Photocatalytic Decarboxylative Coupling of Arylacetic Acids with Aromatic Aldehydes

An efficient protocol was proposed for the preparation of secondary alcohols in good to excellent yields via photoredox-catalyzed decarboxylative couplings between readily available arylacetic acids and a variety of less reactive (hetero)aromatic aldehydes. The formation of carbanion is the key intermediate in this reaction. Various substituted arylacetic acids and aldehydes were all compatible with this transformation under mild reaction conditions. Furthermore, the current protocol was successfully applied to the direct alcoholization of several drug acids

Table1_Multiple epigenetic modification profiles reveal the tumor immune microenvironment and clinical outcomes of uveal melanoma.XLSX

Uveal melanoma (UM) is an aggressive intraocular cancer that, in 50% of cases, spreads to the patient’s other systems. The exact cause of the increased metastatic rate is still unknown. Methylation and immune response, metastasis, and the expansion of cancer cells are closely related. Additionally, proteins linked to RNA methylation have come to light as possible cancer treatment targets. However, the relationship between methylation-related genes (MRGs) and the tumor microenvironment (TME) is still not understood. The goal of this work was to discover important MRGs and create a signature for UM patients’ prognosis prediction. Using two different data sets, we examined the MRG expression patterns in the transcriptional and genomic regions of 106 UM samples. We discovered a connection between the clinicopathological traits of the patients, their prognosis, the capability of TME cells to infiltrate, and various MRG changes. Following that, we developed an MRGs signature to forecast prognosis, and we evaluated the model’s precision in patients with UM. We grouped the patients into multiple categories based on their clinical traits, looked at the survival rates for various groups within various groupings, and tested their accuracy. Additionally, to increase the practical usability of the MRGs model, we created a very accurate nomogram. TIDE scores were higher in the low-risk group. We go over how MGRs could impact UM’s TME, immunotherapy responsiveness, prognosis, and clinically significant features. We looked for different chemotherapeutic drugs and cutting-edge targeted agents for patients in diverse subgroups in order to better understand MRGs in UM. This helped in the creation of customized therapy to open new doors. We could also further research the prognosis and develop more efficient immunotherapy regimens.</p

DataSheet2_DNA methylation regulator-mediated modification pattern defines tumor microenvironment immune infiltration landscape in colon cancer.xlsx

Emerging evidence implies a non-negligible role of DNA methylation in tumor immunity, however, its comprehensive impact on tumor microenvironment (TME) formation and immune activation remains unclear. In this study, we integrated 24 DNA methylation regulators among 754 colon cancer patients to distinguish different modification patterns via an unsupervised clustering method, and explore their TME immune characteristics. Three DNA methylation modification patterns with distinct prognosis and biological behaviors were identified, consistent with three known phenotypes of immune-inflamed, immune-excluded, and immune-desert. We then determined a DNA methylation gene signature and constructed a DNA methylation score (DMS) to quantify modification patterns individually through principal component analysis algorithms. DMS-low group had characteristics of specific molecular subtypes, including microsatellite instability, CpG island methylator phenotype positive, and mutant BRAF, presented by increased mutation burden, activation of DNA damage repair and immune-related pathways, highly TME immune cells infiltration, and hence, a preferable prognosis. Further, low DMS was also demonstrated to be correlated to better response and prolonged survival of anti-PD-L1 antibody, indicating that DMS could be considered as an effective predictive tool for immunotherapy. In conclusion, our work presented a landscape of different DNA methylation modification patterns, and their vital role in the formation of TME diversity and complexity, which could help to enhance understanding of TME immune infiltration characteristics and more importantly, guide immunotherapy strategies more effectively and personalized.</p

DataSheet1_DNA methylation regulator-mediated modification pattern defines tumor microenvironment immune infiltration landscape in colon cancer.docx

Emerging evidence implies a non-negligible role of DNA methylation in tumor immunity, however, its comprehensive impact on tumor microenvironment (TME) formation and immune activation remains unclear. In this study, we integrated 24 DNA methylation regulators among 754 colon cancer patients to distinguish different modification patterns via an unsupervised clustering method, and explore their TME immune characteristics. Three DNA methylation modification patterns with distinct prognosis and biological behaviors were identified, consistent with three known phenotypes of immune-inflamed, immune-excluded, and immune-desert. We then determined a DNA methylation gene signature and constructed a DNA methylation score (DMS) to quantify modification patterns individually through principal component analysis algorithms. DMS-low group had characteristics of specific molecular subtypes, including microsatellite instability, CpG island methylator phenotype positive, and mutant BRAF, presented by increased mutation burden, activation of DNA damage repair and immune-related pathways, highly TME immune cells infiltration, and hence, a preferable prognosis. Further, low DMS was also demonstrated to be correlated to better response and prolonged survival of anti-PD-L1 antibody, indicating that DMS could be considered as an effective predictive tool for immunotherapy. In conclusion, our work presented a landscape of different DNA methylation modification patterns, and their vital role in the formation of TME diversity and complexity, which could help to enhance understanding of TME immune infiltration characteristics and more importantly, guide immunotherapy strategies more effectively and personalized.</p

Palladium-Catalyzed Direct C–H Carbonylation of Free Primary Benzylamines: A Synthesis of Benzolactams

A protocol for palladium-catalyzed C–H carbonylation of readily available free primary benzylamines using NH₂ as the chelating group under an atmospheric pressure of CO has been achieved, providing a general, atom- and step-economic approach to benzolactams, an important structural motif found in many biologically active compounds. Application of this new method is also exemplified in the concise syntheses of two bioactive molecules

Copper-Catalyzed Cascade Radical Addition–Cyclization Halogen Atom Transfer between Alkynes and Unsaturated α‑Halogenocarbonyls

A Cu-catalyzed cascade radical addition/cyclization/halogen atom transfer between alkynes and α-halogeno-γ, δ-unsaturated carbonyl compounds for the synthesis of various substituted cyclopentenes is described. Since up to four Csp³–Csp² bonds, two Csp³–Br bonds, and two carbocycles can be established in a single reaction, this 100% atom-efficient reaction exhibits the advantages of wide substrate scope, high functional group tolerance, and step-economics, and it offers an entry of the atom transfer radical addition/cyclization (tandem ATRA-ATRC) process to the synthesis of substituted cyclopentenes

A Cascade Phosphinoylation/Cyclization/Desulfonylation Process for the Synthesis of 3‑Phosphinoylindoles

3-Phosphinoylindole derivatives play important roles as pharmaceutical drugs and ligands. A new method for the synthesis of 3-phosphinoylindole derivatives has been achieved through silver-mediated cycloaddition between N-Ts-2-alkynylaniline derivatives and H-phosphine oxides. This transformation offers a straightforward route to the formation of the C–P bond, indole ring, and desulfonylation in one step

Specificity of E₂-BSA-FITC binding on BMMs.

<p>Cells were incubated for 15₂-BSA-FITC (1×10⁻⁶ M) in the absence (control) or in the presence of a 10-fold excess of different unlabeled materials: 17β-estradiol (E₂), E₂-BSA, tamoxifen (Ta), ICI 182780 (ICI), or G-15. Fluorescence intensity was analyzed by flow cytometry. The results were verified by at least three independent experiments.</p

Cascade Phosphinoylation/Cyclization/Isomerization Process for the Synthesis of 2‑Phosphinoyl‑9<i>H</i>‑pyrrolo[1,2‑<i>a</i>]indoles

Pyrrolo­[1,2-<i>a</i>]­indole is a common structural motif found in many natural products and pharmaceuticals. A silver-mediated oxidative phosphinoylation of <i>N</i>-propargyl-substituted indoles was used to construct a variety of 2-phosphinoyl-9<i>H</i>-pyrrolo­[1,2-<i>a</i>]­indoles under mild conditions. This transformation offers a straightforward route to the formation of the C–P bond, cyclization, and isomerization in one step

Detection of membrane estrogen receptors in BMMs.

<p>(A) Flow cytometry and (B) confocal laser scanning microscopy analyses of membrane estrogen receptors in BMMs. Intact cells labeled with E₂-BSA-FITC or BSA-FITC alone as a control. For GPR30 detection, intact cells were pretreated with anti-GPR30 followed by FITC-conjugated secondary antibody. (C) Western blotting analyses of GPR30 protein from the membrane (mem), cytoplasmic (cyt), or nuclear (nu) fractions of BMMs. The results were verified by at least three independent experiments. The bar indicates 10 µm.</p