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1.
Nature ; 575(7784): 618-621, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31776491

RESUMEN

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

2.
Proc Natl Acad Sci U S A ; 119(45): e2211228119, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36322742

RESUMEN

Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special "organelle" formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG-coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.


Asunto(s)
Magnetosomas , Magnetospirillum , Nanopartículas , Neoplasias , Ratones , Animales , Proteínas Bacterianas/metabolismo , Magnetosomas/química , Bacterias Gramnegativas/metabolismo , Nanopartículas/química , Campos Magnéticos , Neoplasias/metabolismo , Magnetospirillum/metabolismo
3.
Nano Lett ; 24(15): 4454-4461, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38572779

RESUMEN

Colloidal quantum well (CQW) based light emitting diodes (LEDs) possess extra-high theoretical efficiency, but their performance still lags far behind conventional LEDs due to severe exciton quenching and unbalanced charge injection. Herein, we devised a gradient composition CdxZn1-xS shell to address these issues. The epitaxial shell with gradient composition was achieved through controlling competition between Cd2+ and Zn2+ cations to preferentially bind to the anions S2-. Thus, exciton quenching was suppressed greatly by passivating defects and reducing nonradiative recombination, thereby achieving near-unity photoluminescence quantum yield (PLQY). The gradient energy level of the shell reduced the hole injection barriers and increased the hole injection efficiency to balance the charge injection of LEDs. As a result, the LEDs achieved a high external quantum efficiency (EQE) of 22.83%, luminance of 111,319 cd/m2 and a long operational lifetime (T95@100 cd/m2) over 6,500 h, demonstrating the state-of-the-art performance for the CQW based LEDs.

4.
Nano Lett ; 24(17): 5238-5245, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38629707

RESUMEN

ZnTe colloidal semiconductor nanocrystals (NCs) have shown promise for light-emitting diodes (LEDs) and displays, because they are free from toxic heavy metals (Cd). However, so far, their low photoluminescence (PL) efficiency (∼30%) has hindered their applications. Herein, we devised a novel structure of ZnTe NCs with the configuration of ZnSe (core)/ZnTe (spherical quantum well, SQW)/ZnSe (shell). The inner layer ZnTe was grown at the surface of ZnSe core with avoiding using highly active and high-risk Zn sources. Due to the formation of coherently strained heterostructure which reduced the lattice mismatch, and the thermodynamic growth of ZnTe, the surface or interface defects were suppressed. A high PL efficiency of >60% was obtained for the green light-emitting ZnSe/ZnTe/ZnSe SQWs after ZnS outer layer passivation, which is the highest value for colloidal ZnTe-based NCs. This work paves the way for the development of novel semiconductor NCs for luminescent and display applications.

5.
Nano Lett ; 24(29): 8894-8901, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38990690

RESUMEN

Environmentally friendly InP-based quantum dots (QDs) are promising for light-emitting diodes (LEDs) and display applications. So far, the synthesis of highly emitting InP-based QDs via safe and economically viable amine-phosphine remains a challenge. Herein, we report the synthesis of amine-phosphine based InP/ZnSe/ZnS QDs by introducing an alloyed oxidation-free In-ZnSe transition layer (TL) at the core-shell interface. The TL not only has the essential function of preventing oxidation of the core and relieving interfacial strain but also results in oriented epitaxial growth of shell. The alloyed TL significantly mitigates the nonradiative recombination at core-shell interfacial trap states, thereby boosting the photoluminescence (PL) efficiency of the QDs up to 98%. Also, the Auger recombination is suppressed, extending the biexciton lifetime from 60 to 100 ps. The electroluminescence device based on the InP-based QDs shows a high external quantum efficiency over 10%, further demonstrating high quality QDs synthesized by this process.

6.
BMC Bioinformatics ; 25(1): 267, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160480

RESUMEN

BACKGROUND: The utilization of long reads for single nucleotide polymorphism (SNP) phasing has become popular, providing substantial support for research on human diseases and genetic studies in animals and plants. However, due to the complexity of the linkage relationships between SNP loci and sequencing errors in the reads, the recent methods still cannot yield satisfactory results. RESULTS: In this study, we present a graph-based algorithm, GCphase, which utilizes the minimum cut algorithm to perform phasing. First, based on alignment between long reads and the reference genome, GCphase filters out ambiguous SNP sites and useless read information. Second, GCphase constructs a graph in which a vertex represents alleles of an SNP locus and each edge represents the presence of read support; moreover, GCphase adopts a graph minimum-cut algorithm to phase the SNPs. Next, GCpahse uses two error correction steps to refine the phasing results obtained from the previous step, effectively reducing the error rate. Finally, GCphase obtains the phase block. GCphase was compared to three other methods, WhatsHap, HapCUT2, and LongPhase, on the Nanopore and PacBio long-read datasets. The code is available from https://github.com/baimawjy/GCphase . CONCLUSIONS: Experimental results show that GCphase under different sequencing depths of different data has the least number of switch errors and the highest accuracy compared with other methods.


Asunto(s)
Algoritmos , Polimorfismo de Nucleótido Simple , Polimorfismo de Nucleótido Simple/genética , Humanos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
7.
Diabetologia ; 67(4): 690-702, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38206363

RESUMEN

AIMS/HYPOTHESIS: Type 2 diabetes is a highly heterogeneous disease for which new subgroups ('clusters') have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes. METHODS: We included individuals with type 2 diabetes from the Maastricht Study, who were allocated to clusters based on a nearest centroid approach. We used logistic regression to evaluate the cluster-wise association with diabetes-related complications. We plotted the evolution of HbA1c levels over time and used Kaplan-Meier curves and Cox regression to evaluate the cluster-wise time to reach adequate glycaemic control. Quality of life based on the Short Form 36 (SF-36) was also plotted over time and adjusted for age and sex using generalised estimating equations. The follow-up time was 7 years. Analyses were performed separately for people with newly diagnosed and already diagnosed type 2 diabetes. RESULTS: We included 127 newly diagnosed and 585 already diagnosed individuals. Already diagnosed people in the SIDD cluster were less likely to reach glycaemic control than people in the other clusters, with an HR compared with MARD of 0.31 (95% CI 0.22, 0.43). There were few differences in the mental component score of the SF-36 in both newly and already diagnosed individuals. In both groups, the MARD cluster had a higher physical component score of the SF-36 than the other clusters, and the MOD cluster scored similarly to the SIDD and SIRD clusters. CONCLUSIONS/INTERPRETATION: Disease severity suggested by the clusters of type 2 diabetes is not entirely reflected in quality of life. In particular, the MOD cluster does not appear to be moderate in terms of quality of life. Use of the suggested cluster names in practice should be carefully considered, as the non-neutral nomenclature may affect disease perception in individuals with type 2 diabetes and their healthcare providers.


Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Calidad de Vida , Insulina
8.
Nat Prod Rep ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712365

RESUMEN

Covering: Up to 2024Due to the widespread distribution of protoberberine alkaloids (PBs) and tetrahydroberberine alkaloids (THPBs) in nature, coupled with their myriad unique physiological activities, they have garnered considerable attention from medical practitioners. Over the past few decades, synthetic chemists have devised various total synthesis methods to attain these structures, continually expanding reaction pathways to achieve more efficient synthetic strategies. Simultaneously, the chiral construction of THPBs has become a focal point. In this comprehensive review, we categorically summarized the developmental trajectory of the total synthesis of these alkaloids based on the core closure strategies of protoberberine and tetrahydroberberine.

9.
Nat Prod Rep ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149831

RESUMEN

Retraction of 'Recent advances in total synthesis of protoberberine and chiral tetrahydroberberine alkaloids' by Zhen-Xi Niu et al., Nat. Prod. Rep., 2024, https://doi.org/10.1039/d4np00016a.

10.
Environ Microbiol ; 26(5): e16622, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38757466

RESUMEN

Microbial communities that reduce nitrous oxide (N2O) are divided into two clades, nosZI and nosZII. These clades significantly differ in their ecological niches and their implications for N2O emissions in terrestrial environments. However, our understanding of N2O reducers in aquatic systems is currently limited. This study investigated the relative abundance and diversity of nosZI- and nosZII-type N2O reducers in rivers and their impact on N2O emissions. Our findings revealed that stream sediments possess a high capacity for N2O reduction, surpassing N2O production under high N2O/NO3- ratio conditions. This study, along with others in freshwater systems, demonstrated that nosZI marginally dominates more often in rivers. While microbes containing either nosZI and nosZII were crucial in reducing N2O emissions, the net contribution of nosZII-containing microbes was more significant. This can be attributed to the nir gene co-occurring more frequently with the nosZI gene than with the nosZII gene. The diversity within each clade also played a role, with nosZII species being more likely to function as N2O sinks in streams with higher N2O concentrations. Overall, our findings provide a foundation for a better understanding of the biogeography of stream N2O reducers and their effects on N2O emissions.


Asunto(s)
Bacterias , Óxido Nitroso , Ríos , Óxido Nitroso/metabolismo , Ríos/microbiología , Ríos/química , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Sedimentos Geológicos/microbiología , Oxidación-Reducción , Filogeografía , Filogenia , Microbiota
11.
Small ; 20(6): e2306466, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37775327

RESUMEN

Proteins exhibit complex and diverse multi-dimensional structures, along with a wide range of functional groups capable of binding metal ions. By harnessing the unique characteristics of proteins, it is possible to enhance the synthesis of metal-organic frameworks (MOFs) and modify their morphology. Here, the utilization of biomineralized bovine serum albumin (BSA) protein as a template for synthesizing Mil-100 with superior microwave absorption (MA) properties is investigated. The multi-dimensional structure and abundant functional groups of biomineralized BSA protein make it an ideal candidate for guiding the synthesis of Mil-100 with intricate network structures. The BSA@Mil-100 synthesized using this method exhibits exceptional uniformity and monodispersity of nanocrystals. The findings suggest that the BSA protein template significantly influences the regulation of nanocrystal and microstructure formation of Mil-100, resulting in a highly uniform and monodisperse structure. Notably, the synthesized 2-BSA@Mil-100 demonstrates a high reflection loss value of -58 dB at 8.85 GHz, along with a maximum effective absorption bandwidth value of 6.79 GHz, spanning from 6.01 to 12.8 GHz. Overall, this study highlights the potential of utilizing BSA protein as a template for MOF synthesis, offering an effective strategy for the design and development of high-performance MA materials.

12.
Small ; : e2402752, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822717

RESUMEN

Surface modification of Cu current collectors (CCs) is proven to be an effective method for protecting lithium metal anodes. However, few studies have focused on the quality and efficiency of modification layers. Herein, a novel home-made filtered cathode vacuum arc (FCVA) co-deposition system with high modification efficiency, good repeatability and environmental friendliness is proposed to realize the wide range regulation of film composition, structure and performance. Through this system, ZnMgTiAl quaternary alloy films, which have good affinity with Li are successfully constructed on Cu CCs, and the fully enhanced electrochemical performances are achieved. Symmetrical cells constructed with modified CCs maintained a fairly low voltage hysteresis of only 13 mV after 2100 h at a current density of 1 mA cm-2. In addition, the capacity retention rate is as high as 75.0% after 100 cycles in the full cells. The influence of alloy films on the dynamic evolution process of constructing stable artificial solid electrolyte interphase (SEI) layer is revealed by in situ infrared (IR) spectroscopy. This work provides a promising route for designing various feasible modification films for LMBs, and it displays better industrial application prospects than the traditional chemical methods owing to the remarkable controllability and scale-up capacity.

13.
Nat Mater ; 22(4): 489-494, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36959503

RESUMEN

Pressure-induced magnetic phase transitions are attracting interest as a means to detect superconducting behaviour at high pressures in diamond anvil cells, but determining the local magnetic properties of samples is a challenge due to the small volumes of sample chambers. Optically detected magnetic resonance of nitrogen vacancy centres in diamond has recently been used for the in situ detection of pressure-induced phase transitions. However, owing to their four orientation axes and temperature-dependent zero-field splitting, interpreting these optically detected magnetic resonance spectra remains challenging. Here we study the optical and spin properties of implanted silicon vacancy defects in 4H-silicon carbide that exhibit single-axis and temperature-independent zero-field splitting. Using this technique, we observe the magnetic phase transition of Nd2Fe14B at about 7 GPa and map the critical temperature-pressure phase diagram of the superconductor YBa2Cu3O6.6. These results highlight the potential of silicon vacancy-based quantum sensors for in situ magnetic detection at high pressures.

14.
J Anat ; 244(1): 133-141, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37688452

RESUMEN

Anatomical variations of the right hepatic vein, especially large variant right hepatic veins (≥5 mm), have important clinical implications in liver transplantation and resection. This study aimed to evaluate anatomical variations of the right hepatic vein using quantitative three-dimensional visualization analysis. Computed tomography images of 650 patients were retrospectively analyzed, and three-dimensional visualization was applied using the derived data to analyze large variant right hepatic veins. The proportion of the large variant right hepatic vein was 16.92% (110/650). According to the location and number of the variant right hepatic veins, the configuration of the right hepatic venous system was divided into seven subtypes. The length of the retrohepatic inferior vena cava had a positive correlation with the diameter of the right hepatic vein (rs = 0.266, p = 0.001) and the variant right hepatic veins (rs = 0.211, p = 0.027). The diameter of the right hepatic vein was positively correlated with that of the middle hepatic vein (rs = 0.361, p < 0.001), while it was inversely correlated with that of the variant right hepatic veins (rs = -0.267, p = 0.005). The right hepatic vein diameter was positively correlated with the drainage volume (rs = 0.489, p < 0.001), while the correlation with the variant right hepatic veins drainage volume was negative (rs = -0.460, p < 0.001). The number of the variant right hepatic veins and their relative diameters were positively correlated (p < 0.001). The volume and percentage of the drainage area of the right hepatic vein decreased significantly as the number of the variant right hepatic vein increased (p < 0.001). The findings of this study concerning the variations of the hepatic venous system may be useful for the surgical planning of liver resection or transplantation.


Asunto(s)
Venas Hepáticas , Trasplante de Hígado , Humanos , Venas Hepáticas/diagnóstico por imagen , Venas Hepáticas/anatomía & histología , Venas Hepáticas/cirugía , Estudios Retrospectivos , Vena Cava Inferior/diagnóstico por imagen , Hepatectomía/métodos
15.
Opt Lett ; 49(11): 2966-2969, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824304

RESUMEN

Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

16.
Arch Biochem Biophys ; 756: 109997, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38621443

RESUMEN

The preservation of the native conformation and functionality of membrane proteins has posed considerable challenges. While detergents and liposome reconstitution have been traditional approaches, nanodiscs (NDs) offer a promising solution by embedding membrane proteins in phospholipids encircled by an amphipathic helical protein MSP belt. Nevertheless, a drawback of commonly used NDs is their limited homogeneity and stability. In this study, we present a novel approach to construct covalent annular nanodiscs (cNDs) by leveraging microbial transglutaminase (MTGase) to catalyze isopeptide bond formation between the side chains of terminal amino acids, specifically Lysine (K) and Glutamine (Q). This methodology significantly enhances the homogeneity and stability of NDs. Characterization of cNDs and the assembly of membrane proteins within them validate the successful reconstitution of membrane proteins with improved homogeneity and stability. Our findings suggest that cNDs represent a more suitable tool for investigating interactions between membrane proteins and lipids, as well as for analyzing membrane protein structures.


Asunto(s)
Proteínas de la Membrana , Nanoestructuras , Transglutaminasas , Nanoestructuras/química , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Transglutaminasas/química , Transglutaminasas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo
17.
Value Health ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38795956

RESUMEN

OBJECTIVES: Economic evaluations (EEs) are commonly used by decision makers to understand the value of health interventions. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) provide reporting guidelines for EEs. Healthcare systems will increasingly see new interventions that use artificial intelligence (AI) to perform their function. We developed Consolidated Health Economic Evaluation Reporting Standards for Interventions that use AI (CHEERS-AI) to ensure EEs of AI-based health interventions are reported in a transparent and reproducible manner. METHODS: Potential CHEERS-AI reporting items were informed by 2 published systematic literature reviews of EEs and a contemporary update. A Delphi study was conducted using 3 survey rounds to elicit multidisciplinary expert views on 26 potential items, through a 9-point Likert rating scale and qualitative comments. An online consensus meeting was held to finalize outstanding reporting items. A digital health patient group reviewed the final checklist from a patient perspective. RESULTS: A total of 58 participants responded to survey round 1, 42, and 31 of whom responded to rounds 2 and 3, respectively. Nine participants joined the consensus meeting. Ultimately, 38 reporting items were included in CHEERS-AI. They comprised the 28 original CHEERS 2022 items, plus 10 new AI-specific reporting items. Additionally, 8 of the original CHEERS 2022 items were elaborated on to ensure AI-specific nuance is reported. CONCLUSIONS: CHEERS-AI should be used when reporting an EE of an intervention that uses AI to perform its function. CHEERS-AI will help decision makers and reviewers to understand important AI-specific details of an intervention, and any implications for the EE methods used and cost-effectiveness conclusions.

18.
BMC Med Res Methodol ; 24(1): 112, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734644

RESUMEN

Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Prolinfocítica de Células T , Aprendizaje Automático , Trasplante Homólogo , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Homólogo/métodos , Leucemia Prolinfocítica de Células T/terapia , Leucemia Prolinfocítica de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Enfermedad Aguda
19.
Org Biomol Chem ; 22(22): 4521-4527, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38752482

RESUMEN

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 µM and 20 µM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aß25-35-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 µM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aß25-35-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.


Asunto(s)
Benzopiranos , Fármacos Neuroprotectores , Penicillium , Penicillium/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Benzopiranos/farmacología , Benzopiranos/química , Benzopiranos/aislamiento & purificación , Animales , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Pigmentos Biológicos/farmacología , Pigmentos Biológicos/química , Pigmentos Biológicos/aislamiento & purificación , Humanos , Neuronas/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/química , Estructura Molecular
20.
J Nat Prod ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38687877

RESUMEN

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

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