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1.
Plant Cell ; 35(12): 4199-4216, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37647532

RESUMO

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.


Assuntos
Genoma de Planta , Triticum , Estados Unidos , Triticum/genética , Genoma de Planta/genética , Melhoramento Vegetal , Fenótipo , China , Variação Genética
2.
Clin Immunol ; 265: 110293, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936523

RESUMO

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.

3.
Anal Chem ; 96(22): 9244-9253, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38773697

RESUMO

Sensitive identification and effective inactivation of the virus are paramount for the early diagnosis and treatment of viral infections to prevent the risk of secondary transmission of viruses in the environment. Herein, we developed a novel two-step fluorescence immunoassay using antibody/streptavidin dual-labeled polystyrene nanobeads and biotin-labeled G-quadruplex/hemin DNAzymes with peroxidase-mimicking activity for sensitive quantitation and efficient inactivation of living Zika virus (ZIKV). The dual-labeled nanobeads can specifically bind ZIKV through E protein targeting and simultaneously accumulate DNAzymes, leading to the catalytic oxidation of Amplex Red indicators and generation of intensified aggregation-induced emission fluorescence signals, with a detection limit down to 66.3 PFU/mL and 100% accuracy. Furthermore, robust reactive oxygen species generated in situ by oxidized Amplex Red upon irradiation can completely kill the virus. This sensitive and efficient detection-inactivation integrated system will expand the viral diagnostic tools and reduce the risk of virus transmission in the environment.


Assuntos
DNA Catalítico , Zika virus , DNA Catalítico/química , DNA Catalítico/metabolismo , Imunoensaio/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Limite de Detecção , Quadruplex G , Inativação de Vírus/efeitos da radiação , Humanos
4.
Theor Appl Genet ; 137(6): 128, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733405

RESUMO

KEY MESSAGE: Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55 Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.


Assuntos
Genes de Plantas , Triticum , Alelos , Mapeamento Cromossômico , Haplótipos , Fenótipo , Triticum/genética , Triticum/crescimento & desenvolvimento
5.
J Nat Prod ; 87(5): 1347-1357, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38701173

RESUMO

A chemical investigation of a cold-seep-sediment-derived fungus, Pseudallescheria boydii CS-793, resulted in characterization of 10 novel bergamotene-derived sesquiterpenoids, pseuboyenes A-J (1-10). Their structures were elucidated by spectroscopic and X-ray crystallographic analyses as well as using the modified Mosher's method. Compound 1 represents the first example of a ß-bergamotene containing a 6-oxobicyclo[3.2.1]octane nucleus adducted with a methyl lactate unit, while 8-10 involve a skeletal rearrangement from bergamotene. Compounds 2-5 showed significant antifungal activities against Colletotrichum gloeosporioides Penz. and Fusarium oxysporum with MICs ranging from 0.5 to 8 µg/mL. Compound 4 exhibited an in vitro anti-F. proliferatum effect with an EC50 value of 1.0 µg/mL.


Assuntos
Antifúngicos , Testes de Sensibilidade Microbiana , Pseudallescheria , Sesquiterpenos , Antifúngicos/farmacologia , Antifúngicos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Estrutura Molecular , Colletotrichum/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Cristalografia por Raios X
6.
Bioorg Chem ; 147: 107417, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701596

RESUMO

Marine natural products play an important role in biopesticides. Seven new secondary metabolites with different structural classes, including two cycloheptapeptides, scortide A (1) and scortide B (2), two 19-nor-diterpenoids, talascortene H (3) and talascortene I (4), two diterpenoid acids, talascortene J (5) and talascortene K (6), and one triterpenoid, talascortene L (7) were isolated and identified from the sea-anemone-derived endozoic fungus Talaromyces scorteus AS-242. Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, tandem mass spectrometry, and electronic circular dichroism (ECD) calculations. The result of the antimicrobial assay demonstrated that compounds 1 - 6 have inhibitory activity against several human, aquatic, and plant pathogens with minimum inhibitory concentration (MIC) values ranging from 1 to 64 µg/mL. Specially, compounds 2 and 4 showed significant activities against the pathogenic fungus Curvularia spicifera with the MIC value of 1 µg/mL, providing an experimental basis of 2 and 4 with the potential as lead compounds to be developed into biopesticides.


Assuntos
Testes de Sensibilidade Microbiana , Talaromyces , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Relação Dose-Resposta a Droga , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/isolamento & purificação , Estrutura Molecular , Relação Estrutura-Atividade , Talaromyces/química , Talaromyces/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia
7.
Nature ; 557(7705): 424-428, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29743678

RESUMO

Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat1,2. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing 3 , linked reads and optical mapping4,5. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.


Assuntos
Evolução Molecular , Genoma de Planta/genética , Filogenia , Triticum/classificação , Triticum/genética , Altitude , Cromossomos Artificiais Bacterianos/genética , Cromossomos de Plantas/genética , Elementos de DNA Transponíveis/genética , Variação Genética , Mapeamento Geográfico , Anotação de Sequência Molecular , Doenças das Plantas/microbiologia , Análise de Sequência de DNA , Sintenia/genética
8.
Environ Res ; 245: 118007, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154561

RESUMO

Polychlorinated dibenzothiophenes (PCDTs) are a form of emerging pollutant that has attracted great attention due to their structural resemblance to dioxins, which cast detrimental influence on the ecosystem and human health. This review shows the current status of research on PCDTs, focusing on their environmental occurrence, physicochemical properties, environmental behavior, and toxicity. Studies have suggested that the steps leading to the formation of PCDTs resemble those generating polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs), indicating their probable origin from the same sources. Furthermore, they may undergo a dechlorination process as a result of their photodegradation in the environment and metabolic reaction occurring within organisms, which could result in the conversion of these substances into additional pollutants like dibenzothiophene. PCDTs exist widely in the environmental media and have high logKOW values (>4.0), indicating their tendency to bioaccumulate. Moreover, the prediction results of EPI (Estimation Program Interface) Suite demonstrated a strong accumulation capacity for tetra-CDTs in fish compared to other chlorinated PCDTs. The biotransformation half-life of PCDTs would prolong with an increasing number of substituted Cl atoms in fish. A limited number of studies have also suggested that PCDTs can cause damage to the liver and immune system in living organisms, and the toxicity of PCDTs depends on the number and position of substituted Cl atoms. Future studies should be conducted on processes causing PCDT toxicity as well as their behavior and fate in actual environments.


Assuntos
Benzofuranos , Dioxinas , Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Tiofenos , Animais , Humanos , Dibenzodioxinas Policloradas/análise , Dibenzofuranos , Benzofuranos/toxicidade , Benzofuranos/análise , Ecossistema , Poluentes Ambientais/análise , Dibenzofuranos Policlorados , Peixes/metabolismo , Monitoramento Ambiental
9.
Zhongguo Zhong Yao Za Zhi ; 49(3): 763-769, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621880

RESUMO

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.


Assuntos
Compostos Azo , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Ratos , Animais , Dieta Hiperlipídica/efeitos adversos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/farmacologia , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Camundongos Endogâmicos C57BL , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triglicerídeos/metabolismo , Peso Corporal , Trifosfato de Adenosina/farmacologia
10.
Angew Chem Int Ed Engl ; 63(26): e202403963, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38635317

RESUMO

(±)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a γ-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3-cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase-like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids.


Assuntos
Sistema Enzimático do Citocromo P-450 , Indóis , Penicillium , Sistema Enzimático do Citocromo P-450/metabolismo , Indóis/química , Indóis/metabolismo , Penicillium/enzimologia , Penicillium/metabolismo , Biocatálise , Estereoisomerismo , Estrutura Molecular
11.
Beilstein J Org Chem ; 20: 470-478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440169

RESUMO

Pseudallenes A and B (1 and 2), the new and rare examples of sulfur-containing ovalicin derivatives, along with three known analogues 3-5, were isolated and identified from the culture extract of Pseudallescheria boydii CS-793, a fungus obtained from the deep-sea cold seep sediments. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed and established the structures and absolute configurations of compounds 1-3, thus providing the first characterized crystal structure of an ovalicin-type sesquiterpenoid. In the antimicrobial assays, compounds 1-3 showed broad-spectrum inhibitory activities against several plant pathogens with MIC values ranging from 2 to 16 µg/mL.

12.
Opt Express ; 31(22): 35810-35821, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017745

RESUMO

Alamouti space-time block code (STBC) combined with a simple heterodyne coherent receiver can realize polarization-insensitive phase-diversity detection to reduce the cost. In the receiver, a joint equalizer has been used for STBC's polarization demultiplexing and phase tracking. However, the joint equalizer requires two different step size parameters to update the tap weight coefficients for polarization demultiplexing and the phase noise estimation. This leads to the search process being complex so requiring more iterations for convergence. In this paper, we propose a partially decoupled equalizer that consists of a polarization and phase decoupled equalizer (PPDE) and a pilot-aided blind phase search (P-BPS) algorithm to accelerate the convergence and improve the phase noise tolerance. By theoretically calculating the phase noise, the PPDE can achieve polarization demultiplexing with only one single step size parameter, thus suppressing the searching space and greatly reducing the iterations required for convergence. In the carrier phase recovery stage, the P-BPS algorithm can effectively improve the phase noise tolerance and solve the cyclic slip problem of BPS. We conduct numerical simulations and an experiment to transmit a quadrature phase-shift keying (QPSK) signal. The results demonstrate that the number of iterations required for PPDE convergence is only half of that of the joint equalizer while maintaining polarization-insensitive characteristics in large phase noise. Meanwhile, the achievable linewidth tolerance of P-BPS is increased by three times compared with DD-LMS.

13.
Theor Appl Genet ; 136(3): 51, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36913011

RESUMO

KEY MESSAGE: A high-density genetic map containing 122,620 SNP markers was constructed, which facilitated the identification of eight major flag leaf-related QTL in relatively narrow intervals. The flag leaf plays an important role in photosynthetic capacity and yield potential in wheat. In this study, we used a recombinant inbred line population containing 188 lines derived from a cross between 'Lankao86' (LK86) and 'Ermangmai' to construct a genetic map using the Wheat 660 K single-nucleotide polymorphism (SNP) array. The high-density genetic map contains 122,620 SNP markers spanning 5185.06 cM. It shows good collinearity with the physical map of Chinese Spring and anchors multiple sequences of previously unplaced scaffolds onto chromosomes. Based on the high-density genetic map, we identified seven, twelve, and eight quantitative trait loci (QTL) for flag leaf length (FLL), width (FLW), and area (FLA) across eight environments, respectively. Among them, three, one, and four QTL for FLL, FLW, and FLA are major and stably express in more than four environments. The physical distance between the flanking markers for QFll.igdb-3B/QFlw.igdb-3B/QFla.igdb-3B is only 444 kb containing eight high confidence genes. These results suggested that we could directly map the candidate genes in a relatively small region by the high-density genetic map constructed with the Wheat 660 K array. Furthermore, the identification of environmentally stable QTL for flag leaf morphology laid a foundation for the following gene cloning and flag leaf morphology improvement.


Assuntos
Locos de Características Quantitativas , Triticum , Triticum/genética , Fenótipo , Mapeamento Cromossômico , Folhas de Planta/genética , Folhas de Planta/anatomia & histologia , Polimorfismo de Nucleotídeo Único
14.
Theor Appl Genet ; 136(12): 240, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37930446

RESUMO

KEY MESSAGE: Five environmentally stable QTLs for spikelet number per spike and days to heading were identified using a high-genetic map containing 95,444 SNPs, among which QSns.ucas-5B was validated using residual heterozygous line at multiple environments. Spikelet number per spike (SNS) and days to heading (DTH) play pivotal roles in the improvement of wheat yield. In this study, a high-density genetic map for a recombinant inbred lines (RILs) population derived from Zhengnong 17 (ZN17) and Yangbaimai (YBM) was constructed using 95,444 single-nucleotide polymorphism (SNP) markers from the Wheat660K SNP array. Our study identified a total of five environmentally stable QTLs for SNS and DTH, one of which was named QSns.ucas-5B, with a physical interval of approximately 545.4-552.1 Mb on the 5BL chromosome arm. Importantly, the elite haplotype within QSns.ucas-5B showed a consistent and positive effect on SNS, grain number and weight per spike, without extending the days to heading. These findings provide a foundation for future efforts to map and clone the gene(s) responsible for QSns.ucas-5B and further indicate the potential application of the developed and validated InDel marker of QSns.ucas-5B for molecular breeding purposes, aimed at improving wheat grain yield.


Assuntos
Pão , Triticum , Triticum/genética , Locos de Características Quantitativas , Embaralhamento de DNA , Grão Comestível
15.
Org Biomol Chem ; 21(12): 2575-2585, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36880760

RESUMO

Seven new highly oxygenated natural products with diverse chemical structural types, including three new glucosidic polyketides, talaminiosides A-C (1-3), a pair of racemic aromatic polyketides, (±)-talaminone A (4a and 4b), two new azaphilone polyketides, (+)-5-chloromitorubrinic acid (5) and 7-epi-purpurquinone C (7), and one new drimane sesquiterpene lactone, 11-hydroxyminioluteumide B (8), together with a pinazaphilone B sodium salt (6) and 10 known compounds (9-18), were isolated and identified from the culture extract of Talaromyces minioluteus CS-113, a fungus obtained from deep-sea cold-seep sediments collected from the South China Sea. LCMS results indicated that compounds 3 and 4 might be produced by the real activation of silent BGCs triggered by the histone deacetylase inhibitor SAHA, and some of the other compounds were enhanced minor components. Their structures were elucidated by the detailed interpretation of NMR spectroscopic and mass spectrometric data, X-ray crystallographic analysis, ECD and specific rotation (SR) calculations, and DP4+ probability analysis. Compound 7, an azaphilone derivative, exhibited potent activities against several agricultural pathogenic fungi with MIC values equivalent or comparable to amphotericin B. The structure-activity relationship of the isolated azaphilones is briefly discussed. This is the first report of the chemical diversity study of deep-sea cold-seep-derived fungi triggered by SAHA, providing a useful strategy for the activation of cryptic fungal metabolites from deep-sea-derived fungi.


Assuntos
Anti-Infecciosos , Policetídeos , Talaromyces , Policetídeos/química , Inibidores de Histona Desacetilases , Espectroscopia de Ressonância Magnética , Estrutura Molecular
16.
Surg Endosc ; 37(2): 1173-1180, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36149506

RESUMO

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Ablação por Radiofrequência , Trombose , Trombose Venosa , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/patologia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Trombose/complicações , Terapia Combinada
17.
Mycoses ; 66(1): 59-68, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36111370

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear. METHODS: HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. RESULTS: Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p = .010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p = .011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p = .034). CONCLUSIONS: Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.


Assuntos
Infecções por HIV , Meningite Criptocócica , Humanos , Fluconazol/efeitos adversos , Flucitosina/efeitos adversos , Meningite Criptocócica/complicações , Quimioterapia de Indução , Estudos Retrospectivos , Antifúngicos/efeitos adversos , Quimioterapia Combinada , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV
18.
Mycoses ; 66(4): 308-316, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36520582

RESUMO

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.


Assuntos
Aspergilose , Encefalite , Humanos , Estudos Retrospectivos , Abscesso , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Aspergilose/diagnóstico , Sensibilidade e Especificidade , Mananas , Sistema Nervoso Central
19.
Mar Drugs ; 21(5)2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37233487

RESUMO

Two new quinazolinone diketopiperazine alkaloids, including versicomide E (2) and cottoquinazoline H (4), together with ten known compounds (1, 3, and 5-12) were isolated and identified from Aspergillus versicolor AS-212, an endozoic fungus associated with the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts. Their chemical structures were determined by an extensive interpretation of the spectroscopic and X-ray crystallographic data as well as specific rotation calculation, ECD calculation, and comparison of their ECD spectra. The absolute configurations of (-)-isoversicomide A (1) and cottoquinazoline A (3) were not assigned in the literature reports and were solved in the present work by single-crystal X-ray diffraction analysis. In the antibacterial assays, compound 3 exhibited antibacterial activity against aquatic pathogenic bacteria Aeromonas hydrophilia with an MIC value of 18.6 µM, while compounds 4 and 8 exhibited inhibitory effects against Vibrio harveyi and V. parahaemolyticus with MIC values ranging from 9.0 to 18.1 µM.


Assuntos
Alcaloides , Antozoários , Sesquiterpenos , Animais , Dicetopiperazinas/química , Estrutura Molecular , Fungos , Alcaloides/química , Antibacterianos/química
20.
Chem Biodivers ; 20(4): e202300229, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36866699

RESUMO

Rubenpolyketone A (1), a polyketide featuring a new carbon skeleton having cyclohexenone condensed with a methyl octenone chain and a new linear sesquiterpenoid, chermesiterpenoid D (2), together with seven known secondary metabolites (3-9) were isolated and identified from the Magellan Seamount-derived fungus Penicillium rubens AS-130. Their structures were determined based on detailed analysis of NMR and mass spectroscopic data and the absolute configurations of these two new compounds were elucidated by the combination of quantum mechanical (QM)-NMR and time-dependent density functional (TDDFT) ECD calculation approaches. Chermesiterpenoids B (3) and C (4) showed potent inhibitory activities against the aquatic pathogen Vibrio anguillarum with MIC values of 0.5 and 1 µg/mL, respectively, while chermesin F (6) exhibited activity against Escherichia coli with MIC value of 1 µg/mL.


Assuntos
Penicillium , Policetídeos , Sesquiterpenos , Estrutura Molecular , Policetídeos/química , Sesquiterpenos/química , Penicillium/química
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