Image1_Causal effect of serum 25-hydroxyvitamin D levels on low back pain: A two-sample mendelian randomization study.TIF

Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear.Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83–0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96–1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust.Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.</p

DataSheet1_Causal effect of serum 25-hydroxyvitamin D levels on low back pain: A two-sample mendelian randomization study.docx

Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear.Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83–0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96–1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust.Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.</p

Image2_Causal effect of serum 25-hydroxyvitamin D levels on low back pain: A two-sample mendelian randomization study.TIF

Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear.Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83–0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96–1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust.Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.</p

Facile Fabrication and Enhanced Photocatalytic Performance of Ag/AgCl/rGO Heterostructure Photocatalyst

Graphene/reduced graphene oxide (rGO) modification has been demonstrated to be an efficient route to improve the photocatalytic performance of various photocatalysts by promoting the effective separation of photogenerated electrons and holes. It is highly required to develop facile and environmental-friendly methods for the preparation of graphene-based photocatalytic materials. In this study, the Ag/AgCl/rGO heterostructure photocatalyst was fabricated by a mild oxidization reaction of hydrothermally prepared Ag/rGO in FeCl₃ solution. It was found that the reduction of graphene oxide (GO) was accompanied with the in situ formation of metallic Ag in a Ag­[(NH₃)₂]⁺-immobilized GO solution during hydrothermal treatment, while the following in situ oxidation of metallic Ag by FeCl₃ solution resulted in the formation of strongly coupled Ag/AgCl/rGO heterostructure photocatalyst. The photocatalytic experimental results indicated that all the resultant Ag/AgCl/rGO nanocomposite photocatalysts exhibited a much higher photocatalytic activity than the Ag/AgCl and physically mixed Ag/AgCl/rGO composite, and the Ag/AgCl/rGO (3.2 wt % rGO) showed the highest photocatalytic performance. The enhanced photocatalytic performance of Ag/AgCl/rGO heterostructures can be attributed to the cooperation effect of the effective separation of photogenerated carriers via strongly coupled rGO cocatalyst and the enrichment of organic molecules on the rGO nanosheets. Considering the facile preparation and its high photocatalytic activity, it is possible for the present Ag/AgCl/rGO nanocomposites to be widely applied in various fields such as air purification and wastewater treatment

Discovery of New SIRT2 Inhibitors by Utilizing a Consensus Docking/Scoring Strategy and Structure–Activity Relationship Analysis

SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitors has attracted much attention recently. In this investigation, we adopted a consensus docking/scoring strategy to screen for novel SIRT2 inhibitors. Structural optimization and structure–activity relationship (SAR) analysis were then carried out on highly potent compounds with new scaffolds, which led to the discovery of 2-((5-benzyl-5<i>H</i>-[1,2,4]­triazino­[5,6-<i>b</i>]­indol-3-yl)­thio)-<i>N</i>-(naphthalen-1-yl)­acetamide (<b>SR86</b>). This compound showed good activity against SIRT2 with an IC₅₀ value of 1.3 μM. <b>SR86</b> did not exhibit activity against SIRT1 and SIRT3, implying a good selectivity for SIRT2. In in vitro cellular assays, <b>SR86</b> displayed very good antiviability activity against breast cancer cell line MCF-7. In Western blot assays, <b>SR86</b> showed considerable activity in blocking the deacetylation of α-tubulin, which is a typical substrate of SIRT2. Collectively, because of the new scaffold structure and good selectivity of <b>SR86</b>, it could serve as a promising lead compound, hence deserving further studies