Farnesoid X Receptor (FXR) Aggravates Amyloid-β-Triggered Apoptosis by Modulating the cAMP-Response Element-Binding Protein (CREB)/Brain-Derived Neurotrophic Factor (BDNF) Pathway In Vitro

BACKGROUND: Alzheimer’s disease (AD), which results in cognitive deficits, usually occurs in older people and is mainly caused by amyloid beta (Aß) deposits and neurofibrillary tangles. The bile acid receptor, farnesoid X receptor (FXR), has been extensively studied in cardiovascular diseases and digestive diseases. However, the role of FXR in AD is not yet understood. The purpose of the present study was to investigate the mechanism of FXR function in AD. MATERIAL AND METHODS: Lentivirus infection, flow cytometry, real-time PCR, and western blotting were used to detect the gain or loss of FXR in cell apoptosis induced by Aß. Co-immunoprecipitation was used to analyze the molecular partners involved in Aß-induced apoptosis. RESULTS: We found that the mRNA and protein expression of FXR was enhanced in Ab-triggered neuronal apoptosis in differentiated SH-SY5Y cells and in mouse hippocampal neurons. Overexpression of FXR aggravated Aß-triggered neuronal apoptosis in differentiated SH-SY5Y cells, and this effect was further increased by treatment with the FXR agonist 6ECDCA. Molecular mechanism analysis by co-immunoprecipitation and immunoblotting revealed that FXR interacted with the cAMP-response element-binding protein (CREB), leading to decreased CREB and brain-derived neurotrophic factor (BDNF) protein levels. Low expression of FXR mostly reversed the Aß-triggered neuronal apoptosis effect and prevented the reduction in CREB and BDNF. CONCLUSIONS: These data suggest that FXR regulates Aß-induced neuronal apoptosis, which may be dependent on the CREB/BDNF signaling pathway in vitro

Antibacterial characterization of Bacillus velezensis LG37 and mining of genes related to biosynthesis of antibacterial substances

Bacillus velezensis LG37 secretes various antibacterial substances and inhibits the growth of other bacteria. Here, we analyzed the antibacterial characteristics and the screening and verification of genes related to the synthesis of the antibacterial substance of LG37 by antibacterial activities experiment, Local BLAST+, and RT-PCR. LG37 was isolated from aquaculture water and preserved in our laboratory. The phylogenetic tree was used to analyze the genetic relationship between LG37 and the bacteriostatic test indicator strain. LG37 had a more substantial inhibitory effect on closely related strains, while the inhibitory effect on the more distantly related strains was weak. Combined with the results of genome sequencing, the ribosomal peptide (RP) bacteriocin gene and non-ribosomal peptide synthetase (NRPSs) related gene clusters were screened and analyzed. A total of six gene-coding RP bacteriocins and two genes coding surfactins and fengycin A NRPSs gene cluster were screened. Local BLAST+ analysis revealed a total of 11 NRPSs gene clusters. The active expression of the NRPSs and RP encoding genes was further validated by RT-PCR. The findings revealed various genes and gene clusters encoding RP bacteriocins and NRPSs in B. velezensis LG37. The bacterium is potentially valuable in diverse applications in aquaculture

Intestinal Cgi-58 Deficiency Reduces Postprandial Lipid Absorption

Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes

Research status and development trend of compressed air energy storage in abandoned coal mines

Compressed air energy storage (CAES) has the advantages of low construction cost, small equipment footprint, long storage cycle and environmental protection. Exploring the development of CAES technology in underground space is one of the innovative approaches to achieve China’s “dual-carbon” goal. Underground energy storage reservoirs can be classified into salt caverns, aquifers, depleted oil and gas fields, abandoned coal mines, and caverns. With the increasing number of abandoned coal mines in China, the direct closure of resource-depleted coal mines not only cause a significant waste of underground space resources, but also induce a series of safety, environmental and other issues. Therefore, utilizing the underground space of abandoned coal mines as CAES reservoirs holds great application prospects. The analysis shows that, ① There is a large amount of usable space in abandoned coal mines, and eight reuse modes of underground space in abandoned coal mines have been summarized: agricultural and forestry land, construction land, site greening, watershed utilization, water-heat combination, wetland park, mine park, and space reuse. ② The research on CAES in abandoned coal mines in China started late, the basic theoretical research is weak, the key technologies is immature, and geological conditions in coal mines are complex, the relevant applications of basic research is insufficient, and the commercialization, large-scale promotion and application have not yet been achieved. ③ Three key technologies are summarized and proposed to cope with the CAES in abandoned coal mines, i.e., the evaluation method of site selection for the construction of abandoned coal mine energy storage reservoirs, the key technology for the sealing of abandoned coal mine energy storage reservoirs, and the stability and safety evaluation of abandoned coal mine energy storage reservoirs. A flowchart for siting the construction of CAES reservoirs in abandoned coal mines has been established

Effects of Different Storage Temperatures and Methods for Fresh Tea Leaves on the Quality of Broken Black Tea

This study aimed to investigate the effect of different storage temperatures and methods for fresh tea leaves on the sensory quality, aroma components and biochemical components of broken black tea prepared from‘Yinghong 9’ tea leaves stored at 15, 25, 22–28 (room temperature) or 36–37 ℃ using sensory evaluation and headspace solid phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The results showed that storage of fresh tea leaves at 15 ℃ could enhance the fresh and brick taste, sweetness and sweet volatile compound contents of broken black tea, which was more favorable to the formation of the quality of broken black tea. However, storage at 36–37 ℃ of fresh tea leaves could significantly affect the sensory quality and quality components of broken black tea. These results provide a reference for fresh tea leaf management and the quality improvement of black broken tea

The Correlation between Chemical Composition, as Determined by UPLC-TOF-MS, and Acute Toxicity of Veratrum nigrum

The eighteen incompatible medicaments is an important theory in traditional Chinese medicine. The theory suggests that drugs in the eighteen incompatible medicaments can be toxic when used together. Veratrum nigrum L. and Radix paeoniae alba belong to the eighteen incompatible medicaments and have been prohibited for thousands of years. This study offers preliminary insight into the mechanism and chemical constituents responsible for the incompatibility and toxicity of these two agents. Specifically, we performed toxicology studies to identify and quantify the constituent substances of the two agents. Experiments revealed that acute toxicity increases when the dose of V. nigrum L. is higher than, or equal to, RPA. UPLC-TOF-MS analysis showed that, although the volumes of V. nigrum L. were the same, the content of some veratrum alkaloids changed significantly and had a trend toward a highly positive correlation r≥0.8 with toxicity. This suggests that the increased toxicity of the V. nigrum L. and RPA combination was due mainly to increased content of the special veratrum alkaloids. The cytotoxicity of veratridine in SH-SY5Y cells was decreased with increasing paeoniflorin concentrations. This study provides insight into the mechanism behind the incompatibility theory of TCM

Genomic diversity and evolution analysis of severe fever with thrombocytopenia syndrome in East Asia from 2010 to 2022

BackgroundConducting an up-to-date analysis on the genomic diversity and evolution patterns of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for elucidating the underlying mechanisms of its emergency and pathogenicity, as well as assessing the extent of its threat to public health.MethodsComplete genome sequences of SFTSV were obtained from GenBank until December 19, 2022. A thorough phylogenetic analysis was conducted using comprehensive bioinformatics methods to estimate the genomic diversity and evolution.ResultsThe phylogenetic classification of SFTSV strains yielded seven lineages (A-G) for each genome segment. SFTSV displayed notable variations in evolutionary patterns among different regions and segments, without a linear accumulation of nucleotide substitutions within segments and regions. The comprehensive analysis revealed 54 recombination events and 17 reassortment strains, including the first discovery of recombination events involving sea-crossing and species-crossing. Selection analysis identified three positive sites (2, 671, 1353) in RNA-dependent RNA polymerase, three positive sites (22, 298, 404) in glycoprotein, and two positive sites (9, 289) in nonstructural protein. No positive selection sites were found in nucleoprotein.ConclusionOur study unveiled the existence of multiple evolutionary forces influencing SFTSV, contributing to its increasing genetic diversity, which had the potential to modify its antigenicity and pathogenicity. Furthermore, our study highlights the importance of tracking the spread of SFTSV across regions and species

Halophilic archaea cultivated from surface sterilized middle-late eocene rock salt are polyploid

Peer reviewe

Tislelizumab with gemcitabine and oxaliplatin in patients with relapsed or refractory classic Hodgkin lymphoma: a multicenter phase II trial

Although classic Hodgkin lymphoma (cHL) is highly curable with current treatment paradigms, therapy fails in 10-25% of patients. This prospective multicenter phase II study attempted to investigate the efficacy and safety of the combination of tislelizumab with gemcitabine and oxaliplatin (T-GemOx) in relapsed or refractory cHL. Participants received six to eight courses of gemcitabine (1 g/m2 on day 1) and oxaliplatin (100 mg/m2 on day 1) combined with tislelizumab (200 mg on day 2) at 21-day intervals, followed by tislelizumab maintenance (every 2 months for 2 years). The main outcome measure was the best complete remission rate. As of August 2022, a total of 30 patients had been consecutively enrolled and given induction therapy. The best overall response rate and complete remission rate were 100% (95% confidence interval [CI]: 88.4-100%) and 96.7% (95% CI: 82.8-99.9%), respectively. The median duration of follow-up after initiation of T-GemOx was 15.8 months. The 12-month progression-free survival rate without autologous stem cell transplant was 96% (95% CI: 74.8-99.4%). There were 122 adverse events recorded, of which 93.4% were grade 1 or 2. Thrombocytopenia (10%) and anemia (6.7%) were the most common grade 3 or 4 adverse events. Overall, T-GemOx demonstrated promising antitumor activity with manageable toxicities as a salvage treatment for relapsed or refractory cHL. A longer follow-up duration is required to determine whether maintenance therapy with tislelizumab rather than transplantation can be curative following such a highly active regimen. This trial was registered with the Chinese Clinical Trials Registry (http://www.chictr.org.cn) on June 1, 2020, identifier ChiCTR2000033441