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Abstract Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Abstract Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P

Abstract BES1, as the most important transcription factor responsible for brassinolide (BR) signaling, has been confirmed to play a significant role in regulating plant growth and the improvement of stress resistance. The transcriptional regulatory mechanism of BES1 has been well elucidated in several plants, such as Arabidopsis thaliana (A. thaliana), Triticum aestivum L. (T. aestivum), and Oryza sativa L. (O. sativa). Nevertheless, the genome-wide analysis of the BES1 family in Vitis vinifera L. (V. vinifera). has not been comprehensively carried out. Thus, we have conducted a detailed analysis and identification of the BES1 transcription factors family in V. vinifera; a total of eight VvBES1 genes was predicted, and the phylogenetic relationships, gene structures, and Cis-acting element in their promoters were also analyzed. BES1 genes have been divided into three groups (I, II and III) based on phylogenetic relationship analysis, and most of VvBES1 genes were in group III. Also, we found that VvBES1 genes was located at seven of the total nineteen chromosomes, whereas VvBES1-2 (Vitvi04g01234) and VvBES1-5 (Vitvi18g00924) had a collinearity relationship, and their three copies are well preserved. In addition, the intron–exon model of VvBES1 genes were mostly conserved, and there existed several Cis-acting elements related to stress resistance responsive and phytohormones responsive in BES1s genes promoter. Moreover, the BES1 expressions were different in different V. vinifera organs, and BES1 expressions were different in different V. vinifera varieties under saline-alkali stress and heat stress, the expression of VvBES1 also changed with the prolongation of saline-alkali stress treatment time. The above findings could not only lay a primary foundation for the further validation of VvBES1 function, but could also provide a reference for molecular breeding in V. vinifera.

Abstract Phytohormones play important roles in germination, blossom, senescence, abscission of plants by a series of signal transduction and molecular regulation. The purpose of this research was to investigate the influence of root restriction (RR) cultivation on plant endogenous hormone variation tendency at different growth stages in diverse organs or tissues. ‘Muscat Hamburg’ (Vitis ‘Muscat of Alexandria’ × Vitis ‘Trollinger’) grapevine was used as test material. High Performance Liquid Chromatography (HPLC) was used to quantify hormone levels, qRT-PCR was used to quantify the expression of genes related to hormone biosynthesis pathway, and determined parameters of growth and photosynthetic, aiming to investigate the influence of root restriction on the formation and metabolism of phytohormones, as well as the degree of correlation between phytohormones and plant growth and photosynthetic intensity under root restriction. By measuring the photosynthetic rate of leaves at the stages of core-hardening, veraison and maturity, it was found that root restriction could reduce most photosynthetic parameters. The results also revealed that RR treatment increased abscisic acid (ABA), salicylic acid (SA), zeatin riboside (ZR), N6-(delta 2-isopentenyl)-adenine nucleoside (iPR) concentrations, while reduced auxin (IAA), 3-indolepropionic acid (IPA), 3-indolebutyric acid (IBA), gibberellin A3 (GA3), zeatin (ZT), N6-(delta 2-Isopentenyl)-adenine (iP), kinetin (KT), jasmonic acid (JA) and methyl jasmonate (MeJA) concentrations in most organs and at most developmental stages. RT-qPCR was carried out to further explore the effect of root restriction on genes expression of ABA, SA and IAA biosynthesis pathways at molecular level. Meanwhile, through correlation analysis, we found that different phytohormones contributed differently to physiological indicators, there existed strong correlation of ABA, KT, MeJA, iPR, SA, JA with leaf photosynthesis, GA3, IBA, ZR, IAA, ZT with fruit quality. In addition, we also found that the shoot growth related parameters were closely correlated with JA, IPA and iP. To sum up, our results suggested that RR treatment could significantly increase soluble solid content, regulate the growth and photosynthesis of grapevine, by affecting the biosynthesis of phytohormones. It could further prove that root restriction was a feasible technique to ameliorate the phenomenon of low quality in grape berry in southern China.

Abstract High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.

Abstract A novel polymeric mixed micelle composed of Pluronic F127 and D-α-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and β-galactosidase (β-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT mixed micelles were evaluated both in vitro and in vivo. The FT mixed micelles showed that a average particle size of 20.03 nm, and a low CMC of 0.0031% in water. The in vitro release of Rho123 from Rho123 loaded FT mixed micelles (FT/Rho123) presented a sustained-release property. FT/Rho123 also showed higher efficiency for the accumulation in brain capillary endothelial cells (BCECs) and brain tissues. β-Gal, a model protein, was also delivered and accumulated efficiently in the brain by spontaneous loading in the FT mixed micelles. Therefore, the results indicated that F127/TPGS mixed micelles may be considered as an effective nanocarrier for the brain-targeted delivery of diagnostic and therapeutic drugs.

Abstract Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

Abstract Rhizome rot is a destructive soil-borne disease of Polygonatum kingianum and adversely affects the yield and sustenance of the plant. Understanding how the causal fungus Fusarium oxysporum infects P. kingianum may suggest effective control measures against rhizome rot. In germinating conidia of infectious F. oxysporum, expression of the zinc finger transcription factor gene Zfp1, consisting of two C2H2 motifs, was up-regulated. To characterize the critical role of ZFP1, we generated independent deletion mutants (zfp1) and complemented one mutant with a transgenic copy of ZFP1 (zfp1 tZFP1). Mycelial growth and conidial production of zfp1 were slower than those of wild type (ZFP1) and zfp1 tZFP1. Additionally, a reduced inhibition of growth suggested zfp1 was less sensitive to conditions promoting cell wall and osmotic stresses than ZFP1 and zfp1 tZFP1. Furthermore pathogenicity tests suggested a critical role for growth of zfp1 in infected leaves and rhizomes of P. kingianum. Thus ZFP1 is important for mycelial growth, conidiation, osmoregulation, and pathogenicity in P. kingianum.

Abstract As a core step of obstacle avoidance and path planning, dynamic obstacle detection is critical for autonomous driving. This study aimed to propose a dynamic obstacle detection method based on U–V disparity and residual optical flow for autonomous driving. First, a drivable area of an unmanned vehicle was detected using U–V disparity images. Then, obstacles in the drivable area were detected using U–V disparity images and the geometric relationship between obstacle size and its disparity. Finally, the motion likelihood of each obstacle was estimated by compensating the camera ego-motion. The innovation of the proposed method was that the searching range of the moving obstacles was greatly narrowed by detecting the obstacles in the drivable area, which greatly improved not only the moving obstacle detection efficiency but also the detection accuracy. Datasets from the KITTI benchmark and our self-acquired campus scene data were chosen as testing samples. The experimental results showed that our method could achieve high detection precision, low missed detection rate and less time consumption.

Abstract Accumulating evidence has implicated dietary factors as important risks for rheumatoid arthritis (RA) development, but analyses of the effects of red meat consumption on RA have yielded diverging results. The aim of this study was to explore the association between red meat and RA in a large-scale, cross-sectional study. From June to December 2016, a total of 733 patients were investigated, from which 707 participants were included in the analysis. These patients were divided into two groups according to their consumption of red meat (