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Abstract Background SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression. Methods Here, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer. Results Our results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis. Conclusion Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

Phosphorylation, the most extensive and pleiotropic form of protein posttranslation modification, is central to cellular signal transduction. Throughout the extensive co-evolution of plant hosts and viruses, modifications to phosphorylation have served multiple purposes. Such modifications highlight the evolutionary trajectories of viruses and their hosts, with pivotal roles in regulation and refinement of host-virus interactions. In plant hosts, protein phosphorylation orchestrates immune responses, enhancing the activities of defense-related proteins such as kinases and transcription factors, thereby strengthening pathogen resistance in plants. Moreover, phosphorylation influences the interactions between host and viral proteins, altering viral spread and replication within host plants. In the context of plant viruses, protein phosphorylation controls key aspects of the infection cycle, including viral protein functionality and the interplay between viruses and host plant cells, leading to effects on viral accumulation and dissemination within plant tissues. Explorations of the nuances of protein phosphorylation in plant hosts and their interactions with viruses are particularly important. This review provides a systematic summary of the biological roles of the proteins of plant viruses carrying diverse genomes in regulating infection and host responses through changes in the phosphorylation status. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Free formaldehyde is released due to the addition of aldehyde-based adhesives during the production of fiberboard. This is harmful to human health and pollutes the environment, and for that reason binderless fiberboard has become a research hotspot. There have been reports about pretreatments with white-rot fungi or lignocellulase to produce binderless fiberboard, but there have been no such reports about optimizing the bio-pretreatment conditions. In this study, poplar wood shavings were used for fiberboard production, and the bio-pretreatment conditions with Coriolus versicolor were studied using response surface methodology. After single-factor optimization, the central levels of bran, molasses, and magnesium sulfate were obtained. Further optimization was carried out using Box-Behnken design to study the influence of the factors. A second-order polynomial equation was obtained, and the low p-value (0.001) implied that the model was highly significant. The optimized bio-pretreatment conditions for modulus of rupture (MOR) of the fiberboard were obtained by ridge analysis as 3.021 g of bran, 8.907 g of molasses, and 0.27 g of magnesium sulfate. Under the optimized conditions, MOR of fiberboard reached 27.21±0.64 MPa, which was 2.2 times that of the control fiberboard. Bio-pretreatment with C. versicolor should be a good choice to produce a high-strength binderless fiberboard.

Abstract Rice blast, caused by the filamentous fungus Magnaporthe oryzae (also known as Pyricularia oryzae), is the most severe disease threatening rice yield. Sakuranetin, an important plant phytoalexin, exhibits inhibitory effects on rice blast fungus growth. However, the underlying molecular mechanism by which sakuranetin enhances plant resistance against pathogens remains unclear. A recent study published in Nature Communications by Jiang et al. (Nat. Commun, 2023, https://doi.org/10.1038/s41467-024-47746-y ) elucidated from a cytological perspective how sakuranetin enhances resistance to rice blast disease. The research revealed that elevated accumulation of sakuranetin attenuates the endocytosis of M. oryzae effectors into the cytoplasm of rice host cells. The inhibitory effect of sakuranetin is dosage-dependent and targets clathrin-mediated endocytosis (CME). This study provides novel insights into understanding plant immune mechanisms underlying weakening pathogen virulence weapons.

Background Plasma cell dyscrasias encompass a diverse set of disorders, where early and precise diagnosis is essential for optimizing patient outcomes. Despite advancements, current diagnostic methodologies remain underutilized in applying artificial intelligence (AI) to routine laboratory data. This study seeks to construct an AI-driven model leveraging standard laboratory parameters to enhance diagnostic accuracy and classification efficiency in plasma cell dyscrasias. Methods Data from 1,188 participants (609 with plasma cell dyscrasias and 579 controls) collected between 2018 and 2023 were analyzed. Initial variable selection employed Kruskal-Wallis and Wilcoxon tests, followed by dimensionality reduction and variable prioritization using the Shapley Additive Explanations (SHAP) approach. Nine pivotal variables were identified, including hemoglobin (HGB), serum creatinine, and β2-microglobulin. Utilizing these, four machine learning models (gradient boosting decision tree (GBDT), support vector machine (SVM), deep neural network (DNN), and decision tree (DT) were developed and evaluated, with performance metrics such as accuracy, recall, and area under the curve (AUC) assessed through 5-fold cross-validation. A subtype classification model was also developed, analyzing data from 380 cases to classify disorders such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Results 1. Variable selection: The SHAP method pinpointed nine critical variables, including hemoglobin (HGB), serum creatinine, erythrocyte sedimentation rate (ESR), and β2-microglobulin. 2. Diagnostic model performance: The GBDT model exhibited superior diagnostic performance for plasma cell dyscrasias, achieving 93.5% accuracy, 98.1% recall, and an AUC of 0.987. External validation reinforced its robustness, with 100% accuracy and an F1 score of 98.5%. 3. Subtype Classification: The DNN model excelled in classifying multiple myeloma, MGUS, and light-chain myeloma, demonstrating sensitivity and specificity above 90% across all subtypes. Conclusions AI models based on routine laboratory results significantly enhance the precision of diagnosing and classifying plasma cell dyscrasias, presenting a promising avenue for early detection and individualized treatment strategies.

The internal kink mode is one of the crucial factors affecting the stability of magnetically confined fusion devices. This paper explores the key features influencing the growth rate of internal kink modes using machine learning techniques such as Random Forest, Extreme Gradient Boosting (XGboost), Permutation, and SHapley Additive exPlanations (SHAP). We conduct an in-depth analysis of the significant physical mechanisms by which these key features impact the growth rate of internal kink modes. Numerical simulation data were used to train high-precision machine learning models, namely Random Forest and XGBoost, which achieved coefficients of determination values of 95.07% and 94.57%, respectively, demonstrating their capability to accurately predict the growth rate of internal kink modes. Based on these models, key feature analysis was systematically performed with Permutation and SHAP methods. The results indicate that resistance, pressure at the magnetic axis, viscosity, and plasma rotation are the primary features influencing the growth rate of internal kink modes. Specifically, resistance affects the evolution of internal kink modes by altering current distribution and magnetic field structure; pressure at the magnetic axis impacts the driving force of internal kink modes through the pressure gradient directly related to plasma stability; viscosity modifies the dynamic behavior of internal kink modes by regulating plasma flow; and plasma rotation introduces additional shear forces, affecting the stability and growth rate of internal kink modes. This paper describes the mechanisms by which these four key features influence the growth rate of internal kink modes, providing essential theoretical insights into the behavior of internal kink modes in magnetically confined fusion devices.

Abstract The study aimed to assess the effect and mechanism of safflower injection in preventing retinal vein thrombosis in rabbits. Twenty healthy adult pigmented rabbits were randomly assigned to either the experimental group, receiving safflower injection, or the control group, receiving normal saline. After two weeks of treatment, blood samples were collected to analyze platelet adhesion and aggregation rates. Photodynamic therapy was applied to induce occlusion in the target retinal vein. Fundus photography and fluorescein angiography were recorded using a dynamic microscopic monitoring system, and laser speckle imaging was employed to assess blood flow in the affected vein. The experimental group exhibited significantly lower rates of platelet adhesion and aggregation compared to the control group. Following the induction of retinal vein occlusion, the experimental group showed a lower complete occlusion rate of the target retinal vein. Although initial blood flow in the target vein was similar between groups, the blood flow at 1, 3, and 5 min post-occlusion was significantly higher in the experimental group. Safflower injection delayed retinal vein thrombosis formation, preserved blood flow in the affected retinal area, and reduced platelet adhesion and aggregation. These effects facilitated vascular reperfusion within a limited timeframe.

The nucleoprotein (NP) of type A influenza virus (IAV) is highly conserved across all virus strains, making it an attractive candidate antigen for universal vaccines. While various studies have explored NP-induced mucosal immunity, here we interrogated the mechanistic differences between intramuscular (IM) and intranasal (IN) delivery of a recombinant adenovirus carrying NP fused with a bifunctional CD40 ligand. Despite being less effective than IM delivery in inducing systemic cellular immune responses and antibody-dependent cellular cytotoxicity (ADCC), IN immunization elicited superior antigen-specific recall humoral and cellular response in the nasal associated lymphoid tissue (NALT) of the upper respiratory tract, the initial site of immune recognition and elimination of inhaled pathogens. IN vaccination also induced significantly stronger pulmonary T cell responses in the lower respiratory tract than IM vaccination, in particular the CD8 T cells. Moreover, blocking lymphocyte circulation abrogated IM but not IN immunization induced protection, illustrating the critical role of local memory immune response upon viral infection. Notably, the CD40-targeted nasal delivery not only improved the magnitude but also the breadth of protection, including against lethal challenge with a newly isolated highly pathogenic avian H5N1 strain. These findings are informative for the design of universal mucosal vaccines, where the predominant mode of protection is independent of neutralizing antibodies.

RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.

Background: Transient receptor potential melastatin 4 (TRPM4) affects immune responses by regulating calcium homeostasis, but its role in calcific aortic valve inflammation remains unclear. This study aimed to assess the expression and function of TRPM4 in patients with or without calcific aortic valve disease (CAVD). Methods: The mRNA and protein expression levels of TRPM4 and related factors in calcified and noncalcified tissues were measured using qRT-PCR and Western blot. The proteins interacting with TRPM4 were confirmed by RNA pull-down and RNA immunoprecipitation assays. Dual-Luciferase Reporter Assay was performed to confirm the m6A site of TRPM4. Results: The mRNA expression levels of TRPM4, TLR4, IL-6, MCP-1, TNF-α, and NF-κB p65 were significantly higher in calcified aortic valve tissues than in noncalcified tissues, and TRPM4 was significantly positively correlated with inflammation-related factors. The protein expression level of TRPM4, TLR4 and NF-κB p65 were significantly higher in calcified aortic valve tissues than in noncalcified tissues. N6-methyladenosine (m6A) modification of TRPM4 mRNA by METTL3-YTHDF1 up-regulated its expression in CAVD. And TRPM4 promoted the level of inflammation via activation of the JNK-MAPK signaling pathway, after knockdown TRPM4, the production of proinflammatory cytokines was significantly suppressed. Conclusion: The results indicate the pivotal role of TRPM4 in CAVD and highlight METTL3-mediated m6A modification of TRPM4 in promoting inflammation through JNK-MAPK signaling pathway. This work provides potential therapeutic strategy to impede inflammation in CAVD.

Objective: Hepatic glucose metabolism is profoundly perturbed by excessive alcohol intake. miR-141/200c expression is significantly induced by chronic ethanol feeding. This study aimed at identifying the role of miR-141/200c in glucose homeostasis during chronic ethanol exposure. Methods: WT and miR-141/200c KO mice were fed a control or an ethanol diet for 30 days, followed by a single binge of maltose dextrin or ethanol, respectively. Untargeted metabolomics analysis of hepatic primary metabolites was performed along with analyses for liver histology, gene expression, intracellular signaling pathways, and physiological relevance. Primary hepatocytes were used for mechanistic studies. Results: miR-141/200c deficiency rewires hepatic glucose metabolism during chronic ethanol feeding, increasing the abundance of glucose intermediates including G6P, an allosteric activator for GS. miR-141/200c deficiency replenished glycogen depletion during chronic ethanol feeding accompanied by reduced GS phosphorylation in parallel with increased expression of PP1 glycogen targeting subunits. Moreover, miR-141/200c deficiency prevented ethanol-mediated increases in AMPK and CaMKK2 activity. Ethanol treatment reduced glycogen content in WT-hepatocytes, which was reversed by dorsomorphin, a selective AMPK inhibitor, while KO-hepatocytes displayed higher glycogen content than WT-hepatocytes in response to ethanol treatment. Furthermore, treatment of hepatocytes with A23187, a calcium ionophore activating CaMKK2, lowered glycogen content in WT-hepatocytes. Notably, the suppressive effect of A23187 on glycogen deposition was reversed by dorsomorphin, demonstrating that the glycogen depletion by A23187 is mediated by AMPK. KO-hepatocytes exhibited higher glycogen content than WT-hepatocytes in response to A23187. Finally, miR-141/200c deficiency led to improved glucose tolerance and insulin sensitivity during chronic ethanol feeding. Conclusions: miR-141/200c deficiency replenishes ethanol-mediated hepatic glycogen depletion through the regulation of GS activity and calcium signaling coupled with the AMPK pathway, improving glucose homeostasis and insulin sensitivity. These results underscore miR-141/200c as a potential therapeutic target for the management of alcohol intoxication.

To carry out cell counting, it is common to use neural network models with an encoder-decoder structure to generate regression density maps. In the encoder-decoder structure, skip connections are usually used to retain detailed features. However, skip connections introduce to the encoder multiple reverse propagation paths; the backward propagation gradients along these paths exhibit significant semantic differences, which affect the encoder’s training process and may lead to adverse effects. To remedy this problem, we propose a path-gradient controlling network for cell counting. First, a novel reverse gradient control module is proposed to balance the impact on the encoder of the backward propagation signal from the skip connections. Second, to eliminate noise in the feature maps of the encoder output, the convolutional and channel attention modules are used on the shallowest layer’s skip connection. Finally, we utilise depthwise convolution to reduce information loss during the downsampling process, and we use depthwise separable transposed convolution as the upsampling method to mitigate overfitting. Experiments demonstrate that the proposed method outperforms state-of-the-art techniques such as MSCA-UNet, Two-Path Net, SAU-Net, and Cell-Net in terms of the mean absolute error (MAE) metric on four publicly available cell-counting benchmark datasets. Our model performs better on the synthetic bacterial (VGG) dataset (1.9 ± 0.1) than does the MSCA-UNet (2.0 ± 0.2). On the Modified Bone Marrow (MBM) dataset, our model (3.7 ± 0.2) outperforms SAU-Net (5.7 ± 1.2). On the human subcutaneous adipose tissue (ADI) dataset, our model, with (8.9 ± 0.3), surpasses MSCA-UNet with (9.8 ± 0.7). On the Dublin Cell Counting (DCC) dataset, our model achieves (2.4 ± 0.2) and outperforms SAU-Net with (3.0 ± 0.3). The source code of our method is available at https://github.com/mona-aliye/PGC-Net.

In the dynamic operation of a boom sprayer, the boom oscillation will cause the detection value of the boom height to fluctuate greatly, resulting in failures of the control system. Based on the previously developed static boom height detection model for the entire wheat growth cycle, this study aimed to optimize the model to reduce the impact of boom oscillation on the accuracy of boom height detection. Three ultrasonic sensors were installed on each section boom of a three-section boom sprayer, and dynamic boom height detection tests were conducted at vehicle speeds of 4 to 8 km/h across six growth stages of winter wheat in Beijing, a total detection area within a single fixed operational row of approximately 14 ha. The test results showed that as vehicle speed increased, boom oscillations intensified across all sections. By setting the boom oscillation correction parameters, the detecting value of each section of boom height is corrected. The results show that the fluctuation and deviation degree of the boom height-detecting value are obviously reduced, and the correction effect is obvious. Further analysis of the detecting value of the boom height after the correction shows that the previously established detection model still maintains high detection accuracy under dynamic conditions; that is, the detection position of the ultrasonic sensor does not downward shift. This paper provides a low-cost technical method that can be directly applied to the dynamic detection of boom height.

This document introduces a novel equivalent algorithm for forecasting gas content within deep coal seams, which is subject to constraints stemming from the advancements and precision achieved in well and roadway engineering endeavors. This algorithm meticulously acknowledges that coal seam gas content comprises three fundamental components: the inherent gas emission rate of the equivalent stratum, the residual gas content retained within the coal seam itself, and the influence imparted by the gas content within the coal seam. Furthermore, the approach thoroughly considers variations in the level of porosity development within the coal seam and its surrounding rock formations, as well as the occurrence of gas within these structures. The equivalent layer is classified into two distinct groups: the sandstone zone and the clay zone. The sandstone zone utilizes pertinent parameters pertaining to fine sandstone, whereas the clay zone distinguishes between clay rock and thick mudstone. The influencing factor considerations solely encompass natural elements, such as the coal seam’s occurrence and geological structure. The residual gas content employs either existing measured parameters or acknowledged experimental parameters specific to the coal seam. Based on this predictive approach, an intelligent auxiliary software (V1.0) for mine gas forecasting was devised. The software calculates the gas content of deep coal seams within the mine at intervals of 100 m × 100 m, subsequently fitting the contour lines of gas content across the entire area. The gas content predictions derived from this equivalent algorithm demonstrate robust adaptability to variations in gas content caused by construction activities, and the prediction results exhibit an acceptable level of error on-site. Notably, the prediction process is not constrained by the progress of tunnel engineering, ensuring that the prediction outcomes can accurately represent the distribution characteristics of deep coal seam gas content. After a year of application, the prediction results have consistently met on-site requirements, providing a scientific foundation for the implementation of effective gas prevention and control measures in the mining area. Furthermore, this approach can effectively guide the formulation of medium- and long-term gas prevention and control plans for mines.

Abstract Unclean air discharge refers to the discharge phenomenon of a large number of polluting gases, droplets or solid particles floating in the air, which will cause insulation breakdown and safety accidents for the power transmission equipment that have been left outdoors for a long time. In order to investigate the effects of particle concentration, particle size and dielectric constant on DC breakdown characteristics of unclean air gap, a self‐made discharge chamber was designed in this study. The air was filtered and passed into the discharge chamber to remove the influence of impurities contained in the air on the experimental results. Then, solid particles with different concentration, particle size and particle dielectric constant were added to the discharge chamber to carry out the DC positive polarity breakdown characteristic experiment. The experimental results show that compared with dry clean air, the presence of solid particle increases the breakdown voltage of the gap, and the increase proportion of breakdown voltage is related to the particle concentration, particle size and particle dielectric constant. With the same particle type and particle size, the increase proportion of breakdown voltage increases with the higher concentration, which up to 10.49%. For further investigating, the fluid mechanics model was selected to simulate the process of streamer discharge in unclean air. The results show that compared with dry clean air, the presence of particles enhances the gap discharge ionisation process, but also enhances the adsorption of particles, and the latter has stronger effect than the former, thus increases the gap breakdown voltage. At the same time, the enhancement of adsorption effect increases the electric field intensity of the gap and speeds up the development process of streamer discharge.

Several studies have reported the efficacy of traditional Chinese medicine (TCM) for central serous chorioretinopathy (CSC), while some ophthalmologists are concerned that TCM may be a risk factor for CSC as some chinese herbs contain hormonal ingredients. This study aimed to evaluate the efficacy and safety of TCM in treating patients with CSC. Randomized controlled trials (RCTs) and observational studies of TCM for CSC were searched up to July 10, 2023 on the following biological databases without language and publication time restrictions: PubMed, Ovid Medline, Embase, Cochrane Library, The Chinese National Knowledge Infrastructure Database (CNKI), Technology Periodical Database (VIP), Wanfang, and Chinese Biomedical Literature Service System (SinoMed). Review Manager V.5.4.1 and Stata 14 software were used for data analysis. Finally, thirty-eight studies were finally included including 23 RCTs and 15 cohort studies. The meta-analysis showed that compared with the routine treatment alone, the combination of TCM can not only reduce the recurrence rate (OR = 0.29, 95% CI: 0.21,0.40; I2 = 0%) and central retinal thickness (CRT) (MD = - 35.63, 95% CI: - 45.96,-25.30; I2 = 89%) of CSC, but improve patients' best corrected visual acuity (BCVA) (SMD = 0.86, 95% CI: 0.62,1.11; I2 = 77%); additionally, it has no obvious side effects compared with routine treatment (OR = 0.72, 95% CI: 0.39,1.34; I2 = 10%). Overall, this study shows that the use of TCM does not increase the risk of CSC recurrence; on the contrary, the combination of TCM may reduce the recurrence of CSC and improve BCVA and CRT in patients with CSC compared with conventional treatment.

A 49-year-old female with multiple myeloma complicated by renal failure had dysuria. The urine culture revealed multidrug-resistant aeromonas caviae during her hospital stay. Her symptoms and signs significantly improved after receiving a seven-day course of piperacillin-tazobactam treatment. She had no history of urinary tract infections(UTIs). On follow-up, she felt clinically well. Aeromonas caviae is a rare cause of UTI. We review previous cases of aeromonas caviae UTIs. The purpose of this case report is to assist in the diagnosis and management of aeromonas caviae cystitis.

ABSTRACTInfluenza and Respiratory Syncytial virus (RSV) infections together contribute significantly to the burden of acute lower respiratory tract infections. Despite the disease burden, no approved RSV vaccine is available. While approved vaccines are available for influenza, seasonal vaccination is required to maintain protection. In addition to both being respiratory viruses, they follow a common seasonality, which warrants the necessity for a concerted vaccination approach. Here, we designed bivalent vaccines by utilizing highly conserved sequences, targeting both influenza A and RSV, as either a chimeric antigen or individual antigens separated by a ribosome skipping sequence. These vaccines were found to be effective in protecting the animals from challenge by either virus, with mechanisms of protection being substantially interrogated in this communication.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Background: Endoplasmic reticulum (ER) plays a crucial role in the development of organ injury caused by sepsis. Therefore, it is highly important to devise strategies that specially target ER stress for the treatment of sepsis. Previous research has shown that priming chemokines can enhance the therapeutic effects of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the function and mechanism of exosomes derived from MSCs that were pretreated with IL-1β (IB-exos) in the context of septic ER stress. Methods: Mouse bone MSCs were preconditioned with or without IL-1β and the supernatant was used for exosome extraction. In vitro sepsis cell mode was induced by treating HUVECs with LPS, while in vivo sepsis model was established through cecal ligation and puncture (CLP) operation in mice. Cell viability, apoptosis, motility, and tube formation were assessed using the EDU proliferation assay, flow cytometry analysis, migration assay, and tube formation assay, respectively. The molecular mechanism was investigated using ELISA, qRT-PCR, Western blot, and immunofluorescence staining. Results: Pretreatment with IL-1β enhanced the positive impact of MSC-exos on the viability, apoptosis, motility, and tube formation ability of HUVECs. The administration of LPS or CLP increased ER stress response, but this effect was blocked by the treatment of IB-exos. Additionally, IB-exos reversed the inhibitory effects of LPS or CLP on the expression levels of SIRT1 and ERK phosphorylation. Knockdown of SIRT1 counteracted the effects of IB-exos on HUVEC cellular function and ER stress. In a mouse model, the injection of IB-exos mitigated sepsis-induced lung injury by inhibiting ER stress response through the activation of SIRT1. Conclusion: IB-exos have been found to alleviate sepsis-induced lung injury via inhibiting ER stress through the SIRT1/ERK pathway. These findings indicated that IB-exos could potentially be used as a strategy to mitigate lung injury caused by sepsis.

Existing structural optimization software tools only integrate the Euler buckling function of rods and plates and do not consider the buckling strength constraint of stiffened plates, thus failing to meet the optimization design requirements of thin-walled structures such as ship hulls. In this study, according to the buckling strength specifications for stiffened plates of ships, the custom software development of a structural optimization program with "buckling constraints of stiffened plates" was performed using the HyperMesh optimization design software. The finite-element grid of the stiffened plate was divided; the average stress, stress gradient and other parameters associated with the buckling of stiffened plates were determined; the DRESP3 card was set; the external OML function file was linked and the buckling strength of the stiffened plates was introduced into the dimensional optimization design model as a constraint. The proposed method was used to optimize the structure scantlings of a platform, achieving a reduction of 8.96% compared with the original scheme, while also meeting the requirements of structural strength, deformation and buckling strength. The results demonstrated that the dimensional optimization software with buckling constraints is operable and can aid in the rapid structural optimization design of stiffened plates.

NLRP3 inflammasome mainly controls interleukin-1β (IL-1β) secretion, leading to cell death called pyroptosis constituting a major antiviral host defense and inflammatory diseases upon viral infection. The RAF-MEK1/2-ERK1/2 cascade and downstream c-Jun/Fos and Activator protein-1 (AP1) signaling pathway control the degree of inflammatory response. Influenza A virus (IAV) infection is known to stimulate NLRP3 inflammasome activation and inflammatory responses. Nevertheless, the detailed mechanism by which IAV induces NLRP3 inflammasome activation involved in transcription of pro-IL-1β mRNA remains elusive. In our study, we found that IAV infection promotes pro-IL-1β mRNA transcription and activates NLRP3 inflammasome. Detailed studies reveal that type I interferon (IFN-α/IFN-β) as well as U0126 (a selective inhibitor of MEK-1 and MEK-2) typically inhibit IAV-mediated NLRP3 inflammasome activation via downregulating pro-IL-1β mRNA. Moreover, knock-down of c-Jun decreases pro-IL-1β mRNA and inhibits NLRP3 inflammasome activation upon IAV infection. Overall, the findings uncover that AP-1 signaling pathway promotes NLRP3 inflammasome activation upon IAV infection, which provides a new idea for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Summary: Volume-regulated anion channels (VRACs) are hexamers of LRRC8 proteins that are crucial for cell volume regulation. N termini (NTs) of the obligatory LRRC8A subunit modulate VRACs activation and ion selectivity, but the underlying mechanisms remain poorly understood. Here, we report a 2.8-Å cryo-electron microscopy structure of human LRRC8A that displays well-resolved NTs. Amino-terminal halves of NTs fold back into the pore and constrict the permeation path, thereby determining ion selectivity together with an extracellular selectivity filter with which it works in series. They also interact with pore-surrounding helices and support their compact arrangement. The C-terminal halves of NTs interact with intracellular loops that are crucial for channel activation. Molecular dynamics simulations indicate that low ionic strength increases NT mobility and expands the radial distance between pore-surrounding helices. Our work suggests an unusual pore architecture with two selectivity filters in series and a mechanism for VRAC activation by cell swelling.

Precisely controlling magnetically tagged cells in a complex environment is crucial to constructing a magneto-microfluidic platform. We propose a two-dimensional model for capturing magnetic beads from non-magnetic fluids under a micromagnetic matrix. A qualitative description of the relationship between the capture trajectory and the micromagnetic matrix with an alternating polarity configuration was obtained by computing the force curve of the magnetic particles. Three stages comprise the capture process: the first, where motion is a parabolic fall in weak fields; the second, where the motion becomes unpredictable due to the competition between gravity and magnetic force; and the third, where the micromagnetic matrix finally captures cells. Since it is not always obvious how many particles are adhered to the surface, attachment density is utilized to illustrate how the quantity of particles influences the capture path. The longitudinal magnetic load is calculated to measure the acquisition efficiency. The optimal adhesion density is 13%, and the maximum adhesion density is 18%. It has been demonstrated that a magnetic ring model with 100% adhesion density can impede the capture process. The results offer a theoretical foundation for enhancing the effectiveness of rare cell capture in practical applications.

Proteins from Flammulina filiformis were prepared by sodium chloride extraction and fractionated by ammonium sulfate precipitation with increasing saturation degrees to obtain the protein fractions Ffsp-30, Ffsp-50, Ffsp-70, Ffsp-90, and Ffp-90. Among these protein fractions, Ffsp-50 possessed the most significant cytotoxic effect against three human gastrointestinal cancer cell lines, viz. HT-29, SGC-7901, and HepG2. SDS-PAGE and MALDI-TOF/TOF MS/MS analyses revealed that flammutoxin (FTX) was present as a dominating protein in Ffsp-50, which was further evidenced by HPLC-MS/MS determination. Furthermore, native FTX was purified from Ffsp-50 with a molecular weight of 26.78 kDa, exhibiting notable cytotoxicity against gastrointestinal cancer cell lines. Both Ffsp-50 and FTX exposure could enhance intercellular reactive oxygen species (ROS) generation and induce significant apoptosis in HepG2 cells. FTX was identified to be relatively conserved in basidiomycetes according to phylogenetic analysis, and its expression was highly upregulated in the primordium as well as the pileus of the fruiting body from the elongation and maturation stages, as compared with that in mycelium. Taken together, FTX could remarkably inhibit cell growth and induce ROS and apoptosis in HepG2 cells, potentially participating in the growth and development of the fruiting body. These findings from our investigation provided insight into the antigastrointestinal cancer activity of FTX, which could serve as a biological source of health-promoting and biomedical applications.

Ultrasonic feedback energy is affected by the variety, planting, and growth state of crops; therefore, it is difficult to find applications for this energy in precision agriculture systems. To this end, an ultrasonic sensor was mounted in a spray boom height detection system. Winter wheat was used as the test object to obtain feedback energy values for the spray boom height from the top of the wheat in the field during six critical growth stages: the standing stage, the jointing stage, the booting stage, the heading stage, the filling stage, and the maturity stage. The relationship between the actual value of the height from the spray boom at the top of the wheat (Habw) and the detected value of the height from the spray boom at the top of the wheat (Hdbw) was analyzed. A spray boom height detection model based on the ultrasonic sensor during the full growth cycle of wheat was determined. Field validation tests showed that the applicability of the spray boom height detection distance (Dd) of the spray boom height detection model proposed in the present study was 450~950 mm. Within the applicable Dd range, the detection error of the detection model was ≤50 mm during the full growth cycle. This study provides a method for constructing a boom height detection model based on the whole growth cycle of wheat, which improves the reliability and accuracy of ultrasonic boom height detection for different wheat growth stages. The proposed method solves the problem of low accuracy of repeated detection of low-cost ultrasonic sensors in different environments and can provide technical support for improving field applications of the boom height control system based on ultrasonic sensors.

Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.

A major threat to rice production is the disease epidemics caused by insect-borne viruses that emerge and re-emerge with undefined origins. It is well known that some human viruses have zoonotic origins from wild animals. However, it remains unknown whether native plants host uncharacterized endemic viruses with spillover potential to rice (Oryza sativa) as emerging pathogens. Here, we discovered rice tiller inhibition virus (RTIV), a novel RNA virus species, from colonies of Asian wild rice (O. rufipogon) in a genetic reserve by metagenomic sequencing. We identified the specific aphid vector that is able to transmit RTIV and found that RTIV would cause low-tillering disease in rice cultivar after transmission. We further demonstrated that an infectious molecular clone of RTIV initiated systemic infection and causes low-tillering disease in an elite rice variety after Agrobacterium-mediated inoculation or stable plant transformation, and RTIV can also be transmitted from transgenic rice plant through its aphid vector to cause disease. Finally, global transcriptome analysis indicated that RTIV may disturb defense and tillering pathway to cause low tillering disease in rice cultivar. Thus, our results show that new rice viral pathogens can emerge from native habitats, and RTIV, a rare aphid-transmitted rice viral pathogen from native wild rice, can threaten the production of rice cultivar after spillover.

IntroductionThe incidence of Lyme disease (LD) in Canada and the United States has risen over the last decade, nearing 480,000 cases each year. Borrelia burgdorferi sensu lato, the causative agent of LD, is transmitted to humans through the bite of an infected tick, resulting in flu-like symptoms and often a characteristic bull’s-eye rash. In more severe cases, disseminated bacterial infection can cause arthritis, carditis and neurological impairments. Currently, no vaccine is available for the prevention of LD in humans.MethodsIn this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of B. burgdorferi.ResultsVaccination of C3H/HeN mice with two doses of the candidate vaccine induced significant OspC-type A-specific antibody titres and borreliacidal activity. Analysis of the bacterial burden following needle challenge with B. burgdorferi (OspC-type A) revealed that the candidate vaccine afforded effective protection against homologous infection across a range of susceptible tissues. Notably, vaccinated mice were protected against carditis and lymphadenopathy associated with Lyme borreliosis.DiscussionOverall, the results of this study provide support for the use of a DNA-LNP platform for the development of LD vaccines.

Abstract Thanks to the gustatory system, humans can experience the flavors in foods and drinks while avoiding the intake of some harmful substances. Although great advances in the fields of biotechnology, microfluidics, and nanotechnologies have been made in recent years, this astonishing recognition system can hardly be replaced by any artificial sensors designed so far. Here, taste organoids are coupled with an extracellular potential sensor array to form a novel bioelectronic organoid and developed a taste organoids‐on‐a‐chip system (TOS) for highly mimicking the biological sense of taste ex vivo with high stability and repeatability. The taste organoids maintain key taste receptors expression after the third passage and high cell viability during 7 days of on‐chip culture. Most importantly, the TOS not only distinguishs sour, sweet, bitter, and salt stimuli with great specificity, but also recognizes varying concentrations of the stimuli through an analytical method based on the extraction of signal features and principal component analysis. It is hoped that this bioelectronic tongue can facilitate studies in food quality controls, disease modelling, and drug screening.

Liquid Nitrogen (LN2) cold shock on coal reservoir is a promising technology, and its complex fracture networks are directly related to the temperature effect of each component in coal caused by temperature change. Among them, the typical temperature effects include the expansion difference of different mineral particles, the evaporation of pore water and the volume expansion of gas heated, and the phase transition of water into ice. The above-mentioned effects will all occur in the process of cold shock and temperature returning of coal samples, and further influence the generation of fractures. In this paper, the relationship between minerals, moisture and porosity of six kinds of coals in the range of −30 °C–40 °C and the overall thermal expansion coefficient of coal samples is explored by using low-temperature thermal expansion coefficient tester, low-field nuclear magnetic resonance tester, XRD diffraction analyzer, CT scanner and muffle furnace industrial analyzer. It is found that the main minerals in coal are generally lower than the thermal expansion coefficient of the whole coal. The moisture and porosity of coals are proportional to the overall thermal expansion coefficient of coal samples. Among them, the porosity of small holes accounts for the highest proportion, and its internal moisture and gas have the greatest influence on the overall thermal expansion of coal, which indicates that the temperature effect of pore water evaporation and gas volume expansion in pores plays an important role in the process of coal temperature change.

Abstract The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the “Deltacron”-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

Repeated and missed spraying are common problems during the working of boom sprayers, especially in the breakpoint continuous process. Therefore, the present study investigated a breakpoint continuous spraying system for automatic-guidance boom sprayers based on a hysteresis compensation algorithm for spraying. An operational breakpoint identification algorithm, which combines a real-time kinematic global navigation satellite system (RTK-GNSS) and wheel odometer, was proposed; a pre-adjusted proportional-integral-derivative (PID) control algorithm for the opening degree of the proportional control valve was designed in thus study. Tests were conducted to establish equations correlating the opening degree of the proportional control valve, pump output flow rate, and main pipeline flow rate, with an R2 ≥ 0.9525. The time to adjust to the target flow rate was experimentally tested. The breakpoint identification accuracy of the RTK-GNSS and RTK-GNSS + wheel odometer was experimentally assessed. A field spraying deposition variation experiment was conducted. According to the results, the system effectively eliminated missed spraying, with a maximum repeated spraying distance of ≤3.3 m, and it achieved a flow control error within 3%. This system also reduced the repeated spraying area and enhanced the pesticide spraying quality of breakpoint continuous spraying for automatic-guidance boom sprayers.

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has challenged public health around the world. Currently, there is an urgent need to explore antiviral therapeutic targets and effective clinical drugs. In this study, we systematically summarized two main therapeutic strategies against COVID-19, namely drugs targeting the SARS-CoV-2 life cycle and SARS-CoV-2-induced inflammation in host cells. The development of above two strategies is implemented by repurposing drugs and exploring potential targets. A comprehensive summary of promising drugs, especially cytokine inhibitors, and traditional Chinese medicine (TCM), provides recommendations for clinicians as evidence-based medicine in the actual clinical COVID-19 treatment. Considering the emerging SARS-CoV-2 variants greatly impact the effectiveness of drugs and vaccines, we reviewed the appearance and details of SARS-CoV-2 variants for further perspectives in drug design, which brings updating clues to develop therapeutical agents against the variants. Based on this, the development of broadly antiviral drugs, combined with immunomodulatory, or holistic therapy in the host, is prior to being considered for therapeutic interventions on mutant strains of SARS-CoV-2. Therefore, it is highly acclaimed the requirements of the concerted efforts from multi-disciplinary basic studies and clinical trials, which improves the accurate treatment of COVID-19 and optimizes the contingency measures to emerging SARS-CoV-2 variants.

Rice grassy stunt virus (RGSV), a typical negative single-stranded RNA virus, invades rice and generates several disease signs, including dwarfing, tillering, and sterility. Previous research has revealed that RGSV-encoded proteins can force the host’s ubiquitin-proteasome system to utilize them for viral pathogenesis. However, most of the studies were limited to a single omics level and lacked multidimensional data collection and correlation analysis on the mechanisms of RGSV-rice interactions. Here, we performed a comprehensive association analysis of genome-wide methylation sequencing, transcriptome sequencing, and histone H3K9me3 modification in RGSV-infested as well as non-infested rice leaves, and the levels of all three cytosine contexts (CG, CHG and CHH) were found to be slightly lower in RGSV-infected rice leaves than in normal rice. Large proportions of DMRs were distributed in the promoter and intergenic regions, and most DMRs were enriched in the CHH context, where the number of CHH hypo-DMRs was almost twice as high as that of hyper-DMRs. Among the genes with down-regulated expression and hypermethylation, we analyzed and identified 11 transcripts involved in fertility, plant height and tillering, and among the transcribed up-regulated and hypermethylated genes, we excavated 7 transcripts related to fertility, plant height and tillering. By analyzing the changes of histone H3K9me3 modification before and after virus infestation, we found that the distribution of H3K9me3 modification in the whole rice genome was prevalent, mainly concentrated in the gene promoter and gene body regions, which was distinctly different from the characteristics of animals. Combined with transcriptomic data, H3K9me3 mark was found to favor targeting highly expressed genes. After RGSV infection, H3K9me3 modifications in several regions of CTK and BR hormone signaling-related genes were altered, providing important targets for subsequent studies.

Abstract Sustainable urban systems (SUS) science is a new science integrating work across established and emerging disciplines, using diverse methods, and addressing issues at local, regional, national, and global scales. Advancing SUS requires the next generation of scholars and practitioners to excel at synthesis across disciplines and possess the skills to innovate in the realms of research, policy, and stakeholder engagement. We outline key tenets of graduate education in SUS, informed by historical and global perspectives. The sketch is an invitation to discuss how graduates in SUS should be trained to engage with the challenges and opportunities presented by continuing urbanization.

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.

Zika virus (ZIKV) infection can cause severe neurological disorders, including Guillain–Barre syndrome and meningoencephalitis in adults and microcephaly in fetuses. Here, we reveal that laminin receptor 1 (LAMR1) is a novel host resistance factor against ZIKV infection. Mechanistically, we found that LAMR1 binds to ZIKV envelope (E) protein via its intracellular region and attenuates E protein ubiquitination through recruiting the deubiquitinase eukaryotic translation initiation factor 3 subunit 5 (EIF3S5). We further found that the conserved G282 residue of E protein is essential for its interaction with LAMR1. Moreover, a G282A substitution abolished the binding of E protein to LAMR1 and inhibited LAMR1-mediated E protein deubiquitination. Together, our results indicated that LAMR1 represses ZIKV infection through binding to E protein and attenuating its ubiquitination.

In order to improve compliance in human–robot interaction, a sensorless variable impedance control method is proposed. Variable impedance control is constructed using the end-effector velocity and the human–robot interaction force. Then, the impedance parameters are adjusted online to make the end-effector velocity more compliant with human behavior. Next, a velocity controller is designed to stabilize the end-effector velocity, and a compensation force is designed to avoid the measurement of the interaction force. Based on the velocity controller and the compensation force, an integrated controller is constructed to achieve stable end-effector velocity while compensating the interaction force online. The Lyapunov theory proves that with the sensorless variable impedance control, the system is stable, and the velocity tracking is bounded; simulation results demonstrate its feasibility. The sensorless variable impedance control can achieve more stable velocity and better compliance in human–robot interaction.

Human enterovirus 71 (EV71) is one of the major agents of the hand, foot, and mouth disease (HFMD), and occasionally causes severe neurological complications. There is clinical evidence that EV71 infection increases the exosomes in the serum of severe HFMD patients, suggesting a role of exosomes in EV71 pathogenesis. However, the relationship between exosomes and EV71 replication remains elusive. In this study, we initially found that EV71 infection elevated exosome biogenesis in the cultured cells. Among EV71 non-structural proteins, we identified EV71 3A, but not 3B, constitutively promoted exosome secretion. In detail, EV71 3A protein interacted with vacuolar protein sorting 25 (VPS25), while knock-down of VPS25 reduced EV71 3A protein- and EV71-induced exosome production. Further studies revealed VPS25 located on exosomes and its expression correlated to the exosome production. During EV71 infection, knock-down of VPS25 decreased exosome biogenesis to attenuate viral replication. Consistently, GW4869, an exosome inhibitor, exerted an obviously antiviral activity against EV71 replication companied with the decrease of exosome secretion or formation. These findings suggest the binding of EV71 3A and VPS25 benefited exosome biogenesis, thereby boosting viral replication. This study uncovers a novel mechanism underlying EV71-mediated exosomes in the regulation of viral replication, which provides potential anti-viral strategies against the EV71 infection and transmission in HFMD.

Light is not only a very important source of energy for the normal growth and development of plants, but also a regulator of many development and metabolic processes. The mechanism of plant growth and development under low light conditions is an important scientific question. With the promulgation of the law to stop natural forest cutting, understory regeneration is an important method for artificial forest afforestation. Here, the growth and physiological indexes of Juglans mandshurica, an important hardwood species in Northeast China, were measured under different shade treatments. In addition, transcriptome and metabolome were compared to analyze the molecular mechanism of shade tolerance in J. mandshurica. The results showed that the seedling height of the shade treatment group was significantly higher than that of the control group, and the 50% light (L50) treatment was the highest. Compared with the control group, the contents of gibberellin, abscisic acid, brassinolide, chlorophyll a, and chlorophyll b in all shade treatments were significantly higher. However, the net photosynthetic rate and water use efficiency decreased with increasing shade. Furthermore, the transcriptome identified thousands of differentially expressed genes in three samples. Using enrichment analysis, we found that most of the differentially expressed genes were enriched in photosynthesis, plant hormone signal transduction and chlorophyll synthesis pathways, and the expression levels of many genes encoding transcription factors were also changed. In addition, analysis of differentially accumulated metabolites showed that a total of 470 differential metabolites were identified, and flavonoids were the major differential metabolites of J. mandshurica under light stress. These results improved our understanding of the molecular mechanism and metabolite accumulation under light stress in J. mandshurica.

Improving saccharification of barley malt is beneficial to promoting economic benefits of beer brewers, but there are few detailed reports on the application of cellulase and laccase in barley malt. So, barley malt was pretreated by cellulase and laccase, and the malt wort and brewer's spent grains were analyzed by HPLC, FTIR and SEM in this study. The concentration of malt wort was increased significantly to 8.1 (° Bx), which increased by 28.6% after barley malt was pretreated by cellulase, but laccase could not improve saccharification of barley malt. Through analysis of sugar in malt wort and cellulose and lignin components as well as physical and chemical structures of brewer's spent grains, the increase in sugar content in malt wort was mainly due to the increase in glucose because of hydrolysis of cellulose in barley malt by cellulase. Furtherly, laccase and cellulase should have a mutual inhibition when they are pretreated simultaneously.

Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-β promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-β promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-β1 and IL6 promoters. The specific regulation of SPHK2 on IFN-β promoter through TET3 can in turn recruit HDAC1 to the IFN-β promoter, enhancing the deacetylation of IFN-β promoter, therefore leading to the inhibition of IFN-β transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.

To date, it has been confirmed that the occurrence and development of infectious diseases are tightly associated with regulatory cell death processes, such as apoptosis, autophagy, and necroptosis. Ferroptosis, as a newly discovered form of regulatory cell death characterized by iron-dependent lipid peroxidation, is not only closely associated with tumor progression, but is also found to be tightly related to the regulation of infectious diseases, such as Tuberculosis, Cryptococcal meningitis, Malaria and COVID-2019. The emerging critical roles of ferroptosis that has been found in infectious disease highlight ferroptosis as a potential therapeutic target in this field, which is therefore widely expected to be developed into new therapy strategy against infectious diseases. Here, we summarized the underlying mechanisms of ferroptosis and highlighted the intersections between host immunity and ferroptosis. Moreover, we illuminated the roles of ferroptosis in the occurrence and progression of different infectious diseases, which might provide some unique inspiration and thought-provoking perspectives for the future research of these infectious diseases, especially for the development of ferroptosis-based therapy strategy against infectious diseases.