A facile synthesis of α,ß-unsaturated imines via palladium-catalyzed dehydrogenation.

The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,ß-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,ß-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,ß-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H-F elimination of N-fluoroamide followed by a smooth α,ß-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.

Damping Properties of Selective Laser-Melted Medium Manganese Mn-xCu Alloy.

In this work, selective laser melting (SLM) technology was applied to directly realize the in situ synthesis of medium manganese Mn-xCu (x = 30-40 wt.%) alloys based on the blended elemental powders. The effects of heat treatment on the microstructural evolution and damping properties of the SLMed Mn-xCu alloys were investigated. The metastable miscibility gap was studied by thermodynamic modeling and microhardness measurement. The results showed that γ-(Mn, Cu) phase with dendritic arm spacing (DAS) of 0.9-1.2 µm was the main constituent phase in the as-SLMed alloys, which was one to two orders of magnitude finer than those of the as-cast samples. Aging at 400-480°C for the Mn-30%Cu or 430°C for Mn-40%Cu alloys can induce spinodal decomposition, martensitic transformation, and α-phase precipitation, whose direct evidence was provided for the first time by transmission electron microscopy and 3D atom probe tomography in the work. The miscibility gap obtained from thermodynamics calculation was basically consistent with the microhardness results for the SLMed Mn-xCu alloys. Solution and aging (SA) treatment can improve the microstructure, tensile and damping properties of the SLMed Mn-xCu alloys more obviously than aging treatment. A 2.3-2.8 and 4.3-4.5 times increase was produced in damping capacity in the aged SLMed and SLMed+SAed Mn-xCu samples, respectively.

A Randomized, Single-Dose, Parallel-Controlled Phase 1 Clinical Comparison of an Omalizumab Biosimilar Candidate with Reference Omalizumab in Healthy Chinese Male Volunteers.

This study evaluated the bioequivalence of omalizumab, a humanized monoclonal antibody against immunoglobulin-E (IgE), with one of its biosimilar candidates. The study was designed as a randomized, double-blind, parallel-controlled trial. A total of subjects who met the inclusion criteria and did not meet the exclusion criteria were dynamically randomly assigned to receive the test drug or the reference drug with a single subcutaneous injection of 150 mg by the minimization method. The test group and the reference group had similar demographic characteristics and baseline characteristics of total IgE. The 90% confidence interval of the geometric average ratio of the area under the serum concentration-time curve from the time 0 to the time of last quantifiable concentration, the area under the serum concentration curve from time 0 to infinity, and the maximum observed serum concentration between the 2 groups were within 80%-125%, showing bioequivalence. The changing trend of total and free IgE in the 2 groups was similar after administration, proving the pharmacodynamic similarity. The 2 groups had no significant difference in the positive rate of antidrug antibodies, and the total positive rate of neutralizing antibodies was 0. The incidence of treatment-emergent adverse events and treatment-related adverse events were similar between the 2 groups, with no serious adverse events. This study shows that the test drug had similar pharmacokinetics, immunogenicity, and safety to the reference omalizumab in healthy male subjects.

Drug therapies for treatment of idiopathic pulmonary fibrosis: a systematic review, Bayesian network meta-analysis, and cost-effectiveness analysis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis and a high economic burden for individuals and healthcare resources. Studies of the costs associated with the efficiency of IPF medications are scarce. We aimed to conduct a network meta-analysis (NMA) and cost-effectiveness analysis to identify the optimum pharmacological strategy among all currently available IPF regimens. Methods: We first performed a systematic review and network meta-analysis. We searched eight databases for eligible randomised controlled trials (RCTs) published, in any language, between January 1, 1992 and July 31, 2022, that investigated the efficacy or tolerability (or both) of drug therapies for the treatment of IPF. The search was updated on February 1, 2023. Eligible RCTs were enrolled, with no restriction on dose, duration, or length of follow-up, if they included at least one of: all-cause mortality, acute exacerbation rate, disease progression rate, serious adverse events, and any adverse events under investigation. A subsequent Bayesian NMA within random-effects models was performed, followed by a cost-effectiveness analysis using the data obtained from our NMA, by developing a Markov model from the US payer's perspective. Assumptions were checked by deterministic and probabilistic sensitivity approaches to identify sensitive factors. We prospectively registered the protocol (CRD42022340590) in PROSPERO. Findings: 51 publications comprising 12,551 participants with IPF were analysed for the NMA, and the findings indicated that pirfenidone and N-acetylcysteine (NAC) + pirfenidone were the most efficacious and tolerable. The pharmacoeconomic analysis showed that NAC + pirfenidone was associated with the highest potentiality of being cost-effective at willingness-to-pay (WTP) thresholds of US$150,000 and $200,000, on the basis of quality-adjusted life years (QALYs), disability-adjusted life years (DALYs) and mortality, with the probability ranging from 53% to 92%. NAC was the minimum cost agent. Compared with placebo, NAC + pirfenidone improved effectiveness by increasing QALYs by 7.02, and reducing DALYs by 7.10 and deaths by 8.40, whilst raising overall costs by $516,894. Interpretation: This NMA and cost-effectiveness analysis suggests that NAC + pirfenidone is the most cost-effective option for treatment of IPF at WTP thresholds of $150,000 and $200,000. However, given that clinical practice guidelines have not addressed the application of this therapy, large well-designed and multicentre trials are warranted to provide a better picture of IPF management. Funding: None.

Ginger (Zingiber officinale Roscoe) preparations for prophylaxis of postoperative nausea and vomiting: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger has been proposed for prevention of postoperative nausea and vomiting (PONV), however it remains equivocal whether ginger can be an alternative option and which certain preparation is optimal for PONV prophylaxis. AIM OF THE STUDY: We conducted a network meta-analysis (NMA) to compare and rank relative efficacy for PONV control among all available ginger preparations collected in the databases. METHODS: Eligible records were identified by retrieving Medline (via Pubmed), Embase, Web of Science, CENTRAL, CNKI, WHO ICTRP and ClinicalTrials.gov for randomized controlled trials that investigated the efficacy of ginger therapies for the prophylaxis of PONV. A bayesian NMA within random-effects models was implemented. Certainty of evidence for estimates was investigated following GRADE framework. We prospectively registered the protocol (CRD 42021246073) in PROSPERO. RESULTS: Eighteen publications comprising 2199 participants with PONV were identified. Ginger oil (RR [95%CI], 0.39 [0.16, 0.96]) appeared to have the highest probability of being ranked best to decrease the incidence of postoperative vomiting (POV), with statistical significance compared with placebo, based on high to moderate confidence in estimates. With regard to reducing postoperative nausea (PON), statistically superiority was not observed in ginger regimens compared with placebo based on moderate to low certainty of evidence. Reduction in antemetic use and nausea intensity were noticed in ginger powder and oil. Ginger was significantly associated with better efficacy for Asian, older age, higher dosage, preoperative administration, hepatobiliary and gastrointestinal surgery. CONCLUSIONS: Ginger oil appeared to be superior to other ginger treatments for the prophylaxis of POV. With regard to reducing PON, ginger preparations indicated no obvious advantages.

A Randomized, Single-dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers.

The test drug, a recombinant humanized monoclonal antibody, is a biosimilar candidate for the reference drug. The purpose of this study was to evaluate the bioequivalence of these two drugs. The study was divided into two parts, a pre-study and a formal trial. The pre-study included two subjects who were each given a single intravenous infusion of 6 mg/kg test drug. The formal trial was designed to be a randomized, double-blind, parallel controlled trial in which 70 subjects were randomly assigned 1:1 to receive either test or reference drug as a single 6 mg/kg intravenous infusion. In the pre-study, the immunogenicity was negative in both subjects and the safety of the test drug was considered to be good. The two groups in the formal trial had similar demographic characteristics. The 90% confidence interval of geometric mean ratios of area under the serum concentration-time curve from the time 0 to the time of last quantifiable concentration, area under the serum concentration-curve from time 0 to infinity, and maximum observed serum concentration between the test group and the reference group fell between 80% and 125% and the bioequivalence was recognized. There was no significant difference in the positive rate of antidrug antibodies. The treatment-emergent adverse events in the test group were similar to those in the reference group. This study showed that the test drug has similar pharmacokinetics, immunogenicity, and safety to the reference drug in healthy male subjects.

Application of computer-assisted surgery in pediatric mediastinal tumor surgery.

BACKGROUND: Computer-assisted Surgery system (CAS) is an effective medical imaging simulation tool, which is widely used in preoperative planning of surgery. The objective of this study is to investigate the clinical application of CAS in pediatric mediastinal tumor resection. METHODS: This retrospective study investigated 74 children who underwent mediastinal tumor resection between June 2008 and June 2022 at the pediatric surgical center of the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital. Preoperative chest computed tomography imaging was performed on all children. A total of 44 children (the CAS-assisted group) underwent clinical image 3D reconstruction and preoperative simulation using Hisense CAS. The control group consisted of 30 children who underwent a conventional procedure without CAS. The demographic, preoperative, and complication data were analyzed and compared between the two groups. t-test, Mann-Whitney U test, X2 test, or Fisher's exact test were used accordingly in this study during analysis. RESULTS: The median operative duration was 119.00 min in the CAS-assisted group and 140.50 min in the control group. The median intraoperative blood loss of the CAS-assisted group and the control group was 14.00 and 31.00 ml respectively. Relative to the control groups, the CAS-assisted group experienced shorter operative duration time (p = 0.041), and less intraoperative blood loss (p < 0.001). The difference in postoperative drain indwelling between the CAS-assisted group (median:4.00 days) and the control group (median:7.00 days) reached a statistical significance (p = 0.001). And the duration of hospitalization after the operation for the CAS-assisted group (median:7.00 days) was shorter than that for the control group (median:9.00 days) (p = 0.001). No significant difference could be found in the rate of blood transfusion (p = 0.258) and the incidence of postoperative complications (p = 0.719) between the two groups. CONCLUSION: Hisense CAS could effectively assist surgeons to clearly determine the anatomical site of tumors and provide accurate preoperative simulation for surgeons, so as to assist surgeons to specify effective surgical plans for patients.

Inhibition of alanine-serine-cysteine transporter 2-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between V-9302 and photosensitizer.

The efficiency of reactive oxygen species (ROS)-based photodynamic therapy (PDT) is far from satisfactory, because cancer cells can adapt to PDT by upregulating glutathione (GSH) levels. The GSH levels in tumor cells are determined based on glutamine availability via alanine-serine-cysteine transporter 2 (ASCT2)-mediated entry into cells. Herein, we develop co-assembled nanoparticles (PPa/V-9302 NPs) of the photosensitizer pyropheophorbide a (PPa) and V-9302 (a known inhibitor of ASCT2) in a 1:1 M ratio using a one-step precipitation method to auto-enhance photodynamic therapy. The computational simulations revealed that PPa and V-9302 could self-assemble through different driving forces, such as π-π stacking, hydrophobic interactions, and ionic bonds. Such PPa/V-9302 NPs could disrupt the intracellular redox homeostasis due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302. The in vivo assays reveal that PPa/V-9302 NPs could increase the drug accumulation in tumor sites and suppress tumor growth in BALB/c mice bearing mouse breast carcinoma (4 T1) tumor. Our findings provide a new paradigm for the rational design of the PDT-based combinational cancer therapy.

Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information available regarding the impact of COPD. The aim of this study is to investigate the role of the circadian clock protein BMAL1 and CLOCK in cellular senescence in order to understand the cellular mechanisms of accelerated aging of COPD. Bmal1 and Clock levels were assessed in the plasma samples of non-smokers, smokers, and patients with COPD. The regulation of ciracadian clock expression and cell senescence by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and overexpression of Bmal1 or Clock were employed to investigate the role of circadian clock on cell senescence. Herein, patients with COPD showed lower Bmal1 and Clock expression in the plasma. Interestingly, CSE exposure contributed to the increased cell senescence, decreased Clock and Bmal1 in human bronchial epithelial cells (Beas-2B cells). We found that knockdown of Clock or Bmal1 lead to upregulation of cell senescence in Beas-2B cells, while overexpression of Clock or Bmal1 inhibited cell senescence in Beas-2B cells, which is through the MAPK pathways. Therefore, our findings indicated that Bmal1 or Clock deficiency may be a significant factor to increase cellular senescence of the lung to develop COPD.

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides.

The control of regioselectivity in Heck-type reaction of unactivated alkenes represents a longstanding challenge due to several detachable hydrogens in ß-H elimination step, which generally afford either one specific regioisomer or a mixture. Herein, a copper-catalyzed intermolecular Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides with divergent regioselectivities is reported. The complete switch of regioselectivity mainly depends on the choice of different additives. Employment of alcohol solvent gives access to vinyl products, while the addition of carboxylate leads to the formation of allylic products. In addition, exclusion of these two promoting factors results in ß-lactams via a C-N reductive elimination. This protocol shows a broad substrate scope for both alkenes and structurally diverse N-fluoro-sulfonamides, producing the corresponding products with excellent regio- and stereoselectivities. Further control experiments and DFT calculations provide in-depth insights into the reaction mechanism, highlighting the distinct effect of the additives on a bidentate auxiliary-stabilized Cu(III) intermediate.

Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif.

Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ.

Analysis of hollow wall effect on the fluid dynamics in the orbitally shaken bioreactors.

Orbitally shaking bioreactors (OSRs) have recently been increasingly applied in the biopharmaceutical industry because they can provide a suitable environment for mammalian cell growth and protein expression. Fluid dynamics information is crucial for analyzing or optimizing of different types of bioreactors. Considering that the structure has an important influence on the fluid dynamics in a bioreactor, it necessary to design or optimize its structure by the computational fluid dynamics (CFD) approach. The aim of this study is to optimize the wall structure of a hollow cylinder OSR proposed in our previous work. Based on previous research, the influences of the hollow wall of the OSR on fluid dynamics and the volumetric mass transfer coefficient ([Formula: see text]) were analysed by the established CFD model. The results showed that the mixing performance of OSR could be improved by decreasing the installation height of the hollow wall. An installation height of 30 mm was found to be most favourable for mixing. The reliability of the CFD model was verified by comparing the liquid wave height and liquid wave shape between the simulation and experiment. The shear stress in the hollow cylinder OSR was proven gentle for mammalian cell cultivation.

Effect of Levosimendan on Acute Decompensated Right Heart Failure in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Aims: Acute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). Methods: This retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up. Results: Oxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort. Conclusions: Levosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

Development and assessment of an online virtual orthodontic curriculum.

INTRODUCTION: Due to break space and time limits, an entirely new online curriculum of orthodontic education with online evaluation system has been structured and developed in the dental school, based on virtual reality simulation. CURRICULUM: At Nanjing Medical University, a new online orthodontic curriculum with programmatic assessment process was constructed and implemented based on competency-based education (CBE). It was consisted of the online orthodontic theoretical lectures based on the National Open Online Course "Orthodontics," the online journal club via the online "flipped classroom," and the online orthodontic pre-clinical training via the virtual learning network platform. In order to evaluate this curriculum, 94 Year 4 dental students took part to complete the online orthodontic curriculum. The mean total score of all the students was 91.99, and the element scores of the online theoretical lectures, journal club, virtual pre-clinical training, and online final examination were respectively 96.83, 79.49, 96.00, and 87.02, which showed a good performance. According to the student feedback toward this curriculum via the online questionnaire, nearly 98% of the students showed agreement or strong agreement that the online orthodontic curriculum has enhanced their orthodontic theoretical understanding and orthodontic practical ability. CONCLUSION: As a student-centered CBE, this online orthodontic curriculum with online evaluation system could provide both orthodontic theory and practice teaching for all the dental students at all times and places based on the online virtual mode, which enriched learners' critical thinking, problem solving, and assessment skills.

Kernel Causality Among Teacher Self-Efficacy, Job Satisfaction, School Climate, and Workplace Well-Being and Stress in TALIS.

Teachers play an important role in the educational system. Teacher self-efficacy, job satisfaction, school climate, and workplace well-being and stress are four individual characteristics shown to be associated with tendency to turnover. In this article, data from the Teaching and Learning International Survey (TALIS) 2018 teacher questionnaire are analyzed, with the goal to understand the interplay amongst these four individual characteristics. The main purposes of this study are to (1) measure extreme response style for each scale using unidimensional nominal response models, and (2) investigate the kernel causal paths among teacher self-efficacy, job satisfaction, school climate, and workplace well-being and stress in the TALIS-PISA linked countries/economies. Our findings support the existence of extreme response style, the rational non-normal distribution assumption of latent traits, and the feasibility of kernel causal inference in the educational sector. Results of the present study inform the development of future correlational research and policy making in education.

A Prediction Model for Cognitive Impairment Risk in Colorectal Cancer after Chemotherapy Treatment.

BACKGROUND: A prediction model can be developed to predict the risk of cancer-related cognitive impairment in colorectal cancer patients after chemotherapy. METHODS: A regression analysis was performed on 386 colorectal cancer patients who had undergone chemotherapy. Three prediction models (random forest, logistic regression, and support vector machine models) were constructed using collected clinical and pathological data of the patients. Calibration and ROC curves and C-indexes were used to evaluate the selected models. A decision curve analysis (DCA) was used to determine the clinical utility of the line graph. RESULTS: Three prediction models including a random forest, a logistic regression, and a support vector machine were constructed. The logistic regression model had the strongest predictive power with an area under the curve (AUC) of 0.799. Age, BMI, colostomy, complications, CRA, depression, diabetes, QLQ-C30 score, exercise, hypercholesterolemia, diet, marital status, education level, and pathological stage were included in the nomogram. The C-index (0.826) and calibration curve showed that the nomogram had good predictive ability and the DCA curves indicated that the model had strong clinical utility. CONCLUSIONS: A prediction model with good predictive ability and practical clinical value can be developed for predicting the risk of cognitive impairment in colorectal cancer after chemotherapy.

Role of MMP-9 in epithelial-mesenchymal transition of thyroid cancer.

BACKGROUND: The purpose of this study is to explore the role and mechanism of MMP-9 in the EMT process of thyroid cancer (TC), so as to provide a basis for clinical exploration of invasion and metastasis process of TC, looking for biological markers of tumor metastasis and molecular intervention therapy. METHODS: Western blot and RT-PCR were employed to detect the expression of MMP-9 in human normal thyroid cell line HT-ori3 and human TC cell lines IHH-4 (PTC), FTC-133, and 8505C. Expression levels of EMT-related markers: epithelial cell marker E-cadherin and stromal cell marker Vimentin in TGF-1-induced TC cell lines were detected by Western blot and RT-PCR, respectively. The effects of MMP-9 downregulation on cell invasion and metastasis were investigated by wound-healing assay and cell invasion experiment. RESULTS: The protein and mRNA expression levels of MMP-9 in TC cell lines were increased compared with the human normal thyroid cell line HT-ori3. When TGF-ß1 was added, the expression of EMT and Vimentin increased while the expression of E-cadherin decreased. Compared with the control group, the TC cells stably transfected with MMP-9 shRNA showed inhibited EMT, decreased Vimentin expression, and increased E-cadherin expression. The induction of TGF-ß1 did not promote the occurrence of EMT in TC cells which were stably transformed with MMP-9 shRNA. The addition of TGF-ß1 to TC cells increased the ability of the cells to migrate and invade. Compared with the control group, the migration and invasion ability of TC cells stably transfected with MMP-9 shRNA was significantly reduced, and the induction of TGF-ß1 could not restore the migration and invasion ability of cells without MMP-9. CONCLUSIONS: In conclusion, we found that MMP-9 can be used as a biomarker for TC, which can promote the EMT process of TGF-ß1 induced TC, and thus affecting the cell migration and invasion ability.

Comparative efficacy of vitamin supplements on prevention of major cardiovascular disease: Systematic review with network meta-analysis.

BACKGROUND: Vitamins are commonly used in the prevention of major cardiovascular disease. However, the efficacy and optimum choice remain controversial. OBJECTIVE: To compare and rank the relative efficacy among all available vitamin preparations for cardiovascular disease through a network meta-analysis. METHODS: Eligible studies were identified by searching PubMed, Embase, Medline, Cochrane library and Web of Science for randomized controlled trials. A random effects model was applied within a frequentist framework. RESULTS: Forty-two articles (45 comparisons, 384,248 participants), including nine vitamin interventions, were identified. Vitamin D had the highest probability of being ranked best in effectiveness (0.84 [0.72, 0.98]) on prevention of cardiovascular events. With regard to reducing death of cardiovascular disease rate, vitamin E was considered better efficacy. CONCLUSIONS: Vitamin B, D and E could reduce the incidence of cardiovascular events to varying degrees. At the same time, the combination of vitamins can not show improvement on the efficacy.

Directing-Group-Based Strategy Enabling Intermolecular Heck-Type Reaction of Cycloketone Oxime Esters and Unactivated Alkenes.

A new type of coupling between unactivated olefins and nonstabilized alkyl radicals was achieved, which enabled the first intermolecular Heck-type reaction of cycloketone oxime esters and unactivated alkenes. This directing-group-based strategy was compatible with various unactivated alkenes and cyclobutanone-, cyclopentanone-, and cyclohexanone-derived oxime esters. Density functional theory calculations showed that both excellent regioselectivities and good diastereoselectivities could be ascribed to the 2-butanol-assisted concerted H-OBz elimination of the conformationally strained metallacyclic transition state.