Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes

Classical swine fever virus (CSFV) is a classic Flavivirus that causes the acute, febrile, and highly contagious disease known as classical swine fever (CSF). Inflammasomes are molecular platforms that trigger the maturation of proinflammatory cytokines to engage innate immune defenses that are induced upon cellular infection or stress. However, the relationship between the inflammasome and CSFV infection has not been thoroughly characterized. To understand the function of the inflammasome response to CSFV infection, we infected porcine peripheral blood monocytes (PBMCs) with CSFV. Our results indicated that CSFV infection induced both the generation of pro-interleukin-1β (pro-IL-1β) and its processing in monocytes, leading to the maturation and secretion of IL-1β through the activation of caspase 1. Moreover, CSFV infection in PBMCs induced the production and cleavage of gasdermin D (GSDMD), which is an inducer of pyroptosis. Additional studies showed that CSFV-induced IL-1β secretion was mediated by NLRP3 and that CSFV infection could sufficiently activate the assembly of the NLRP3 inflammasome in monocytes. These results revealed that CSFV infection inhibited the expression of NLRP3, and knockdown of NLRP3 enhanced the replication of CSFV. In conclusion, these findings demonstrate that the NLRP3 inflammasome plays an important role in the innate immune response to CSFV infection

Genome and secretome analysis of Pochonia chlamydosporia provide new insight into egg-parasitic mechanisms

Pochonia chlamydosporia infects eggs and females of economically important plant-parasitic nematodes. The fungal isolates parasitizing different nematodes are genetically distinct. To understand their intraspecific genetic differentiation, parasitic mechanisms, and adaptive evolution, we assembled seven putative chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs (~44 Mb, including 7.19% of transposable elements) and compared them with the genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode. We focus on secretomes of the fungus, which play important roles in pathogenicity and fungus-host/environment interactions, and identified 1,750 secreted proteins, with a high proportion of carboxypeptidases, subtilisins, and chitinases. We analyzed the phylogenies of these genes and predicted new pathogenic molecules. By comparative transcriptome analysis, we found that secreted proteins involved in responses to nutrient stress are mainly comprised of proteases and glycoside hydrolases. Moreover, 32 secreted proteins undergoing positive selection and 71 duplicated gene pairs encoding secreted proteins are identified. Two duplicated pairs encoding secreted glycosyl hydrolases (GH30), which may be related to fungal endophytic process and lost in many insect-pathogenic fungi but exist in nematophagous fungi, are putatively acquired from bacteria by horizontal gene transfer. The results help understanding genetic origins and evolution of parasitism-related genes.This work was supported by the National Key Research and Development (R&D) Plan of China (2016YFC1201100), and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IVFCAAS)

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

A Quasi-Randomized Controlled Trial of an Integrated Healthcare Model for Patients with Coronary Heart Disease

Background: An increasing number of coronary heart disease (CHD) patients with an aging population are demanding available and effective out-of-hospital continuous healthcare services. However, great efforts still need to be made to promote out-of-hospital healthcare services for better CHD secondary prevention. This study aims to evaluate the effectiveness of a hospital-community-family (HCF)-based integrated healthcare model on treatment outcomes, treatment compliance, and quality of life (QoL) in CHD patients. Methods: A quasi-randomized controlled trial was conducted at the Department of Cardiology, a tertiary A-level hospital, Wuhan, China from January 2018 to January 2020 in accordance with the Consolidated Standards of Reporting Trials guidelines. CHD patients were enrolled from the hospital and quasi-randomly assigned to either HCF-based integrated healthcare model services or conventional healthcare services. The treatment outcomes and QoL were observed at the 12-month follow-up. Treatment compliance was observed at the 1-month and 12-month follow-ups. Results: A total of 364 CHD patients were quasi-randomly assigned to either integrated healthcare model services (n = 190) or conventional healthcare services (n = 174). Treatment outcomes including relapse and readmission rate (22.6% vs 41.9%; relative risk [RR] = 0.54; 95% confidence interval [CI], 0.40–0.74; p = 0.0031), the occurrence of major cardiovascular events (19.5% vs 45.4%; RR = 0.43; 95% CI, 0.30–0.59; p = 0.0023), complication rate (19.5% vs 35.0%; RR = 0.56; 95% CI, 0.39–0.79; p = 0.0042), and the control rate of CHD risk factors (p 0.05, average p = 0.872). Treatment compliance at the 12-month follow-up in the intervention group, including correct medication, reasonable diet, adherence to exercise, emotional control, self-monitoring, and regular re-examination, was higher than that of the control group (p < 0.05, average p = 0.007). No difference was found in the compliance with smoking cessation and alcohol restriction at the 12-month follow-up between groups (p = 0.043). QoL at the 12-month follow-up in the intervention group was better than that of the control group (86.31 ± 9.39 vs 73.02 ± 10.70, p = 0.0048). Conclusions: The integrated healthcare model effectively improves treatment outcomes, long-term treatment compliance, and QoL of patients, and could be implemented as a feasible strategy for CHD secondary prevention

Developmental Differences between Anthers of Diploid and Autotetraploid Rice at Meiosis

Newly synthetic autotetraploid rice shows lower pollen fertility and seed setting rate relative to diploid rice, which hinders its domestication and breeding. In this study, cytological analysis showed that at meiosis I stage, an unbalanced segregation of homologous chromosomes, occurred as well as an early degeneration of tapetal cells in autotetraploid rice. We identified 941 differentially expressed proteins (DEPs) in anthers (meiosis I), including 489 upregulated and 452 downregulated proteins. The DEPs identified were related to post-translational modifications such as protein ubiquitination. These modifications are related to chromatin remodeling and homologous recombination abnormalities during meiosis. In addition, proteins related to the pentose phosphate pathway (BGIOSGA016558, BGIOSGA022166, and BGIOSGA028743) were downregulated. This may be related to the failure of autotetraploid rice to provide the energy needed for cell development after polyploidization, which then ultimately leads to the early degradation of the tapetum. Moreover, we also found that proteins (BGIOSGA017346 and BGIOSGA027368) related to glutenin degradation were upregulated, indicating that a large loss of glutenin cannot provide nutrition for the development of tapetum, resulting in early degradation of tapetum. Taken together, these evidences may help to understand the differences in anther development between diploid and autotetraploid rice during meiosis

Prognostic Values of Prothrombin Time and Inflammation-Related Parameter in Acute Ischemic Stroke Patients After Intravenous Thrombolysis with rt-PA

In previous studies, prothrombin time (PT), systemic inflammation response index (SIRI) and systemic immune inflammation Index (SII) levels might be the prognostic factors for patients with ischemic stroke. However, the association between these coagulation and inflammation biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) remains unclear and needs further study. Thus, this study aimed to investigate the relationship between these biomarkers and clinical prognosis after IVT in AIS patients. We included patients at the Hebei general hospital diagnosed with AIS who received standard-dose IVT with rt-PA from September 2017 to August 2022. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included short-term outcome at 24 h and functional outcome at 3 months. We enrolled 281 patients in this study. In total, 16 patients had END within 24 h, and 106 patients had an unfavorable outcome at the 3-month visit. In the multivariate analysis, PT level (OR = 1.833; 95% CI: 1.161–2.893; P = 0.009), SIRI level (OR = 2.166; 95% CI: 1.014–4.629; P = 0.046) and SII level (OR = 1.002; 95% CI: 1.000–1.003; P = 0.021) were independently associated with 3-month poor outcome in AIS patients with IVT. In conclusion, the higher PT, SIRI and SII levels were independently associated with poor prognosis in AIS patients after IVT. Additionally, PT, SIRI and SII all can be novel short-term prognostic biomarkers for AIS patients treated with IVT

LncRNA LIMT (LINC01089) contributes to sorafenib chemoresistance via regulation of miR-665 and epithelial to mesenchymal transition in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide and HCC patients often develop drug resisitene. Long non-coding RNAs (LncRNAs) are closely related to cell cycle, growth, development, differentiation, and apoptosis. Abnormally expressed lncRNAs have been proved to mediate drug resistance in tumor cells. However, the effect of LIMT on drug resistance has not been explored in HCC. In this study, we explored the effect of long non-coding RNA LIMT on drug resistance and its underlying mechanism in hepatocellular carcinoma (HCC). Our results showed that LncRNA LINC01089 (LIMT) expression is downregulated in 78.57% (44/56) of 56 HCC tumor tissue samples. LIMT expression is also downregulated in HCC cells compared with that in normal liver LO2 cells. Inhibition of LIMT increases the resistance to sorafenib and promotes cell invasion via regulation of epithelial to mesenchymal transition (EMT) in HCC. StarBase V3.0 was used to predict the potential binding site of miR-665 in LIMT. Furthermore, miR-665 participates in sorafenib resistance and also regulates the level of EMT-related proteins in HCC cells. A rescue experiment demonstrated that silencing of LIMT eliminats the inhibitory effect of the miR-665 inhibitor on sorafenib resistance in HCC cells. Taken together, our findings revealed that downregulation of LIMT increases the resistance of HCC to sorafenib via miR-665 and EMT. Therefore, LIMT, which serves as a therapeutically effective target, will provide new hope for the treatment of HCC

BrPARP1, a Poly (ADP-Ribose) Polymerase Gene, Is Involved in Root Development in Brassica rapa under Drought Stress

PARP proteins are highly conserved homologs among the eukaryotic poly (ADP-ribose) polymerases. After activation, ADP-ribose polymers are synthesized on a series of ribozymes that use NAD+ as a substrate. PARPs participate in the regulation of various important biological processes, such as plant growth, development, and stress response. In this study, we characterized the homologue of PARP1 in B. rapa using RNA interference (RNAi) to reveal the underlying mechanism responding to drought stress. Bioinformatics and expression pattern analyses demonstrated that two copy numbers of PARP1 genes (BrPARP1.A03 and BrPARP1.A05) in B. rapa following a whole-genome triplication (WGT) event were retained compared with Arabidopsis, but only BrPARP1.A03 was predominantly transcribed in plant roots. Silencing of BrPARP1 could markedly promote root growth and development, probably via regulating cell division, and the transgenic Brassica lines showed more tolerance under drought treatment, accompanied with substantial alterations including accumulated proline contents, significantly reduced malondialdehyde, and increased antioxidative enzyme activity. In addition, the findings showed that the expression of stress-responsive genes, as well as reactive oxygen species (ROS)-scavenging related genes, was largely reinforced in the transgenic lines under drought stress. In general, these results indicated that BrPARP1 likely responds to drought stress by regulating root growth and the expression of stress-related genes to cope with adverse conditions in B. rapa