Characterization of cancer-driving nucleotides (CDNs) across genes, cancer types, and patients.

A central goal of cancer genomics is to identify, in each patient, all the cancer-driving mutations. Among them, point mutations are referred to as cancer-driving nucleotides (CDNs), which recur in cancers. The companion study shows that the probability of recurrent hits in patients would decrease exponentially with ; hence, any mutation with ≥ 3 hits in The Cancer Genome Atlas (TCGA) database is a high-probability CDN.

Congested heptacyclic meroterpenoids with anti-SARS-CoV-2 and anti-inflammatory activities from mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041.

Under the guidance of LC‒MS/MS-based molecular networking, three previously undescribed berkeleyacetal type meroterpenoids, amestolknoids A-C (1-3), together with ten known analogues (4-13) were isolated and identified from the mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041. Amestolknoids A (1) and B (2) are unprecedentedly congested 6/7/6/5/5/5/5 heptacyclic scaffolds characterized by two chiral spiroketal centers. Amestolknoids A (1) and C (3) represent the first examples of chlorinated berkeleyacetal type meroterpenoids.

Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.

Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity.

Epidemiology, genetic characteristics, and association with meteorological factors of human metapneumovirus infection in children in southern China: A 10-year retrospective study.

Objectives: This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of meteorological factors on infection.

Methods: 14,817 children (≤14 years) with acute respiratory tract infections from 2010 to 2019 were examined for HMPV and other respiratory viruses by real-time quantitative polymerase chain reaction. Full-length F gene of 54 positive samples were sequenced and subjected to phylogenetic analysis.

m A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.

The importance of mRNA N6-methyladenosine (m A) modification during tumor metastasis is controversial as it plays distinct roles in different biological contexts. Moreover, how cancer cell plasticity is shaped by m A modification is interesting but remains uncharacterized. Here, this work shows that m A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is remarkably upregulated in metastatic lung adenocarcinoma (LUAD) and indicates worse prognosis of patients.

PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis.

Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation.

ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.

The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells.

Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation.

Germline-encoded pattern recognition receptors (PRRs) recognize molecules frequently found in pathogens (pathogen-associated molecular patterns [PAMPs]) during viral infection. This process induces production of IFNs, leading to expression of IFN-stimulated genes to establish a cellular antiviral state against viral infection. However, aberrant activation of the IFN system may cause immunopathological damage and systemic autoimmune diseases such as systemic lupus erythematosus.

Design, synthesis, and biological evaluation of novel 2'-methyl-2'-fluoro-6-methyl-7-alkynyl-7-deazapurine nucleoside analogs as anti-Zika virus agents.

Zika virus (ZIKV) is a mosquito-borne flavivirus and outbreaks of ZIKV have been reported in Africa, Americas and other parts of the world lately. The ZIKV epidemic has received extensive attention due to its ability to cause serious medical consequences and complications such as microcephaly and Guillain-Barre syndrome in recent years. Up to now, there are no specific treatments or vaccines available for ZIKV infection, which highlights the urgent need for developing new therapies.

The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer.

Although chemotherapy can stimulate antitumor immunity by inducing interferon (IFN) response, the functional role of tumor-associated macrophages in this scenario remains unclear. Here, we found that IFN-activated proinflammatory macrophages after neoadjuvant chemotherapy enhanced antitumor immunity but promoted cancer chemoresistance. Mechanistically, IFN induced expression of cytoplasmic long noncoding RNA IFN-responsive nuclear factor-κB activator (IRENA) in macrophages, which triggered nuclear factor-κB signaling via dimerizing protein kinase R and subsequently increased production of protumor inflammatory cytokines.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

Background: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China.

Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China.

Loss of ATF4 leads to functional aging-like attrition of adult hematopoietic stem cells.

Aging of hematopoietic stem cells (HSCs) directly contributes to dysfunction of hematopoietic and immune systems due to aging-associated alterations in HSC features. How the function of adult HSCs is regulated during aging so that relevant pathologic abnormalities may occur, however, remains incompletely understood. Here, we report that ATF4 deficiency provokes severe HSC defects with multifaceted aging-like phenotype via cell-autonomous mechanisms.

An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus.