Structural basis for the multimerization of nonstructural protein nsp9 from SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of a potentially fatal disease named coronavirus disease 2019 (COVID-19), has raised significant public health concerns globally. To date, the COVID-19 pandemic has caused millions of people to be infected with SARS-CoV-2 worldwide. It has been known since the 2003 SARS epidemic that coronaviruses (CoVs) have large RNA genomes, the replication of which requires an RNA-dependent RNA replication/transcription complex.

The Diagnostic Value of Radiomics-Based Machine Learning in Predicting the Grade of Meningiomas Using Conventional Magnetic Resonance Imaging: A Preliminary Study.

The purpose of the current study is to investigate whether texture analysis-based machine learning algorithms could help devise a non-invasive imaging biomarker for accurate classification of meningiomas using machine learning algorithms. The study cohort was established from the hospital database by reviewing the medical records. Patients were selected if they underwent meningioma resection in the neurosurgery department between January 2015 and December 2018.

Ferulin C triggers potent PAK1 and p21-mediated anti-tumor effects in breast cancer by inhibiting Tubulin polymerization in vitro and in vivo.

Ferulin C, a natural sesquiterpene coumarin, isolated from the roots of Ferula ferulaeoides (Steud.) Korov, displaying potent antiproliferatory activity against breast cancer cells. This study aimed to elucidate the underlying molecular mechanisms of Ferulin C-induced breast cancer cells death in vitro and in vivo.

"Shanghuo" increases disease susceptibility: Modern significance of an old TCM theory.

Ethnopharmacological Relevance: "Shanghuo", a concept based on Traditional Chinese Medicine (TCM) theory, describes a status of Yin-Yang imbalance when Yang overwhelms Yin. The imbalance of Yin-Yang resembles the breaking of homeostasis and manifests by the impaired physiological functions, which leads to the onset, recurrence, and progression of diseases. Since ancient times, Chinese Materia Medica (CMM), such as herbal tea, has been applied as a treatment for "Shanghuo".

Design and synthesis of novel spirooxindole-indenoquinoxaline derivatives as novel tryptophanyl-tRNA synthetase inhibitors.

In the current study, we used an integrated approach combining bioinformatics, rational drug design, one-pot synthesis, and biological experiments in vitro for the potential discovery of novel tryptophanyl-tRNA synthetase (TrpRS) inhibitors. Atom economic and diastereoselective syntheses were used to generate several Spirooxindole-indenoquinoxaline derivatives in situ from isatin and amino acids viz. proline, phenylglycine, and sarcosine through targeting the 1,3-dipolar cycloaddition of azomethine ylides.

Temporal DNA methylation pattern and targeted therapy in colitis-associated cancer.

DNA methylation plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). However, the global and temporal DNA methylation pattern during initiation and progression of colitis-associated cancer (CAC) are still unknown, including the potential therapeutic strategy of targeting methylation for CAC. In the present study, the global DNA methylation pattern was determined at different time points during CAC using DNA methylation sequencing, followed by the Starburst plot integrating alterations and potential functional prediction analysis.

Negative cooperativity between Gemin2 and RNA provides insights into RNA selection and the SMN complex's release in snRNP assembly.

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA).

Phloretin ameliorates hyperuricemia-induced chronic renal dysfunction through inhibiting NLRP3 inflammasome and uric acid reabsorption.

Background: Hyperuricemia (HUA) is an important risk factor for renal diseases and contributes to renal fibrosis. It has been proved that phloretin has antioxidant and anti-inflammatory properties and could inhibit uric acid (UA) uptake in vitro. However, whether phloretin has a renal protective role in vivo remains unknown.

Differential Expression of Renin-Angiotensin System-related Components in Patients with Rheumatoid Arthritis and Osteoarthritis.

Background: The purpose of this study was to demonstrate the role of renin-angiotensin system (RAS)-related components, vascular endothelial growth factor (VEGF) and atrial metalloproteinase-13 (MMP-13) in synovial tissue and synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Materials And Methods: Thirty-four patients with RA and 41 patients with OA were included in the study. Renin, angiotensin-converting enzyme (ACE), VEGF and MMP-13 protein levels in the synovial fluid were measured by enzyme-linked immunosorbent assay.

Contrast-Enhanced MRI Texture Parameters as Potential Prognostic Factors for Primary Central Nervous System Lymphoma Patients Receiving High-Dose Methotrexate-Based Chemotherapy.

Introduction: The purpose of this study was to evaluate the prognostic value of texture features on contrast-enhanced magnetic resonance imaging (MRI) for patients with primary central nervous system lymphoma (PCNSL).

Methods: In this retrospective study, fifty-two patients diagnosed with PCNSL were enrolled from October 2010 to March 2017. The texture feature of tumor tissue on the histogram-based matrix (histo-) and the grey-level co-occurrence matrix (GLCM) was retrieved by contrast-enhanced T1-weighted imaging before any antitumor treatment.

Cancer Targeted Gene Therapy for Inhibition of Melanoma Lung Metastasis with eIF3i shRNA Loaded Liposomes.

Eukaryotic translation initiation factors 3i (eIF3i) is a proto-oncogene that is overexpressed in various tumors, reducing its expression by eIF3i shRNA is a promising strategy to inhibit tumor growth or metastasis. Tumor cell is the target of eIF3i shRNA so that tumor-site accumulation could be important for fulfilling its therapeutic effect. Thus, the iRGD modified liposome (R-LP) was rationally synthesized to enhance the antitumor effect by active targeted delivery of eIF3i shRNA to B16F10 melanoma cells.

Radiomics-Based Machine Learning Technology Enables Better Differentiation Between Glioblastoma and Anaplastic Oligodendroglioma.

The aim of this study was to test whether radiomics-based machine learning can enable the better differentiation between glioblastoma (GBM) and anaplastic oligodendroglioma (AO). This retrospective study involved 126 patients histologically diagnosed as GBM ( = 76) or AO ( = 50) in our institution from January 2015 to December 2018. A total number of 40 three-dimensional texture features were extracted from contrast-enhanced T1-weighted images using LIFEx package.

Targeting Autophagy with Small-Molecule Modulators in Immune-Related Diseases.

Autophagy, a highly conserved and multistep lysosomal degradation process, plays a pivotal role in maintaining cellular and physiological homeostasis. Of note, autophagy controls intracellular homeostasis and cell responses to stresses by regulating the self-renewal, maturation, and survival of immune cells. And dysregulation of autophagy in immune cells may contribute to the inflammatory disorders and defect in immune responses against invasive pathogens.

RGD-Modified Nanocarrier-Mediated Targeted Delivery of Plasmid DNA to Cerebrovascular Endothelial Cells for Ischemic Stroke Treatment.

Studies have shown that the use of proangiogenic genes can improve the prognosis of ischemic stroke by promoting angiogenesis at the injury site. For example, within this study, hypoxia-inducible factor 1-α (HIF-1α) has exhibited an angiogenic effect. Our previous study reported a more stable HIF-1α mutant form (HIF-1α-AA), which was transfected into mesenchymal stem cells to provide neuroprotective effects against ischemic stroke.

Active DNA unwinding and transport by a membrane-adapted helicase nanopore.

Nanoscale transport through nanopores and live-cell membranes plays a vital role in both key biological processes as well as biosensing and DNA sequencing. Active translocation of DNA through these nanopores usually needs enzyme assistance. Here we present a nanopore derived from truncated helicase E1 of bovine papillomavirus (BPV) with a lumen diameter of c.

The prognostic value of pretreatment inflammatory biomarkers in primary angiosarcoma.

Background: Recent studies have suggested a significant relationship between inflammatory indexes such as the neutrophil-to-lymphocyte ratio (NLR) and survival outcomes in various cancers. The aim of the present study was to evaluate the prognostic value of 6 pretreatment inflammatory markers in patients with primary angiosarcoma (AS) which is a rare and highly malignant type of soft tissue sarcoma.

Methods: Fifty-six patients diagnosed with primary AS at West China Hospital between August 2009 and July 2016 were retrospectively enrolled.

Structural basis of the mechanism of β-methyl epimerization by enzyme MarH.

Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the β-position of (3R)-β-methyl-indolepyruvate (MeInPy), forming (3S)-β-MeInPy.

Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis.

Breast cancer is the most common female cancer with considerable metastatic potential, which urges the need for developing novel potential drug candidate to inhibit tumor metastasis. Signal transducer and activator of transcription 3 (Stat3) have critical roles in cancer growth and metastasis and have been confirmed as a promising anticancer target. Here, we report our finding with pectolinarigenin, a flavonoid compound isolated from the aerial parts of .

Is Preoperative Fibrinogen Associated with the Survival Prognosis of Gastric Cancer Patients? A Multi-centered, Propensity Score-Matched Retrospective Study.

Background: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy.

Methods: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated.

Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer.

A new series of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives were designed, synthesized and demonstrated to act as tubulin polymerization inhibitors. These new derivatives showed significant antitumor activities, among which SKLB0533 demonstrated to be the most potent compound, with IC values ranging from 44.5 to 135.

Transcripto-based network analysis reveals a model of gene activation in tongue squamous cell carcinomas.

Background: Tongue squamous cell carcinoma (TSCC) is the most common malignant tumor derived from the oral cavity, yet its specific molecular mechanisms have not been fully clarified. The aim of this study was to evaluate the association between potential genes and clinical features through constructing gene co-expression networks.

Methods: The weighted gene co-expression network analysis was used to construct gene co-expression networks and to identify candidate key modules and hub genes.

SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

SARI (suppressor of AP-1, regulated by IFN) impaired tumour growth by promoting apoptosis and inhibiting cell proliferation and tumour angiogenesis in various cancers. However, the role of SARI in regulating tumour-associated inflammation microenvironment is still elusive. In our study, the colitis-dependent and -independent primary model were established in SARI deficiency mice and immuno-reconstructive mice to investigate the functional role of SARI in regulating tumour-associated inflammation microenvironment and primary colon cancer formation.