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Powdery mildew, caused by Blumeria graminis f. sp. tritici ( Bgt ), is one of the most destructive diseases that pose a great threat to wheat production. Wheat landraces represent a rich source of powdery mildew resistance. Here, we report the map-based cloning of powdery mildew resistance gene Pm24 from Chinese wheat landrace Hulutou. It encodes a tandem kinase protein (TKP) with putative kinase-pseudokinase domains, designated WHEAT TANDEM KINASE 3 (WTK3). The resistance function of Pm24 was validated by transgenic assay, independent mutants, and allelic association analyses. Haplotype analysis revealed that a rare 6-bp natural deletion of lysine-glycine codons, endemic to wheat landraces of Shaanxi Province, China, in the kinase I domain (Kin I) of WTK3 is critical for the resistance function. Transgenic assay of WTK3 chimeric variants revealed that only the specific two amino acid deletion, rather than any of the single or more amino acid deletions, in the Kin I of WTK3 is responsible for gaining the resistance function of WTK3 against the Bgt fungus. Powdery mildew is a major threat to world wheat yields. Here the authors describe the map-based cloning of Pm24 , a gain-of-function powdery mildew resistance allele that encodes a tandem kinase-pseudokinase protein with a deletion in a kinase domain that is endemic to certain wheat landraces.

Prognostics and health management (PHM) are gradually being applied to production management processes as industrial production is gradually undergoing a transformation, turning into intelligent production and leading to increased demands on the reliability of industrial equipment. Remaining useful life (RUL) prediction plays a pivotal role in this process. Accurate prediction results can effectively provide information about the condition of the equipment on which intelligent maintenance can be based, with many methods applied to this task. However, the current problems of inadequate feature extraction and poor correlation between prediction results and data still affect the prediction accuracy. To overcome these obstacles, we constructed a new fusion model that extracts data features based on a broad learning system (BLS) and embeds long short-term memory (LSTM) to process time-series information, named as the B-LSTM. First, the LSTM controls the transmission of information from the data to the gate mechanism, and the retained information generates the mapped features and forms the feature nodes. Then, the random feature nodes are supplemented by an activation function that generates enhancement nodes with greater expressive power, increasing the nonlinear factor in the network, and eventually the feature nodes and enhancement nodes are jointly connected to the output layer. The B-LSTM was experimentally used with the C-MAPSS dataset and the results of comparison with several mainstream methods showed that the new model achieved significant improvements.

Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Here, we illustrated that the expression of SIRT4 is markedly reduced in cancerous tissues, and closely associated with malignancy stage, grade, and prognosis. In ccRCC cells, SIRT4 exerted its proapoptotic activity through enhancing intracellular reactive oxygen species (ROS). Heme oxygenase-1 (HO-1) is part of an endogenous defense system against oxidative stress. Nevertheless, overexpression of SIRT4 hindered the upregulation of HO-1 in von Hippel–Lindau (VHL)-proficient cells and repressed its expression in VHL-deficient cells. This discrepancy indicated that competent VHL withstands the inhibitory role of SIRT4 on HIF-1α/HO-1. Functionally, overexpression of HO-1 counteracted the promotional effects of SIRT4 on ROS accumulation and apoptosis. Mechanistically, SIRT4 modulates ROS and HO-1 expression via accommodating p38-MAPK phosphorylation. By contrast, downregulation of p38-MAPK by SB203580 decreased intracellular ROS level and enhanced the expression of HO-1. Collectively, this work revealed a potential role for SIRT4 in the stimulation of ROS and the modulation of apoptosis. SIRT4/HO-1 may act as a potential therapeutic target, especially in VHL-deficient ccRCCs.

Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36 , originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance. Powdery mildew is a fungal leaf disease that reduces yield and grain quality in susceptible wheat varieties. Here, the authors report the cloning of the wild emmer wheat originated powdery mildew resistance gene Pm36 as a membrane associated tandem kinase and its possible resistance mechanism.

Key messageA new spot blotch (Bipolaris sorokiniana) resistance gene Sb4 was mapped in a genomic interval of 1.34 Mb on wheat chromosome 4BL.Spot blotch, caused by Bipolaris sorokiniana, has emerged as a serious concern for cultivation of wheat in warmer and humid regions of the world, which results in substantial yield losses and descends with quality. In this study, we identified and mapped a spot blotch resistance gene, designated as Sb4, against B. sorokiniana in wheat. Bulked segregant RNA-Seq (BSR-Seq) analysis and single-nucleotide polymorphism mapping showed that Sb4 is located on the long arm of chromosome 4B. A genetic linkage map of Sb4 was constructed using an F4 mapping population developed from the cross between ‘GY17’ and ‘Zhongyu1211,’ and Sb4 was delimited in a 7.14-cM genetic region on 4BL between markers B6811 and B6901. Using the Chinese Spring reference sequences of chromosome arm 4BL, 13 new polymorphic markers were developed. Finally, Sb4 was mapped in a 1.19-cM genetic interval corresponding to a 1.34-Mb physical genomic region of Chinese Spring chromosome 4BL containing 21 predicted genes. This study provides a foundational step for further cloning of Sb4 using a map-based approach.

Key messagePowdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS.Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.

Improving wheat yield is essential to meet the increasing demand for food production. This study aims to identify quantitative trait loci (QTL) associated with grain traits and plant height (PH) in winter wheat, using a recombinant inbred line (RIL) population derived from a cross between Zhongke 331 and Nongda 399. The RIL population was genotyped using the 16K GenoBaits Wheat single nucleotide polymorphism (SNP) array. A genetic linkage map was established, comprising 14,868 SNPs and spanning 3846.91 cM, with an average interval of 1.11 cM between markers. These SNPs were categorized into 3463 SNP bin markers, with 1653, 1508, and 302 located in the A, B, and D sub-genomes, respectively. QTL analysis for thousand-grain weight (TGW), grain length (GL), grain width (GW), and PH revealed 61 QTL influencing these traits across six environments. Loci qPH-4B.1 and qPH-4D.1 were consistently detected in five environments. QTL clusters with pleiotropic effects that regulate multiple grain traits were identified on chromosomes 4B and 4D. Furthermore, the combination of qPH-4B.1 and qPH-4D.1 resulted in a reduced plant height compared to the presence of either locus alone, indicating an additive effect between these loci.

Due to various environmental pollution issues, cancers have become the \"first killer\" of human beings in the 21st century and their control has become a global strategy of human health. The increasing development of emerging information technologies has provided opportunities for prevention, early detection, diagnosis, intervention, prognosis, nursing, and rehabilitation of cancers. In recent years, the literature associated with emerging technologies in cancer has grown rapidly, but few studies have used bibliometrics and a visualization approach to conduct deep mining and reveal a panorama of this field. To explore the dynamic knowledge evolution of emerging information technologies in cancer literature, we comprehensively analyzed the development status and research hotspots in this field from bibliometrics perspective. We collected 7,136 articles (2000-2017) from the Web of Science database and visually displayed the dynamic knowledge evolution process via the analysis on time-sequence changes, spatial distribution, knowledge base, and hotspots. Much institutional cooperation occurs in this field, and research groups are relatively concentrated. BMC Bioinformatics, PLOS One, Journal of Urology, Scientific Reports, and Bioinformatics are the top five journals in this field. Research hotspots are mainly concentrated in two dimensions: the disease dimension (e.g., cancer, breast cancer, and prostate cancer), and the technical dimension (e.g., robotics, machine learning, data mining, and etc.). The emerging technologies in cancer research is fast ascending and promising. This study also provides researchers with panoramic knowledge of this field, as well as research hotspots and future directions.

Wheat has evolved diverse resistance genes against powdery mildew, typically controlled by single-gene-encoded proteins. Here, we report the map-based cloning of PmWR183 , a resistance locus encoding two adjacent NLR proteins ( PmWR183-NLR1 and PmWR183-NLR2 ) from wild emmer wheat. Stable transformation and CRISPR/Cas9 knockout experiments demonstrate that the two NLRs function cooperatively: neither gene alone confers resistance, but their co-expression restores immunity, while disruption of either gene abolishes resistance. PmWR183 mediates a developmental stage-dependent response, with susceptibility at the seedling stage and strong resistance at the adult stage. Protein interaction assays reveal constitutive association of PmWR183-NLR1 and PmWR183-NLR2, supporting their cooperative role. Geographical and haplotype analyses show the locus originates from wild emmer and is rare in cultivated wheat, exhibiting at least nine haplotypes. Together, our findings uncover a rare NLR gene pair conferring effective resistance to powdery mildew, providing valuable resources for wheat breeding. Wheat powdery mildew resistance is typically controlled by single-gene-encoded resistance protein. Here, the authors report the cloning of powdery mildew resistance locus PmWR183 and show that it encodes two adjacent nucleotide-binding leucine-rich repeat proteins originated from wild emmer wheat.

Hearing loss has an extremely high prevalence worldwide and brings incredible economic and social burdens. Mechanisms such as epigenetics are profoundly involved in the initiation and progression of hearing loss and potentially yield definite strategies for hearing loss treatment. Non-coding genes occupy 97% of the human genome, and their transcripts, non-coding RNAs (ncRNAs), are widely participated in regulating various physiological and pathological situations. NcRNAs, mainly including micro-RNAs (miRNAs), long-stranded non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are involved in the regulation of cell metabolism and cell death by modulating gene expression and protein-protein interactions, thus impacting the occurrence and prognosis of hearing loss. This review provides a detailed overview of ncRNAs, especially miRNAs and lncRNAs, in the pathogenesis of hearing loss. We also discuss the shortcomings and issues that need to be addressed in the study of hearing loss ncRNAs in the hope of providing viable therapeutic strategies for the precise treatment of hearing loss.