Hypermethylation of CDKN2A CpG island drives resistance to PRC2 inhibitors in SWI/SNF loss-of-function tumors.

Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations.

Application of eye organoids in the study of eye diseases.

The eyes are one of the most important sensory organs in the human body. Currently, diseases such as limbal stem cell deficiency, cataract, retinitis pigmentosa and dry eye seriously threaten the quality of people's lives, and the treatment of advanced blinding eye disease and dry eye is ineffective and costly. Thus, new treatment modalities are urgently needed to improve patients' symptoms and suffering.

Role of microglia in diabetic neuropathic pain.

Approximately one-third of the patients with diabetes worldwide suffer from neuropathic pain, mainly categorized by spontaneous and stimulus-induced pain. Microglia are a class of immune effector cells residing in the central nervous system and play a pivotal role in diabetic neuropathic pain (DNP). Microglia specifically respond to hyperglycemia along with inflammatory cytokines and adenosine triphosphate produced during hyperglycemic damage to nerve fibers.

Simulated skin model for evaluation of insertion performance of microneedles: design, development, and application verification.

Microneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin.

A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity.

The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3.

A selective Fibroblast Growth Factor Receptor 1/2 PROTAC degrader with antitumor activity.

The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3.

Investigating the mechanism of cornel iridoid glycosides on type 2 diabetes mellitus using serum and urine metabolites in rats.

Ethnopharmacological Relevance: Cornel iridoid glycosides (CIG) are extracted from Corni fructus, a herbal medicine used in traditional Chinese medicine to treat diabetes. However, the antidiabetic effects of CIG and the underlying metabolic mechanisms require further exploration.

Aim Of The Study: This study aimed to assess the antidiabetic effects and metabolic mechanism of CIG by performing metabolomic analyses of serum and urine samples of rats.

Immune cell receptor-specific nanoparticles as a potent adjuvant for nasal split influenza vaccine delivery.

Mucosal delivery systems have gained much attention as effective way for antigen delivery that induces both systemic and mucosal immunity. However, mucosal vaccination faces the challenges of mucus barrier and effective antigen uptake and presentation. In particular, split, subunit and recombinant protein vaccines that do not have an intact pathogen structure lack the efficiency to stimulate mucosal immunity.

Coated Porous Microneedles for Effective Intradermal Immunization with Split Influenza Vaccine.

In order to alleviate the pain associated with subcutaneous injections, microneedles (MNs) are gaining increasing attention as a novel transdermal drug delivery modality. Among them, porous microneedles (pMNs) are particularly suitable for the delivery of drugs and vaccines whose activity is sensitive to the microneedle preparation process. They can carry drugs actively to achieve an effective load and deliver drugs into the skin.

An edge-device-compatible algorithm for valvular heart diseases screening using phonocardiogram signals with a lightweight convolutional neural network and self-supervised learning.

Background And Objectives: Detection and classification of heart murmur using mobile-phone-collected sound is an emerging approach to the scale-up screening of valvular heart disease at a population level. Nonetheless, the widespread adoption of artificial intelligence (AI) methods for this type of mobile health (mHealth) application requires highly accurate and lightweight AI models that can be deployed in consumer-grade mobile devices. This study presents a lightweight deep learning model and a self-supervised learning (SSL) method to utilise unlabelled data to improve the accuracy of valvular heart disease classification using phonocardiogram data.

Quantifying the Two-Dimensional Driving Patterns of Chemisorbed Oxygen and Particle Size on NO Reduction Activity and Mechanism.

Quantification in the driving patterns of activity descriptors on structure-activity relationships and reaction mechanisms over heterogeneous catalysts is still a great challenge and needs to be addressed urgently. Herein, with the example of typical Mn-based catalysts, based on the activity regularity and many characterizations, the chemisorbed oxygen density (ρ) and particle size () have been proposed as the two-dimensional descriptors for selective catalytic reduction of NO, whose role is in quantifying the contents of vacancy defects and the amounts of active sites located on terraces or interfaces, respectively. They can be utilized to construct and quantify the driving patterns for the structure-activity relationships and reaction mechanisms of NO reduction.

StarmapVis: An interactive and narrative visualisation tool for single-cell and spatial data.

Current single-cell visualisation techniques project high dimensional data into 'map' views to identify high-level structures such as cell clusters and trajectories. New tools are needed to allow the transversal through the high dimensionality of single-cell data to explore the single-cell local neighbourhood. StarmapVis is a convenient web application displaying an interactive downstream analysis of single-cell expression or spatial transcriptomic data.

Porous Microneedles for Therapy and Diagnosis: Fabrication and Challenges.

The use of microneedles (MNs), an innovative transdermal technology, enables efficient, convenient, painless, and controlled-release drug delivery. Porous microneedles (pMNs), special MNs with abundant interconnected pores that can produce capillary action, are gaining increasing attention as a novel MNs technology. pMNs can actively adsorb bioactive ingredients from solutions of drugs or vaccines for in vivo delivery or from interstitial skin fluids (ISFs) for wearable and point-of-care testing (POCT) products.

An Improved Mixture Density Network for 3D Human Pose Estimation with Ordinal Ranking.

Estimating accurate 3D human poses from 2D images remains a challenge due to the lack of explicit depth information in 2D data. This paper proposes an improved mixture density network for 3D human pose estimation called the Locally Connected Mixture Density Network (LCMDN). Instead of conducting direct coordinate regression or providing unimodal estimates per joint, our approach predicts multiple possible hypotheses by the Mixture Density Network (MDN).

A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA.

The cyclic GMP-AMP (cGAMP) synthase (cGAS) is a key DNA sensor that initiates STING-dependent signaling to produce type I interferons through synthesizing the secondary messenger 2'3'-cGAMP. In this study, we confirm previous studies showing that cGAS is located both in the cytoplasm and in the nucleus. Nuclear accumulation is observed when leptomycin B is used to block the exportin, CRM1 protein.

Classification of Electromyographic Hand Gesture Signals Using Modified Fuzzy C-Means Clustering and Two-Step Machine Learning Approach.

Understanding and classifying electromyogram (EMG) signals is of significance for dexterous prosthetic hand control, sign languages, grasp recognition, human-machine interaction, etc.. The existing research of EMG-based hand gesture classification faces the challenges of unsatisfied classification accuracy, insufficient generalization ability, lack of training data and weak robustness.

An Allosteric PRC2 Inhibitor Targeting EED Suppresses Tumor Progression by Modulating the Immune Response.

Aberrant activity of polycomb repressive complex 2 (PRC2) is involved in a wide range of human cancer progression. The WD40 repeat-containing protein EED is a core component of PRC2 and enhances PRC2 activity through interaction with H3K27me3. In this study, we report the discovery of a class of pyrimidone compounds, represented by BR-001, as potent allosteric inhibitors of PRC2.

Tensile Properties and Corrosion Behavior of Extruded Low-Alloyed Mg⁻1Sn⁻1Al⁻1Zn Alloy: The Influence of Microstructural Characteristics.

A low-alloyed Mg⁻Sn⁻Al⁻Zn system was developed and successfully fabricated through the extrusion process. The dependence of tensile properties and corrosion behavior on microstructural characteristics of the studied alloy has been investigated. After extrusion, the alloy consists of fine dynamically recrystallized (DRXed) grains of ~2.

Influence of Equal Channel Angular Pressing Passes on the Microstructures and Tensile Properties of Mg-8Sn-6Zn-2Al Alloy.

An I-phase containing Mg-8Sn-6Zn-2Al (wt %; TZA862) alloy was fabricated and subjected to different number of passes of equal channel angular pressing (ECAP) processing at 300 °C. The results showed that the alloys exhibited a bimodal microstructure, which consisted of fine dynamically recrystallized (DRX) grains and coarse non-DRX grains. When increasing the number of ECAP passes from 2 to 6, the fraction of DRX grains and the dispersed second phase particles subsequently increase.

The Ubiquitin Ligase RNF125 Targets Innate Immune Adaptor Protein TRIM14 for Ubiquitination and Degradation.

Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor that facilitates innate immune signaling. Upon virus infection, the expression of TRIM14 is significantly induced, which stimulates the production of type-I IFNs and proinflammatory cytokines. As excessive immune responses lead to harmful consequences, TRIM14-mediated signaling needs to be tightly balanced.

An enantioselective synthesis of (+)-(S)-[n]-gingerols via the L-proline-catalyzed aldol reaction.

An enantioselective approach to (+)-(S)-[n]-gingerols (1a-c) has been developed. The requisite stereogenic centers of target molecules are facilely constructed by the proline-catalyzed cross-aldol reaction from readily available achiral starting materials.

[Studies on anti-hyperglycemic effect and its mechanism of Clinopodium chinense].

Objective: To investigate the anti-hyperglycemic effect and its mechanism of ethanol extraction from Calamintha chinensis (EJCT).

Method: Fasting serum glucose (FSG) in normal mice was determined after oral administration of EJCT. Effects of EJCT on hyperglycemia mice induced by adrenaline were investigated by observing the contents of FSG and liver glucogen.