Palladium-Catalyzed Enantioselective Cyclization of 1,6-Enynes to Access Chiral γ-Butyrolactam.

A palladium-catalyzed asymmetric chlorocyclization of 1,6-enynes has been described. Controlling the chloride ion concentration in the system by substrate design is the key to achieving asymmetric chlorinated cyclization. In the presence of Pd(PhCN)Cl and chiral phosphoramidite ligands, the reaction accesses diverse chiral ()-α-chloromethylene-γ-butyrolactams with excellent selectivity and enantioselectivity.

Electrochemical Oxidative Cascade Cyclization of Alkenyl Alcohols with External Nucleophiles to Access Amino- and Hydroxy-Functionalized -Heterocycles.

A convenient electrochemical oxidative cascade cyclization of alkenes equipped with pendant alcohols with general nucleophiles was developed. Using readily available diarylmethanimine and carboxylic acids as nucleophilic sources, a broad range of internal alkene and terminal alkene substrates could produce RCO- and ArCN-functionalized -heterocycles in moderate to high yields without the requirement for external oxidants and metals. These resulting products can subsequently be hydrolyzed to yield valuable NH- and OH-functionalized tetrahydrofurans and tetrahydropyranes under mild conditions.

CT and MRI bimodal radiomics for predicting EGFR status in NSCLC patients with brain metastases: A multicenter study.

Background: Leveraging the radiomics information from non-small cell lung cancer (NSCLC) primary lesion and brain metastasis (BM) to develop and validate a bimodal radiomics nomogram that can accurately predict epidermal growth factor receptor (EGFR) status.

Methods: A total of 309 NSCLC patients with BM from three independent centers were recruited. Among them, the patients of Center I were randomly allocated into the training and internal test cohorts in a 7:3 ratio.

generated CFCHN with 3-ylideneoxindoles to access CF-containing pyrazolo[1,5-]quinazolines derivatives.

Toward a selective and facile method for the synthesis of CF-containing pyrazolo[1,5-]quinazolines, we developed a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade involving generated CFCHN and 3-ylideneoxindoles with DBU as a base. The reaction is distinguished by its mild conditions, metal-free process, operational simplicity, and broad functional group tolerance, thus presenting a convenient protocol for the construction of pyrazolo[1,5-]quinazolines that are of interest in medicinal chemistry.

De Novo Synthesis of α-Ketoamides via Pd/TBD Synergistic Catalysis.

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge.

Hypomethylation-enhanced CRTC2 expression drives malignant phenotypes and primary resistance to immunotherapy in hepatocellular carcinoma.

The cyclic AMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a crucial regulator of hepatic lipid metabolism and gluconeogenesis and correlates with tumorigenesis. However, the mechanism through which CRTC2 regulates hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that increased CRTC2 expression predicted advanced tumor grade and stage, as well as worse prognosis in patients with HCC.

CRISPR/Cas9 screen reveals that targeting TRIM34 enhances ferroptosis sensitivity and augments immunotherapy efficacy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by complex heterogeneity and drug resistance. Resistance to ferroptosis is closely related to the progression of HCC. While HCC tumors vary in their sensitivity to ferroptosis, the precise factors underlying this heterogeneity remain unclear.

Palladium-Catalyzed Carbohalogenation of Olefins with Alkynyl Oxime Ethers: Rapid Access to Chlorine-Containing Isoxazoles.

A palladium-catalyzed carbohalogenation of olefins with alkynyl oxime ethers has been described, which provides efficient and practical access to various chlorine-containing isoxazoles. This method exhibits excellent regioselectivity, good functional group compatibility, and mild reaction conditions. The mechanistic studies suggest that the reaction proceeds via a stabilized π-benzyl palladium intermediate, which is essential for the formation of C(sp)-Cl bonds.

Hepatocyte Deubiquitinating Enzyme OTUD5 Deficiency is a Key Aggravator for Metabolic Dysfunction-Associated Steatohepatitis by Disturbing Mitochondrial Homeostasis.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a common chronic liver disease worldwide. No effective pharmacologic therapies for MASH have been developed; to develop such promising drugs, the underlying mechanisms regulating MASH need to be elucidated. Here, we aimed to determine the role of ovarian tumor domain-containing protein 5 (OTUD5) in MASH progression and identify a specific mechanism.

Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The tumor microenvironment (TME) contributes to the poor response of patients with HCC to current therapies, while tumor vascular endothelial cells (ECs) are fundamental TME components that significantly contribute to tumor progression. However, the specific functions and mechanisms of tumor vascular ECs in HCC remain unclear.

Thymidine kinase 1 drives hepatocellular carcinoma in enzyme-dependent and -independent manners.

Metabolic reprogramming plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the key drivers of metabolic reprogramming underlying HCC progression remain unclear. Using a large-scale transcriptomic database and survival correlation screening, we identify thymidine kinase 1 (TK1) as a key driver.

Impact of high-sensitivity troponin elevation and dynamic changes on 90-day mortality in patients with acute ischemic stroke after mechanical thrombectomy: results from an observational cohort.

Background: A study was undertaken to evaluate the impact of high-sensitivity cardiac troponin I (hs-cTnI) elevation and hs-cTnI dynamic changes on 90-day mortality in patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT).

Methods: Patients with AIS receiving MT were included in the study. Sixty hours after AIS onset, hs-cTnI levels were measured before and after MT to determine elevated and dynamic changes.

Research progress on the relationship between mitochondrial function and heart failure: A bibliometric study from 2002 to 2021.

Heart failure is one of the major public health problems in the world. In recent years, more and more attention has been paid to the relationship between heart failure and mitochondrial function. In the past 2 decades, a growing number of research papers in this field have been published.

Clinical Application of Thromboelastography in Acute Ischemic Stroke.

Acute ischemic stroke (AIS), characterized by high morbidity and mortality, has imposed a considerable burden on society. Despite rapid development in the treatment of AIS, there is still a high risk of recurrence. Furthermore, there is a time delay in waiting for the results of conventional coagulation tests in candidate patients for intravenous thrombolysis therapy.

Albumin Infusion May Improve the Prognosis of Critical COVID-19 Patients with Hypoalbuminemia in the Intensive Care Unit: A Retrospective Cohort Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused enormous mortality worldwide. Low albumin level is a risk factor for increasing mortality among patients in the intensive care unit (ICU). This study investigated the effect of albumin infusion on critical COVID-19 patients with hypoalbuminemia.

Etomidate elicits anti-tumor capacity by disrupting the JAK2/STAT3 signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading malignancy of the digestive system, especially in China. Although radiotherapy, chemotherapy, and transarterial chemoembolization have achieved tremendous success, surgical resection remains the primary treatment for HCC patients. Recent studies have shown that intravenous anesthetic drugs may affect the malignant behaviors of tumor cells, ultimately leading to differences in the postoperative prognosis of patients.

Pan-cancer analysis identifies as a novel prognostic marker associated with immune infiltration in lung adenocarcinoma through bioinformatics analysis.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy. However, the expression of cell division cycle-associated protein-3 () and its significance in LUAD remain unclear. In this study, we investigated the functional role of in LUAD through bioinformatics analysis and expected to provide a new direction for clinical treatment.

Palladium-Catalyzed Enantioselective Cyclization of 1,6-Enynes through Intramolecular Chlorine Transfer as a Novel Strategy for Asymmetric Halopalladation.

Palladium-catalyzed enantioselective cyclization of enynes has contributed significantly to the construction of chiral cyclic molecules. In contrast, the catalytic asymmetric cyclization involving halopalladation remains an unresolved challenge with the inevitable disturbance of the halide ions. Herein, an intramolecular chlorine transfer strategy is used to accomplish the enantioselective chloropalladation cyclization of 1,6-enynes.

Identification and Validation of Long Non-Coding RNA LCIIAR as a Biomarker in LUAD.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers.

Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma.

Objective: Upper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%-50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted.