TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection.

The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps ∼ 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.

KIAA0101 promotes cisplatin resistance through regulating cell apoptosis in lung cancer cells.

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.

Efficacy and safety of moxibustion on cancer-related fatigue: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. METHODS: Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). RESULTS: In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = - 1.66, 95% CI = - 2.05, - 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. CONCLUSION: Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality.

Predictors of post-stroke depression: the perspective from the social convoy model.

BACKGROUND: Post-stroke depression (PSD) as one of the most common neuropsychiatric disorders after a stroke and is caused by many factors. However, the relationships among different factors and their potential contributions to PSD remain unclear. METHODS: Two hundred and seventy-six patients were recruited into this study. The general information questionnaire, the Patient Health Questionnaire-9, the Perceived Social Support Scale, the Family Assessment Device, the General Well-Being Scale, the Barthel Index, and the modified Rankin Scale were used to assess the condition of patients. Subsequently, we identify the main causes associated with the PSD and then performed a path analysis to clarify the direct, indirect and total effects among the variables. RESULTS: We found that age, stroke with coronary heart disease, neurological function, family function, social support, and general well-being had a significant impact on PSD (P < 0.05). Of these, neurological function had the largest total effect on PSD (ß = 0.451), social support contributed the most as a direct effect (ß = -0.306), and family function showed the largest indirect effect (ß = -0.264). CONCLUSION: Individual, disease, and social-psychological factors all contributed to the development of PSD. We should pay more attention to comprehensive assessment, especially for those with poor neurological function, and lacking family or social support. In addition, it would be preferable to provide them with necessary support and care strategies to reduce the incidence of PSD.

Xiaotansanjiefang inhibits the viability of colorectal cancer cells via Jagged 1/Notch 3/Snail signaling pathway.

The purpose of this study is to explore the anti-colorectal cancer of Xiaotansanjiefang, a famous traditional Chinese medicine, and its potential anti-cancer mechanism. In this study, the HCT116 cell spheres were prepared as in vitro study model. We found the Xiaotansanjiefang medication was able to inhibit the proliferation of HCT116 cell spheres in a dose-dependent manner, especially in 3 and 6 mg/ml Xiaotansanjiefang medication treated groups. We also found the high concentration of Xiaotansanjiefang medication could suppress the migration and promote the apoptosis of HCT116 cell spheres. Moreover, we found the expression of Jagged 1, Notch 3, Snail, and Hes 1 were decreased in HCT116 cell spheres treated with Xiaotansanjiefang medication. Furthermore, the proliferation and apoptosis behaviors of HCT116 cell spheres treated with Xiaotansanjiefang medication were reversed with the addition of Jagged 1 Fc chimera protein. The expression of Jagged 1, Notch 3, Snail, and Hes 1 were also increased again in HCT116 cells treated with Xiaotansanjiefang medication plus with Jagged 1 Fc chimera protein. The presented study may provide a promising strategy to treat and prevent colorectal cancer.

Effect of Scraping Therapy on Chronic Low Back Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The purpose of this study was to review the literature on the effect of scraping therapy on chronic low back pain (LBP) from randomized controlled trials (RCTs). METHODS: Three English medical electronic databases (PubMed, Embase, and the Cochrane Library) and 2 Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials related to the effects of scraping therapy on chronic LBP were included in this systematic review. Study selection, data extraction, and validation were conducted independently by 2 reviewers. The methodological quality of the studies was evaluated by the Cochrane risk-of-bias tool. RevMan 5.3 software was applied to perform meta-analysis of the data. RESULTS: Ten studies comprising 627 participants were included. Overall, the quality of evidence was moderate owing to a lack of blinding and allocation concealment in some studies and unclear risk of selective reporting. Meta-analysis of 9 RCTs indicated that scraping therapy had a statistically significant effect on pain reduction (standard mean difference = -0.66, 95% confidence interval [CI], -0.83 to -0.49, P < .001). However, if only a single scrape treatment was carried out, the results did not show that scraping was superior to the control group regarding pain relief (mean difference = -0.35, 95% CI, -1.23 to 0.53, P = .44). Moreover, the results of 6 RCTs involving 468 participants showed significantly greater improvement in lumbar dysfunction (mean difference = -10.05, 95% CI, -13.52 to -2.32, P < .001). In addition, the results of 5 RCTs involving 393 participants showed a favorably significant effect on the overall efficacy (odds ratio = 4.74, 95% CI, 2.34-9.62, P < .001). As for follow-up effects, meta-analysis of 3 RCTs involving 241 participants showed a promising effect on pain reduction and lumbar function improvement at 1 month and 3 months after the end of treatment, respectively. Only 1 study reported adverse effects, and none were serious. CONCLUSION: Scraping therapy may have a therapeutic effect for some individuals with chronic LBP. However, due to the limited amount of research and the low methodological quality of the included studies, additional large-scale, multicenter, high-quality RCTs on relieving pain intensity and improving lumbar dysfunction are still necessary.

Curcumin Alleviates Oxaliplatin-Induced Peripheral Neuropathic Pain through Inhibiting Oxidative Stress-Mediated Activation of NF-κB and Mitigating Inflammation.

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.

Coralloluteibacterium stylophorae gen. nov., sp. nov., a new member of the family Lysobacteraceae isolated from the reef-building coral Stylophora sp.

A bacterial strain, designated Sty a-1T, was isolated from a reef-building coral Stylophora sp., collected off coast of Southern Taiwan and characterized using the polyphasic taxonomy approach. Cells of strain Sty a-1T were Gram-staining-negative, aerobic, poly-ß-hydroxybutyrate accumulating, motile by means of flagella, non-spore forming, straight rod-shaped and colonies were yellow and circular. Growth occurred at 15-40 °C (optimum, 30-35 °C), at pH 6-10 (optimum, pH 6.5-8) and with 0-7% NaCl (optimum, 2-3%). The predominant fatty acids were iso-C15:0, iso-C17:1 ω9c, summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c) and iso-C17:0. The major isoprenoid quinone was Q-8 and the DNA G+C content was 68.5 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, an uncharacterized aminophospholipid and three uncharacterized lipids. The major polyamines were spermidine, putrescine and homospermidine. Phylogenetic analyses based on 16S rRNA and four housekeeping gene sequences (recA, atpD, rpoA and rpoB) showed that strain Sty a-1T forms a distinct lineage with respect to closely related genera in the family Lysobacteraceae, most closely related to Lysobacter, Silanimonas, Arenimonas and Luteimonas and the levels of 16S rRNA gene sequence similarity with respect to the type species of related genera are less than 95%. On the basis of the genotypic and phenotypic data, strain Sty a-1T represents a novel genus and species of the family Lysobacteraceae, for which the name Coralloluteibacterium stylophorae gen. nov., sp. nov. is proposed. The type strain is Sty a-1T (= BCRC 80968T = LMG 29479T = KCTC 52167T).

Litoribrevibacter euphylliae sp. nov., isolated from the torch coral Euphyllia glabrescens.

Strain Eup a-2T, isolated from the torch coral Euphyllia glabrescens, was characterized using a polyphasic taxonomy approach. Cells of strain Eup a-2T were Gram-negative, aerobic and motile by three polar flagella and formed translucent colonies. Optimal growth occurred at 25 °C, pH 6-8 and in the presence of 2-4 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Eup a-2T belonged to the genus Litoribrevibacter and showed the highest levels of sequence similarity with respect to Litoribrevibacter albus Y32T (97.8 %). Strain Eup a-2T contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the predominant fatty acids. The predominant isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphophatidylglycerol. Genomic DNA G+C content of strain Eup a-2T was 49.1 mol%. The DNA-DNA hybridization value for strain Eup a-2T with L. albus Y32T was less than 30 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain Eup a-2T should be classified as a novel species of the genus Litoribrevibacter, for which the name Litoribrevibactereuphylliae sp. nov. is presented. The type strain is Eup a-2T (=BCRC 81004T=LMG 29725T=KCTC 52438T).

Thalassotalea coralli sp. nov., isolated from the torch coral Euphyllia glabrescens.

Strain Eup a-8T, isolated from a torch coral Euphyllia glabrescens, was characterized using a polyphasic taxonomy approach. Cells of strain Eup a-8T were Gram-staining-negative, aerobic, motile by means of a single polar flagellum, poly-ß-hydroxybutyrate-containing, rod-shaped and formed white colonies. Optimal growth occurred at 25-30 °C, pH 7-8, and in the presence of 2 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Eup a-8T belonged to the genus Thalassotalea and showed the highest levels of sequence similarity with respect to Thalassotalea ganghwensis JC2041T (97.1 %). Strain Eup a-8T contained C17 : 1ω8c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C14 : 0 and iso-C16 : 0 as the predominant fatty acids. The only isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and one uncharacterized phospholipid. Genomic DNA G+C content of strain Eup a-8T was 41.5 mol%. The DNA-DNA hybridization value for strain Eup a-8T with Thalassotalea ganghwensis JC2041T was less than 70 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain Eup a-8T should be classified as a novel species of the genus Thalassotalea, for which the name Thalassotalea coralli sp. nov. is proposed. The type strain is Eup a-8T (=BCRC 80967T=LMG 29478T=KCTC 52169T).

Parvibium lacunae gen. nov., sp. nov., a new member of the family Alcaligenaceae isolated from a freshwater pond.

A bacterial strain designated KMB9T was isolated from a freshwater pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain KMB9T were Gram-stain-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, motile by means of a monopolar flagellum, non-spore-forming and rods surrounded by a thick capsule and forming white-coloured colonies. Growth occurred at 20-40 °C (optimum, 25-37 °C), at pH 6.5-7.5 (optimum, pH 7.0) and with 0-0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene and four housekeeping gene sequences (recA, rpoA, rpoB and atpD) showed that strain KMB9T forms a distinct phyletic line within the family Alcaligenaceae, and the levels of 16S rRNA gene sequence similarity to its closest relatives with validly published names were less than 93.3 %. The predominant fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C18 : 1ω7c. The major isoprenoid quinone was Q-8. The major polyamine was putrescine. The polar lipid profile revealed the presence of phosphatidylethanolamine, phosphatidylglycerol and several uncharacterized aminophospholipids, aminolipids, phospholipids and lipids. The genomic DNA G+C content of strain KMB9T was 54.5 mol%. On the basis of the genotypic and phenotypic data, strain KMB9T represents a novel species of a new genus in the family Alcaligenaceae, for which the name Parvibium lacunae gen. nov., sp. nov. is proposed. The type strain is KMB9T (=BCRC 81053T=LMG 30055T=KCTC 52814T).

Salsuginimonas clara gen. nov., sp. nov., a member of the family Pseudoalteromonadaceae isolated from a brackish river.

A bacterial strain designated LSN-49T was isolated from a brackish river in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain LSN-49T were Gram-staining-negative, aerobic, poly-ß-hydroxybutyrate accumulating, motile by means of a monopolar flagellum, non-spore forming, straight rods and formed shiny and translucent colonies. Growth occurred at 20-40 °C (optimum, 25-30 °C), at pH 6-10 (optimum, pH 7-8) and with 0-3 % (w/v) NaCl [optimum, 0-1 % (w/v)]. The predominant fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C17 : 1ω8c and C16 : 0. The polar lipid profile consisted of a mixture of phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine, (PC), two uncharacterized aminophospholipids (APL1 and APL2), one uncharacterized glycolipid (GL1), four uncharacterized phospholipids (PL1-PL4) and four uncharacterized lipids (L1-L4). The major polyamine was putrescine. The major isoprenoid quinone was Q-8 and the DNA G+C content was 51.0 mol%. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that LSN-49T formed a distinct lineage with respect to closely related genera in the family Pseudoalteromonadaceae. LSN-49T was most closely related to Pseudoalteromonas, Algicola and Psychrosphaera and showed 89.3-92.1 % sequence similarity with members of the family Pseudoalteromonadaceae with validly published names. On the basis of the genotypic and phenotypic data, LSN-49T represents a novel genus and species of the family Pseudoalteromonadaceae, for which the name Salsuginimonas clara gen. nov., sp. nov. is proposed. The type strain is LSN-49T (=BCRC 81005T=LMG 29726T=KCTC 52439T).

Formosimonas limnophila gen. nov., sp. nov., a new member of the family Burkholderiaceae isolated from a freshwater lake.

Strain AHQ-12T, isolated from a freshwater lake in Taiwan, was characterized using a polyphasic taxonomy approach. Cells of strain AHQ-12T were Gram-staining-negative, aerobic, non-motile, non-spore forming, straight rods and formed translucent white-coloured colonies. Optimal growth occurred at 20 °C, pH 6.0 and with 0 % NaCl. The predominant fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The major isoprenoid quinone was Q-8, and the DNA G+C content was 50.4 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized aminophospholipids and lipids. The major polyamine was cadaverine. 16S rRNA gene sequence analysis demonstrated that this isolate was unique, showing less than 91 % sequence similarity to its closest relatives, including members of the genera Ralstonia (89.7-90.8 %), Cupriavidus (88.8-90.3 %), Polynucleobacter (88.2-89.5 %), Burkholderia (86.6-90.3 %) and Pandoraea (89.2-90.1 %). Phylogenetic analyses demonstrated that strain AHQ-12T formed a distinct clade closely related to species of the family Burkholderiaceae. On the basis of the phylogenetic inference and phenotypic data, strain AHQ-12T should be classified as a novel species of a new genus in the family Burkholderiaceae, for which the name Formosimonas limnophila gen. nov., sp. nov. is proposed. The type strain is AHQ-12T (=BCRC 80690T=LMG 27847T=KCTC 32501T).

[Palmitoylation of heat shock protein 90 in mouse sperm].

Protein palmitoylation, one of post-translation modifications, refers to the addition of saturated 16-carbon palmitic acid to cysteine residues via the thioester bond. It plays key roles in various functional activities, such as the interaction, stability and location of proteins. Heat shock protein 90 (Hsp90), an important molecular chaperone, has been reported to be involved in sperm capacitation. However, it remains unclear whether protein palmitoylation exists in sperm and whether Hsp90 in sperm is palmitoylated under different physiological conditions. In this study, we examined whether the protein palmitoylation is present in mouse cauda epididymis sperm using acyl-biotin exchange method, predicted the potential palmitoylated sites of Hsp90 by the software CSS-Palm 4.0 and detected the palmitoylated Hsp90 in the mouse sperm from caput epididymis and cauda epididymis by immunoprecipitation. We found that some proteins, approximately 50, 65, 72, 85 and 130 kDa, were palmitoylated in mouse cauda epididymis sperm. Five sites in two Hsp90 isoforms were predicted to be palmitoylated. The results also showed that Hsp90 in mouse sperm was palmitoylated and its palmitoylation level was involved in different physiological conditions: the palmitoylation level of cauda epididymis sperm was higher than that of caput epididymis sperm; and the palmitoylation level after capacitation was much higher than that before capacitation. In conclusion, this study reveals that protein palmitoylation is present in mouse sperm and the palmitoylated Hsp90 is associated with different physiological conditions in sperm.

Peptide toxins and small-molecule blockers of BK channels.

Large conductance, Ca(2+)-activated potassium (BK) channels play important roles in the regulation of neuronal excitability and the control of smooth muscle contractions. BK channels can be activated by changes in both the membrane potential and intracellular Ca(2+) concentrations. Here, we provide an overview of the structural and pharmacological properties of BK channel blockers. First, the properties of different venom peptide toxins from scorpions and snakes are described, with a focus on their characteristic structural motifs, including their disulfide bond formation pattern, the binding interface between the toxin and BK channel, and the functional consequence of the blockage of BK channels by these toxins. Then, some representative non-peptide blockers of BK channels are also described, including their molecular formula and pharmacological effects on BK channels. The detailed categorization and descriptions of these BK channel blockers will provide mechanistic insights into the blockade of BK channels. The structures of peptide toxins and non-peptide compounds could provide templates for the design of new channel blockers, and facilitate the optimization of lead compounds for further therapeutic applications in neurological disorders or cardiovascular diseases.

The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA.

TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA.

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study.

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.

Causal relationships between gut microbrome and digestive system diseases: A two-sample Mendelian randomization study.

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.

Study on the Synergistic Suppression Effect and Mechanism of N2/Ultrafine Water Mist on Liquefied Petroleum Gas Explosion.

Liquefied petroleum gas (LPG) is widely used for its cleanliness and high efficiency in industry and city life. In order to improve the suppression effect on LPG explosion, a constant volume combustion bomb was used to investigate the synergistic influence of N2/ultrafine water mist on the explosion and combustion characteristics of 6% premixed LPG/air gas. The results showed that (1) the effect of a single ultrafine water mist on suppressing LPG explosion is unstable. When the concentration of ultrafine water mist is low, the flame acceleration in the initial stage of explosion is promoted, and when the ultrafine water mist with a mass fraction of 420 g/m3 is introduced, the maximum pressure rise rate increases. (2) The combination of N2/ultrafine water mist has a synergistic effect on LPG explosion. Compared to the individual suppression effects, the combination of N2/ultrafine water mist showed more effective suppression on the explosion pressure, flame propagation, and flame instability of LPG explosion. (3) Through the mechanism analysis, it is found that the combined action of N2/ ultrafine water mist can better reduce the mole fraction and ROP peak of active free radicals such as H, O, and OH by inhibiting the main reaction of generating H, O, and OH radicals during the explosion of LPG, resulting in the reduction of flame free radicals in the explosion system, thus effectively inhibiting the chain reaction of ignition and explosion of LPG. This research can provide guidance for a better understanding and implementation of gas-liquid two-phase suppression technology for LPG explosion.

Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.