Comprehensive evaluation of heat resistance in 68 Vitis germplasm resources

Temperature is a crucial factor limiting plant growth. Grapevine is frequently subjected to high temperature during its maturation stage, and this seriously influences grape growth and development. Here, we selected 68 grapevine varieties and examined the heat damage index, relative electrolyte leakage, and Fv/Fm after exposure to 50 °C. 'Red Seedless', 'Hong Yuli', 'At Suma', 'Hupei 3#', and 'Tamina' were tolerant to high-temperature stress; however, 'Brazil', 'Shenfeng', 'Gold Finger', 'Heimeixiang', 'Kaiji', and 'Zuijinxiang' varieties were sensitive to high-temperature stress and died after exposure to 50 °C. Our findings provide a valuable insight into resistance breeding programs for grapevine

Protective effect of Alhagi sparsifolia against acetaminophen-induced liver injury in mice

Purpose: To investigate the hepatoprotective effects of Alhagi sparsifolia extract against acetaminophen (APAP)-induced liver injury in mice.Methods: Three doses of Alhagi sparsifolia (600, 300 and 150 mg/kg) were were administered to separate groups of mice orally once a day for three days. One-hour after the last dose, APAP (300 mg/kg) was intraperitoneally injected. Liver tissue was taken and tested for levels of serum aspartate aminotransferase (AST) and alanine transaminase (ALT) as biomarkers of liver injury; malonaldehyde (MDA); hydrogen peroxide (H2O2); glutathione (GSH) as an indicator of liver redox; and antioxidant enzyme activity using super oxide dismutase (SOD) assay. Additionally, western blotting was used to measure the expression of protein cytochrome P450 2E1 (CYP2E1) as the key enzyme of APAP metabolism.Results: Blood serum of ALT and AST and levels of CYP2E1 were markedly reduced, while the levels of MDA, H2O2, and SOD were elevated in a dose-dependent manner in mice treated with Alhagi sparsifolia compared to control group treated with APAP alone.Conclusion: The results demonstrate that Alhagi sparsifolia protects mice liver tissue against APAPinduced hepatic injury partly via decreased oxidative stress and inhibition of CYP2E1 expression.Keywords: Alhagi sparsifolia, Polysaccharide, Acetaminophen, CYP2E1, Antioxidan

Hepatoprotective effect of Alhagi sparsifolia against Alcoholic Liver injury in mice

Overconsumption of alcohol leads to alcoholic liver disease (ALD). Natural compounds have been investigated previously for their hepatoprotective activities against liver injury. This study investigated the protective effect of Alhagi sparsifolia on ALD. Alcohol was administered to mice for three consecutive days; either alone or in combination with Alhagi sparsifolia extract (150, 300, 600 mg/kg). Serum aspartate aminotransferase and alanine transaminase as biomarkers of liver injury, the content of malonaldehyde, hydrogen peroxide (H2O2) and glutathione which indicated the redox status of liver and the antioxidant enzyme activity of super oxide dismutase were detected, respectively. Moreover, the expression of protein cytochrome P450 2E1 (CYP2E1) the key enzyme of alcohol metabolism, and also tested by western blot experiment. Subsequently, the mRNA levels of inflammatory factors including TNF- α and TLR4 was determined real-time PCR. Results showed that Alhagi sparsifolia significantly alleviated alcohol-induced liver injury by reducing serum ALT and AST, inhibiting MDA and H2O2 content, increasing SOD, and GSH level in the liver (P< 0.05). In addition, the Alhagi sparsifolia treatment inhibited the expression of CYP2E1 (P< 0.05). The results suggest that Alhagi sparsifolia could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury

Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

Purification and Characterization of Bioactive Compounds from Styela clava

The immunomodulatory activity of extract from Styela clava was studied systematically based on activity tracking in vitro in order to find out novel-structured secondary metabolite. The proliferation rates of mouse splenic lymphocytes and peritoneal macrophages were used as screening index, as well as NO release promoting activities. The crude extract (CE) and its different polar fractions from S. clava all exhibited proliferative activity of splenolymphocytes and mouse macrophages, as well as NO release promoting activities, among which petroleum ether fraction (PE) showed the strongest effect. The antioxidant experiment in vitro showed that CE demonstrated antioxidant ability in 1,1-diphenyl-2-picrylhydrazyl (DPPH) system and the beta carotene-linoleic acid system; the activity of ethyl acetate fraction (ET) was much stronger than that of the others. Further isolated by silica gel column chromatography, ET was classified into seven sub-components (E1∼E7) listed in the order of activity as E5 > E6 > E4 > E3 > E7 > E2 > E1. Five compounds were separated as (1) cholesteric-7-en-3 -ol, (2) cholesteric-4-en-3 ,6 -diol, (3) cholesterol, (4) batilol, and (5) ceramide, among which (1), (2), and (4) were isolated for the first time from S. clava

Factors that affect the growth and photosynthesis of the filamentous green algae, Chaetomorpha valida, in static sea cucumber aquaculture ponds with high salinity and high pH

Chaetomorpha valida, dominant filamentous green algae, can be harmful to sea cucumber growth in aquaculture ponds of China. In order to understand the environmental factors affecting the growth of C. valida in sea cucumber aquaculture ecosystems, a combination of field investigations and laboratory experiments were conducted. Field surveys over one year revealed that C. valida survived in sea cucumber aquaculture ponds in salinities ranging from 24.3 ± 0.01‰ to 32.0 ± 0.02‰ and a pH range of 7.5 ± 0.02–8.6 ± 0.04. The high salinity and pH during the period of low C. valida biomass from January to May lay the foundation for its rapid growth in the following months of June to October. Many factors interact in the field environment, thus, laboratory experiments were conducted to determine the isolated effects of pH and salinity on C. valida growth. In laboratory experiments, samples were incubated under different salinity and pH conditions at 25 °C, with a light intensity of 108 μmol photon·m−2·s−1, and a photoperiod of 12 L:12 D. Results showed that salinity and pH significantly affect the growth and Fv/Fm (quantum yield of photosynthesis) of C. valida (p < 0.01). C. valida grew the longest at a salinity of 34‰ and a pH of 8.0. At 34‰ salinity, C. valida grew to 26.44 ± 5.89 cm in 16 days. At a pH of 8.0, C. valida grew to 67.96 ± 4.45 cm in 32 days. Fv/Fm was 0.635 ± 0.002 at a salinity of 32‰, and 0.550 ± 0.006 to 0.660± 0.001 at pH 7.0 to 8.5. Based on these results, we conclude that C. valida can bloom in sea cucumber ponds due to the high salinity and pH of coastal sea waters, which promote growth and maintain the photosynthetic activity of C. valida

Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer

Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention

Transcriptome Analysis of H2O2-Treated Wheat Seedlings Reveals a H2O2-Responsive Fatty Acid Desaturase Gene Participating in Powdery Mildew Resistance

Hydrogen peroxide (H2O2) plays important roles in plant biotic and abiotic stress responses. However, the effect of H2O2 stress on the bread wheat transcriptome is still lacking. To investigate the cellular and metabolic responses triggered by H2O2, we performed an mRNA tag analysis of wheat seedlings under 10 mM H2O2 treatment for 6 hour in one powdery mildew (PM) resistant (PmA) and two susceptible (Cha and Han) lines. In total, 6,156, 6,875 and 3,276 transcripts were found to be differentially expressed in PmA, Han and Cha respectively. Among them, 260 genes exhibited consistent expression patterns in all three wheat lines and may represent a subset of basal H2O2 responsive genes that were associated with cell defense, signal transduction, photosynthesis, carbohydrate metabolism, lipid metabolism, redox homeostasis, and transport. Among genes specific to PmA, ‘transport’ activity was significantly enriched in Gene Ontology analysis. MapMan classification showed that, while both up- and down- regulations were observed for auxin, abscisic acid, and brassinolides signaling genes, the jasmonic acid and ethylene signaling pathway genes were all up-regulated, suggesting H2O2-enhanced JA/Et functions in PmA. To further study whether any of these genes were involved in wheat PM response, 19 H2O2-responsive putative defense related genes were assayed in wheat seedlings infected with Blumeria graminis f. sp. tritici (Bgt). Eight of these genes were found to be co-regulated by H2O2 and Bgt, among which a fatty acid desaturase gene TaFAD was then confirmed by virus induced gene silencing (VIGS) to be required for the PM resistance. Together, our data presents the first global picture of the wheat transcriptome under H2O2 stress and uncovers potential links between H2O2 and Bgt responses, hence providing important candidate genes for the PM resistance in wheat

Legionella pneumophila Secretes a Mitochondrial Carrier Protein during Infection

The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionella nucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets