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Acute hepatopancreatic necrosis (AHPND) is a bacterial disease caused by Vibrio bacteria that severely affects the Pacific white shrimp farming industry. Since AHPND was first identified in China and Vietnam in 2010, it was subsequently identified in Malaysia (2011), Thailand (2012), Mexico (2013), the Philippines (2014), South Korea (2016), Bangladesh (2017), the United States (US) (2017), and Japan (2020). AHPND causes significant economic losses of more than 7 billion US＄ annually to the global shrimp farming industry. It has severely restricted the development of the global shrimp farming industry. Many studies have shown that the pathogens of AHPND are Vibrio spp., including V. parahaemolyticus, V. owensii, V. campbellii, V. harveyi, V. punensis, and V. anguillarum. The virulence of these pathogenic strains was derived from a 70 kb virulent plasmid (pVA1-type plasmid). The pVA1-type plasmid carries pirAB genes encoding the binary toxin pirAB homologous to the insecticidal protein of Photobacterium phosphoreum. The pVA1-type plasmid has been confirmed to carry a novel trb type Ⅳ secretion system (T4SS). Trb-T4SS can mediate the conjugative transfer of the pVA1-type plasmid at high cell density for interspecific horizontal transfer.The quorum sensing (QS) system is also known as the density-sensing system. In the surrounding environment, the QS system allows bacteria to regulate the expression of multiple genes by sensing changes in the concentration of autoinducer signaling molecules. At high cell density, high concentrations of autoinducer signaling molecules bind to receptor proteins to inhibit phosphorylation cascades and high cell density master regulator OpaR is normally expressed. OpaR is involved in the regulation of various biological processes, such as biofilm-forming ability, motility, and the expression of the type Ⅲ and type Ⅳ secretion systems. Reportedly, high concentrations of signaling molecules in the QS system regulate the expression of key genes of the T4SS to increase the conjugative transfer efficiency of drug-resistant plasmids. However, the regulation of the T4SS by opaR in AHPND is not yet reported.In this study, OpaR, the high cell density master regulator of the QS system in V. parahaemolyticus, was selected to explore the relationship between the QS system and T4SS expression, as well as the conjugative transfer of the pVA1-type plasmid. The V. parahaemolyticus 20130629002S01::cat (Vp2S01::cat) strain, a pathogenic strain of AHPND, was used as the starting strain. The opaR gene was replaced with the erythromycin resistance gene (ermB) by homologous recombination and electroporation. The opaR mutant strain (Vp2S01::catΔopaR) was successfully constructed. The effects of OpaR on Vp2S01::cat were explored by performing growth curve and motility assays.Vp2S01::cat and Vp2S01::catΔopaR were cultured continuously for approximately 24 h in a shaking bed at 28 ℃ and 180 r/min. OD600 was measured every 2 h to compare the difference in growth. The results showed that there were no significant differences in the growth curves for Vp2S01::cat and Vp2S01::catΔopaR. Biofilm-forming ability was detected using a crystal violet staining assay. The results showed that the biofilm-forming ability of Vp2S01::catΔopaR was significantly reduced. Growth zone diameter was recorded in 0.3% (swimming) LB agar plates at 28 ℃ for 8 h to analyze the difference in swimming ability. We found that the swimming ability of Vp2S01::catΔopaR increased significantly by 2.67 times compared with that of Vp2S01::cat. Growth zone diameter was recorded in 1.5% (swarming) LB agar plates at 28 ℃ for 12 h to analyze the difference in swarming ability. The results showed that there was no significant difference in swarming ability between Vp2S01::cat and Vp2S01::catΔopaR. However, Vp2S01::catΔopaR had more missing colonies. Using VcLMB29 as the receptor strain, the conjugative transfer efficiency of Vp2S01::cat and Vp2S01::catΔopaR was compared at different time points. We found that the conjugative transfer efficiency of Vp2S01::catΔopaR increased after 12 and 24 h. The conjugative transfer efficiency after 24 h was increased by a factor of 265.43. RNA of Vp2S01::cat and Vp2S01::catΔopaR was extracted after 24 h of conjugative transfer and reverse-transcribed into cDNA for real-time quantitative fluorescence PCR (RT-qPCR). GyrB was used as the reference gene. AphA-qRT, opaR-qRT, and T4SS-qRT primers were used for RT-qPCR. The relative expression levels of genes were calculated using the 2–ΔΔCt method. The results showed that the relative expression levels of T4SS in the Vp2S01::catΔopaR experimental group were significantly increased by 1.13–3.21 times and that the relative expression levels of the key conjugative transfer genes traF, trbE, and traG were significantly increased by 1.96, 1.92, and 3.21 times, respectively.In conclusion, the opaR gene does not affect the growth and swarming motility but does affect the biofilm-forming and swimming ability of Vp2S01::cat. The high cell density master regulator OpaR may affect the conjugative transfer efficiency of the virulent plasmid by regulating the expression levels of T4SS. This study provides fundamental data for analyzing the mechanism by which the QS system regulates the expression of T4SS and the conjugative transfer of the pVA1-type plasmid in AHPND pathogenic bacteria, offering technical support for the control of the horizontal transfer of the virulent plasmid in AHPND-causing bacteria.

Cardiovascular disease (CVD) is one of the leading causes of mortality in humans, and oxidative stress plays a pivotal role in disease progression. This phenomenon typically arises from weakening of the cellular antioxidant system or excessive accumulation of peroxides. This review focuses on a specialized form of oxidative stress—disulfide stress—which is triggered by an imbalance in the glutaredoxin and thioredoxin antioxidant systems within the cell, leading to the accumulation of disulfide bonds. The genesis of disulfide stress is usually induced by extrinsic pathological factors that disrupt the thiol-dependent antioxidant system, manifesting as sustained glutathionylation of proteins, formation of abnormal intermolecular disulfide bonds between cysteine-rich proteins, or irreversible oxidation of thiol groups to sulfenic and sulfonic acids. Disulfide stress not only precipitates the collapse of the antioxidant system and the accumulation of reactive oxygen species, exacerbating oxidative stress, but may also initiate cellular inflammation, autophagy, and apoptosis through a cascade of signaling pathways. Furthermore, this review explores the detrimental effects of disulfide stress on the progression of various CVDs including atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. This review also proposes several potential therapeutic avenues to improve the future treatment of CVDs.

The ultra-high voltage direct current (UHVDC) transmission composed of modular multilevel converters (MMC) is an important technology for large-scale centralized transmission of renewable energy. In UHVDC system, temporary faults in the AC power grid system are a high probability fault, and the fault control strategy affects the safety and reliability of system operation. This paper studies on the condition of AC power grid faults occurring at the receiving converter station. Firstly, study the system characteristics after the occurrence of AC faults, and use theoretical analysis to derive the trend of DC voltage changes of each converter valve. Then, an AC fault ride-through control strategy with high power transmission capability is proposed with hierarchical connection structure, the strategy controls the system to synchronously reduce DC voltage and AC active power after a fault, maximizing the retention of the system’s transmission capacity during the occurrence of faults, thereby reduce power shock in the system. Finally, a simulation model of the dual ended system has built based on the PSCAD simulation platform. The simulation results show that when a single-phase ground fault and a three-phase ground fault occur in the high valve group at the receiving station, the system can retain about 83% and 50% of the transmission capacity during the fault period, respectively. Meanwhile, there is no serious overvoltage or overcurrent phenomenon in the system. The simulation results verified the effectiveness of the proposed control strategy.

Abstract Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well‐characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A‐driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA β-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

Commonly, articular osteochondral tissue exists significant differences in physiological architecture, mechanical function, and biological microenvironment. However, the development of biomimetic scaffolds incorporating upper cartilage, middle tidemark-like, and lower subchondral bone layers for precise articular osteochondral repair remains elusive. This study proposed here a novel strategy to construct the trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment of both mechanical and biological factors. The cartilage-specific microenvironment was achieved through the grafting of kartogenin (KGN) into gelatin via p-hydroxyphenylpropionic acid (HPA)-based enzyme crosslinking reaction as the upper cartilage layer. The bone-specific microenvironment was achieved through the grafting of atorvastatin (AT) into gelatin via dual-crosslinked network of both HP-based enzyme crosslinking and glycidyl methacrylate (GMA)-based photo-crosslinking reactions as the lower subchondral bone layer. The introduction of tidemark-like middle layer is conducive to the formation of well-defined cartilage-bone integrated architecture. The in vitro experiments demonstrated the significant mechanical difference of three layers, successful grafting of drugs, good cytocompatibility and tissue-specific induced function. The results of in vivo experiments also confirmed the mechanical difference of the trilayered bionic scaffold and the ability of inducing osteogenesis and chondrogenesis. Furthermore, the articular osteochondral defects were successfully repaired using the trilayered biomimetic hydrogel scaffolds by the activation of endogenous recovery, which offers a promising alternative for future clinical treatment.

The rapid expansion of aquaculture ponds at the end of the last century raised concerns about their environmental and ecological impacts in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). This study aims to comprehensively investigate the spatiotemporal evolutionary characteristics and explore the influencing factors of aquaculture development in the GBA. An automated approach was established to extract the aquaculture pond areas on the Google Earth Engine (GEE) platform using Landsat images and showed high accuracy. The aquaculture development in the GBA underwent three phases of rapid expansion (1986–1996), constant transformation (1996–2010), and drastic contraction (2010–2020), and was closely related to the important aquaculture policies in China and Guangdong Province. The local aquaculture ponds showed three evolutionary patterns of continuous shrinkage, earlier shrinkage, and later shrinkage, which were mainly influenced by the economic development level and urbanization in each city. Rapid urbanization created great demands for aquaculture products and intense land use competition, which drove the conversion of aquaculture ponds into impervious land and migration from the central GBA towards the surrounding coast and upstream areas. Government policies promoted the initial rapid increase and regulated the aquaculture ponds to develop towards a more environment-friendly and intensive mode, which led to a steady increase of aquaculture products despite the drastic decrease in aquaculture pond areas in the past decade. These evolutionary features are of significance for policymakers and farmers to maintain the sustainable development of aquaculture in the GBA and Guangdong Province.

Abstract Recent studies have reported worldwide vegetation suppression in response to increasing atmospheric vapor pressure deficit (VPD). Here, we integrate multisource datasets to show that increasing VPD caused by warming alone does not suppress vegetation growth in northern peatlands. A site-level manipulation experiment and a multiple-site synthesis find a neutral impact of rising VPD on vegetation growth; regional analysis manifests a strong declining gradient of VPD suppression impacts from sparsely distributed peatland to densely distributed peatland. The major mechanism adopted by plants in response to rising VPD is the “open” water-use strategy, where stomatal regulation is relaxed to maximize carbon uptake. These unique surface characteristics evolve in the wet soil‒air environment in the northern peatlands. The neutral VPD impacts observed in northern peatlands contrast with the vegetation suppression reported in global nonpeatland areas under rising VPD caused by concurrent warming and decreasing relative humidity, suggesting model improvement for representing VPD impacts in northern peatlands remains necessary.

Abstract Background Hyperhomocysteinemia (HHcy) has been linked to development of Alzheimer’s disease (AD) neuropathologically characterized by the accumulation of amyloid β (Aβ). Microglia (MG) play a crucial role in uptake of Aβ fibrils, and its dysfunction worsens AD. However, the effect of HHcy on MG Aβ phagocytosis remains unstudied. Methods We isolated MG from the cerebrum of HHcy mice with genetic cystathionine-β-synthase deficiency (Cbs −/− ) and performed bulk RNA-seq. We performed meta-analysis over transcriptomes of Cbs −/− mouse MG, human and mouse AD MG, MG Aβ phagocytosis model, human AD methylome, and GWAS AD genes. Results HHcy and hypomethylation conditions were identified in Cbs −/− mice. Through Cbs −/− MG transcriptome analysis, 353 MG DEGs were identified. Phagosome formation and integrin signaling pathways were found suppressed in Cbs −/− MG. By analyzing MG transcriptomes from 4 AD patient and 7 mouse AD datasets, 409 human and 777 mouse AD MG DEGs were identified, of which 37 were found common in both species. Through further combinatory analysis with transcriptome from MG Aβ phagocytosis model, we identified 130 functional-validated Aβ phagocytic AD MG DEGs (20 in human AD, 110 in mouse AD), which reflected a compensatory activation of Aβ phagocytosis. Interestingly, we identified 14 human Aβ phagocytic AD MG DEGs which represented impaired MG Aβ phagocytosis in human AD. Finally, through a cascade of meta-analysis of transcriptome of AD MG, functional phagocytosis, HHcy MG, and human AD brain methylome dataset, we identified 5 HHcy-suppressed phagocytic AD MG DEGs (Flt1, Calponin 3, Igf1, Cacna2d4, and Celsr) which were reported to regulate MG/MΦ migration and Aβ phagocytosis. Conclusions We established molecular signatures for a compensatory response of Aβ phagocytosis activation in human and mouse AD MG and impaired Aβ phagocytosis in human AD MG. Our discoveries suggested that hypomethylation may modulate HHcy-suppressed MG Aβ phagocytosis in AD.

Soil disinfestation has been widely used as an effective strategy to improve soil health and crop yield by suppression of soil-borne plant pathogens, but its effect on soil organic carbon (SOC), a crucial factor linked to climate change, remains unknown. A microcosm trial was conducted to evaluate microbial residue carbon (MRC) and its contribution to SOC under chemical soil disinfestation (CSD) with quicklime (QL) and chloropicrin (CP), as well as anaerobic soil disinfestation (ASD) with maize straw (MASD) and soybean straw (SASD). The SOC concentrations were increased by both CSD and ASD. Also, total SOC-normalized MRC concentration was enhanced, with a considerable increase in soil bacterial and fungal MRC, particularly evident under CP and SASD treatment. Due to broad-spectrum biocidal activities, decreased SOC-normalized microbial biomass carbon (MBC) was consistent with the reductions in bacterial and fungal phospholipid fatty acids (PLFAs), consequently increasing MRC accumulation under CSD. Similarly, ASD decreased fungal PLFAs while shifting bacterial PLFAs from aerobic to anaerobic taxa or from gram-negative to -positive taxa, both of which contributed to both MBC and MRC buildup. Collectively, the findings demonstrate that ASD can efficiently increase SOC concentration, with distinct mechanisms underlying MRC generation when compared to traditional CSD.

Summary: Type 1 innate lymphoid cells (ILC1s) possess adaptive immune features, which confer antigen-specific memory responses against haptens and viruses. However, the transcriptional regulation of memory ILC1 responses is currently not known. We show that retinoic acid receptor-related orphan receptor alpha (RORα) has high expression in memory ILC1s in murine contact hypersensitivity (CHS) models. RORα deficiency diminishes ILC1-mediated CHS responses significantly but has no effect on memory T cell-mediated CHS responses. During sensitization, RORα promotes sensitized-ILC1 expansion by suppressing expression of cell-cycle repressors in draining lymph nodes. RORα programs gene-expression patterns related to cell survival and is required for the long-term maintenance of memory ILC1s in the liver. Our findings reveal RORα to be a key transcriptional factor for sensitized-ILC1 expansion and long-term maintenance of memory ILC1s.

Angiogenesis is critical for wound healing and tissue repair. Umbilical cord mesenchymal stem cells (UCMSCs)-conditioned medium has certain actions to promote angiogenesis, and is expected for wound healing and tissue repair. However, recent studies showed that the pro-angiogenic efficacy of unprocessed MSCs-conditioned medium is low, and insufficient for tissue repair. Autophagy is a process for protein recycling and a contributor for cell exocrine, which may enhance pro-angiogenic efficacy of the conditioned medium by stimulating cytokine release from UCMSCs. Therefore, in this study we attempted to obtain enhanced autophagy in UCMSCs using different concentrations of rapamycin and compared pro-angiogenic functions of the conditioned media. The in vitro data showed that although 100 nM-10 μM rapamycin all could induce autophagy in UCMSCs, 100 nM was the best dose to optimize the angiogenic effect of the conditioned medium. The in vivo data also showed that pro-angiogenic effect of the optimized conditioned medium was more obvious than that of the control conditioned medium (0 nM group) in the injected matrigel plaques. Further, the expressions of VEGF, FGF-2, MMP-9, PDGF-α and PDGF-β were markedly increased in UCMSCs treated with 100 nM rapamycin. In conclusion, appropriately enhancing autophagy of UCMSC can improve pro-angiogenic efficacy of the conditioned medium, which may optimize therapeutic applications of UCMSCs-conditioned medium in wound healing and tissue repair.

Abstract Rapid damage prediction for wind disasters is significant in emergency response and disaster mitigation, although it faces many challenges. In this study, a 1-km grid of wind speeds was simulated by the Holland model using the 6-h interval records of maximum wind speed (MWS) for tropical cyclones (TC) from 1949 to 2020 in South China. The MWS during a TC transit was used to build damage rate curves for affected population and direct economic losses. The results show that the Holland model can efficiently simulate the grid-level MWS, which is comparable to the ground observations with R 2 of 0.71 to 0.93 and mean absolute errors (MAEs) of 3.3 to 7.5 m/s. The estimated damage rates were in good agreement with the reported values with R 2 = 0.69–0.87 for affected population and R 2 = 0.65–0.84 for GDP loss. The coastal areas and the Guangdong-Hong Kong-Macao Greater Bay Area have the greatest risk of wind disasters, mainly due to the region’s high density of population and developed economy. Our proposed method is suitable for rapid damage prediction and supporting emergency response and risk assessment at the community level for TCs in the coastal areas of China.

Abstract Background Cross breeding is an important way to improve livestock performance. As an important livestock and poultry resource in Henan Province of China, Bohuai goat was formed by crossing Boer goat and Huai goat. After more than 20 years of breeding, BoHuai goats showed many advantages, such as fast growth, good reproductive performance, and high meat yield. In order to better develop and protect Bohuai goats, we sequenced the whole genomes of 30 BoHuai goats and 5 Huai goats to analyze the genetic diversity, population structure and genomic regions under selection of BoHuai goat. Furthermore, we used 126 published genomes of world-wide goat to characterize the genomic variation of BoHuai goat. Results The results showed that the nucleotide diversity of BoHuai goats was lower and the degree of linkage imbalance was higher than that of other breeds. The analysis of population structure showed that BoHuai goats have obvious differences from other goat breeds. In addition, the BoHuai goat is more closely related to the Boer goat than the Huai goat and is highly similar to the Boer goat. Group by selection signal in the BoHuai goat study, we found that one region on chromosome 7 shows a very strong selection signal, which suggests that it could well be the segment region under the intense artificial selection results. Through selective sweeps, we detected some genes related to important traits such as lipid metabolism (LDLR, STAR, ANGPTL8), fertility (STAR), and disease resistance (CD274, DHPS, PDCD1LG2). Conclusion In this paper, we elucidated the genomic variation, ancestry composition, and selective signals related to important economic traits in BoHuai goats. Our studies on the genome of BoHuai goats will not only help to understand the characteristics of the crossbred but also provide a basis for the improvement of cross-breeding programs.

On 5 September 2022, the Ms 6.8 Luding earthquake occurred at 29.59°N and 102.08°E in China. To investigate the variations in geomagnetic signals before the earthquake, this study analyzes the geomagnetic data from nine stations around the epicenter. First, we apply the Multi-channel Singular Spectrum Analysis to reconstruct the periodic components of the geomagnetic data from multiple stations. Second, we employ K-means clustering to rule out the possibility of occasional anomalies caused by a single station. Subsequently, we construct a geomagnetic topology network considering the remaining stations. Network centrality is defined as a measure of overall network connectivity, where the higher the correlation between multiple stations, the greater the network centrality. Finally, we examine the network centrality 45 days before and 15 days after the Luding earthquake. The results show that several anomalies in network centrality are extracted about one week before the earthquake. We further validate the significance of the anomalies in terms of time as well as space and verify the utility of the centrality anomalies through the SEA technique. The anomalies are found to have a statistical correlation with the earthquake event. We consider that this study provides a new way and a novel observational perspective for earthquake precursor analysis of ground-based magnetic data.

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic swine coronavirus that causes diarrhea and high mortality in piglets, resulting in significant economic losses within the global swine industry. Nonstructural protein 3 (Nsp3) is the largest in coronavirus, playing critical roles in viral replication, such as the processing of polyproteins and the formation of replication-transcription complexes (RTCs). In this study, three monoclonal antibodies (mAbs), 7G4, 5A3, and 2D7, targeting PEDV Nsp3 were successfully generated, and three distinct linear B-cell epitopes were identified within these mAbs by using Western blotting analysis with 24 truncations of Nsp3. The epitope against 7G4 was located on amino acids 31-TISQDLLDVE-40, the epitope against 5A3 was found on amino acids 141-LGIVDDPAMG-150, and the epitope against 2D7 was situated on amino acids 282-FYDAAMAIDG-291. Intriguingly, the epitope 31-TISQDLLDVE-40 recognized by the mAb 7G4 appears to be a critical B-cell linear epitope due to its high antigenic index and exposed location on the surface of Nsp3 protein. In addition, bioinformatics analysis unveiled that these three epitopes were highly conserved in most genotypes of PEDV. These findings present the first characterization of three novel linear B-cell epitopes in the Nsp3 protein of PEDV and provide potential tools of mAbs for identifying host proteins that may facilitate viral infection.

Objective To identify profiles of nurses’ perceived professional benefits as well as their predictors.Design Cross-sectional study.Setting The study was carried out online in China.Methods From 6 July to 27 July 2022, a total of 1309 registered nurses participated in the survey by convenient sampling. We collected the Nurses’ Perceived Professional Benefits Questionnaire and demographic data. Using latent profile analysis (LPA), subgroups of nurses’ perceived professional benefits were identified. Moreover, univariate and multinomial logistic regression analyses were conducted to find the factors that were linked with the profiles.Results The survey was validly completed by 1309 nurses, with a 92.9% effective return rate. The findings of the LPA demonstrated three unique profiles: low-perceived professional benefits (11.8%), moderate-perceived professional benefits (57.1%) and high-perceived professional benefits (31.1%). There was a correlation between marital status, the number of night shifts per month and leadership role.Conclusions According to our research, registered nurses have three unique professional benefit profiles. In order to sustain the nursing workforce, despite the fact that nurses get a high level of professional benefits, interventions are necessary to increase nurses’ perception of their professional value.

Boreal peatlands, a crucial stock of dissolved organic matter (DOM), are susceptible to increased reactive nitrogen (N) inputs. However, the response of DOM characteristics to elevated N availability in these ecosystems is still obscure. Here, we investigated the seasonal variability of DOM quantity and characteristics in surface water and soil pore water after 5-year multi-level N addition (0, 3, 6, and 12 g N m−2 year−1) in a permafrost peatland of Northeast China. In this study, we used the excitation-emission matrix fluorescent spectroscopy combined with fluorescence regional integration, parallel factor analysis, and fluorescence parameters to decipher the effects of N addition on DOM composition, origin, and fate. Irrespective of N addition level, increased N availability reduced dissolved organic carbon concentrations in surface water and soil pore water. However, DOM characteristics are more responsive to N addition in soil pore water than in surface water. Nitrogen addition did not affect DOM composition in surface water, but altered the proportions of tyrosine-, tryptophan-, fulvic acid-, and humic-like DOM in soil pore water. Moreover, the changing trends of DOM composition were diverse during the growing season. In addition, compositional transformations of DOM did not change its biogenic signals, freshness, and humification in both surface water and soil pore water across the growing season. Our results suggest that increased N availability reduces DOM quantity and alters DOM chemical composition, which will improve our understanding of soil organic matter dynamics in boreal peatlands.

Abstract Background Colorectal cancer (CRC) is a prevalent malignancy of the gastrointestinal. Circular RNAs (circRNAs) act as important roles in CRC malignant progression. However, the role of circ_0039857 in CRC is still unclear. Therefore, this study aimed to explore the function and mechanism of hsa_circ_0039857 in the CRC. Methods The mRNA and protein expression were measured via RT-qPCR. RNase R assay and Actinomycin D were employed to evaluate the stability of circ_0039857. Functional experiments, such as proliferation and apoptosis, were applied to study the function of circ_0039857 in CRC cells. The underlying mechanisms of circ_0039857 were then analyzed by bioinformatics, dual-luciferase reporter gene assay, RNA pull-down and rescue experiments. Results We revealed that circ_0039857 was significantly enhanced in CRC. Circ_0039857 was stabler than linear RNA in cells and valuable for the disease diagnosis. In addition, circ_0039857 knockdown inhibited proliferation and promoted apoptosis. Mechanistically, circ_0039857 positively regulated the expression of RAB32 via sponging miR-338-3p. Conclusion This study demonstrated that circ_0039857 knockdown suppressed CRC malignant progression through miR-338-3p/RAB32 axis. Most importantly, this will help us to better understand the circRNA network in CRC, and may find potential biomarkers and targets for CRC clinical treatment.

Abstract Background In molecular biology studies, the selection of optimal reference genes is of vital importance for accurately quantifying gene expression. The purpose of the present study was to screen the most stable reference genes in different muscle tissues of New Zealand white rabbits and Yufeng yellow rabbits. Methods and results Results indicated that the most stable reference genes in the muscle tissues of New Zealand white rabbits were HPRT1, ACTB and PPIC, while HPRT1, PPIC, and RPL13A were the most stable reference genes in muscle tissues of Yufeng yellow rabbits. However, in the longissimus dorsi muscle and the abdominal wall muscle of both varieties, the most stable reference genes were HPRT1, RPL13A, and SDHA. In the quadriceps femoris muscle, the most stable reference genes were ACTB, HPRT1, and SDHA. Furthermore, the relative abundance of MYOG, MYH3 and MSTN was used to confirm the suitability and reliability of the selected most stable reference genes and the most unstable reference gene. Results revealed the same expression patterns of these myogenic genes when normalized according to the most stable genes, while normalization against the unstable reference gene altered the observed expression patterns. Conclusions Taken together, our results demonstrated that the most stable reference genes varied among different muscle tissues and different breeds of rabbits. However, HPRT1, PPIC and SDHA presented high stability among all examined reference genes; thus, the combined analysis of HPRT1/ PPIC/ SDHA gene provides the best reference for RT-qPCR in muscle tissues of New Zealand white rabbits and Yufeng yellow rabbits, while HPRT1 is a better choice than other reference genes when using a single reference gene to assess target gene expression. Our results provide basic data for better measuring target gene expression profiles in muscle tissues of rabbits.

Abstract Little is known about the relationship between baseline systolic blood pressure (SBP) and subsequent clinical events in patients with different lesion patterns on diffusion weighted imaging (DWI). We analyzed the Acute Non‐disabling Cerebrovascular Events (CHANCE) trial dataset. Patients were categorized into negative DW imaging (no detectable lesions), lacunar infarction (single lesion ≤15 mm) and non‐lacunar infarction (single lesion >15 mm or multiple lesions) based on lesion patterns on DWI. The primary outcome was recurrent stroke within 90 days. Cox proportional hazards models were used to assess the association between SBP levels and stroke outcomes in patients with different lesion patterns. A total of 1089 patients were analyzed. We found 258 cases (23.7%) with negative DW imaging, 392 (36.0%) with lacunar infarction and 439 (40.3%) with non‐lacunar infarction. Patients with non‐lacunar infarction had the highest incidence of stroke at 90‐day (P

A molecular-level understanding of the Au-catalyzed CO oxidation on a fast time-resolved scale is still lacking. Here the authors monitor the rapid dynamic changes during CO oxidation over Au/TiO2 using in situ DRIFTS and UV-Vis spectroscopy, and reveal that the catalyst undergoes a surprising structural change at the beginning of the reaction.

Glioma is the worst prognostic neoplasm in the central nervous system. A polarity-regulating GTPase in cells, known as cell division cycle 42 (CdC42), has been proven to have its overactivation tightly connected to high tumor malignancy. The RNA-seq and protein expression of CDC42 in tumor and comparison tissues were analyzed based on the online tools; CDC42 was remarkably boosted in tumor tissues compared to normal controls. A total of 600 patients in the analysis set from The Cancer Genome Atlas (TCGA) database and 657 patients in the validation set from the Chinese Glioma Genome Atlas (CGGA) database were adopted. The expression of CDC42 in clinical features and biological functions of glioma was analyzed, including differential expression analysis, survival analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis. The enrichment of CDC42 was shown to be strongly associated with poor prognosis and terrible clinical indexes of glioma, including higher World Health Organization scale grade, wild-type isocitrate dehydrogenase 1 expression, O6-methylguanine-DNA methyltransferase non-methylated status, and 1p19q non-codeletion status (p < 0.0001). Functional enrichment analysis showed that CDC42 was highly correlated with immune and inflammatory responses in glioma. Additionally, the concentration extent of CDC42 was closely related to immune infiltration, immune checkpoints, and regulatory T (Treg) cell markers (CD4, CD25, and CD127). All evidence suggested that CDC42 may be a potential target for glioma immunotherapy.

In the low-lying, river-rich Pearl River Delta in South China, an extensive network of flood defense levees, spanning over 4400 km, plays a crucial role in urban flood management. These levees are designed to withstand floods and storm surges, yet their failure can lead to significant human and economic losses, highlighting the need for robust urban flood defense strategies. This necessitates the development of a sophisticated geographic information system for the levee network and rapid, accurate assessment methods for levee conditions to support water management and flood mitigation efforts. This study focuses on the levees along the Hengmen waterway in the Pearl River Delta, utilizing airborne Light Detection and Ranging (LiDAR) technology to gather 3D spatial data of the levees. Employing the Cloth Simulation Filter (CSF) algorithm, non-ground point cloud data were extracted. The study improved upon the region-growing algorithm, using a seed point set approach for the automatic extraction of levee point cloud data. The accuracy and completeness of levee extraction were evaluated using the quality index. This method achieved effective extraction of four levee types, showing significant improvements over traditional algorithms, with extraction quality ranging from 72% to 83%. Key research outcomes include the development of a novel method for detecting localized levee depressions based on the computation of the variance of angles between normal vectors in single-phase levee point cloud data. An adaptive optimal neighborhood approach was utilized to accurately determine the normal vectors, effectively representing the local morphology of the levee point clouds. Applied in three levee depression detection experiments, this method proved effective, demonstrating the capability of single-phase data in identifying regions of levee depression deformation. This advancement in levee monitoring technology marks a significant step forward in enhancing urban flood defense capabilities in regions such as the cities of the Pearl River Delta in China.

Calcium (Ca2+), a ubiquitous second messenger, plays a crucial role in many cellular functions. Viruses often hijack Ca2+ signaling to facilitate viral processes such as entry, replication, assembly, and egress. Here, we report that infection by the swine arterivirus, porcine reproductive and respiratory syndrome virus (PRRSV), induces dysregulated Ca2+ homeostasis, subsequently activating calmodulin-dependent protein kinase-II (CaMKII) mediated autophagy, and thus fueling viral replication. Mechanically, PRRSV infection induces endoplasmic reticulum (ER) stress and forms a closed ER-plasma membrane (PM) contacts, resulting the opening of store operated calcium entry (SOCE) channel and causing the ER to take up extracellular Ca2+, which is then released into the cytoplasm by inositol trisphosphate receptor (IP3R) channel. Importantly, pharmacological inhibition of ER stress or CaMKII mediated autophagy blocks PRRSV replication. Notably, we show that PRRSV protein Nsp2 plays a dominant role in the PRRSV induced ER stress and autophagy, interacting with stromal interaction molecule 1 (STIM1) and the 78 kDa glucose-regulated protein 78 (GRP78). The interplay between PRRSV and cellular calcium signaling provides a novel potential approach to develop antivirals and therapeutics for the disease outbreaks.

Abstract Background Acute kidney disease (AKD) evolves a spectrum of acute and subacute kidney disease requiring a global strategy to address. The present study aimed to explore the impact of AKD on the prognosis of ischemic stroke. Methods The Third China National Stroke Registry (CNSR-III) was a nationwide registry of ischemic stroke or transient ischemic attack between August 2015 and March 2018. As a subgroup of CNSR-III, the patients who had serum creatinine (sCr) and serum cystatin C (sCysC) centrally tested on admission and at 3-month, and with 1-year follow-up data were enrolled. Modified AKD criteria were applied to identify patients with AKD during the first 3 months post stroke according to the guidelines developed by the Kidney Disease: Improving Global Outcomes in 2012. The primary clinical outcome was 1-year all-cause death, and secondary outcomes were stroke recurrence and post stroke disability. Results Five thousand sixty-five patients were recruited in the study. AKD was identified in 3.9%, 6.7%, 9.9% and 6.2% of the patients by using sCr, sCr-based estimated glomerular filtration rate (eGFRsCr), sCysC-based eGFR (eGFRsCysC), and combined sCr and sCysC-based eGFR (eGFRsCr+sCysC) criteria, respectively. AKD defined as sCr or eGFRsCr criteria significantly increased the risk of all-cause mortality (adjusted HR 2.67, 95% CI: 1.27–5.61; adjusted HR 2.19, 95% CI: 1.17–4.10) and post stroke disability (adjusted OR 1.60, 95% CI: 1.04–2.44; adjusted OR 1.51, 95% CI: 1.08–2.11). AKD diagnosed by eGFRsCysC or eGFRsCr+sCysC criteria had no significant impact on the risk of all-cause death and post stroke disability. AKD, defined by whichever criteria, was not associated with the risk of stroke recurrence in the adjusted model. Conclusions AKD, diagnosed by sCr or eGFRsCr criteria, were independently associated with 1-year all-cause death and post stroke disability in Chinese ischemic stroke patients.

The rhizosphere microenvironment is crucial to plant–soil physiological processes. The differences among microbial communities in the rhizosphere and non-rhizosphere peatland topsoil (0–15 cm) and subsoil (15–30 cm) in five plant communities dominated by Carex schmidtii, Chamaedaphne calyculata, Ledum palustre, Betula fruticosa, and Vaccinium uliginosum, as well as non-rhizosphere soil in discontinuous and continuous permafrost regions, were studied. We found that the bacteria and nifH gene abundances in the C. calyculata rhizosphere soil in the discontinuous permafrost region were higher than those in continuous permafrost region, while the nirK and nifH gene abundances in the non-rhizosphere soil of the discontinuous permafrost region were lower than those in the continuous permafrost region. The ratio of bacteria to fungi decreased and that of nirK to nirS increased significantly from the discontinuous to the continuous permafrost region, indicating that permafrost degradation can change soil microbial community composition. Fungal abundance was higher in the rhizosphere than the non-rhizosphere soils, suggesting that plant roots provide a more suitable environment for fungi. Moreover, the abundances of the topsoil bacteria; the fungi; and the nirK, nirS, and nifH genes were higher than those in the subsoil because of the organic matter from plant litter as a source of nutrients. The microbial abundance in the subsoil was also more affected by nutrient availability. To sum up, the microbial abundance varied among the different types of rhizosphere and non-rhizosphere soils, and the carbon and nitrogen cycling processes mediated by soil microorganisms may be greatly altered due to permafrost degradation under climate warming.

Regarding global warming, the threat of flooding is projected to increase due to the change in intensity and frequency of single drivers and amplification caused by multi-driver interactions. This interaction becomes more complicated in developing regions with rapidly changing land cover. As a result, demands on flood risk management are rising especially in small watersheds, which are more vulnerable to driver disturbances compared with large watersheds. Existing studies focused on large watersheds rather than small watersheds. However, the findings derived from large-scale analysis cannot be transferred to small watersheds directly. This research investigated the flood responses in the Yonghe River Watershed (YRW) (63.8 km2) in Guangzhou, China, considering the impact of land cover change. The YRW experienced a disastrous compound flood on 22 May 2020. A hydrodynamic model integrating the Hydrologic Engineering Center’s Hydrologic Modeling System and River Analysis System (HEC-HMS and HEC-RAS, respectively) was established and calibrated using the inundation depths observed during the flood. Model analysis using multiple scenarios showed that the watershed is river-dominated, and flood responses to the three factors are nonlinear but with different increasing rates. The response curves for tide levels and land cover changes increase faster at high values, whereas the rainfall intensity curves vary slightly. These findings highlight the importance of integrating tidal impacts into flood risk management, even in river-dominated coastal watersheds. The study further recommends that in small watersheds, 50% imperviousness is an indicator of the urgent demand for flood risk management measures.

The right aortic arch (RAA) is a rare congenital vascular variant disease. We reported a case of subclavian steal syndrome associated with RAA. The primary clinical symptoms were vertigo and ischemic symptoms of the left upper extremity. We diagnosed the condition using aortic computed tomography angiography and digital subtraction angiography. The patient underwent carotid-subclavian bypass surgery.

Abstract Natural peatlands contribute significantly to global carbon sequestration and storage of biomass, most of which derives from Sphagnum peat mosses. Atmospheric CO2 levels have increased dramatically during the twentieth century, from 280 to > 400 ppm, which has affected plant carbon dynamics. Net carbon assimilation is strongly reduced by photorespiration, a process that depends on the CO2 to O2 ratio. Here we investigate the response of the photorespiration to photosynthesis ratio in Sphagnum mosses to recent CO2 increases by comparing deuterium isotopomers of historical and contemporary Sphagnum tissues collected from 36 peat cores from five continents. Rising CO2 levels generally suppressed photorespiration relative to photosynthesis but the magnitude of suppression depended on the current water table depth. By estimating the changes in water table depth, temperature, and precipitation during the twentieth century, we excluded potential effects of these climate parameters on the observed isotopomer responses. Further, we showed that the photorespiration to photosynthesis ratio varied between Sphagnum subgenera, indicating differences in their photosynthetic capacity. The global suppression of photorespiration in Sphagnum suggests an increased net primary production potential in response to the ongoing rise in atmospheric CO2, in particular for mire structures with intermediate water table depths.

Litter decomposition is an important source of carbon accumulation in the permafrost peatlands. Climate warming has led to shrub expansions and accelerated litter mixing with soils and fluctuations in the water table. However, little is known about how changes in the position of the litter will affect litter decomposition under climate warming. To reveal the mechanisms of response of the location of litter in the soil and climate warming to litter decomposition in permafrost peatlands. Here, we selected the evergreen shrub, Chamaedaphne calyculata, and the deciduous shrub, Vaccinium uliginosum, from the permafrost peatlands of the Greater Hing’an Mountains, China. The leaf litter was placed on the soil surface (no-mixing) and mixed with the soil (soil-litter mixing), and then it was incubated for 124 days at 15°C (control) and 20°C (warming). Our results showed that warming significantly increased the CO2 emission rates of C. calyculata and V. uliginosum by 19.9 and 17.4%, respectively. When compared to no-mixing, the CO2 emission rates were reduced (not significantly) by 1.5 (C. calyculata) and increased 13.6% (V. uliginosum) with soil-litter mixing. Interestingly, soil-litter mixing suppressed the positive effect of warming on the CO2 emission rates relative to no-mixing, and the suppressing effects in the V. uliginosum subplot were stronger than those in the C. calyculata subplot. Specifically, warming significantly increased the CO2 emissions of C. calyculata by 27.4% under no-mixing but the increase decreased to 13.1% under soil-litter mixing. Similarly, warming induced significant increases in the CO2 emissions of V. uliginosum, with an increase of 38.8% under no-mixing but non-significant increases (1.9%) were observed under soil-litter mixing. The combination of the enzyme activities of β-1,4-glucosidase, β-1,4-xylosidase and β-D-1,4-cellobiosidase and laccase and phenolics explained more than 60.0% of the variability in the CO2 emissions of C. calyculata and V. uliginosum, respectively. Our study highlights the importance of litter positions in mediating the responses of litter decomposition to climate warming and shrub expansions in the northern peatlands.

Changes in soil CO2 and N2O emissions due to climate change and nitrogen input will result in increased levels of atmospheric CO2 and N2O, thereby feeding back into Earth’s climate. Understanding the responses of soil carbon and nitrogen emissions mediated by microbe from permafrost peatland to temperature rising is important for modeling the regional carbon and nitrogen balance. This study conducted a laboratory incubation experiment at 15 and 20°C to observe the impact of increasing temperature on soil CO2 and N2O emissions and soil microbial abundances in permafrost peatland. An NH4NO3 solution was added to soil at a concentration of 50 mg N kg−1 to investigate the effect of nitrogen addition. The results indicated that elevated temperature, available nitrogen, and their combined effects significantly increased CO2 and N2O emissions in permafrost peatland. However, the temperature sensitivities of soil CO2 and N2O emissions were not affected by nitrogen addition. Warming significantly increased the abundances of methanogens, methanotrophs, and nirK-type denitrifiers, and the contents of soil dissolved organic carbon (DOC) and ammonia nitrogen, whereas nirS-type denitrifiers, β-1,4-glucosidase (βG), cellobiohydrolase (CBH), and acid phosphatase (AP) activities significantly decreased. Nitrogen addition significantly increased soil nirS-type denitrifiers abundances, β-1,4-N- acetylglucosaminidase (NAG) activities, and ammonia nitrogen and nitrate nitrogen contents, but significantly reduced bacterial, methanogen abundances, CBH, and AP activities. A rising temperature and nitrogen addition had synergistic effects on soil fungal and methanotroph abundances, NAG activities, and DOC and DON contents. Soil CO2 emissions showed a significantly positive correlation with soil fungal abundances, NAG activities, and ammonia nitrogen and nitrate nitrogen contents. Soil N2O emissions showed positive correlations with soil fungal, methanotroph, and nirK-type denitrifiers abundances, and DOC, ammonia nitrogen, and nitrate contents. These results demonstrate the importance of soil microbes, labile carbon, and nitrogen for regulating soil carbon and nitrogen emissions. The results of this study can assist simulating the effects of global climate change on carbon and nitrogen cycling in permafrost peatlands.

The alterations of plant composition and diversity pose a threat to the stability of the carbon pool in boreal peatland under climate change. We collected the samples of three plant functional types (deciduous shrubs, evergreen shrubs, and sedge) in seven permafrost peatlands of the Great Hing’an Mountains, China, and measured the properties of total carbon (TC), nitrogen (TN), and phosphorus (TP), their stoichiometric ratios (C:N, C:P, and N:P), and the stable isotope values (δ13C and δ15N) of six tissues (ranging from leaves to roots). For TC, TN, and TP, the contents had an average of 470.69 ± 1.56, 8.03 ± 0.23, and 1.71 ± 0.61 mg·g−1, respectively. TC contents of sedge were lower than those of shrubs for the whole plant. The allocations of N and P to shrub leaves were higher than to stems and roots. There was a similar trend of TN and TP contents, and stoichiometric ratios from leaves to roots between deciduous shrubs and evergreen shrubs. Shrubs and sedge have similar C: N in leaves and fine roots, while leaves of sedge C:P and N:P ratios were higher than shrubs, mainly showed that sedge is N and P co-limitation and shrubs are N limitation. The values of δ13C and δ15N were significantly higher in leaves and roots of sedge than those of shrubs, which means shrubs have higher nutrient acquisition strategies. These results support the shrubs are expanding in the boreal peatland under climate warming through nutrient competition. TC contents of all deciduous shrubs and sedge tissues were positively linear correlated to MAT and the values of δ13C and δ15N in sedge had significant relationships with MAT and MAP. Our results imply warming can increase plant photosynthesis in boreal peatland, and sedge was more sensitive to climate change. These findings would be helpful to understanding the responses of different plant tissues to climate changes in permafrost peatland.

Cerium dioxide (CeO2, ceria) has long been regarded as one of the key materials in modern catalysis, both as a support and as a catalyst itself. Apart from its well-established use (three-way catalysts and diesel engines), CeO2 has been widely used as a cocatalyst/catalyst in energy conversion and storage applications. The importance stems from the oxygen storage capacity of ceria, which allows it to release oxygen under reducing conditions and to store oxygen by filling oxygen vacancies under oxidizing conditions. However, the nature of the Ce active site remains not well understood because the degree of participation of f electrons in catalytic reactions is not clear in the case of the heavy dependence of catalysis theory on localized d orbitals at the Fermi energy EF. This review focuses on the catalytic applications in energy conversion and storage of CeO2-based nanostructures and discusses the mechanisms for several typical catalytic reactions from the perspectives of electronic properties of CeO2-based nanostructures. Defect engineering is also summarized to better understand the relationship between catalytic performance and electronic properties. Finally, the challenges and prospects of designing high efficiency CeO2-based catalysts in energy storage and conversion have been emphasized.

Rotator cuff tear of shoulder is a common tendon injury. Current therapeutic strategies are unsatisfactory because of poor biomechanical properties of the repaired rotator cuff tendons. To solve this problem, a newly biofabricated tenogenic patch by uniaxial cold-drawing technology was applied for the treatment of acute rotator cuff tear and its therapeutic effects were evaluated in vitro and in vivo. The cytocompatibility results indicated that the engineered patch was capable of promoting the spreading, migration and proliferation of tendon fibroblasts in vitro. Stress–strain curves of the sutured patch indicated improved elasticity followed by the yield phenomena, nonlinear plasticity and obviously delaminated rupture. The tenogenic patch also showed significantly enhanced collagen I deposition and better tendon-to-bone healing in the rat rotator cuff tear models in vivo. Furthermore, implantation with the tenogenic patch also promoted the fibrocartilage formation in Safranin-O/Fast green-staining. The analysis of biomechanical properties showed that the tenogenic patch is capable of improving the ultimate load of the repaired tendon. Therefore, the tenogenic patch may constitute an efficient strategy to enhance tendon-to-bone healing for clinical repair applications of rotator cuff tear.

Dynamic nuclear polarization (DNP) greatly improves the NMR sensitivity, but its implementation in aqueous solutions is challenging. Here the authors demonstrate carbon polarization enhancement via in situ Overhauser DNP in small biomolecules in water at room temperature and high magnetic field.

Porcine circovirus type 2 (PCV2) is a swine pathogen that causes postweaning multisystemic wasting syndrome, associated with a number of other disease symptoms in pigs. It has caused high economic losses for pig industries in China and worldwide. Vimentin is a cytoskeletal protein involved in the lifecycle of numerous viruses. In this study, the role of Vimentin in PCV2 replication in pig alveolar macrophage (3D4/21) cells was studied. A 3D4/21 cell line overexpressing Vimentin was established using a lentivirus expression system, in which PCV2 replication was significantly enhanced. Meanwhile, in the Vimentin silenced 3D4/21 cells, PCV2 replication was significantly reduced. Furthermore, we found that PCV2 infection in 3D4/21 cells promoted Vimentin phosphorylation and rearranged Vimentin distribution in cells. By inhibition of CaMKII pathway, Vimentin phosphorylation was significantly suppressed and PCV2 replication was significantly inhibited. The results in this study indicated that in 3D4/21 cells, PCV2 promoted CaMKIIγ-medicated Vimentin phosphorylation and altered its cellular distributions to accomplish its own replication.

T cell immune dysfunction is a prominent characteristic of chronic lymphocytic leukemia (CLL) and the main cause of failure for immunotherapy and multi-drug resistance. There remains a lack of specific biomarkers for evaluating T cell immune status with outcome for CLL patients. T cell factor 1 (TCF1, encoded by the TCF7 gene) can be used as a critical determinant of successful anti-tumor immunotherapy and a prognostic indicator in some solid tumors; however, the effects of TCF1 in CLL remain unclear. Here, we first analyzed the biological processes and functions of TCF1 and co-expressing genes using the GEO and STRING databases with the online tools Venny, Circos, and Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the expression and prognostic values of TCF1 and its partner gene B cell leukemia/lymphoma 11B (BCL11B) were explored for 505 CLL patients from 6 datasets and validated with 50 CLL patients from Henan cancer hospital (HNCH). TCF1 was downregulated in CLL patients, particularly in CD8+ T cells, which was significantly correlated with poor time-to-first treatment (TTFT) and overall survival (OS) as well as short restricted mean survival time (RMST). Function and pathway enrichment analysis revealed that TCF1 was positively correlated with BCL11B, which is involved in regulating the activation and differentiation of T cells in CLL patients. Intriguingly, BCL11B was highly consistent with TCF1 in its decreased expression and prediction of poor prognosis. More importantly, the combination of TCF1 and BCL11B could more accurately assess prognosis than either alone. Additionally, decreased TCF1 and BCL11B expression serves as an independent risk factor for rapid disease progression, coinciding with high-risk indicators, including unmutated IGHV, TP53 alteration, and advanced disease. Altogether, this study demonstrates that decreased TCF1 and BCL11B expression is significantly correlated with poor prognosis, which may be due to decreased TCF1+CD8+ T cells, impairing the effector CD8+ T cell differentiation regulated by TCF1/BCL11B.

Abstract Long non-coding RNAs (lncRNAs) are a new arm of gene regulatory mechanism as discovered by sequencing techniques and follow-up functional studies. The lncRNAs regulation of pseudorabies virus (PRV) infection has rarely been reported so far. Using RNA sequencing analysis, 225 lncRNAs with significant altered expressions in 3D4/21 cells infected with PRV (ZJ01) were identified. Five lncRNAs upregulated in PRV-infected cells were verified in cells infected with different PRV strains by qRT-PCR. By down- and up-regulation of lnc641, the accelerating effect of lnc641 on PRV replication was confirmed. Furthermore, we found that lnc641 regulated PRV replication by inhibiting the JAK-STAT1 pathway. This study suggests that lnc641 could be a new host factor target for developing antiviral therapies against PRV infection.

The SiXianJiao (SXJ) is the first-order exchange node of the West River and the North River and redistributes water (mass) to the downstream river network in the Pearl River Delta (PRD), South China. The lateral SXJ waterway plays a critical role in flow (mass) diversion between the West River and the North River, forming a unique H-shaped compound river node. Previous studies mainly focused on Y-shaped bifurcation and confluence nodes, and there is a lack of research on deltaic H-shaped river nodes. This study established the Delft3D model to investigate the driving forces and influences of flood diversion at the SXJ node. The results showed that the H-shaped SXJ river node was usually in hydraulic equilibrium but was often disturbed by large water level differences between the two rivers, due to unbalanced and asynchronous upstream flood waves. The large water level differences drove mutual flood diversion through the lateral SXJ waterway, which synchronized the downstream discharge and reduced the peak water levels (flood hazards), resulting in similar water levels or hydraulic equilibrium in the two rivers. There exists a critical flow fraction—about 75.9% (West River)—at which the incoming flow from both rivers presents similar water levels at the SXJ node, resulting in little flood diversion. Above the threshold, the flood water will divert from the West River to the North River with a maximum rate of −11,900 m3/s, accounting for 20% of the West River, reducing the peak water level up to 1.48 m at Makou. Below the threshold, the flood water will divert from the North River to the West River with a maximum rate of 11,990 m3/s, accounting for 55% of the North River, reducing the peak water level up to 6.63 m at Sanshui. Meanwhile, the discharge fraction at downstream Makou (Sanshui) maintained a near-constant value during individual floods and fluctuated around 76.6% (23.4%). This critical discharge fraction and the analytical approach are of significance in flood-risk management and hydraulic engineering design in the PRD. The concept model of the H-shaped compound river node clearly elucidates the flood diversion mechanism via the lateral SXJ waterway and may work for other similar river nodes as well.

Tropical Cyclones (TCs) are the most severe natural disasters in the Western North Pacific Ocean (WNP). While previous studies reported evident changes over certain regions or seasons between typical periods, there is a lack of a complete picture of the long-term variations in TC activities in the WNP. This study carried out a comprehensive investigation on the spatiotemporal variations in TC genesis locations and transit pathways in the WNP, based on the TC best-track datasets from the China Meteorological Administration Shanghai Typhoon Institute. The results showed that the TC genesis and occurrence frequencies showed drastic decreases and westward shifts in the WNP from 1950 to 2019. The greatest decrease in TC genesis occurred for Tropical Depressions (TDs: 10.8−17.1 m/s) and Typhoons (TYs: > 32.7 m/s). The number of Tropical Storms (TSs: 17.2−32.6 m/s) and the mean intensity (2 min maximum sustained wind speed) of TCs overall showed no evident change. The decadal average of TC genesis frequency increased by 63% in the near-coast seas (WNPO), but decreased by 46% near the central Pacific Ocean (WNCP), demonstrating a westward shift for TC genesis locations. The TC genesis and occurrence frequencies also showed significant declines in the southern Philippine Sea (SPS) and South China Sea (SCS), while they showed a lower reduction in the Eastern East China Sea (EECS), the northern ocean edge of TC genesis areas, resulting in an increase in the average latitude of TC genesis locations, a spurious northward shift. The La Niña and El Niño years showed contrasting effects on TC genesis frequency and landfall ratios. There were greater instances of TC genesis and greater landfall ratios during the La Niña mature phase, while there were fewer TC formations and lower landfall ratios during the short duration (SD) El Niño developing phase. The TC genesis locations showed a distinct northwestward shift during La Niña years compared to those during El Niño years.

(Sr0.4Ce0.4)1-xNdxTi0.8Mg0.2O3 [(SC)NdTMgO3, x = 0.1–0.4] non-stoichiometric system were obtained through conventional solid-state synthesis technique. All perovskite peaks were attributed to either single (x ≤ 0.3) and/or mixed (x = 0.4) like phases. A solid solution of cubic structure was obtained for x ≤ 0.2, however, for x ≥ 0.3, the (SC)NdTMgO3 compound, exhibits structure instability and (200)/(310) peaks splitting. The peaks splitting indicates cubic (C-phase) to tetrogonal (T-phase) structure phase transition. All ceramic samples appear nearly dense, presenting a non-uniform grain size distribution. The observed trend of the microwave dielectric properties (εr, τf, Q × f) is mainly related to the formation of structure phase transition, packing fraction, relative density and ionic polarizability. A key microwave (MW) dielectric properties of εr = 53, Q × f = 26,700 GHz and τf = +2.8 pmm/°C could be obtained for composition with x = 0.4.

Abstract Background Native cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. Jiaxian Red, a Chinese native cattle breed, is reported to have originated from crossbreeding between taurine and indicine cattle; their history as a draft and meat animal dates back at least 30 years. Using whole-genome sequencing (WGS) data of 30 animals from the core breeding farm, we investigated the genetic diversity, population structure and genomic regions under selection of Jiaxian Red cattle. Furthermore, we used 131 published genomes of world-wide cattle to characterize the genomic variation of Jiaxian Red cattle. Results The population structure analysis revealed that Jiaxian Red cattle harboured the ancestry with East Asian taurine (0.493), Chinese indicine (0.379), European taurine (0.095) and Indian indicine (0.033). Three methods (nucleotide diversity, linkage disequilibrium decay and runs of homozygosity) implied the relatively high genomic diversity in Jiaxian Red cattle. We used θπ, CLR, F ST and XP-EHH methods to look for the candidate signatures of positive selection in Jiaxian Red cattle. A total number of 171 (θπ and CLR) and 17 (F ST and XP-EHH) shared genes were identified using different detection strategies. Functional annotation analysis revealed that these genes are potentially responsible for growth and feed efficiency (CCSER1), meat quality traits (ROCK2, PPP1R12A, CYB5R4, EYA3, PHACTR1), fertility (RFX4, SRD5A2) and immune system response (SLAMF1, CD84 and SLAMF6). Conclusion We provide a comprehensive overview of sequence variations in Jiaxian Red cattle genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Jiaxian Red cattle. We observed a high level of genomic diversity and low inbreeding in Jiaxian Red cattle. These results provide a basis for further resource protection and breeding improvement of this breed.

Abstract Background To describe the objective, design and baseline characteristics of the Jidong Eye Cohort Study (JECS), a community-based cohort in China based on etiology, imaging and biomarkers. The JECS will clarify the pathogenesis of visual impairment and status of ocular indicators in the occurrence and progression of cardio-cerebrovascular and neurological diseases. Methods Between August 2019 and January 2020, the JECS recruited consecutive participants aged 18 years and older from the Jidong communities in China. The demographic and clinical characteristics were collected by trained site personnel via face-to-face interviews. The relevant biological samples were also collected. The participants underwent comprehensive ophthalmic examination, such as retinal photography and optical coherence tomography (OCT) angiography. The following outcomes were measured annually: ocular vascular abnormality, optic nerve degeneration, cardiovascular diseases (CVD) and neurological diseases. The study will be performed until 2024. Results Among 3377 participants, the average age was 45.0 ± 12.5 years and 1809 (53.6%) were women. Hypertension occurred in 825 individuals (25.0%), diabetes in 258 (7.7%), hyperglycemia in 474 (14.2%), and a CVD history in 100 (3.0%). The mean best-corrected visual acuity was 0.1 logMAR in the recruited subjects. The average OCT signal index was 8.2 ± 1.2. Additionally, the mean vessel densities for the entire measured area were 46.4% and 50.8% for the superficial and deep vascular complex, respectively. Mean area and perimeter of foveal avascular zone was 0.3 mm2 and 2.3 mm. Conclusions The JECS is a large community-based prospective cohort in North China. Rich data collected from this study will provide the opportunity to identify risk factors, imaging, and biomarkers of visual impairment (either ocular vascular anomalies or optic nerve degeneration) and to evaluate their associations with CVD and neurological diseases.

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven compounds had high binding potential to NTPase and showed drug-like property. Among them, ZINC12899676 was identified to significantly inhibit the NTPase activity of PEDV by targeting its active pocket and causing its conformational change, and ZINC12899676 significantly inhibited PEDV replication in IPEC-J2 cells. It first demonstrated that ZINC12899676 inhibits PEDV replication by targeting NTPase, and then, NTPase may serve as a novel target for anti-PEDV.

The NLRP3 inflammasome is a crucial constituent of the body’s innate immune system, and a multiprotein platform which is initiated by pattern recognition receptors (PRRs). Its activation leads to caspase-1 maturation and release of inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, and subsequently causes pyroptosis. Recently, the excess activation of NLRP3 inflammasome has been confirmed to mediate inflammatory responses and to participate in genesis and development of atherosclerosis. Therefore, the progress on the discovery of specific inhibitors against the NLRP3 inflammasome and the upstream and downstream inflammatory factors has become potential targets for clinical treatment. Here we review the recently described mechanisms about the NLRP3 inflammasome activation, and discuss emphatically the pharmacological interventions using statins and natural medication for atherosclerosis associated with NLRP3 inflammasome.

Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at −135, −134, and −170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS.

Abstract Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in suckling piglets, leading to severe economic losses worldwide. There is an urgent need to find new therapeutic methods to prevent and control PEDV. Not only is there a shortage of commercial anti-PEDV drugs, but available commercial vaccines fail to protect against highly virulent PEDV variants. We screened an FDA-approved library of 911 natural products and found that tomatidine, a steroidal alkaloid extracted from the skin and leaves of tomatoes, demonstrates significant inhibition of PEDV replication in Vero and IPEC-J2 cells in vitro. Molecular docking and molecular dynamics analysis predicted interactions between tomatidine and the active pocket of PEDV 3CL protease, which were confirmed by fluorescence spectroscopy and isothermal titration calorimetry (ITC). The inhibiting effect of tomatidine on 3CL protease was determined using cleavage visualization and FRET assay. Tomatidine-mediated blocking of 3CL protease activity in PEDV-infected cells was examined by western blot detection of the viral polyprotein in PEDV-infected cells. It indicates that tomatidine inhibits PEDV replication mainly by targeting 3CL protease. In addition, tomatidine also has antiviral activity against transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), encephalo myocarditis virus (EMCV) and seneca virus A (SVA) in vitro. These results may be helpful in developing a new prophylactic and therapeutic strategy against PEDV and other swine disease infections.