Search

Two complementary regiodivergent C–H alkynylations of 2-arylthiazoles are reported. When RuII catalysis is employed, an aryl ortho-alkynylation process is favored. The alkynylated products are gained in good yields. With the use of PdII catalysis, a thiazole C5-alkynylation process is developed, allowing for the construction of C5-alkynylated products. This strategy not only expands the methods for the functionalization of 2-arylthiazoles, but also provides new opportunities for the rapid assembly of complex molecular structures, which may have great potential in organic synthesis, medicinal chemistry, and materials science. [ABSTRACT FROM AUTHOR]

We report an innovative synthetic strategy for the generation of polysubstituted indoles from indolines, aryldiazonium salts, and azoles. The methodology encompasses an electrophilic substitution reaction affording C5-indoline intermediates which undergo an iodine-mediated oxidative transformation coupled with C–H functionalization to yield the indole derivatives. [ABSTRACT FROM AUTHOR]

For the dynamic takeout delivery vehicle routing problem, which faces fluctuating order demand and time-varying speeds, this study presents a novel approach. We analyze the time distribution of takeout orders and apply a Receding Horizon Control (RHC) strategy to convert the dynamic challenge into a static one. The driving speed of delivery vehicles on different roads at different times is determined based on the subdivision criteria of the urban road network and a traffic congestion measurement method. We propose a dynamic takeout delivery vehicle routing optimization model and a time-varying subdivision road network is established to minimize the total delivery cost. We validated the model through simulation examples. The optimization results show that the total distribution cost is reduced after considering the time-varying subdivision road network, with the penalty cost decreasing by 39%. It is evident that considering the subdivision of the road network can enhance order delivery efficiency and optimize the overall dining experience. The sensitivity analysis of various parameters reveals that the delivery platform must appropriately determine the time domain and allocate the number of delivery personnel based on order scale to avoid escalating delivery costs. These findings provide theoretical guidance for vehicle routing planning in the context of delivery platforms. [ABSTRACT FROM AUTHOR]

A directing-group-free strategy for oxidative regioselective aminochalcogenation of indolines with amines and dichalconides is presented. This strategy combines tandem coupling sequences and oxidative dehydrogenation methods in a multi-component reaction, enabling the fast construction of a series of C2,3- or C2,5-aminochalcogenated indole derivatives. Moreover, the application of this synthetic approach is demonstrated through the late-stage modification of pharmaceuticals and the derivatization of the products, highlighting its potential and significance. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A one‐pot synthesis of vicinal diamines using indoles, azoles and phenothiazines in a tandem multi‐component reaction is developed. The utilization of a copper‐iodine co‐catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields. An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions, showcasing its potential as an alternative approach for synthesizing vicinal diamines. Moreover, the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry. [ABSTRACT FROM AUTHOR]

The development of a rational protocol to realize the complete regioselectivity and the capability to switch regioselectivity is an appealing yet challenging task. Herein, a regiodivergent C−H arylation of 2‐pyridylthiophenes has been demonstrated via the choice of RuII and PdII catalysts. The reactions proceeded smoothly in a good regioselective manner to afford the corresponding C3‐ and C5‐arylated thiophenes. Late‐stage diversification of biologically relevant scaffold derived from estrone and successful transformation of the products further highlighted the potential utility and importance of this synthetic strategy. [ABSTRACT FROM AUTHOR]

A novel and effective RhIII- and PdII-controlled switchable C–H alkenylation of 2-pyridylthiophenes with alkenes is realized. The alkenylation reactions proceeded smoothly in a highly regio- and stereo-selective manner to afford a broad range of C3- and C5-alkenylated products. Depending on the catalyst employed, the reactions involve two typical approaches: C3-alkenylation via chelation-assisted rhodation and C5-alkenylation via electrophilic palladation. This regiodivergent synthetic protocol was successfully applied for the straightforward building of π-conjugated difunctionalized 2-pyridylthiophenes, which may show great potential in organic electronic materials. [ABSTRACT FROM AUTHOR]

Introduction: Rocuronium intravenous pain is common in induction of general anesthesia. The aim of our study was to determine the median effective dose (ED50) of prophylactic intravenous remifentanil for the prevention of rocuronium injection pain and to explore the effect of age on the ED50. Methods: Eighty-nine adult patients undergoing elective general anesthesia, ASA I or II, regardless of gender or weight, were stratified according to age: group R1 18–44 years, group R2 45–59 years, and group R3 60–80 years. The initial dose of prophylactic remifentanil before rocuronium injection was set at 1 μg/kg lean body weight (LBW). The remifentanil doses were adjusted according to the degree of injection pain using the Dixon sequential method, with a ratio of 1.1 between adjacent doses. Injection pain was graded, and the occurrence of injection pain and adverse reactions were recorded. The ED50 and 95% confidence intervals (CIs) of remifentanil were calculated using the Dixon–Massey formula. Patients were asked whether they recalled feeling any injection pain in the post-anesthesia care unit (PACU). Results: The ED50 (95% CIs) of prophylactic remifentanil for the prevention of rocuronium injection pain were 1.266 μg/kg (1.186–1.351 μg/kg), 1.188 μg/kg (1.065–1.324 μg/kg), and 1.070 μg/kg (1.014–1.129 μg/kg) LBW in group R1, group R2, and group R3, respectively. No adverse reactions to remifentanil occurred in any group. In PACU, 84.6, 86.7, and 85.7% of patients who experienced injection pain had memories of the pain in group R1, group R2, and group R3, respectively. Conclusions: Prophylactic intravenous remifentanil can prevent rocuronium injection pain, and its ED50 decreases with age, with 1.266 μg/kg (18–44 years), 1.188 μg/kg (45–59 years), and 1.070 μg/kg LBW (60–80 years), respectively. Trial Registration: ClinicalTrials.gov: NCT05217238 (registration date 18 Dec 2021). [ABSTRACT FROM AUTHOR]

With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of drug resistance, and the increase of population that is vulnerable to IFDs. Moreover, the COVID-19 pandemic worsened IFDs as a globe health threat as it predisposes the patients to secondary life-threatening fungi. In this mini-review, we provide a perspective on the advances and strategies for combating IFDs with antifungal therapies. [ABSTRACT FROM AUTHOR]

The position‐selective functionalization of the poorly reactive benzenoid nucleus of indoles has remained a great challenge in organic chemistry. Here we describe a directing‐group‐free, three‐component tandem C3‐acylation/C5,6‐H disulfenylation of indoles via an iodine‐, Lewis acid‐ and Brønsted acid‐cooperated mediated strategy. This protocol is remarkable for its exceptional regio‐ and chemo‐selectivity, broad substrate scope, good functional group tolerance and mild reaction conditions. Advantageously, the present protocol offers great potential for the development of general site‐selective functionalization at the benzenoid nucleus of indoles, removing the requirement for neighbouring activating groups. [ABSTRACT FROM AUTHOR]

The Fine-Gray proportional sub-distribution hazards (PSH) model is among the most popular regression model for competing risks time-to-event data. This article develops a fast safe feature elimination method, named PSH-SAFE, for fitting the penalized Fine-Gray PSH model with a Lasso (or adaptive Lasso) penalty. Our PSH-SAFE procedure is straightforward to implement, fast, and scales well to ultrahigh dimensional data. We also show that as a feature screening procedure, PSH-SAFE is safe in a sense that the eliminated features are guaranteed to be inactive features in the original Lasso (or adaptive Lasso) estimator for the penalized PSH model. We evaluate the performance of the PSH-SAFE procedure in terms of computational efficiency, screening efficiency and safety, run-time, and prediction accuracy on multiple simulated datasets and a real bladder cancer data. Our empirical results show that the PSH-SAFE procedure possesses desirable screening efficiency and safety properties and can offer substantially improved computational efficiency as well as similar or better prediction performance in comparison to their baseline competitors. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are organelles with good natural biocompatibility that are abundant in eukaryotic cells and are considered good candidates for use in biological delivery inside cells. Importantly, numerous studies have reported that LDs also participate in immune processes. Here, we investigated whether LDs can also be used as vaccine adjuvants. We designed and prepared a variety of artificial nano-LDs with a nanometer size (200–300 nm) to test this possibility. Artificial nano-LDs have the same monolayer lecithin membrane as natural LDs; in contrast to natural LDs, artificial nano-LDs do not have proteins on their surfaces, which is beneficial to ensure better biocompatibility. Compared with other oil-in-water emulsion adjuvants (MF59 [AddaVax] and AS03 [AddaS03] used in licensed vaccines), vitamin E was used instead of squalene as the oil phase. The artificial nano-LDs (V3, V11, and V12) prepared in this study have structures similar to those of MF59 (AddaVax) and AS03-(AddaS03) under scanning electron microscopy and transmission electron microscopy and have better stability than MF59 (AddaVax) and AS03 (AddaS03); they can even withstand high-temperature sterilization at 120 °C for 30 min. In vivo test results showed that the artificial nano-LDs had good biocompatibility. Recombinant hepatitis B surface antigen and recombinant varicella-zoster virus glycoprotein E were used as model antigens to evaluate the adjuvant effect. We found that our artificial nano-LDs induced excellent humoral and cellular immunity (comparable to that of MF59 [AddaVax]). In addition, apart from the initial increase in the particle size upon high-temperature sterilization, the adjuvant effect of artificial nano-LDs did not decrease. [ABSTRACT FROM AUTHOR]

An efficient intermolecular C−H aminohalogenation of indoles with azoles and NXS (X = F, Cl, Br, I) has been developed. This mild protocol provides a straightforward entry to structurally valuable 2‐azolyl‐3‐halogenated indoles in one single operation. In addition, this attractive route for the synthesis of polyfunctionalized indoles is of great significance due to the product's versatile reactivity for further transformations. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine has controversial influence on cardiac electrophysiology. The aim of this study was to explore the effects of dexmedetomidine on perioperative cardiac electrophysiology in patients undergoing general anesthesia. Methods: Eighty-one patients were randomly divided into four groups: groups D1, D2, D3 receiving dexmedetomidine 1, 1, 0.5 μg/kg over 10 min and 1, 0.5, 0.5 μg/kg/h continuous infusion respectively, and control group (group C) receiving normal saline. Twelve-lead electrocardiograms were recorded at the time before dexmedetomidine/normal saline infusion (T1), loading dose finish (T2), surgery ending (T6), 1 h (T7) after entering PACU, 24 h (T8), 48 h (T9), 72 h (T10) and 1 month (T11) postoperatively. Cardiac circulation efficiency (CCE) were also recorded. Results: Compared with group C, QTc were significantly increased at T2 in groups D1 and D2 while decreased at T7 and T8 in group D3 (P < 0.05), iCEB were decreased at T8 (P < 0.05). Compared with group D1, QTc at T2, T6, T7, T9 and T10 and iCEB at T8 were decreased, and CCE at T2-T4 were increased in group D3 significantly (P < 0.05). Compared with group D2, QTc at T2 and iCEB at T8 were decreased and CCE at T2 and T3 were increased in group D3 significantly (P < 0.05). Conclusions: Dexmedetomidine at a loading dose of 0.5 μg/kg and a maintenance dose of 0.5 μg/kg/h can maintain stability of cardiac electrophysiology during perioperative period and has no significant adverse effects on CCE. Trial registration: ClinicalTrials.gov NCT04577430 (Date of registration: 06/10/2020). [ABSTRACT FROM AUTHOR]

Trivalent-phosphorus-containing molecules are widely used in fields ranging from catalysis to materials science. Efficient catalytic methods for their modifications, providing straightforward access to novel hybrid structures with superior catalytic activities, are highly desired to facilitate reaction improvement or discovery. We have recently developed new methods for synthesizing polyfunctional phosphines by C–C cross-couplings through rhodium-catalyzed C–H bond activation. These methods use a native P(III) atom as a directing group, and can be used in regioselective late-stage functionalization of phosphine ligands. Interestingly, some of the modified phosphines outperform their parents in Pd-catalyzed cross-coupling reactions. 1 Introduction 2 Early Examples of Transition-Metal-Catalyzed P(III)-Directed C–H Bond Activation/Functionalizations 3 Synthesis of Polyfunctional Biarylphosphines by Late-Stage Alkylation: Application in Carboxylation Reactions 4 Synthesis of Polyfunctional Biarylphosphines by Late-Stage Alkenylation: Application in Amidation Reactions 5 Conclusion [ABSTRACT FROM AUTHOR]

The doubly stochastic functional gradient descent algorithm (DSG) that is memory friendly and computationally efficient can effectively scale up kernel methods. However, in solving the highly ill-conditioned large-scale nonlinear machine learning problem, the convergence speed of DSG is quite slow. This is because the condition number of the Hessian matrix of this problem is quite large, which will make stochastic gradient methods converge very slowly. Fortunately, gradient preconditioning is a well-established technique in optimization aiming to reduce the condition number. Therefore, we propose a preconditioned doubly stochastic functional gradient descent algorithm (P-DSG) by combining DSG with gradient preconditioning. P-DSG first uses the gradient preconditioning to adaptively scale the individual components of the estimated functional gradient obtained by DSG, and then utilizes the preconditioned functional gradient as the descent direction in each iteration. Theoretically, an appropriate preconditioner is always the inverse of the Hessian matrix at the optimum, which is not easy to get due to its high computation cost. Therefore, we first choose an empirical covariance matrix of random Fourier features to approximate the Hessian matrix, and then perform a low-rank approximation to the empirical covariance matrix. P-DSG has a fast convergence rate O (1 / t) and produces a smaller constant factor in the boundary than that of DSG while remains O (t) memory friendly and O (t d) computationally efficient. Finally, we test the performance of P-DSG on the kernel ridge regression, kernel support vector machines, and kernel logistic regression, respectively. The experimental results show that P-DSG speeds up convergence and achieves better performance. [ABSTRACT FROM AUTHOR]

In this study, the sources of potentially toxic elements (PTEs) from atmospheric deposition in the waters of Guizhou's Caohai Lake were investigated in addition to the potential risks to human health. Moss bags were used to enrich PTEs from atmospheric deposition, and eight monitoring sites that best represented geographic variation were established around Caohai Lake. Moss bags were collected and examined at every 3 months to identify spatiotemporal patterns of dry and wet atmospheric deposition of PTEs. Zn was the most abundant metal identified from deposition in Caohai (72.07%–95.94%), followed by Pb and Cd, while Hg was the least abundant (0.008%–0.354%). The contributions of wet deposition of PTEs were greater than those of dry deposition, and deposition during the heating season from December to April was greater than that between April to July. Hg was mainly derived from atmospheric dry deposition (65.38%–84.44%). Spatial distribution analysis indicated that atmospheric deposition was associated with the intensity of human activities and heating emissions. Exposure via hand-to-mouth contact accounted for over 99% of the total exposure risk although overall exposure was lower than threshold acceptable levels for carcinogenic and non-carcinogenic metals, indicating an overall lack of risk towards human health. Nevertheless, the health risk from atmospheric deposition of PTEs in Caohai Lake may be reduced by focusing on Zn, Pb, and Cd deposition in rainfall and minimizing the hazards associated with hand-to-mouth exposure to PTEs. [ABSTRACT FROM AUTHOR]

As one of the indispensable elements of body, mineral elements can be divided into major elements such as calcium, phosphorus, magnesium, sodium, potassium and trace elements such as iron, copper, zinc, manganese, selenium and so on. Different mineral elements are widely involved in various life activities of animals in different ways, such as constituting body tissues and participating in enzymatic reactions. Mineral elements play a very important role in metabolism, immune function, production performance and reproductive performance of dairy cows. The paper reviews the nutritional effect of mineral elements and their application in dairy production, to provide reference for the application of mineral elements in dairy cow production. [ABSTRACT FROM AUTHOR]

Alfalfa is a perennial herb with high yield and high quality. It is a common feed for livestock and poultry. In the paper, the evaluation methods of forage value of alfalfa hay were reviewed by physical evaluation, wet analysis, near infrared spectroscopy (NIRS) and cornell net carbohydrate and protein system (CNCPS), and the problems existing in the application and evaluation of alfalfa hay in ruminant production are summarized, to provide a reference for the rational application of alfalfa hay in ruminant production. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Kosinostatin (KST) contains an uncommon aminopyrrole moiety, whose biosynthesis has remained elusive. Herein, aminopyrrolinic acid, which was generated by an L‐ectoine synthase‐like enzyme KstB3 via cyclization of L‐glutamine, was identified to be the real substrate of adenylation enzyme KstB1. Subsequently, a FAD‐dependent dehydrogenase KstB4 along with a transglutaminase‐like enzyme KstB6 were also involved in formation of aminopyrrole. These results provided an unusual pathway for 2‐aminopyrrole formation in KST biosynthesis. [ABSTRACT FROM AUTHOR]

To determine the effects of peak inspiratory pressure (PIP)-guided intracuff pressure (ICP) modulation of laryngeal mask airway (LMA) Supreme™ during laparoscopic cholecystectomy. Totally 120 patients were randomly divided using computer-generated numbers into a control group (n = 60; ICP, 60 cmH2O) and a PIP group (n = 60), in which ICP was increased with 5 cmH2O each time from PIP level until no air leaks from the oropharynx. PIP, ICP, cuff volume (CV), oropharyngeal leak pressure (OLP) and leak fraction (LF) were recorded before and after pneumoperitoneum establishment. Postoperative pharyngolaryngeal complications (sore throat, dysphagia, pharyngeal hematoma, and dysphonia) were also recorded. Demographic data were similar in the two groups. The CV and ICP before and after pneumoperitoneum were significantly lower in the PIP group (CV: 15.6 ± 2.3 mL and 21.0 ± 2.6 mL; ICP: 14.3 ± 2.9 cmH2O and 20.5 ± 3.4 cmH2O) than in the control group (CV: 33.0 ± 2.8 mL and 32.8 ± 1.9 mL; ICP: 60.0 ± 0.1 cmH2O and 60.0 ± 0.1 cmH2O) (P < 0.05). Although OLP was lower in the PIP group (P < 0.05), the LF was similar in the two groups (P > 0.05). There were fewer postoperative pharyngolaryngeal complications in the PIP group (P < 0.05). Compared with a fixed ICP of 60 cmH2O, PIP-guided ICP modulation during LMA Supreme™ use provided effective airway sealing at a lower CV and ICP, and produced fewer postoperative pharyngolaryngeal complications in patients undergoing laparoscopic cholecystectomy. [ABSTRACT FROM AUTHOR]

Some interesting recent studies have shown that safe feature elimination screening algorithms are useful alternatives in solving large scale and/or ultra-high-dimensional Lasso-type problems. However, to the best of our knowledge, the plausibility of adapting the safe feature elimination screening algorithm to survival models is rarely explored. In this study, we first derive the safe feature elimination screening rule for adaptive Lasso Cox model. Then, using both simulated and real-world datasets, we demonstrate that the resulting algorithm can outperform Lasso Cox and adaptive Lasso Cox prediction methods in terms of its predictive performance. In addition to its good predictive performance, we illustrate that the proposed algorithm has a key computational advantage over the above competing methods in terms of computation efficiency. [ABSTRACT FROM AUTHOR]

Fuzzy c-means (FCM) is one of the most frequently used methods for clustering. However, with increasing amount of data, FCM suffers from slow convergence and a large amount of calculation because all samples are involved in updating the solutions per iteration without considering the current clustering results. In this article, a new membership scaling FCM (MSFCM) is proposed, based on the observation that the samples, whose nearest cluster center is v, aid the convergence of v, whereas the remaining samples prevent the convergence of v. In the new algorithm, many samples whose nearest cluster centers do not change in the next iteration are chosen by using the triangle inequality. A new scheme for scaling the membership degrees of the chosen samples is suggested to boost the effect of the in-cluster samples and to weaken the effect of the out-of-cluster samples in the clustering process. The new scheme not only accelerates the convergence of the algorithm but also maintains the high clustering quality. Many experimental results on synthetic and real-world data sets have verified the effectiveness of the proposed algorithm in improving the speed of the convergence of the fuzzy clustering. In particular, compared with FCM, MSFCM saves at least two thirds of the total rounds of iterations without significantly increasing the cost per iteration. [ABSTRACT FROM AUTHOR]

To evaluate the optimal dose of dexmedetomidine for perioperative blood glucose regulation in non-diabetic patients with gastrointestinal malignant tumor. One hundred patients were randomly divided into four groups: control group (group C), dexmedetomidine 1 μg/kg + 0.25 mcg/kg/h (group D1); + 0.5 mcg/kg/h (group D2); and + 1 mcg/kg/h (group D3). Blood glucose concentrations were measured before dexmedetomidine infusion (T1), 1 h after surgery beginning (T2), at the end of surgery (T3), and 1 h in PACU (T4). Duration of surgery, extubation time, anesthetics doses, adverse reactions, postoperative pulmonary infection, total peritoneal drainage 2 days after surgery and hospital stay were recorded. Compared with T1, blood glucose concentrations were higher at T4 in group C and at T2–4 in groups D1, D2, and D3 (p < 0.01). Compared with group C, blood glucose concentrations were higher at T2 and T3 in groups D2 and D3 (p < 0.05), but significantly lower at T4 in groups D1, D2, and D3 (p < 0.01). Propofol and remifentanil consumption in groups D1, D2, and D3 decreased significantly compared with group C (p < 0.01). In group D3, doses of ephedrine (p < 0.05) and atropine (p < 0.01) were higher, and extubation time was prolonged (p < 0.01) compared with the other groups. The incidence of bradycardia was higher in group D3 than that in group C (p < 0.05). Dexmedetomidine loading dose of 1 mcg/kg followed by maintenance with 0.25 mcg/kg/h can regulate perioperative blood glucose well in non-diabetic patients undergoing gastrointestinal malignant tumor resection and reduce doses of anesthetics without extending extubation time. [ABSTRACT FROM AUTHOR]

Objective To determine the median effective dose (ED50) of prophylactic intravenous lidocaine for the prevention of propofol medium-chain triglyceride/long-chain triglyceride (MCT/LCT) emulsion injection pain. Design Prospective trial, Dixon up-and-down sequential method. Setting Operating room of a single hospital. Patients Thirty patients aged 18–65 years with American Society of Anesthesiologists (ASA) status I or II who were scheduled for elective surgery under general anesthesia (GA) were included. Interventions The initial dose of prophylactic lidocaine before propofol MCT/LCT emulsion injection was set at 0.5 mg/kg lean body weight (LBW). The lidocaine dose was adjusted according to the degree of patients' injection pain using the Dixon up-and-down sequential method. Measurements The ED50 and 95% confidence intervals (CIs) of lidocaine were calculated using the Dixon–Massey formula. Vital signs and adverse effects were recorded. In the postanesthesia care unit (PACU), patients were asked if they recalled feeling any injection pain with visual analog scale (VAS) evaluation. Results The ED50 of lidocaine for the prevention of propofol MCT/LCT emulsion injection pain was 0.306 mg/kg LBW (95% CI, 0.262–0.357 mg/kg LBW). No adverse reactions to lidocaine occurred. In the PACU, 90.9% of patients who experienced injection pain recalled this pain (VAS score, 2.8±1.8). Conclusions Prophylactic intravenous lidocaine (0.306 mg/kg LBW) effectively prevented propofol MCT/LCT emulsion injection pain in 50% of patients scheduled for elective surgery under GA with no adverse reaction occurring. [ABSTRACT FROM AUTHOR]

Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, and can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway of compounds in the citridone family through heterologous reconstitution of the pfp pathway. We demonstrate that multiple members of this family can be accessed from a reactive ortho‐quinone methide (o‐QM) intermediate through electrocyclization, cycloisomerization, or conjugate addition. Formation of the quaternary carbon center in citridone B is catalyzed by an epoxide‐forming P450 enzyme, followed by carbon skeletal rearrangement. Our results showcase how nature harvests the reactivities of an o‐QM intermediate to biosynthesize complex natural products. [ABSTRACT FROM AUTHOR]

Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, and can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway of compounds in the citridone family through heterologous reconstitution of the pfp pathway. We demonstrate that multiple members of this family can be accessed from a reactive ortho‐quinone methide (o‐QM) intermediate through electrocyclization, cycloisomerization, or conjugate addition. Formation of the quaternary carbon center in citridone B is catalyzed by an epoxide‐forming P450 enzyme, followed by carbon skeletal rearrangement. Our results showcase how nature harvests the reactivities of an o‐QM intermediate to biosynthesize complex natural products. [ABSTRACT FROM AUTHOR]

We report the C−H alkylation of biarylphosphines at the ortho′ position(s) with alkenes by using rhodium(I) catalysis, which provides straightforward access to a large library of multifunctionalized phosphines. Some of these modified ligands outperformed commercially available phosphines in the Pd‐catalyzed carboxylation of aryl bromides with carbon dioxide in the presence of a photoredox catalyst. [ABSTRACT FROM AUTHOR]

We report the C−H alkylation of biarylphosphines at the ortho′ position(s) with alkenes by using rhodium(I) catalysis, which provides straightforward access to a large library of multifunctionalized phosphines. Some of these modified ligands outperformed commercially available phosphines in the Pd‐catalyzed carboxylation of aryl bromides with carbon dioxide in the presence of a photoredox catalyst. [ABSTRACT FROM AUTHOR]

RuIII incorporated with magnetic nanosized CMC/Fe3O4 hybrid (RuIII@CMC/Fe3O4) has readily developed by a very simple self-organized procedure of RuCl3 and Na–CMC/Fe3O4 organic/inorganic hybrid. The self-organized fresh and recovered catalyst was well characterized by ICP-AES, FTIR, XRD, TGA–DSC–DTG, SEM–EDS-mapping, TEM, and XPS techniques. The elemental maps confirmed that the RuIII species are well dispersed in a homogeneous manner on the surface of CMC/Fe3O4 magnetic hybrid nanoparticles. After full characterization, its catalytic activity was investigated in the synthesis of pyranopyrazole and polyhydroquinoline derivatives. Under optimal conditions, all reactions proceeded well and afforded the desired products in excellent yields. There was no significant effect of electron withdrawing or donating nature of substituent on aryl aldehydes in the formation of these target compounds. The salient features of the present new protocol are broad substrate scope, mild reaction conditions, good-to-excellent yields, operational simplicity, energy-efficiency, high atom-economy, easy isolation of products and no column chromatographic separation. Moreover, RuIII@CMC/Fe3O4 can be easily recovered by using a magnetic field and directly reused for several cycles without significant loss of its activity. The recovered catalyst was confirmed by TEM, XPS, XRD, and SEM–EDS analyses. One-pot multicomponent reactions for green synthesis of pyranopyrazole and polyhydroquinoline derivatives have been performed using a self-organized RuIII@CMC/Fe3O4 nanocatalyst. [ABSTRACT FROM AUTHOR]

Herein, we disclose an interesting iron-catalyzed approach for the carbonylation of a tertiary carbon radical. The tertiary carbon radical generated from a 1,5-hydrogen atom transfer can be captured by CO gas smoothly. Various six-membered lactams were constructed chemo-selectively in high yields. [ABSTRACT FROM AUTHOR]

Phosphorus containing molecules have seen widespread applications in the development of innovative metal-ligand catalysts and materials. In recent years, the implementation of late-stage modifications of phosphorus derivatives via ortho-regioselective C–H bond functionalisation has led to faster and better ways for the synthesis of complex ligands by creating new reactions with low impact on the environment. This Feature article highlights transition-metal catalysed regioselective C–H bond functionalisation of phosphorus-containing molecules, in which the phosphorus containing unit plays the role of a directing group for C–H bond activation and the synthesis of new functional phosphorus derivatives. [ABSTRACT FROM AUTHOR]

The Pd nanoparticles (Pd NPs) embedded on magnetically retrievable carboxymethylcellulose/Fe3O4 (Pd0@CMC/Fe3O4) organic/inorganic hybrid were prepared via the conventional simple process. The presence of the hydroxyl and carboxyl groups within the framework of the magnetic hybrid enables the facile preparation and stabilization of Pd NPs in this organic/inorganic hybrid. This hybrid catalyst was very effective in the Suzuki -Miyaura reaction of a variety of aryl halides with arylboronic acid to afford excellent product yields. The catalyst showed good stability and could be easily recovered with an external magnetic field and reused for several times without a significant loss in its catalytic activity. Furthermore, the Pd0@CMC/Fe3O4 hybrid catalyst was fully characterized by UV-Vis, FT-IR, XRD, SEM, EDX, TEM, XPS and TGA techniques. The hot filtration test suggests that a homogeneous mechanism is operative in Suzuki -Miyaura reaction. [ABSTRACT FROM AUTHOR]

Non-convex optimization problems with multiple local optima are frequently encountered in machine learning. Graduated optimization algorithm (GOA) is a popular method for obtaining the global optima of non-convex problems by minimizing a sequence of locally strong convex functions that smooth the original non-convex problem with increasing approximation. Recently, GradOpt, a GOA-based algorithm, has demonstrated remarkable theoretical and experimental results. However, to optimize problems consisting of both convex and non-convex parts, GradOpt considers the entire objective function as a single non-convex function, leading to significant gaps between the smoothed and original functions. In this study, we propose two new algorithms: SVRG-GOA and PSVRG-GOA. They gradually smooth the non-convex part of the problem and then minimize the smoothed function using either the stochastic variance reduced gradient (SVRG) or proximal SVRG (Prox-SVRG) method. Both the algorithms are proven to have lower iteration complexity (O(1/ε)) than GradOpt (O(1/ε²)). Some tricks, such as larger shrinkage factor, projection step, stochastic gradient, and mini-batch skill are also applied to accelerate convergence of the proposed algorithms. Experimental results illustrate that two new algorithms with similar performance can converge to the "global" optima of a non-convex problem comparatively faster than GradOpt or non-convex Prox-SVRG. [ABSTRACT FROM AUTHOR]

Ethylenediamine functionalized poly(vinyl chloride) (PVC-EDA) was conveniently synthesized by treatment of commercially available PVC powder with ethylenediamine solution. This amine-functionalized PVC was subsequently immersed in copper sulfate solution to form the supported copper catalyst [PVC-EDA-Cu(II)]. The as-prepared catalyst was well characterized with FT-IR, SEM, DSC, TGA, and ICP methods. It was found to catalyze efficiently the CuAAC reaction for the regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles from benzyl halides, phenylacetylenes, and sodium azide in the presence of sodium ascorbate in water to give the corresponding products under mild and environmentally benign conditions. Various benzyl halides containing electron-withdrawing groups and electron-donating groups afforded the desired products in up to 98% yield. The present procedure has the merits of short reaction time and simple reaction work-up. Moreover, this catalyst can be recovered by simple filtration and reused for at least five consecutive runs without any loss of its catalytic activity. [ABSTRACT FROM AUTHOR]

Hybrid materials of polysebacic anhydride (PSA) with graphene oxide (GO) were successfully synthesized for drug controlled release applications. Lomefloxacin (LMF) was chosen as a model antibacterial drug to investigate its release properties. The LMF-contained pills of the GO/PSA and PLA blend were made by preheating and compressing in a mold, and then controlled release behavior of these pills was investigated. The in vitro drug release indicated that the release rate was depended on the GO content in hybrid materials. Within a month, these hybrids exhibited ideal zero-order release behavior with highly effective drug release amount. The cumulative release equations was Y4% = 2.75567X + 4.70247 for 4%GO/PSA/PLA/LMF pills, with a high correlation coefficient of 99.734% and effective drug release amount of 85.9%. This suggested that GO/PSA hybrids were promising new systems for biological and medical applications. [ABSTRACT FROM AUTHOR]

A biodegradable local drug release system consisting of poly(sebacic anhydride) and polylactic acid was developed for the purpose of osteomyelitis therapy. Five kinds of poly(sebacic anhydride) with different molecular weights were synthesized, and levofloxacin was chosen as a model antibacterial drug in the in vitro release within 38 days. As the molecular weight of poly(sebacic anhydride) increased, the melting point (Tm) of the matrices increased and the surface morphology became smoother. Consequently, the initial burst effect was reduced and the release rate significantly decreased. In addition, the kinetics of pills containing poly(sebacic anhydride) (Mw=13,000) were close to zero order release. The release profile reveals that the thermodynamic properties and morphology of these matrices, which are affected by the molecular weight, are essential for developing controllable delivery systems. The drug release rate could be easily controlled by the molecular weight of the poly(sebacic anhydride). Finally, these prospective results allow the biodegradable controlled release systems to be employed as carriers for the treatment of chronic osteomyelitis, as well as for other medical applications. [ABSTRACT FROM AUTHOR]

Background: To investigate the optimal dose of pretreated-dexmedetomidine in fentanyl-induced cough (FIC) suppression. Methods: Patients of 180 undergoing elective surgery with general anesthesia, aged 18–65 years, BMI 18.5–30 kg/m2, ASA I or II, were equally randomized into four groups (n = 45) to receive intravenous pretreatment of dexmedetomidine with 0 (group 1), 0.3 (group 2), 0.6 (group 3) and 0.9 (group 4) mcg/kg over 10 mins, respectively. After the pretreatment, all patients were given a 5-s intravenous injection of fentanyl 4 mcg/kg. The symptoms of irritating cough including the severity and onset time were recorded for 1 min after fentanyl injection. General anesthesia induction was completed with midazolam, propofol and cisatracurium, then endotracheal tube or laryngeal mask was inserted and connected to an anesthesia machine. MAP, HR and SpO2 at the beginning of pretreatment (T0), 3 min (T1), 6 min (T2), 9 min (T3) and 12 min (T4) after the beginning of pretreatment were recorded. Side effects of dexmedetomidine, such as bradycardia, hypertension, hypotension, and respiratory depression were also recorded during the course. Results: Totally 168 patients completed the study. The incidences of cough were 52.4, 42.9, 11.9, and 14.3% in groups 1, 2, 3, and 4, respectively, with no significant differences between groups 1 and 2 (P > 0.05) and between groups 3 and 4 (P > 0.05). The incidence and severity of cough in groups 3 and 4 were significantly lower than those in groups 1 and 2 (P < 0.05). Compared to T0, HR at T2 (P < 0.05), T3 (P < 0.01), and T4 (P < 0.01) decreased significantly and MAP at T4 decreased significantly (P < 0.05) in group 4. Bradycardia occurred in 1 case and respiratory depression occurred in 1 case in group 4. Compared to group 1, the onset time of cough in the other 3 groups were delayed significantly (P < 0.05). Conclusion: Pretreated dexmedetomidine 0.6 mcg/kg blous intravenous infusion over 10 mins could reduce FIC effectively without side effects. Trial registration: This study was registered in ClinicalTrials.gov (NCT03126422), April 13, 2017. [ABSTRACT FROM AUTHOR]