Genome-wide characterization of the wall-associated kinase-like (WAKL) family in sesame (Sesamum indicum) identifies a SiWAKL6 gene involved in resistance to Macrophomina Phaseolina.

BACKGROUND: Sesame charcoal rot caused by Macrophomina phaseolina is one of the most serious fungal diseases in sesame production, and threatens the yield and quality of sesame. WAKL genes are important in the plant response to biotic stresses by sensing and transmitting external signals to the intracellular receptor. However, there is still a lack about the WAKL gene family and its function in sesame resistance to M. phaseolina. The aim of this study was to interpret the roles of WAKL genes in sesame resistance to M. phaseolina. RESULTS: In this study, a comprehensive study of the WAKL gene family was conducted and 31 WAKL genes were identified in the sesame genome. Tandem duplication events were the main factor in expansion of the SiWAKL gene family. Phylogenetic analysis showed that the sesame SiWAKL gene family was divided into 4 groups. SiWAKL genes exhibited different expression patterns in diverse tissues. Under M. phaseolina stress, most SiWAKL genes were significantly induced. Notably, SiWAKL6 was strongly induced in the resistant variety "Zhengzhi 13". Functional analysis showed that SiWAKL6 was induced by salicylic acid but not methyl jasmonate in sesame. Overexpression of SiWAKL6 in transgenic Arabidopsis thaliana plants enhanced their resistance to M. phaseolina by inducing the expression of genes involved in the salicylic acid signaling pathway and reconstructing reactive oxygen species homeostasis. CONCLUSIONS: Taken together, the results provide a better understanding of functions about SiWAKL gene family and suggest that manipulation of these SiWAKL genes can improve plant resistance to M. phaseolina. The findings contributed to further understanding of functions of SiWAKL genes in plant immunity.

Decoupling between Economic Growth and Carbon Emissions: Based on Four Major Regions in China.

This paper constructs a decoupling model for four major economic regions of China, based on the Tapio decoupling index method and VAR model for carbon emissions to compare and measure the impact of decoupling between carbon emissions and economic growth in China during 1997 to 2019. The results show that the degree of decoupling between economic growth and carbon emissions varies among different economic regions, and the decoupling status is better in all regions at the beginning of the 21st century. In general, the decoupling status in the eastern and western regions is more ideal than that in the central and northeastern regions. The impulse response and variance decomposition results show that renewable energy consumption could always reduce the growth of carbon emission intensity, and its effects are most significant in the western region. The above findings help to reveal the link between economic growth, renewable energy consumption and carbon emissions in China in recent years, and how to ensure a stable economic growth in China while increasing the share of clean energy consumption in each region to achieve carbon neutrality.

Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS. METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545. FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed. INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment. FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Complete genome sequence of a novel fusarivirus from the phytopathogenic fungus Corynespora cassiicola.

Corynespora cassiicola is an important phytopathogenic fungus that severely impairs crop production. Here, we report the molecular characterization of a novel positive-sense single-stranded RNA (+ssRNA) mycovirus, Corynespora cassiicola fusarivirus 1 (CcFV1), isolated from C. cassiicola strain 20200826-3-1. Excluding the poly(A) tail, the genome of the virus is 6491 nt in length and contains three putative open reading frames (ORFs). The large ORF1 encodes a polypeptide of 1524 aa with a conserved RNA-dependent RNA polymerase (RdRp) domain and a helicase (Hel) domain. BLASTp analysis showed that CcFV1 ORF1 has the highest similarity to Setosphaeria turcica fusarivirus 1 (StFV1, 50.45% identity, E-value 0.0). ORF2 encodes a polypeptide with a conserved chromosome segregation ATPase (Smc) domain. The smaller ORF3 encodes a polypeptide with an unknown function. Phylogenetic analysis based on the ORF1- encoded polypeptide showed that CcFV1 is phylogenetically related to members of the newly proposed family "Fusariviridae". Thus, we suggest that CcFV1 might be a novel member of the family "Fusariviridae", and is the first to be discovered in C. cassiicola.

Oral Administration of Strontium Gluconate Effectively Reduces Articular Cartilage Degeneration Through Enhanced Anabolic Activity of Chondrocytes and Chondrogenetic Differentiation of Mesenchymal Stromal Cells.

Osteoarthritis (OA), a common degenerative disease affecting articular cartilage, is caused by multiple factors, and currently, there are few approaches to effectively delay its progression. This study aimed to evaluate whether a strontium compound (in the form of strontium gluconate, Glu-Sr) could reduce OA pathology severity in osteoarthritic rat models by directly targeting chondrocytes, including catabolic/anabolic activities and/or chondrogenic differentiation. Glu-Sr was administered to OA rats by oral gavage beginning during OA induction and continuing for 8 weeks. Glu-Sr treatment was found to significantly reduce cartilage degeneration and delay OA progression. Further examination showed that collagen II, Sox9, and aggrecan (ACAN) genes were up-regulated whereas IL-1ß was down-regulated in chondrocytes isolated from Glu-Sr-treated rats. Glu-Sr also antagonized the catabolic effects of IL-1ß on chondrocytes. Furthermore, Glu-Sr was shown to promote the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), possibly through promoting chondrogenic gene expression, including CTGF and FGF1, as revealed by RNA-sequencing (RNA-seq). These results suggest that systemic administration of Glu-Sr may be useful in prophylactic and therapeutic treatment of chronic cartilage degradation through affecting multiple steps from chondrogenic differentiation of progenitors to matrix formation in mature chondrocytes.

Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration.

Rationale The small molecule Kartogenin (KGN) promotes cartilage regeneration in osteoarthritis (OA) by activating stem cells differentiation, but its pharmacological mode-of-action remains unclear. KGN can be cleaved into 4-aminobiphenyl (4-ABP) and phthalic acid (PA) following enzymolysis of an amide bond. Therefore, this study investigated whether 4-ABP or PA exerted the same action as KGN. Methods KGN, 4-ABP and PA were analyzed in cartilage of mice after oral, intravenous or intra-articular administration of KGN by liquid chromatography-mass spectrometry method. Their effect on proliferation and chondrogenic differentiation of mesenchymal stem cells (MSC) was evaluated in vitro. Furthermore, their effect on cartilage preservation was tested in mice OA model induced by destabilization of medial meniscus. OA severity was quantified using OARSI histological scoring. Transcriptional analysis was used to find the possible targets of the chemicals, which were further validated. Results We demonstrated that while oral or intra-articular KGN delivery effectively ameliorated OA phenotypes in mice, only 4-ABP was detectable in cartilage. 4-ABP could induce chondrogenic differentiation and proliferation of MSC in vitro and promote cartilage repair in OA mouse models mainly by increasing the number of CD44+/CD105+ stem-cell and prevention of matrix loss. These effect of 4-ABP was stronger than that of KGN. Transcriptional profiling of 4-ABP-stimulated MSC suggested that RPS6KA2 and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in RPS6KA2-knockdown MSC or RPS6KA2-deficient mice.Conclusion 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.

Core regulatory RNA molecules identified in articular cartilage stem/progenitor cells during osteoarthritis progression.

Aim: To assess cartilage-derived stem/progenitor cells (CSPCs) in osteoarthritis (OA) by employing mRNA-miRNA-circRNA-lncRNA network biology approach. Methods: Differentially expressed (DE) RNAs in CSPCs from 2-/4-/8-month-old STR/Ort and CBA mice were identified to construct networks via RNA sequencing. Results: Compared with age-matched CBA mice, 4-/8-month-old STR/Ort mice had cartilage lesions and their CSPCs exhibited lower proliferative and differentiation capacity (decreased CD44 and CD90), and identified 7082 DE RNAs in STR/Ort mice were associated with strain differences or OA progression. OA-related core RNAs were identified via the networks constructed with the predominant DE RNAs, which were involved in the signaling pathways (NF-κB/MAPK/Hippo/Wnt/TGF-ß/cytoskeleton organization). The core RNAs (miR-322-5p/miR-493-5p/miR-378c/CPNE1/Cdh2/PRDM16/CTGF/NCAM1) were validated in CSPCs from OA patients. Conclusion: RNA-based networks identifying core RNAs and signaling pathways contribute to CSPC-dependent OA mechanisms.

[Effects of diazoxide on the mitochondrial ultrastructure and permeability in donor rat myocardium].

OBJECTIVE: To investigate the effect of diazoxide (DE) on the myocardial ultrastructure and opening of maitochondrial permeability transition pore (MPTP) in donor rat heart suffered from long-term hypothermic preservation. METHODS: The Langendorff model of isolated rat heart was used. The hearts were stored in 4 degrees C Celsior solution containing different concentration of DE (15, 30, or 45 micromol/L) for 9 h followed by 60 min of reperfusion. The recovery of rate-pressure product (RPP) was observed. The opening of MPTP and myocardial mitochondria ultrastructure were also evaluated. RESULTS: (1) As compared with the celsior solution preserved group, DE (30 micromol/L) increased recovery of RPP during reperfusion and inhibited the opening of MPTP. DE also alleviated the myocardial mitochondrial ultrastucture damage induced by long-term hypothermic preservation. (2) The above effects of DE were attenuated by a mitoK(ATP) channel inhibitor 5-hydroxydecanoate and a MPTP opener atractyloside. CONCLUSION: In the donor rat heart, DE protects myocardial mitochondria ultrastructure against long-term hypothermic preservation injury via inhibiting the opening of MPIP.