WRAD core perturbation impairs DNA replication fidelity promoting immunoediting in pancreatic cancer.

It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in the context of oncogenic stress. Here, we identify the WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator of DNA replication in pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that the WRAD core interacts with the replisome complex, with disruption of DPY30 resulting in DNA re-replication, DNA damage, and chromosomal instability (CIN) without affecting cancer cell proliferation.

Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.

Key mechanisms underlying chronic pain occur within the dorsal horn. Genome-wide association studies (GWASs) have identified genetic variants predisposed to chronic pain. However, most of these variants lie within regulatory non-coding regions that have not been linked to spinal cord biology.

Fixed Airflow Obstruction in Asthma Can Be Identified Early by Low FEF25-75% and is Associated with Environmental Exposure.

Purpose: This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25-75% (FEF25-75%) and FAO.

Patients And Methods: We analyzed data from 312 han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <-0.

Adaptive Log-Euclidean Metrics for SPD Matrix Learning.

Symmetric Positive Definite (SPD) matrices have received wide attention in machine learning due to their intrinsic capacity to encode underlying structural correlation in data. Many successful Riemannian metrics have been proposed to reflect the non-Euclidean geometry of SPD manifolds. However, most existing metric tensors are fixed, which might lead to sub-optimal performance for SPD matrix learning, especially for deep SPD neural networks.

Therapeutic targeting of Syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers.

The therapeutic benefit of recently developed mutant KRAS (mKRAS) inhibitors has been limited by the rapid onset of resistance. Here, we aimed to delineate the mechanisms underlying acquired resistance to mKRAS inhibition and identify actionable targets for overcoming this clinical challenge. Previously, we identified Syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by mKRAS.

Regression convolutional neural network models implicate peripheral immune regulatory variants in the predisposition to Alzheimer's disease.

Alzheimer's disease (AD) involves aggregation of amyloid β and tau, neuron loss, cognitive decline, and neuroinflammatory responses. Both resident microglia and peripheral immune cells have been associated with the immune component of AD. However, the relative contribution of resident and peripheral immune cell types to AD predisposition has not been thoroughly explored due to their similarity in gene expression and function.

Risk factor analysis and nomogram for predicting poor symptom control in smoking asthmatics.

Background: Smoking induces and modifies the airway immune response, accelerating the decline of asthmatics' lung function and severely affecting asthma symptoms' control level. To assess the prognosis of asthmatics who smoke and to provide reasonable recommendations for treatment, we constructed a nomogram prediction model.

Methods: General and clinical data were collected from April to September 2021 from smoking asthmatics aged ≥14 years attending the People's Hospital of Zhengzhou University.

Elucidating the deactivation mechanism of beta zeolite catalyzed linear alkylbenzene production with oxygenated organic compound contaminated feedstocks.

Zeolite catalyzed alkylation of benzene with long-chain α-olefins is a promising method for the detergent industry. Considering the long-chain α-olefins from Fischer-Tropsch synthesis always contain some oxygenated organic compounds, the effect of which on the alkylation of benzene with 1-dodecene was comprehensively investigated over beta zeolite herein. -heptanol, -heptaldehyde and -heptanoic acid were selected as the model oxygenated organic compounds, and it was revealed that an obvious decrease of lifetime occurred when only trace amount of oxygenated organic compounds were added into the feedstocks.

Clonal dominance defines metastatic dissemination in pancreatic cancer.

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination.

SPD Manifold Deep Metric Learning for Image Set Classification.

By characterizing each image set as a nonsingular covariance matrix on the symmetric positive definite (SPD) manifold, the approaches of visual content classification with image sets have made impressive progress. However, the key challenge of unhelpfully large intraclass variability and interclass similarity of representations remains open to date. Although, several recent studies have mitigated the two problems by jointly learning the embedding mapping and the similarity metric on the original SPD manifold, their inherent shallow and linear feature transformation mechanism are not powerful enough to capture useful geometric features, especially in complex scenarios.

A magnetic multi-layer soft robot for on-demand targeted adhesion.

Magnetic soft robots have shown great potential for biomedical applications due to their high shape reconfigurability, motion agility, and multi-functionality in physiological environments. Magnetic soft robots with multi-layer structures can enhance the loading capacity and function complexity for targeted delivery. However, the interactions between soft entities have yet to be fully investigated, and thus the assembly of magnetic soft robots with on-demand motion modes from multiple film-like layers is still challenging.

An AFM-Based Model-Fitting-Free Viscoelasticity Characterization Method for Accurate Grading of Primary Prostate Tumor.

Viscoelasticity is a crucial property of cells, which plays an important role in label-free cell characterization. This paper reports a model-fitting-free viscoelasticity calculation method, correcting the effects of frequency, surface adhesion and liquid resistance on AFM force-distance (FD) curves. As demonstrated by quantifying the viscosity and elastic modulus of PC-3 cells, this method shows high self-consistency and little dependence on experimental parameters such as loading frequency, and loading mode (Force-volume vs.

Zwitterion modified cochlear implants resist postoperative infection and inflammation.

The cochlear implant (CI), an advanced electronic device replacing the entire cochlear function, is the ultimate treatment for over 466 million people with disabling hearing loss. Infection after cochlear implantation is a common and worrisome complication despite the routine administration of the antibiotic. The bacterial biofilms formed on the surface of CI are the main cause of antibiotic failure.

An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.

Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB.

Elaidic acid induced hepatocyte pyroptosis via autophagy-CTSB-NLRP3 pathway.

Elaidic acid (EA, C18:1 trans) is a kind of principal Trans fatty acid (TFA) and is widely found in processed food. Pyroptosis is a form of programmed cell death, distinct from apoptosis and traditional necrosis. Excessive pyroptosis could induce body injury and serious inflammation.

SMARCB1 regulates the hypoxic stress response in sickle cell trait.

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor . Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT.

Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis.

Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I.

Noncoding translation mitigation.

Translation is pervasive outside of canonical coding regions, occurring in long noncoding RNAs, canonical untranslated regions and introns, especially in ageing, neurodegeneration and cancer. Notably, the majority of tumour-specific antigens are results of noncoding translation. Although the resulting polypeptides are often nonfunctional, translation of noncoding regions is nonetheless necessary for the birth of new coding sequences.

Bacteria-Targeted Combined with Photothermal/NO Nanoparticles for the Treatment and Diagnosis of MRSA Infection In Vivo.

Currently, undeveloped diagnosis and delayed treatment of bacteria-infected sites in vivo not only expand the risk of tissue infection but are also a major clinical cause of multiple drug-resistant bacterial infections. Herein, an efficient nanoplatform for near-infrared (NIR)-light-controlled release and bacteria-targeted delivery of nitric oxide (NO) combined with photothermal therapy (PTT) is presented. Using maltotriose-decorated mesoporous polydopamine (MPDA-Mal) and BNN6, a smart antibacterial (B@MPDA-Mal) is developed to combine bacterial targeting, gas-controlled release, and PTT.

Collateral activity of the CRISPR/RfxCas13d system in human cells.

CRISPR/Cas13 systems are increasingly used for programmable targeting of RNAs. While Cas13 nucleases are capable of degrading both target RNAs and bystander RNAs in vitro and in bacteria, initial studies fail to detect collateral degradation of non-target RNAs in eukaryotic cells. Here we show that RfxCas13d, also known as CasRx, a widely used Cas13 system, can cause collateral transcriptome destruction when targeting abundant reporter RNA and endogenous RNAs, resulting in proliferation defect in target cells.

Melatonin Prevents against Ethanol-Induced Liver Injury by Mitigating Ferroptosis via Targeting Brain and Muscle ARNT-like 1 in Mice Liver and HepG2 Cells.

The circadian clock acts a pivotal part in human daily physiology and metabolism. Excess alcohol consumption disturbs the circadian rhythm of several metabolism-related genes of the liver. Melatonin is a member of the foremost hormones secreted by the pineal gland with numerous pharmacological properties in quite a number of diseases.

Learning a discriminative SPD manifold neural network for image set classification.

Performing pattern analysis over the symmetric positive definite (SPD) manifold requires specific mathematical computations, characterizing the non-Euclidian property of the involved data points and learning tasks, such as the image set classification problem. Accompanied with the advanced neural networking techniques, several architectures for processing the SPD matrices have recently been studied to obtain fine-grained structured representations. However, existing approaches are challenged by the diversely changing appearance of the data points, begging the question of how to learn invariant representations for improved performance with supportive theories.