Miltefosine reinvigorates exhausted T cells by targeting their bioenergetic state.

T cell exhaustion presents a major challenge for the efficacy of both immune checkpoint inhibitors (ICBs) and chimeric antigen receptor T (CAR-T) cell immunotherapies. To address this issue, we generate hypofunctional CAR-T cells that imitate the exhaustion state. By screening a Food and Drug Administration (FDA)-approved small molecule library using this model, we identify miltefosine as a potent molecule that restores the impaired function of CAR-T cells in a PD-1/PD-L1-independent manner.

Construction of the prognostic nomogram and treatment recommendation in patients with mixed endometrial carcinoma treated with hysterectomy.

Mixed endometrial carcinomas (MECs) account for approximately 3%-10% of all endometrial carcinomas (ECs). These are defined as a combination of two or more distinct histologic subtypes, with at least one being a type II tumor that constitutes at least 5% of the overall tumor. However, the associated prognostic factors and treatment of MECs remain unclear.

Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.

Background: Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80-90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies.

MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function Targeting HIF-1α and E2F3.

Background: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS.

Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS.

Sex-Specific Entorhinal Cortex Functional Connectivity in Cognitively Normal Older Adults with Amyloid-β Pathology.

Sex and apolipoprotein E (APOE) genotype have been shown to influence the risk and progression of Alzheimer's disease (AD). However, the impact of these factors on the functional connectivity of the entorhinal cortex (ERC) in clinically unpaired older adults (CUOA) with amyloid-β (Aβ +) pathology remains unclear. A total of 1022 cognitively normal older adults with Aβ + (603 females and 586 APOE ε4 +) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were included in this study.

An in vitro feasibility study of 355 nm laser atherectomy for the treatment of peripheral atherosclerotic lesions.

In this study, we utilized a novel 355 nm laser to ablate porcine aortas in the presence of physiological saline and contrast agent. Subsequently, we investigated the shape and depth of the resulting injuries. After ablating bovine tendons and aortas with the laser, we analyzed the size and quantity of particles postablation.

Comparison of surgical excision followed by adjuvant radiotherapy and laser combined with steroids for the treatment of keloids: A systematic review and meta-analysis.

This meta-analysis aims to evaluate and compare the effect of surgical excision followed by adjuvant radiotherapy and laser combined with steroids on keloids. Relevant studies reporting the recurrence rate or incidence of adverse events (AEs) were retrieved from the PubMed, Web of Science, Embase and Cochrane Library databases through August 2023. The quality of noncomparative single-arm clinical trials was evaluated using the methodological index for nonrandomised studies (MINORS) Methodological items.

Dopamine multilocus genetic profile influence on reward network in chronic insomnia disorder with depression.

Background: Chronic insomnia disorder (CID) is frequently comorbid with depression, and both conditions are believed to involve disruptions in the reward network. However, the potential effects of genetic polymorphisms in modulating this network remain largely unexplored.

Methods: In this study, we recruited 50 CID patients with high (CID-HD) and low (CID-LD) depressive symptoms and assessed their reward networks using resting-state functional MRI.

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of and Cardiac Fibrosis.

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM.

Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA.

Background: Common genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown.

Methods: Multi-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255).

EEG Reveals Alterations in Motor Imagery in People With Amnestic Mild Cognitive Impairment.

Objectives: Motor imagery has been used to investigate the cognitive mechanism of motor control. Although behavioral and electrophysiological changes in motor imagery in people with amnestic mild cognitive impairment (aMCI) have been reported, deficits in different types of imagery remain unclear. To explore this question, we used electroencephalography (EEG) to study neural correlates of visual imagery (VI) and kinesthetic imagery (KI) and their relationship to cognitive function in people with aMCI.

Axenic cultivation and genome diploidization of the moss for horticulture utilization.

Mosses are widely used in the establishment of greenery. However, little research has been conducted to choose a suitable species or improve their performance for this application. In our study, we examined (), a robust moss that is widely distributed in temperate, subtropical, and tropical Asia with varying environmental conditions.

Long Non-Coding RNAs of Plants in Response to Abiotic Stresses and Their Regulating Roles in Promoting Environmental Adaption.

Abiotic stresses triggered by climate change and human activity cause substantial agricultural and environmental problems which hamper plant growth. Plants have evolved sophisticated mechanisms in response to abiotic stresses, such as stress perception, epigenetic modification, and regulation of transcription and translation. Over the past decade, a large body of literature has revealed the various regulatory roles of long non-coding RNAs (lncRNAs) in the plant response to abiotic stresses and their irreplaceable functions in environmental adaptation.

Spectral missing color correction based on an adaptive parameter fitting model.

With the development of remote sensing technology, true-color visualization of hyperspectral LiDAR echo signals has become a hotspot for both academic research and commercial applications. The limitation of the emission power of hyperspectral LiDAR causes the loss of spectral-reflectance information in some channels of the hyperspectral LiDAR echo signal. The color reconstructed based on the hyperspectral LiDAR echo signal is bound to have serious color cast problem.

Current trends and insights on EMS mutagenesis application to studies on plant abiotic stress tolerance and development.

Ethyl methanesulfonate (EMS)-induced mutagenesis is a powerful tool to generate genetic resource for identifying untapped genes and characterizing the function of genes to understand the molecular basis of important agronomic traits. This review focuses on application of contemporary EMS mutagenesis in the field of plant development and abiotic stress tolerance research, with particular focuses on reviewing the mutation types, mutagenesis site, mutagen concentration, mutagenesis duration, the identification and characterization of mutations responsible for altered stress tolerance responses. The application of EMS mutation breeding combined with genetic engineering in the future plant breeding and fundamental research was also discussed.

Testis- specific Y-encoded- like protein 1 and cholesterol metabolism: Regulation of expression through Wnt signaling.

The cytochromes P450 (CYPs) represent a large gene superfamily that plays an important role in the metabolism of both exogenous and endogenous compounds. We have reported that the testis-specific Y-encoded-like proteins (TSPYLs) are novel gene transcriptional regulators. However, little is known of mechanism(s) by which TSPYLs regulate expression or the functional consequences of that regulation.

Long non-coding RNA NCK1-AS1 functions as a ceRNA to regulate cell viability and invasion in esophageal squamous cell carcinoma via microRNA-133b/ENPEP axis.

This study is designed to explore the role of long non-coding RNAs (lncRNAs) NCK1-AS1 in proliferative and invasive activities of esophageal squamous cell carcinoma (ESCC) cells by binding to microRNA-133b (miR-133b) to regulate ENPEP. Differentially expressed lncRNAs, miRs, genes and their targeting relationships were screened on ESCC-related gene expression datasets GSE17351 and GSE6188. The targeting relationships among NCK1-AS1, miR-133b, and ENPEP were verified using functional assays.

Glucocorticoids unmask silent non-coding genetic risk variants for common diseases.

Understanding the function of non-coding genomic sequence variants represents a challenge for biomedicine. Many diseases are products of gene-by-environment interactions with complex mechanisms. This study addresses these themes by mechanistic characterization of non-coding variants that influence gene expression only after drug or hormone exposure.

An improved spectral estimation method based on color perception features of mobile phone camera.

We use the mobile phone camera as a new spectral imaging device to obtain raw responses of samples for spectral estimation and propose an improved sequential adaptive weighted spectral estimation method. First, we verify the linearity of the raw response of the cell phone camera and investigate its feasibility for spectral estimation experiments. Then, we propose a sequential adaptive spectral estimation method based on the CIE1976 L*a*b* (CIELAB) uniform color space color perception feature.

Cytochrome P450 Transcriptional Regulation by Testis-Specific Y-Encoded-Like Protein: Identification of Novel Upstream Transcription Factors.

Cytochrome P450s () display significant inter-individual variation in expression, much of which remains unexplained by known single-nucleotide polymorphisms (SNPs). Testis-specific Y-encoded-like proteins (s) are transcriptional regulators for several drug-metabolizing including However, transcription factors (TFs) that might influence expression through an effect on expression are unknown. Therefore, we studied regulators of expression in hepatic cell lines and their possible SNP-dependent variation.

Glucocorticoids mediate transcriptome-wide alternative polyadenylation: Potential mechanistic and clinical implications.

Alternative polyadenylation (APA) is a common genetic regulatory mechanism that generates distinct 3' ends for RNA transcripts. Changes in APA have been associated with multiple biological processes and disease phenotypes. However, the role of hormones and their drug analogs in APA remains largely unknown.

Regulation of Heat Stress in () Provides Novel Insight into the Functions of Plant RNase H1s.

RNase H1s are associated with growth and development in both plants and animals, while the roles of RNase H1s in bryophytes have been rarely reported. Our previous data found that a member of the family, could regulate the development of by regulating the auxin. In this study, we further investigated the biological functions of and found may participate in response to heat stress by affecting the numbers and the mobilization of lipid droplets and regulating the expression of heat-related genes.

ACE2 and TMPRSS2 SARS-CoV-2 infectivity genes: deep mutational scanning and characterization of missense variants.

The human angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) proteins play key roles in the cellular internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the coronavirus disease of 2019 (COVID-19) pandemic. We set out to functionally characterize the ACE2 and TMPRSS2 protein abundance for variant alleles encoding these proteins that contained non-synonymous single-nucleotide polymorphisms (nsSNPs) in their open reading frames (ORFs). Specifically, a high-throughput assay, deep mutational scanning (DMS), was employed to test the functional implications of nsSNPs, which are variants of uncertain significance in these two genes.