Casz1 and Znf101/Zfp961 differentially regulate apolipoproteins A1 and B, alter plasma lipoproteins, and reduce atherosclerosis.

High apolipoprotein B-containing (apoB-containing) low-density lipoproteins (LDLs) and low apoA1-containing high-density lipoproteins (HDLs) are associated with atherosclerotic cardiovascular diseases. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both significantly decreases apoB and increases apoA1 expression by inducing mRNA degradation of 2 different transcription factors, Znf101 and Casz1.

Covert perioperative strokes in older patients having non-cardiac surgery (PRECISION): a prospective cohort analysis.

Background: Perioperative strokes may promote postoperative neurocognitive dysfunction. We thus evaluated the incidence of postoperative strokes and the association between strokes and postoperative neurocognitive outcomes in older patients recovering from non-cardiac surgery.

Methods: PRECISION was a two-center prospective cohort study.

Single and joint exposure of Pb, Cd, Hg, Se, Cu, and Zn were associated with cognitive function of older adults.

Background: Impaired cognitive function following exposure to heavy metals has emerged as a significant global health concern. Nevertheless, the impact of combined exposure to multiple heavy metals on cognitive impairment remains unclear.

Objective: This study aimed to explore the association between multiple heavy metals exposure and cognitive function to provide theoretical evidence to guide prevention strategies.

Effect of boundary angle on aero-optical imaging deviation of the blunt-headed side-window vehicle.

This paper defines the intersection angle between the tangent plane at the boundary of aero-optical flow field and the body axis as the boundary angle and focuses on the influence of the boundary angle on the imaging deviation. This paper shows that the boundary angle of the aero-optical flow field is different at different flight conditions, which means the location of the zero value of imaging deviation is different.  With the increase of the line of sight angle, the imaging deviation decreases first and then increases in the opposite direction.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking.

Characterization of a novel picornavirus prevalent in experimental rabbits ().

Here, using viral metagenomic method a novel picornavirus (named UJS-2019picorna, GenBank accession number OP821762) was discovered in fecal and blood samples of experimental rabbits (). The complete genome size of UJS-2019picorna is 7832 bp excluding the poly(A)-tail, with GC content of 44.00% and a nucleotide composition of 28.

Influence of 0°-15° attack angle on aero-optical imaging deviation of a blunt-nose vehicle.

A turbulent flow field is created in a vehicle's head during high-speed flight, and this flow field causes the airborne optical system's receiving target images to be displaced, blurred, and jittered. In this study, we examine the impact of a 0°-15° angle of attack on the aero-optical imaging deviation. With the use of modeling and meshing software, we created a model of a conventional blunt-headed vehicle.

Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders.

Background: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

Methods: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors.

TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response.

Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging.

Integrating CD4 T cell help for therapeutic cancer vaccination in a preclinical head and neck cancer model.

Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered.

Risk Prediction in Patients With Heart Failure With Preserved Ejection Fraction Using Gene Expression Data and Machine Learning.

Heart failure with preserved ejection fraction (HFpEF) has become a major health issue because of its high mortality, high heterogeneity, and poor prognosis. Using genomic data to classify patients into different risk groups is a promising method to facilitate the identification of high-risk groups for further precision treatment. Here, we applied six machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), the least absolute shrinkage and selection operator (LASSO), random forest, ridge regression, support vector machine, and the conventional logistic regression model, to predict HFpEF risk and to identify subgroups at high risk of death based on gene expression data.

Epigenetic modulation of immunotherapy and implications in head and neck cancer.

Cancer progression is facilitated by distinct mechanisms developed by cancer cells to avoid immune recognition and clearance. The clinical application of immune checkpoint blockade (ICB), via monoclonal antibodies blocking PD-1/PD-L1 and CTLA4, has achieved promising durable therapeutic response in various cancer types, including recurrent and metastatic head and neck squamous cell carcinomas (HNSCC). HNSCC represents a rational target of ICB treatment given its relatively high mutation burden and the presence of immune infiltrates.

Personalized cancer vaccination in head and neck cancer.

Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC.

Dihydrotanshinone I inhibits ovarian cancer cell proliferation and migration by transcriptional repression of PIK3CA gene.

Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, was found to be the most effective compound of tanshen extracts against cancer cells in our previous studies. However, the therapeutic benefits and underlying mechanisms of DHTS on ovarian cancer remain uncertain. In this study, we demonstrated the cytocidal effects of DHTS on chemosensitive ovarian cancer cells with or without platinum-based chemotherapy.

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

Purpose: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.

Patients And Methods: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation.

Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis.

Melatonin has been recognized to slow breast cancer growth. The molecular mechanisms may involve long non-coding RNAs (lncRNAs). However, little is known on how melatonin affects lncRNA expression and function in breast cancer.

Sophorolipid biosynthesis and production from diverse hydrophilic and hydrophobic carbon substrates.

Sophorolipids (SLs), mainly synthesized by yeasts, were a sort of biosurfactant with the highest fermentation level at present. In recent years, SLs have drawn extensive attention for their excellent physiochemical properties and physiological activities. Besides, issues such as economics, sustainability, and use of renewable resources also stimulate the shift from chemical surfactants towards green or microbial-derived biosurfactants.

MiR-29 Regulates Lipogenesis in the Liver and Circulating Triglyceride Levels in a Sirt1-Dependent Manner.

MicroRNAs (miRNAs) are known regulators of lipid homeostasis. We recently demonstrated that miR-29 controls the levels of circulating cholesterol and triglycerides, but the mechanisms remained unknown. In the present study, we demonstrated that systemic delivery of locked nucleic acid inhibitor of miR-29 (LNA29) through subcutaneous injection effectively suppresses hepatic expression of miR-29 and dampens lipogenesis (DNL) in the liver of chow-fed mice.

Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer.

Background: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes.

Methods: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM.

Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer.

Purpose: Anti-programmed death-1 (PD-1) receptor-based therapeutics improve survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC), but many do not benefit due to a low response rate. Herein, we identified EZH2 as a therapeutic target that enhanced tumor cell antigen presentation and subsequently sensitized resistant tumors to anti-PD-1 therapy.

Experimental Design: EZH2 regulation of antigen presentation was defined using EZH2 inhibitors (GSK126 and EPZ6438) in human and mouse HNSCC cell lines.

The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer.

Background: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms.

Methods: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC.

Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice.

MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (including miR-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin resistance (IR).

The mediating roles of caregiver social support and self-efficacy on caregiver burden in Parkinson's disease.

Background: Most studies in Parkinson's disease (PD) have focused on the direct effects of social support and self-efficacy on caregiver burden. This study aimed to test our prediction that caregiver self-efficacy and social support were two chaining mediator variables on the paths for patient factors affecting caregiver burden, caregiver anxiety, and depression.

Method: We enrolled patients with PD and their caregivers from the First Affiliated Hospital of Shanxi Medical University in China between July and December 2017.