SARS-CoV-2 and oncolytic EV-D68-encoded proteases differentially regulate pyroptosis.

Pyroptosis, a pro-inflammatory programmed cell death, has been implicated in the pathogenesis of coronavirus disease 2019 and other viral diseases. Gasdermin family proteins (GSDMs), including GSDMD and GSDME, are key regulators of pyroptotic cell death. However, the mechanisms by which virus infection modulates pyroptosis remain unclear. Here, we employed a mCherry-GSDMD fluorescent reporter assay to screen for viral proteins that impede the localization and function of GSDMD in living cells. Our data indicated that the main protease NSP5 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) blocked GSDMD-mediated pyroptosis via cleaving residues Q29 and Q193 of GSDMD. While another SARS-CoV-2 protease, NSP3, cleaved GSDME at residue G370 but activated GSDME-mediated pyroptosis. Interestingly, respiratory enterovirus EV-D68-encoded proteases 3C and 2A also exhibit similar differential regulation on the functions of GSDMs by inactivating GSDMD but initiating GSDME-mediated pyroptosis. EV-D68 infection exerted oncolytic effects on human cancer cells by inducing pyroptotic cell death. Our findings provide insights into how respiratory viruses manipulate host cell pyroptosis and suggest potential targets for antiviral therapy as well as cancer treatment.IMPORTANCEPyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory enterovirus D68 (EV-D68) proteases on host cell pyroptosis. We found that SARS-CoV-2-encoded proteases NSP5 and NSP3 inactivate gasdermin D (GSDMD) but initiate gasdermin E (GSDME)-mediated pyroptosis, respectively. We also discovered that another respiratory virus EV-D68 encodes two distinct proteases 2A and 3C that selectively trigger GSDME-mediated pyroptosis while suppressing the function of GSDMD. Based on these findings, we further noted that EV-D68 infection triggers pyroptosis and produces oncolytic effects in human carcinoma cells. Our study provides new insights into the molecular mechanisms underlying virus-modulated pyroptosis and identifies potential targets for the development of antiviral and cancer therapeutics.

Utilizing transcriptomics and metabolomics to unravel key genes and metabolites of maize seedlings in response to drought stress.

BACKGROUND: Drought stress can substantially restrict maize growth and productivity, and global warming and an increasing frequency of extreme weather events are likely to result in more yield losses in the future. Therefore, unraveling the molecular mechanism underlying the response to drought stress is essential for breeding drought-resilient crops. RESULTS: In this study, we subjected the 3-leaf-period plants of two maize inbred lines, a drought-tolerant line (si287) and a drought-sensitive line (X178), to drought stress for seven days while growing in a chamber. Subsequently, we measured physiological traits and analyzed transcriptomic and metabolic profiles of two inbred lines. Our KEGG analysis of genes and metabolites revealed significant differences in pathways related to glycolysis/gluconeogenesis, flavonoid biosynthesis, starch and sucrose metabolism, and biosynthesis of amino acids. Additionally, our joint analysis identified proline, tryptophan and phenylalanine are crucial amino acids for maize response to drought stress. Furthermore, we concentrated on tryptophan (Trp), which was found to enhance tolerance via IAA-ABA signaling, as well as SA and nicotinamide adenine dinucleotide (NAD) consequent reactive oxygen species (ROS) scavenging. We identified three hub genes in tryptophan biosynthesis, indole-3-acetaldehyde oxidase (ZmAO1, 542,228), catalase 1 (ZmCAT1, 542,369), and flavin-containing monooxygenase 6 (ZmYUC6, 103,629,142), High expression of these genes plays a significant role in regulating drought tolerance. Two metabolites related to tryptophan biosynthesis, quinolinic acid, and kynurenine improved maize tolerance to drought stress by scavenging reactive oxygen species. CONCLUSIONS: This study illuminates the mechanisms underlying the response of maize seedlings to drought stress. Especially, it identifies novel candidate genes and metabolites, enriching our understanding of the role of tryptophan in drought stress. The identification of distinct resistance mechanisms in maize inbred lines will facilitate the exploration of maize germplasm and the breeding of drought-resilient hybrids.

cGAS-STING-mediated novel nonclassic antiviral activities.

Stimulatorof interferon genes (STING) is an intracellular sensor of cyclic dinucleotides involved in the innate immune response against pathogen- or self-derived DNA. For years, interferon (IFN) induction of cyclic GMP-AMP synthase (cGAS)-STING has been considered as a canonical pattern defending the host from viral invasion. The mechanism of the cGAS-STING-IFN pathway has been well-illustrated. However, other signalling cascades driven by cGAS-STING have emerged in recent years and some of them have been found to possess antiviral ability independent of IFN. Here, we summarize the current progress on cGAS-STING-mediated nonclassic antiviral activities with an emphasis on the nuclear factor-κB and autophagy pathways, which are the most-studied pathways. In addition, we briefly present the primordial function of the cGAS-STING pathway in primitive species to show the importance of IFN-unrelated antiviral activity from an evolutionary angle. Finally, we discuss open questions that need to be solved for further exploitation of this field.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Enhanced Na+ and Cl- sequestration and secretion selectivity contribute to high salt tolerance in the tetraploid recretohalophyte Plumbago auriculata Lam.

MAIN CONCLUSION: Enhanced secretion of Na+ and Cl- in leaf glands and leaf vacuolar sequestration of Na+ or root retention of Cl-, combined with K+ retention, contribute to the improved salt tolerance of tetraploid recretohalophyte P. auriculata. Salt stress is one of the major abiotic factors threatening plant growth and development, and polyploids generally exhibit higher salt stress resistance than diploids. In recretohalophytes, which secrete ions from the salt gland in leaf epidermal cells, the effects of polyploidization on ion homeostasis and secretion remain unknown. In this study, we compared the morphology, physiology, and ion homeostasis regulation of diploid and autotetraploid accessions of the recretohalophyte Plumbago auriculata Lam. after treatment with 300 mM NaCl for 0, 2, 4, 6, and 8 days. The results showed that salt stress altered the morphology, photosynthetic efficiency, and chloroplast structure of diploid P. auriculata to a greater extent than those of its tetraploid counterpart. Moreover, the contents of organic osmoregulatory substances (proline and soluble sugars) were significantly higher in the tetraploid than in the diploid, while those of H2O2 and malondialdehyde (MDA) were significantly lower. Analysis of ion homeostasis revealed that the tetraploid cytotype accumulated more Na+ in stems and leaves and more Cl- in roots but less K+ loss in roots compared with diploid P. auriculata. Additionally, the rate of Na+ and Cl- secretion from the leaf surface was higher, while that of K+, Mg2+, and Ca2+ secretion was lower in tetraploid plants. X-ray microanalysis of mesophyll cells revealed that Na+ mainly accumulated in different cellular compartments in the tetraploid (vacuole) and diploid (cytoplasm) plants. Our results suggest that polyploid recretohalophytes require the ability to sequester Na+ and Cl-(via accumulation in leaf cell vacuoles or unloading by roots) and selectively secrete these ions (through salt glands) together with the ability to prevent K+ loss (by roots). This mechanism required to maintain K+/Na+ homeostasis in polyploid recretohalophytes under high salinity provides new insights in the improved maintenance of ion homeostasis in polyploids under salt stress.

SARS-CoV-2, HIV, and HPV: Convergent evolution of selective regulation of cGAS-STING signaling.

Recognizing aberrant cytoplasmic double-stranded DNA and stimulating innate immunity is essential for the host's defense against viruses and tumors. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2'3'-cGAMP and subsequently activates stimulator of interferon genes (STING)-mediated activation of TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and the production of type I interferon (IFN-I). Both the cGAS-STING-mediated IFN-I antiviral defense and the countermeasures developed by diverse viruses have been extensively studied. However, recent studies have revealed a convergent evolutionary feature of severe acute respiratory syndrome coronavirus 2 and human immunodeficiency virus (HIV) viral proteins in terms of the selective regulation of cGAS-STING-mediated nuclear factor-κB (NF-κB) signaling without any effect on cGAS-STING-mediated TBK1/IRF3 activation and IFN production. The potential beneficial effect of this cGAS-STING-mediated, NF-κB-dependent antiviral effect, and the possible detrimental effect of IFN-I in the pathogenesis of coronavirus disease 2019 and HIV infection deserve more attention and future investigation.

DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS-STING-triggered innate immune activation.

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the cGAS-STING pathway. However, the function of STING in infected cells and the mechanism by which HPV18 E7 antagonizes STING-induced Interferon beta production remain unknown. We report that HPV18 E7 selectively antagonizes STING-triggered nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation but not IRF3 activation. HPV18 E7 binds to STING in a region critical for NF-κB activation and blocks the nuclear accumulation of p65. Moreover, E7 inhibition of STING-triggered NF-κB activation is related to HPV pathogenicity but not E7-Rb binding. HPV18 E7, severe acute respiratory syndrome coronavirus-2 open reading frame 3a, human immunodeficiency virus-2 viral protein X, and Kaposi's sarcoma-associated herpesvirus KSHV viral interferon regulatory factor 1 selectively inhibited STING-triggered NF-κB or IRF3 activation, suggesting a convergent evolution among these viruses toward antagonizing host innate immunity. Collectively, selective suppression of the cGAS-STING pathway by viral proteins is likely to be a key pathogenic determinant, making it a promising target for treating oncogenic virus-induced tumor diseases.

SARS-CoV-2 ORF3a inhibits cGAS-STING-mediated autophagy flux and antiviral function.

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-Type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral evasion of STING-triggered autophagy-mediated antiviral function are scarce. In the present study, we have discovered that SARS-CoV-2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING-LC3 interaction, thus blocking cGAS-STING-induced autophagy but not IRF3-Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome-lysosome fusion, is a selective inhibition of STING-triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING-triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING-induced autophagy appears to be an acquired function of SARS-CoV-2 ORF3a, since SARS-CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID-19.

A highly efficient Mn4+ activated Nb-based oxyfluoride red fluorescent material with excellent water stability: preparation and performance analysis.

In this study, an efficient non-rare earth Mn4+-doped K3(NbOF5)(HF2) red fluorescent material was synthesized by using the coprecipitation method. Replacing KF with K2CO3 effectively solved the problem that KF was difficult to stir due to its strong water absorption. The sample was composed of rods. The excitation spectra consisted of two strong excitation peaks at 366 nm and 468 nm. The emission spectra consisted of a series of narrow-band emissions between 580 nm and 680 nm. Besides, the luminescence quantum efficiency (QE) reached 84.3% under the excitation of 468 nm. The fluorescent lifetime of K3(NbOF5)(HF2):Mn4+ was less than 4 ms, which can achieve fast response display in backlight display applications. The WLED was fabricated with K3(NbOF5)(HF2):Mn4+ and commercial YAG:Ce3+ and the commercial InGaN blue chip. At a 30 mA drive current, the WLED device exhibited excellent luminescence properties. The correlated color temperature (CCT) was 3853 K, the Ra was 90.1 and the luminous efficiency was 310.432 lm W-1. Therefore, K3(NbOF5)(HF2):Mn4+ has very broad prospects in WLED lighting and backlight display applications.

Robust wireless power transfer using a nonlinear parity-time-symmetric circuit.

Considerable progress in wireless power transfer has been made in the realm of non-radiative transfer, which employs magnetic-field coupling in the near field. A combination of circuit resonance and impedance transformation is often used to help to achieve efficient transfer of power over a predetermined distance of about the size of the resonators. The development of non-radiative wireless power transfer has paved the way towards real-world applications such as wireless powering of implantable medical devices and wireless charging of stationary electric vehicles. However, it remains a fundamental challenge to create a wireless power transfer system in which the transfer efficiency is robust against the variation of operating conditions. Here we propose theoretically and demonstrate experimentally that a parity-time-symmetric circuit incorporating a nonlinear gain saturation element provides robust wireless power transfer. Our results show that the transfer efficiency remains near unity over a distance variation of approximately one metre, without the need for any tuning. This is in contrast with conventional methods where high transfer efficiency can only be maintained by constantly tuning the frequency or the internal coupling parameters as the transfer distance or the relative orientation of the source and receiver units is varied. The use of a nonlinear parity-time-symmetric circuit should enable robust wireless power transfer to moving devices or vehicles.

Low-temperature corn straw-degrading bacterial agent and moisture effects on indigenous microbes.

While the in situ return of corn straw can improve soil fertility and farmland ecology, additional bacterial agents are required in low-temperature areas of northern China to accelerate straw degradation. Moisture is an important factor affecting microbial activity; however, owing to a lack of bacterial agents adapted to low-temperature complex soil environments, the effects of soil moisture on the interaction between exogenous bacterial agents and indigenous soil microorganisms remain unclear. To this end, we explored the effect of the compound bacterial agent CFF constructed using Pseudomonas putida and Acinetobacter lwoffii, developed to degrade corn straw in low-temperature soils (15 °C), on indigenous bacterial and fungal communities under dry (10% moisture content), slightly wet (20%), and wet (30%) soil-moisture conditions. The results showed that CFF application significantly affected the α-diversity of bacterial communities and changed both bacterial and fungal community structures, enhancing the correlation between microbial communities and soil-moisture content. CFF application also changed the network structure and the species of key microbial taxa, promoting more linkages among microbial genera. Notably, with an increase in soil moisture, CFF enhanced the rate of corn straw degradation by inducing positive interactions between bacterial and fungal genera and enriching straw degradation-related microbial taxa. Overall, our study demonstrates the alteration of indigenous microbial communities using bacterial agents (CFF) to overcome the limitations of indigenous microorganisms for in situ straw-return agriculture in low-temperature areas. KEY POINTS: • Low-temperature and variable moisture conditions (10-30%) were compared • Soil microbial network structure and linkages between genera were altered • CFF improves straw degradation via positive interactions between soil microbes.

Diagnosis of Metastatic Lymph Nodes in Patients With Hepatocellular Carcinoma Using Dual-Energy Computed Tomography.

OBJECTIVE: Our study aimed to investigate the role of quantitative parameters derived from dual-energy computed tomography (DECT) in discriminating metastatic from nonmetastatic lymph nodes in hepatocellular carcinoma (HCC). METHODS: Forty-two patients (34 males; mean age, 53.7 years) with HCC underwent unenhanced computed tomography scans and triple-phase DECT scans of the upper abdomen. A total of 72 suspected lymph nodes were resected, including 43 nonmetastatic and 29 metastatic lymph nodes. The maximum short-axis diameter of the lymph nodes, iodine concentration, normalized iodine concentration (NIC), and slope of the spectral curve were analyzed for the HCC primary lesions and the suspected lymph nodes. Lymph node metastasis was confirmed by pathologic examination. RESULTS: A maximum short-axis diameter of >10 mm had a sensitivity and a specificity of 75.9% (22/29) and 53.5% (23/43) in diagnosing metastatic lymph nodes. The iodine concentration, NIC, and slope of the spectral curve of the nonmetastatic lymph nodes were significantly higher than those of the primary HCC lesions and the metastatic lymph nodes (all P < 0.05). Among all the analyzed spectral parameters, the NIC in the arterial phase had the highest sensitivity and specificity of 88.4% and 86.2% in diagnosing metastatic lymph nodes. CONCLUSIONS: The arterial phase NIC of DECT has superior diagnostic performance than the traditional lymph node size in diagnosing metastatic lymph nodes in HCC.

Pre-anesthesia ultrasound monitoring of subclavian vein diameter changes induced by modified passive leg raising can predict the occurrence of hypotension after general anesthesia: a prospective observational study.

BACKGROUND: Perioperative hypotension increases postoperative complication rates and prolongs postoperative recovery time. Whether Passive Leg Raising test (PLR) and Subclavian Vein Diameter (DSCV) can effectively predict post-anesthesia hypotension remains to be tested. This study aimed to identify specific predictors of General Anesthesia (GA)induced hypotension by measuring DSCV in the supine versus PLR position. METHODS: A total of 110 patients who underwent elective gynecological laparoscopic surgery under general anesthesia, were enrolled in this study. Before anesthesia, DSCV and theCollapsibility Index of DSCV(DSCV-CI) were measured by ultrasound, and the difference in maximal values of DSCV between supine and PLR positions was calculated, expressed as ΔDSCV. Hypotension was defined as Mean Blood Pressure (MBP) below 60mmhg or more than 30% below the baseline. Patients were divided into two groups according to the presence (Group H) or absence (Group N) of postanesthesia hypotension. The area under the receiver operating characteristic curve (ROC) and logistic regression analyses were used to evaluate the predictability of DSCV and other parameters for predicting preincision hypotension. RESULTS: Three patients were excluded due to unclear ultrasound scans, resulting in a total of 107 patients studied. Twenty-seven (25.2%) patients experienced hypotension. Area under the ROC curve of ΔDSCV was 0.75 (P < 0.001) with 95% confidence interval (0.63-0.87), while DSCV and DSCV-CI were less than 0.7. The odds ratio (OR)of ΔDSCV was 1.18 (P < 0.001, 95%CI 1.09-1.27) for predicting the development of hypotension. ΔDSCV is predictive of hypotension following induction of general anesthesia. CONCLUSIONS: ΔDSCV has predictive value for hypotension after general anesthesia. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 04/10/2021.

Abscisic acid (ABA) alleviates cadmium toxicity by enhancing the adsorption of cadmium to root cell walls and inducing antioxidant defense system of Cosmos bipinnatus.

Cadmium (Cd) pollution is a global problem affecting soil ecology and plant growth. Abscisic acid (ABA) acts as a growth and stress hormone, regulates cell wall synthesis, and plays an important role in plant responses to stress. There are few studies on the mechanisms behind abscisic acid alleviation of cadmium stress in Cosmos bipinnatus, especially in regards to regulation of the root cell wall. This study examined the effects of different concentrations of abscisic acid at different concentrations of cadmium stress. Through adding 5 µmol/L and 30 µmol/L cadmium, followed by spraying 10 µmol/L and 40 µmol/L ABA in a hydroponic experiment, it was found that under two concentrations of cadmium stress, low concentration of ABA improved root cell wall polysaccharide, Cd, and uronic acid content. Especially in pectin, after the application of low concentration ABA, the cadmium concentration was significantly increased by 1.5 times and 1.2 times compared with the Cd concentration under Cd5 and Cd30 treatment alone, respectively. Fourier-Transform Infrared spectroscopy (FTIR) demonstrated that cell wall functional groups such as -OH and -COOH were increased with exposure to ABA. Additionally, the exogenous ABA also increased expression of three kinds of antioxidant enzymes and plant antioxidants. The results of this study suggest that ABA could reduce Cd stress by increasing Cd accumulation, promoting Cd adsorption on the root cell wall, and activating protective mechanisms. This result could help promote application of C. bipinnatus for phytostabilization of cadmium-contaminated soil.

Association between gut microbial diversity and technique failure in peritoneal dialysis patients.

BACKGROUND: Gut dysbiosis in peritoneal dialysis (PD) patients causes chronic inflammation and metabolic disorders which result in a series of complications, probably playing an important role in PD technique failure. The reduction in gut microbial diversity was a common feature of gut dysbiosis. The objective was to explore the relationship between gut microbial diversity and technique failure in PD patients. METHODS: The gut microbiota was analyzed by 16s ribosomal RNA gene amplicon sequencing. Cox proportional hazards models were used to identify association between gut microbial diversity and technique failure in PD patients. RESULTS: In this study, a total of 101 PD patients were enrolled. During a median follow-up of 38 months, we found that lower diversity was independently associated with a higher risk of technique failure (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.319-5.456; p = 0.006). In addition, older age (HR, 1.034; 95% CI, 1.005-1.063; p = 0.020) and the history of diabetes (HR, 5.547; 95% CI, 2.218-13.876; p < 0.001) were also independent predictors for technique failure of PD patients. The prediction model constructed on the basis of three independent risk factors above performed well in predicting technique failure at 36 and 48 months (36 months: area under the curve [AUC] = 0.861; 95% CI, 0.836-0.886; 48 months: AUC = 0.815; 95% CI, 0.774-0.857). CONCLUSION: Gut microbial diversity was independently correlated with technique failure in PD patients, and some specific microbial taxa may serve as a potential therapeutic target for decreasing PD technique failure.

TRIM21-mediated proteasomal degradation of SAMHD1 regulates its antiviral activity.

SAMHD1 possesses multiple functions, but whether cellular factors regulate SAMHD1 expression or its function remains not well characterized. Here, by investigating why cultured RD and HEK293T cells show different sensitivity to enterovirus 71 (EV71) infection, we demonstrate that SAMHD1 is a restriction factor for EV71. Importantly, we identify TRIM21, an E3 ubiquitin ligase, as a key regulator of SAMHD1, which specifically interacts and degrades SAMHD1 through the proteasomal pathway. However, TRIM21 has no effect on EV71 replication itself. Moreover, we prove that interferon production stimulated by EV71 infection induces increased TRIM21 and SAMHD1 expression, whereas increasing TRIM21 overrides SAMHD1 inhibition of EV71 in cells and in a neonatal mouse model. TRIM21-mediated degradation of SAMHD1 also affects SAMHD1-dependent restriction of HIV-1 and the regulation of interferon production. We further identify the functional domains in TRIM21 required for SAMHD1 binding and the ubiquitination site K622 in SAMHD1 and show that phosphorylation of SAMHD1 at T592 also blocks EV71 restriction. Our findings illuminate how EV71 overcomes SAMHD1 inhibition via the upregulation of TRIM21.

The Proportion of Memory CD8+ T Cell Predicts Infection Event in Patients with Peritoneal Dialysis.

INTRODUCTION: The immune senescence marked by the inflation of memory T cell is established in end-stage renal disease (ESRD) patients with peritoneal dialysis (PD). These patients suffer high incidence of infectious disease, which has been relevant to immune dysfunction. However the association of immune senescence with infection in PD patients is not clear. This prospective study aimed to investigate the relationship between proportion of T cell subsets and infection event in patients on PD. METHODS: We enrolled patients on PD >6 months from January 1, 2016 to December 30, 2016 and followed them until April 30, 2020. Baseline T cell subsets from blood were collected at the time of recruitment. The primary end point was infection event including peritonitis, exit site infection, pneumonia, urinary tract infection, and other infection. RESULTS: There were 94 patients (46 male) with a mean age of 56.1 ± 14.9 years old enrolled during the follow-up period, and 26 patients suffered infection events. A higher proportion of effector memory (EM) CD8+ T cells was found in patients with infection than in those without infection. There was no difference in the distribution of EM CD8+ T cells between PD-related and non-dialysis infection. Increased level of EM CD8+ T cells was risk factor for first infection event in PD patients. CONCLUSION: High level of EM CD8+ T cells could be a significant predictor of infection event in patients on PD.

Low-molecular-weight organic acid-mediated tolerance and Pb accumulation in centipedegrass under Pb stress.

Lead (Pb) is one of the most harmful, toxic pollutants to the ecological environment and humans. Centipedegrass, a fast-growing warm-season turfgrass, is excellent for Pb pollution remediation. Exogenous low-molecular-weight organic acid (LMWOA) treatment is a promising approach for assisted phytoremediation. However, the effects of this treatment on the tolerance and Pb accumulation of centipedegrass are unclear. This study investigated these effects on the physiological growth response and Pb accumulation distribution characteristics of centipedegrass. Applications of 400 µM citric acid (CA), malic acid (MA) and tartaric acid (TA) significantly reduced membrane lipid peroxidation levels of leaves and improved biomass production of Pb-stressed plants. These treatments mainly increased peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) activities and enhanced free protein (Pro), ascorbic acid (AsA) and phytochelatins (PCs) contents, ultimately improving the Pb tolerance of centipedegrass. Their promoting effects decreased as follows: TA>CA>MA. All the treatments decreased root Pb concentrations and increased stem and leaf Pb concentrations, thus increasing total Pb accumulation and TF values. MA had the best and worst effects on Pb accumulation and Pb transportation, respectively. CA had the best and worst effects on Pb transportation and Pb accumulation, respectively. TA exhibited strong effects on both Pb accumulation and transport. Furthermore, all treatments changed the subcellular Pb distribution patterns and distribution models of the chemical forms of Pb in each tissue. The root Pb concentration was more highly correlated with the Pb subcellular fraction distribution pattern, while the stem and leaf Pb concentrations were more highly correlated with the distribution models of the chemical forms of Pb. Overall, TA improved plant Pb tolerance best and promoted both Pb absorption and transportation well and is considered the best candidate for Pb-contaminated soil remediation with centipedegrass. This study provides a new idea for Pb-contaminated soil remediation with centipedegrass combined with LMWOAs.

Efficiency of heterogeneous chelating agents on the phytoremediation potential and growth of Sasa argenteostriata (Regel) E.G. Camus on Pb-contaminated soil.

Ethylenediaminetetraacetic acid (EDTA) is one of the most effective chelating agents for enhancing lead (Pb) accumulation in various plant organs. However, it has a higher risk of causing secondary pollution than other chelating agents. To reduce such environmental risks and increase remediation efficiency, EDTA can be combined with degradable chelating agents for use in phytoremediation, but there are few reports on the combination of EDTA and nitrilotriacetic acid (NTA). This study evaluated the effects of combined EDTA and NTA application at different concentrations (900, 1200, or 1500 mg/kg) and with different methods (1 application or 3 applications) on dwarf bamboo (Sasa argenteostriata (Regel) E.G. Camus) growth and phytoremediation efficiency and on the soil environment in pot experiments with Pb-contaminated soil. Applying EDTA and NTA together resulted in lower soil water-soluble Pb concentrations than applying EDTA alone and therefore resulted in lower environmental risk. The increased availability of soil Pb produced a stress response in the dwarf bamboo plants, which increased their biomass significantly. Moreover, under the chelating treatments, the soil Pb availability increased, which promoted Pb translocation in plants. The Pb content in the aerial parts of the dwarf bamboo increased significantly in all treatments (translocation factors increased by 300~1500% compared with that in CK). The Pb content increase in the aerial parts caused high proline accumulation in dwarf bamboo leaves, to alleviate Pb toxicity. Maximum Pb accumulation was observed in the EN1500 treatment, which was significantly higher than that in the other treatments except the EN900 treatment. This study elucidates the choice of remediation techniques and the physiological characteristics of the plants used in such studies. In conclusion, the EN900 treatment resulted in the lowest environmental risk, greatest biomass production, and highest phytoremediation efficiency of all treatments, indicating that it has great potential for application in phytoremediation with dwarf bamboo in Pb-contaminated soil.

Disulfiram ameliorates ischemia/reperfusion-induced acute kidney injury by suppressing the caspase-11-GSDMD pathway.

Acute kidney injury (AKI) is a serious condition with high mortality. The most common cause is kidney ischemia/reperfusion (IR) injury, which is thought to be closely related to pyroptosis. Disulfiram is a well-known alcohol abuse drug, and recent studies have shown its ability to mitigate pyroptosis in mouse macrophages. This study investigated whether disulfiram could improve IR-induced AKI and elucidated the possible molecular mechanism. We generated an IR model in mouse kidneys and a hypoxia/reoxygenation (HR) injury model with murine tubular epithelial cells (MTECs). The results showed that IR caused renal dysfunction in mice and triggered pyroptosis in renal tubular epithelial cells, and disulfiram improved renal impairment after IR. The expression of proteins associated with the classical pyroptosis pathway (Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-related specific protein (ASC), caspase-1, N-GSDMD) and nonclassical pyroptosis pathway (caspase-11, N-GSDMD) were upregulated after IR. Disulfiram blocked the upregulation of nonclassical but not all classical pyroptosis pathway proteins (NLRP3 and ASC), suggesting that disulfiram might reduce pyroptosis by inhibiting the caspase-11-GSDMD pathway. In vitro, HR increased intracellular ROS levels, the positive rate of PI staining and LDH levels in MTECs, all of which were reversed by disulfiram pretreatment. Furthermore, we performed a computer simulation of the TIR domain of TLR4 using homology modeling and identified a small molecular binding energy between disulfiram and the TIR domain. We concluded that disulfiram might inhibit pyroptosis by antagonizing TLR4 and inhibiting the caspase-11-GSDMD pathway.