Male infertility has been increasing over the last decades and being a pressing health problem nowadays. Cistanche tubulosa (CT) is a traditional Chinese medicine used to boost male sexual function. ...Echinacoside (ECH) is one of the major compounds exist in CT and might be a potential agent to protect testis and sperm injury.
To investigate the mechanisms behind the possible protective effects of CT and ECH against testicular and sperm toxicity.
CT was identified by 5.8s gene sequencing. The major compositions (echinacoside and acteoside) of CT were quantified by HPLC method. The adult male Sprague-Dawley rats were exposed to BPA, CT or ECH for 42 consecutive days. The sperm parameters were observed by dark-field microscope; serum hormone levels (FSH, LH and testosterone) were tested by radio immunosorbent; LDH-x activity were evaluated using commercial kits; the expressions of the key steroidogenic enzymes were evaluated by qRT-PCR, heat map, immunofluorescence and western blot.
The CT and ECH treatments against BPA-induced testicular and sperm toxicity showed that CT and ECH have reversed BPA-induced abnormality in sperm characteristics, testicular structure and normalized serum testosterone. This was concomitant with the increased expression of LDH-x as well as the key steroidogenic enzymes including StAR, CYP11A1, 3β-HSD, 17β-HSD and CYP17A1, suggesting that CT and ECH enhanced testosterone biosynthesis.
CT and ECH attenuated poor sperm quality and testicular toxicity in rats through up-regulation steroidogenesis enzymes and ECH is the active compound of CT as a potential natural reproductive agent.
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Soil salinity is one of the main problems that affects global crop yield. Researchers have attempted to alleviate the effects of salt stress on plant growth using a variety of approaches, including ...genetic modification of salt-tolerant plants, screening the higher salt-tolerant genotypes, and the inoculation of beneficial plant microbiome, such as plant growth-promoting bacteria (PGPB). PGPB mainly exists in the rhizosphere soil, plant tissues and on the surfaces of leaves or stems, and can promote plant growth and increase plant tolerance to abiotic stress. Many halophytes recruit salt-resistant microorganisms, and therefore endophytic bacteria isolated from halophytes can help enhance plant stress responses. Beneficial plant-microbe interactions are widespread in nature, and microbial communities provide an opportunity to understand these beneficial interactions. In this study, we provide a brief overview of the current state of plant microbiomes and give particular emphasis on its influence factors and discuss various mechanisms used by PGPB in alleviating salt stress for plants. Then, we also describe the relationship between bacterial Type VI secretion system and plant growth promotion.
Background. In Japan, “Shinrin-yoku” or forest bathing (spending time in forests) is a major practice used for relaxation. However, its effects on promoting human mental health are still under ...consideration. The objective of this study was to investigate the physiological and psychological relaxation effects of forest walking on adults. Sixty participants (50% males; 50% females) were trained to walk 15-minute predetermined courses in a bamboo forest and a city area (control). The length of the courses was the same to allow comparison of the effects of both environments. Blood pressure and EEG results were measured to assess the physiological responses and the semantic differential method (SDM) and STAI were used to study the psychological responses. Blood pressure was significantly decreased and variation in brain activity was observed in both environments. The results of the two questionnaires indicated that walking in the bamboo forest improves mood and reduces anxiety. Moreover, the mean meditation and attention scores were significantly increased after walking in a bamboo forest. The results of the physiological and psychological measurements indicate the relaxing effects of walking in a bamboo forest on adults.
Bisphenol A (BPA) is an endocrine disruptor, that can cause immune dysfunction. Cineole (CIN) has that effect of regulating immune function and resist oxidation. Neutrophil extracellular traps (NETs) ...are one of the ways to resist pathogen invasion. In order to explore the effects of BPA and CIN on the release of chicken NETs and the antagonistic effect of CIN, take chicken peripheral blood neutrophils as object of study, grouping as NC, CIN, BPA + CIN and BPA. SEM, flow cytometry, RT-PCR, Western-blot and other methods were used to detect related indicators. The results showed that BPA inhibited the activities of GPX, SOD and CAT, increased the contents of MDA and NO, increased the activity of iNOS. BPA exposure inhibited the expression of myeloperoxidase (MPO), neutrophil elastase (NE) and histone, and inhibited the release of NETs. BPA activated downstream apoptosis and necroptosis through the p38 mitogen-activated protein kinase (p38-MAPK) pathway, which increased the expression of cytochrome C (CytC), bcl-2 associated K protein gene (bak), cysteinyl aspartate specific proteinase 3 (caspase-3), cysteinyl aspartate specific proteinase 9 (caspase-9), receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 1 (RIPK3) and mixed lineage kinase domain-like protein (MLKL), decreased the expression of B-cell lymphoma-2 (bcl-2). However, the co-exposure of CIN and BPA partially recovered the release of NETs, alleviated BPA-induced oxidative stress, and inhibited the activation of p38-MAPK pathway, necroptosis, and mitochondrial apoptosis pathway. These results indicated that CIN modulated p38 pathway alleviated BPA-induced neutrophil necroptosis and apoptosis, and increased NETs formation.
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•BPA inhibited the release of NETs by inducing necroptosis and apoptosis.•CIN can alleviate the oxidative stress and programmed cell death induced by BPA.•CIN via p38 pathway alleviates BPA-induced neutrophil injury.•Enriched the research on toxicology of BPA and detoxification mechanism of CIN.
Abstract
Acetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin ...acetyltransferase from
Astragalus membranaceus
. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3′/C4′-
O
-acetyltransferse of astragaloside IV (
1
). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/
1
and AmAT7-3
A310G
/
1
are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3′-
O
and C4′-
O
acetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.
The emergence of bacterial resistance poses a serious threat to public health. One of the most important resistance mechanisms against β-lactam antibiotics is the production of metallo-β-lactamases ...(MBLs). In this study, α-lipoic acid (LA) and methimazole (MMI), which have been used in clinical practice as non-antibacterial drugs and as a supplement, were chosen to explore their potential to be metallo-β-lactamases inhibitors (MBLIs). Enzyme inhibition assays showed that LA and MMI had moderate inhibitory activity against NDM-1 but no activity against VIM-2 and IMP-7. Antibacterial assays to determine synergy, demonstrated that the combination of LA or MMI with meropenem (MER) reduced the MIC value of MER against NDM-1 producing E. coli 16 times and 4 times, respectively, lower than that of MER alone. The fractional inhibitory concentration index (FICI) values were calculated to be less than 0.5, indicating that both LA and MMI had synergistic antibacterial effects with MER against all three MBLs expressing E. coli strains. The time-kill studies also suggested that LA and MMI were effective in restoring the antibacterial effect of MER. These findings revealed that LA and MMI are potential carbapenem enhancers, and provide a starting point for the development of potent MBLIs.
The human-pathogenic Enterobacter species are widely distributed in diverse environmental conditions, however, the understanding of the virulence factors and genetic variations within the genus is ...very limited. In this study, we performed comparative genomics analysis of 49 strains originated from diverse niches and belonged to eight Enterobacter species, in order to further understand the mechanism of adaption to the environment in Enterobacter. The results showed that they had an open pan-genome and high genomic diversity which allowed adaptation to distinctive ecological niches. We found the number of secretion systems was the highest among various virulence factors in these Enterobacter strains. Three types of T6SS gene clusters including T6SS-A, T6SS-B and T6SS-C were detected in most Enterobacter strains. T6SS-A and T6SS-B shared 13 specific core genes, but they had different gene structures, suggesting they probably have different biological functions. Notably, T6SS-C was restricted to E. cancerogenus. We detected a T6SS gene cluster, highly similar to T6SS-C (91.2%), in the remote related Citrobacter rodenitum, suggesting that this unique gene cluster was probably acquired by horizontal gene transfer. The genomes of Enterobacter strains possess high genetic diversity, limited number of conserved core genes, and multiple copies of T6SS gene clusters with differentiated structures, suggesting that the origins of T6SS were not by duplication instead by independent acquisition. These findings provide valuable information for better understanding of the functional features of Enterobacter species and their evolutionary relationships.
Acetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the ...antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-induced hepatotoxicity, as well as the putative mechanisms involved. Mice were treated with 4-HPA (6, 12, or 25 mg/kg) for 3 days, 1 h after the last administration of 4-HPA, a single dose of APAP was intraperitoneally infused for mice. APAP caused a remarkable increase of oxidative stress markers, peroxynitrite formation, and fewer activated phase II enzymes. 4-HPA increased Nrf2 translocation to the nucleus and enhanced the activity of phase II and antioxidant enzymes, and could thereby ameliorate APAP-induced liver injury. Studies reveal that 4-HPA, as an active area of bioactive dietary constituents, could protect the liver against APAP-induced injury, implying that 4-HPA could be a new promising strategy and natural hepatoprotective drug.
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•The SARS-CoV-2 main protease is the target to combat COVID-19.•Ebsulfur and Ebselen strongly inhibited the main protease(IC50 = 0.074-0.91 μM).•The Ebsulfur tightly and irreversibly ...bound the main protease by forming an SS bond.
The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (Mpro) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 Mpro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC50) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074–0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against Mpro, followed by Ebselen 1i (IC50 = 0.074 μM) and Ebsulfur 2k (IC50 = 0.11 μM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to Mpro, while molecular docking suggested that 2k formed an SS bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of Mpro to combat COVID-19.
Translanguaging as pedagogical practice and a theory of language has gained increasing importance in recent years. However, little research has reported Chinese English-as-a-foreign-language ...students’ perceptions of translanguaging; neither has research examined the predictive effects of the factors contributing to the amount of student translanguaging in the Chinese English-as-a-foreign-language classrooms. This study intended to fill the gap by inviting 292 Chinese English-as-a-foreign-language students to respond to a questionnaire that explores students’ perception of translanguaging. Two research questions were addressed: first, how do students’ attitudes to translanguaging vary across second-language proficiency? Second, how is the amount of student translanguaging predicted by students’ attitudes to translanguaging and the amount of teacher translanguaging? The results of a one-way analysis of variance revealed a statistically significant difference among the four groups in attitudes to teacher translanguaging and students’ translanguaging. A post hoc test found that non-English major first-year university students had a significantly higher level of acceptance of teachers’ and students’ translanguaging than English major first-year university students. Multiple regression analysis showed that the amount of teacher translanguaging and student attitudes to translanguaging explained a significant quantity of the variance in the amount of student translanguaging. The implications of the study were also discussed.
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