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ABSTRACT Deciphering the genetic control of grape berry traits is crucial for optimizing yield, fruit quality, and consumer acceptability. In this study, an association panel of 179 grape genotypes comprising a mixture of ancient cultivars, landraces, and modern varieties collected worldwide were genotyped with genotyping-by-sequencing using a genome-wide association approach based on 32,311 single-nucleotide polymorphism (SNP) markers. Genome-wide efficient mixed-model association was selected as the optimal statistical model based on the results of known control loci of grape berry color traits. Many of the associated SNPs identified in this study were in accordance with the previous QTL analyses using biparental mapping. The grape skin color locus was found to be associated with a mybA transcription factor on chromosome 2. Two strong and distinct association signals associated with berry development periods were found on chromosome 16. Most candidate genes of the interval were highlighted as receptor-like protein kinase. For berry weight, significant association loci were identified on chromosome 18, as previously known, and on chromosome 19 and chromosome 17, as newly mapped. Berry flesh texture was newly located on chromosome 16; candidate genes in the interval were related to calcium. Berry flavor was determined on chromosome 5. Genomic regions were further investigated to reveal candidate genes. In this work, we identified interesting genetic determinants of grape berry-related traits. The identification of the markers closely associated with these berry traits may be useful for grape molecular breeding. Grapes: The genetic basis of fruit traits Genetic analysis of 179 types of vine has revealed regions of the genome and associated genes and proteins that control many of the key traits in the grapes. These traits are crucial for determining fruit quality and yield, in addition to conferring flavors that are highly valued by consumers and wine makers. Researchers in China, led by Da-Long Guo at Henan University of Science and Technology, used DNA sequencing to analyze genetic markers in a mixture of ancient, traditionally cultivated and modern grape varieties. The analysis identified specific regions of the genome linked to grape fruit development, weight, texture, skin color and flavor. The molecular basis of the effects of the identified genetic regions were also explored. The findings will help generate new varieties of grapes for the food and wine industries.

Heat stress is a serious and widespread threat to the quality and yield of many crop species, including grape (Vitis vinifera L.), which is cultivated worldwide. Here, we conducted phosphoproteomic and acetylproteomic analyses of leaves of grape plants cultivated under four distinct temperature regimes. The phosphorylation or acetylation of a total of 1011 phosphoproteins with 1828 phosphorites and 96 acetyl proteins with 148 acetyl sites changed when plants were grown at 35 degrees C, 40 degrees C, and 45 degrees C in comparison with the proteome profiles of plants grown at 25 degrees C. The greatest number of changes was observed at the relatively high temperatures. Functional classification and enrichment analysis indicated that phosphorylation, rather than acetylation, of serine/arginine-rich splicing factors was involved in the response to high temperatures. This finding is congruent with previous observations by which alternative splicing events occurred more frequently in grapevine under high temperature. Changes in acetylation patterns were more common than changes in phosphorylation patterns in photosynthesis-related proteins at high temperatures, while heat-shock proteins were associated more with modifications involving phosphorylation than with those involving acetylation. Nineteen proteins were identified with changes associated with both phosphorylation and acetylation, which is consistent with crosstalk between these posttranslational modification types.

Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD) and have been implicated as mediators of intestinal inflammation. We investigated the hypothesis that N-acetylcysteine (NAC) as a glutathione (GSH) precursor attenuates disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model. A colitis model was induced by adding 5% DSS into the drinking water for 7 days. BALB/c mice were injiciatur enema with saline, 5-ASA, N-acetylcysteine, respectively, and free drinking water as control group. DSS-treated mice developed severe colitis as shown by bloody diarrhea, weight loss, and pathologic involvement. Colon lengths were significantly decreased in DSS-treated mice with decreased GSH activity too (P < 0.01). ROS in the colon, the level of interleukin 1β (IL-1β) in colonic mucosa, serum tumor necrosis factor a (TNF-α), MPO, and MDA were significantly increased in DSS-treated animals (P < 0.01), with decreased PON1 activity (P < 0.01). However, NAC significantly decreased colonic MPO activity, ROS, TNF-α and IL-1β levels and increased PON1 activity and GSH concentration. Moreover, NAC attenuated the macroscopic colonic damage and the histopathologic changes-induced by DSS while similar to 5-ASA group. These results suggest that NAC may be effective in the treatment of colitis through its up-regulating PON1 and scavenging oxygen-derived free radicals.

Recently, cardiac resynchronization therapy （CRT） with multipoint left ventricular （LV） pacing in a single coronary sinus branch （MultiPointTM Pacing [MPP], St. Jude Medical, Inc., Sylmar, CA, USA） has been introduced commercially. The CRT system with MPP feature offers a new strategy for physicians to further enhance CRT in patients with heart failure. Early clinical studies have shown that MPP, compared with conventional biventricular （BiV） pacing, provides acute benefits to LV dP/dtmax, LV dyssynchrony, LV peak radial strain, and LV electrical activation, and improves CRT response at 12 months. In this report, we presented two MPP CRT cases in China with acute hemodynamic assessment under various MPP and conventional BiV pacing configurations, demonstrating that MPP can offer further benefits to patients.

In this paper, PCA combined with Mass Profiler Professional (MPP) bioinformatics software were used to build the dose-effect relationship of traditional Chinese medicine which based on the overall effect of metabonomics. The dataset from Da Cheng Qi Decoction (DCQD) water extract administrated rats plasma collected by UHPLC-Q-TOF-MS and used to demonstrate this method. The approach was confirmed to be an effective and time-saving tool for describing the dose-effect relationship of traditional Chinese medicine.

Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn（0.5 mm） every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.

Aging is a major risk factor for prostate cancer （PCa）, and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors （ARs） by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA （shRNA）, matrix metalloproteinase （MMP） expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

Relaxor ferroelectrics are highly desired for pulse-power dielectric capacitors, however it has become a bottleneck that substantial enhancements of energy density generally sacrifice energy efficiency under superhigh fields. Here, we demonstrate a novel concept of highly polarizable concentrated dipole glass in delicately-designed high-entropy (Bi 1/3 Ba 1/3 Na 1/3 )(Fe 2/9 Ti 5/9 Nb 2/9 )O 3  ceramic achieved via substitution of multiple heterovalent ferroelectric-active principal cation species on equivalent lattice sites. The atomic-scaled polar heterogeneity of dipoles with different polar vectors between adjacent unit cells enables diffuse reorientation process but disables appreciable growth with electric fields. These unique features cause superior recoverable energy density of ~15.9 J cm −3 and efficiency of ~93.3% in bulk ceramics. We also extend the highly polarizable concentrated dipole glass to the prototype multilayer ceramic capacitor, which exhibits record-breaking recoverable energy density of ~26.3 J cm −3 and efficiency of ~92.4% with excellent temperature and cycle stability. This research presents a distinctive approach for designing high-performance energy-storage dielectric capacitors. The authors introduce the concept of highly polarizable concentrated dipole glass, involving the reduction of polar order scale from the nanoscaled polar nanodomains in traditional relaxor ferroelectrics to atomic-scale individual dipoles.

The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)−3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1 . Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.