Penicichrysol A: an unprecedented polyketide produced by .

Penicichrysol A (1), a highly oxygenated polyketide with an unprecedented skeleton, uniquely defined by multiple contiguous quaternary carbons, was isolated as a racemate from an endophytic fungus that was sourced from the bulbs of the medicinal plant . Besides, three known biosynthetically related metabolites 2-4 were also obtained. The structure including the configuration of 1 was established a combination of NMR spectroscopy and single-crystal X-ray diffraction analysis.

Real-world Effectiveness of Azacitidine in Treatment-Naive Patients With Higher-risk Myelodysplastic Syndromes.

Introduction: Azacitidine (AZA) is an approved frontline therapy for higher-risk myelodysplastic syndromes (HR-MDS); however, poor survival denotes unmet needs to increase depth/duration of response (DOR).

Methods: This retrospective study with patient chart review evaluated AZA effectiveness in 382 treatment-naive patients with HR-MDS from a US electronic health record (EHR)-derived database. Responses were assessed using International Working Group (IWG) 2006 criteria; real-world equivalents were derived from EHRs.

Dipeniroqueforins A-B and Peniroqueforin D: Eremophilane-Type Sesquiterpenoid Derivatives with Cytotoxic Activity from .

Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (-) were isolated and identified from fungus , which was separated from the root soil of plant collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (-), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D () represents the first example of a 1,2- eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system.

Three new amide derivatives from the fungus Alternaria brassicicola.

Three new amide derivatives (alteralkaloids A-C, 1-3) and three known alkaloids (4-6) were afforded after phytochemical investigation of fungus Alternaria brassicicola. The structures of these compounds were confirmed by NMR spectroscopic and HRESIMS data. Furthermore, the absolute configuration of 1 was determined using the single-crystal X-ray diffraction analysis.

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti.

Two novel compounds including a cyclohelminthol type polyketide (namely oxaleimide K, 1) and a maleimide derivative (namely peniroquefortine A, 2), and a new natural product (namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide, 3), together with four known compounds (4-7), were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment.

Ten undescribed eremophilane and guaiane sesquiterpenes from Penicillium roqueforti.

Nine undescribed eremophilane sesquiterpenes, one undescribed guaiane sesquiterpene, along with ten known analogues were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures were elucidated on the basis of various spectroscopic analyses, mainly including NMR and HRESIMS data, C NMR calculations with DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments.

Drimane sesquiterpenoids from a wetland soil-derived fungus Aspergillus calidoustus TJ403-EL05.

Soil-derived fungi represent an insufficiently tapped reservoir for discovering new and bioactive natural products (NPs), and despite an ever-increasing number of unknown NPs have been discovered over the past few decades, much of the hidden biosynthetic potential is still in an urgent need to be disclosed. In this research, a chemical investigation was performed on a wetland soil-derived fungus Aspergillus calidoustus TJ403-EL05, leading to the isolation of a total of fourteen drimane sesquiterpenoids (1-14), incorporating three new ones, namely ustusols F-H (1-3). Their structures, comprising absolute configurations, were completely authenticated by widespread spectroscopic data, quantum chemical C NMR and ECD calculations, and X-ray crystallography experiments.

Structurally diverse metabolites from a soil-derived fungus Aspergillus calidoustus.

Fifteen secondary metabolites, including five new sesquiterpenoids (1-5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6-9 and 12-14), were isolated and characterized from fungus Aspergillus calidoustus, which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation.

Asperanstinoids A-E: Undescribed 3,5-dimethylorsellinic acid-based meroterpenoids from Aspergillus calidoustus.

Large-scale culture is a complementary and practical method for genome mining and OSMAC approaches to discover novel natural products through accumulation and reprocessing effects. By employing a large-scale culture approach, twelve 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoids, including five undescribed compounds, namely asperanstinoids A-E, were obtained from fungus Aspergillus calidoustus, which was isolated from the wetland soil collected at Dianchi Lake, Yunnan Province. The structures and absolute configurations of asperanstinoids A-E were determined by various spectroscopic analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations, and the absolute configurations of three known compounds, dehydroaustinol, austinol, and austin, were confirmed via single-crystal X-ray diffraction for the first time.

3-year Treatment of Tenofovir Alafenamide . Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China.

Background And Aims: Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).

Inducing new bioactive metabolites production from coculture of Pestalotiopsis sp. and Penicillium bialowiezense.

Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained.

Bioassay-Directed Isolation of Antibacterial Metabolites from an Arthropod-Derived .

Bioassay-directed isolation of secondary metabolites from an extract of TJ403-CA4 isolated from the medicinally valuable arthropod afforded five new and 10 known compounds (-). All the compounds (except ) belong to a minor class of highly rigid 6-5-5-5-fused tetracyclic cyclopiane-type diterpenes known to be exclusively produced by members of the genus. The structures and absolute configurations of the new compounds (-) were elucidated by extensive spectroscopic analyses, including HRESIMS and 1D and 2D NMR, single-crystal X-ray diffraction, and comparison of the experimental electronic circular dichroism data.

Terreuspyridine: An Unexpected Pyridine-Fused Meroterpenoid Alkaloid with a Tetracyclic 6/6/6/6 Skeleton from .

Terreuspyridine (), the first 3,5-demethylorsellinic acid (DMOA) derived meroterpenoid alkaloid, was isolated from the fungus , which represents a new type of meroterpenoid possessing an unexpected tetracyclic 6/6/6/6 architecture. The structure of with absolute configuration was determined by X-ray diffraction analysis. Biogenetically, it was proposed to be derived from the fusion of a DMOA-meroterpenoid and a glutamate.

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis.

Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686).

A new abietane-type diterpenoid and a new long-chain alkenone from fungus sp. TJ403-LS1.

A new abietane-type diterpenoid, dalterpenoid A (), a new long-chain alkenone derivative, (3,5,10)-8-hydroxytrideca-3,5,10,12-tetraen-2-one (), together with six known compounds (-), namely -guaidiol A (), xylaranol A (), daldinone C (), -3,4-dihydroxy-3,4-dihydro-anofinic acid (), ()-6-hydroxymellein (), helicascolide A (), were obtained from fungus sp. TJ403-LS1, which was originally isolated from roots of the medicinally valuable plant . The structures of compounds and were established based on widespread spectroscopic methods, mainly including 1D & 2D NMR and HRESIMS analyses, and the absolute configuration of was further confirmed by electronic circular dichroism (ECD) calculation.

Fusaresters A-E, new γ-pyrone-containing polyketides from fungus Fusarium sp. Hungcl and structure revision of fusariumin D.

Marine-derived fungi have been regarded as an under-explored and promising reservoir of structurally novel and bioactive natural products. In this study, five new γ-pyrone-containing polyketides, fusaresters A-E (1-5), were isolated and identified from the culture extracts of a marine-derived fungus Fusarium sp. Hungcl.

The ethanol extract of Involcucrum castaneae ameliorated ovalbumin-induced airway inflammation and smooth muscle thickening in guinea pigs.

Ethnopharmacological Relevance: Involucrum castaneae(IC)is used in Chinese folk medicine to treat various lung diseases, as well as for its reducing phlegm and anti-inflammatory properties.

Aim Of The Study: The purpose of this experiment is to verify the effect of IC on airway inflammation, responsiveness in ovalbumin (OVA)-induced asthmatic guinea pigs. The main chemical components of IC were also analyzed.

Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial.

Background: Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1 and KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFRα are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib versus imatinib as first-line therapy for patients with advanced GISTs.

Group sequential tests for long-term survival comparisons.

Sometimes in clinical trials, the hazard rates are anticipated to be nonproportional, resulting in potentially crossing survival curves. In these cases, researchers are usually interested in which treatment has better long-term survival. The log-rank test and the weighted log-rank test may not be appropriate or efficient to use here, because they are sensitive to differences in survival at any time and don't just focus on long-term outcomes.