Synthesis of Dioxo-Azabicyclo[3.2.1]octanes via Hypervalent Iodine-Mediated Domino Reaction.

Bicyclo[3.2.1]octane (BCO) skeleton widely exists in natural products and biologically active molecules, whereas the development of convenient approaches to construct this structure remains a challenge.

Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.

DNA damage is considered to be a potentially unifying driver of ageing, and the stalling of DNA damage repair accelerates the cellular senescence. However, augmenting DNA repair has remained a great challenge due to the intricate repair mechanisms specific for multiple types of lesions. Herein, we miniaturized our modified detecting system for homologous recombination (HR) into a 96-well-based platform and performed a high-throughput chemical screen for FDA-approved drugs.

Serum exosomal miRNA promote glioma progression by targeting SOS1 via abscopal effect of radiation.

Introduction: Local exposure to ionizing radiation (IR) can induce changes in biological processes in distant tissues and organs. Exosomes are nanoscale vesicles that transport biomolecules, mediate communication between cells and tissues, and can affect the abscopal effects of radiotherapy.

Methods: Mice were treated with 8.

Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y receptor antagonists based on the scaffold hopping strategy. The optimized compound (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC: 0.

The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.

MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells.

KTN1 mediated unfolded protein response protects keratinocytes from ionizing radiation-induced DNA damage.

Background: The unfolded protein response (UPR) is one of the cytoprotective mechanisms against various stresses and essential for the normal function of skin. Skin injury caused by ionizing radiation (IR) is a common side effect of radiotherapy and it is unclear how UPR affects IR-induced skin injury.

Objectives: To verify the effect of UPR on IR-induced DNA damage in keratinocytes and the relation between an endoplasmic reticulum (ER) protein KTN1 and UPR.

Higher affinities of fibers with cell receptors increase the infection capacity and virulence of human adenovirus type 7 and type 55 compared to type 3.

HAdV-3, -7, and -55 are the predominant types causing acute respiratory disease outbreaks and can lead to severe and fatal pneumonia in children and adults. In recent years, emerging or re-emerging strains of HAdV-7 and HAdV-55 have caused multiple outbreaks globally in both civilian and military populations, drawing increased attention. Clinical studies have reported that HAdV-7 and HAdV-55 cause more severe pneumonia than HAdV-3.

Synthesis of Oxazolidines and Dihydroxazines via Cyclization of α-Aminated Ketones.

A new approach to oxazolidines and dihydroxazines was developed by regioselective cyclization of α-aminated ketones under transition metal-free conditions. Oxazolidine derivatives were generated in the presence of chloro benziodoxole and TFA, while dihydroxazines were formed without a hypervalent iodine reagent. The reaction was performed under room temperature and gave the products in good to excellent yields.

Injectable cell-targeting fiber rods to promote lipolysis and regulate inflammation for obesity treatment.

Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of R fiber rods loaded with chrysin and grafted with hyaluronic acid and F fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs).

The role of miR-4469 as a tumor suppressor regulating inflammatory cell infiltration in colorectal cancer.

Background: MicroRNA (miRNA) regulates gene expression posttranscriptionally, and some of them function in tumor suppression and can be used in drug development. As a result, identifying and screening miRNAs that suppress tumors would be a significant addition to tumor treatment.

Methods: In this study, we analyzed the miRNA expression profile of colorectal cancer (CRC), constructed a negative regulatory network of the miRNA-target genes, and identified miR-4469 as one of the key tumor suppressors miRNAs.

Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer miR-375/miR-365a-3p/NF-κB Axis.

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells.

Synthesis of Dihydroxazines and Fluorinated Oxazepanes Using a Hypervalent Fluoroiodine Reagent.

Application of a hypervalent fluoroiodane for the regiodivergent synthesis of dihydroxazines and fluorinated oxazepanes from allylaminoethanol was investigated. The reaction was carried out under mild conditions and gave the products in moderate to good yields. The selectivity of this transformation is controlled by the substituents of the allylaminoethanol.

Synergistic Treatment of Obesity via Locally Promoting Beige Adipogenesis and Antioxidative Defense in Adipose Tissues.

Obesity is a primary risk factor for type 2 diabetes, cardiovascular diseases, cancer, and other chronic diseases. Current antiobesity medications need frequent administration and show limited efficacy with severe side effects. Herein, browning agent rosiglitazone (Rsg) and antioxidant manganese tetroxide nanoparticles (MnNPs, around 250 nm) are integrated into electrospun short fibers (SF@Rsg-Mn) with a 1.

Divergent synthesis of oxazolidines and morpholines PhI(OAc)-mediated difunctionalization of alkenes.

Herein we describe the PhI(OAc)2-mediated 1,1- and 1,2-difunctionalization of alkenes with N-tosyl amino alcohols to form oxazolidine and morpholine derivatives. This transformation was realized under mild reaction conditions and allows application to various substrates furnishing the multi-substituted oxazolidines and morpholines with yields up to 98%. A deuterium-labeling experiment was carried out and the result indicated that a phenyl group migration occurred to generate oxazolidine products.

Recent progress of 1,1-difunctionalization of olefins.

Olefins are a very important class of compounds and broadly used in the construction of various synthetic building blocks and practical industrial production. The difunctionalization of olefins provides one of the most powerful methods for the C-C or C-X bond formation with a rapid increase of the molecular complexity and synthetic value economically and effectively. Compared with the vigorous growth and abundant achievements of 1,2-difunctionalization of olefins, 1,1-difunctionalization is a relatively emerging and inadequately exploited research direction, despite being tremendously attractive from synthetic perspectives.

Exosomal Small RNA Sequencing Uncovers Dose-Specific MiRNA Markers for Ionizing Radiation Exposure.

Introduction: Acute exposure to ionizing radiation (IR) is hazardous or even lethal. Accurate estimation of the doses of IR exposure is critical to wisely determining the following treatments. Exosomes are nanoscale vesicles harboring biomolecules and mediate the communications among cells and tissues to influence biological processes.

Electrocatalytically Active Fe-(O-C ) Single-Atom Sites for Efficient Reduction of Nitrogen to Ammonia.

Single-atom catalysts have demonstrated their superiority over other types of catalysts for various reactions. However, the reported nitrogen reduction reaction single-atom electrocatalysts for the nitrogen reduction reaction exclusively utilize metal-nitrogen or metal-carbon coordination configurations as catalytic active sites. Here, we report a Fe single-atom electrocatalyst supported on low-cost, nitrogen-free lignocellulose-derived carbon.

Chloroquine promotes gefitinib‑induced apoptosis by inhibiting protective autophagy in cutaneous squamous cell carcinoma.

Aberrant expression of the epidermal growth factor receptor (EGFR) plays vital roles in tumor development and progression. In the present study, ultraviolet irradiation induced the upregulation of EGFR in skin‑derived keratinocytes, which may contribute to the development of cutaneous squamous cell carcinoma (CSCC). This was supported by the high expression of EGFR in CSCC clinical samples.

Hypervalent iodane mediated reactions of N-acetyl enamines for the synthesis of oxazoles and imidazoles.

A hypervalent iodane reagent used for the intramolecular cyclization of N-acetyl enamines and intermolecular cyclocondensation of enamines and nitriles was investigated. The reaction was performed under mild conditions and gave oxazoles and imidazoles, respectively, in moderate to excellent yields. This transformation exhibits good reactivity, selectivity and functional group tolerance.

Magnetic properties and correlation with heavy metals in mangrove sediments, the case study on the coast of Fujian, China.

To characterize the magnetic signature of sediment heavy metal contamination and identify sources of heavy metals in mangroves, 83 sediment specimens were collected from three mangroves in Fujian, China; various magnetic parameters and heavy metal concentrations were then determined. Variation in magnetic magnetization among specimens was linked to changes in pseudo-single-domain magnetite. Average values of Co, Cu, Ni, and Zn (but not Cr or Pb) were slightly lower than background levels.

Assessment of the therapeutic accuracy of cone beam computed tomography-guided nasopharyngeal carcinoma radiotherapy.

The aim of the present study was to determine the ability of cone beam computed tomography (CBCT) to improve the accuracy of nasopharyngeal carcinoma (NPC) radiotherapy by analyzing the setup and inter-fraction errors at different levels and directions of the target volumes. A total of 113 patients with NPC who were undergoing intensity-modulated radiotherapy were recruited for the present study. Each patient had at least three CBCT exams prior to the start of radiation therapy.

Gefitinib-mediated apoptosis is enhanced via inhibition of autophagy by chloroquine diphosphate in cutaneous squamous cell carcinoma cells.

The development of cutaneous squamous cell carcinoma (cSCC) is associated with activation of the epidermal growth factor receptor (EGFR). EGFR-targeting presents a promising strategy for improving therapeutic efficacy. However, recent studies have suggested that tumours overexpressing EGFR depend on autophagy for survival and exhibit resistance to EGFR-targeting drugs.

MicroRNA-664 functions as an oncogene in cutaneous squamous cell carcinomas (cSCC) via suppressing interferon regulatory factor 2.

Background: Aberrant expression of microRNA-664 was involved in tumor growth and metastasis of various cancers. The specific role of miR-664 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated.

Objective: The present study aimed to investigate the molecular mechanisms underpinning of cSCC development and provide translational insights for future therapeutics.