Androgen receptor promotes arachidonic acid metabolism and angiogenic microenvironment in AFP-negative hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is a classic biomarker for hepatocellular carcinoma (HCC). AFP-positive HCC (AFP HCC) has been intensively investigated; however, the genomic, transcriptomic and microenvironmental characteristics of AFP-negative HCC (AFP HCC) remain to be deciphered. Here we show that tumors display mild differences in genetic alterations between AFP HCC and AFP HCC patients, while AFP HCC exhibits hyperactive arachidonic acid metabolism.

Single-cell transcriptomic landscape indicates the potential role of immunotherapy in metastatic pancreatic angiosarcoma.

Background: Pancreatic angiosarcoma is a rare and highly aggressive tumor originating from lymphatic or vascular endothelial cells, with poor prognosis and few effective treatments. In this study, we aimed to characterize the tumor ecosystem of metastatic pancreatic angiosarcoma, along with its potential treatment strategies.

Methods: Single-cell RNA-sequencing and bioinformatics analysis were performed on samples obtained from one patient, including at total of 16,841 cells from pancreatic angiosarcoma liver metastasis and adjacent normal liver tissue.

M6Allele: a toolkit for detection of allele-specific RNA N6-methyladenosine modifications.

Background: Allelic gene-specific regulatory events are crucial mechanisms in organisms, pivotal to many fundamental biological processes such as embryonic development and chromosome inactivation. Allelic gene imbalance manifests at both RNA expression and epigenetic levels. Recent research has unveiled allelic-specific regulation of RNA N6-methyladenosine (m6A), emphasizing the need for its precise identification.

Single-Cell Analysis Clarifies Pathological Heterogeneity in Tenosynovial Giant Cell Tumor and Identifies Biomarkers for Predicting Disease Recurrence.

Diffuse-type tenosynovial giant cell tumor (D-TGCT) and localized-type tenosynovial giant cell tumor (L-TGCT) share common genomic aberrations and histopathological features, but the former has a more aggressive nature and a higher recurrence rate, leading to worse prognoses for patients. In this study, single-cell RNA sequencing (scRNA-seq) on human D-TGCT and L-TGCT lesions is conducted to discover transcriptional differences. A unique cluster of tumor cells in D-TGCT is identified that regulated differentiation of CD34 fibroblasts into MMP3 fibroblasts or APOE fibroblasts via COL6A3 - (ITGAV + ITGB8) interaction.

Single-Cell Transcriptomic Analysis Reveals an Aggressive Basal-Like Tumor Cell Subpopulation Associated With Poor Prognosis in Intrahepatic Cholangiocarcinoma.

Background And Aim: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer whose incidence is increasing globally. However, the high tumor heterogeneity of ICC restricts the efficacy of available systematic therapies. We aim to dissect the tumor heterogeneity of ICC utilizing high-resolution single-cell RNA sequencing to identify novel therapeutic targets.

Addressing persistent challenges in digital image analysis of cancer tissue: resources developed from a hackathon.

The National Cancer Institute (NCI) supports numerous research consortia that rely on imaging technologies to study cancerous tissues. To foster collaboration and innovation in this field, the Image Analysis Working Group (IAWG) was created in 2019. As multiplexed imaging techniques grow in scale and complexity, more advanced computational methods are required beyond traditional approaches like segmentation and pixel intensity quantification.

Progressive plasticity during colorectal cancer metastasis.

As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition.

Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics.

High-quality schematic illustrations are fundamental to the publication of scientific achievements in biomedical research, which are crucial for effectively conveying complex biomedical concepts. However, creating such illustrations remains challenging for many researchers due to the need to devote a significant amount of time and effort to accomplish it. To address this need, we present the Generic Diagramming Platform (GDP, https://BioGDP.

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics.

There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, and toxicity have been reported in previous studies.

Wait or Pass? Promoting intersection's cooperation via identifying vehicle's social behavior.

Lack of communication between road users can reduce traffic efficiency and cause safety issues like traffic accidents. Researchers are exploring how intelligent vehicles should communicate with the environment, other vehicles, and road users. This study explores the impact of social information communication on traffic safety and efficiency at intersections through vehicle-to-vehicle (V2V) communication.

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system.

Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.

The efficacy of chemotherapy varies significantly among patients with gastric cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoids retain histological characteristics of their corresponding primary GC tissues.

The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1.

Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression.

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA.

A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.

Unlabelled: Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors.

PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness.

Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase.

Exploring COVID-19 causal genes through disease-specific Cis-eQTLs.

Genome-wide association study (GWAS) analysis has exposed that genetic factors play important roles in COVID-19. Whereas a deeper understanding of the underlying mechanism of COVID-19 was hindered by the lack of expression of quantitative trait loci (eQTL) data specific for disease. To this end, we identified COVID-19-specific cis-eQTLs by integrating nucleotide sequence variations and RNA-Seq data from COVID-19 samples.

An enhanced broad-spectrum peptide inhibits Omicron variants in vivo.

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker, which showed significantly improved antiviral activity. Further cholesterol (Chol) modification at the C terminus of A1L35HR2m greatly enhanced the inhibitory activities against SARS-CoV-2, SARS-CoV-2 VOCs, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) pseudoviruses, with IC values ranging from 0.

BioTreasury: a community-based repository enabling indexing and rating of bioinformatics tools.

The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments. Therefore, to aid scientists in making informed choices, a community-based platform that indexes and rates bioinformatics tools is urgently needed. In this study, we introduce BioTreasury ( http://biotreasury.

Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application.

Patients with biliary tract cancer (BTC) show different responses to chemotherapy, and there is no effective way to predict chemotherapeutic response. We have generated 61 BTC patient-derived organoids (PDOs) from 82 tumors (74.4%) that show similar histological and genetic characteristics to the corresponding primary BTC tissues.

Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19.

Introduction: Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future.

Objectives: This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment.

Hypoxia-driven tumor stromal remodeling and immunosuppressive microenvironment in scirrhous HCC.

Background And Aims: Scirrhous HCC (SHCC) is one of the unique subtypes of HCC, characterized by abundant fibrous stroma in the tumor microenvironment. However, the molecular traits of SHCC remain unclear, which is essential to develop specialized therapeutic approaches for SHCC.

Approach And Results: We presented an integrative analysis containing single-cell RNA-sequencing, whole-exome sequencing, and bulk RNA-sequencing in SHCC and usual HCC samples from 134 patients to delineate genomic features, transcriptomic profiles, and stromal immune microenvironment of SHCC.