Serum uric acid as a predictor of mortality in patients with stroke: results from National Health and Nutrition Examination Survey 2007-2016.

Objective: This research endeavors to explore the relationship between serum uric acid (SUA) concentration and all-cause mortality in stroke patients. Methods: We undertook a cross-sectional analysis utilizing data derived from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. The concentrations of SUA served as the independent variable, while the dependent variable was defined as all-cause mortality in stroke patients. The quartile method was utilized to classify uric acid levels into four distinct categories. Subsequently, three models were developed, and Cox proportional hazards regression was used to assess the effect of varying uric acid concentrations on the risk of all-cause mortality among stroke patients. Results: The study included a total of 10,805 participants, of whom 395 were stroke patients. Among all populations, the group with elevated levels of uric acid (Q4) exhibited a significant association with the overall mortality risk among stroke patients in all three models (model 1 p < 0.001, model 2 p < 0.001, model 3 p < 0.001). In the male population, there was no significant correlation observed between uric acid levels and the overall mortality risk among stroke patients in model 3 (Q2 p = 0.8, Q3 p = 0.2, Q4 p = 0.2). However, within the female population, individuals with high uric acid levels (Q4) demonstrated a noteworthy association with the overall mortality risk among stroke patients across all three models (model 1 p < 0.001, model 2 p < 0.001, model 3 p < 0.001). Conclusion: This cross-sectional investigation reveals a significant correlation between SUA levels and all-cause mortality in stroke patients, with a noticeable trend observed among females. Consequently, SUA may serve as a promising biomarker for assessing the prognosis of individuals affected by stroke.

Integrative analysis of the transcriptome and metabolome reveals the importance of hepatokine FGF21 in liver aging.

Aging is a contributor to liver disease. Hence, the concept of liver aging has become prominent and has attracted considerable interest, but its underlying mechanism remains poorly understood. In our study, the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted therapy. An aged rat liver model was established with d-galactose, and two other senescent hepatocyte models were established by treating HepG2 cells with d-galactose and H2O2. We then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte models. In livers, genes related to peroxisomes, fatty acid elongation, and fatty acid degradation exhibited down-regulated expression with aging, and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these genes. In senescent hepatocytes, similar to the results found in aged livers, FGF21 expression was also decreased. Moreover, the expressions of cell cycle-related genes were significantly down-regulated, and the down-regulated gene E2F8 was the key cell cycle-regulating transcription factor. We then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging liver. We successfully validated the results from cellular and animal experiments using human liver and blood samples. Our study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases.

20.2% Efficiency Organic Photovoltaics Employing a π-Extension Quinoxaline-Based Acceptor with Ordered Arrangement.

Organic solar cells, as a cutting-edge sustainable renewable energy technology, possess a myriad of potential applications, while the bottleneck problem of less than 20% efficiency limits the further development. Simultaneously achieving an ordered molecular arrangement, appropriate crystalline domain size, and reduced nonradiative recombination poses a significant challenge and is pivotal for overcoming efficiency limitations. This study employs a dual strategy involving the development of a novel acceptor and ternary blending to address this challenge. A novel non-fullerene acceptor, SMA, characterized by a highly ordered arrangement and high lowest unoccupied molecular orbital energy level, is synthesized. By incorporating SMA as a guest acceptor in the PM6:BTP-eC9 system, it is observed that SMA staggered the liquid-solid transition of donor and acceptor, facilitating acceptor crystallization and ordering while maintaining a suitable domain size. Furthermore, SMA optimized the vertical morphology and reduced bimolecular recombination. As a result, the ternary device achieved a champion efficiency of 20.22%, accompanied by increased voltage, short-circuit current density, and fill factor. Notably, a stabilized efficiency of 18.42% is attained for flexible devices. This study underscores the significant potential of a synergistic approach integrating acceptor material innovation and ternary blending techniques for optimizing bulk heterojunction morphology and photovoltaic performance.

Three-dimensional chromatin landscapes in somatotroph tumour.

BACKGROUND: The three-dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored. METHODS: We employed Hi-C and RNA-seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns. RESULTS: We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi-C and RNA-seq data demonstrated that changes inhigher-order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/ß-Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT-PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro. CONCLUSION: Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.

Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging.

PURPOSE: To determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. MATERIAL AND METHODS: Forty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. RESULTS: Compared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. CONCLUSION: Multi-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.

Validation of biomechanical assessment of coronary plaque vulnerability based on intravascular optical coherence tomography and digital subtraction angiography.

Background: It has been suggested that biomechanical factors may influence plaque development. However, key determinants for assessing plaque vulnerability remain speculative. Methods: In this study, a two-dimensional (2D) structural mechanical analysis and a three-dimensional (3D) fluid-structure interaction (FSI) analysis were conducted based on intravascular optical coherence tomography (IV-OCT) and digital subtraction angiography (DSA) data sets. In the 2D study, 103 IV-OCT slices were analyzed. An in-depth morpho-mechanic analysis and a weighted least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to identify the crucial features related to plaque vulnerability via the tuning parameter (λ). In the 3D study, the coronary model was reconstructed by fusing the IV-OCT and DSA data, and a FSI analysis was subsequently performed. The relationship between vulnerable plaque and wall shear stress (WSS) was investigated. Results: The influential factors were selected using the minimum criteria (λ-min) and one-standard error criteria (λ-1se). In addition to the common vulnerable factor of the minimum fibrous cap thickness (FCTmin), four biomechanical factors were selected by λ-min, including the average/maximal displacements and average/maximal stress, and two biomechanical factors were selected by λ-1se, including the average/maximal displacements. Additionally, the positions of the vulnerable plaques were consistent with the sites of high WSS. Conclusions: Functional indices are crucial for plaque status assessment. An evaluation based on biomechanical simulations might provide insights into risk identification and guide therapeutic decisions.

Multifunctional Trifluoroborate Additive for Simultaneous Carrier Dynamics Governance and Defects Passivation to Boost Efficiency and Stability of Inverted Perovskite Solar Cells.

The main obstacles to promoting the commercialization of perovskite solar cells (PSCs) include their record power conversion efficiency (PCE), which still remains below the Shockley-Queisser limit, and poor long-term stability, attributable to crystallographic defects in perovskite films and open-circuit voltage (Voc) loss in devices. In this study, potassium (4-tert-butoxycarbonylpiperazin-1-yl) methyl trifluoroborate (PTFBK) was employed as a multifunctional additive to target and modulate bulk perovskite defects and carrier dynamics of PSCs. Apart from simultaneously passivating anionic and cationic defects, PTFBK could also optimize the energy-level alignment of devices and weaken the interaction between carriers and longitudinal optical phonons, resulting in a carrier lifetime of greater than 3 µs. Furthermore, it inhibited non-radiative recombination and improved the crystallization capacity in the target perovskite film. Hence, the target rigid and flexible p-i-n PSCs yielded champion PCEs of 24.99 % and 23.48 %, respectively. More importantly, due to hydrogen bonding between formamidinium and fluorine, the target devices exhibited remarkable thermal, humidity, and operational tracking at maximum power point stabilities. The reduced Young's modulus and residual stress in the perovskite layer also provided excellent bending stability for flexible target devices.

Non-Fullerene Acceptors Assisted Target Therapy for Interface Treatment Enable High Performance Inverted Perovskite Solar Cells.

Targeted treatment of the interface between electron transport layers (ETL) and perovskite layers is highly desirable for achieving passivating effects and suppressing carrier nonradiative recombination, leading to high performance and long-term stability in perovskite solar cells (PSCs). In this study, a series of non-fullerene acceptors (NFAs, Y-H, Y-F, and Y-Cl) are introduced to optimize the properties of the perovskite/ETL interface. This optimization involves passivating Pb2+ defects, releasing stress, and modulating carrier dynamics through interactions with the perovskite. Remarkably, after modifying with NFAs, the absorption range of perovskite films into the near-infrared region is extended. As expected, Y-F, with the largest electrostatic potential, facilitates the strongest interaction between the perovskite and its functional groups. Consequently, champion power conversion efficiencies of 21.17%, 22.21%, 23.25%, and 22.31% are achieved for control, Y-H-, Y-F-, and Y-Cl-based FA0.88Cs0.12PbI2.64Br0.36 (FACs) devices, respectively. This treatment also enhances the heat stability and air stability of the corresponding devices. Additionally, these modifier layers are applied to enhance the efficiency of Cs0.05(FA0.95MA0.05)0.95PbI2.64Br0.36 (FAMA) devices. Notably, a champion PCE exceeding 24% is achieved in the Y-F-based FAMA device. Therefore, this study provides a facile and effective approach to target the interface, thereby improving the efficiency and stability of PSCs.

The biological mechanism and emerging therapeutic interventions of liver aging.

Research on liver aging has become prominent and has attracted considerable interest in uncovering the mechanism and therapeutic targets of aging to expand lifespan. In addition, multi-omics studies are widely used to perform further mechanistic investigations on liver aging. In this review, we illustrate the changes that occur with aging in the liver, present the current models of liver aging, and emphasize existing multi-omics studies on liver aging. We integrated the multi-omics data of enrolled studies and reanalyzed them to identify key pathways and targets of liver aging. The results indicated that C-X-C motif chemokine ligand 9 (Cxcl9) was a regulator of liver aging. In addition, we provide a flowchart for liver aging research using multi-omics analysis and molecular experiments to help researchers conduct further research. Finally, we present emerging therapeutic treatments that prolong lifespan. In summary, using cells and animal models of liver aging, we can apply a multi-omics approach to find key metabolic pathways and target genes to mitigate the adverse effects of liver aging.

Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study.

PURPOSE: This study aimed to investigate the associations of atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries with severity of white matter hyperintensities (WMHs) in symptomatic patients using magnetic resonance (MR) imaging. METHOD: Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter study of CARE-II. Luminal stenosis of intracranial and extracranial carotid arteries, carotid plaque compositional features, and WMHs were evaluated by brain structural and vascular MR imaging. The atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries were compared between patients with and without moderate-to-severe WMHs (Fazekas score > 2), and their associations with severity of WMHs were analyzed using logistic regression. RESULTS: Of the recruited 622 patients (mean age, 58.7 ± 10.9 years; 422 males), 221 (35.5 %) had moderate-to-severe WMHs with higher prevalence of moderate-to-severe luminal stenosis (17.0 % vs. 10.4 %), intraplaque hemorrhage (15.7 % vs. 9.0 %), thin/ruptured fibrous cap (30.2 % vs. 20.4 %), calcification (44.4 % vs. 22.2 %) and lipid-rich necrotic core (63.8 % vs. 51.1 %) in carotid artery compared to those without (all P < 0.05). Multivariate logistic regression showed that carotid calcification (OR, 1.854; 95 % CI, 1.187-2.898; P = 0.007) was independently associated with moderate-to-severe WMHs after adjusting for confounding factors. No significant association was found between intracranial atherosclerotic stenosis and moderate-to-severe WMHs (P > 0.05). CONCLUSION: Carotid atherosclerotic plaque features, particularly presence of calcification, were independently associated with severity of WMHs, but such association was not found in intracranial atherosclerotic stenosis, suggesting that carotid atherosclerotic plaque characteristics may have closer association with severity of WMHs compared to intracranial atherosclerosis.

A novel chimeric RNA originating from BmCPV S4 and Bombyx mori HDAC11 transcripts regulates virus proliferation.

Polymerases encoded by segmented negative-strand RNA viruses cleave 5'-m7G-capped host transcripts to prime viral mRNA synthesis ("cap-snatching") to generate chimeric RNA, and trans-splicing occurs between viral and cellular transcripts. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV), an RNA virus belonging to Reoviridae, is a major pathogen of silkworm (B. mori). The genome of BmCPV consists of 10 segmented double-stranded RNAs (S1-S10) from which viral RNAs encoding a protein are transcribed. In this study, chimeric silkworm-BmCPV RNAs, in which the sequence derived from the silkworm transcript could fuse with both the 5' end and the 3' end of viral RNA, were identified in the midgut of BmCPV-infected silkworms by RNA_seq and further confirmed by RT-PCR and Sanger sequencing. A novel chimeric RNA, HDAC11-S4 RNA 4, derived from silkworm histone deacetylase 11 (HDAC11) and the BmCPV S4 transcript encoding viral structural protein 4 (VP4), was selected for validation by in situ hybridization and Northern blotting. Interestingly, our results indicated that HDAC11-S4 RNA 4 was generated in a BmCPV RNA-dependent RNA polymerase (RdRp)-independent manner and could be translated into a truncated BmCPV VP4 with a silkworm HDAC11-derived N-terminal extension. Moreover, it was confirmed that HDAC11-S4 RNA 4 inhibited BmCPV proliferation, decreased the level of H3K9me3 and increased the level of H3K9ac. These results indicated that during infection with BmCPV, a novel mechanism, different from that described in previous reports, allows the genesis of chimeric silkworm-BmCPV RNAs with biological functions.

Diffusing capacity of lungs for carbon monoxide associated with subclinical myocardial impairment in systemic sclerosis: A cardiac MR study.

BACKGROUND: Systemic sclerosis (SSc) is characterised by microvascular and fibrotic lesions, which are located not only in skin but also in lungs and heart. OBJECTIVE: This study aimed to investigate the association between lung function and myocardial T1 values using cardiac MR (CMR) imaging in patients with SSc without cardiovascular symptoms. METHODS: The SSc patients and age- and sex-matched healthy subjects underwent CMR. The cardiac function and native T1 values of myocardium and lung function were measured. Spearman's rank correlations and linear regression analyses were performed to determine the association between lung function and myocardial T1. RESULTS: Forty-five SSc patients (aged 47.7±13.2 years, 40 females) and 23 (aged 46.0±14.4 years, 20 females) healthy subjects were enrolled. SSc patients exhibited considerably higher native T1 values compared with healthy subjects (1305.9±49.8 ms vs 1272.6±37.6 ms, p=0.006). Linear regression analysis revealed that decrease of diffusing capacity of lungs for carbon monoxide (DLCO) in SSc patients was notably associated with myocardial native T1 value before (ß -1.017; 95% CI -1.883 to -0.151; p=0.022) and after adjusting for confounding factors (ß -1.108; 95% CI -2.053 to -0.164; p=0.023). Moderate-to-severe decrease of DLCO was found to be significantly associated with myocardial native T1 value (ß 48.006; 95% CI 17.822 to 78.190; p=0.003) after adjusting for confounding factors. CONCLUSION: DLCO inversely correlates with myocardial native T1 values in SSc patients, particularly moderate-to-severely decreased DLCO, suggesting that DLCO might be a potential indicator for subclinical myocardial impairment in SSc patients.

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis. METHODS: The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis. RESULTS: There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR). CONCLUSION: A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.

Performance evaluation of H2S and NH3 removal by biological trickling filter reactors with various fillers under heterotrophic conditions.

A pilot-scale biological trickling filter (BTF) reactor (13.5 L) packed with different fillers (Pine bark, Cinder, Straw, and MBBR (mobile bed biofilm reactor) filler was employed to evaluate their removal performance of H2S and NH3 after heterotrophic bacterium addition, and some parameters, including different packing heights, empty bed residence time (EBRT), inlet titers, loading ratios, and restart trial, were investigated in this study. According to the experimental results, BTF filled with pine bark exhibited better removal efficiency than other reactors under a variety of conditions. The removal efficiency of H2S and NH3 reached to as high as 81.31 % and 91.72 %, respectively, with the loading range of 3.29-67.70 g/m3·h. Moreover, due to the addition of heterotrophic bacterium, the removal efficiency was enhanced and capable to eliminate majority of H2S and NH3 even though the packing height was reduced to 400 mm. After 15 days of idle, the BTF reactor was able to resume rapidly and execute deodorization with high efficiency. The degradation mechanism was further explored by a thorough examination of microbial species which degraded contaminants, as well as by functional prediction and correlation analyses. In a word, these results laid a foundation for the application of heterotrophic microorganisms in BTF, which could improve the removal efficiency of biological deodorization.

Quality and Reliability of Liver Cancer-Related Short Chinese Videos on TikTok and Bilibili: Cross-Sectional Content Analysis Study.

BACKGROUND: Liver cancer incidence has been increasing in China in the recent years, leading to increased public concern regarding the burden of this disease. Short videos on liver cancer are disseminated through TikTok and Bilibili apps, which have gained popularity in recent years as an easily accessible source of health information. However, the credibility, quality, and usefulness of the information in these short videos and the professional knowledge of the individuals uploading health information-based videos in these platforms have not yet been evaluated. OBJECTIVE: Our study aims to assess the quality of the information in Chinese short videos on liver cancer shared on the TikTok and Bilibili short video-sharing platforms. METHODS: In March 2023, we assessed the top 100 Chinese short videos on liver cancer in TikTok and Bilibili (200 videos in total) for their information quality and reliability by using 2 rating tools, namely, global quality score (GQS) and the DISCERN instrument. Correlation and Poisson regression analyses were applied to discuss the factors that could impact video quality. RESULTS: Compared to Bilibili, TikTok is more popular, although the length of the videos on TikTok is shorter than that of the videos on Bilibili (P<.001). The quality of the short videos on liver cancer in TikTok and Bilibili was not satisfactory, with median GQS of 3 (IQR 2-4) and 2 (IQR 1-5) and median DISCERN scores of 5 (IQR 4-6) and 4 (IQR 2-7), respectively. In general, the quality of videos sourced from professional institutions and individuals was better than that of those sourced from nonprofessionals, and videos involving disease-related knowledge were of better quality than those covering news and reports. No significant differences were found in the quality of videos uploaded by individuals from different professions, with the exception of those uploaded by traditional Chinese medicine professionals, which demonstrated poorer quality. Only video shares were positively correlated with the GQS (r=0.17, P=.01), and no video variables could predict the video quality. CONCLUSIONS: Our study shows that the quality of short videos on health information related to liver cancer is poor on Bilibili and TikTok, but videos uploaded by health care professionals can be considered reliable in terms of comprehensiveness and content quality. Thus, short videos providing medical information on TikTok and Bilibili must be carefully considered for scientific soundness by active information seekers before they make decisions on their health care management.

Interaction between Bombyx mori Cytoplasmic Polyhedrosis Virus NSP8 and BmAgo2 Inhibits RNA Interference and Enhances Virus Proliferation.

Some insect viruses encode suppressors of RNA interference (RNAi) to counteract the antiviral RNAi pathway. However, it is unknown whether Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) encodes an RNAi suppressor. In this study, the presence of viral small interfering RNA (vsiRNA) in BmN cells infected with BmCPV was confirmed by small RNA sequencing. The Dual-Luciferase reporter test demonstrated that BmCPV infection may prevent firefly luciferase (Luc) gene silencing caused by particular short RNA. It was also established that the inhibition relied on the nonstructural protein NSP8, which suggests that NSP8 was a possible RNAi suppressor. In cultured BmN cells, the expressions of viral structural protein 1 (vp1) and NSP9 were triggered by overexpression of nsp8, suggesting that BmCPV proliferation was enhanced by NSP8. A pulldown assay was conducted with BmCPV genomic double-stranded RNA (dsRNA) labeled with biotin. The mass spectral detection of NSP8 in the pulldown complex suggests that NSP8 is capable of direct binding to BmCPV genomic dsRNA. The colocalization of NSP8 and B. mori Argonaute 2 (BmAgo2) was detected by an immunofluorescence assay, leading to the hypothesis that NSP8 interacts with BmAgo2. Coimmunoprecipitation further supported the present investigation. Moreover, vasa intronic protein, a component of RNA-induced silencing complex (RISC), could be detected in the coprecipitation complex of NSP8 by mass spectrum analysis. NSP8 and the mRNA decapping protein (Dcp2) were also discovered to colocalize to processing bodies (P bodies) for RNAi-mediated gene silencing in Saccharomyces cerevisiae. These findings revealed that by interacting with BmAgo2 and suppressing RNAi, NSP8 promoted BmCPV growth. IMPORTANCE It has been reported that the RNAi pathway is inhibited by binding RNAi suppressors encoded by some insect-specific viruses belonging to Dicistroviridae, Nodaviridae, or Birnaviridae to dsRNAs to protect dsRNAs from being cut by Dicer-2. However, it is unknown whether BmCPV, belonging to Spinareoviridae, encodes an RNAi suppressor. In this study, we found that nonstructural protein NSP8 encoded by BmCPV inhibits small interfering RNA (siRNA)-induced RNAi and that NSP8, as an RNAi suppressor, can bind to viral dsRNAs and interact with BmAgo2. Moreover, vasa intronic protein, a component of RISC, was found to interact with NSP8. Heterologously expressed NSP8 and Dcp2 were colocalized to P bodies in yeast. These results indicated that NSP8 promoted BmCPV proliferation by binding itself to BmCPV genomic dsRNAs and interacting with BmAgo2 through suppression of siRNA-induced RNAi. Our findings deepen our understanding of the game between BmCPV and silkworm in regulating viral infection.

BmCPV replication is suppressed by the activation of the NF-κB/autophagy pathway through the interaction of vsp21 translated by vcircRNA_000048 with ubiquitin carboxyl-terminal hydrolase.

Bombyx mori cypovirus (BmCPV), a typical double-stranded RNA virus, was demonstrated to generate a viral circRNA, vcircRNA_000048, which encodes a vsp21 with 21 amino acid residues to suppress viral replication. However, the regulatory mechanism of vsp21 on virus infection remained unclear. This study discovered that vsp21 induces reactive oxygen species (ROS) generation, activates autophagy, and attenuates virus replication by inducing autophagy. Then we confirmed that the effect of vsp21-induced autophagy on viral replication was attributed to the activation of the NF-κB signaling pathway. Furthermore, we clarified that vsp21 interacted with ubiquitin carboxyl-terminal hydrolase (UCH) and that ubiquitination and degradation of phospho-IκB-α were enhanced by vsp21 via competitive binding to UCH. Finally, we validated that vsp21 activates the NF-κB/autophagy pathway to suppress viral replication by interacting with UCH. These findings provided new insights into regulating viral multiplication and reovirus-host interaction.

Identification and characterization of extrachromosomal circular DNA in the silk gland of Bombyx mori.

The silk gland cells of silkworm are special cells which only replicate DNA in the nucleus without cell division throughout the larval stage. The extrachromosomal circular DNAs (eccDNAs) have not yet been reported in the silk gland of silkworms. Herein, we have explored the characterization of eccDNAs in the posterior silk gland of silkworms. A total of 35 346 eccDNAs were identified with sizes ranging from 30 to 13 569 549 bp. Motif analysis revealed that dual direct repeats are flanking the 5' and 3' breaking points of eccDNA. The sequences exceeding 1 kb length in eccDNAs present palindromic sequence characteristics flanking the 5' and 3' breaking points of the eccDNA. These motifs might support possible models for eccDNA generation. Genomic annotation of the eccDNA population revealed that most eccDNAs (58.6%) were derived from intergenic regions, whereas full or partial genes were carried by 41.4% of eccDNAs. It was found that silk protein genes fib-H, fib-L, and P25, as well as the transcription factors SGF and sage, which play an important regulatory role in silk protein synthesis, could be carried by eccDNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes carried by eccDNAs were mainly associated with the development and metabolism-related signaling pathways. Moreover, it was found that eccDNAfib-L could promote the transcription of fib-L gene. Overall, the results of the present study not only provide a novel perspective on the mechanism of silk gland development and silk protein synthesis but also complement previously reported genome-scale eccDNA data supporting that eccDNAs are common in eukaryotes.