Establishing and internally validating a predictive model for coronary heart disease incorporating triglyceride-glucose index, monocyte-to-high-density lipoprotein cholesterol ratio and conventional risk factors in patients experiencing chest pain and referred for invasive coronary angiography.

Background: Coronary heart disease (CHD) represents a severe form of ischemic cardiac condition that necessitates timely and accurate diagnosis. Although coronary angiography (CAG) remains widely used to detect CHD, healthcare facilities, medical expenses, and equipment technology often limit its availability. Therefore, it is imperative to identify a non-invasive diagnostic approach with high accuracy for CHD.

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry.

The association of 24-hour behavior rhythms with stroke among American adults with prediabetes/diabetes: evidence from NHANES 2011-2014.

Background: Emerging evidence suggests that circadian rhythms play a role in the regulation of cardiovascular diseases (CVDs). We aim to examine the relationship between the 24-hour behavior rhythms (activity-rest and feeding-fasting rhythms) and stroke.

Methods: The study included 3201 adult participants with prediabetes/diabetes from the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial.

Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up.

Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity.

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry.

Divergent Reactions of α-Diazo 1,3-Dicarbonyl Compounds with Allylic Carbonates Involving Ketene versus Carbene Intermediates Enabled by Cooperative Rh(II)/Pd(0) Dual Catalysis.

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that enabled divergent reactions of α-diazo 1,3-dicarbonyl compounds with allylic carbonates involving ketene versus carbene intermediates is described. The efficient synthesis of α-quaternary allylated β-keto-esters was accomplished by the Rh(II)/Pd(0) dual-catalysis allylic alkylation of α-diazo 1,3-dicarbonyl compounds. Alternatively, an unprecedented (1+4) annulation of α-diazo 1,3-dicarbonyl compounds with 2-(hydroxymethyl)allyl carbonates via Rh(II)/Pd(0) dual catalysis was also successfully developed, affording a wide variety of α-quaternary tetrahydrofurans in good to high yields.

Trends and Disparities in Diet Quality and Nutrient Intake among US Adults by Bodyweight Status.

The prevalence of obesity has been increasing in the US. Among the multifactorial contributors to obesity, dietary factors stand out as primary drivers. Using data from NHANES, we investigated the trends and disparities in diet quality and nutrient intake among US adults with different bodyweight statuses.

Antibody-drug conjugate monotherapy refines the oncological efficacy as compared to therapy of physicians' choices in advanced breast cancers: a systematic review and meta-analysis.

Background: Antibody-drug conjugate (ADC) is an emerging therapy that bestows advanced breast tumors with encouraging clinical activity and manageable toxicity; however, the outcomes of phase 2/3 randomized controlled trials (RCTs) are heterogeneous. Our study aims to assess the clinical utilities [i.e.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer.

Background: Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.

Methods: Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.

Electronegative clusters modulate folding status and RNA binding of unstructured RNA-binding proteins.

Electronegative clusters (ENCs) made up of acidic residues and/or phosphorylation sites are the most abundant repetitive sequences in RNA-binding proteins. Previous studies have indicated that ENCs inhibit RNA binding for structured RNA-binding domains (RBDs). However, this is not the case for the unstructured RBD in histone pre-mRNA stem-loop binding protein (SLBP).

Association of rest-activity circadian rhythm with chronic respiratory diseases, a cross-section survey from NHANES 2011-2014.

Objective: A growing number of studies have examined the 24-h rest-activity characteristics in relation to health outcomes. Up to now, few studies have paid attention to the role of rest-activity circadian rhythm in chronic respiratory diseases (CRDs); therefore, to fill this gap, our study innovatively explored the association of rest-activity circadian rhythm indices with CRDs.

Methods: A total of 7412 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this study.

The association of diet carbohydrates consumption with cognitive function among US older adults modification by daily fasting duration.

Dietary carbohydrate consumption was related to cognitive function. Whereas, there was no study investigate the association of dietary carbohydrate consumption with cognitive function modification by daily fasting duration. This study aims to examine the association between dietary carbohydrate consumption and cognitive function among participants with different daily fasting duration.

Molecular and structural basis of interactions of vitamin D3 hydroxyderivatives with aryl hydrocarbon receptor (AhR): An integrated experimental and computational study.

To better understand the molecular and structural basis underlying the interaction of vitamin D3 hydroxyderivatives with AhR, molecular simulation was used to probe the binding of 1,20(OH)D3, 1,25(OH)D3, 20,23(OH)D3 and 20(OH)D3 to AhR. qPCR showed that vitamin D3 derivatives stimulate expression of cyp1A1 and cyp1B1 genes that are downstream targets of AhR signaling. These secosteroids stimulated the translocation of the AhR to the nucleus, as measured by flow cytometry and western blotting.

IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation.

Background: Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization.

Chemical synthesis, biological activities and action on nuclear receptors of 20S(OH)D, 20S,25(OH)D, 20S,23S(OH)D and 20S,23R(OH)D.

New and more efficient routes of chemical synthesis of vitamin D (D) hydroxy (OH) metabolites, including 20S(OH)D, 20S,23S(OH)D and 20S,25(OH)D, that are endogenously produced in the human body by CYP11A1, and of 20S,23R(OH)D were established. The biological evaluation showed that these compounds exhibited similar properties to each other regarding inhibition of cell proliferation and induction of cell differentiation but with subtle and quantitative differences. They showed both overlapping and differential effects on T-cell immune activity.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

Background: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases.

Real-World Efficacy of Fulvestrant Monotherapy as the First Treatment or Maintenance Treatment in Patients with Metastatic Breast Cancer.

Background: Fulvestrant 500 mg monotherapy is recommended as the first-line endocrine treatment in postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). It is also used in MBC maintenance treatment. However, few studies have compared the efficacy of fulvestrant during the initial treatment with that during maintenance treatment.

Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study.

The epidemiologic correlation between the poor prognosis of SARS-CoV-2 infection and vitamin D deficiency has been observed worldwide, however, their molecular mechanisms are not fully understood. In this study, we used combined molecular docking, molecular dynamics simulations and binding free energy analyses to investigate the potentials of vitamin D3 and its hydroxyderivatives as TMPRSS2 inhibitor and to inhibit the SARS-CoV-2 receptor binding domain (RBD) binding to angiotensin-converting enzyme 2 (ACE2), as well as to unveil molecular and structural basis of 1,25(OH)D3 capability to inhibit ACE2 and SARS-CoV-2 RBD interactions. The results show that vitamin D3 and its hydroxyderivatives are favorable to bind active site of TMPRSS2 and the binding site(s) between ACE2 and SARS-CoV2-RBD, which indicate that vitamin D3 and its biologically active hydroxyderivatives can serve as TMPRSS2 inhibitor and can inhibit ACE2 binding of SARS-CoV-2 RBD to prevent SARS-CoV-2 entry.

Chemotherapy or endocrine therapy, first-line treatment for patients with hormone receptor-positive HER2-negative metastatic breast cancer in China: a real-world study.

Background: Although endocrine therapy (ET) is the preferred option for hormone receptor-positive HER2-negative metastatic breast cancer (HR+/HER2- MBC), chemotherapy (CT) is still commonly used. The objective of this real-world study was to present the actual choice of first-line treatment for patients with HR+/HER2- MBC and evaluate the consistency with guidelines in China.

Methods: Patients with HR+/HER2- MBC between 1996 and September 2018 were identified from of the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC).

Sam68 promotes hepatic gluconeogenesis via CRTC2.

Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes.

Vitamin D and lumisterol derivatives can act on liver X receptors (LXRs).

The interactions of derivatives of lumisterol (L3) and vitamin D3 (D3) with liver X receptors (LXRs) were investigated. Molecular docking using crystal structures of the ligand binding domains (LBDs) of LXRα and β revealed high docking scores for L3 and D3 hydroxymetabolites, similar to those of the natural ligands, predicting good binding to the receptor. RNA sequencing of murine dermal fibroblasts stimulated with D3-hydroxyderivatives revealed LXR as the second nuclear receptor pathway for several D3-hydroxyderivatives, including 1,25(OH)D3.