Ruthenium-Catalyzed C–H Arylation of Aromatic Acids with <i>ortho</i>-Haloaniline To Access Phenanthridinones

Phenanthridinone is a significant moiety in pharmaceutical and material science; thus, it is highly desirable to develop an efficient and robust method to construct phenanthridinone from readily available starting materials. Herein, we report a Ru-catalyzed C–H arylation of aromatic carboxylic acids with ortho-haloanilines, followed by intramolecular dehydration to afford phenanthridinones in high yields

Data_Sheet_1_Association of caffeine intake with all-cause and cardiovascular mortality in elderly patients with hypertension.XLSX

BackgroundCaffeine is widely consumed not only in coffee but also in soft drinks and tea. However, the long-term health effects of caffeine are still controversial, especially in people with high cardiovascular risk such as elderly patients with hypertension.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey 2003–2018. Caffeine intake was calculated by two 24-h dietary recall interviews. Complex sampling-weighted multivariable Cox proportional hazards models were used to compare the hazard ratios (HRs) of all-cause and cardiovascular mortality in elderly hypertensive patients with different caffeine intake (ResultsThis study included 6,076 elderly hypertensive patients. The mean ± standard error follow-up duration was 6.86 ± 0.12 years. During this period, a total of 2,200 all-cause deaths occurred, of which 765 were cardiovascular deaths. Taking patients with caffeine intake ConclusionModerate caffeine intake is associated with reduced risk of all-cause and cardiovascular mortality in elderly hypertensive patients.</p

Genotype distributions of the TPCN2 rs3829241, rs1551305 and rs3750965 polymorphisms in controls and T2DM patients.

<p>Genotype distributions of the TPCN2 rs3829241, rs1551305 and rs3750965 polymorphisms in controls and T2DM patients.</p

Comparison of clinical and biochemistry characteristics between the two groups.

<p>Comparison of clinical and biochemistry characteristics between the two groups.</p

LD between 4 SNPs in the study cohort.

<p>LD between 4 SNPs in the study cohort.</p

Main characteristics of the 3 SNPs.

<p>Main characteristics of the 3 SNPs.</p

Allele frequencies of TPCN2 polymorphisms.

<p>Allele frequencies of TPCN2 polymorphisms.</p

Comparisons of quantitative traits among the three rs1551305 genotypes.

<p>Comparisons of quantitative traits among the three rs1551305 genotypes.</p

Highly Sensitive Method for Specific, Brief, and Economical Detection of Glycoproteins in Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis by the Synthesis of a New Hydrazide Derivative

A new hydrazide derivative was synthesized and used for the first time as a specific, brief, and economical probe to selectively visualize glycoproteins in 1-D and 2-D sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with high sensitivity. The detection limit of the newly developed staining method is 2- and 4-fold higher than that of the widely used Pro-Q Emerald 300 and 488 stains, respectively

Raw images of WB and IHC assays in article "Suppressing Aberrant Hedgehog Pathway and Overcoming Resistance to Smoothened Antagonists via Targeting Super-enhancer-driven Transcriptional Dependencies"

Aberrant activation of Hedgehog (Hh) signaling pathway plays important roles in both oncogenesis and targeted therapy of many cancers. The clinical application of FDA-approved Hh-targeted Smoothened inhibitor (SMOi) drugs is hindered due to the emergence of various primary or acquired drug resistance, indicating the need of novel anti-Hh therapies. Our previous studies demonstrate that epigenetic/transcriptional targeted therapies represent a promising direction for anti-Hh drug development. In this study, we identified CDK9 and CDK12, two transcription elongation regulators, as novel therapeutic targets for antagonizing the aberrant Hh pathway and overcoming SMOi resistance. CDK9 inhibition and CDK12 inhibition exhibited similarly potent anti-Hh activities when treating various SMOi responsive or resistant Hh-driven tumor models as previously reported BET inhibition or CDK7 inhibition. We also utilized SHH-subtype medulloblastoma (SHH-MB) as the representative Hh-driven cancer model to perform Super-enhancer (SE) analysis and elucidate the crucial roles of SE in Hh-driven oncogenesis and above-mentioned anti-Hh epigenetic/transcriptional targeted therapies. Furthermore, we identified IRS1, encoding a critical component and cytoplasmic adaptor protein of the IGF pathway, as an oncogenic Hh-driven SE target gene and effective therapeutic target of multiple Hh-driven tumor models, including the SMOi-resistant ones. Collectively, our study demonstrates that the SE-driven transcriptional dependencies represent promising therapeutic vulnerabilities for suppressing the aberrant Hh pathway and overcoming the SMOi resistance. As CDK9 inhibitor and IRS inhibitor drugs have already entered human clinical trials for cancer treatment, our study provides comprehensive preclinical support for expanding their trials to Hh-driven cancers in near future.</p