Sulfonyl-PYBOX Ligands Enable Kinetic Resolution of α-Tertiary Azides by CuAAC.

We report the first highly selective kinetic resolution of racemic α-chiral azides via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Newly developed pyridine-bisoxazoline (PYBOX) ligands, bearing a C4 sulfonyl group, enable effective kinetic resolution of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, and their asymmetric CuAAC to afford α-tertiary 1,2,3-triazoles with high to excellent ee values. DFT calculations and control experiments reveal that the C4 sulfonyl group decreases the Lewis basicity of the ligand and increases the electrophilicity of the copper center for better recognition of azides, and functions as a shielding group to make the chiral pocket of the catalyst more effective.

Single-cell sequencing resolves the landscape of immune cells and regulatory mechanisms in HIV-infected immune non-responders.

Immune non-responder after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infections and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here, we performed scRNA-seq, and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from immune non-responder (INR) and responder (IR) HIV-1-infected subjects. We found low expression of mucosal-associated invariant T (MAIT) cells in INRs, which exhibited transcriptional profiles associated with impaired mitochondrial function and apoptosis signaling.

Dihydroartemisinin Reduces Irradiation-Induced Mitophagy and Radioresistance in Lung Cancer A549 Cells via CIRBP Inhibition.

Radiotherapy is a major therapeutic strategy for lung cancer, and radiation resistance (radioresistance) is an important cause of residual and recurring cancer after treatment. However, the mechanism of radioresistance remains unclear. Mitochondrial autophagy (mitophagy), an important selective autophagy, plays an important role in maintaining cell homeostasis and affects the response to therapy.

Identification of immune-related cells and genes in the breast invasive carcinoma microenvironment.

The clinical prognosis of breast cancer is closely related to its infiltrating immune status. The study sought to explore tumor-infiltrating immune cells (TILs) and immune-associated genes in the tumor microenvironment of breast invasive carcinoma (BRCA). The ESTIMATE algorithm was used to evaluate the microenvironment of breast cancer patients in TCGA database.

NIR Laser Responsive Nanoparticles for Ovarian Cancer Targeted Combination Therapy with Dual-Modal Imaging Guidance.

Purpose: Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating BiS, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography).

Methods And Results: The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties.

Highly Enantioselective CuAAC of Functional Tertiary Alcohols Featuring an Ethynyl Group and Their Kinetic Resolution.

The first highly enantioselective Cu -catalyzed azide-alkyne cycloaddition (CuAAC) of tertiary alcohols and their kinetic resolution is reported. This approach allows facile access to multifunctional tertiary alcohols featuring an α-ethynyl or α-triazole moiety, and represents the first successful kinetic resolution of racemates with a tetrasubstituted carbon stereocenter via CuAAC. Newly developed pyridinebisoxazoline (PYBOX) ligands with a C4 phosphonate group play a key role.

Enantioselective Cu(I)-Catalyzed Cycloaddition of Prochiral Diazides with Terminal or 1-Iodoalkynes.

We report an unprecedented highly enantioselective desymmetric Cu(I)-catalyzed 1,3-dipolar cycloaddition of diazides with terminal alkynes and 1-iodoalkynes, affording tertiary alcohols bearing a 1,2,3-triazole moiety in high yield and excellent ee value. PYBOX ligands with a C4 shielding group once again show the promising ability to achieve higher enantioselectivity.

Homologous recombination enhances radioresistance in hypopharyngeal cancer cell line by targeting DNA damage response.

Background: Radiotherapy is a central treatment option for hypopharyngeal squamous cell carcinoma, but the prognoses of patients treated with radiotherapy only are not satisfactory due to radioresistance. The underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of radioresistance are currently unavailable.

Methods: In this study, we first established a specifically radioresistant FaDu cell line by repeated exposure to ionizing radiation with a total dose of 60 Gy (FaDu-RR).

RPA1 downregulation enhances nasopharyngeal cancer radiosensitivity via blocking RAD51 to the DNA damage site.

Background/aim: Nasopharyngeal cancer (NPC) has a high local recurrence rate due to its resistance to ionizing radiation (IR). Replication protein A1 (RPA1) is one of the main elements in the homologous repair (HR) pathway, which is closely associated with the repair of DNA double strand breaks (DDBs). Studies on the relationship between RPA1 and the radiosensitivity of NPC are substantially limited.

Depletion of NFBD1/MDC1 Induces Apoptosis in Nasopharyngeal Carcinoma Cells Through the p53-ROS-Mitochondrial Pathway.

NFBD1, a signal amplifier of the p53 pathway, is vital for protecting cells from p53-mediated apoptosis and the early phase of DNA damage response under normal culture conditions. Here we investigated its expression in patients with nasopharyngeal carcinoma (NPC), and we describe the biological functions of the NFBD1 gene. We found that NFBD1 mRNA and protein were more highly expressed in NPC tissues than in nontumorous tissues.

2-Methoxyestradiol inhibits the proliferation and migration and reduces the radioresistance of nasopharyngeal carcinoma CNE-2 stem cells via NF-κB/HIF-1 signaling pathway inactivation and EMT reversal.

Accumulating evidence indicates that cancer stem cells (CSCs) are a source of resistance to radiation therapy (RT); however, the mechanism of this resistance remains unclear. 2-Methoxyestradiol (2-ME2) is a metabolic product of estrogen in the body. Recent studies have found that 2-ME2 regulates the activation of transcription factors, including nuclear factor (NF)-κB/hypoxia-inducible factor-1 (HIF-1), thus contributing to tumor cell apoptosis and chemosensitivity.

ALEX1 may be a novel biomarker for human cervical squamous cell carcinoma.

Unlabelled: The armadillo repeat proteins were first found in armadillo gene of Drosophila. Since then a number of proteins containing armadillo repeats have been noticed and studied. These proteins that consist of 6 to 13 armadillo repeat domains are classified as family of armadillo repeat proteins.

Catalytic asymmetric sulfenylation to structurally diverse dithioketals.

We report the first example of the highly enantioselective synthesis of structurally diverse chiral dithioketals via asymmetric sulfenylation of various types of S-based nucleophiles, catalyzed by a cheap cinchona alkaloid derivative, dihydroquinine.

Michael Addition Catalyzed by Chiral Secondary Amine Phosphoramide Using Fluorinated Silyl Enol Ethers: Formation of Quaternary Carbon Stereocenters.

A chiral secondary amine phosphoramide was developed and identified as a powerful catalyst for the Mukaiyama-Michael addition of fluorinated enol silyl ethers to tetrasubstituted olefins. The resulting products are obtained with high enantioselectivities and contain a quaternary carbon stereocenter bearing either a difluoroalkyl or monofluoroalkyl group.

Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells.

Lung cancer is the most common cause of cancer-related death in the world. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC); non small cell lung carcinoma (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma, Non small cell lung carcinoma accounts for about 80% of the total lung cancer cases. Dihydroartemisinin (DHA) inhibits cell proliferation and induces apoptosis in several cancer cell lines.

Effect of asphyxia on non-protein-bound iron and lipid peroxidation in newborn infants.

The effect of asphyxia on iron metabolism and lipid peroxidation in newborn infants with hypoxic-ischemic encephalopathy (HIE) was investigated. Non-protein-bound iron (NPBI) and lipid peroxidation (thiobarbituric-acid-reactive species; TBARS) in plasma and hematological iron indices were measured in 15 healthy newborn infants (mean gestational age 39 04 weeks, SD 1); 15 asphyxiated infants without neurological abnormalities (AS-HIE; mean gestational age 38.8 weeks, SD 0.

Effect of different durations of exercise on transferrin-bound iron uptake by rat erythroblast.

This study evaluated effects of different durations of exercise on transferrin receptor (TfR) expression on the membrane of rat erythroblasts. Female rats were assigned to six groups: 3, 6 and 12 months of strenuous exercise (swimming 2 h/day, 5 days/wk) groups and their corresponding controls. At the end of experiments, the erythroblasts were isolated for Tf binding assay and transferrin-bound iron (Tf-Fe) uptake.