Enantioselective Hydroalkoxylation of 1,3-Dienes via Ni-Catalysis.

As an advance in hydrofunctionalization, we herein report that alcohols add to 1,3-dienes with high regio- and enantioselectivity. Using Ni-DuPhos, we access enantioenriched allylic ethers. Through the choice of solvent-free conditions, we control the reversibility of C-O bond formation. This work showcases a rare example of methanol as a reagent in asymmetric synthesis.

Molecular understanding of the Helmholtz capacitance difference between Cu(100) and graphene electrodes.

Unraveling the origin of Helmholtz capacitance is of paramount importance for understanding the interfacial structure and electrostatic potential distribution of electric double layers (EDL). In this work, we combined the methods of ab initio molecular dynamics and classical molecular dynamics and modeled electrified Cu(100)/electrolyte and graphene/electrolyte interfaces for comparison. It was proposed that the Helmholtz capacitance is composed of three parts connected in series: the usual solvent capacitance, water chemisorption induced capacitance, and Pauling repulsion caused gap capacitance. We found the Helmholtz capacitance of graphene is significantly lower than that of Cu(100), which was attributed to two intrinsic factors. One is that graphene has a wider gap layer at interface, and the other is that graphene is less active for water chemisorption. Finally, based on our findings, we provide suggestions for how to increase the EDL capacitance of graphene-based materials in future work, and we also suggest that the new understanding of the potential distribution across the Helmholtz layer may help explain some experimental phenomena of electrocatalysis.

Enantioselective Selenol-ene Using Rh-Hydride Catalysis.

This study showcases the first enantioselective hydroselenation of styrenes. Organoselenium building blocks are accessed with selectivity for the branched isomer. Through a Rh-hydride pathway, C-Se bonds can be forged with excellent regio- and enantiocontrol.

Disturbance of serum lipid metabolites and potential biomarkers in the Bleomycin model of pulmonary fibrosis in young mice.

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

The energetics of electron and proton transfer to CO2 in aqueous solution.

The electrocatalytic reduction of CO2 is considered an effective method to reduce CO2 emissions and achieve electrical/chemical energy conversion. It is crucial to determine the reaction mechanism so that the key reaction intermediates can be targeted and the overpotential lowered. The process involves the interaction with the electrode surface and with species, including the solvent, at the electrode-electrolyte interface, and it is therefore not easy to separate catalytic contributions of the electrode from those of the electrolyte. We have used density functional theory-based molecular dynamics to calculate the Gibbs free energy of the proton and electron transfer reactions corresponding to each step in the electroreduction of CO2 to HCOOH in aqueous media. The results show thermodynamic pathways consistent with the mechanism proposed by Hori. Since electrodes are not included in this work, differences between the calculated results and the experimental observations can help determine the catalytic contribution of the electrode surface.

Pooled analysis of Xpert Bladder Cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma.

BACKGROUND: Xpert Bladder Cancer is a detection method developed in recent years, designed with the functions of integrating sample automatically, nucleic acid amplification, and target sequence detection. It is a urine assay targeting five mRNAs (CRH, IGF2, UPK1B, ANXA10, and ABL1). The purpose of this article is to review the accuracy of Xpert Bladder Cancer in the follow-up diagnosis of bladder cancer and evaluate the role of Xpert Bladder Cancer in detecting the recurrence of non-muscle-invasive bladder cancer in the round. METHODS: In the database of Embase, PubMed, Web of Science, and Cochrane Library, the articles published up to October 13, 2020, were searched and screened based on the exclusion and inclusion criteria, and data were extracted from the included studies. The sensitivity, specificity, negative likelihood ratio, positive likelihood ratio summary of receiver operating characteristic curves, and diagnostic odds ratio were combined by the Meta-DiSc 1.4 software. The Stata 12.0 software was used to obtain the assessment of publication bias. RESULTS: A total of 8 articles involving eight fourfold tables were finally identified. The pooled sensitivity and specificity of Xpert Bladder Cancer in the diagnosis of bladder cancer were 0.71 and 0.81, respectively. The positive likelihood ratio and negative likelihood ratio were 3.74 and 0.34, respectively. The area under the curve was 0.8407. The diagnostic odds ratio was 11.99. Deeks' funnel plot asymmetry test manifested no publication bias. CONCLUSIONS: In summary, Xpert Bladder Cancer presents high accuracy and specificity in monitoring bladder cancer compared with cystoscopy. More researches are still required to further confirm this conclusion.

[Inhibition effect of active fraction from clove on PI3K/Akt/mTOR signaling pathway to induce apoptosis of human colon cancer HCT116 cells].

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 µg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/ß-actin after treatment of AFC(100 µg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 µg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.

[Analysis and considerations on revision of instructions for traditional Chinese medicine injections].

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

Enantioselective Addition of Pyrazoles to Dienes*.

We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic pyrazoles can be generated with excellent regioselectivity. Mechanistic studies support a pathway distinct from previous hydroaminations: a Pd0 -catalyzed ligand-to-ligand hydrogen transfer (LLHT). This hydroamination tolerates a range of functional groups and advances the field of diene hydrofunctionalization.

Chemical Deprenylation of N6 -Isopentenyladenosine (i6 A) RNA.

N6 -isopentenyladenosine (i6 A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i6 A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i6 A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i6 A.

Catalytic Hydrothiolation: Counterion-Controlled Regioselectivity.

In this Article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway in which regioselectivity is dictated by the choice of counterion associated with the Rh center. Non-coordinating counterions, such as SbF6-, allow for η4-diene coordination to Rh complexes and result in allylic sulfides. In contrast, coordinating counterions, such as Cl-, favor neutral Rh complexes in which the diene binds η2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4- anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (ß-farnesene), we achieve the first enantioselective synthesis of (-)-agelasidine A.

Rootstock-Mediated Effects on Cabernet Sauvignon Performance: Vine Growth, Berry Ripening, Flavonoids, and Aromatic Profiles.

Rootstocks are widely used in viticulture due to their resistance to biotic and abiotic stress. Additionally, rootstocks can affect vine growth and berry quality. This study evaluated the effects of eight rootstocks (101-14, 110R, 5A, 5BB, Ganzin 1, Harmony, Riparia Gloire, and SO4) on the vine growth, berry ripening, and flavonoids and aromatic profiles of Cabernet Sauvignon in two consecutive seasons (2015⁻2016). With few exceptions, minor differences were observed among grafted and own-rooted vines. Own-rooted vines produced the least pruning weight but the highest yield. 101-14, 5BB, and SO4 slightly reduced total soluble solids, but increased acidity, showing tendencies for retarding maturation. Ganzin 1 inhibited the accumulation of flavan-3-ols in berry skins. Furthermore, concentrations and proportions of epicatechin-3-O-galate were decreased by rootstocks, except for 110R. 5A, Harmony, and Riparia Gloire enhanced flavonol concentrations. SO4 slightly decreased most of the individual anthocyanin concentrations. With respect to volatile compounds, 110R, Riparia Gloire, and SO4 induced reductions in concentrations of total esters, whilst 101-14, Ganzin 1, 110R, and 5BB led to increases in the concentrations of C13-norisoprenoids. Therefore, with respect to the negative effects of SO4 on berry ripening and the accumulation of anthocyanin and volatile esters, SO4 is not recommended in practice.

[Species of Fistular Onion Stalk in Zhouhou Beiji Fang].

Congchi Decoction in Zhouhou Beiji Fang is a prescription commonly used in treating light exterior wind-cold syndrome.Fistular Onion Stalk in the prescription has the effects in inducing sweat and dispelling exogenous evils and accelerating Yang Qi,and has been recorded in many medical books. In addition to be used to treat light exterior wind-cold syndrome,Fistular Onion Stalk is also used extensively and uniquely to treat restlessness after cholera,febrile disease,thoracic obstruction,Yin-Yang toxin syndrome,consumptive disease,bellyache due to spleen Qi deficiency according to Zhouhou Beiji Fang. However,there is still lack of the research on whether Fistular Onion Stalk is derived from shallot or scallion. The authors analyzed the sources of Fistular Onion Stalk in the prescription of Congchi Decoction by consulting ancient books,and studying the plant morphology of shallot,the characteristic and effect of Fistular Onion Stalk and the historical physicians' clinical application of Fistular Onion Stalk,the completion and popularity of Zhouhou Beiji Fang,the ratio of water to medicine of Congchi Decoction and the chemical ingredients of Fistular Onion Stalk. Finally,the authors concluded that Fistular Onion Stalk in the Congchi Decoction refers to Scallion bulbs.

[Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice].

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Scalable Enantioselective Total Synthesis of (-)-Goniomitine.

A scalable enantioselective total synthesis of (-)-goniomitine has been developed by using an iridium-catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson-Claisen rearrangement, and one-pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (-)-goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)-1,2-dehydroaspidospermidine, (+)-aspidospermidine, and (+)-vincadifformine were also achieved.

Catalytic Hydrothiolation: Regio- and Enantioselective Coupling of Thiols and Dienes.

We report a Rh-catalyzed hydrothiolation of 1,3-dienes, including petroleum feedstocks. Either secondary or tertiary allylic sulfides can be generated from the selective addition of a thiol to the more substituted double bond of a diene. The catalyst tolerates a wide range of functional groups, and the loading can be as low as 0.1 mol %.

Elevated homocysteine increases the risk of left atrial/left atrial appendage thrombus in non-valvular atrial fibrillation with low CHA2DS2-VASc score.

Aims: To assess the association and the predictive value of plasma homocysteine (Hcy) levels with LA/LAA thrombus in non-valvular Atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Methods and results: Eight hundred and eighty-eight consecutive patients in non-valvular AF with CHA2DS2-VASc score of 0 and 1 were enrolled. All patients routinely underwent transthoracic echocardiography and transoesophageal echocardiography. A total of thirty-two patients had LA/LAA thrombus. Compared with patients without LA/LAA thrombus, plasma Hcy levels were significantly higher in patients with LA/LAA thrombus (16.5 ± 4.8 mmol/L vs. 13.4 ± 4.1 mmol/L, P = 0.009). In multivariate analysis, Hcy was independently associated with LA/LAA thrombus (OR 1.048, 95% CI 1.007-1.090, P = 0.022). Hcy demonstrated a significant predictive value with area under the curve of 0.722 (95% CI 0.662-0.781, P < 0.001). The optimal cut-off point for Hcy predicting LA/LAA thrombus was 13.5 mmol/L (sensitivity 67%, specificity 65%). Patients with Hcy ≥13.5 mmol/L had higher prevalence of LA/LAA thrombus compared with those with Hcy <13.5 mmol/L (6.1% vs. 2.1%, P < 0.001). Elevated Hcy significantly increased the risk of LA/LAA thrombus in patients with CHA2DS2-VASc score of 0 and 1 (OR 11.789, 95% CI 1.437-96.746, P = 0.022; OR 2.256, 95% CI 1.007-5.155, P = 0.048, respectively). Conclusion: Elevated plasma Hcy increases the risk of LA/LAA thrombus in non-valvular AF patients with low CHA2DS2-VASc score, thus it should be taken into account in prediction of thromboembolism.

Rhodium-Catalyzed Hydrofunctionalization: Enantioselective Coupling of Indolines and 1,3-Dienes.

We communicate a strategy for the hydrofunctionalization of 1,3-dienes via Rh-hydride catalysis. Conjugated dienes are coupled to nucleophiles to demonstrate the feasibility of novel C-C, C-O, C-S, and C-N bond forming processes. In the presence of a chiral JoSPOphos ligand, hydroamination generates chiral allylic amines with high regio- and enantioselectivity. Tuning both the pKa and steric properties of an acid-additive is critical for enantiocontrol.

Intermolecular Hydroamination of 1,3-Dienes To Generate Homoallylic Amines.

We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the intermolecular coupling of amines and 1,3-dienes. By tuning the ligand properties and Brønsted acid additive, we find that a combination of rac-BINAP and mandelic acid is critical for achieving anti-Markovnikov selectivity.