Deciphering genetic associations with blood pressure in peripheral blood mononuclear cells through single-cell transcriptomic profiling.

Functional genes within genomic loci associated with blood pressure (BP) identified by genome-wide association studies (GWASs) are cell type-specific. This study aims to identify such genes in immune cells by employing single-cell transcriptomic analysis in peripheral blood mononuclear cells (PBMCs). By integration of single-cell transcriptomic sequencing data with GWAS (1 million individuals) findings using the summary data-based Mendelian randomization (SMR) method, we identified candidate BP-associated genes across diverse immune cell subsets.

New perspectives on molecular mechanisms underlying exercise-induced benefits in Parkinson's disease.

Exercise offers neuroprotective benefits in Parkinson's disease (PD) by enhancing neurotrophic factors (e.g., BDNF, GDNF), improving mitochondrial function, reducing inflammation, and promoting autophagy.

In-situ localised alignment assisted salting-out enhanced ionogels with high strength, toughness and impact resistance.

Ionic gels have promise in a range of applications but are limited in extreme environments. Here, we report a method for preparation of an ionic gel with improved mechanical properties, through the formation of a micro-orientated structure and increased crystallisation and aggregation of polymer chains. The resulting ionic gels exhibit tunable mechanical properties, including high strength (18.

SIRT6 Lysine-Demyristoylates ATF2 to Ameliorate Vascular Injury via PRKCD/VE-Cadherin Pathway Regulating Vascular Endothelial Barrier.

Cardiovascular diseases (CVDs) progression is significantly modulated by epigenetic mechanisms, particularly through Sirtuin 6 (SIRT6), a key NAD⁺-dependent deacetylase in the sirtuin family. Though essential for cardiovascular homeostasis, the effects of SIRT6-mediated lysine myristoylation on CVDs progression remain largely unexplored due to detection limitations. This study developes an innovative lysine-myristoylated peptide enrichment technique, identifying mutant SIRT6 (H133Y) with high myristoyl affinity but deficient demyristoylase activity.

Magnetic Field Induced Quantum Metric Dipole in Dirac Semimetal Cd_{3}As_{2}.

The quantum geometry, comprising Berry curvature and quantum metric, plays a fundamental role in governing electron transport phenomena in solids. Recent studies show that the quantum metric dipole drives scattering-free nonlinear Hall effect in topological antiferromagnets, prompting the questions of whether this effect can occur in nonmagnetic systems and be externally tuned by a magnetic field. Our work addresses these frontiers by demonstrating that the quantum metric dipole is actively tuned by an external magnetic field to generate a time-reversal-odd nonlinear Hall response in a nonmagnetic topological Dirac semimetal Cd_{3}As_{2}.

Kinesin-related genes stratified the prognosis and immune responses of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive form of kidney cancer. Recently, the identification of suitable subtypes in ccRCC for the prediction of prognosis and immune infiltration remains limited. Kinesin superfamily proteins (KIFs), a group of molecular motor proteins, have been found to play crucial roles in tumor progression and patient prognosis in various cancers.

Molecular docking and biological evaluation of a novel IWS1 inhibitor for the treatment of human retroperitoneal liposarcoma.

IWS1 is a key assembly factor of the RNA polymerase II (RNAPII) elongation complex, and its overexpression is associated with worse outcomes in patients with liposarcoma (LPS). This study aimed to identify compounds that can disrupt the IWS1/Spt6 interaction and assess their biological effects in dedifferentiated LPS (DDLPS). Using the AlphaFold-predicted structure of IWS1, we identified a core binding region (AA 545-694) for its interaction with Spt6.

FAM49B Fragmentation by Asparagine Endopeptidase Promotes Vascular Smooth Muscle Cell Migration in Atherogenesis.

Background: The migration of vascular smooth muscle cells (VSMCs) is critical for the development of atherosclerosis. However, the underlying molecular mechanisms are not completely understood. Here, we detected FAM49B (family with sequence similarity 49 member B) fragments in atherosclerotic plaques and identified their roles in VSMC migration and atherogenesis.

Development of Positron Emission Tomography Radiotracers for Imaging α-Synuclein Aggregates.

Neurodegenerative diseases (NDDs) that are characterized by the accumulation of alpha-synuclein (α-syn) aggregates in both neurons and the non-neuronal cells of the brain are called synucleinopathies. The most common synucleinopathies includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Significant progress has been made in the development of positron emission tomography (PET) radiotracers for synucleinopathies, yielding several α-syn tracers that have entered clinical studies.

Epigenetic Regulation of PEPT2 as a Novel Strategy to Improve the Antitumor Efficacy of Lenalidomide in Clear Cell Renal Cell Carcinoma.

The poor prognosis of clear cell renal cell carcinoma (ccRCC) is primarily attributed to inherent resistance and malignant progression, yet the underlying mechanism and effective strategies remain poorly understood. Renal drug transporters play an indispensable role in regulating the intracellular concentration of tumor cells. Therefore, this study aims to investigate the role of proton-coupled oligopeptide transporter 2 (PEPT2) in ccRCC.

Endothelial-to-mesenchymal transition in cardiovascular diseases.

Endothelial-to-mesenchymal transition (EndMT) represents a dynamic process during which endothelial cells (ECs) loosen intercellular interactions, break down the basement membrane and undergo alterations in cell polarity to attain a mesenchymal phenotype. The intermediate stage of EndMT, known as partial EndMT, enables cells to exhibit partial functions and characteristics of both ECs and mesenchymal cells. This endows ECs with a unique physiological function and reflects the potential for reversing the EndMT process.

Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition.

Background: Asparagine endopeptidase (AEP) is implicated in the pathogenesis of Alzheimer's disease (AD) by cleaving Tau at residue N368, accelerating its hyperphosphorylation and aggregation. The Tau N368/t-Tau ratio in cerebrospinal fluid (CSF) serves as a superior biomarker compared to established biomarkers (p-Tau 181/217) for correlating with tau pathology and synaptic dysfunction in patients with AD, highlighting its diagnostic and therapeutic potential.

Methods: We evaluated the therapeutic efficacy of a Tau N368-specific antibody in two mouse models: Tau P301S (tauopathy) and 3xTg (AD with Aβ/tau pathology).

Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) and the nigrostriatal dopaminergic neuronal degeneration. Depression is one of the most common non-motor symptoms of PD patients. However, the pathogenic connection between PD and depression is not well understood.

Proteomic Profiling of Serum-Derived Extracellular Vesicles in Diffuse Idiopathic Skeletal Hyperostosis Patients.

This study focuses on the proteomic profiles of serum-derived EVs in diffuse idiopathic skeletal hyperostosis (DISH), aiming to identify the potential diagnostic biomarkers for DISH. Serum-EVs were separated using a differential centrifugation technique. Then, label-free-liquid chromatography mass spectrometry (LC-MS/MS) was utilized to identify differentially expressed proteins (DEPs) highly associated with DISH.

Development of an Ophthalmic Hydrogel to Deliver MG53 and Promote Corneal Wound Healing.

A clinical need exists for more effective therapeutics and sustained drug delivery systems to promote ocular surface healing. This study tested the hypothesis that a novel biodegradable, thermoresponsive hydrogel loaded with the human recombinant (rh)MG53 protein, which we have demonstrated to promote corneal healing without fibrosis, would exhibit safety and biocompatibility in vitro and in vivo. Hydrogel optimization was performed based on varying concentrations of poloxamer 407, poloxamer 188, and hydroxypropyl methylcellulose.

O-Arm Navigated MIS-TLIF Avoids Violation and Delays Degeneration of the Supradjacent Facet Joint.

Objective: O-arm navigated MIS-TLIF is one of the novel surgical techniques for treating lumbar spondylolisthesis, but there still lacks enough evidence regarding intraoperative facet joint violation (FJV) and postoperative facet joint degeneration (FJD). This study aimed to compare clinical outcomes, accuracy of screw placement, and supradjacent FJV between the O-arm navigated MIS-TLIF group (NavMIS-TLIF group) and the open-TLIF group for the treatment of low-grade lumbar spondylolisthesis, and further, to investigate the risk factors influencing FJD.

Methods: We retrospectively reviewed a cohort of patients with low-grade lumbar spondylolisthesis who had received O-Arm navigated MIS-TLIF or open TLIF from May 2018 to May 2023.

Performance Evaluation of a Solar-Assisted Multistage Heat Pump Drying System Based on the Optimal Drying Conditions for L.

This study aims to evaluate the drying performance of a multi-stage solar-assisted heat pump drying system for tomatoes. The method involves theoretical calculations based on the optimal drying process and experimental investigations to assess the impact of different drying temperatures and relative humidity on drying characteristics. The results from the theoretical calculations reveal that the multi-stage solar-assisted heat pump drying system outperforms a single-stage system, particularly under lower ambient temperatures or higher fresh air volumes.

One-Pot Stereoselective Synthesis of -Glycosyl Amino Acids with Vicinal Stereocenters.

A palladium-catalyzed cascade coupling between glycals and racemic α-nitroesters enables the stereoselective construction of -glycosyl amino acids bearing two contiguous stereocenters, achieving dual stereocontrol (exclusive β-C1, up to 10:1 diastereomeric ratio at C7). This one-pot protocol at room temperature accommodates diverse substrates (25 examples). Mechanistic studies demonstrate that decarboxylation-induced C4-oxyanion directs 1,4- selectivity, while steric modulation governs C7 stereochemistry.

MXene Assisted Shear Thickening Fluids Reinforced Anti-Impact Composite Aerogel with Superior Electromagnetic Shielding and Flame Retardant Performance.

The ubiquitous mechanical and thermal damage in extreme environments puts new demands on protective equipment. At the same time, with the continuous development of electronic equipment, electromagnetic hazards and information leakage risks are increasing, so equipment with force/thermal/magnetic protection performance needs to be developed urgently. Herein, a shear thickened composite aerogel (MS) with host-guest structure is developed by a two-step reinforcement process involving unidirectional freeze casting and ultrasonic assisted penetration of shear thickening fluid (STF).

Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Induced Brain Hemorrhagic Transformation After Ischemic Stroke.

Background: Thrombolytic treatment with tissue plasminogen activator (tPA) is one of the approved pharmacological therapies for acute ischemic stroke. However, the use of tPA is limited due to hemorrhagic transformation (HT) and the narrow therapeutic time window. Previous studies demonstrated that asparagine endopeptidase (AEP), a widely expressed pH-dependent endo-lysosomal cysteine protease, can induce neuronal death during ischemia-reperfusion injury.

Study on the quality characteristics of jujube slices under different pretreatment and drying methods.

This study investigates the effects of different pretreatment methods, cold plasma (CP) and ultrasound (US), as well as different drying techniques, including vacuum freeze-drying (FD), hot air drying (HAD), and microwave coupled with pulsed vacuum drying (MPVD), on the quality characteristics of winter jujube slices. The physical, chemical, and functional properties were analyzed, encompassing farinograph attributes, particle size, cation exchange capacity, total phenolic and flavonoid content, and flavor compounds were analyzed. In terms of physical properties, jujube slices subjected to MPVD demonstrate superior water-holding capacity at 2.

The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that are composed of aggregated α-synuclein (α-Syn). However, the factors that regulate α-Syn pathology and nigrostriatal dopaminergic degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD.

Irisin promotes autophagy and attenuates NLRP3 inflammasome activation in Parkinson's disease.

Parkinson's disease (PD) is characterized by the aggregation and prion-like propagation of α-synuclein (α-syn). Irisin is an exercise-induced myokine that regulates energy metabolism and exerts protective effects in PD by reducing α-syn pathology. However, the molecular mechanisms underlying the role of irisin are not fully understood.

Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.

Histone deacetylation represents a significant epigenetic mechanism that involves the removal of acetyl groups from histones, subsequently influencing gene transcription. Overexpression of histone deacetylases (HDACs) is prevalent across various cancer types, positioning HDAC inhibitors as broadly applicable therapeutic agents. These inhibitors are known to enhance tumor immune antigenicity, potentially slowing tumor progression.

Innate and adaptive immunity in neurodegenerative disease.

Neurodegenerative diseases (NDs) are a group of neurological disorders characterized by the progressive loss of selected neurons. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs. Pathologically, NDs are characterized by progressive failure of neural interactions and aberrant protein fibril aggregation and deposition, which lead to neuron loss and cognitive and behavioral impairments.