Metal-free radical selenothiocyanation of terminal and internal alkynes.

We report herein a synthetic strategy for the generation of direct selenothiocyanation from both terminal and internal alkynes a radical process. Alkynes derived from bioactive molecules, such as L(-)-borneol and L-menthol, are suitable for selenothiocyanation reaction. This method features metal-free conditions and readily available reagents.

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

Background: Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective.

Methods: A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.

Diastereo- and Enantioselective Synthesis of Eight-Membered N-Heterocycles from Benzofuran-Derived Azadienes and Ynones.

Enantioselective synthesis of eight-membered N-heterocycles represents a long-standing challenge in organic synthesis. Here, by combining the squaramide and DBU catalysis, a sequential asymmetric conjugate addition/cyclization reaction between benzofuran-derived azadienes and ynones has been well-developed, providing straightforward access to chiral eight-membered N-heterocycles in high yields with stereoselectivities. This protocol features the use of a bifunctional squaramide catalyst for controlling the enantioselectivity of products, while the DBU is utilized to achieve intramolecular cyclization and improve the diastereoselectivity of products.

Synthesis of Chiral Diarylmethylamides via Catalytic Asymmetric Aza-Michael Addition of Amides to -Quinomethanes.

Chiral diarylmethylamides are a privileged skeleton in many bioactive molecules. However, the enantioselective synthesis of such molecules remains a long-standing challenge in organic synthesis. Herein, we report a chiral bifunctional squaramide catalyzed asymmetric aza-Michael addition of amides to generated -quinomethanes, affording enantioenriched diarylmethylamides in good yields with excellent enantioselectivities.

Cost-effectiveness analysis of selexipag for the combined treatment of pulmonary arterial hypertension.

Adding selexipag to the combined treatment of endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitor (PDE5i) reduces the risk of clinical worsening events in patients with pulmonary arterial hypertension (PAH) but at a considerably higher cost. This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of ERA and PDE5i in patients with PAH from a Chinese healthcare system perspective. A Markov model was developed to assess costs and quality-adjusted life years (QALYs) of macitentan + tadalafil + selexipag vs.

Metal-free and enantioselective synthesis of 1,4-benzoxazepines from -quinone methide derivatives and α-bromohydroxamates.

A sequential asymmetric conjugate addition/cyclisation of α-bromohydroxamates with -quinone methide derivatives has been developed, which provides enantioenriched 1,4-benzoxazepines in generally high yields (up to 95%) and good enantioselectivities (up to 97 : 3 er). This protocol not only offers a novel and straightforward strategy for constructing chiral 1,4-benzoxazepines, but also demonstrates the potential of α-bromohydroxamates as three-atom synthons in asymmetric cyclisation reactions.

Visible light-induced oxidative α-hydroxylation of β-dicarbonyl compounds catalyzed by ethylenediamine-copper(ii).

We have developed an efficient oxidative α-hydroxylation of β-keto esters with firstly using the structurally simple ethylenediamine-copper(ii) as a catalyst for β-keto esters activation and using visible light as the driving force for generating more active singlet oxygen (O) from triplet state oxygen (O) in the air, providing a series of α-hydroxy β-keto esters in excellent yields (up to 99%) under extremely low photosensitizer loading (0.01 mol%) and catalyst loading (1 mol%) within a short time. Moreover, the gram-scale synthesis showed the practical utility of this protocol.

Copper-catalyzed asymmetric 1,6-conjugate addition of generated -quinone methides with β-ketoesters.

A Cu-catalyzed asymmetric 1,6-conjugate addition of generated -quinone methides (-QMs) with β-ketoester has been developed to construct a ketoester skeleton bearing an adjacent tertiary-quaternary carbon stereocenter in good yields and high enantioselectivities. This is the first example of metal-catalyzed asymmetric transformations of the generated -QMs, avoiding using pre-synthesized -QMs requiring bulky 2,6-substitutions and highlighting a new dual catalytic activation with the chiral bis(oxazoline)-metal complex acting as a normal Lewis acid to activate the β-ketoesters and a source of Brønsted acid responsible for generating the -QMs .

Asymmetric bis(oxazoline)-Ni(II) catalyzed α-hydroxylation of cyclic β-keto esters under visible light.

Using visible light as a driving force and molecular oxygen as a green oxidant, we developed bis(oxazoline)-Ni(acac)2 catalyzed asymmetric α-hydroxylation of β-keto esters under low photosensitizer loading, and the protocol enabled an efficient transformation to provide the desired chiral α-hydroxy-β-keto esters in high yields (up to 99%) and enantioselectivities (up to 99% ee) at room temperature.

Regio- and Enantioselective Friedel-Crafts Benzhydrylation of Indoles in Carbocyclic Ring with -Quinomethanes: Access to Chiral Diarylindolylmethanes.

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel-Crafts benzhydrylation of hydroxyindoles with in situ generated -quinomethanes in oil-water biphases, allowing an efficient access to varied diarylindolylmethanes with a wide substrate scope. The high yields, excellent stereoselectivities, mild conditions, low catalyst loading, and easy scalability also demonstrated the interest of this novel methodology.

Asymmetric copper-catalyzed fluorination of cyclic β-keto esters in a continuous-flow microreactor.

A highly enantioselective homogeneous fluorination of cyclic β-keto esters catalyzed by diphenylamine linked bis(oxazoline)-Cu(OTf)2 complexes has been established in a continuous flow microreactor. The microreactor allowed an efficient transformation with reaction times ranging from 0.5 to 20 min, and the desired products were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) at a low catalyst loading of 1 mol%.

Pharmacokinetic-Based Drug-Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review.

Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug Administration and/or the European Medicines Agency for use during the treatment of ALK-gene-rearrangement forms of NSCLC.

Regioselective catalytic asymmetric N-alkylation of isoxazol-5-ones with para-quinone methides.

A highly regioselective and enantioselective N-alkylation of isoxazol-5-ones with para-quinone methides promoted by bi-functional squaramide catalysts was developed. This unexpected asymmetric N-addition of isoxazolinones afforded a series of enantioenriched N-diarylmethane substituted isoxazolinones with high yields and enantioselectivities (up to 97 : 3 er). This reaction not only provides a useful approach for intermolecular chiral C-N bond formation but also demonstrates the immense potential of isoxazol-5-ones as N-nucleophiles in catalytic asymmetric reactions.

Prolonged low-dose infusion for gemcitabine: a systematic review.

Background: The present standard dose of gemcitabine (Gem), a pyrimidine antimetabolite, is 1,000-1,250 mg/m, and the infusion time is 30 min. However, pharmacological studies have demonstrated that Gem with prolonged infusion could attain a better accumulation rate of Gem triphosphate (active metabolites of Gem), indicating that Gem with prolonged infusion is superior to 30-min infusion. Thus, this systematic review aims to provide some references for Gem administered as a prolonged infusion.

Asymmetric fluorination of indanone-2-carboxylates using a polystyrene-supported diphenylamine-linked bis(oxazoline) complex.

A highly enantioselective fluorination of indanone-2-carboxylates catalyzed by a polystyrene-supported diphenylamine-linked bis(oxazoline) (PS-box)-Cu(OTf) complex has been developed in a continuous flow system. The supported complex exhibited extremely efficient catalytic performance with high activity, affording the corresponding products in excellent yields (up to 99% yield) with excellent enantioselectivities (up to 99% ee) and more than 4000 turnover number (TON).

Meta-analysis of gemcitabine in brief versus prolonged low-dose infusion for advanced non-small cell lung cancer.

Objective: To evaluate the efficacy and safety of gemcitabine (GEM) at 30 min standard-dose infusion (30 min-SDI) compared with prolonged low-dose infusion (P-LDI) in patients with advanced non-small-cell lung cancer (NSCLC).

Methods: Electronic databases including Pubmed, EMbase, Cochrane Library, CNKI, CBM, and VIP were searched using keywords "GEM", "P-LDI", and "NSCLC". Review Manager 5.

Asymmetric conjugate additions of 2-substituted benzofuran-3(2H)-ones to α,β-unsaturated ketones catalyzed by chiral copper complexes.

A highly enantioselective conjugate addition of 2-substituted benzofuran-3(2H)-ones to α,β-unsaturated ketones promoted by chiral copper complexes has been developed, affording the Michael addition products with quaternary stereocenters in good to high yields (up to 95% yield) with excellent enantioselectivities (up to 99% ee). The chiral Michael adducts could be readily converted to the polycyclic benzofuran-type framework via the Robinson annulation.

Structure effect on graphene-modified enzyme electrode glucose sensors.

Using structural characterizations and electrochemical measurements, we explored and investigated the effect of the structure of enzyme electrodes with glucose oxidase (GOD) that were modified by reduced graphene oxide (rGO) sheets. The rGO sheets with different defect density, layers, and oxygen concentrations were chosen to modify the enzyme electrode, and all the modified enzyme electrodes exhibited excellent electrocatalytic activities and performances towards glucose. The abundant defects in rGO induce easy absorption of GOD.

Angiogenesis inhibition and cell cycle arrest induced by treatment with Pseudolarix acid B alone or combined with 5-fluorouracil.

Angiogenesis inhibitors combined with chemotherapeutic drugs have significant efficacy in the treatment of a variety of cancers. Pseudolarix acid B (PAB) is a traditional pregnancy-terminating agent, which has previously been shown to reduce tumor growth and angiogenesis. In this study, we used the high content screening assay to examine the effects of PAB on human umbilical vein endothelial cells (HUVECs).

Development of ELISA for metallothionein-II allows determination of heavy metal pollution of fresh water.

Metallothionein (MT), a metal-binding protein induced primarily by heavy metals in vertebrates, is considered a biomarker for environmental heavy-metal contamination. To investigate heavy metal pollution in the freshwater environment, MT-I and MT-II were purified from livers of crucian carp (Carassius carassius) by gel exclusion chromatography and ion exchange chromatography. To detect the purified MT-II, a specific monoclonal antibody (mAb) against crucian carp MT-II was produced from the hybridoma strains by cell-cell fusion.

Cloning of crucian carp (Carassius cuvieri) metallothionein-II gene and characterization of its gene promoter region.

The genomic DNA of crucian carp (Carassius cuvieri) metallothionein-II (ccMT-II), with its upstream region, was obtained. The sequence analysis of its upstream region revealed several putative cis-acting elements including seven metal regulatory elements (MREs), three activator protein 1 (AP1), two glucocorticoid response elements (GREs), etc. The seven MREs locate into two clusters, a distal cluster with four MREs within -800/-600bp from the translation start site and a proximal cluster with three MREs close to TATA box.