Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with most sporadic cases lacking clear genetic causes. Abnormal pre-mRNA splicing is a fundamental mechanism in neurodegenerative diseases. For example, TAR DNA-binding protein 43 (TDP-43) loss-of-function (LOF) causes widespread RNA mis-splicing events in ALS.

Preparation of carboxymethyl cellulose membrane flexible SERS substrate and its application in the detection of metabolites and pH in urine.

Uric acid, urea, and other metabolites in urine after exercise often reflect chronic injury syndrome in athletes. However, traditional urine detection methods have issues such as high costs and low detection sensitivity. SERS can rapidly, continuously, and sensitively monitor metabolites in human urine.

The Role of Epicardial Adipose Tissue-Derived Proteins in Heart Failure with Preserved Ejection Fraction and Atrial Fibrillation: A Bioinformatics Analysis.

Background: The accumulation of epicardial adipose tissue (EAT) is associated with cardiometabolic risks and adverse outcomes in heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). This study aims to identify genes secreted by EAT that contribute to the shared pathogenesis of HFpEF and AF, potentially serving as biomarkers for diagnosis.

Methods: Data sets from the GEO database for HFpEF-EAT, HFpEF-heart tissue, AF-EAT, AF-PBMC, and AF-heart tissue were analyzed.

The impact of digital transformation on corporate green governance under carbon peaking and neutrality goals: Evidence from China.

Digital transformation, as a significant shift in optimizing enterprise resource allocation and enhancing information connectivity, offers the opportunity to stimulate the endogenous dynamics of corporate green governance. Employing a sample of 3,002 listed companies in China, a fixed-effects model, and the entropy power method to formulate a green governance index system, this study examines how digital transformation affects corporate green governance concerning carbon peaking and carbon neutrality objectives. According to these findings, the implementation of the digital transformation improves corporate green governance, each unit increase in digital transformation correlates with a 1.

Dysfunctional circadian clock accelerates cancer metastasis by intestinal microbiota triggering accumulation of myeloid-derived suppressor cells.

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis.

Beyond Spirometry: Linking Wasted Ventilation to Exertional Dyspnea in the Initial Stages of COPD.

Exertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics - as those in the initial stages of the disease - the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space.

Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity.

The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets.

Bacterial cellulose loaded with silver nanoparticles as a flexible, stable and sensitive SERS-active substrate for detection of the shellfish toxin DTX-1.

Diarrheal shellfish toxins are considered one of the most lethal red tide algae toxins in the worldwide. In this work, we propose an Ag NPs-loaded bacterial cellulose membrane (BCM) surface-enhanced Raman scattering (SERS) sensor based on an aptamer (Apt) for the ultrasensitive detection of dinophysistoxin (DTX-1), a type of diarrheal shellfish toxin. During drying, Ag NPs can be further densified on "gel-like" BCM to form high-density SERS "hot spots".

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease.

Background: CAVD is a common cardiovascular disease, but currently there is no drug treatment. Therefore, it is urgent to find new and effective drug therapeutic targets. Recent evidence has shown that the infiltration of M1 macrophages increased in the calcified aortic valve tissues, but the mechanism has not been fully elucidated.

Preparation of SERS substrate with 2D silver plate and nano silver sol for plasticizer detection in edible oil.

As a widely used industrial additive of plastic products, phthalate ester (PAE) plasticizers can easily migrate into food, threatening human health. In this work, we proposed a rapid, precise, and reliable method to detect PAE plasticizers in edible oils by using surface-enhanced Raman spectroscopy (SERS) technology. A two-dimensional (2D) silver plate synergizing with a nanosilver sol was prepared as a substrate for SERS to detect potassium hydrogen phthalate (PHP), a hydrolysate of a PAE plasticizer.

Syntheses, Structures and Insulin-Like Activity of Two Oxidovanadium(V) Complexes with Similar Nicotinohydrazone Ligands.

Two new oxidovanadium(V) complexes, [VOL1(HQ)] (1) and [VOL2(SAH)] (2), were prepared by the reaction of [VO(acac)2] (where acac = acetylacetonate) with N'-(3-ethoxy-2-hydroxybenzylidene)nicotinohydrazide (H2L1) and 8-hydroxyquinoline (HHQ), and N'-(2-hydroxy-4-methoxybenzylidene)nicotinohydrazide (H2L2) and salicylhydroxamic acid (HSAH), respectively, in methanol. Crystal and molecular structures of the complexes were determined by elemental analysis, infrared spectroscopy and single crystal X-ray diffraction. The V atoms in both complexes are in octahedral coordination.

SATB2 Defect Promotes Colitis and Colitis-associated Colorectal Cancer by Impairing Cl-/HCO3- Exchange and Homeostasis of Gut Microbiota.

Background: SATB2 is a diagnostic biomarker and a favourable prognostic marker for colorectal cancer [CRC], but its role in colitis and colitis-associated colorectal cancer [CAC] is unknown.

Methods: Colitis was induced in intestinal epithelial-specific Satb2 knockout [Satb2 IEC-KO] and control mice using dextran sulphate sodium [DSS]. RNA-seq analysis was performed on colonic tissues, and 16S rDNA-Seq on faecal bacterial DNA from Satb2 IEC-KO and control mice.

Dynamic airway function during exercise in COPD assessed via impulse oscillometry before and after inhaled bronchodilators.

Assessing airway function during exercise provides useful information regarding mechanical properties of the airways and the extent of ventilatory limitation in COPD. The primary aim of this study was to use impulse oscillometry (IOS) to assess dynamic changes in airway impedance across a range of exercise intensities in patients with GOLD 1-4, before and after albuterol administration. A secondary aim was to assess the reproducibility of IOS measures during exercise.

Aptamer assisted CRISPR-Cas12a strategy for small molecule diagnostics.

Molecular diagnostics are vital for the identification, prevention, and treatment of numerous diseases and are of particular demand in point-of-care (POC) settings. Nevertheless, most reported biosensors based on the CRISPR-Cas system have focused on nucleic-acid targets. Here, we report a versatile diagnostic strategy for small molecules called Molecular Radar (Random Molecular Aptamer-Dependent CRISPR-Assist Reporter), The workflow is simple, convenient, and rapid (conducted at 37 °C in under 25 min), indicating the substantial potential of the proposed assay could be adapted into a biosensor for POC settings and on-site molecular diagnostics.

Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer.

The mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases.

Circadian Clock Disruption Suppresses PDL1 Intraepithelial B Cells in Experimental Colitis and Colitis-Associated Colorectal Cancer.

Background & Aims: The circadian clock is crucial for physiological homeostasis including gut homeostasis. Disorder of the circadian clock may contribute to many diseases including inflammatory bowel disease (IBD). However, the role and the mechanisms of circadian clock involvement in IBD still are unclear.

Grifolin, neogrifolin and confluentin from the terricolous polypore Albatrellus flettii suppress KRAS expression in human colon cancer cells.

In our search for bioactive mushrooms native to British Columbia, we determined that the ethanol extracts from fruiting bodies of the terrestrial polypore Albatrellus flettii had potent anti-cell viability activity. Using bioassay-guided fractionation, mass spectrometry and nuclear magnetic resonance, we successfully isolated three known compounds (grifolin, neogrifolin and confluentin). These compounds represent the major anti-cell viability components from the ethanol extracts of A.

Characterizing the interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IMP1) and KRAS expression.

Insulin-like growth factor 2 mRNA-binding protein-1 (IMP1) has high affinity for KRAS mRNA, and it can regulate KRAS expression in cells. We first characterized the molecular interaction between IMP1 and KRAS mRNA. Using IMP1 variants with a point mutation in the GXXG motif at each KH domain, we showed that all KH domains play a critical role in the binding of KRAS RNA.

Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death.

The pathogenesis and key functional molecules involved in inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) remain unclear. Here, we reported that Erbin, a protein required for the polarity of epithelial cells, is conserved across species and highly expressed in the intestinal mucosa in mice and zebrafish. Pathologically, Erbin expression in the intestinal mucosa was significantly decreased in DSS induced acute colitis mice, IL-10 deficient mice and clinical biopsy specimens from patients with ulcerative colitis.

Inhibition of GLI1 Expression by Targeting the CRD-BP-GLI1 mRNA Interaction Using a Specific Oligonucleotide.

The stabilization of glioma-associated oncogene 1 (GLI1) mRNA by coding region determinant binding protein (CRD-BP) through the Wnt/β-catenin signaling pathway is implicated in the proliferation of colorectal cancer and basal cell carcinoma. Here, we set out to characterize the physical interaction between CRD-BP and GLI1 mRNA so as to find inhibitors for such interaction. Studies using CRD-BP variants with a point mutation in the GXXG motif at each KH domain showed that KH1 and KH2 domain are critical for the binding of GLI1 RNA.