Leveraging single-cell RNA-seq for uncovering naïve B cells associated with better prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a typical highly heterogeneous solid tumor with high morbidity and mortality worldwide, especially in China; however, the immune microenvironment of HCC has not been clarified so far. Here, we employed single-cell RNA sequencing (scRNA-seq) on diethylnitrosamine (DEN)-induced mouse HCC model to dissect the immune cell dynamics during tumorigenesis. Our findings reveal distinct immune profiles in both precancerous and cancerous lesions, indicating early tumor-associated immunological alterations.

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases.

Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated.

EXOC4 Promotes Diffuse-Type Gastric Cancer Metastasis via Activating FAK Signal.

Unlabelled: In comparison with intestinal-type gastric cancer, diffuse-type gastric cancer (DGC) is more likely to recur, metastasize, and exhibit worse clinical outcomes; however, the underlying mechanism of DGC recurrence remains elusive. By employing an LC/MS-MS proteomic approach, we identified that exocyst complex component 4 (EXOC4) was significantly upregulated in DGC with recurrence, compared to those with nonrecurrence. High expression of EXOC4 was correlated with tumor metastasis and poor prognosis in patients with DGC.

OTUD6A promotes prostate tumorigenesis via deubiquitinating Brg1 and AR.

Ovarian tumor (OTU) subfamily deubiquitinases are involved in various cellular processes, such as inflammation, ferroptosis and tumorigenesis; however, their pathological roles in prostate cancer (PCa) remain largely unexplored. In this study, we observed that several OTU members displayed genomic amplification in PCa, among which ovarian tumor deubiquitinase 6A (OTUD6A) amplified in the top around 15-20%. Further clinical investigation showed that the OTUD6A protein was highly expressed in prostate tumors, and increased OTUD6A expression correlated with a higher biochemical recurrence risk after prostatectomy.

Triple-signaling amplification strategy based electrochemical sensor design: boosting synergistic catalysis in metal-metalloporphyrin-covalent organic frameworks for sensitive bisphenol A detection.

A covalent organic framework (COF) is a promising type of porous material with customizable surface characteristics. Confining multiple catalytic units within a mesoporous COF can generate abundant active sites and improve the catalytic performance. In this work, a COF with both metalloporphyrin and a metal nanoparticle complex denoted as hemin/TAPB-DMTP-COF/AuNPs (TAPB: 1,3,5-tris(4-amino-phenyl)benzene, DMTP: 2,5-dimethoxyterephaldehyde, AuNPs: Au nanoparticles) has been successfully fabricated through a hierarchical encapsulation method.

In-situ anchoring bimetallic nanoparticles on covalent organic framework as an ultrasensitive electrochemical sensor for levodopa detection.

Covalent organic frameworks (COFs) have been studied in many fields. However, their electrochemical properties were seldom reported. In this work, a novel high electrocatalytic material was synthesized by incorporating bimetallic nanoparticles (AgCoNPs) in a two-dimensional (2D) porous TAPB-DMTP-COF, (AgCo/TAPB-DMTP-COF, TAPB, 1,3,5-tris(4-aminophenyl)benzene; DMTP, 2,5-dimethoxyterephaldehyde).

LZP is required for hepatic triacylglycerol transportation through maintaining apolipoprotein B stability.

The conserved zona pellucida (ZP) domain is found in hundreds of extracellular proteins that are expressed in various organs and play a variety of roles as structural components, receptors and tumor suppressors. A liver-specific zona pellucida domain-containing protein (LZP), also named OIT3, has been shown to be mainly expressed in human and mouse hepatocytes; however, the physiological function of LZP in the liver remains unclear. Here, we show that Lzp deletion inhibited very low-density lipoprotein (VLDL) secretion, leading to hepatic TG accumulation and lower serum TG levels in mice.

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer.

Background: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.

Investigating higher-order interactions in single-cell data with scHOT.

Single-cell genomics has transformed our ability to examine cell fate choice. Examining cells along a computationally ordered 'pseudotime' offers the potential to unpick subtle changes in variability and covariation among key genes. We describe an approach, scHOT-single-cell higher-order testing-which provides a flexible and statistically robust framework for identifying changes in higher-order interactions among genes.

A simple bacterial expression system for human ppGalNAc-T and used for the synthesis of O-GalNAc glycosylated interleukin 2.

Mucin-type O-glycosylation (hereafter referred to as O-GalNAc glycosylation) is one of the most abundant glycosylation on proteins. It is initiated by the members of polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts) family. The ppGalNAc-Ts could be used as tool enzymes to modify target proteins including therapeutic glycoprotein drugs with O-GalNAc glycosylation at specific glycosylated sites in vitro.

O-linked N-acetylgalactosamine modification is present on the tumor suppressor p53.

Background: Mucin-type O-glycosylation (referred to as O-GalNAc glycosylation) is the most abundant O-glycosylation on membrane and secretory proteins. Recently several evidences suggest that nuclear or cytoplasmic proteins might also have O-GalNAc glycosylation. However, what nucleocytoplasmic proteins are O-GalNAc glycosylated and what the biological function of this modification in cells are still poorly understood.

3,4,5-Tri-O-caffeoylquinic acid methyl ester isolated from Lonicera japonica Thunb. Flower buds facilitates hepatitis B virus replication in HepG2.2.15 cells.

Caffeoylquinic acids are well known for their prominent antiviral activities. Beyond our expectations, we initially found 3,4,5-Tri-O-caffeoylquinic acid methyl ester (3,4,5-CQME) from L. japonica can facilitate HBV DNA and antigens secretion.

Mutational and transcriptomic landscapes of a rare human prostate basal cell carcinoma.

Background: As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization.

Methods: Here, we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34βE12 /P63 /PAP /PSA ). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained.

Chemical Cocktail Induces Hematopoietic Reprogramming and Expands Hematopoietic Stem/Progenitor Cells.

Generation of hematopoietic stem/progenitor cells (HSPCs) via cell expansion or cell reprogramming has been widely achieved by overexpression of transcription factors. Herein, it is reported that without introducing exogenous genes, mouse fibroblasts can be reprogrammed into hemogenic cells based on lineage tracing analysis, which further develop into hematopoietic cells, by treatment of cocktails of chemical compounds. The chemical cocktails also reprogram differentiated hematopoietic cells back into HSPC-like cells.

Mild cognitive impairment understanding: an empirical study by data-driven approach.

Background: Cognitive decline has emerged as a significant threat to both public health and personal welfare, and mild cognitive decline/impairment (MCI) can further develop into Dementia/Alzheimer's disease. While treatment of Dementia/Alzheimer's disease can be expensive and ineffective sometimes, the prevention of MCI by identifying modifiable risk factors is a complementary and effective strategy.

Results: In this study, based on the data collected by Centers for Disease Control and Prevention (CDC) through the nationwide telephone survey, we apply a data-driven approach to re-exam the previously founded risk factors and discover new risk factors.

The diagnostic and prognostic usage of circulating tumor DNA in operable hepatocellular carcinoma.

Circulating tumor DNA (ctDNA) is a promising noninvasive biomarker for hepatocellular carcinoma (HCC). In this study, we aimed to assess the diagnostic and prognostic value of ctDNA in HCC. Twenty-six operable HCC, 10 hepatitis and 10 cirrhosis patients were enrolled in this study.

Assessing tumor heterogeneity using ctDNA to predict and monitor therapeutic response in metastatic breast cancer.

Tumor heterogeneity was associated with treatment outcome of metastatic cancers but few studies have examined whether tumor heterogeneity in circulating tumor DNA (ctDNA) can be used to predict treatment outcome. ctDNA analysis was performed in 37 HER2-positive metastatic breast cancer patients treated with pyrotinib. Patients with high tumor heterogeneity had significantly worse PFS outcomes, with a median PFS of 30.

Mendelian Randomization Analysis Support Causal Associations of HbA1c with Circulating Triglyceride, Total and Low-density Lipoprotein Cholesterol in a Chinese Population.

Previous observational studies supported a positive association of glycated hemoglobin A1c (HbA1c) level with serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). However, the causal relationship between HbA1c and either one of them was unclear in the East Asians. We performed a Mendelian Randomization (MR) analysis in a community-based study sample in Shanghai, China (n = 11,935).

Genome-wide profiling of Epstein-Barr virus integration by targeted sequencing in Epstein-Barr virus associated malignancies.

: Epstein-Barr virus (EBV) is associated with multiple malignancies with expression of viral oncogenic proteins and chronic inflammation as major mechanisms contributing to tumor development. A less well-studied mechanism is the integration of EBV into the human genome possibly at sites which may disrupt gene expression or genome stability. : We sequenced tumor DNA to profile the EBV sequences by hybridization-based enrichment.

Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD.

Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning.

Background: To better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC.

Methods: We performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis.

Results: Mutational analysis identified eight significantly mutated genes in CC including four genes (, , and ), which have not previously been reported in CC.

Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia.

Background: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.

Methods: Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.

Results: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism.

Molecular Characterization of HBV DNA Integration in Patients with Hepatitis and Hepatocellular Carcinoma.

Infection by chronic hepatitis B virus (HBV) is one of the major causes of liver cirrhosis and primary hepatocellular carcinoma (HCC). Viral DNA integration into the host cell genome is a key mechanism of hepatocarcinogenesis. However, the molecular characterization and the potential clinical implications of HBV DNA integration into patients suffering from different hepatitis and HCC remain unclear.

SCF-mediated degradation of Brg1 suppresses gastric cancer metastasis.

Brg1/SMARCA4 serves as the ATPase and the helicase catalytic subunit for the multi-component SWI/SNF chromatin remodeling complex, which plays a pivotal role in governing chromatin structure and gene transcription. However, the upstream signaling pathways regulating Brg1 protein stability and its physiological contribution to carcinogenesis remain largely elusive. Here we report that Brg1 is a bona fide ubiquitin substrate of SCF.

Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.

The -linked β--acetylglucosamine (-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers. However, the precise connexion between -GlcNAc-modified proteins and their function in cells is largely undefined for most cases. Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.