Sex Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

Exploring the Diverse Landscape of Fungal Cytochrome P450-Catalyzed Regio- and Stereoselective Dimerization of Diketopiperazines.

Dimeric indole-containing diketopiperazines (di-DKPs) are a diverse group of natural products produced through cytochrome P450-catalyzed C-C or C-N coupling reactions. The regio- and stereoselectivity of these reactions plays a significant role in the structural diversity of di-DKPs. Despite their pivotal role, the mechanisms governing the selectivity in fungi are not fully understood. Employing bioinformatics analysis and heterologous expression experiments, five undescribed P450 enzymes (AmiP450, AcrP450, AtP450, AcP450, and AtuP450) responsible for the regio- and stereoselective dimerization of diketopiperazines (DKPs) in fungi are identified. The function of these P450s is consistent with phylogenetic analysis, highlighting their dominant role in controlling the dimerization modes. Combinatorial biosynthesis-based pathway reconstitution of non-native gene clusters expands the chemical space of fungal di-DKPs and reveals that the regioselectivity is influenced by the substrate. Furthermore, multiple sequence alignment and molecular docking of these enzymes demonstrate a C-terminal variable region near the substrate tunnel entrance in AtuP450 that is crucial for its regioselectivity. These findings not only reveal the secret of fungal di-DKPs diversity but also deepen understanding of the mechanisms and catalytic specificity involved in P450-catalyzed dimerization reactions.

Antibacterial p-terphenyl and α­pyrone derivates isolated from the marine-derived actinomycete Nocardiopsis sp. HDN154086.

Assisted by OSMAC strategy, one new p-terphenyl and two new α­pyrone derivates, namely nocarterphenyl I (1) and nocardiopyrone D-E (2-3), were obtained and characterized from the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The structures of these compounds were determined on the basis of MS, NMR spectroscopic data and single-crystal X-ray diffraction. Compound 1 with a rare 2,2'-bithiazole structure among natural products showed promising activity against five bacteria with MIC values ranging from 0.8 to 1.6 µM and 3 exhibited notable antibacterial activity against MRSA compared the positive control ciprofloxacin.

Overexpression of Global Regulator SCrp Leads to the Discovery of New Angucyclines in Streptomyces sp. XS-16.

Six angucyclines including three unreported compounds (1-3) were isolated from Streptomyces sp. XS-16 by overexpressing the native global regulator of SCrp (cyclic AMP receptor). The structures were characterized based on nuclear magnetic resonance (NMR) and spectrometry analysis and assisted by electronic circular dichroism (ECD) calculations. All compounds were tested for their antitumor and antimicrobial activities, and compound 1 showed different inhibitory activities against various tumor cell lines with IC50 values ranging from 0.32 to 5.33 µM.

Microbial Dimerization and Chlorination of Isoflavones by a Takla Makan Desert-Derived Streptomyces sp. HDN154127.

Sixteen new biisoflavones, bisoflavolins A-N (1-16), were discovered from cultures of the Takla Makan desert-derived strain Streptomyces sp. HDN154127. The chemical structures, including axial chirality, were elucidated by NMR, MS, and ECD analyses. Antibacterial activity of dimerized compounds was tested against seven different bacteria. The dimerized compounds showed better activity (MIC from 0.8 to 50.0 µM) than the corresponding monomers (daidzein and genistein, MIC > 50.0 µM). The rare dimeric and chlorinated structures in 1-16 were proved to be biotransformation products obtained from soy isoflavones and sodium chloride, which constituted the culture medium. This is the first report of an actinomycete that promotes both dimerization and chlorination utilizing natural isoflavones as skeletons sources.

Risk of all-cause mortality in subjects with varying degrees of renal impairment with or without dietary protein restriction.

BACKGROUND AND OBJECTIVE: Low-protein diet (less than 0.8g/kg/day) has been practiced in the management of chronic kidney disease (estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2 or urine albumin-to-creatinine ratios [UACR] ≥30mg/g) for decades. However, its effect on all-cause mortality is unclear. We investigated the association between a low-protein intake and all-cause mortality in subjects with varying degrees of renal impairment. MATERIALS AND METHODS: We analyzed participants in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2010. They were divided into four groups according to their eGFR (≥60 or <60ml/min/1.73m2) and UACR (≥30 or <30mg/g). Daily protein intake of the NHANES participants could be assessed using information from the dietary interview questionnaires. The mortality data was retrieved by linking to the National Death Index till the end of 2011. The hazard ratios for all-cause mortality were evaluated by the weighted Cox proportional hazards regression models. RESULTS: A total of 8093 participants were analyzed. During a median follow-up of 4.7 years, participants with UACR≥30mg/g (with or without eGFR<60ml/min/1.73m2) had a higher risk of all-cause mortality compared with those having UACR<30mg/g and eGFR≥60ml/min/1.73m2 (reference group). The higher risk of mortality in participants with UACR≥30mg/g was consistently observed in those with or without a low-protein intake. CONCLUSIONS: A low-protein intake was not associated with a lower risk of all-cause mortality in subjects with varying degrees of renal impairment.

Antibacterial angucyclinone and α-pyrone derivatives from desert-derived Nocardiopsis dassonvillei HDN 154151.

One new angucyclinone derivative, Kanglemycin N (1), and two new biogenetically related α-Pyrones, nocapyrones U-V (2-3), were isolated from a desert-derived Actinomycete Nocardiopsis dassonvillei HDN 154151. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compound 1 exhibited potent antibacterial activity against Bacillus subtilis, Proteus sp., Vibrio Parahaemolyticus, Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 0.39 µM to 1.56 µM, and notably the effect of 1 against MRSA significantly exceeded the positive control ciprofloxacin. In addition, compound 1 also showed moderate cytotoxic activity against H69AR, MDA-MB-231, ASPC-1 and K562 cell lines, with IC50 values of 10.46, 8.78, 9.28 and 8.61 µM, respectively.

Citreobenzofuran D-F and Phomenone A-B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494.

Five new sesquiterpenoids, citreobenzofuran D-F (1-3) and phomenone A-B (4-5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E-F (2-3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 µM.

Dimeric Tetracenomycin Derivatives from a Taklamakan Desert-Derived Streptomyces sp. HDN154193.

Bitetracenomycin A (1) and its diastereomers [(±)-bitetracenomycin B, (±)-2] were discovered from the cultures of Streptomyces sp. HDN154193. Compounds 1 and (±)-2 were the first tetracenomycin dimers obtained from a natural source with sp3 methine protons at the bridge positions (C-12/12'), which also exhibited broad-spectrum antibacterial activity. The racemate (±)-2 was semisynthesized and separated into enantiomers (+)-2 and (-)-2, and the absolute configurations were determined by specific rotation and ECD data. These metabolites exhibited potent antibacterial activity especially against drug-resistant strains (MRSA and MRCNS) with MIC values ranging from 1.0 to 1.9 µg/mL.

Saliniquinone Derivatives, Saliniquinones G-I and Heraclemycin E, from the Marine Animal-Derived Nocardiopsis aegyptia HDN19-252.

Four new anthraquinone derivatives, namely saliniquinones G-I (1-3) and heraclemycin E (4), were obtained from the Antarctic marine-derived actinomycete Nocardiopsis aegyptia HDN19-252, guided by the Global Natural Products Social (GNPS) molecular networking platform. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compounds 1 and 2 showed promising inhibitory activity against six tested bacterial strains, including methicillin-resistant coagulase-negative staphylococci (MRCNS), with MIC values ranging from 3.1 to 12.5 µM.

Spherical Hole-Transporting Interfacial Layer Passivated Defect for Inverted NiOx-Based Planar Perovskite Solar Cells with High Efficiency of over 20.

In this study, we achieved a facile and low-cost (18-22 USD/g) synthesis of spiro[fluorene-9,9-phenanthren-10-one]-based interfacial layer materials (MSs; designated MS-PC, MS-PA, MS-OC, and MS-OA). Carbazoles and dimethylacridine substituents with an extended π-conjugation achieved through ortho- or para-orientations were used as donors at the spiro[fluorene-9,9'-phenanthren-10'-one] moiety. Highly efficient and stable inverted perovskite solar cells (PSCs) with the device architecture of ITO/NiOx/MSs/perovskite/PC61BM/BCP/Ag can be achieved to improve the surface morphology of NiOx when MSs are adopted as the interfacial layer. During a morphological study, the ortho-orientated donor of MS-OC and MS-OA has spherical structures indicated that the films were smooth and that the films of perovskite deposited on them had large grain size and uniformity. The photoluminescence properties of the perovskite layers on the NiOx/MSs were showed better hole-transporting capabilities than the bare NiOx. The dual-functional interfacial layer has shown defect passivation effect, it not only improved the surface morphology of NiOx but also enlarged the perovskite layer grain size. The best PSC device performance of the NiOx/MS-OC was characterized by 22.34 mA cm-2 short-circuit current density (Jsc), 1.128 V open-circuit voltage (Voc), and 80.8% fill factor (FF), resulting in 20.34% power conversion efficiency (PCE). The NiOx/MS-OC PSCs showed good long-term device stability, even retained the original PCE of 93.16% after 370 days under argon (25 °C). Owing to the superior perovskite morphologies of the NiOx/MSs, the resulting devices outperformed the bare NiOx-based PSCs.

Antibacterial p-Terphenyl with a Rare 2,2'-Bithiazole Substructure and Related Compounds Isolated from the Marine-Derived Actinomycete Nocardiopsis sp. HDN154086.

Assisted by MS/MS-based molecular networking and X-ray diffraction analysis, five new p-terphenyl derivatives, namely, nocarterphenyls D-H (1-5), were obtained and characterized from the cultures of the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The skeleton of nocarterphenyl D (1) was defined to possess a rare 2,2'-bithiazole scaffold, naturally occurring for the first time, and nocarterphenyls E-H (2-5) are p-terphenylquinones with unusual thioether linked fatty acid methyl ester substitutions. Compound 1 showed promising activity against multiple bacteria with MIC values ranging from 1.5 to 6.2 µM, and 2 exhibited notable antibacterial activity against MRSA which surpassed the positive control ciprofloxacin.

Staprexanthones, Xanthone-Type Stimulators of Pancreatic ß-Cell Proliferation from a Mangrove Endophytic Fungus.

This project was focused on the discovery of novel compounds that promote endogenous ß-cell regeneration. Screening of extracts identified the fungus Stachybotrys chartarum as a promising candidate. After fermentation and extraction of S. chartarum, we isolated five new prenylated xanthones, namely, staprexanthones A-E (1-5), with staprexanthone A (1) being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Compounds 1, 2, and 5 significantly increased ß-cell numbers in vivo in a zebrafish model. Further analysis revealed that 2 and 5 promoted ß-cell mass expansion by increasing proliferation of existing ß-cells though promotion of cell-cycle progression at the G1/S transition. These findings indicate that prenylated xanthones are potential new drug leads for antidiabetes therapy by stimulating ß-cell regeneration.

Monacycliones G-K and ent-Gephyromycin A, Angucycline Derivatives from the Marine-Derived Streptomyces sp. HDN15129.

Six new angucycline derivatives, named monacycliones G-K (1-5) and ent-gephyromycin A (6), as well as three known ones (7-9) were discovered from the marine sediment-derived actinomycete Streptomyces sp. HDN15129 guided by Global Natural Products Social (GNPS) molecular networking. Structures including absolute configurations were elucidated by extensive NMR, MS, and ECD analyses. Among them, monacyclione G (1) possesses a unique scaffold featuring a xanthone core linked to the aminodeoxysugar ossamine, and monacycliones H-J (2-4) are rare examples of natural angucyclines with an S-methyl group. Monacycliones I and J (3 and 4) showed cytotoxic activity against multiple human cancer cell lines, with IC50 values ranging from 3.5 to 10 µM.

Secondary Metabolites from Deep-Sea Derived Microorganisms.

Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function. In this review, we particularly summarize those successful research on secondary metabolites produced by deep-sea derived microorganisms with inclusion of structural characteristics, biological activities, together with biogenetic origins and taxonomic features of the source microorganisms, from which, we expect to provide more comprehensive understanding of small molecules obtained from deep-sea environment and benefit the ongoing scholarly endeavors in the search for novel pharmaceutical agents from the deep-sea derived microorganisms.

α-Pyrone derivatives with cyto-protective activity from two Takla Makan desert soil derived actinomycete Nocardiopsis strains recovered in seawater based medium.

In this paper, we described the discovery of two Nocardiopsis strains HDN154-146 and HDN154-168 from Takla Makan desert soil samples using seawater based medium. Chemical investigation of these two strains led to the discovery of eight new α-pyrone derivatives named nocahypyrones A-H (1-8), together with one known analogue germicidin G (9). The structures of these compounds, including absolute configurations, were elucidated by extensive NMR, MS, and CD analyses. Compounds 1-9 were tested for their cyto-protective activities and for the first time we found α-pyrones 5 and 8 exhibited capabilities to induce expression of phase II detoxifying enzymes.

[60]Fulleropyrrolidines bearing π-conjugated moiety for polymer solar cells: contribution of the chromophoric substituent on C60 to the photocurrent.

Two fullerene-terthiophene dyads without hexyl chains (3T-C60) and with hexyl chains (3TH-C60) on the terthiophene substituent are synthesized by 1,3-dipolar cycloaddition of corresponding azomethine ylides to C60. The cyclic voltammetry studies indicate no apparent electronic communication between the terthiophene pendent group and the fulleropyrrolidine core in the ground state. However, a significant florescence quenching is observed for 3T-C60 and 3TH-C60, compared to their fluorescent terthiophene (3T) and 3TH precursors, respectively, suggesting the occurrence of strong intramolecular electron/energy transfers in the photoexcited state. Furthermore, these new fulleropyrrolidine derivatives are applied as electron acceptors to fabricate poly(3-hexylthiophene) (P3HT) based bulk heterojunction solar cells. The incident photon-to-current efficiency (IPCE) value of the P3HT/3T-C60 device is significantly higher than that of the P3HT/PCBM cell in wavelengths of 350-420 nm. This finding provides direct evidence for the contribution of 3T excitons to the photocurrent. Replacing 3T-C60 with 3TH-C60 effectively improves the morphology of the photoactive layer and widens the window of optimal D/A ratios, raising the power conversion efficiency (PCE) from 2.14% to 2.54%. Importantly, these devices exhibit superior stability of PCE against high-temperature aging.