The Development of a High-Strength Mg-10.3Gd-4.4Y-0.9Zn-0.7Mn Alloy Subjected to Large Differential-Thermal Extrusion and Isothermal Aging.

The large differential-thermal extrusion (LDTE) process, a novel approach for efficiently fabricating a high-strength Mg-10.3Gd-4.4Y-0.

The effects of pollution by multiple metals derived from long-term smelting activities on soil mite communities in arable soils under different land use types in East China.

Soil pollution represents a threat to soil biodiversity and to soil and human health. However, many ecotoxicological issues, such as the impact of heavy metal pollution on the soil mite community and its spatial distribution in areas with complex environmental factors, are not fully understood. Here, an investigation was conducted in an arable area (about 11 km) enclosed by surrounding mountains.

Discovery of diminazene as a dual inhibitor of SARS-CoV-2 human host proteases TMPRSS2 and furin using cell-based assays.

The proteases TMPRSS2 (transmembrane protease serine 2) and furin are known to play important roles in viral infectivity including systematic COVID-19 infection through priming of the spike protein of SARS-CoV-2 and related viruses. To discover small-molecules capable of inhibiting these host proteases, we established convenient and cost-effective cell-based assays employing Vero cells overexpressing TMPRSS2 and furin. A cell-based proteolytic assay for broad-spectrum protease inhibitors was also established using human prostate cancer cell line LNCaP.

Production and Structural Diversification of Withanolides by Aeroponic Cultivation of Plants of Solanaceae: Cytotoxic and Other Withanolides from Aeroponically Grown .

Withanolides constitute one of the most interesting classes of natural products due to their diversity of structures and biological activities. Our recent studies on withanolides obtained from plants of Solanaceae including and a number of species grown under environmentally controlled aeroponic conditions suggested that this technique is a convenient, reproducible, and superior method for their production and structural diversification. Investigation of aeroponically grown afforded 29 withanolides compared to a total of 13 obtained previously from the wild-crafted plant and included 12 new withanolides, physacoztolides I-M (-), 15-acetoxy-28-hydroxyphysachenolide C (), 28-oxophysachenolide C (), and 28-hydroxyphysachenolide C (), 5-chloro-6-hydroxy-5,6-dihydrophysachenolide D (), 15-acetoxy-5-chloro-6β-hydroxy-5,6-dihydrophysachenolide D (), 28-hydroxy-5-chloro-6-hydroxy-5,6-dihydrophysachenolide D (), physachenolide A-5-methyl ether (), and 17 known withanolides -, , and -.

Ring A/B-Modified 17β-Hydroxywithanolide Analogues as Antiproliferative Agents for Prostate Cancer and Potentiators of Immunotherapy for Renal Carcinoma and Melanoma.

Physachenolide C () is a 17β-hydroxywithanolide natural product with a unique anticancer potential, as it exhibits potent and selective in vitro antiproliferative activity against prostate cancer (PC) cells and promotes TRAIL-induced apoptosis of renal carcinoma (RC) and poly I:C-induced apoptosis of melanoma cells. To explore the effect of ring A/B modifications of physachenolide C () on these biological activities, 23 of its natural and semisynthetic analogues were evaluated. Analogues - were prepared by chemical transformations of a readily accessible compound, physachenolide D ().

Physachenolide C induces complete regression of established murine melanoma tumors via apoptosis and cell cycle arrest.

Melanoma is an aggressive skin cancer that metastasizes to other organs. While immune checkpoint blockade with anti-PD-1 has transformed the treatment of advanced melanoma, many melanoma patients fail to respond to anti-PD-1 therapy or develop acquired resistance. Thus, effective treatment of melanoma still represents an unmet clinical need.

Strobiloscyphones A-F, 6-Isopentylsphaeropsidones and Other Metabolites from sp. AZ0266, a Leaf-Associated Fungus of Douglas Fir.

Six new 6-isopentylsphaeropsidones, strobiloscyphones A-F (-), and a new hexadecanoic acid, (2,4,6)-8,9-dihydroxy-10-oxohexadeca-2,4,6-trienoic acid (), together with sphaeropsidone () and its known synthetic analogue 5-dehydrosphaeropsidone () were isolated from sp. AZ0266, a fungus inhabiting the leaf litter of Douglas fir (). The structures of - were established on the basis of their high-resolution mass and 1D and 2D NMR spectroscopic data, and their relative and/or absolute configurations were determined by NOE, comparison of experimental and calculated ECD spectra, and application of the modified Mosher's ester method.

Cycloartane- and Lanostane-Type Triterpenoids from the Resin of AZ-2, a Byproduct of Guayule Rubber Production.

A total of 12 new cycloartane- and lanostane-type triterpenoids including 16-deoxyargentatin A (), 16-deoxyisoargentatin A (), 7-oxoisoargentatin A (), 24--argentatin H (), 24---anisoylargentatin C (), 24---cinnamoylargentatin C (), 16-dehydroargentatin C (), 16,17(20)-didehydroargentatin C (), isoargentatin C (), isoargentatin H (), 3--quisquagenin (), and isoquisquagenin () together with 10 known triterpenoids (-) were isolated from the resin of AZ-2 obtained as a byproduct of Bridgestone guayule rubber production. The structures of new triterpenoids - and argentatin H (), which has previously been characterized as its diacetate (), were elucidated by extensive analysis of their spectroscopic data and chemical conversions, and the known compounds - were identified by comparison of their spectroscopic data with those reported. Of these, , , and exhibited weak cytotoxic activity for several cancer cell lines.

Cytotoxic Physalins from Aeroponically Grown .

Aeroponically grown afforded five new and six known withanolides including 10 physalins. The structures of the new withanolides, acutifolactone (), 5β,6β-epoxyphysalin C (), 5α-chloro-6β-hydroxyphysalin C (), and an inseparable mixture of 5β,6β-epoxy-2,3-dihydrophysalin F-3β--sulfate () and 5β,6β-epoxy-2,3-dihydrophysalin C-3β--sulfate (), were elucidated by analysis of their spectroscopic data and chemical interconversions. The known withanolides were identified as physalins B (), D (), F (), H (), I (), and U () by comparison of their spectroscopic data with those reported.

Ultrastrong low-carbon nanosteel produced by heterostructure and interstitial mediated warm rolling.

Ultrastrong materials can notably help with improving the energy efficiency of transportation vehicles by reducing their weight. Grain refinement by severe plastic deformation is, so far, the most effective approach to produce bulk strong nanostructured metals, but its scaling up for industrial production has been a challenge. Here, we report an ultrastrong (2.

Microstructure and Mechanical Properties of a Cold-Rolled Ultrafine-Grained Dual-Phase Steel.

A new processing route to produce Ultrafine-Grained Dual-Phase steel has been proposed, involving cold-rolling and subsequent intercritical annealing of a fibrous ferrite⁻martensite starting structure. Ultrafine-grained DP (UFG-DP) steel with an average ferrite grain size of about ~2.7 μm and an average martensite island size of ~2.

Assessment of toxicity of heavy metal-contaminated soils toward Collembola in the paddy fields supported by laboratory tests.

Effects on soil Collembola of Cu, Zn, Pb, and Cd pollution from Cu smelters over 40 years were investigated in paddy fields from an area of Eastern China. We compared the field effects to those observed in single-species laboratory tests employing the hemiedaphic collembolan Folsomia candida and the epedaphic Sinella curviseta obtained from laboratory cultures and exposed to field-collected polluted soil. The results indicated that different collembolan species responded differently to the pollution in the fields and could be divided into sensitive, indifferent, and tolerant types accordingly.

17β-Hydroxy-18-acetoxywithanolides from Aeroponically Grown Physalis crassifolia and Their Potent and Selective Cytotoxicity for Prostate Cancer Cells.

When cultivated under aeroponic growth conditions, Physalis crassifolia produced 11 new withanolides (1-11) and seven known withanolides (12-18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1-11 and 16 were evaluated for their potential anticancer activity using five tumor cell lines.

Sesquiterpenes and other constituents of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp.

Oxygenated guaiane-type sesquiterpenes, xylaguaianols A-D (1-4), an iso-cadinane-type sesquiterpene isocadinanol A (5), and an α-pyrone 9-hydroxyxylarone (6), together with five known sesquiterpenes (7-11), and four known cytochalasins (12-15) were isolated from a culture broth of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp. The structures of all compounds were elucidated by the analysis of their spectroscopic data and relative configurations of 1-5 were determined with the help of NMR NOESY experiments.

Discovery of Potent 17β-Hydroxywithanolides for Castration-Resistant Prostate Cancer by High-Throughput Screening of a Natural Products Library for Androgen-Induced Gene Expression Inhibitors.

Prostate cancer (PC) is the second most prevalent cancer among men in Western societies, and those who develop metastatic castration-resistant PC (CRPC) invariably succumb to the disease. The need for effective treatments for CRPC is a pressing concern, especially due to limited durable responses with currently employed therapies. Here, we demonstrate the successful application of a high-throughput gene-expression profiling assay directly targeting genes of the androgen receptor pathway to screen a natural products library leading to the identification of 17β-hydroxywithanolides 1-5, of which physachenolide D (5) exhibited potent and selective in vitro activity against two PC cell lines, LNCaP and PC-3.

Structure-activity relationships for withanolides as inducers of the cellular heat-shock response.

To understand the relationship between the structure and the remarkably diverse bioactivities reported for withanolides, we obtained withaferin A (WA; 1) and 36 analogues (2-37) and compared their cytotoxicity to cytoprotective heat-shock-inducing activity (HSA). By analyzing structure-activity relationships for the series, we found that the ring A enone is essential for both bioactivities. Acetylation of 27-OH of 4-epi-WA (28) to 33 enhanced both activities, whereas introduction of β-OH to WA at C-12 (29) and C-15 (30) decreased both activities.

Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: structure-activity relationships of geopyxins and their analogues.

Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3.

Smardaesidins A-G, isopimarane and 20-nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus.

Five new isopimarane diterpenes, smardaesidins A-E (1- 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C-F (10-13) were isolated from an endophytic fungal strain, Smardaea sp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus . Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers.

Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum.

Wound-healing assay-guided fractionation of an EtOAc extract of the fungal strain Fusarium oxysporum EPH2RAA endophytic in Ephedra fasciculata afforded beauvericin (1), (-)-oxysporidinone (2), and two new N-methyl-2-pyridones, (-)-4,6'-anhydrooxysporidinone (3) and (-)-6-deoxyoxysporidinone (4). Beauvericin (1) inhibited migration of the metastatic prostate cancer (PC-3M) and breast cancer (MDA-MB-231) cells and showed antiangiogenic activity in HUVEC-2 cells at sublethal concentrations. Cytotoxicity-guided fractionation of an EtOAc extract of F.

Synthesis and preliminary biological evaluation of beta-carotene and retinoic acid oxidation products.

Synthesis of the beta-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-beta-apo-carotene-13-one (1) was achieved in six steps starting from beta-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10beta-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10beta-epoxy-5,8,9,10-tetrahydroretinoate (15).

Cytotoxic and other metabolites of Aspergillus inhabiting the rhizosphere of Sonoran desert plants.

In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts of four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490beta) (3) were isolated from As. terreus occurring in the rhizosphere of Ambrosia ambrosoides, whereas As.