Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3-year survival update and multi-omics analysis.

Background: Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi-centre phase II study. This report updates 3-year survival outcomes and multi-omics analysis to identify potential response biomarkers.

Methods: Forty-three intention-to-treat (ITT) patients received intravenous administration of atezolizumab and bevacizumab every 3 weeks.

Wave aberration corrections in PSF ellipticity measurements of astronomical telescopes using a multi-objective optimization.

The weak gravitational lensing (WGL) produces a shear effect on the observed galactic ellipticity that is much smaller than the endogenous ellipticity of the galaxy itself. Achieving such a high-level astronomical observation requires the superior performance of telescopes. To ensure the optical properties of telescopes to be competent in WGL detections, it is very necessary to measure point spread function (PSF) ellipticity of telescopes in labs.

Design of low polarization off-axis three-mirror reflective optical systems.

Off-axis optical systems have several important advantages over on-axis ones. However, high polarization aberrations, which play important roles in many applications, become critical disadvantages of off-axis systems. Thanks to the seven free design parameters, three-mirror reflective systems have a good potential to achieve low polarization.

Systemic administration of STING agonist promotes myeloid cells maturation and antitumor immunity through regulating hematopoietic stem and progenitor cell fate.

STING is a pivotal mediator of effective innate and adaptive anti-tumor immunity; however, intratumoral administration of STING agonists have shown limited therapeutic benefit in clinical trials. The systemic effect of the intravenous delivery of STING agonists in cancer is not well-defined. Here, we demonstrated that systemic administration of STING agonist inhibited melanoma growth, improved inflammatory effector cell infiltration, and induced bone marrow mobilization and extramedullary hematopoiesis, causing widespread changes in immune components in the peripheral blood.

A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.

The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma.

Photoredox catalytic radical fluorosulfonylation of olefins enabled by a bench-stable redox-active fluorosulfonyl radical precursor.

Sulfonyl fluorides have attracted considerable and growing research interests from various disciplines, which raises a high demand for novel and effective methods to access this class of compounds. Radical flurosulfonylation is recently emerging as a promising approach for the synthesis of sulfonyl fluorides. However, the scope of applicable substrate and reaction types are severely restricted by limited known radical reagents.

Erratum: MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways: Erratum.

[This corrects the article DOI: 10.7150/thno.30516.

Alignment algorithm of nonsymmetric off-axis reflective astronomical telescopes based on the modified third-order nodal aberration theory.

For pupil-offset off-axis reflective astronomical telescopes with designed tilts and decenters, owing to the absence of symmetry, axial and lateral misalignments exhibit strong coupling. The astigmatic and coma aberration fields of the misaligned optical systems are not only effected by lateral misalignments but also closely related to axial misalignments. However, the traditional misalignment algorithm based on nodal aberration theory (NAT) usually ignore the effect of axial misalignments on the aberration fields of optical systems when constructing calculation models.

Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment.

Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress from optical coherence tomography (OCT) is hereby developed. All intermediate lesions from a previous OCT study were enrolled.

EZH2 Inhibitor Enhances the STING Agonist‒Induced Antitumor Immunity in Melanoma.

STING agonists are a new class of drugs for cancer immunotherapy that activate both innate and adaptive antitumor immunity. Recently, multiple clinical trials of STING agonists have been conducted in hematological malignancies and solid tumors. However, STING is commonly suppressed in melanoma through mechanisms that remain unclear.

Introducing A New Class of Sulfonyl Fluoride Hubs via Radical Chloro-Fluorosulfonylation of Alkynes.

Sulfonyl fluorides have widespread applications in many important fields, including ligation chemistry, chemical biology, and drug discovery. Therefore, new methods to increase the synthetic efficiency and expand the available structures of sulfonyl fluorides are highly in demand. Here, we introduce a new and powerful class of sulfonyl fluoride hubs, β-chloro alkenylsulfonyl fluorides (BCASF), which can be constructed via radical chloro-fluorosulfonyl difunctionalization of alkynes under photoredox conditions.

Radical Fluorosulfonylation: Accessing Alkenyl Sulfonyl Fluorides from Alkenes.

Sulfonyl fluorides have widespread applications in many fields. In particular, their unique biological activity has drawn considerable research interest in the context of chemical biology and drug discovery in the past years. Therefore, new and efficient methods for the synthesis of sulfonyl fluorides are highly in demand.

Decarboxylative thiolation of redox-active esters to free thiols and further diversification.

Thiols are important precursors for the synthesis of a variety of pharmaceutically important sulfur-containing compounds. In view of the versatile reactivity of free thiols, here we report the development of a visible light-mediated direct decarboxylative thiolation reaction of alkyl redox-active esters to free thiols based on the abundant carboxylic acid feedstock. This transformation is applicable to various carboxylic acids, including primary, secondary, and tertiary acids as well as natural products and drugs, forging a general and facile access to free thiols with diverse structures.

Decarboxylative Thiolation of Redox-Active Esters to Thioesters by Merging Photoredox and Copper Catalysis.

Thioesters and related thiols are critically important to biological systems and also widely employed in the synthesis of pharmaceutically important molecules and polymeric materials. However, known synthetic methods often suffer from the disadvantage of being specific only to certain substrates. Herein, we describe a facile decarboxylative thioesterification of alkyl acid derived redox-active esters by merging photoredox catalysis and copper catalysis.

Metal-free dehydrosulfurization of thioamides to nitriles under visible light.

A visible light-mediated, metal-free dehydrosulfurization reaction of thioamides to nitriles is described. This reaction features high yields, mild reaction conditions, and the use of a cheap organic dye as the photoredox catalyst and air as the oxidant.

A Functional Synonymous Variant in Is Associated with Better Survival in Acral Melanoma.

: Polymorphisms of genes in the platelet-derived growth factor (PDGF) signaling pathway have been found to predict cutaneous melanoma (CM) survival, but their clinical effects in acral melanoma (AM) patients have not been explored. The aim of this study was to characterize the functional effect of the tag single-nucleotide polymorphism (SNP) rs2228230:C>T and assess its association with clinical outcomes in AM patients. : The effect of rs2228230:C>T on mRNA structures and codon usage values were evaluated using analyses.

Visible-Light-Induced Deaminative Thioesterification of Amino Acid Derived Katritzky Salts via Electron Donor-Acceptor Complex Formation.

A visible-light-mediated deaminative thioesterification of amino acid derived Katritzky salts with thiobenzoic acid has been developed, which provides a novel synthetic method for the synthesis of α-mercapto acid derivatives under mild conditions. This photoredox catalyst-free generation of alkyl radicals via C-N bond cleavage is enabled by the formation of an electron-donor-acceptor (EDA) complex between the Katritzky salt and thiobenzoic acid anion, which represents a new entry for EDA complex chemistry.

A rapid access to aliphatic sulfonyl fluorides.

The past few years have witnessed a fast-growing research interest on the study of sulfonyl fluorides as reactive probes in chemical biology and molecular pharmacology, which raises an urgent need for the development of effective synthetic methods to expand the toolkit. Herein, we present the invention of a facile and general approach for the synthesis of aliphatic sulfonyl fluorides via visible-light-mediated decarboxylative fluorosulfonylethylation. The method is based on abundant carboxylic acid feed stock, applicable to various alkyl carboxylic acids including primary, secondary, and tertiary acids, and is also suitable for the modification of natural products like amino acids, peptides, as well as drugs, forging a rapid, metal-free approach to build sulfonyl fluoride compound libraries of considerable structural diversity.

Identification of a functional polymorphism within the 3'-untranslated region of denticleless E3 ubiquitin protein ligase homolog associated with survival in acral melanoma.

Background: High expression of denticleless E3 ubiquitin protein ligase homologue (DTL) correlates with poor disease-free survival and overall survival in cutaneous melanoma, but the molecular features and clinical significance of this gene in acral melanoma (AM) remain unclear.

Methods: The expression levels of DTL were compared between AM and benign melanocytic nevi using existing Gene Expression Omnibus data and validated in fresh frozen tissues. Two candidate tag single-nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'UTR) of DTL in patients with AM were sequenced and analysed for their association with survival in a discovery cohort (n = 570), and the significant SNP was subjected to a replication cohort (n = 201).

miR-let-7b and miR-let-7c suppress tumourigenesis of human mucosal melanoma and enhance the sensitivity to chemotherapy.

Background: Mucosal melanoma with poor prognosis is a common histopathologic subtype of melanoma among Chinese and other Asian peoples. Regulated microRNAs (miRNAs) have been reported as oncogenes or tumour suppressors in melanoma. However, the roles of specific miRNAs in mucosal melanoma remain largely unknown.

RBCK1 promotes p53 degradation via ubiquitination in renal cell carcinoma.

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and the incidence of RCC continues to rise worldwide. Although RCC can be treated with surgery at an early stages, the five-year survival rates have been observed to decline dramatically in patients with advanced disease. Most patients with RCC treated with cytotoxic or targeted drugs will develop resistance at some point during therapy.

MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways.

Mucosal melanoma (MM) is the second most common melanoma subtype in Asian populations. Deregulation of microRNAs (miRNAs) has been extensively investigated in various cancers, including cutaneous melanoma. However, the roles of miRNAs in MM are unclear.

Potential Mutations in Uveal Melanoma Identified Using Targeted Next-Generation Sequencing.

Uveal melanoma (UM) is the most common intraocular malignancy and has a high tendency to metastasize to the liver. Although primary tumours can be successfully treated, there is currently no effective treatment for metastatic UM. To gain insight into the genetics of UM, we performed the targeted next-generation sequencing (NGS) of UM samples from a non-Caucasian population.