Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.

Background And Aims: TM6SF2 rs58542926 (E167K) is related to an increased prevalence of metabolic dysfunction-associated steatotic liver disease. Conflicting mouse study results highlight the need for a human model to understand this mutation's impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies.

Paclitaxel Attenuates Atherosclerosis by Suppressing Macrophage Ferroptosis and Improving Lipid Metabolism via the Sirt1/Nrf2/GPX4 Pathway.

Atherosclerosis is a leading cause of cardiovascular disorders such as coronary heart disease, heart failure, and stroke. Ferroptosis, a novel type of cell death, plays an important role in atherosclerosis progression, especially macrophage ferroptosis. Paclitaxel (PTX) is an antiproliferative drug that has been developed in recent decades and is helpful in the treatment of atherosclerosis.

Dynamic Path Planning for Unmanned Autonomous Vehicles Based on CAS-UNet and Graph Neural Networks.

This paper proposes a deeply integrated model called CAS-GNN, aiming to solve the collaborative path-planning problem for multi-agent vehicles operating in dynamic environments. Our proposed model integrates CAS-UNet and Graph Neural Network (GNN), and, by introducing a dynamic edge enhancement module and a dynamic edge weight update module, it improves the accuracy of obstacle boundary recognition in complex scenarios and adaptively changes the influence of different edges during the information transmission process. We generate data through online trajectory optimization to enhance the model's adaptability to dynamic environments.

Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load.

Working memory (WM) is a fundamental cognitive function crucial adaptive behavior. The intricate interplay between the frontal cortex and striatum in governing WM maintenance and updating remains a central question. In this study, we employed optogenetics to demonstrate that inhibiting both dorsomedial striatum (DMS) D1R- and D2R-neurons enhances WM, while their activation impairs it across T-maze and operant-based delayed-non-match-to-place (DNMTP) paradigms in mice.

Bioprinting of human primary and iPSC-derived islets with retained and comparable functionality.

Currently, type 1 diabetes (T1D) can be treated through implantation of allogenic islets, which replenish the beta cell population, however this method requires an extensive post-implantation immunosuppressant regimen. Personalized cellular therapy can address this through implantation of an autologous cell population, induced pluripotent stem cells (iPSCs). Cellular therapy, however, requires an encapsulation device for implantation, and so to achieve this uniformly with cells in a clinical setting, bioprinting is a useful option.

PML1-Mediated Feedforward Loop Through PI3K and MAPK Axes Drives Endocrine Resistance.

Unlabelled: Treatment of estrogen receptor-positive (ER+) breast cancer is significantly hindered by endocrine resistance. We identified PML1 as a key therapeutic entity that can be targeted to overcome resistance. Endocrine-resistant breast cancer cells share three key characteristics: elevated PML1 protein levels, enhanced activity of PI3K, MAPK, or both signaling pathways, and reduced ER activity.

Remembering the past affects new learning: The temporal dynamics of integrative encoding.

Memories link elements across event boundaries, integrating overlapping content experienced at different times and places. Such memory representations are thought to rely on memory integration mechanisms. The present study used multivariate pattern analysis (MVPA) of electroencephalographic (EEG) data to elucidate the temporal dynamics of integrative encoding memory processes.

Research on seismic activity and seismic structural characteristics of the Shandong region.

This study provides a comprehensive analysis of seismic activity and structural characteristics in Shandong Province, China, with a focus on identifying seismic belts and potential epicentral zones critical for regional seismic safety. A detailed database was developed, integrating regional seismicity statistics, earthquake distribution patterns, significant geotectonic movements, and recent neotectonic activities. The results reveal that seismic activity in Shandong is heterogeneously distributed, with moderate to strong earthquakes predominantly associated with active fault zones and exhibiting zonal clustering.

Exploring the boundary of quantum correlations with a time-domain optical processor.

Contextuality is a hallmark feature of the quantum theory that captures its incompatibility with any noncontextual hidden-variable model. The Greenberger-Horne-Zeilinger (GHZ)-type paradoxes are proofs of contextuality that reveal this incompatibility with deterministic logical arguments. However, the GHZ-type paradox whose events can be included in the fewest contexts and that brings the strongest nonclassicality remains elusive.

Mitoxantrone inhibits and downregulates ER through binding at the DBD-LBD interface.

Targeting the estrogen receptor (ER or ERα) through competitive antagonists, receptor downregulators, or estrogen synthesis inhibition remains the primary therapeutic strategy for luminal breast cancer. We have identified a novel mechanism of ER inhibition by targeting the critical interface between its DNA-binding domain (DBD) and ligand-binding domain (LBD). We demonstrate that mitoxantrone (MTO), a topoisomerase II inhibitor, binds at this previously unexplored DBD-LBD interface.

Targeting the glymphatic system to promote α-synuclein clearance: a novel therapeutic strategy for Parkinson's disease.

The excessive buildup of neurotoxic α-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease, highlighting the urgent need for innovative therapeutic strategies to promote α-synuclein clearance, particularly given the current lack of disease-modifying treatments. The glymphatic system, a recently identified perivascular fluid transport network, is crucial for clearing neurotoxic proteins. This review aims to synthesize current knowledge on the role of the glymphatic system in α-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.

A Pan-Cancer Analysis of the Oncogenic Role of CD276 in Human Tumors.

: B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family that has been found to be associated with the growth and progression of a variety of tumors, but no pan-cancer evaluations of CD276 have been performed so far. In this study, we aimed to perform a pan-cancer analysis of the oncogenic role of CD276 in human tumors; : We used a series of databases to perform a pan-cancer analysis of CD276, including the expression level of CD276 in pan-cancer and its relationship to tumor progression, patient survival duration, the immune cell infiltration within the tumor, and the potential signaling pathways and molecular mechanisms associated with CD276; : We found that CD276 was a potential biomarker for the prognosis of most cancers. The high expression of CD276 was associated with tumor progression, leading to poor survival.

Entanglement-Enabled Advantage for Learning a Bosonic Random Displacement Channel.

We show that quantum entanglement can provide an exponential advantage in learning properties of a bosonic continuous-variable (CV) system. The task we consider is estimating a probabilistic mixture of displacement operators acting on n bosonic modes, called a random displacement channel. We prove that if the n modes are not entangled with an ancillary quantum memory, then the channel must be sampled a number of times exponential in n in order to estimate its characteristic function to reasonable precision; this lower bound on sample complexity applies even if the channel inputs and measurements performed on channel outputs are chosen adaptively or have unrestricted energy.

The effects of episodic context on memory integration.

Information encountered in different events, such as people and objects, can be interlinked in memory. Such memory integration supports novel inferences about the world. This study investigates the role of episodic context on memory integration in two experiments using an associative inference task.

Single cell analysis identified a basal cell transition state associated with the development and progression of bladder cancer.

Background: Bladder cancer (BC) is a prevalent malignancy characterized by significant cellular heterogeneity. While single-cell multi-omics studies have provided valuable insights, much of the existing data remains underexplored, limiting our understanding of BC's molecular mechanisms. Uncovering the pathogenesis of BC and finding new treatment methods are urgent problems to be solved.

[Protective Effect and Mechanism of miR-328-3p on Coronary Artery Endothelial Cell Injury Induced by Oxidized Low-density Lipoprotein].

Objective: To investigate the protective effect of miR-328-3p on oxidized low-density lipoprotein (ox-LDL)-induced coronary artery endothelial cell injury and the potentially relevant mechanisms.

Methods: Human coronary artery endothelial cells (HCAECs) were induced with ox-LDL, and the cells were divided into a control group consisting of normal cells, an ox-LDL group receiving ox-LDL treatment, an ox-LDL+miR-NC group transfected with miR-NC and treated with ox-LDL, an ox-LDL+miR-328-3p group transfected with miR-328-3p and treated with ox-LDL, and ox-LDL+miR-328-3p+pcDNA group co-transfected miR-328-3p and pcDNA and treated with ox-LDL, and an ox-LDL+miR-328-3p+insulin-like growth factor 2 (IGF2) group co-transfected miR-328-3p and IGF2 and treated with ox-LDL. The expression level of miR-328-3p was determined with RT-qPCR.

Single-cell analysis reveals alternations between the aged and young mice prostates.

Background: Aging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood.

Methods: Prostate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis.

Orientation optimization for high performance MgSbthermoelectric films via thermal evaporation.

Low-cost, highly efficient thermoelectric thin-film materials are becoming increasingly popular as miniaturization progresses. MgSbhas great potential due to its low cost and high performance. However, the fabrication of MgSbthin films with high power factors (PFs) poses a certain challenge.

The geological origins and soil properties of loess-like silty clay: a case study in the jinan area.

This study, using Jinan as a case study, systematically investigates the characteristics and geological genesis of loess-like silty clay in the middle and lower reaches of the Yellow River. The primary distribution of loess-like silty clay is revealed through field surveys, laboratory experiments, and previous literature reviews. The chemical and physical properties of the loess-like silty clay were examined, in addition to investigations into its mineral composition, microstructural characteristics, and engineering mechanical properties, in order to enhance comprehension of its attributes and formation mechanisms.

The prognostic impact of tumor location in nonmuscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing Chinese multicenter and SEER registries.

Objective: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach.

Halide Perovskite Inducing Anomalous Nonvolatile Polarization in Poly(vinylidene fluoride)-based Flexible Nanocomposites.

Ferroelectric materials have important applications in transduction, data storage, and nonlinear optics. Inorganic ferroelectrics such as lead zirconate titanate possess large polarization, though they are rigid and brittle. Ferroelectric polymers are light weight and flexible, yet their polarization is low, bottlenecked at 10 μC cm.

A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA.

The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.

The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model.