Data_Sheet_1_Causal effect of early life adiposity on gestational diabetes mellitus and mediating roles of lipidomic biomarkers.docx

ObjectiveThe causal relationship between early life adiposity and gestational diabetes mellitus (GDM) and the underlying mechanisms remains unclear. This study aimed to investigate the independent causal association between early life adiposity and GDM and identify potential metabolic mediators and their mediating effects on this relationship.MethodsUsing genome-wide association study (GWAS) summary statistics from the publicly available database of early life adiposity (5,530 cases and 8,318 controls) and GDM (11,279 cases and 179,600 controls), a two-step, two-sample Mendelian randomization (MR) was conducted to estimate the causal mediation effects of lipidomic biomarkers including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, apolipoprotein A-Ι, and apolipoprotein B on the relationship between early life adiposity and GDM.ResultsGenetically predicted childhood adiposity was positively associated with risk of GDM (OR: 1.21, 95%CI: 1.09–1.34, p = 4.58 × 10−4). This causal relationship remained after accounting for adult adiposity traits in the multivariable MR analyses. Two-step MR identified three candidate mediators that partially mediated the effect of early life adiposity on GDM, including HDL-C (5.81, 95%CI: 3.05–8.57%), apolipoprotein A-Ι (4.16, 95%CI: 1.64–6.69%), and triglyceride (2.20, 95%CI: 0.48–3.92%).ConclusionThis MR study demonstrated that the causal effect of childhood obesity on future GDM risk was independent of adult adiposity. We identified three mediators, including HDL-C, apolipoprotein A-Ι, and triglyceride, in this association pathway. Our results provide insights into the pathogenesis of GDM and suggest additional prevention and treatment targets for GDM related to early life adiposity.</p

DNA-Grafted Polypeptide Molecular Bottlebrush Prepared via Ring-Opening Polymerization and Click Chemistry

A new type of DNA grafted polypeptide molecular brush was synthesized via a combination of ring-opening polymerization (ROP) and click chemistry. This conjugation method provides an easy and efficient approach to obtain a hybrid DNA-grafted polypeptide molecular bottlebrush. The structure and assembly behaviors of this hybrid brush were investigated using electrophoresis, UV–vis spectroscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM). Hierarchical supramolecular assemblies can be obtained through hybridization of two kinds of polypeptide-<i>g</i>-DNA molecular bottlebrushes containing complementary DNA side chains. We further demonstrated that such polypeptide-<i>g</i>-DNA can be hybridized with ds-DNA and DNA-grafted gold nanoparticles to form a supermolecular bottlebrush and hybrid bottlebrush, respectively. In addition, DNA-polypeptide hydrogel can be prepared by hybridization of polypeptide-<i>g</i>-DNA with a linker-ds-DNA, which contains the complementary “sticky ends” to serve as cross-linkers

Additional file 1 of Causal associations between leisure sedentary behaviors and sleep status with frailty: insight from Mendelian randomization study

Supplementary Material

Selective Hydrogenolysis of Dibenzofuran over Highly Efficient Pt/MgO Catalysts to <i>o</i>‑Phenylphenol

Direct selective hydrogenolysis of dibenzofuran (DBF) derived from coal and shale oil to a value-added chemical, <i>ortho</i>-phenylphenol (OPP), with high selectivity (80%) and yield (48%) has been achieved over Pt/MgO at 400 °C and 1.0 MPa by controlling the C–O bond cleavage as well as minimizing the extent of hydrogenation of aromatic rings. Meanwhile, Pt/SiO₂, Pt/Al₂O₃, and Pt/MgO/Al₂O₃ catalysts were used for the DBF hydrogenolysis and showed lower selectivity for OPP. The influence of reaction parameters has been studied to unveil the optimal reaction conditions. And the phenomenon of OPP dehydrogenation is found over various catalysts for the hydrogenation reaction of OPP. Extensive reactions and catalyst characterizations demonstrated that the OPP selectivity and the dehydrogenation of OPP to DBF follows the order of supports basicity: MgO-900 > MgO > SiO₂ > MgO/Al₂O₃ > Al₂O₃, which shows that the acid–base properties of supports impact the adsorption and desorption behaviors of DBF and OPP, and results in the disparity of OPP selectivity and the dehydrogenation of OPP. Finally, a plausible reaction pathway and mechanistic understanding are proposed

Role of Re and Ru in Re–Ru/C Bimetallic Catalysts for the Aqueous Hydrogenation of Succinic Acid

To obtain an effective supported metallic catalyst for aqueous hydrogenation of succinic acid (SA), C-supported Re–Ru catalysts with different Re/Ru ratios were sought by using a convenient and environmentally friendly microwave-assisted thermolytic method. The results indicate that the as-prepared Re–Ru/C catalysts exhibit high dispersion with fairly small average particle size (0.7–1.6 nm) and well-structural properties. During the transformation of SA, the Ru composition is responsible for the hydrogenolysis of SA, while the Re composition favors the hydrogenation of SA. The bimetallic Re–Ru interaction promotes the formation of 1,4-butanediol (selectivity is 70.1% with complete conversion), which could rarely be detected when using Re/C or Ru/C monometallic catalysts. The kinetic study further reveals that the introduction of Ru significantly reduces the apparent activation energy from 62 to 40 kJ mol^–1 and increases the saturation ability of hydrogenation intermediates on the surface of catalysts compared with Re/C. A Re–Ru/C bimetallic catalyst accelerates the formation rate of 1,4-butanediol relative to that of tetrahydrofuran. According to a kinetic mechanism, ring opening of γ-butyrolactone is favored at low temperature, while direct hydrogenation is favored at high temperature

Highly Stable Nb₂O₅–Al₂O₃ Composites Supported Pt Catalysts for Hydrodeoxygenation of Diphenyl Ether

Various TiO₂, SiO₂, Al₂O₃, and Nb₂O₅–Al₂O₃ supported Pt catalysts have been prepared by urea precipitation method for catalytic hydrodeoxygenation (HDO) of diphenyl ether (DPE) as a 4-O-5 aryl-ether lignin model compound. The selectivity toward deoxygenated product cyclohexane increased obviously with Nb₂O₅·<i>n</i>H₂O decorated, owing to the significant promotion effect of NbO_<i>x</i> species and acid sites on C–O bond cleavage. At higher pressure (3.0 MPa H₂), DPE underwent a HYD route, while direct hydrogenolysis route occurred at low pressure (0.1 MPa H₂). In addition, the reaction rate constants and activation energies were obtained in the temperature range from 160 to 220 °C. Based on the Arrhenius law, the activation energy for the cleavage of the C–O bond in DPE was calculated to be 91.22 kJ/mol. It was noteworthy that the Pt/20Nb–Al₂O₃ showed higher stability than Pt/Al₂O₃ for hydrodeoxygenation of diphenyl ether, which can be attributed to its water-tolerant Lewis acid sites

DataSheet1_SLC2A9 rs16890979 reduces uric acid absorption by kidney organoids.docx

Introduction: The excretion and absorption of uric acid (UA) by the kidneys helps regulate serum UA levels. GLUT9, encoded by SLC2A9, is mainly expressed in the renal tubules responsible for UA absorption. SLC2A9 polymorphisms are associated with different serum UA levels. However, the lack of proper in vitro models has stalled research on the mechanisms of single nucleotide polymorphisms (SNPs) that affect UA metabolism in human urate transporters.Methods: In this study, we constructed a gene-edited human embryonic stem cells-9 (ESC-H9) derived kidney organoid bearing rs16890979, an SLC2A9 missense mutation with undetermined associations with hyperuricemia or hypouricemia. Kidney organoids derived from ESC-H9 with genetical overexpression (OE) and low expression (shRNA) of SLC2A9 to serve as controls to study the function of SLC2A9. The function of rs16890979 on UA metabolism was evaluated after placing the organoids to urate-containing medium and following histopathological analysis.Results: The kidney organoids with heterozygous or homozygous rs16890979 mutations showed normal SLC2A9 expression levels and histological distribution, phenotypically similar to the wild-type controls. However, reduced absorption of UA by the kidney organoids with rs16890979 mutants was observed. This finding together with the observation that UA absorption is increased in organoids with SLC2A9 overexpression and decreased in those with SLC2A9 knockdown, suggest that GLUT9 is responsible for UA absorption, and the rs16890979 SNP may compromise this functionality. Moreover, epithelial-mesenchymal transition (EMT) was detected in organoids after UA treatment, especially in the kidney organoid carrying GLUT9OE, suggesting the cytobiological mechanism explaining the pathological features in hyperuricosuria-related renal injury.Discussion: This study showing the transitional value of kidney organoid modeling the function of SNPs on UA metabolism. With a defined genetic background and a confirmed UA absorption function should be useful for studies on renal histological, cellular, and molecular mechanisms with this organoid model.</p

Stereoselective Hydrolysis of Epoxides by re<i>Vr</i>EH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity

To provide more options for the stereoselective hydrolysis of epoxides, an epoxide hydrolase (<i>Vr</i>EH3) gene from Vigna radiata was cloned and expressed in Escherichia coli. Recombinant <i>Vr</i>EH3 displayed the maximum activity at pH 7.0 and 45 °C and high stability at pH 4.5–7.5 and 55 °C. Notably, re<i>Vr</i>EH3 exhibited high and complementary regioselectivity toward styrene oxides <b>1a</b>–<b>3a</b> and high enantioselectivity (<i>E</i> = 48.7) toward <i>o</i>-cresyl glycidyl ether <b>9a</b>. To elucidate these interesting phenomena, the interactions of the three-dimensional structure between <i>Vr</i>EH3 and enantiomers of <b>1a</b> and <b>9a</b> were analyzed by molecular docking simulation. Using E. coli/<i>vreh3</i> whole cells, gram-scale preparations of (<i>R</i>)-<b>1b</b> and (<i>R</i>)-<b>9a</b> were performed by enantioconvergent hydrolysis of 100 mM <i>rac</i>-<b>1a</b> and kinetic resolution of 200 mM <i>rac</i>-<b>9a</b> in the buffer-free water system at 25 °C. These afforded (<i>R</i>)-<b>1b</b> with >99% ee_p and 78.7% overall yield after recrystallization and (<i>R</i>)-<b>9a</b> with >99% ee_s, 38.7% overall yield, and 12.7 g/L/h space-time yield

Data_Sheet_1_SbbR/SbbA, an Important ArpA/AfsA-Like System, Regulates Milbemycin Production in Streptomyces bingchenggensis.docx

<p>Milbemycins, a group of 16-membered macrolide antibiotics, are used widely as insecticides and anthelmintics. Previously, a limited understanding of the transcriptional regulation of milbemycin biosynthesis has hampered efforts to enhance antibiotic production by engineering of regulatory genes. Here, a novel ArpA/AfsA-type system, SbbR/SbbA (SBI_08928/SBI_08929), has been identified to be involved in regulating milbemycin biosynthesis in the industrial strain S. bingchenggensis BC04. Inactivation of sbbR in BC04 resulted in markedly decreased production of milbemycin, while deletion of sbbA enhanced milbemycin production. Electrophoresis mobility shift assays (EMSAs) and DNase I footprinting studies showed that SbbR has a specific DNA-binding activity for the promoters of milR (the cluster-situated activator gene for milbemycin production) and the bidirectionally organized genes sbbR and sbbA. Transcriptional analysis suggested that SbbR directly activates the transcription of milR, while represses its own transcription and that of sbbA. Moreover, 11 novel targets of SbbR were additionally found, including seven regulatory genes located in secondary metabolite biosynthetic gene clusters (e.g., sbi_08420, sbi_08432, sbi_09158, sbi_00827, sbi_01376, sbi_09325, and sig24_sbh) and four well-known global regulatory genes (e.g., glnR_sbh, wblA_sbh, atrA_sbh, and mtrA/B_sbh). These data suggest that SbbR is not only a direct activator of milbemycin production, but also a pleiotropic regulator that controls the expression of other cluster-situated regulatory genes and global regulatory genes. Overall, this study reveals the upper-layer regulatory system that controls milbemycin biosynthesis, which will not only expand our understanding of the complex regulation in milbemycin biosynthesis, but also provide a basis for an approach to improve milbemycin production via genetic manipulation of SbbR/SbbA system.</p

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<p><i>From</i>: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). <i>P</i>referred <i>R</i>eporting <i>I</i>terns for <i>S</i>ystematic Reviews and <i>M</i>eta-<i>A</i>nalyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:<a href="https://doi.org/10.1371/joumal.pmed1000097" target="_blank">10.1371/joumal.pmed1000097</a>. <b>For more information, visit</b><a href="http://www.prisma-statement.org" target="_blank">www.prisma-statement.org</a><b>.</b></p