Visible-Light-Induced Photoredox 1,2-Dialkylation of Styrenes with α-Carbonyl Alkyl Bromides and Pyridin-1-ium Salts.

A visible-light-driven photoredox dialkylation of styrenes with α-carbonyl alkyl bromides and pyridin-1-ium salts for the synthesis of polysubstituted 1,4-dihydropyridines is reported. This reaction enables the formation of two new C(sp3)-C(sp3) bonds in a single reaction step and provides a strategy that employs pyridin-1-ium salts as the functionalized alkylating reagents via dearomatization to directly trap the resulting alkyl radicals from radical addition of alkenes and then terminate the alkene dialkylation.

Nickel-Catalyzed Reductive Cross-Coupling of Propargylic Acetates with Chloro(vinyl)silanes: Access to Silylallenes.

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality, and significant heterogeneity among patients. In this study, we aimed to explore the role and mechanism of CLK2 in CRC, a kinase that phosphorylates SR proteins involved in splicing. Based on the analysis from The Cancer Genome Atlas (TCGA) dataset and tissue microarray, we found that CLK2 was upregulated in CRC tissues and associated with a higher tumor stage and poorer overall survival. Consistent with the bioinformatics analysis, the functional experiments validated that CLK2 acted as a tumor-promoting factor in CRC progression. CLK2 knockdown suppressed aggressive cell proliferation, migration, and invasion in vitro, as well as restrained tumor growth in vivo. In terms of mechanism, we found that the Wnt/ß-catenin signaling pathway was responsible for the CLK2-induced CRC progression, based on the results of pathway enrichment analysis and subsequent experimental validation. Thus, our study, for the first time, identified the role of CLK2 in CRC development and provided a compelling biomarker for targeted therapy in CRC treatment.

Direct synthesis of alkenyl iodides via indium-catalyzed iodoalkylation of alkynes with alcohols and aqueous HI.

A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions. This catalytic protocol offers an attractive approach for the synthesis of a diverse range of alkenyl iodides in good to excellent yields.

Cetuximab versus nimotuzumab for the treatment of advanced nasopharyngeal carcinoma: A network meta-analysis.

PURPOSE: We conducted a network meta-analysis to evaluate the efficacy and toxicity of cetuximab and nimotuzumab in the treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: A systematic literature search was performed though Pubmed, Embase, Cochran Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and Wanfang databases. Totally, 19 randomized controlled trials (RCTs) (n=1201) met the study selection criteria and were incorporated in this network meta-analysis. RESULTS: Compared with cetuximab, the results of network meta-analysis indicated that nimotuzumab may achieve higher complete remission rate (CRR) or overall remission rate (ORR) of the primary tumor, but no difference was noticed in 1- and 2-year overall survival (OS) rate and certain toxicities such as myelosuppression, radiodermatitis, mucositis and gastrointestinal reactions. Although nimotuzumab increased the 3-year OS rate, compared with cetuximab, this result needs to be interpreted cautiously because of the studies' heterogeneity. CONCLUSION: Even though we didn't find significant difference between cetuximab and nimotuzumab in terms of survival outcomes, nimotuzumab is more advantageous in short-term efficacy.

[Study on ecological environment and accompanying plants' community characteristics study of wild Panax japonicus in Enshi].

The paper is aimed to study the distribution, population density, soil conditions and community characteristics of accompanying plants' in Enshi sub-regional different areas, with a typical habitats investigation method. The results showed that the wild Panax japonicus mainly distributed in moist places under the forests, by streams, or secondary forests of high grass, within east longitude 29°-30°, north latitude 108°-110°and about 1 000-15 00 meters above sea level. The soils were mainly tide soil and humus with yellow-brown soil, yellow soil and red soil, and the humus thickness was5-30 centimeter, pH 6.0-6.8, the moisture content of 16.8%-24.2%, soil bulk density of 1.39-2.12. Its geographical vegetation types were mainly evergreen coniferous forest, evergreen-deciduous mixture broad leaved forest and evergreen coniferous forest mixed deciduous broad-leaved forest, including three levels community structure of arbors, shrubs and herbaceous; Its accompanying plants reached 86 families, 118 genera, 134 species of seed plants, the arbors included 15 families, 21 genera, 26 species and the dominant species community mainly Pinaceae such as Pinus massoniana, P. tabuliformis, P. henryi and Taxodiaceae such as Cunninghamia lanceolata, Cryptomeria fortunei etc. The shrubs included 39 families, 54 genera, 62 species with the dominant species such as Camellia oleifera, Kalopanax septemlobus, Akebia trifoliata, Trachycarpusfortunei, Rhamnus globosa, Smilax corbularia and so on. The herbaceous included 32 families, 43 genera, 46 species, and Ferns such as the black-footed Dryopteris, Dryopteris crassirhizom, Coniogramme affinis, Polystichum tripteron, Adiantum pedatum, Lunathyrium acrostichoides, Woodsia ilvensis and Woodwardia japonica were dominant species. The cover layer covered a large number of lichens and mosses. The wild P. japonicus can be found among the P. massoniana, P. tabuliformis, P. henryi, lichens and mosses. These may indicate that the wild P. japonicusin Enshi requires higher demands on the ecological environment, its accompanying plants are mainly the tree layer-shrub layer-herb layer, and vertical structure is obvious. The study provides a basis for domestication and conservation of P. japonicus resources.

Combination treatment with antiEGFR monoclonal antibodies in advanced nasopharyngeal carcinoma : a meta-analysis.

PURPOSE: The objective of this study was to compare the efficacy of the conventional treatment (radiotherapy/RT and chemotherapy/CT) and the combination treatment with antiepidermal growth factor receptor (anti EGFR) monoclonal antibodies in patients with primary nasopharyngeal cancer (NPC) using meta-analysis of data retrieved from the literature. METHODS: Seven databases (Pubmed, Embase, Cochrane Library, CBM, CNKI, Wanfang,VIP) were searched. Of 537 identified articles, 12 satisfied our eligibility criteria and entered this meta-analysis. A total of 821 patients in 12 randomized controlled clinical trials (RCTs) were included in the study to compare the effect in the short-term and long-term treatment. RESULTS: The combination treatment improved the objective complete remission rate (CR) of primary NPC and the metastatic lymph nodes, and the 1-year distant metastasis-free survival (MFS) rate relative risk (RR=1.40, 95%CI:1.29-1.53, p=0.00; RR=1.29, 95%CI:1.18-1.42, p=0.00; RR%1.17, 95%CI:1.01-1.35, p=0.03, respectively). There was no difference in the 2- and 3-year MFS rate (RR=1.06, 95%CI:0.85-1.33, p=0.60 ; RR=0.87, 95%CI:0.63-1.22) p=0.43, respectively). CONCLUSION: The combination with anti EGFR monoclonal antibodies and conventional treatment (RT and/or CT) improved the short-term therapeutic effect, but this benefit disappeared after 1 year.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Cobalt-Promoted Electroreductive Cross-Coupling of Prop-2-yn-1-yl Acetates with Chloro(vinyl)silanes.

An electroreductive cross-coupling of prop-2-yn-1-yl acetates with chloro(vinyl)silanes for producing tetrasubstituted silylallenes is developed. The method enables the formation of a new C─Si bond through the cathodic reduction formation of the silyl radical, radical addition across the C≡C bond, the alkenyl anion intermediate formation, and deacetoxylation and represents a mild, practical route to the synthesis of silylallenes. Mechanistic studies reveal that CoCl2 acts as the mediator to promote the formation of the alkenyl anion intermediate via electron transfer.

Fouling evolution of extracellular polymeric substances in forward osmosis based microalgae dewatering.

Membrane fouling was still a challenge for the potential application of forward osmosis (FO) in algae dewatering. In this study, the fouling behaviors of Chlorella vulgaris and Scenedesmus obliquus were compared in the FO membrane filtration process, and the roles of their soluble-extracellular polymeric substances (sEPS) and bound-EPS (bEPS) in fouling performance were investigated. The results showed that fouling behaviors could be divided into two stages including a quickly dropped and later a stable process. The bEPS of both species presented the highest flux decline (about 40.0%) by comparison with their sEPS, cells and broth. This performance was consistent with the largest dissolved organic carbon losses in feed solutions, and the highest interfacial free energy analyzed by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The chemical characterizations of algal foulants further showed that the severe fouling performance was also consistent with a proper ratio of carbohydrates and proteins contents in the cake layer, as well as the higher low molecular weight (LMW) components. Compared with the bEPS, the sEPS was crucial for the membrane fouling of S. obliquus, and an evolution of the membrane fouling structure was found in both species at the later filtration stage. This work clearly revealed the fundamental mechanism of FO membrane fouling caused by real microalgal suspension, and it will improve our understanding of the evolutionary fouling performances of algal EPS.

Palladium-Catalyzed ß-C(sp3)-H Arylation of Silyl Prop-1-en-1-ol Ethers with Aryl Halides: Entry to α,ß-Unsaturated Ketones.

A palladium(0)-catalyzed ß-C(sp3)-H arylation of silyl prop-1-en-1-ol ethers with aryl halides for the synthesis of α,ß-unsaturated ketones is presented. In contrast to the reported ß-C(sp3)-H arylation of ketones, the chemoselectivity of this current method relies on the Pd(0) catalytic systems and reaction temperatures: While using the Pd(dba)2/DavePhos/KF system at 80 °C resulted in ß-C(sp3)-H monoarylation to produce ß-monoarylated α,ß-unsaturated ketones, harnessing the Pd(OAc)2/t-Bu XPhos/K2HPO4 system at 110 °C induced ß-C(sp3)-H diarylation to afford ß,ß-diarylated α,ß-unsaturated ketones. The method provides a versatile route that uses readily available ketone-derivatized α-nonsubstituted silyl prop-1-en-1-ol ethers as the alkene sources and is characterized by a good functional group compatibility, a broad substrate scope, and an excellent selectivity.

Preparation of mulberry branch biomass char and its usage in wastewater treatment.

Biomass char was prepared from mulberry branches by physical activation. An examination by Fourier transform infrared spectroscopy (FTIR) indicated that the functional groups of Si-O were mostly burnt out, significantly decreasing the ash content Analysis of data from a scanning electron microscope (SEM) and a Brunauer-Emmett-Teller (BET) test also revealed increased surface roughness and pore structure, which improved the adsorption capacity of biomass char after preparation. The optimum conditions for preparation were found to be pyrolysis at 700 degrees C for 30 minutes, and then activation at 750 degrees C for one hour, with 3.4% steam content for the activating agent. The prepared biomass char was then employed to adsorb ammonium, copper(II) actetate [Cu(II)] and hexavalent chromium [Cr(VI)] in a solution. The results indicated that the prepared biomass char had a better adsorptive performance than the raw material. Moreover, the removal of determinands increased along with the dosage, and the highest adsorption efficiency of ammonium, copper(II) acetate [Cu(II)] and hexavalent chromium [Cr(VI)] were found to be 20%, 100% and 50%, respectively. The adsorptions of ammonium and hexavalent chromium [Cr(VI)] can be simulated by a pseudo-second order model, while the adsorption of copper(II) acetate [Cu(II)] is better simulated by a pseudo-first order model. The adsorption isotherms of copper(II) acetate [Cu(II)] by biomass char were also investigated, and the Langmuir isotherm was found to best describe the adsorption process.

[Efficacy comparison between micro invasive occlusion procedure and extracorporeal circulation procedure for treating patients with simple ventricular septal defect].

OBJECTIVE: To compare the efficacy between micro invasive occlusion procedure and extracorporeal circulation procedure for treating patients with simple ventricular septal defect. METHODS: Two hundred and twenty patients with simple ventricular septal defect (except subarterial ventricular septal defect) were randomly divided into micro invasive group (n = 116) and traditional cardiopulmonary bypass surgery group (n = 104). Clinical data were collected and compared at baseline and at 3, 30 and 180 days after surgery. RESULTS: Age, gender, body weight and ventricular septal defect type were similar between the two groups (all P > 0.05). Operation time and hospitalization duration were significantly shorter in the micro invasive group than the traditional cardiopulmonary bypass surgery group (all P < 0.05). The proportion of blood transfusion was less in micro invasive group than the traditional cardiopulmonary bypass surgery group [2.59% (3/116) vs. 72.12% (75/104), P < 0.01]. Three days after surgery, incidence of mild and above tricuspid insufficiency was less in micro invasive group than the traditional cardiopulmonary bypass surgery group [0.86% (1/116) vs. 2.88% (3/104), P < 0.05]. There was one patient developed mild pericardial effusion at 30 days post surgery in micro invasive group. There was no intracardiac infection in the two groups during follow-up. At 30 and 180 days post surgery, incidence of residual shunt was also less in micro invasive group than the traditional cardiopulmonary bypass surgery group [1.72% (2/116) vs. 7.69 (8/104) and 0(0/116) vs. 7.69(8/104), all P < 0.05]. After surgery for 3, 30 and 180 days, transthoracic echocardiography derived chamber size, left ventricular end-diastolic volume index and left ventricular ejection fraction were similar between the two groups (all P > 0.05). CONCLUSIONS: The efficacy is similar for patients with simple ventricular septal defect (except subarterial ventricular septal defect) using micro invasive occlusion therapy or extracorporeal circulation surgery. Micro invasive occlusion procedure can shorten operation and hospitalization time, and reduce the need for blood transfusion and risk of developing procedural-related tricuspid insufficiency and post-procedural residual shunt.

[Echocardiography guided coated stent-graft implantation for patients with Stanford B aortic dissection].

OBJECTIVE: To evaluate the feasibility, safety and efficacy of transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) guided coated stent-graft implantation for patients with Stanford B aortic dissection. METHODS: In 5 patients with CT confirmed Stanford B aortic dissection, TEE and TTE were used to determine the parameters for pre-surgery diagnosis and selection of suitable coated stent. During surgery, TEE and TTE provided real-time and dynamic monitoring and guiding for precise implantation of the coated stent to effectively seal the tear of the aortic dissection. After surgery, efficacy of implanted coated stent was evaluated by TTE. RESULTS: In all 5 patients, the coated stents were successfully implanted in the true lumen, a small distal tear was not covered in 1 case. Displacement of stent-graft or new endoleak was not observed at follow-up examinations performed at 3 months post-surgery. There were no aortic perforation, renal failure, paraplegia or other complications. The medians of left ventricular ejection fraction (LVEF) in 2 days before surgery, 1 month post-surgery and 3 months post-surgery are 59.9%, 67.4% and 68.1% and the medians of fraction shortening (FS) are 31.4%, 33.7% and 39.1%. Compared with 2 days before surgery, significant increase of LVEF and FS was observed in 1 month post-surgery and 3 months post-surgery (all P < 0.05). CONCLUSION: Our results showed that echocardiography guided coated stent-graft implantation for patients with Stanford B aortic dissection was safe and effective with lower risk of complications.

Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction.

BACKGROUND: Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel (LTCC). The aim of this study was to evaluate whether p110alpha also controls cardiac contractility by regulating the LTCC. METHODS AND RESULTS: Genetic ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as Pik3cb), in cardiac myocytes of adult mice reduced I(Ca,L) and blocked insulin signaling in the heart. p110alpha-null myocytes had a reduced number of LTCCs on the cell surface and a contractile defect that decreased cardiac function in vivo. Similarly, pharmacological inhibition of p110alpha decreased I(Ca,L) and contractility in canine myocytes. Inhibition of p110beta did not reduce I(Ca,L). CONCLUSIONS: PI3K p110alpha but not p110beta regulates the LTCC in cardiac myocytes. Decreased signaling to p110alpha reduces the number of LTCCs on the cell surface and thus attenuates I(Ca,L) and contractility.

Correction to: The chemodiversity of paddy soil dissolved organic matter correlates with microbial community at continental scales.

An amendment to this paper has been published and can be accessed via the original article.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Involvement of cytochrome P450 3A4 and P-glycoprotein in first-pass intestinal extraction of omeprazole in rabbits.

AIM: To quantitatively evaluate in vivo first-pass intestinal extraction of omeprazole and to investigate the possible involvement of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in this process in rabbits. METHODS: Pharmacokinetic parameters were examined after intraduodenal (id), intraportal venous (ipv), and intravenous (iv) administration of omeprazole at various doses to intestinal and vascular access-ported rabbits. Extraction ratios in the liver and intestinal tract were determined from the area under the plasma concentration-time curve (AUC). In addition, omeprazole was administered by id or iv to rabbits alone or 30 min after the id administration of CYP3A4 or P-gp inhibitors (ketoconazole or verapamil, respectively). RESULTS: Pharmacokinetic parameters of omeprazole were dose-dependent after id, ipv, and iv administration at various doses. After id administration of 3 mg/kg omeprazole, the hepatic and intestinal extraction ratio was 57.18%+/-2.73% and 54.94%+/-1.85%, while the value was 59.29%+/-3.14% and 54.20%+/-1.53% after given 6 mg/kg, respectively. Compared with the control group, the presence of ketoconazole (60 mg/kg) or verapamil (9 mg/kg) significantly increased the area under the plasma concentration time curve (AUC) and the peak concentration (C(max)) of id-administered omeprazole, while it had no significant effect on omeprazole administered by iv. CONCLUSION: Oral omeprazole undergoes marked extraction in the small intestine, and increased bioavailability of the drug after id administration of ketoconazole and verapamil suggests that this increase results from inhibition of CYP3A4 and P-gp function in the intestine rather than the liver.

Black soldier fly larvae (Hermetia illucens) strengthen the metabolic function of food waste biodegradation by gut microbiome.

Vermicomposting using black soldier fly (BSF) larvae (Hermetia illucens) has gradually become a promising biotechnology for waste management, but knowledge about the larvae gut microbiome is sparse. In this study, 16S rRNA sequencing, SourceTracker, and network analysis were leveraged to decipher the influence of larvae gut microbiome on food waste (FW) biodegradation. The microbial community structure of BSF vermicompost (BC) changed greatly after larvae inoculation, with a peak colonization traceable to gut bacteria of 66.0%. The relative abundance of 11 out of 21 metabolic function groups in BC were significantly higher than that in natural composting (NC), such as carbohydrate-active enzymes. In addition, 36.5% of the functional genes in BC were significantly higher than those in NC. The changes of metabolic functions and functional genes were significantly correlated with the microbial succession. Moreover, the bacteria that proliferated in vermicompost, including Corynebacterium, Vagococcus, and Providencia, had strong metabolic abilities. Systematic and complex interactions between the BSF gut and BC bacteria occurred over time through invasion, altered the microbial community structure, and thus evolved into a new intermediate niche favourable for FW biodegradation. The study highlights BSF gut microbiome as an engine for FW bioconversion, which is conducive to bioproducts regeneration from wastes.

Role of granular activated carbon in the microalgal cultivation from bacteria contamination.

Microalgal wastewater treatment has been considered as one of the most promising measures to treat nitrogen and phosphorus in the municipal wastewater. While the municipal wastewater provides sufficient nitrogen and phosphorus for microalgal growth, the microalgae still faces serious biological contamination caused by bacteria in wastewater. In this study, the commercial granular activated carbon (GAC) was added into the simulated municipal wastewater to avoid the influence of bacteria on the growth of microalgae. The extracellular organic matter (EOM) in microalgal broth was then characterized to enlighten the role of GAC in reducing the bioavailability of EOM. The results showed that the GAC addition could increase the dry weight of microalgae from 0.06mgL-1 to 0.46mgL-1 under the condition of bacterial inoculation. The GAC could mitigate bacterial contamination mainly due to its adsorption of both bacteria and EOM that might contain algicidal extracellular substances. Moreover, compared to the control group, the GAC addition could mitigate the microalgal lysis caused by bacteria and thus greatly reduce the bioavailability of EOM from 2.80mgL-1 to 0.61mgL-1, which was beneficial for the improvement of biostability and reuse of effluent after the microalgal harvesting.