Supplemental_Material_2 - Chinese Herbal Medicine Versus Other Interventions in the Treatment of Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

<p>Supplemental_Material_2 for Chinese Herbal Medicine Versus Other Interventions in the Treatment of Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials by Ao Yu, David Adelson, and David Mills in Journal of Evidence-Based Integrative Medicine</p

A Computational Reinvestigation of the Formation of <i>N</i>-Alkylpyrroles via Intermolecular Redox Amination

A detailed mechanism of N-alkylpyrrole formation from 3-pyrroline and 2-phenylpropanal in the presence of a Brønsted acid catalyst was investigated in depth using the MP2 and DFT theories. The two mechanisms proposed earlier in recent literatures for this internal redox process were evaluated and were found not to account perfectly for the transition state and the energetic barrier of its formation. Based on the present calculations, a new mechanism was put forth

Supplementary_Table - Chinese Herbal Medicine Versus Other Interventions in the Treatment of Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

<p>Supplementary_Table for Chinese Herbal Medicine Versus Other Interventions in the Treatment of Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials by Ao Yu, David Adelson, and David Mills in Journal of Evidence-Based Integrative Medicine</p

Nano CaCO₃ “Lysosomal Bombs” Enhance Chemotherapy Drug Efficacy via Rebalancing Tumor Intracellular pH

Successful delivery of drugs to the target site is half the battle against tumors as intracellular alkalization pH (pHi) microenvironments severely restricted the efficacy of chemotherapy drugs delivered into tumor cells. Herein, a redox-selective pH-triggered “lysosomal bomb” (DSA/CC-DOX) is developed based on vaterite calcium carbonate and disulfide-cross-linked sodium alginate (DSA) with doxorubicin (DOX) encapsulated. Benefiting from the acid-triggered volume expansion of CaCO3, DSA/CC-DOX NPs can act like a “lysosomal bomb” that rapidly tears the lysosomal membrane with the release of acidic inclusions and the loaded DOX, and then the alkalized pHi in human liver tumor cells (HepG2) can be decreased from 7.61 to 7.09, thus promoting the intracellular accumulation of DOX nearly 3 times more than the free drug. In addition, facilitated by the responsive break of the disulfide bond to GSH, the release of DOX in HepG2 is nearly 8 times that of human normal liver cell (LO2). Notably, DSA/CC-DOX treatment increased the tumor inhibition rate of free drug by 16% and effectively reduced the cardiotoxicity of DOX in the mouse H22 liver cancer model. Overall, acidifying the tumor intracellular environment is a prospective way to improve the antitumor capacity of chemotherapy drug

Theoretical Study of the Peripheral Disulfide Bridge Substituent Effects on the Antioxidant Properties of Naphthyridine Diol Derivatives

The effect of a peripheral disulfide bridge substituent on the phenolic O−H bond dissociation energy (BDE) and the ionization potential (IP) of naphthyridine diol has been studied by density functional theory (DFT) calculation. Compared with naphthalene diol, the substituent of a peripheral disulfide bridge group is very efficient in reducing the BDE, whereas the insertion of nitrogen atoms into the naphthalenic ring only slightly changes the BDE of O−H bond but dramatically enhances the IP. It is similar with the stereoelectronic effect of the heterocyclic ring for the well-known α-tocopherol antioxidant and leads to a highly delocalized spin distribution. With the incorporation of these two aspects, a potential antioxidant is expected to be more active and more stable than α-tocopherol

DFT Study of Functional Reduction of CO₂ with BH₃NMe₃: The Real Role of Organic Catalyst TBD

The detailed mechanism of transition metal-free-catalyzed monomethylation of 2-naphthyl acetonitrile (1a) with CO2 in the presence of triazabicyclodecene (TBD) and BH3NMe3 was investigated using density functional theory. The C-methylation process proved to generate formaldehyde followed by the formation of the product via an alcohol rather than a methoxyborane intermediate. During the reaction, CO2 is activated to form the TBD-CO2 adduct and BH3NMe3 is changed into TBD-BH2 (IM2) in the presence of TBD. IM2 plays a real reducing role within the system due to the unique coordination capability of the B atom. In addition to enhancing the nucleophilicity of 1a through deprotonation by tBuOK, our research also indicates that the generated tBuOH not only assists in proton transfer to generate an alcohol intermediate but also promotes the regeneration of TBD

Computation of p<i>K</i>_a Values of Substituted Aniline Radical Cations in Dimethylsulfoxide Solution

A newly developed computation strategy was used to calculate the absolute pKa values of 18 substituted aniline radical cations in dimethylsulfoxide (DMSO) solution with the error origin elucidated and deviation minimized. The B3LYP/6-311++G(2df,2p) method was applied and was found to be capable of reproducing the gas-phase proton-transfer free energies of substituted anilines with a precision of 0.83 kcal/mol. The IEF-PCM solvation model with gas-phase optimized structures was adopted in calculating the pKa values of the substituted neutral anilines in DMSO, regenerating the experimental results within a standard deviation of 0.4 pKa unit. When the IEF-PCM solvation model was applied to calculate the standard redox potentials of anilide anions, it showed that the computed values agreed well with experiment, but the redox potentials of substituted anilines were systematically overestimated by 0.304 eV. The cause of this deviation was found to be related to the inaccuracy of the calculated solvation free energies of aniline radical cations. By adjusting the size of the cavity in the IEF-PCM method, we derived a reliable procedure that can reproduce the experimental pKa values of aniline radical cations within 1.2 pKa units to those from experiment

Mechanisms of Metal-Free Aerobic Oxidation To Prepare Benzoxazole Catalyzed by Cyanide: A Direct Cyclization or Stepwise Oxidative Dehydrogenation and Cyclization?

The detailed mechanism of the cyanide-catalyzed synthesis of benzoxazole from 2-aminophenol and benzaldehyde was investigated in depth using density functional theory (DFT). The metal-free aerobic oxidative process as well as the dehydrogenation detail were examined and described. Cyanide anion was proved to assist the oxygen atoms to undergo an aerobic dehydrogenation rather than direct cyclization which was predicted according to Baldwin’s 5-<i>exotet</i> rule. The dehydrogenation pathway was thermodynamically favored over cyclization with an activation energy difference of 24.2 kcal/mol. Another point noteworthy was the observation that a trace amount of water could reduce the activation energy effectively during the condensation step (ΔΔ<i>G</i>^⧧ = 22.3 kcal/mol)

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Fig A. Salt Assessment was done by NMDS. Visually, the closer the labels are to the “Actual seawater”, the more similar the brand composition is to the real-life seawater. Table A. Salt assessment of nine brands of commercial salt through analyzing major cations, major anions, and nutrients contained. Fig B. Survival probability of infected snails and uninfected snails in 0.38 ppt salinity treatment group. Time is presented in weeks. The survival probability does not significantly differ between infected snails and uninfected snails in the 0.38 ppt salinity treatment group (p > 0.05) over this time period. Table B. Estimate, SE, t ratio, and p value of pairwise comparisons of snail survival between salinity treatments. Table C. Estimate, SE, t ratio, and p value of pairwise comparisons of snail egg mass production between salinity treatments. Fig C. Egg mass output for infected snails in treatment groups 0.38 ppt, 1.9 ppt, 3.8 ppt, and 5.7 ppt. No salinity treatments had significantly different reproductive output. The horizontal lines on the violin plot represent data quantiles of 25%, 50%, and 75%. For pairwise comparisons see supplement Table S4. Table D Estimate, SE, t ratio, and p value of pairwise comparisons of infected snail egg mass production between salinity treatments. Table E. Estimate, SE, t ratio, and p value of pairwise comparisons of snail infection prevalence between salinity treatments. Fig D. Cercariae output in treatment groups 0.38 ppt, 1.9 ppt, 3.8 ppt, and 5.7 ppt. The horizontal lines on the violin plot represent data quantiles of 25%, 50%, and 75%. Table F. Estimate, SE, t ratio, and p value of pairwise comparisons of cercariae count between salinity treatments. Table G. Estimate, SE, t ratio, and p value of pairwise comparisons of cercarial survival between salinity treatments. (DOCX)</p

Iron(III) Chloride Catalyzed Oxidative Coupling of Aromatic Nuclei

Easily available and nontoxic FeCl3 catalyzes intramolecular oxidative coupling for the direct construction of the phenanthrene ring using meta-chloroperbenzoic acid as sole oxidant at room temperature in excellent yields. The mechanistic investigations show that FeCl3-catalyzed coupling proceeds through the heterolytic coupling (A+ + B). The catalytic approach has been applied to intermolecular biaryl coupling of 2-naphthols and phenol ether