Copper-Based Metal-Organic Framework with a Tetraphenylethylene-Tetrazole Linker for Visible-Light-Driven CO2 Photoconversion.

The design of efficient and inexpensive photocatalysts for CO2 photoreduction under visible light is of great significance for the sustainable development of the entire society. Herein, a copper-based metal-organic framework (MOF) (CUST-804) using a bulky tetraphenylethylene-tetrazole linker is synthesized and successfully used as a photocatalyst for CO2 reduction. The structural characterizations, as well as the photophysical properties, are investigated systematically. In the heterogeneous catalytic system, CUST-804 exhibits a robust CO production activity up to 2.71 mmol g-1 h-1 with excellent recyclability along with a selectivity of 82.8%, which is comparable with those of the reported copper-based MOF system. Theoretical calculations demonstrated that, among three kinds of coordinated model, only the 5-coordinated Cu site is active for CO2 reduction, in which the *COOH intermediate is stabilized and CO is readily desorbed. The results obtained herein can provide fresh insights into the realization of efficient copper-functionalized crystalline photocatalysts for CO2 reduction.

Reduction of N2O by H2 Catalyzed by Keggin-Type Phosphotungstic Acid Supported Single-Atom Catalysts: An Insight from Density Functional Theory Calculations.

In the present paper, the mechanisms of N2O reduction by H2 were systemically examined over various polyoxometalate-supported single-atom catalysts (SACs) M1/PTA (M = Fe, Co, Mn, Ru, Rh, Os, Ir, and Pt; PTA = [PW12O40]3-) by means of density functional theory calculations. Among these M1/PTA SACs, Os1/PTA SAC possesses high activity for N2O reduction by H2 with a relatively low rate-determining barrier. The favorable catalytic pathway involves the first and second N2O decomposition over the Os1/PTA SAC and hydrogenation of the key species after the second N2O decomposition. Molecular geometry and electronic structure analyses along the favorable reaction pathway indicate that a strong charge-transfer cooperative effect of metal and support effectively improves the catalytic activity of Os1/PTA SAC. The isolated Os atom not only plays the role of adsorption and activation of the N2O molecule but also works as an electron transfer medium in the whole reaction process. Meanwhile, the PTA support with very high redox stability has also been proven to be capable of transporting the electron to promote the whole reaction. We expect that our computation results can provide ideas for designing new SACs for N2O reduction by using H2 selective catalytic reduction technology.

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus.

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0×10(8), 2.5×10(9), and 1.25×10(10) viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0×10(8), 2.5×10(9), and 1.25×10(10) VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose>5×10(10) VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25×10(10) VP/kg) and beagles (2.5×10(9) VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35×10(10) VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67×10(8) VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent.

Tuina combined with diet and exercise for simple obesity: A protocol for systematic review.

BACKGROUND: The incidence of simple obesity is increasing annually, with the number of obese people in all age groups increasing significantly. Obesity has become an important public health concern. Simple obesity affects not only appearance but also health. Obesity has an increasing impact on individuals, families, and society. Therefore, the treatment of obesity is becoming increasingly important. Prior studies have shown that Tuina combined with diet and exercise is capable of producing improvements in body weight and fasted health markers. In recent years, there are many clinical studies on the intervention of simple obesity by Tuina combined with diet and exercise, however, no study systematically evaluated the clinical efficacy. The purpose of this study is to evaluate its effects of Tuina combined with diet and exercise on people with simple obesity. METHODS: We will search the following electronic databases: PubMed, EMBASE, MEDLINE, Web of science, Cochrane Library, WanFang Data, CBM, CNKI, and VIP from the inception of the coverage of these databases to December 2021. Randomized controlled clinical trials related to Tuina combined with diet and exercise intervention on simple obesity will be included. Cochrane's collaboration tool will be used to assess the quality of the studies. RevMan 5.3 software will be used for the data analysis. RESULTS: This study will provide a standardized evaluation for the efficacy of Tuina combined with diet and exercise for simple obesity. CONCLUSION: The conclusion of this study will provide evidence for the safety and effectiveness of Tuina combined with diet and exercise on weight loss. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: INPLASY202210079.

Abdominal massage: A review of clinical and experimental studies from 1990 to 2021.

OBJECTIVE: To systematically review the current state and holistic application of abdominal massage (AM). DESIGN: A systematic review of qualitative evidence was conducted. All English articles exploring the topic of AM that had been published until the end of June 2021 were retrieved. DATA SOURCES: The PubMed, Cochrane library, and Embase databases were accessed. Some original texts were obtained from Google Scholar. DATA EXTRACTION AND SYNTHESIS: Two authors independently evaluated all search data to identify relevant studies. Disagreements were settled by discussion with a third author. Results were independently extracted into standardized sheets and checked for accuracy. MAIN RESULTS: A total of 107 full-text reports were eligible for inclusion. Adult digestive disorders, pediatric disorders, gynecological disorders, obstetric disorders, metabolic disorders, psychological disorders, the side effects of AM, and animal experiments accounted for 49.53%, 14.02%, 7.48%, 7.48%, 4.67%, 4.67%, 5.61%, and 6.54% of all these papers, respectively, with most reports focusing on clinical studies. CONCLUSION: The variety of diseases treated with AM is gradually increasing, and the treatment programs of AM for many diseases are being gradually optimized. Different forms of AM, especially mechanical AM, have been widely studied; the side effects of AM have also been considered; and the possible mechanisms of AM therapy continue to be discovered. In general, AM is an effective and safe therapy and can be widely used in various diseases, but further studies are necessary to clarify the mechanism of AM for different diseases. In the future, AM could become an even safer, more popular, and more modern therapy.

Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer.

Chemotherapy is still one of the principal treatments for gastric cancer, but the clinical application of 5-FU is limited by drug resistance. Here, we demonstrate that ferroptosis triggered by STAT3 inhibition may provide a novel opportunity to explore a new effective therapeutic strategy for gastric cancer and chemotherapy resistance. We find that ferroptosis negative regulation (FNR) signatures are closely correlated with the progression and chemoresistance of gastric cancer. FNR associated genes (GPX4, SLC7A11, and FTH1) and STAT3 are upregulated in 5-FU resistant cells and xenografts. Further evidence demonstrates that STAT3 binds to consensus DNA response elements in the promoters of the FNR associated genes (GPX4, SLC7A11, and FTH1) and regulates their expression, thereby establishing a negative STAT3-ferroptosis regulatory axis in gastric cancer. Genetic inhibition of STAT3 activity triggers ferroptosis through lipid peroxidation and Fe2+ accumulation in gastric cancer cells. We further develop a potent and selective STAT3 inhibitor, W1131, which demonstrates significant anti-tumor effects in gastric cancer cell xenograft model, organoids model, and patient-derived xenografts (PDX) model partly by inducing ferroptosis, thus providing a new candidate compound for advanced gastric cancer. Moreover, targeting the STAT3-ferroptosis circuit promotes ferroptosis and restores sensitivity to chemotherapy. Our finding reveals that STAT3 acts as a key negative regulator of ferroptosis in gastric cancer through a multi-pronged mechanism and provides a new therapeutic strategy for advanced gastric cancer and chemotherapy resistance.

Efficacy and safety evaluation of acupuncture in the treatment of impaired glucose regulation: A protocol for systematic review and meta-analysis.

BACKGROUND: Impaired of glucose regulation belongs to the stage of prediabetes, which is a state of glucose metabolism between diabetes and normal blood glucose. The prevalence of prediabetes in people over 20 years old in China is significantly higher than that in diabetic patients. If no measures are taken to prevent the transition from prediabetes to diabetes, the number of diabetic patients in China will further increase. This study conducted a meta-analysis of the effectiveness of acupuncture in the treatment of impaired glucose regulation by collecting relevant literatures. METHODS: Nine electronic databases: PubMed, EMBASE, Cochrane library, Web of Science, Google Scholar, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched for randomized clinical trails of acupuncture for impaired glucose regulation. The screening process will be developed by 2 independent reviewers, and meta-analysis will be performed with RevMan (V5.3.5) software. RESULTS: This meta-analysis further confirmed the benefits of acupuncture in the treatment of impaired of glucose regulation. CONCLUSION: This study will provide a high-quality evidence of the efficacy and safety of acupuncture on patients with impaired glucose regulation. PROSPERO REGISTRATION NUMBER: INPLASY202170058. ETHICS AND DISSEMINATION: This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of impaired of glucose regulation. Since all the data included were published, the systematic review did not require ethical approval.

Community intervention study of viscera massage in overweight/obese type 2 diabetes high-risk population.

BACKGROUND: Prediabetes is an intermediate metabolic state between normoglycemia and diabetes. Without intervention, prediabetes often progresses to diabetes and prediabetes is associated with increased risk of cardiovascular disease, cancer, renal disease, and dementia. Lifestyle modification play a major role in controlling prediabetes. But lifestyle interventions are often with poor compliance and side effects of drugs are often be dislike by people. As a non-invasive therapy with no side effects, abdominal massage (AM), also called viscera massage in China, has been used to treat prediabetes and obesity-associated diseases. The gut microbiota has been recognized as an important factor in the development of metabolic diseases. Individuals with prediabetes have aberrant intestinal microbiota character. Colonic transport time and stool consistency are strongly associated with gut microbiota. Viscera massage can ease constipation by reducing colonic transport time and promoting intestinal motility. We can infer that viscera massage can modulate composition of gut microbiota affects human metabolism. So, in this trial, we will explore the mechanism of viscera massage on prediabetes from the perspective of intestinal microbiota. METHODS AND DESIGN: Eighty prediabetes individuals will be recruited for this study. Eighty prediabetes individuals will be divided into lifestyle intervention group and viscera massage + lifestyle intervention group by a simple random method. Each group will have 40 individuals. The manipulation of the viscera massage + lifestyle intervention group will be mainly carried out through rubbing the abdomen, kneading abdomen, vibrating abdomen, and pressing the abdomen, 30 minutes per time, once a day, with 2 days off every 5 days. Lifestyle interventions will be performed by combining pushing healthy lifestyle guidance information through Wechat application and giving face-to-face advice together daily. The lifestyle intervention group will receive healthy lifestyle intervention only. All the intervention will be conducted for 4 weeks. Weight, body mass index (BMI), waist circumference, waist-to-hip ratio, and waist-to-height ratio will be measured at the last day of every week. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood-glucose, 2-hour post-meal blood glucose (2hPG) and glycosylated hemoglobin, fasting insulin and insulin resistance index will be tested at the first day and last day of the intervention course. The fecal samples of subjects will be gathered at the first day and last day of the intervention course and will be performed 16S rRNA gene sequencing and metagenomic detection. Finally, the effect and potential mechanism of viscera massage on prediabetes will be discussed in combination with all the results. DISCUSSION: The results of this study will be used to verify the effect of AM on prediabetes and explore the mechanism of AM on prediabetes from the perspective of gut microbiota.

Degradation Mechanism of Benzo[a]pyrene Initiated by the OH Radical and 1O2: An Insight from Density Functional Theory Calculations.

The degradation mechanism of benzo[a]pyrene (BaP) initiated by •OH and 1O2 in aqueous solution is investigated by density functional theory calculations. The main degradation products are BaP-1,6-quinone, BaP-3,6-quinone, BaP-4,6-quinone, and BaP-6,12-quinone. •OH and HO2 are the main intermediate radical species. At a low initial concentration of •OH, 1O2 could be a primary driver for BaP degradation. The degradation mechanism includes six consecutive elementary reactions: (1) 1O2 initiation forming BaP-6-OO. (2) 1,3 H-shift (H atom shifts to the OO group) that is promoted by H2O, forming BaP-6-OOH. (3) BaP-6-OOH decomposes into the •OH radical and BaP-6-O. (4) •OH addition to BaP-6-O forming BaP-6-O-1(3,4,12)-OH. (5) Extracting the H atom from the carbon with the OH group by 1O2. (6) Extracting the H atom from the OH group by HO2. At a high initial concentration of •OH, the •OH-initiated and 1O2-initiated degradation reactions of BaP are both feasible. The degradation mechanism includes six consecutive elementary reactions: (1) •OH initiation forming BaP-6-OH or 1O2 initiation forming BaP-6-OO. (2) 1O2 addition to BaP-6-OH forming BaP-6-OH-12(1,3,4)-OO or •OH addition to BaP-6-OO forming BaP-6-OO-12(1,3,4)-OH. (3) Extracting the H atom from the carbon with the OH group by 1O2, forming HO2. (4) 1,3 H-shift (H-shift from the carbon to the OO group), promoted by H2O. (5) The loss of the OH radical. (6) Abstracting the H atom from the OH group by HO2. In this paper, the formation of BaP-4,6-quinone via the BaP degradation is first reported. Water participates in the elementary reaction in which the H atom attached on the aromatic ring shifts to the OO group, serving as a bridge that stabilizes the transition state and transports the proton. A comprehensive investigation explains the degradation mechanism of BaP initiated by •OH and 1O2 in aqueous solution.

ß-elemene suppresses Warburg effect in NCI-H1650 non-small-cell lung cancer cells by regulating the miR-301a-3p/AMPKα axis.

ß-elemene has been evidenced to suppress the development of numerous cancers including lung cancer. Previous research has found that in A549 cells, ß-elemene increased the expression of adenosine monophosphate-activated protein kinase (AMPK) α (AMPKα), which negatively regulates the Warburg effect. Bioinformatics predicted that binding sites exist between AMPKα and miR-301a-3p, an miRNA that has shown oncogenic function in many cancers. The aim of this work was to investigate the effect of ß-elemene on the Warburg effect in non-small-cell lung cancer (NSCLC) cells and its mechanism. Herein, the expression of miR-301a-3p was evaluated in NSCLC cells. Then, miR-301a-3p was overexpressed or silenced by mimics or inhibitors, respectively, followed by treatment with AMPK agonists or antagonists. NSCLC cells subjected to miR-301a-3p overexpression or inhibition were further treated with ß-elemene. The results demonstrated that AMPKα was targeted and negatively regulated by miR-301a-3p. AMPKα agonists attenuated the Warburg effect in NSCLC cells induced by miR-301a-3p, as evidenced by the decrease in glucose level, lactic acid level, and expression of metabolism-related enzymes (glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA)). Additionally, ß-elemene suppressed the expression of miR-301a-3p, enhanced that of AMPKα, and inhibited the Warburg effect in NSCLC cells. The results indicated that ß-elemene attenuates the Warburg effect in NSCLC cells, possibly by mediating the miR-301a-3p/AMPKα axis.

Activation mechanism of hydrogen peroxide by a divanadium-substituted polyoxometalate [γ-PV2W10O38(µ-OH)2]3-: A computational study.

In the present paper, the reaction mechanism corresponding to activation of hydrogen peroxide (H2O2) by a divanadium-substituted polyoxometalate (POM) [γ-PV2W10O38(µ-OH)2]3- (I) to form catalytic active species, peroxo complex [γ-PV2W10O38(µ-η2,η2-O2)]3- (III), was studied by using the density functional theory (DFT) calculations method with B3LYP functional. The results indicate that coordination of H2O2 to I proceeds via a vanadium-center-assisted proton transfer pathway to remove the first water molecule and form a hydroperoxy intermediate [γ-PV2W10O38(µ-OH) (µ-OOH)]3- (II). And intermediate II occurs through three successive water-assisted proton transfer steps to remove the second water molecule and finally forms catalytic active species. The calculated overall energy profiles show that coordination of H2O2 to vanadium center requires a proton transfer barrier of about 24 kcal mol-1. A detailed comparison of molecular geometries and electronic structure shows that the catalytic active species has a very interesting structural feature, where a superoxide radical (O2-) was embedded into two vanadium centers, and may be a potential nucleophile. The unique withdrawing electron properties and flexible bonding ability of the γ-Keggin-type POM ligand contribute to the formation of O2- radical. The tunable alternate arrangement of W-O bond series in γ-Keggin-type POM ligand contributes to the flexibility of the γ-Keggin-type POM ligand. Meanwhile, our DFT calculations show a good performance of B3LYP-gauge-independent atomic orbital (IGAIM) method for the calculation of 1H NMR parameters of divanadium-substituted phosphotungstate.

Seven major genomic deletions of vaccinia virus Tiantan strain are sufficient to decrease pathogenicity.

Attenuated strain TTVAC7, as a multi-gene-deleted vaccinia virus Tiantan strain (VTT), was constructed by knocking out parts of non-essential genes related to virulence, host range and immunomodulation of VTT, and by combining double marker screening with exogenous selectable marker knockout techniques. In this study, shuttle vector plasmids pTC-EGFP, pTA35-EGFP, pTA66-EGFP, pTE-EGFP, pTB-EGFP, pTI-EGFP and pTJ-EGFP were constructed, which contained seven pairs of recombinant arms linked to the early and late strong promoter pE/L, as well as to enhanced green fluorescent protein (EGFP) as an exogenous selectable marker. BHK cells were co-transfected/infected successively with the above plasmids and VTT or gene-deleted VTT, and homologous recombination and fluorescence plaque screening methods were used to knock out the gene fragments (TC: TC7L ∼ TK2L; TA35: TA35L; TA66: TA66R; TE: TE3L ∼ TE4L; TB: TB13R; TI: TI4L; TJ: TJ2R). The Cre/LoxP system was then applied to knock out the exogenous selectable marker, and ultimately the gene-deleted attenuated strain TTVAC7 was obtained. A series of in vivo and in vitro experiments demonstrated that not only the host range of TTVAC7 could be narrowed and its toxicity weakened significantly, but its high immunogenicity was maintained at the same time. These results support the potential of TTVAC7 to be developed as a safe viral vector or vaccine.