Chiral gem-difluoroalkyl reagents: gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols.

Chiral fluorinated reagents provide new opportunities for the discovery of drugs and functional materials because the introduction of a fluorinated group significantly alters a molecule's physicochemical properties. Chiral gem-difluoroalkyl fragments (R-CF2-C*) are key motifs in many drugs. However, the scarcity of synthetic methods and types of chiral gem-difluoroalkyl reagents limits the applications of these compounds. Herein, we report two types of chiral gem-difluoroalkyl reagents chiral gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols and their synthesis by means of methods involving rhodium-catalyzed enantioselective B-H bond insertion reactions of carbenes and Lewis acid-promoted allenylation reactions. The mild, operationally simple method features a broad substrate scope and good functional group tolerance. These two types of reagents contain easily transformable boron and alkynyl or allenyl moieties and thus might facilitate rapid modular construction of chiral molecules containing chiral gem-difluoroalkyl fragments and might provide new opportunities for the discovery of chiral gem-difluoroalkyl drugs and other functional molecules.

Highly Enantioselective Brønsted Acid Catalyzed Heyns Rearrangement.

Herein we report the first method for highly enantioselective Brønsted acid catalyzed Heyns rearrangements. These reactions, catalyzed by a chiral spiro phosphoric acid, afforded synthetically valuable chiral α-aryl-α-aminoketones which cannot be obtained by means of previously reported Heyns rearrangement methods. This method features low catalyst loadings, high yields and high enantioselectivities, making these reactions highly practical. We used the method to efficiently synthesize various chiral amines, including some biologically active molecules. We experimentally proved that these acid-catalyzed Heyns rearrangements proceeded via a proton-transfer process involving an enol intermediate and the stereocontrol was realized during the proton-transfer step.

Iron-Catalyzed Vinylzincation of Terminal Alkynes.

Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C-H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.

Dirhodium-Catalyzed Enantioselective B-H Bond Insertion of gem-Diaryl Carbenes: Efficient Access to gem-Diarylmethine Boranes.

The scarcity of reliable methods for synthesizing chiral gem-diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium-catalyzed B-H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem-diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B-H bond was most likely the rate-determining step.

[Clinical effects between cannulated screw and bone plate internal fixation for humeral tuberosity fracture:a Meta analysis].

OBJECTIVE: To compare clinical effect of cannulated screw and bone plate for the treatment of humeral fracture of greater tuberosity. METHODS: From January 2010 to January 2020, clinical trial literatures on the treatment of humeral tuberosity fractures with cannulated screw and bone plate were searched by PubMed, EMbase, Cochrane Library, Wanfang, CNKI, CBM Database, VIP Database and other databases. Independent literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Revman5.2 software was used to perform Meta analysis. RESULTS: Totally 5 clinical randomized controlled trials and 12 cohort studies were selected, including 1 068 patientsin which 559 patients were treated by cannulated screw internal fixation and 509 patients treated by bone plate internal fixation. Meta analysis resluts showed that there were satistical differences in operation time[MD=-23.03, 95% CI(-29.69, -16.36), P<0.000 1], blood loss[MD=-36.39, 95% CI(-53.73, -19.04), P<0.000 1], hospital stay[MD=-1.86, 95%CI(-3.09, -0.64), P=0.003], fracture healing time [MD=-2.23, 95% CI (-4.27, -0.18), P=0.03], postoperative incidence of infection [OR=0.17, 95%CI (0.03, 0.97), P=0.05], failure rate of internal fixation [OR=3.56, 95% CI (1.29, 9.81), P=0.01] bwteen two groups. While there were no differences in postoperative visual analogue scale (VAS)[MD=-1.34, 95% CI (-2.77, 0.09), P=0.07], American Shoulder and Elbow Surgeons(ASES)[MD=0.26, 95% CI(-6.43, 6.96), P=0.94], Constant shoulder score [MD=-4.05, 95% CI(-8.51, 0.42), P=0.08], excellent rate of Constant shoulder score[MD=-1.30, 95% CI(0.46, 3.72), P=0.62], excellent rate of Neer shoulder joint score[OR=2.04, 95% CI(0.97, 4.28), P=0.06], total complication rate[OR=1.50, 95% CI (0.42, 5.35), P=0.53], incidence of postoperative pain[OR=0.74, 95% CI(0.04, 14.49), P=0.84] and incidence of postoperative acromion syndrome [OR=0.88, 95% CI (0.02, 40.63), P=0.95] between two groups. CONCLUSION: Compared with bone plate, cannulated screw for the treatment of humeral fracture of greater tuberosity has advantages of shorter opertaion time, less blood loss, shorter hospital stay, lower incidence rate of postopertaive infection, and more benefit for fracture healing.

AIE-Based Dynamic in Situ Nanoscale Visualization of Amyloid Fibrillation from Hen Egg White Lysozyme.

Protein misfolding and denaturation, represented by amyloid fibrillation, are associated with many diseases. However, as a general chemical biological process, the dynamic structure information on amyloid fibrillation has not been demonstrated categorically. Herein, hen egg white lysozyme (HEWL) was used as the model protein of interest to realize in situ nanoscale imaging of protein fibrillation process using the fluorophores with aggregation-induced emission (AIE) activity. The AIE-active fluorophores exhibit the reversible capability of association and dissociation with ß-sheet structure and thus dynamic binding-induced emission, which causes the spontaneous switching of fluorescence. The entire HEWL denaturation process induced by sodium dodecyl sulfate (SDS) at ambient conditions was demonstrated in detail by using two AIE-active fluorophores (TPE-NaSO3 and PD-BZ-OH) through reversible electrostatic interaction and specific labeling between AIE probes and ß-sheet structures of amyloid fibrils, respectively. The results indicate that PD-BZ-OH is more specific AIE probe for amyloid fibrils than TPE-NaSO3. In comparison, the SEM and TEM results show the same denaturation process of protein fibrillation induced by SDS at different concentrations. The static super-resolution imaging of amyloid fibrils is performed with a resolution of 35 nm using PD-BZ-OH aqueous solution without additional auxiliary conditions. The dynamic evolution process of HEWL amyloid fibrillation is in situ visualized through super-resolution fluorescent microscopy with nanoscale resolution. Both static and dynamic super-resolution imaging of amyloid fibrillation provides detailed nanoscale structure information exceeding 50 nm resolution, which is of great significance in the exploration of amyloid fibrillation and related diseases.

Management of paediatric obstructive sleep apnoea: A systematic review and network meta-analysis.

BACKGROUND: Obstructive sleep apnoea (OSA) affects many children, and adenotonsillar hypertrophy is the most common cause of paediatric OSA. AIM: Despite the growing treatment options, there is no comprehensive comparison of all interventions. We aimed to compare and rank the effectiveness of various treatments in a network meta-analysis. DESIGN: Literature was searched from inception to 13 May 2018 for paediatric OSA with adenotonsillar hypertrophy. The outcomes were the changes in apnoea-hypopnea index (AHI), oxyhaemoglobin desaturation index (ODI), and lowest arterial oxygen saturation (SaO2 ). Frequentist approach to network meta-analysis was used. Treatment hierarchy was summarized according to the surfaces under the cumulative ranking curves. RESULTS: Fourteen trials comprising 1064 paediatric OSA participants evaluating ten interventions (adenotonsillectomy, adenotonsillectomy + pharyngoplasty, adenotonsillotomy, antimicrobial therapy, steroids, leukotriene receptor antagonists [LTRAs], steroids + LTRAs, rapid maxillary expansion [RME], placebo, and no treatment) were identified for network meta-analysis. In terms of effectiveness in AHI reduction, surgical approach was still the most effective intervention than no treatment. RME was one of the most effective interventions to improve lowest SaO2 . No comparisons showed statistical significance in reducing ODI. CONCLUSIONS: Irrespective of the intervention used, complete resolution of OSA was not achieved in most trials.

Statistical approaches to adjusting weights for dependent arms in network meta-analysis.

Network meta-analysis compares multiple treatments in terms of their efficacy and harm by including evidence from randomized controlled trials. Most clinical trials use parallel design, where patients are randomly allocated to different treatments and receive only 1 treatment. However, some trials use within person designs such as split-body, split-mouth, and crossover designs, where each patient may receive more than one treatment. Data from treatment arms within these trials are no longer independent, so the correlations between dependent arms need to be accounted for within the statistical analyses. Ignoring these correlations may result in incorrect conclusions. The main objective of this study is to develop statistical approaches to adjusting weights for dependent arms within special design trials. In this study, we demonstrate the following 3 approaches: the data augmentation approach, the adjusting variance approach, and the reducing weight approach. These 3 methods could be perfectly applied in current statistical tools such as R and STATA. An example of periodontal regeneration was used to demonstrate how these approaches could be undertaken and implemented within statistical software packages and to compare results from different approaches. The adjusting variance approach can be implemented within the network package in STATA, while reducing weight approach requires computer software programming to set up the within-study variance-covariance matrix.

Hematinic deficiencies and anemia statuses in anti-gastric parietal cell antibody-positive or all autoantibodies-negative erosive oral lichen planus patients.

BACKGROUND/PURPOSE: Approximately 27% of erosive oral lichen planus (EOLP) patients have serum anti-gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA or EOLP itself was a significant factor that caused hematinic deficiencies and anemia statuses in GPCA-positive or autoantibodies-negative EOLP patients (GPCA+/EOLP and Abs-/EOLP patients). METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 41 GPCA+/EOLP patients, 198 Abs-/EOLP patients, and 184 healthy control subjects. RESULTS: GPCA+/EOLP patients had significantly lower mean Hb, iron (for women only), and vitamin B12 level as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. Moreover, GPCA+/EOLP patients had significantly lower serum vitamin B12 level and significantly higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than Abs-/EOLP patients. Furthermore, Abs-/EOLP patients did have significantly lower mean Hb, MCV, iron (for women only), vitamin B12, and folic acid levels as well as significantly greater frequencies of Hb and iron deficiencies than healthy control subjects. CONCLUSION: We conclude that serum GPCA is the major factor that causes vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/EOLP patients. Approximately 29-32% GPCA-positive EOLP patients have vitamin B12 deficiency or macrocytosis and about 23-25% vitamin B12 deficiency or macrocytosis EOLP patients have pernicious anemia. ELOP itself does play a significant role in causing anemia and hematinic deficiencies in Abs-/EOLP patients.

Comparisons of periodontal regenerative therapies: A meta-analysis on the long-term efficacy.

AIM: We conducted a meta-analysis for the long-term differences in treatment outcomes between periodontal regeneration therapies and flap operation. METHODS: A systematic literature search was conducted using the EMBASE, PubMed and Cochrane databases up to June 2016. Treatment outcomes were changes in probing pocket depth and clinical attachment level. We extracted data reported at different time points after periodontal surgery and incorporated all data into the same model. The restricted cubic spline regression was used to estimate the non-linear trend in treatment outcomes. As some studies reported outcomes at multiple time points, we considered several correlation structures for data reported by the same study. RESULTS: A total of 52 randomized controlled trials were included in our longitudinal meta-analysis. The follow-up length ranged from 0.5 year to 10 years. The trends in the treatment outcomes were similar under different correlation structures. Enamel matrix derivatives (EMD) and guided tissue regeneration (GTR) achieved greater probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain than flap operation (FO) in the long-term follow up, but no differences were found between EMD and GTR. CONCLUSION: Compared with FO, periodontal regeneration surgeries achieved greater PPD reduction and gain in CAL after 1 year, and its effects may last for 5-10 years.

[Mechanism of Soil Eco-Functional Stability Under Pyrene/Cadmium Simplex and Combined Pollution Stress].

In current scenario,the soil pollution has become very severe and its effects on agricultural and ecological security issues cannot be ignored as various contaminants are discharged into soil.Thus,the soil pollution is exigent and has to be solved.This research took soil resistance (Rt),resilience (Rl) and stability (Sb) as evaluation indexes for judging soil quality by exerting different concentration (concentration ratio) gradient of pyrene (PYR),cadmium (Cd) and pyrene/cadmium (PYR/Cd) combined pollutants.A sympathetic description was showed from the aspects of microbial activity,diversity and abundance of soil ecosystem,and the models were constructed to describe the dose-response relationship between PYR-Sb and Cd-Rt.The research showed that different types of pollutants had certain inhibition on soil DOC content.In Cd and PYR simplex pollution,soil microbial mean biomass and colony number decreased with increasing concentration of pollutants.In PYR/Cd combined pollution,the ratio of PYR and Cd had a negative correlation with the decreasing rate of DOC and resistance,meanwhile Cd had a prominent influence on the above-mentioned correlations,in other words,the soil with higher concentration of Cd had lower DOC decrease rate and resistance,and Cd would have dominant inhibition effect on microorganisms under PYR/Cd combined pollution.In addition,this study found the significant correlation of cPYR-Sb and cCd-Rt,and built the binomial forecasting model to describe the dose-response relationship of cPYR-Sb and cCd-Rt.