A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives.

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions. Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-ß1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN. Key Messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.

Poly (ADP-ribose) polymerase 1 promotes HuR/ELAVL1 cytoplasmic localization and inflammatory gene expression by regulating p38 MAPK activity.

Post-transcriptional regulation of cytokine/chemokine mRNA turnover is critical for immune processes and contributes to the mammalian cellular response to diverse inflammatory stimuli. The ubiquitous RNA-binding protein human antigen R (HuR) is an integral regulator of inflammation-associated mRNA fate. HuR function is regulated by various post-translational modifications that alter its subcellular localization and ability to stabilize target mRNAs. Both poly (ADP-ribose) polymerase 1 (PARP1) and p38 mitogen-activated protein kinases (MAPKs) have been reported to regulate the biological function of HuR, but their specific regulatory and crosstalk mechanisms remain unclear. In this study, we show that PARP1 acts via p38 to synergistically promote cytoplasmic accumulation of HuR and stabilization of inflammation-associated mRNAs in cells under inflammatory conditions. Specifically, p38 binds to auto-poly ADP-ribosylated (PARylated) PARP1 resulting in the covalent PARylation of p38 by PARP1, thereby promoting the retention and activity of p38 in the nucleus. In addition, PARylation of HuR facilitates the phosphorylation of HuR at the serine 197 site mediated by p38, which then increases the translocation of HuR to the cytoplasm, ultimately stabilizing the inflammation-associated mRNA expression at the post-transcriptional level.

FOXP4-mediated induction of PTK7 activates the Wnt/ß-catenin pathway and promotes ovarian cancer development.

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Genome-Wide Identification of BrCMF Genes in Brassica rapa and Their Expression Analysis under Abiotic Stresses.

CCT MOTIF FAMILY (CMF) genes belong to the CCT gene family and have been shown to play a role in diverse processes, such as flowering time and yield regulation, as well as responses to abiotic stresses. CMF genes have not yet been identified in Brassica rapa. A total of 25 BrCMF genes were identified in this study, and these genes were distributed across eight chromosomes. Collinearity analysis revealed that B. rapa and Arabidopsis thaliana share many homologous genes, suggesting that these genes have similar functions. According to sequencing analysis of promoters, several elements are involved in regulating the expression of genes that mediate responses to abiotic stresses. Analysis of the tissue-specific expression of BrCMF14 revealed that it is highly expressed in several organs. The expression of BrCMF22 was significantly downregulated under salt stress, while the expression of BrCMF5, BrCMF7, and BrCMF21 was also significantly reduced under cold stress. The expression of BrCMF14 and BrCMF5 was significantly increased under drought stress, and the expression of BrCMF7 was upregulated. Furthermore, protein-protein interaction network analysis revealed that A. thaliana homologs of BrCMF interacted with genes involved in the abiotic stress response. In conclusion, BrCMF5, BrCMF7, BrCMF14, BrCMF21, and BrCMF22 appear to play a role in responses to abiotic stresses. The results of this study will aid future investigations of CCT genes in B. rapa.

An IrRuOx catalyst supported by oxygen-vacant Ta oxide for the oxygen evolution reaction and proton exchange membrane water electrolysis.

The sustainable development of proton exchange membrane water electrolysis (PEMWE) requires a dramatic reduction in Ir while maintaining good catalytic activity and stability for the oxygen evolution reaction (OER). Herein, high-surface-area Ta2O5 with abundant oxygen vacancies is synthesized via a facile process, followed by anchoring IrRuOx onto a Ta2O5 support (IrRuOx/Ta2O5). IrRuOx and Ta2O5 work synergistically to afford excellent catalytic performance for the acidic OER. At 0.3 mgIr cm-2, IrRuOx/Ta2O5 only needed an overpotential of 235 mV to deliver 10 mA cm-2 in an acidic half cell and needed a cell potential of 1.91 V to deliver 2 A cm-2 in a PEM water electrolyzer. The characterization results show that doping Ir into RuOx significantly improves the stability and the electrochemically active surface area of RuOx. In IrRuOx/Ta2O5, IrRuOx interacts with Ta2O5 through more electron-rich Ir, indicating strong synergy between the catalyst and the support. The use of a metal oxide support improves the catalyst dispersion, optimizes electronic structures, facilitates mass transport, and stabilizes active sites. This work demonstrates that compositing Ir with less expensive Ru and anchoring catalyst nanoparticles on platinum-group metal (PGM)-free metal oxide supports represents one of the most promising strategies to reduce Ir loading and achieve an activity-stability trade-off. Such a strategy can benefit future catalyst design for other energy storage and conventional processes.

CENPK orchestrates ovarian cancer progression via GOLPH3-Mediated activation of mTOR signaling.

Ovarian cancer stands as a formidable clinical challenge, with limited therapeutic options. This investigation delves into the intricate molecular mechanisms governing ovarian cancer progression and uncovers Centromere Protein K (CENPK) as a central figure in disease pathogenesis. Elevated CENPK levels within ovarian cancer tissues conspicuously align with adverse clinical outcomes, positioning CENPK as a promising prognostic biomarker. Deeper exploration reveals a direct transcriptional connection between CENPK and the E2F1 transcription factor and clearly establishes E2F1's role as the master regulator of CENPK expression in ovarian cancer. Our inquiry revealing a suppression of tumor-promoting signaling pathways, most notably the mTOR pathway, upon CENPK silencing. Intriguingly, CENPK renders ovarian cancer cells more responsive to the mTOR inhibitor rapamycin, introducing a promising avenue for therapeutic intervention. In summation, our study unravels the multifaceted role of CENPK in ovarian cancer progression. It emerges as a prognostic indicator, a pivotal mediator of cell proliferation and tumorigenicity, and a regulator of the mTOR pathway, shedding light on potential therapeutic avenues for this formidable disease.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

The RopGEF Gene Family and Their Potential Roles in Responses to Abiotic Stress in Brassica rapa.

Guanine nucleotide-exchange factors (GEFs) genes play key roles in plant root and pollen tube growth, phytohormone responses, and abiotic stress responses. RopGEF genes in Brassica rapa have not yet been explored. Here, GEF genes were found to be distributed across eight chromosomes in B. rapa and were classified into three subfamilies. Promoter sequence analysis of BrRopGEFs revealed the presence of cis-elements characteristic of BrRopGEF promoters, and these cis-elements play a role in regulating abiotic stress tolerance and stress-related hormone responses. Organ-specific expression profiling demonstrated that BrRopGEFs were ubiquitously expressed in all organs, especially the roots, suggesting that they play a role in diverse biological processes. Gene expression analysis revealed that the expression of BrRopGEF13 was significantly up-regulated under osmotic stress and salt stress. RT-qPCR analysis revealed that the expression of BrRopGEF13 was significantly down-regulated under various types of abiotic stress. Protein-protein interaction (PPI) network analysis revealed interactions between RopGEF11, the homolog of BrRopGEF9, and the VPS34 protein in Arabidopsis thaliana, as well as interactions between AtRopGEF1, the homolog of BrRopGEF13 in Arabidopsis, and the ABI1, HAB1, PP2CA, and CPK4 proteins. VPS34, ABI1, HAB1, PP2CA, and CPK4 have previously been shown to confer resistance to unfavorable environments. Overall, our findings suggest that BrRopGEF9 and BrRopGEF13 play significant roles in regulating abiotic stress tolerance. These findings will aid future studies aimed at clarifying the functional characteristics of BrRopGEFs.

Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that causes bacterial pneumonia. However, with increasing bacterial resistance, there is an urgent need to develop new drugs to treat S. pneumoniae infections. Nanodefensin with a 14-carbon saturated fatty acid (ND-C14) is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of human α-defensin 5 (HD5) via an amide bond. However, it is unclear whether ND-C14 is effective against lung infections caused by S. pneumoniae. METHODS: In vitro, three groups were established, including the control group, and the HD5 and ND-C14 treatment groups. A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S. pneumoniae. The morphological changes of S. pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy. In vivo, mice were divided into sham, vehicle, and ND-C14 treatment groups. Mice in the sham group were treated with 25 µL of phosphate-buffered saline (PBS). Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25 µL of bacterial suspension with 2×108 CFU/mL (total bacterial count: 5×106 CFU), and then the mice were given 25 µL PBS or intratracheally injected with 25 µL of ND-C14 (including 20 µg or 50 µg), respectively. Survival rates were evaluated in the vehicle and ND-C14 treatment groups. Bacterial burden in the blood and bronchoalveolar lavage fluid were counted. The lung histology of the mice was assessed. A propidium iodide uptake assay was used to clarify the destructive effect of ND-C14 against S. pneumoniae. RESULTS: Compared with HD5, ND-C14 had a better bactericidal effect against S. pneumoniae because of its stronger ability to destroy the membrane structure of S. pneumoniae in vitro. In vivo, ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S. pneumoniae. ND-C14 reduced bacterial burden and lung tissue injury. Moreover, ND-C14 had a membrane permeation effect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration. CONCLUSION: The ND-C14 may improve bactericidal effects on S. pneumoniae both in vitro and in vivo.

FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression.

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

Analysis of Effect of Quality Control Circle Management Model on the Error Rate of Disposable Item Distribution and Efficiency of Medical Workers in Sterilization Supply Center.

Objective: To explore the effectiveness of quality control circle (QCC) management model in reducing the error rate of dispensing disposable items. Methods: Our hospital's sterilization supply center implemented QCC management model from May 2021 to December 2021 to compare the error rate of disposable items dispensed before and after the implementation of the QCC activities. Results: The one-time item dispensing error rate was lower after the QCC activities, the order claim error rate, print order error rate, and inventory error rate were also reduced, and the required loading time and delivery time were shortened (P < .05). Conclusion: QCC activities can reduce the error rate of dispensing disposable items, save time, improve efficiency, and enhance clinical satisfaction.

Effects of Sleep Deprivation and Hazard Types on the Visual Search Patterns and Hazard Response Times of Taxi Drivers.

The present study attempted to explore the effects of sleep deprivation on the visual search patterns and hazard response times of taxi drivers when they encountered different types of hazards. A two (driver groups: sleep deprivation or control) × two (hazard types: covert hazard or overt hazard) mixed experimental design was employed. A total of 60 drivers were recruited, half of whom were in the sleep-deprived group and half of whom were in the control group. A validated video-based hazard perception test that either contained covert hazards (12 video clips) or overt hazards (12 video clips) filmed from the drivers' perspective was presented to participants. Participants were instructed to click the left mouse button quickly once they detected a potentially dangerous situation that could lead to an accident. Participants' response time and eye movements relative to the hazards were recorded. The sleep-deprived group had a significantly longer response time and took a longer time to first fixate on covert hazards than the control group, while they had a shorter response time to overt hazards than the control group. The first fixation duration of sleep-deprived drivers was longer than that of the control group for overt hazards, while the duration of the first fixation of the two driver groups was similar for covert hazards. Sleep deprivation affects the visual search patterns and response times to hazards, and the adverse effects of sleep deprivation were worse in relation to covert hazards. The findings have some implications for classifying and evaluating high-risk taxi drivers whose hazard perception ability might be affected by insufficient sleep.

The role of N6-methyladenosine (m6A) in kidney diseases.

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit a variety of modifications that play important regulatory roles in various biological processes. More than 170 modifications have been identified in RNA molecules, among which the most common internal modifications include N6-methyladenine (m6A), n1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanine nucleotide (m7G). The most widely affected RNA modification is m6A, whose writers, readers, and erasers all have regulatory effects on RNA localization, splicing, translation, and degradation. These functions, in turn, affect RNA functionality and disease development. RNA modifications, especially m6A, play a unique role in renal cell carcinoma disease. In this manuscript, we will focus on the biological roles of m6A in renal diseases such as acute kidney injury, chronic kidney disease, lupus nephritis, diabetic kidney disease, and renal cancer.

Phosphorylation of KAT-2B by WKS1/Yr36 redirects the lipid flux to jasmonates to enhance resistance against wheat stripe rust.

Wheat (Triticum aestivum) is one of the most essential human energy and protein sources. However, wheat production is threatened by devastating fungal diseases such as stripe rust, caused by Puccinia striiformis Westend. f. sp. tritici (Pst). Here, we reveal that the alternations in chloroplast lipid profiles and the accumulation of jasmonate (JA) in the necrosis region activate JA signaling and trigger the host defense. The collapse of chloroplasts in the necrosis region results in accumulations of polyunsaturated membrane lipids and the lipid-derived phytohormone JA in transgenic lines of Yr36 that encodes Wheat Kinase START 1 (WKS1), a high-temperature-dependent adult plant resistance protein. WKS1.1, a protein encoded by a full-length splicing variant of WKS1, phosphorylates and enhances the activity of keto-acyl thiolase (KAT-2B), a critical enzyme catalyzing the ß-oxidation reaction in JA biosynthesis. The premature stop mutant, kat-2b, accumulates less JA and shows defects in the host defense against Pst. Conversely, overexpression of KAT-2B results in a higher level of JA and limits the growth of Pst. Moreover, JA inhibits the growth and reduces pustule densities of Pst. This study illustrates the WKS1.1‒KAT-2B‒JA pathway for enhancing wheat defense against fungal pathogens to attenuate yield loss.

The role of monocytes in thrombotic diseases: a review.

Cardiovascular and cerebrovascular diseases are the number one killer threatening people's life and health, among which cardiovascular thrombotic events are the most common. As the cause of particularly serious cardiovascular events, thrombosis can trigger fatal crises such as acute coronary syndrome (myocardial infarction and unstable angina), cerebral infarction and so on. Circulating monocytes are an important part of innate immunity. Their main physiological functions are phagocytosis, removal of injured and senescent cells and their debris, and development into macrophages and dendritic cells. At the same time, they also participate in the pathophysiological processes of pro-coagulation and anticoagulation. According to recent studies, monocytes have been found to play a significant role in thrombosis and thrombotic diseases of the immune system. In this manuscript, we review the relationship between monocyte subsets and cardiovascular thrombotic events and analyze the role of monocytes in arterial thrombosis and their involvement in intravenous thrombolysis. Finally, we summarize the mechanism and therapeutic regimen of monocyte and thrombosis in hypertension, antiphospholipid syndrome, atherosclerosis, rheumatic heart disease, lower extremity deep venous thrombosis, and diabetic nephropathy.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Suppressing ASPARTIC PROTEASE 1 prolongs photosynthesis and increases wheat grain weight.

The elongation of photosynthesis, or functional staygreen, represents a feasible strategy to propel metabolite flux towards cereal kernels. However, achieving this goal remains a challenge in food crops. Here we report the cloning of wheat CO2 assimilation and kernel enhanced 2 (cake2), the mechanism underlying the photosynthesis advantages and natural alleles amenable to breeding elite varieties. A premature stop mutation in the A-genome copy of the ASPARTIC PROTEASE 1 (APP-A1) gene increased the photosynthesis rate and yield. APP1 bound and degraded PsbO, the protective extrinsic member of photosystem II critical for increasing photosynthesis and yield. Furthermore, a natural polymorphism of the APP-A1 gene in common wheat reduced APP-A1's activity and promoted photosynthesis and grain size and weight. This work demonstrates that the modification of APP1 increases photosynthesis, grain size and yield potentials. The genetic resources could propel photosynthesis and high-yield potentials in elite varieties of tetraploid and hexaploid wheat.

Isoliquiritigenin inhibits virus replication and virus-mediated inflammation via NRF2 signaling.

BACKGROUND: The transcription factor NRF2 is a master redox switch that regulates the cellular antioxidant response. However, recent advances have revealed new roles for NRF2, including the regulation of antiviral responses to various viruses, suggesting that pharmacological NRF2-activating agents may be a promising therapeutic drug for viral diseases. Isoliquiritigenin (ISL), a chalcone isolated from liquorice (Glycyrrhizae Radix) root, is reported to be a natural NRF2 agonist and has has antiviral activities against HCV (hepatitis C virus) and IAV (influenza A virus). However, the spectrum of antiviral activity and associated mechanism of ISL against other viruses are not well defined. PURPOSE: This study investigated the antiviral activity and underlying mechanism of ISL against vesicular stomatitis virus (VSV), influenza A virus (H1N1), encephalomyocarditis virus (EMCV), herpes simplex virus type 1 (HSV-1). METHODS: We evaluated the antiviral activity of ISL against VSV, H1N1, EMCV, and HSV-1 using flow cytometry and qRT-PCR analysis. RNA sequencing and bioinformatic analysis were performed to investigate the potential antiviral mechanism of ISL. NRF2 knockout cells were used to investigate whether NRF2 is required for the antiviral activity of ISL. The anti-apoptosis and anti-inflammatory activities of ISL were further measured by counting cell death ratio and assessing proinflammatory cytokines expression in virus-infected cells, respectively. In addition, we evaluated the antiviral effect of ISL in vivo by measuring the survival rate, body weights, histological analysis, viral load, and cytokine expression in VSV-infected mouse model. RESULTS: Our data demonstrated that ISL effectively suppressed VSV, H1N1, HSV-1, and EMCV replication in vitro. The antiviral activity of ISL could be partially impaired in NRF2-deficient cells. Virus-induced cell death and proinflammatory cytokines were repressed by ISL. Finally, we showed that ISL treatment protected mice against VSV infection by reducing viral titers and suppressing the expression of inflammatory cytokines in vivo. CONCLUSION: These findings suggest that ISL has antiviral and anti-inflammatory effects in virus infections, which are associated with its ability to activate NRF2 signaling, thus indicating that ISL has the potential to serve as an NRF2 agonist in the treatment of viral diseases.

Suppression of ZEAXANTHIN EPOXIDASE 1 restricts stripe rust growth in wheat.

Reducing losses caused by pathogens is an effective strategy for stabilizing crop yields. Daunting challenges remain in cloning and characterizing genes that inhibit stripe rust, a devastating disease of wheat (Triticum aestivum) caused by Puccinia striiformis f. sp. tritici (Pst). We found that suppression of wheat zeaxanthin epoxidase 1 (ZEP1) increased wheat defense against Pst. We isolated the yellow rust slower 1 (yrs1) mutant of tetraploid wheat in which a premature stop mutation in ZEP1-B underpins the phenotype. Genetic analyses revealed increased H2O2 accumulation in zep1 mutants and demonstrated a correlation between ZEP1 dysfunction and slower Pst growth in wheat. Moreover, wheat kinase START 1.1 (WKS1.1, Yr36) bound, phosphorylated, and suppressed the biochemical activity of ZEP1. A rare natural allele in the hexaploid wheat ZEP1-B promoter reduced its transcription and Pst growth. Our study thus identified a novel suppressor of Pst, characterized its mechanism of action, and revealed beneficial variants for wheat disease control. This work opens the door to stacking wheat ZEP1 variants with other known Pst resistance genes in future breeding programs to enhance wheat tolerance to pathogens.

Exercise sustains motor function in Parkinson's disease: Evidence from 109 randomized controlled trials on over 4,600 patients.

Physical exercise has been widely identified as a supplementary therapy for Parkinson's disease (PD). Evaluating changes in motor function over long-term periods of exercise and comparing efficacy of various exercise types will enable a better understanding of the effects of exercise on PD. In the current study, a total of 109 studies that covered 14 types of exercise were included in the analyses, enrolling 4,631 PD patients. The results of meta-regression revealed that chronic exercise delays the progression of PD motor symptoms, mobility, and balance decline deterioration, whereas for the non-exercise PD groups, motor function progressively decline. Results from network meta-analyses suggest that dancing is the optimal exercise for general motor symptoms of PD. Furthermore, Nordic walking is the most efficient exercise to mobility and balance performance. The results from network meta-analyses also suggest that Qigong may have specific benefit in improving hand function. The findings of the current study provide further evidence that chronic exercise preserves the progression of motor function decline in PD and suggest that dancing, yoga, multimodal training, Nordic walking, aquatic training, exercise gaming, and Qigong are effective PD exercises. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=276264, identifier: CRD42021276264.