Iridium-Catalyzed Regio- and Enantioselective C7-Allylic Alkylation of 4-Aminoindoles.

The first iridium-catalyzed direct intermolecular indole C7-allylic alkylation of 4-aminoindoles and racemic branched allylic esters was reported. Various substituted substrates were applicable to give the corresponding C7-allylated products in moderate to high yields (43-80%) with high regio- and enantioselectivities (82-99% ee) under mild reaction conditions. Representative transformations of the vinyl group in the product were carried out to examine the utility of this protocol.

Facilitators and barriers to implementing a social franchising model of delivering eye care services in rural China: a qualitative study using the updated Consolidated Framework for Implementation Research.

Objectives: To identify the barriers and facilitators to implementing the social franchising model '' for delivering eye care services to children in rural China, using the updated Consolidated Framework for Implementation Research (CFIR 2.0) as a theoretical basis to evaluate implementation performance drivers and propose strategies for effective scaling and sustainability.

Design: This qualitative study involved semi-structured interviews with key stakeholders from both the supply side and demand side.

Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer. Loss of ( and the consequent activation of hypoxia-inducible factor-α (HIFα, especially HIF2α) plays an essential role in ccRCC initiation and progression. The approved HIF2α inhibitor belzutifan faces the challenge of resistance, presenting an opportunity of co-targeting HIF2α and another vulnerability.

Development and validation of a risk prediction model for kinesiophobia in postoperative lung cancer patients: an interpretable machine learning algorithm study.

Kinesiophobia is particularly common in postoperative lung cancer patients, which causes patients may be reluctant to cough and move due to misperception, internal fear or fear of pain, and avoid rehabilitation training affecting postoperative recovery. Therefore, it is clinically important to discover the factors associated with the occurrence of kinesiophobia and to develop a prediction model. This study aims to investigate the occurrence of kinesiophobia in postoperative lung cancer patients and to develop a prediction model to assess its performance, thereby providing a reference for clinical decision-making.

Dynamic conditional survival nomogram for primary hepatocellular carcinoma: a population-based analysis.

Background And Purpose: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. While 5-year overall survival (OS) is a common prognostic metric, it does not reflect the evolving prognosis of long-term survivors. The study aimed to evaluate dynamic changes in real-time survival among HCC patients over time using conditional survival (CS) analysis and to develop an individualized, time-updated prognostic model.

Switchable divergent synthesis of chiral indole derivatives catalytic asymmetric dearomatization of 2,3-disubstituted indoles.

A strategy allowing the switchable divergent synthesis of chiral indole derivatives was established chiral phosphoric acid-catalyzed asymmetric dearomatization of 2,3-disubstituted indoles using naphthoquinone monoimines as electrophiles. The products were switched between chiral indolenines and fused indolines according to the post-processing conditions. Both two types of products were obtained in good to high yields with generally excellent enantioselectivities.

Exploring the Preferences of Parents of Children with Myopia in Rural China for Eye Care Services Under Privatization Policy: Evidence from a Discrete Choice Experiment.

Objectives: This study aims to measure the preferences and valuations of parents of students with myopia parents for eye care service attributes in rural China, and to quantify the potential welfare impacts of privatization policy on children's eye care services.

Methods: A discrete choice experiment was designed and implemented among a sample of parents of children with myopia in rural China. We randomly selected 350 participants from the list of subjects obtained from local town schools and family doctors using a random number table method.

Valorization of Phaeodactylum tricornutum for integrated preparation of diadinoxanthin and fucoxanthin.

Integrated preparation of high-purity carotenoids from marine microalgae using green and efficient methods still faces enormous challenges. In this study, valorization of the economic Phaeodactylum tricornutum using integrated preparation of diadinoxanthin (Ddx) and fucoxanthin (Fx) was explored containing four steps including algae cultivation, solvent extraction, ODS open-column chromatography, and ethanol precipitation for the first time. Several essential key factors were optimized for simultaneously extracting Ddx and Fx from P.

TRIM6 silencing for inhibiting growth and angiogenesis of gliomas by regulating VEGFA.

Gliomas are the highest prevalent primary central nervous system (CNS) cancers with poor overall survival rate. There is an urgent need to conduct more research into molecular therapies targeting critical elements of gliomas. This study herein targeted to assess the impact of tripartite motif protein 6 (TRIM6) on gliomas.

ANKRD22 promotes glioma proliferation, migration, invasion, and epithelial-mesenchymal transition by upregulating E2F1-mediated MELK expression.

Ankyrin repeat domain protein 22 (ANKRD22) has been implicated in various types of cancers but its expression and potential functions have not been investigated in gliomas. In this study, the high expression of ANKRD22 in gliomas and its correlation with survival were identified based on the Cancer Genome Atlas database. Similar expression trends were observed in glioma tissues and cell lines.

High-Purity Fucoxanthin Can Be Efficiently Prepared from by Ethanol-Based Green Method Coupled with Octadecylsilyl (ODS) Column Chromatography.

The exploitation of new economically valuable microalgae as a sustainable source of minor high-value products can effectively promote the full utilization of microalgae. The efficient preparation of minor products from microalgae remains the challenge, owing to the coexistence of various components with a similar polarity in the microalgae biomass. In this study, a novel approach based on the sustainable-oriented strategy for fucoxanthin (FX) production was proposed, which consisted of four steps, including the culture of microalga, ethanol extraction, ODS column chromatography, and ethanol precipitation.

The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells.

Aminoglycosides can cause ototoxicity and lead to hair cell damage. Neomycin-induced ototoxicity is related to increased production of reactive oxygen species (ROS) and triggering hair cell apoptosis. The c-Jun-N-terminal kinase (JNK) pathway plays an essential role during hair cell damage.

High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection.

Adeno-associated virus (AAV) is one of the most important gene delivery vehicles for gene therapy. Intramuscular (i.m.

One-Pot Enantioselective Synthesis of 2-Pyrrolidinone Derivatives Bearing a Trifluoromethylated All-Carbon Quaternary Stereocenter.

A new methodology for the one-pot enantioselective construction of 2-pyrrolidinone derivatives bearing a trifluoromethylated all-carbon quaternary stereocenter at the 4-position has been described. This strategy combines an organocatalytic conjugate addition of nitroalkanes to isatin-derived α-trifluoromethyl acrylates and a reduction/lactamization process, affording the corresponding products in moderate to high yields (50-95%) with generally excellent stereoselectivities (up to 96% ee and >20:1 dr).

Dystrophin R16/17 protein therapy restores sarcolemmal nNOS in trans and improves muscle perfusion and function.

Background: Delocalization of neuronal nitric oxide synthase (nNOS) from the sarcolemma leads to functional muscle ischemia. This contributes to the pathogenesis in cachexia, aging and muscular dystrophy. Mutations in the gene encoding dystrophin result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

Role of PM in the development and progression of COPD and its mechanisms.

Background: A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD).

Fine-particulate matter aggravates cigarette smoke extract-induced airway inflammation via Wnt5a-ERK pathway in COPD.

Background: Exposure to environmental particulate matter (PM) ≤2.5 μm in diameter (PM) and smoking are common contributors to COPD, and pertinent research implicates both factors in pulmonary inflammation. Using in vivo mouse and in vitro human cellular models, we investigated the joint impact of PM pollution, and cigarette smoke (CS) in mice or cigarette-smoke extract (CSE) in cells on COPD inflammation, and explored potential mechanisms.

Chiral Phosphoric-Acid-Catalyzed Regioselective and Enantioselective C7-Friedel-Crafts Alkylation of 4-Aminoindoles with Trifluoromethyl Ketones.

A highly regioselective and enantioselective C7-Friedel-Crafts alkylation of 4-aminoindoles with trifluoromethyl ketones promoted by a spirocyclic phosphoric acid was developed. This strategy was applicable to various substituted trifluoromethyl ketones and 4-aminoindole derivatives, affording the corresponding C7-functionalized indole derivatives, bearing a pharmaceutically interesting trifluoromethylated tertiary alcohol scaffold, in 21%-98% yields with up to >99% enantiomeric excess (ee).

Design of AAV Vectors for Delivery of Large or Multiple Transgenes.

Adeno-associated virus (AAV)-mediated gene therapy has evolved from bench to bedside, and now is the therapy of choice for certain inherited diseases. However, the small packaging capacity of AAV vectors prevents this technique from treating genetic diseases with mutations of large genes. Multiple strategies, including split AAV gene delivery and oversized AAV gene delivery, have been explored to deliver large gene expression cassettes.

Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOSμ.

Background: Loss of sarcolemmal nNOSμ is a common manifestation in a wide variety of muscle diseases and contributes to the dysregulation of multiple muscle activities. Given the critical role sarcolemmal nNOSμ plays in muscle, restoration of sarcolemmal nNOSμ should be considered as an important therapeutic goal.

Methods: nNOSμ is anchored to the sarcolemma by dystrophin spectrin-like repeats 16 and 17 (R16/17) and the syntrophin PDZ domain (Syn PDZ).

B(CF) catalyzed direct nucleophilic substitution of benzylic alcohols: an effective method of constructing C-O, C-S and C-C bonds from benzylic alcohols.

An efficient and general method of nucleophilic substitution of benzylic alcohols catalyzed by non-metallic Lewis acid B(CF) was developed. The reaction could be carried out under mild conditions and more than 35 examples of ethers, thioethers and triarylmethanes were constructed in high yields. Some bioactive organic molecules were synthesized directly using the methods.

Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients.

Based on structure modification and a high-throughput Jurkat-Lat cell screening model, we found that GIBH-LRA002, ethyl-2-amino-3-cyano-9-methyl-4-(trifluoromethyl)-4,9-dihydropyrano[2,3-]indole-4-carboxylate, effectively reactivated the latent proviruses in a Jurkat-Lat cell line and primary CD4+ T cells from both chronic SIV-infected rhesus macaques and HIV-1 patients but without inducing systemic activation, making this compound attractive for potentially treating HIV-1 infection.

Cappariloside A shows antiviral and better anti-inflammatory effects against influenza virus via regulating host IFN signaling, in vitro and vivo.

Aims: This study aimed to evaluate the efficacy and mechanisms of Cappariloside A, a chemically synthesized compound, against virus and inflammation induced by influenza virus.

Main Methods: The inhibitory activity of Cappariloside A against influenza virus was determined by plaque assay and cytopathic effect inhibition assay. Quantitative real-time PCR, enzyme-linked immunosorbent assay and Bio-Plex methods were used to quantify cytokine and chemokine expression profiles.

Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4T lymphocytes in Kazakh patients with hypertension from the Xinjiang region.

Background And Aim: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.