miR-451-targeted PSMB8 promotes PRRSV infection by degrading IRF3.

Porcine respiratory and reproductive syndrome (PRRS) is one of the most devastating infectious diseases of pigs, causing reproductive failures in sows and severe respiratory symptoms in piglets and growing pigs. MicroRNAs (miRNAs) are reported to play an essential role in virus-host interactions. In this study, we demonstrated that miR-451 enhanced type I interferon (IFN-I) production through targeting proteasome subunit ß8 (PSMB8), therefore restricting PRRS virus (PRRSV) replication. We showed that the expression of PSMB8 was upregulated by PRRSV infection, and knockdown of PSMB8 inhibited PRRSV replication by promoting IFN-I production. Moreover, we demonstrated that PSMB8 interacted with the regulatory domain of IRF3 to mediate K48-linked polyubiquitination and degradation of IRF3. Also, importantly, we showed that PSMB8, as a target gene of miR-451, negatively regulated IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to modulate innate immune responses. IMPORTANCE: Porcine respiratory and reproductive syndrome virus (PRRSV), as a huge threat to the swine industry, is a causative agent that urgently needs to be solved. The dissecting of PRRSV pathogenesis and understanding of the host-pathogen interaction will provide insights into developing effective anti-PRRSV strategies. In this study, we showed that miR-451 dramatically inhibited PRRSV replication by targeting proteasome subunit ß8 (PSMB8), a subunit of the immunoproteasome. Mutation of PSMB8 is often related to autoinflammatory diseases due to the elevated IFN production. We revealed that PSMB8 downregulated IFN production by promoting IRF3 degradation. In addition, we showed that PRRSV infection upregulated PSMB8 expression. Taken together, our findings reveal that miR-451 is a negative regulator of PRRSV replication, and PSMB8, a target gene of miR-451, negatively regulates IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to regulate innate immune responses.

Pregnancy-induced physiological hypertrophic preconditioning attenuates pathological myocardial hypertrophy by activation of FoxO3a.

Previous studies show a woman's pregnancy is correlated with post-reproductive longevity, and nulliparity is associated with higher risk of incident heart failure, suggesting pregnancy likely exerts a cardioprotection. We previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning (PHP) can also protect the heart against subsequent pathological hypertrophic stress. We aimed to clarify the phenomenon of PHP and its mechanisms. The pluripara mice whose pregnancy-induced physiological hypertrophy regressed and the nulliparous mice underwent angiotensin II (Ang II) infusion or transverse aortic constriction (TAC). Echocardiography, invasive left ventricular hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. Silencing or overexpression of Foxo3 by adeno-associated virus was used to investigate the role of FoxO3a involved in the antihypertrophic effect. Compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang II infusion, or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with PHP. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3ß (p-GSK3ß)/ß-catenin/Cyclin D1. Silencing or overexpression of Foxo3 attenuated or enhanced the anti-hypertrophic effect of PHP in mice with pathological stimulation. Our findings demonstrate that PHP confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3ß pathway.

Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone.

BACKGROUND: Substrate-based ablation can treat uninducible or hemodynamically instability scar-related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown. OBJECTIVE: To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR. METHODS: Thirty-six patients with scar-related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier. RESULTS: Forty-five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels. CONCLUSION: Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate-based ablation strategies for scar-related VT and shorter procedure times.

Bioinformatics exploration of potential common therapeutic targets for systemic and pulmonary arterial hypertension-induced myocardial hypertrophy.

Systemic and pulmonary arterial hypertension (PAH) can induce left and right ventricular hypertrophy, respectively, but common therapeutic targets for both left and right hypertrophy are limited. In this study, we attempt to explore potential common therapeutic targets and screen out potential target drugs for further study. Cardiac mRNA expression profiles in mice with transverse aortic constriction (TAC) and pulmonary arterial constriction (PAC) are obtained from online databases. After bioinformatics analyses, we generate TAC and PAC mouse models to validate the phenotypes of cardiac remodelling as well as the identified hub genes. Bioinformatics analyses show that there are 214 independent differentially expressed genes (DEGs) in GSE136308 (TAC related) and 2607 independent DEGs in GSE30922 (PAC related), while 547 shared DEGs are associated with the function of the extracellular matrix (ECM) or involved in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and ECM-receptor interactions. We identifyd Fn1, Il6, Col1a1, Igf1, Col1a2, Timp1, Col3a1, Cd44, Ctgf and Postn as hub genes of the shared DEGs, and most of them are associated with myocardial fibrosis. Those hub genes and phenotypes of cardiac remodelling are validated in our TAC and PAC mouse models. Furthermore, we identify dehydroisoandrosterone (DHEA), iloprost and 4,5-dianilinophthalimide (DAPH) as potential therapeutic drugs targeting both left and right ventricular hypertrophy and validate the effect of DHEA. These findings suggest that DHEA could be an effective drug for pressure overload-induced left or right ventricular hypertrophy by regulating the shared hub differentially expressed genes associated with fibrosis.

Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhrt779.

BACKGROUND: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5 to 6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. METHODS: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning [EHP] group) and sedentary mice (control group) then underwent transverse aortic constriction or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated with echocardiography, invasive left ventricular hemodynamic measurement, and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay, and comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot were used to investigate the role of Mhrt779 involved in the antihypertrophic effect induced by EHP. RESULTS: At 1 and 4 weeks after transverse aortic constriction, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after transverse aortic constriction, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction revealed that the long noncoding myosin heavy chain-associated RNA transcript Mhrt779 was one of the markedly upregulated lncRNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with transverse aortic constriction and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. Using chromatin immunoprecipitation assay and quantitative polymerase chain reaction, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779. Comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot showed that Mhrt779 can bind SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (Brg1) to inhibit the activation of the histone deacetylase 2 (Hdac2)/phosphorylated serine/threonine kinase (Akt)/phosphorylated glycogen synthase kinase 3ß(p-GSK3ß) pathway induced by pressure overload. CONCLUSIONS: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779/Brg1/Hdac2/p-Akt/p-GSK3ß.

Phencynonate hydrochloride exerts antidepressant effects by regulating the dendritic spine density and altering glutamate receptor expression.

Phencynonate hydrochloride (PCH) is a drug that crosses the blood-brain barrier. Cellular experiments confirmed that PCH protects against glutamate toxicity and causes only weak central inhibition and limited side effects. As shown in our previous studies, PCH alleviates depression-like behaviours induced by chronic unpredictable mild stress (CUMS). Here we administered PCH at three different doses (4, 8 and 16 mg/kg) to male rats for two continuous days after CUMS and conducted behavioural tests to assess the dose-dependent antidepressant effects of PCH and its effects on the neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). Meanwhile, we measured the spine density and expression of related proteins to illustrate the mechanism of PCH. PCH treatment (8 mg/kg) significantly alleviated depression-like behaviours induced by CUMS. All doses of PCH treatment reversed the spine loss in prelimbic and CA3 regions induced by CUMS. Kalirin-7 expression was decreased in the hippocampus and mPFC of the CUMS group. The expression of the NR1 and NR2B subunits in the hippocampus, and NR2B in mPFC are increased by CUMS. PCH treatment (8 and 16 mg/kg) reversed all of these changes of Kalirin-7 in PFC and hippocampus, as well as NR1 and NR2B expression in the hippocampus. PCH is expected to be developed as a new type of rapid antidepressant. Its antidepressant effect may be closely related to the modulation of dendritic spine density in the prelimbic and CA3 regions and the regulation of Kalilin-7 and N-methyl-D-aspartic acid receptor levels in the hippocampus.

MicroRNA-135a-5p promotes neuronal differentiation of pluripotent embryonal carcinoma cells by repressing Sox6/CD44 pathway.

MicroRNA-135a-5p has been reported to play a potential role in the generation of new neurons. However, the underlying targets of miR-135a-5p in regulating neuronal differentiation have been poorly understood. Our study recently has uncovered that Sox6 and CD44 genes were significantly downregulated during neuronal differentiation of P19 cells, a multipotent cell type. We then found that Sox6 directly bound to the promoter of CD44. Importantly, we identified Sox6 as a direct target of miR-135a-5p. Additionally, we demonstrated that miR-135a-5p is crucial for the neuronal differentiation of P19 cells. More significantly, we found that Sox6 overexpression could overturn miR-135a-5p-mediated neuronal differentiation and dendrite development. In conclusion, these findings indicated that miR-135a-5p/Sox6/CD44 axis provides an important molecular target mechanism for neurodifferentiation.

Phencynonate mediates antidepressant response by activating sirtuin 6-SOD2/Prdx6 pathway.

Major depression is a highly prevalent disorder with no effective medical treatments available. Recent evidence has shown that sirtuins (SIRTs) signaling has been implicated to play an essential in the pathogenesis of depression. Here in this study, we aimed to investigate the potential role of the phencynonate hydrochloride (PHH) in rat models of chronic unpredictable mild stress (CUMS)-induced depression. SIRT6 expression was up-regulated by PHH via increasing NAD+/NADH ratio in the prefrontal cortex. PHH was able to suppress CUMS-induced oxidative stress and enhance the antioxidant capacity and antioxidant proteins activity, such as superoxide dismutase 2 (SOD2) and peroxiredoxin 6 (Prdx6). In vitro study, we found that SIRT6 directly bound to SOD2 and Prdx6 and deacetylated them at Lys68/122 and Lys63/209, which were acetylated by p300/CBP-associated factor (PCAF). Finally, we showed that PHH ameliorated CUMS-induced depressive phenotypes by up-regulating SIRT6 deacetylation activity. In summary, PHH-mediating SIRT6 pathway is required for antidepressant response and PHH can be used as a novel therapeutic to effectively treat depression.

Immunization with a suicidal DNA vaccine expressing the E glycoprotein protects ducklings against duck Tembusu virus.

BACKGROUD: Duck Tembusu virus (DTMUV), a pathogenic flavivirus, emerged in China since 2010 and causing huge economic loss in the Chinese poultry industry. Although several vaccines have been reported to control DTMUV disease, few effective vaccines are available and new outbreaks were continuously reported. Thus, it is urgently to develop a new effective vaccine for prevention of this disease. METHODS: In this study, a suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon and DTMUV E glycoprotein gene was constructed and the efficacy of this new vaccine was assessed according to humoral and cell-mediated immune responses as well as protection against the DTMUV challenge in ducklings. RESULTS: Our results showed that the recombinant SFV replicon highly expressed E glycoprotein in DEF cells. After intramuscular injection of this new DNA vaccine in ducklings, robust humoral and cellular immune responses were observed in all immunized ducklings. Moreover, all ducklings were protected against challenge with the virulent DTMUV AH-F10 strain. CONCLUSIONS: In conclusion, we demonstrate that this suicidal DNA vaccine is a promising candidate facilitating the prevention of DTMUV infection.

Molecular characterization of a novel reovirus isolated from Pekin ducklings in China.

The complete genome sequence of a novel duck orthoreovirus, designated DRV strain TH11(DRV-TH11), was determined and characterized. The DRV-TH11 genome is comprised of 23,417 bp and its genome organization is more similar to that of avian orthoreoviruses (ARVs) of chicken origin than other reoviruses. The results of comparative sequence analysis and dendrograms based on the µB- and σC-encoding genes indicated that TH11 may be derived from the reassortment of ARVs and classic Muscovy duck reovirus (MDRV). A possible recombinant event was identified using the SimPlot program, and it occurred in the M2 segment. The results indicated that reassortment and mutation play a role in the evolution of duck reovirus.

Extracellular vesicles enhance the in vivo antitumor effects of millettia species-derived compounds in chronic myelogenous leukemia therapy.

Several Millettia species are being investigated as medicinal ingredients due to their promising anti-cancer and anti-inflammatory properties. However, the application of Millettia species-derived compounds has been severely hindered by their poor aqueous solubility, rapid metabolism, and low bioavailability. Extracellular vesicles (EVs), which as membrane-bound phospholipid vesicle initiatively secreted through a variety of mammalian cells, are increasingly recognized as promising drug delivery vehicles. Therefore, EVs are with great potential to enhance both the stability and efficacy of the Millettia species-derived compounds in treatment. In this study, extracellular vesicles derived from chronic myelogenous leukemia cells are developed for delivering the extracts of Millettia speciosa Champ and Millettia pachyloba Drake-derived Homobutein. Notably, Homobutein-loaded EV (hEV) formed a stable and homogenous nanosized particle with high entrapment efficiency up to 55.7%. Moreover, EVs loaded with Homobutein were significantly more potent than free drugs in inhibiting K562 cell proliferation. The results demonstrated that intravenous injection of EV loaded with Homobutein effectively inhibits tumor growth in tumor-bearing mice compared to free Homobutein. Hence, this strategy can effectively enhance the efficacy of Millettia species-derived drugs in chronic myelogenous leukemia therapy.

ASFV pA151R negatively regulates type I IFN production via degrading E3 ligase TRAF6.

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly mortal and hemorrhagic infectious disease in pigs. Previous studies have indicated that ASFV modulates interferon (IFN) production. In this study, we demonstrated that ASFV pA151R negatively regulated type I IFN production. Ectopic expression of pA151R dramatically inhibited K63-linked polyubiquitination and Ser172 phosphorylation of TANK-binding kinase 1 (TBK1). Mechanically, we demonstrated that E3 ligase TNF receptor-associated factor 6 (TRAF6) participated in the ubiquitination of TBK1 in cGAS-STING signaling pathway. We showed that pA151R interacted with TRAF6 and degraded it through apoptosis pathway, leading to the disruption of TBK1 and TRAF6 interaction. Moreover, we clarified that the amino acids H102, C109, C132, and C135 in pA151R were crucial for pA151R to inhibit type I interferon production. In addition, we verified that overexpression of pA151R facilitated DNA virus Herpes simplex virus 1 (HSV-1) replication by inhibiting IFN-ß production. Importantly, knockdown of pA151R inhibited ASFV replication and enhanced IFN-ß production in porcine alveolar macrophages (PAMs). Our findings will help understand how ASFV escapes host antiviral immune responses and develop effective ASFV vaccines.

Emerging fatal gout disease in Chinese goslings linked to acute kidney injury induced by novel goose astrovirus infection.

A novel goose astrovirus (GAstV) has broken out across China in recent years, causing widespread damage to the poultry industry. In goslings infected with GAstV, the leading cause of death is visceral gout. However, our understanding of the mechanism of gout formation in GAstV infection is largely inadequate. The aim of this study was to examine the pathogenicity of a GAstV strain and explore the molecular mechanisms of visceral gout caused by viral infection in goslings. The virulent GAstV strain HR2105/1 was effectively isolated from the visceral tissue of goslings in gout-affected areas. The whole genome of the HR2105/1 strain was sequenced and analyzed. Subsequently, we established a gosling gout models with experimental GAstV infection. Finally, we conducted a study on the mechanism of GAstV induced acute kidney injury. Phylogenetic analysis of the complete genome sequence showed that it was closely related to the strain circulating in China since 2016, and it was grouped within the GAstV-1 cluster. The clinical signs were reproduced by experimental infection of healthy goslings with the isolated strain and were found to be similar to those reported in clinical cases. Moreover, the virus exhibits strong renal tropism. Infection with the GAstV strain HR2105/1 was found to cause acute kidney injury, as evidenced by increased levels of uric acid and creatinine as well as severe pathological damage. Mechanistic experiments with Masson and Picrosirius Red staining revealed fibrosis in renal tissues after GAstV infection. Furthermore, TUNEL staining revealed that GAstV infection triggered renal cell apoptosis. Additionally, RT-qPCR revealed that GAstV infection caused an excessive inflammatory response by upregulating the expression of IL-1ß, IL-6, IL-10, TGF-ß, and iNOS in renal tissues. Overall, our findings demonstrate that GAstV infection causes renal damage by inducing renal cell apoptosis, fibrosis, and excessive inflammatory response, which subsequently leads to hyperuricemia and lethal visceral gout formation. This is the first systematic study on the etiology of lethal gout in goslings caused by GAstV infection, and we believe that the findings can guide vaccine development and therapeutic targets for GAstV-associated renal diseases.

Natural product nanozymes of herbal extract galangin in managing hepatocellular carcinoma.

Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive •OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both in vitro and in vivo results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis.

Establishment of a reverse genetics system for virulent systemic feline calicivirus using circular polymerase extension reaction.

Feline caliciviruses can cause oral and upper respiratory tract infections in cats. However, a virulent and systemic feline calicivirus (VS-FCV) variant implicated in multisystem lesions and death in cats has emerged recently. To date, the mechanism underlying virulence variations in VS-FCV remains unclear. The aim of the present study was to provide a tool for exploring genetic variation in VS-FCV, by constructing an infectious clone of VS-FCV SH/2014. First, a full-length cDNA molecular clone of VS-FCV SH/2014 strain, which contains an Xba I recognition site generated by mutating one base (A→T) as a genetic marker, was constructed using the circular polymerase extension reaction (CPER) method. Second, the full-length cDNA clone was introduced into Crandell-Rees feline kidney cells using liposomes to rescue recombinant VS-FCV SH/2014 (rVS-FCV SH/2014). Third, the rescued viruses were identified by real-time PCR, immunofluorescence assay, western blotting, and electron microscopy. The full-length cDNA molecular clone of the VS-FCV SH/2014 strain was successfully constructed and that rVS-FCV SH/2014 could be rescued efficiently. rVS-FCV SH/2014 had the expected genetic markers and morphology and growth characteristics similar to those of the parental virus. The reverse genetics system provides a research platform for future studies on VS-FCV genetic variation and pathogenesis.

Research on adaptive combined wind speed prediction for each season based on improved gray relational analysis.

The stability of the power grid and the operational security of the power system depend on the precise prediction of wind speed. In consideration of the nonlinear and non-stationary characteristics of wind speed in different seasons, this paper employs the weight of wind resource index calculated by triangular fuzzy analytic hierarchy process (TF-AHP), criteria importance through inter-criteria correlation (CRITIC), and entropy weight method (EWM) to improve gray correlation analysis (GRA) and obtain the gray correlation degree of each season. In addition, a wind speed prediction model is provided that includes single-layer and two-layer weighting and is based on both deep and shallow machine learning models. At first, we establish each quarter's wind resource characteristics at typical monthly intervals of 10 min, 30 min, 60 min, and 120 min. The GRA's TF-AHP-CRITIC-EWM, enhanced with subjective and objective weights, is used to assess the available wind resources in each season and to compute the forecasted combination of wind speed for each season. As the final prediction results, the prediction values of each layer model are evaluated independently. For the intervals with considerable errors, we apply wavelet denoising and replacement combination. The simulation findings show that the proposed combined model surpasses earlier benchmark models in terms of goodness of fit, prediction accuracy, and generalizability.

Hierarchical Tantalum Oxide Composite for Efficient Solar-Driven Water Purification.

Applying solar energy to generate drinking water is a clean and low-energy exhaust route to address the issue of water purification. The current challenge with solar vapor generation is constructing nano/micro-hierarchical structures that can convert solar irradiation into exploitable thermal energy with high efficiency. Although various structures and material designs have been reported in recent years, solar vapor conversion can be improved by integrating light harvesting, thermal concentration, and water diffusion. Because of the optimized solar harvesting, enhanced heat capacity, and specified diffusive path endowed by the hierarchical composite structure, amorphous tantalum oxide/carbon-based yolk-shell structures (α-Ta2O5/C YS) for highly efficient solar vapor generation under 1 sun illumination are applied in this study. As a result, the α-Ta2O5/C YS realized a water evaporation rate of 3.54 kg m-2 h-1 with a solar-thermal conversion efficiency of 91% under one sun irradiation (1 kW m-2) with excellent evaporation stability. The collected water from seawater meets the World Health Organization drinking water standard. Importantly, reactive oxygen species enabled by α-Ta2O5 could be produced for water sterilization, exhibiting a facile way for application in various scenarios to acquire drinkable water.

Reversible phase separation of ESCRT protein ALIX through tyrosine phosphorylation.

Cytokinetic abscission, the last step of cell division, is regulated by the ESCRT machinery. In response to mitotic errors, ESCRT proteins, namely, ALIX, CHMP4B, and CHMP4C, accumulate in the cytosolic compartments termed "abscission checkpoint bodies" (ACBs) to delay abscission and prevent tumorigenesis. ALIX contributes to the biogenesis and stability of ACBs via an unknown mechanism. We show that ALIX phase separates into nondynamic condensates in vitro and in vivo, mediated by the amyloidogenic portion of its proline-rich domain. ALIX condensates confined CHMP4 paralogs in vitro. These condensates dissolved and reformed upon reversible tyrosine phosphorylation of ALIX, mediated by Src kinase and PTP1B, and sequestration of CHMP4C altered their Src-mediated dissolution. NMR analysis revealed how ALIX triggers the activation of CHMP4 proteins, which is required for successful abscission. These results implicate ALIX's phase separation in the modulation of ACBs. This study also highlights how posttranslational modifications can control protein phase separation.

miR-204 suppresses porcine reproductive and respiratory syndrome virus (PRRSV) replication via inhibiting LC3B-mediated autophagy.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) has been regarded as a persistent challenge for the swine farms worldwide. microRNAs (miRNAs) play key roles in regulating almost every important biological process, including virus-host interaction. In this study, we found that miR-204 was highly expressed in cells that were not permissive to PRRSV infection compared with cells susceptible to PRRSV infection. Subsequently, we demonstrated that overexpression of miR-204 significantly inhibited PRRSV replication in porcine alveolar macrophages (PAMs). Through bioinformatic analysis, we found that there existed a potential binding site of miR-204 on the 3'UTR of microtubule associated protein 1 light chain 3B (MAP1LC3B, LC3B), a hallmark of autophagy. Applying experiments including luciferase reporter assay and UV cross-linking and immunoprecipitation (CLIP) assay, we demonstrated that miR-204 directly targeted LC3B, thereby downregulating autophagy. Meanwhile, we investigated the interplay between autophagy and PRRSV replication in PAMs, confirming that PRRSV infection induces autophagy, which in turn facilitates viral replication. Overall, we verify that miR-204 suppresses PRRSV replication via inhibiting LC3B-mediated autophagy in PAMs. These findings will provide a novel potential approach for us to develop antiviral therapeutic agents and controlling measures for future PRRSV outbreaks.

African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation.

Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as an inhibitor of cGAS. Specifically, we found that overexpression of QP383R suppressed type I interferons (IFNs) activation stimulated by dsDNA and cGAS/STING, resulting in decreased transcription of IFNß and downstream proinflammatory cytokines. In addition, we showed that QP383R interacted directly with cGAS and promoted cGAS palmitoylation. Moreover, we demonstrated that QP383R suppressed DNA binding and cGAS dimerization, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. Finally, the truncation mutation analysis indicated that the 284-383aa of QP383R inhibited IFNß production. Considering these results collectively, we conclude that QP383R can antagonize host innate immune response to ASFV by targeting the core component cGAS in cGAS-STING signaling pathways, an important viral strategy to evade this innate immune sensor.