Proteogenomic Analysis Identifies Clinically Relevant Subgroups of Collecting Duct Carcinoma.

Collecting duct carcinoma (CDC) is a rare but aggressive form of renal cell carcinoma (RCC) that has limited understanding and an undefined systemic therapeutic regimen. Herein, we conducted a comprehensive proteogenomic analysis of CDC tumors and normal adjacent tissues to elucidate the biology of the disease. CDC exhibited high heterogeneity in tumor mutational burden, and enhanced ribosome biogenesis was the most striking malignant feature of CDC, even compared with other common kidney carcinomas.

Prevalence and overlap of white blood cell counts, procalcitonin and C-reactive protein in neonates with invasive bacterial infections.

Background: Neonatal invasive bacterial infections (IBIs) are associated with substantial mortality. We aimed to elucidate the prevalence and overlapping effects of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in neonates with IBIs.

Methods: We conducted a retrospective cohort study in 17 Chinese hospitals from 2012 to 2021.

Host lncRNA assists the nuclear import of influenza A virus protein PB2 in a species-specific manner.

Long noncoding RNAs (lncRNAs) have been reported to modulate immune responses to viral infections. However, it remains largely unexplored how viruses exploit host lncRNAs to promote viral replication. Here, we found that an lncRNA, called lnc-ALOX12, is upregulated specifically in cells infected by influenza A virus (IAV).

High Maternal Glycine Levels Increase the Risk of Developing Atrial Septal Defect in the Offspring.

Amino acid imbalance is linked to increased congenital heart disease risk. Here, we found women carrying rs2545801 C/C genotypes exhibited increased glycine levels and increased risk for atrial septal defects (ASDs) in their offspring. Elevated maternal glycine levels during the first trimester were correlated with a higher ASD risk in the offspring.

Protective effects of metformin against volatile organic compounds-induced developmental toxicity in zebrafish embryos.

Volatile organic compounds (VOCs) are widespread environmental pollutants associated with various health risks, including developmental toxicity. Our previous studies revealed a correlation between indoor VOCs exposure and an increased risk of congenital heart diseases (CHDs), which was confirmed by establishing a zebrafish exposure model. Metformin (MET), a classic hypoglycemic drug, has been identified to possess multiple properties.

Proteogenomic characterization reveals that lipid droplet formation promotes esophageal squamous cell cancer progression.

Esophageal cancer is one of the most common cancers and a leading cause of cancer-related mortality in the world. Here, we have performed comprehensive characterization of genetic, transcriptomic, proteomic, and phosphoproteomic features in 293 patients with esophageal squamous cell carcinoma (ESCC). Chromosome 12q13.

SLFN11 Restricts LINE-1 Mobility.

Long interspersed element-1 (LINE-1) is the only active autonomous transposon comprising about 17% of human genomes. LINE-1 transposition can cause the mutation and rearrangement of the host's genomic DNA. The host has, therefore, developed multiple mechanisms to restrict LINE-1 mobility.

Host factor Rab4b promotes the replication of influenza A virus.

Rab proteins are involved in all facets of the vesicular transport process and play significant roles in different steps of the viral life cycle. Rab4b is a pivotal player in the endocytic recycling of proteins, whereas its roles in viral replication are still largely unknown. Our earlier work identified Rab4b as a host factor required to replicate the influenza A virus (IAV).

Integrated clinical and proteomic-based model for diagnostic and prognostic prediction in pRCC.

Papillary renal cell carcinoma (pRCC), a main pathological subtype of non-clear cell RCC (nccRCC), has strong heterogeneity. Comparing to other nccRCC subtypes, advanced pRCC has the poorest prognosis. Due to its lower incidence compared to ccRCC, clinical research and exploration of non-invasive biomarkers for pRCC are limited, and it is often misclassified.

Cirrhosis Promotes Cardiac Fibrosis Development by Inhibiting Notch1 in Cardiac Fibroblasts.

Cardiovascular disease risk is elevated in patients with cirrhosis. However, the underlying molecular mechanisms remain poorly understood. Herein, we found that high levels of circulating transforming growth factor (TGF)-β1 were associated with an increased risk of cardiomyopathy in cirrhosis patients.

Maximal inhibitory effect of MOV10 on LINE-1 retrotransposition requires both the MOV10/LINE-1 association and granule formation.

LINE-1 is the only active autonomous mobile element in the human, and its mobilization is tightly restricted by the host to maintain genetic stability. We recently reported that human MOV10 recruits DCP2 to decap LINE-1 RNA by liquid-liquid phase separation (LLPS), resulting in the inhibition of LINE-1 retrotransposition, while the detailed mechanism still awaits further exploration. In this report, we found that the extended motif II (563-675aa) and the C-terminal domain (907-1003aa) of MOV10 cooperated to achieve maximal inhibition on LINE-1 retrotransposition.

Discovery and rational optimization of 2, 2'-((1H-indole-2,3-diyl) bis (thio))diacetamide as novel SARS-CoV-2 RdRp inhibitors.

The COVID-19 pandemic has significantly strained global health infrastructures while profoundly affecting the socio-economic landscape. RNA-dependent RNA polymerase (RdRp) plays a pivotal role in the replication and transcription of RNA viruses, making it a critical target for antiviral drug development. In this work, we describe the discovery, rational optimization, and synthesis of a novel series of non-nucleoside SARS-CoV-2 RdRp inhibitors featuring a 2,2'-((1H-indole-2,3-diyl)bis (thio))diacetamide core.

Maternal di(2-ethylhexyl) phthalate exposure increases the risk of congenital heart disease in mice offspring.

Abstrct: BACKGROUD: Epidemiological data suggest that maternal occupational exposure to mixed phthalates comprising di(2-ethylhexyl) phthalate (DEHP) increases the risk of congenital heart disease (CHD). In this study, we used mice as an animal model to validate impact of first-trimester DEHP exposure on the risk of CHD in offspring, to elucidate the possible mechanisms and to provide a potential feasible intervention.

Methods And Results: Eight-week-old C57BL/6J pregnant mice were randomly divided into standard and DEHP diet groups.

SLC31A1 loss depletes mitochondrial copper and promotes cardiac fibrosis.

Background And Aims: Metals serve as co-factors for a host of metalloenzymes involved in mitochondrial metabolic reprogramming. Modifications in metal homeostasis are linked to epigenetic mechanisms. However, the epigenetic mechanisms through which metal affects cardiac fibrosis (CF) remain poorly understood.

Discovery and optimization of phenazopyridine hydrochloride as novel SARS-CoV-2 RdRp inhibitors.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen of coronavirus disease (COVID-19) causing a pandemic with growing global transmission. The viral RNA-dependent RNA polymerase (RdRp) is conserved especially for variants of concern (VOCs), making it as an effective antivirals target. Due to the proofreading activity of coronavirus nsp14/nsp10, limited the efficacy of nucleoside analogs in vivo.

Cryogenic in-memory computing using magnetic topological insulators.

Machine learning algorithms have proven to be effective for essential quantum computation tasks such as quantum error correction and quantum control. Efficient hardware implementation of these algorithms at cryogenic temperatures is essential. Here we utilize magnetic topological insulators as memristors (termed magnetic topological memristors) and introduce a cryogenic in-memory computing scheme based on the coexistence of a chiral edge state and a topological surface state.

Weak Antilocalization and Negative Magnetoresistance of the Gate-Tunable PbTe Thin Films.

We have systematically studied the electromagnetic transport properties of PbTe thin films under gate voltage modulation. The system demonstrates pronounced electron-electron interactions exclusively within the gate voltage range where only hole carriers are present. Furthermore, the Berry phase is utilized to qualitatively elucidate the transition between weak antilocalization (WAL) and weak localization (WL) through the regulation of gate voltage and temperature.

High fructose levels inhibit the proliferation of cardiomyocytes via the Notch1 signaling pathway.

Fructose, as a natural and simple sugar, is not significantly harmful to the human body when consumed in moderation and can provide energy for the body. High-fructose diets have been linked to an increased risk of a range of metabolic disorders, including hypertriglyceridemia, hypertension, and diabetes mellitus. These conditions are known to be associated with an elevated risk of developing cardiometabolic diseases.

Targeted mitochondrial function for cardiac fibrosis: An epigenetic perspective.

Mitochondria, commonly referred to as "energy factories"of cells, play a crucial role in the function and survival of cardiomyocytes. However, as research on cardiac fibrosis has advanced, mitochondrial dysfunction(including changes in energy metabolism, calcium ion imbalance, increased oxidative stress, and apoptosis)is now recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression, which also negatively affects the function and structure of the heart. In recent years, research focusing on targeting mitochondria has gained significant attention, offering new approaches for treating cardiac fibrosis.

Synthesis and biological evaluation of substituted quinolines containing piperazine moieties against Influenza A virus.

Influenza A virus (IAV) poses a serious global threat to public health. There is an urgent need to develop new anti-IAV agents due to the limitations of the current antiviral drugs in clinical practice. Herein, based on compound I-13e, we designed and synthesized 23 substituted quinoline derivatives containing piperazine moieties and evaluated their in vitro anti-IAV activity.

Branched-chain amino acids deficiency promotes diabetic cardiomyopathy by activating autophagy of cardiac fibroblasts.

More than half of the patients with type II diabetes mellitus (T2D) develop diabetic cardiomyopathy (DCM). Glycemic control alone cannot effectively prevent or alleviate DCM. Herein, we concentrated on the variations in levels of metabolites between DCM and T2D patients without cardiomyopathy phenotype.

Epigenetic regulation of mitochondrial fission and cardiac fibrosis via sFRP3 promoter methylation.

In the process of cardiac fibrosis, the balance between the Wnt/β-catenin signalling pathway and Wnt inhibitory factor genes plays an important role. Secreted frizzled-related protein 3 (sFRP3), a Wnt inhibitory factor, has been linked to epigenetic mechanisms. However, the underlying role of epigenetic regulation of sFRP3, which is crucial in fibroblast proliferation and migration, in cardiac fibrosis have not been elucidated.

Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data.

Unlabelled: Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression.

NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.

Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism.