Discovery of a new function of human butyrylcholinesterase and the catalytic activity of its natural variants toward homocysteine thiolactone hydrolysis.

Abnormal activity level of human butyrylcholinesterase (BChE) was detected in patients with cardiovascular disease and neurodegenerative disorders, however, the specific role of BChE in the pathology of these diseases are not known yet. Homocysteine thiolactone (HTL) is a toxic thioester metabolite of homocysteine in conditions of hyperhomocysteinemia (HHcy). Experimental evidences suggest that HTL and resultant N-Hcy proteins that disrupt normal protein function, are associated with the pathology of HHcy-related complications such as cardiovascular diseases.

The critical role of DNA damage-inducible transcript 4 (DDIT4) in stemness character of leukemia cells and leukemia initiation.

Leukemia stem cells (LSCs) are critical for leukemia initiation, and the stemness properties of LSCs are related to disease relapse. Stemness properties, including quiescence, self-renewal, and chemoresistance, are maintained through an interplay between leukemia cells and the bone marrow (BM) niche. Here, we demonstrated that DNA damage-inducible transcript 4 (DDIT4) can be induced in a hypoxic BM niche and is required for the quiescence and self-renewal of AML1-ETO9a (AE9a)-transformed leukemia cells in vitro.

Single-Stranded DNA Triple Allosteric-Assisted Logic Gates Enabled Photoelectrochemical Multiplex Detection of Waterborne Viruses.

Conventional photoelectrochemical (PEC) sensors with a single recognition interface frequently exhibit limitations in delivering comprehensive concentration information for target analytes in multiplex detection systems. The present work leverages the triple allostery of single-stranded DNA conformation to construct a "signal-on" and "signal-off" switchable PEC sensing platform, thereby propelling the advancement of DNA logic gate-integrated PEC analytical systems toward precise quantification and multiplex qualitative analysis of viruses in aquatic environments. The engineered OR-type logic gate-integrated PEC platform, harnessing the dual metal ion enzyme-mediated cascade signal amplification system, exhibited superior quantitative performance for dual-virus detection with a wider linear range from 0.

Biochemical and Functional Characterization of Aminopeptidase N: A New Role as a 6-Monoacetylmorphine Hydrolase.

6-monoacetylmorphine (6-MAM), a primary active metabolite of heroin that reaches the human brain, plays a crucial role in producing heroin-associated physiological and lethal effects. Therefore, 6-MAM has emerged as a key target for alleviating the adverse consequences of heroin abuse. In this study, the proposed 6-MAM hydrolase aminopeptidase N (eAPN) was recombinantly produced, and its biochemical and functional profiles were investigated.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Structural modelling of student volleyball athletes' intimacy, social adjustment, perceived stress, and learning-related anxiety: mediating role of psychological safety.

Background: Psychological safety is crucial for student-athletes, impacting their stress levels and academic anxiety. Understanding how interpersonal factors like intimacy and social adjustment impact psychological safety can guide interventions to enhance student-athlete well-being.

Objectives: This study investigates the relationships between intimacy, social adjustment, psychological safety, perceived stress, and learning-related anxiety among student-athletes.

Dynamic Detection of the E3-PROTAC-Target Protein Ternary Complex and Bimolecular Fluorescence Complementation.

Proteolysis-targeting chimeras (PROTACs) have played an important role in the development of protein-targeted degradation drugs. However, effective tools are urgently required for the further development and validation of PROTACs. We developed a high-potency reporter (AKT-PROTAC-Reporter; APR) for PROTACs that specifically targets AKT.

Endosome-microautophagy targeting chimera (eMIATAC) for targeted proteins degradation and enhance CAR-T cell anti-tumor therapy.

Since oncogene expression products often exhibit upregulation or abnormally activated activity, developing a technique to regulate abnormal protein levels represent a viable approach for treating tumors and protein abnormality-related diseases. We first screened out eMIATAC components with high targeted degradation efficiency and explored the mechanism by which eMIATAC induced target protein degradation, and verified the degradation efficiency of the target protein by protein imprinting and flow cytometry. Next, we recombined eMIATAC with some controllable elements to verify the regulatable degradation performance of the target protein.

Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.

Homocysteine thiolactone (HTL), a toxic metabolite of homocysteine (Hcy) in hyperhomocysteinemia (HHcy), is known to modify protein structure and function, leading to protein damage through formation of N-Hcy-protein. HTL has been highly linked to HHcy-associated cardiovascular and neurodegenerative diseases. The protective role of HTL hydrolases against HTL-associated vascular toxicity and neurotoxicity have been reported.

Slow-replicating leukemia cells represent a leukemia stem cell population with high cell-surface CD74 expression.

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell-tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label-retaining slow-cycling leukemia cell population from AML1-ETO9a (AE9a) leukemic mice.

Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit α3 (ITGA3) in human cancers.

The integrin subunit α3 (ITGA3) is a member of the integrin alpha chain protein family, which could promote progression, metastasis, and invasion in some cancers. Still, its function in the tumor microenvironment (TME), cancer prognosis, and immunotherapy remains unclear. A multifaceted analysis of ITGA3 in pan-cancer utilizing various databases and online web tools revealed ITGA3 was aberrantly expressed in tumor tissues and upregulated in most cancers, which may be related to ITGA3 genomic alterations and methylation modification.

Distance-Regulated Photoelectrochemical Sensor "Signal-On" and "Signal-Off" Transitions for the Multiplexed Detection of Viruses Exposed in the Aquatic Environment.

Photochemical (PEC) sensors were severely limited for multiplex detection applications due to the cross interference between multiplex signals at the single recognition interface. In this work, a distance-regulated PEC sensor was developed for multiplex detection by using an i-Motif sequence with conformational transformation activity as the signal transduction unit. Through dynamic regulation of the spatial distance between the end site of the functional sequence and the electrode material, the photogenerated electrons on the surface of the sensor were directionally transferred.

[Bone Marrow Osteoblasts Promotes the Proliferation Leukemia Stem Cell by Up-regulating Interleukin-1].

Objective: To explore the extrinsic regulation mechanism of bone marrow microenvironment in leukemia cells, and investigate the promoting effect of osteoblast niche on the proliferation and self-renewal of leukemia stem cell by up-regulating the expression of interleukin-1 (IL-1) in leukemia cell.

Methods: The gene expression profiles on leukemia cells derived from AE9a mouse bone marrow endosteum and central bone marrow were determined by RNA sequencing and gene set enrichment analysis (GSEA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of IL-1 in AE9a mouse leukemia cells co-cultured with or without osteoblasts in vitro.

Watson for oncology decision system for treatment consistency study in breast cancer.

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study.

Spatial attentional biases toward height-related words in young males with physical stature dissatisfaction.

By recording event-related potentials (ERPs) during a dot-probe task, the present study examined the neural dynamics of attentional bias toward height-related words among height dissatisfied males. Sixty male participants screened by Negative Physical Self Scale-Stature Concerns subscale (NPS-S) were assigned into a high height dissatisfaction (HHD) group and a low height dissatisfaction (LHD) group. The results showed that tall-related versus neutral words elicited larger N2pc for both HHD and LHD groups, whereas short-related versus neutral words elicited larger N2pc only for the HHD group.

Long-Term Treatment Outcomes of the Elder Patients with Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma with Definitive Chemoradiotherapy or Radiotherapy.

Background: Few randomized trials are available to guide clinical management of elderly patients with esophageal cancer. Therefore, treatment approaches for the elderly are challenging.

Objective: We believe that chemotherapy and radiotherapy are more effective than radiotherapy alone.