilton-Jacobi-Bellman equation is solved by a single critic neural network with a modified updating law which guarantees the weight error dynamic to be asymptotically stable. Through using input-output data, the approximate optimal containment control protocol of each follower is obtained by applying the critic neural network. The closed-loop containment error system is guaranteed to be stable under the proposed optimal containment control scheme. Simulation results demonstrate the effectiveness of the presented control scheme.

Glycerol is Released from a New Path in MGL Lipase Catalytic Process.

Traditionally, it is believed that the substrate and products of a monoacylglycerol lipase (MGL) share the same path to enter and exit the catalytic site. Glycerol (a product of MGL), however, was recently hypothesized to be released through a different path. In order to improve the catalytic efficacy and thermo-stability of MGL, it is important to articulate the pathways of a MGL products releasing. In this study, with structure biological approaches, biochemical experiments, and in silico methods, we prove that glycerol is released from a different path in the catalytic site indeed. The fatty acid (another product of MGL) does share the same binding path with the substrate. This discovery paves a new road to design MGL inhibitors or optimize MGL catalytic efficacy.

Unraveling the mechanism of alkaloids from Sophora alopecuroides Linn combined with immune checkpoint blockade in the treatment of non-small cell lung cancer based on systems pharmacology.

Quinolizidine alkaloids, as essential active ingredients extracted from Sophora alopecuroides Linn (SAL), have been proven to be pharmacologically active in a variety of cancers including non-small cell lung cancer (NSCLC). However, whether these alkaloids have substantial benefits in combination with immune checkpoint blockade (ICB) for the treatment of NSCLC is unknown. Here, we explore the potential of these alkaloids in combination with ICB therapy based on a systems pharmacology and bioinformatics approach. We found that 37 alkaloids in SAL have highly similar characteristics in the molecular skeleton, pharmacological properties, and targets. The expression of targets of these alkaloids are significantly correlated with the infiltration level of tumor infiltrating lymphocytes and the expression levels of multiple immune checkpoints in NSCLC. They share similar molecular mechanisms in antitumor immunity. Sophocarpine (Sop) is one of the most representative constituents of these alkaloids. We demonstrated that the Sop promotes PD-L1 expression to improve the effects of PD-L1 blockade treatment via the ADORA1-ATF3 axis. In conclusion, our study identified these alkaloids as promising candidates for the treatment of NSCLC, either alone or in combination with ICB, with potential value for drug development and may provide a promising strategy for improving the survival of NSCLC patients.

Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007.

The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a α-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases.

Improving Both the Thermostability and Catalytic Efficiency of Phospholipase D from Moritella sp. JT01 through Disulfide Bond Engineering Strategy.

Mining of Phospholipase D (PLD) with high activity and stability has attracted strong interest for investigation. A novel PLD from marine Moritella sp. JT01 (MsPLD) was biochemically and structurally characterized in our previous study; however, the short half-life time (t1/2) under its optimum reaction temperature seriously hampered its further applications. Herein, the disulfide bond engineering strategy was applied to improve its thermostability. Compared with wild-type MsPLD, mutant S148C-T206C/D225C-A328C with the addition of two disulfide bonds exhibited a 3.1-fold t1/2 at 35 °C and a 5.7 °C increase in melting temperature (Tm). Unexpectedly, its specific activity and catalytic efficiency (kcat/Km) also increased by 22.7% and 36.5%, respectively. The enhanced activity might be attributed to an increase in the activation entropy by displacing more water molecules by the transition state. The results of molecular dynamics simulations (MD) revealed that the introduction of double disulfide bonds rigidified the global structure of the mutant, which might cause the enhanced thermostability. Finally, the synthesis capacity of the mutant to synthesize phosphatidic acid (PA) was evaluated. The conversion rate of PA reached about 80% after 6 h reaction with wild-type MsPLD but reached 78% after 2 h with mutant S148C-T206C/D225C-A328C, which significantly reduced the time needed for the reaction to reach equilibrium. The present results pave the way for further application of MsPLD in the food and pharmaceutical industries.

A New Phospholipase D from Moritella sp. JT01: Biochemical Characterization, Crystallization and Application in the Synthesis of Phosphatidic Acid.

A new phospholipase D from marine Moritella sp. JT01 (MsPLD) was recombinantly expressed and biochemically characterized. The optimal reaction temperature and pH of MsPLD were determined to be 35 °C and 8.0. MsPLD was stable at a temperature lower than 35 °C, and the t1/2 at 4 °C was 41 days. The crystal structure of apo-MsPLD was resolved and the functions of a unique extra loop segment on the enzyme activity were characterized. The results indicated that a direct deletion or fastening of the extra loop segment by introducing disulfide bonds both resulted in a complete loss of its activity. The results of the maximum insertion pressure indicated that the deletion of the extra loop segment significantly decreased MsPLD's interfacial binding properties to phospholipid monolayers. Finally, MsPLD was applied to the synthesis of phosphatidic acid by using a biphasic reaction system. Under optimal reaction conditions, the conversion rate of phosphatidic acid reached 86%. The present research provides a foundation for revealing the structural-functional relationship of this enzyme.

Licorice extract inhibits growth of non-small cell lung cancer by down-regulating CDK4-Cyclin D1 complex and increasing CD8+ T cell infiltration.

BACKGROUND: Targeting tumor microenvironment (TME) may provide therapeutic activity and selectivity in treating cancers. Therefore, an improved understanding of the mechanism by which drug targeting TME would enable more informed and effective treatment measures. Glycyrrhiza uralensis Fisch (GUF, licorice), a widely used herb medicine, has shown promising immunomodulatory activity and anti-tumor activity. However, the molecular mechanism of this biological activity has not been fully elaborated. METHODS: Here, potential active compounds and specific targets of licorice that trigger the antitumor immunity were predicted with a systems pharmacology strategy. Flow cytometry technique was used to detect cell cycle profile and CD8+ T cell infiltration of licorice treatment. And anti-tumor activity of licorice was evaluated in the C57BL/6 mice. RESULTS: We reported the G0/G1 growth phase cycle arrest of tumor cells induced by licorice is related to the down-regulation of CDK4-Cyclin D1 complex, which subsequently led to an increased protein abundance of PD-L1. Further, in vivo studies demonstrated that mitigating the outgrowth of NSCLC tumor induced by licorice was reliant on increased antigen presentation and improved CD8+ T cell infiltration. CONCLUSIONS: Briefly, our findings improved the understanding of the anti-tumor effects of licorice with the systems pharmacology strategy, thereby promoting the development of natural products in prevention or treatment of cancers.

Effects of Nanoplastics and Butyl Methoxydibenzoylmethane on Early Zebrafish Embryos Identified by Single-Cell RNA Sequencing.

Nanoplastics with small particle sizes and high surface area/volume ratios easily absorb environmental pollutants and affect their bioavailability. In this study, polystyrene nanoplastic beads (PS-NPBs) with a particle size of 100 nm and butyl methoxydibenzoylmethane (BMDBM) sunscreen in personal-care products were chosen as target pollutants to study their developmental toxicity and interactive effects on zebrafish embryos. The exposure period was set from 2 to 12 h postfertilization (hpf). BMDBM and PS-NPBs significantly upregulated genes related to antioxidant enzymes and downregulated the gene expression of aromatase and DNA methyltransferases, but the influenced genes were not exactly the same. The combined exposure reduced the adverse effects on the expression of all genes. With the help of the single-cell RNA sequencing technology, neural mid cells were identified as the target cells of both pollutants, and brain development, head development, and the notch signaling pathway were the functions they commonly altered. The key genes and functions that are specifically affected by BMDBM and/or PS-NPBs were identified. BMDBM mainly affects the differentiation and fate of neurons in the central nervous system through the regulation of her5, her6, her11, lfng, pax2a, and fgfr4. The PS-NPBs regulate the expression of olig2, foxg1a, fzd8b, six3a, rx1, lhx2b, nkx2.1a, and sfrp5 to alter nervous system development, retinal development, and stem cell differentiation. The phenotypic responses of zebrafish larvae at 120 hpf were tested, and significant inhibition of locomotor activity was found, indicating that early effects on the central nervous system would have a sustained impact on the behavior of zebrafish.

TaWRKY74 participates copper tolerance through regulation of TaGST1 expression and GSH content in wheat.

Glutathione S-transferase (GST) is the key enzyme in glutathione (GSH) synthesis, and plays a crucial role in copper (Cu) detoxification. Nonetheless, its regulatory mechanisms remain largely unclear. In this study, we identified a Cu-induced glutathione S-transferase 1 (TaGST1) gene in wheat. Yeast one-hybrid (Y1H) screened out TaWRKY74, which was one member from the WRKY transcription factor family. The bindings between TaGST1 promoter and TaWRKY74 were further verified by using another Y1H and luciferase assays. Expression of TaWRKY74 was induced more than 30-folds by Cu stress. Functions of TaWRKY74 were tested by using transiently silence methods. In transiently TaWRKY74-silenced wheat plants, TaWRKY74 and TaGST1 expression, GST activity, and GSH content was significantly inhibited by 25.68%, 19.88%, 27.66%, and 12.68% in shoots, and 53.81%, 52.11%, 23.47%, and 17.11% in roots, respectively. However, contents of hydrogen peroxide, malondialdehyde, or Cu were significantly increased by 2.58%, 12.45%, or 37.74% in shoots, and 25.24%, 53.84%, and 103.99% in roots, respectively. Notably, exogenous application of GSH reversed the adverse effects of transiently TaWRKY74-silenced wheat plants during Cu stress. Taken together, our results suggesting that TaWRKY74 regulated TaGST1 expression and affected GSH accumulation under Cu stress, and could be useful to ameliorate Cu toxicity for crop food safety.

Systems-level analysis identifies key regulators driving epileptogenesis in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most prevalent and often devastating form of epilepsy. The molecular mechanism underlying the development of TLE remains largely unclear, which hinders the discovery of effective antiepileptogenic drugs. Here we adopted a systems-level approach integrating transcriptomic profiles of three epileptogenesis stages to identify key regulators underlying epilepsy progression. Associating stage-specific gene meta-signatures with brain cell-specialized modules revealed positive regulation of glial migration and adhesion, cytokine production, and neuron death, and downregulation of synaptic transmission and ion transport during epileptogenesis. We identified 265 key regulators driving these processes and 72 of them were demonstrated associating with seizure frequency and/or hippocampal sclerosis in human TLE. Importantly, the upregulation of FAM107A, LAMB2, LTBP1 and TGIF1, which are mainly involved in nervous system development, were found contributing to both conditions. Our findings present the evolution landscape of epileptogenesis and provide candidate regulators that may serve as potential antiepileptogenic targets.