MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling

Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3's transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.</p

Comparison of two simplified approaches for ground temperature estimations in Australia

Developing an accurate and practical method for ground temperature estimations are critical for the ground source heat pump system design and energy calculation procedures. In Australia, Baggs' method is a common procedure for ground temperatures predictions as a function of depth and time of year. Xing and Spitler developed a new procedure for ground temperature estimations for engineering applications at 4112 sites worldwide. This new procedure considers the variations of surface cover conditions (bare soil, vegetated, asphalt or concrete), effects of snow cover and soil freezing or melting. These important factors, which significantly affect the ground temperature results accuracy either are neglected or are simplified in Baggs' method. In this paper, we selected 6 sites in Australia which belongs to two climates: warm climates and arid or dry summer climates. Xing and Spitler's method and Baggs' method are used respectively to calculate the ground temperatures at depths of 10cm, 20cm, 50cm and 100cm. Calculation results of two methods are both compared to the 3-14 years of measurement results at the 6 sites and validation results are discussed and investigated. Results demonstrate the Xing and Spitler's method averaged root mean square error (RMSE) is 2.2°C of the 6 sites; Baggs' method averaged RMSE is 3.4°C of the 6 sites. This paper presents a new and improved procedure for ground temperature estimations in Australia. It enables a more accurate design of the ground heat exchangers so as to reduce the capital cost of the installed ground source heat pump systems

Adopting a Theophylline-Responsive Riboswitch for Flexible Regulation and Understanding of Glycogen Metabolism in Synechococcus elongatus PCC7942

Cyanobacteria are supposed to be promising photosynthetic microbial platforms that recycle carbon dioxide driven into biomass and bioproducts by solar energy. Glycogen synthesis serves as an essential natural carbon sink mechanism, storing a large portion of energy and organic carbon source of photosynthesis. Engineering glycogen metabolism to harness and rewire carbon flow is an important strategy to optimize efficacy of cyanobacteria platforms. ADP-glucose pyrophosphorylase (GlgC) catalyzes the rate-limiting step for glycogen synthesis. However, knockout of glgC fails to promote cell growth or photosynthetic production in cyanobacteria, on the contrary, glgC deficiency impairs cellular fitness and robustness. In this work, we adopted a theophylline-responsive riboswitch to engineer and control glgC expression in Synechococcus elongatus PCC7942 and achieved flexible regulation of intracellular GlgC abundance and glycogen storage. With this approach, glycogen synthesis and glycogen contents in PCC7942 cells could be regulated in a range from about 40 to 300% of wild type levels. In addition, the results supported a positive role of glycogen metabolism in cyanobacteria cellular robustness. When glycogen storage was reduced, cellular physiology and growth under standard conditions was not impaired, while cellular tolerance toward environmental stresses was weakened. While when glycogen synthesis was enhanced, cells of PCC7942 displayed optimized cellular robustness. Our findings emphasize the significance of glycogen metabolism for cyanobacterial physiology and the importance of flexible approaches for engineering and understanding cellular physiology and metabolism

Slr1670 from Synechocystis sp. PCC 6803 Is Required for the Re-assimilation of the Osmolyte Glucosylglycerol

When subjected to mild salt stress, the cyanobacterium Synechocystis sp. PCC 6803 produces small amounts of glycerol through an as of yet unidentified pathway. Here, we show that this glycerol is a degradation product of the main osmolyte of this organism, glucosylglycerol (GG). Inactivation of ggpS, encoding the first step of GG-synthesis, abolished de novo synthesis of glycerol, while the ability to hydrolyze exogenously supplied glucoslylglycerol was unimpaired. Inactivation of glpK, encoding glycerol kinase, had no effect on glycerol synthesis. Inactivation of slr1670, encoding a GHL5-type putative glycoside hydrolase, abolished de novo synthesis of glycerol, as well as hydrolysis of GG, and led to increased intracellular concentrations of this osmolyte. Slr1670 therefore presumably displays GG hydrolase activity. A gene homologous to the one encoded by slr1670 occurs in a wide range of cyanobacteria, proteobacteria, and archaea. In cyanobacteria, it co-occurs with genes involved in GG-synthesis

Drug-coated balloons: A better revascularization strategy in patients with multivessel coronary artery disease undergoing one-stop hybrid coronary revascularization surgery

Background: The optimal revascularization strategy for non-left anterior descending coronary artery (LAD) lesions during one-stop hybrid coronary revascularization (HCR) surgery lacks current evidence.Aims: This study aimed to compare the outcomes of the drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in patients with non-small non-LAD lesions undergoing one-stop HCR.Methods: A total of 141 consecutive patients with multivessel coronary artery disease (MVCAD) undergoing one-stop HCR between June 1, 2018 and March 1, 2022 were retrospectively included in this study. In-hospital outcomes and mid-term major adverse cardiovascular and cerebrovascular events (MACCE) were observed. Kaplan-Meier curve analysis was used to evaluate the MACCE-free survival rate. The Cox proportional hazard model was used to identify risk factors of mid-term MACCE.Results: Thirty-eight and 103 patients received only DCB or DES therapy, respectively, in this study. There were no significant differences in demographic characteristics and laboratory parameters between the two groups. The in-hospital MACCE rate in the DES group was numerically higher than that in the DCB group (9.7% vs. 5.3%, respectively), but the difference was not statistically significant (P = 0.4). The incidence of MACCE after patients’ discharge was significantly higher in the DES group (22% vs. 5.3%, respectively, P = 0.02) during a median follow-up of 20 months. After multivariable Cox proportional hazard analysis, DCB therapy was independently associated with reduced risk of mid-term MACCE (hazard ratio, 0.21; 95% confidence interval, 0.06–0.91; P = 0.04).Conclusion: For patients with MVCAD undergoing one-stop HCR, DCB therapy may be the optimal revascularization strategy for non-small non-LAD coronary artery lesions with a significantly lower rate of mid-term MACCE

Saffron for &quot;toning down&quot; COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence.

AIM: To assess the potential role of saffron in downregulating inflammation and cytokine storm during COVID-19. MAIN FINDINGS: Three main compounds of saffron, i.e., crocetin esters, picrocrocin, and safranal, present strong antioxidant and anti-inflammatory action for several disease states (e.g., Alzheimer&apos;s, cancer, and depression) but have also been studied in COVID-19. In particular, based on our comprehensive review of both in vitro and in silico studies, saffron&apos;s essential oils and other constituents appear to have both immunomodulatory and anti-asthmatic actions; these actions can be particularly helpful to treat patients with respiratory symptoms due to COVID-19. Moreover, crocin appears to reduce the COVID-19-related cytokine cascade and downregulate angiotensin-converting enzyme 2 (ACE2) gene expression. Last, in silico studies suggest that saffron&apos;s astragalin and crocin could have inhibitory actions on SARS-CoV-2 protease and spike protein, respectively. CONCLUSION: Saffron represents a promising substance for toning down cytokine storm during COVID-19, as well as a potential preventive treatment for COVID-19. However, appropriate randomized clinical trials, especially those using biomarkers as surrogates to assess inflammatory status, should be designed in order to assess the clinical efficacy of saffron and allow its use as an adjunct treatment modality, particularly in resource-poor settings where access to drugs may be limited

Quality of systematic reviews with meta-analyses of resveratrol:A methodological systematic review

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013–2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were “positive.” As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 (“Structured summary”), 5 (“Protocol and registration”), 8 (“Search”), 9 (“Study selection”), 10 (“Data collection process”), 12 (“Risk of bias in individual studies”), and 24 (“Summary of evidence”) based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p &gt; 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.</p

Causal relationship of milk and coffee intake with nonalcoholic fatty liver disease:a two-sample Mendelian randomization study

Objective To investigate whether there is a causal relationship between the intake of milk or coffee and the risk of non-alcoholic fatty liver disease (NAFLD). Methods Using a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or coffee intake were used as instrumental variables, and genome-wide association study data on NAFLD were used as the outcome event. Inverse-variance weighted (IVW) and MR-Egger methods were employed to investigate the causal effect of milk or coffee intake on the risk of NAFLD. Results Both analyses indicated no causal association between milk or coffee intake and the risk of NAFLD (P&gt;0.05). Sensitivity analysis indicated the robustness of the main findings, with no outliers, heterogeneity, horizontal pleiotropy, or significant influence of individual SNPs. Conclusion This study does not support a causal relationship between the intake of milk or coffee and the risk of NAFLD.</p

Causal relationship of milk and coffee intake with nonalcoholic fatty liver disease:a two-sample Mendelian randomization study

Objective To investigate whether there is a causal relationship between the intake of milk or coffee and the risk of non-alcoholic fatty liver disease (NAFLD). Methods Using a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or coffee intake were used as instrumental variables, and genome-wide association study data on NAFLD were used as the outcome event. Inverse-variance weighted (IVW) and MR-Egger methods were employed to investigate the causal effect of milk or coffee intake on the risk of NAFLD. Results Both analyses indicated no causal association between milk or coffee intake and the risk of NAFLD (P&gt;0.05). Sensitivity analysis indicated the robustness of the main findings, with no outliers, heterogeneity, horizontal pleiotropy, or significant influence of individual SNPs. Conclusion This study does not support a causal relationship between the intake of milk or coffee and the risk of NAFLD.</p