RESUMO
Liquid crystal (LC) gratings have played important roles in light field control due to the advantages of being lightweight, low cost, having no moving parts, and low power consumption. However, the chromatic aberration limits the bandwidth of the LC device and affects the efficiency of the grating. To solve the chromatic aberration issue, a broadband wavelength designable achromatic grating is proposed. Different grating structures are integrated into a single-layer templated cholesteric liquid crystal (CLC) device, and the achromatic diffraction wavelength of the grating can be freely designed from the visible spectral region to the infrared range within the Bragg reflection band of the CLCs. The diffraction intensity of different orders can be changed with the electric field applied to meet the need for dynamic modulation. This grating shows suitable potential applications in optical communication and displays.
RESUMO
Three diphenyl ethers (1-3) and a cyclopentenone (4), together with seven known compounds (5-11), were isolated from the fermentation broth of the marine sediment-derived fungus Spiromastix sp. SCSIO F190. Compounds 3 and 4 were found to exist as a pair of atropisomers (3a, 3b) and racemates (4a, 4b), respectively. The planar structures of compounds 1-4 were elucidated on the basis of NMR and HRESIMS data sets. The absolute configurations of 2 and 3 were determined by spectroscopic and single-crystal X-ray diffraction analyses, whereas the configuration of 4 was determined by spectroscopic and chiral analyses. All compounds, except for 4 and 11, displayed activities against various pathogenic bacteria. Notably, compounds 1-4, especially 1, exhibited strong activity against Gram-positive bacteria, including methicillin-resistant bacterial strains of Staphylococcus aureus (MRSA), Enterococcus faecalis ATCC 29212, and Bacillus subtilis BS01, with MIC values ranging from 0.5 to 4 µg/mL. Moreover, the structure-activity relationship analyses of the active compounds and their analogues revealed the critical structural features correlating to the observed antimicrobial activities, herein providing insights for antimicrobial drug development.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Policetídeos , Antibacterianos/química , Policetídeos/química , Estrutura Molecular , Fungos , Espectroscopia de Ressonância Magnética , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A-B (1-2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A-C (5-7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.
Assuntos
Actinobacteria , Antozoários , Actinobacteria/química , Actinomyces , Animais , Carbazóis , Recifes de Corais , AreiaRESUMO
Through precursor-directed biosynthesis, feeding halogenated (F-, Cl-, Br-, I-) or methoxy-substituted 4-methyl-3-hydroxyanthranilic acid (4-MHA) analogues to the acnGHLM-deleted mutant strain of Streptomyces costaricanus SCSIO ZS0073 led to the production of ten new actinomycin analogues (4-13). Several of the actinomycin congeners displayed impressive antimicrobial activities, with MIC values spanning 0.06-64 µg/mL to clinically derived antibiotic resistant pathogens, including Staphylococcus aureus, Enterococcus faecium, and Candida albicans, with low cytotoxicity.
Assuntos
Anti-Infecciosos/farmacologia , Dactinomicina/análogos & derivados , Streptomyces/metabolismo , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Enterococcus faecium/efeitos dos fármacos , Halogenação , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Streptomyces/genéticaRESUMO
Two new cyclodecapeptides, atratumycins B (1) and C (2), containing substituted cinnamoyl side chains were generated by converging elements of the atratumycin (3) and atrovimycin (4) biosynthetic pathways. The structures of 1 and 2 were determined on the basis of HRESIMS, 1D and 2D NMR data, and X-ray single-crystal diffraction studies. Atratumycin B (1) is active against autoluminescent Mycobacterium tuberculosis H37Rv, displaying a minimum inhibitory concentration of 3.1 µg/mL (2.3 µM).
Assuntos
Antituberculosos/farmacologia , Depsipeptídeos/química , Mycobacterium tuberculosis/química , Streptomyces/química , Antituberculosos/química , Vias Biossintéticas , Cristalografia por Raios X , Depsipeptídeos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/metabolismoRESUMO
Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (1-12), bearing various nonproteinogenic amino acids, along with ilamycins E1 (13) and F (14), from a 200 L scale culture of the marine-derived mutant actinomycete Streptomyces atratus SCSIO ZH16 ΔilaR. Importantly, bioassays against Mycobacterium tuberculosis H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 µM. The structures of 1-12 were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound 10 was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.
Assuntos
Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Streptomyces/química , Antineoplásicos/química , Antituberculosos/química , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Borrelidins M-O (1-3), along with four previously known family members (4-7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1-3 were elucidated by extensive spectral analyses of HR-ESI-MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1-7 were evaluated enabling us to propose some tentative structure-activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Streptomyces/química , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Two julichrome monomers, julichromes Q11 (1) and Q12 (2), along with five known julichromes (Q10 , Q3 â 5 , Q3 â 3 , Q6 â 6 , Q6 , 3-7) and four known anthraquinones (chrysophanol, 4-acetylchrysophanol, islandicin, huanglongmycin A, 8-11), were isolated from the marine gastropod mollusk Batillaria zonalis-associated Streptomyces sampsonii SCSIO 054. This is the first report of julichromes isolated from a marine source. Extensive dissection of 1D and 2D NMR datasets combined with X-ray crystallography enabled rigorous elucidation of the previously reported configurations of julichrome Q3 â 5 (4) and related julichrome Q3 â 3 (5); both of the configuration at C(9) needs to be revised. In addition, julichrome Q12 (2) was found to display antibacterial activity against Micrococcus luteus and Bacillus subtilis with MICs of 2.0 and 8.0â µg mL-1 ; four compounds (1, 3, 6, 7) also showed inhibitory activities against an array of methicillin-resistant Staphylococcus aureus, S. aureus and S. simulans AKA1 with MIC values ranging from 8 to 64â µg mL-1 .
Assuntos
Antibacterianos/química , Gastrópodes/microbiologia , Naftalenos/química , Streptomyces/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Conformação Molecular , Naftalenos/isolamento & purificação , Naftalenos/farmacologia , Filogenia , Estereoisomerismo , Streptomyces/classificação , Streptomyces/metabolismoRESUMO
Three new kendomycin analogues, kendomycins B-D (1-3), were discovered from the marine-derived actinomycete Verrucosispora sp. SCSIO 07399. The structures of 1-3 were elucidated using diverse spectroscopic data analyses, X-ray crystallography, and semisynthetic derivatization. In vitro antimicrobial assays revealed that 1-3 all display good antibacterial activities against six Gram-positive bacteria with MIC values ranging from 0.5 to 8.0 µg/mL. Additionally, 1-3 were found to be moderately cytotoxic against MGC803, A549, HeLa, HepG2, MCF-7, and RKO human tumor cell lines; IC50 values ranged from 2.2 to 44 µM.
Assuntos
Antineoplásicos/farmacologia , Biologia Marinha , Micromonosporaceae/química , Rifabutina/análogos & derivados , Antibacterianos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Estrutura Molecular , Rifabutina/química , Rifabutina/farmacologia , Análise Espectral/métodosRESUMO
Candida albicans is a type of commensal fungi which causes serious infections in immunocompromised patients and contributes to high mortality. In the present study, we identified that the extract from Streptomyces olivaceus SCSIO T05 inhibited hypha and biofilm formation of C. albicans. Seven compounds were isolated and evaluated for their effects on the biological functions and virulence of C. albicans. Two leading compounds, compound 1 (sorbicillin) and compound 2 (3-methyl-N-(2'-phenethyl)-butyrylamide) were identified as exhibiting strong activity against C. albicans morphological transition, adhesion activity, cytotoxicity, and adhesion to human cells, in a dose-dependent manner. Notably, compound 2 inhibited C. albicans infection in mouse oral mucosal models. Transcriptomic analysis and real-time PCR results revealed that compound 2 most likely inhibited the biological functions of C. albicans cells by regulating the expression levels of HWP1, TEC1, ALS1, IFD6, and CSH1, which are associated with filament formation and cell adhesion. Our results suggest that the candidate compounds present excellent efficacy against C. albicans pathogenicity and that they can be developed as potential options for the clinical treatment of candidiasis.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Streptomyces/química , Virulência/efeitos dos fármacos , Células A549 , Animais , Biofilmes/efeitos dos fármacos , Candida albicans/genética , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas Fúngicas/genética , Humanos , Hifas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Bucal/microbiologia , Resorcinóis/farmacologia , Transcriptoma/efeitos dos fármacosRESUMO
Bioactive secondary metabolites from Streptomycetes are important sources of lead compounds in current drug development. Streptomyces costaricanus SCSIO ZS0073, a mangrove-derived actinomycete, produces actinomycin D, a clinically used therapeutic for Wilm's tumor of the kidney, trophoblastic tumors and rhabdomyosarcoma. In this work, we identified the actinomycin biosynthetic gene cluster (BGC) acn by detailed analyses of the S. costaricanus SCSIO ZS0073 genome. This organism produces actinomycin D with a titer of ~69.8 µg mL-1 along with traces of actinomycin Xoß. The acn cluster localized to a 39.8 kb length region consisting of 25 open reading frames (ORFs), including a set of four genes that drive the construction of the 4-methyl-3-hydroxy-anthranilic acid (4-MHA) precursor and three non-ribosomal peptide synthetases (NRPSs) that generate the 4-MHA pentapeptide semi-lactone, which, upon dimerization, affords final actinomycin D. Furthermore, the acn cluster contains four positive regulatory genes acnWU4RO, which were identified by in vivo gene inactivation studies. Our data provide insights into the genetic characteristics of this new mangrove-derived actinomycin D bioproducer, enabling future metabolic engineering campaigns to improve both titers and the structural diversities possible for actinomycin D and related analogues.
Assuntos
Vias Biossintéticas/fisiologia , Dactinomicina/metabolismo , Streptomyces/metabolismo , Família Multigênica/fisiologia , Peptídeo Sintases/metabolismo , ortoaminobenzoatos/metabolismoRESUMO
Atratumycin is a cyclodepsipeptide with activity against Mycobacteria tuberculosis isolated from deep-sea derived Streptomyces atratus SCSIO ZH16NS-80S. Analysis of the atratumycin biosynthetic gene cluster (atr) revealed that its biosynthesis is regulated by multiple factors, including two LuxR regulatory genes (atr1 and atr2), two ABC transporter genes (atr29 and atr30) and one Streptomyces antibiotic regulatory gene (atr32). In this work, three regulatory and two transporter genes were unambiguously determined to provide positive, negative and self-protective roles during biosynthesis of atratumycin through bioinformatic analyses, gene inactivations and trans-complementation studies. Notably, an unusual Streptomyces antibiotic regulatory protein Atr32 was characterized as a negative regulator; the function of Atr32 is distinct from previous studies. Five over-expression mutant strains were constructed by rational application of the regulatory and transporter genes; the resulting strains produced significantly improved titers of atratumycin that were ca. 1.7-2.3 fold greater than wild-type (WT) producer. Furthermore, the atratumycin gene cluster was successfully expressed in Streptomyces coelicolor M1154, thus paving the way for the transfer and recombination of large DNA fragments. Overall, this finding sets the stage for understanding the unique biosynthesis of pharmaceutically important atratumycin and lays the foundation for generating anti-tuberculosis lead compounds possessing novel structures.
Assuntos
Organismos Aquáticos/genética , Proteínas de Bactérias/genética , Depsipeptídeos/biossíntese , Redes Reguladoras de Genes , Streptomyces/genética , Antituberculosos , Organismos Aquáticos/metabolismo , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Biologia Computacional , Depsipeptídeos/genética , Depsipeptídeos/farmacologia , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Família Multigênica , Mycobacterium tuberculosis/efeitos dos fármacos , Alinhamento de Sequência , Streptomyces/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from Streptomyces rochei SCSIO ZJ89 originating from a mangrove-derived sediment sample. These structurally diverse metabolites enabled a number of new structure-activity relationships (SARs) to be identified, especially with respect to the different configurations at the C11-OH and C12-C15 double bonds for which the absolute configurations were determined using spectroscopic methods. Importantly, borrelidin H (4) was found to have a therapeutic window superior to that of borrelidin A (1) in vitro and could inhibit migration of cancer cells.
Assuntos
Antineoplásicos/farmacologia , Streptomyces/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Cicatrização/efeitos dos fármacosRESUMO
Four known compounds, rishirilide B (1), rishirilide C (2), lupinacidin A (3), and galvaquinone B (4), representing two anthracene scaffolds typical of aromatic polyketides, were isolated from a culture of the deep-sea-derived Streptomyces olivaceus SCSIO T05. From the S. olivaceus producer was cloned and sequenced the rsd biosynthetic gene cluster (BGC) that drives rishirilide biosynthesis. The structural gene rsdK2 inactivation and heterologous expression of the rsd BGC confirmed the single rsd BGC encodes construction of 1-4 and, thus, accounts for two anthracene scaffolds. Precursor incubation experiments with 13C-labeled acetate revealed that a Baeyer-Villiger-type rearrangement plays a central role in construction of 1-4. Two luciferase monooxygenase components, along with a reductase component, are presumably involved in the Baeyer-Villiger-type rearrangement reaction enabling access to the two anthracene scaffold variants. Engineering of the rsd BGC unveiled three SARP family transcriptional regulators, enhancing anthracene production. Inactivation of rsdR4, a MarR family transcriptional regulator, failed to impact production of 1-4, although production of 3 was slightly improved; most importantly rsdR4 inactivation led to the new adduct 6 in high titer. Notably, inactivation of rsdH, a putative amidohydrolase, substantially improved the overall titers of 1-4 by more than 4-fold.
Assuntos
Antracenos/isolamento & purificação , Genes Bacterianos , Família Multigênica , Streptomyces/genética , Antracenos/metabolismo , Rearranjo Gênico , Oceanos e Mares , Microbiologia da ÁguaRESUMO
Depressive disorder is a severe psychiatric problem all over the world. Clinical therapeutic agents for the treatment of depression in the market targeting on monoamine neurotransmitters are far from satisfaction due to their adverse effects. Novel classes of antidepressant agents with different mechanisms and low toxicity are needed. Natural products from traditional Chinese medicines have been revealed as new sources to cure the depressive symptoms with various chemical structures and promising activities. This paper reviews natural products as antidepressants documented in Chinese patents so far.
Assuntos
Antidepressivos , Produtos Biológicos , Medicina Tradicional Chinesa , Transtorno Depressivo , Humanos , Estrutura MolecularRESUMO
Acute upper limb ischemia is a rare, potentially limb- or life-threatening vascular emergency that may lead to limb dysfunction or amputation. We present a patient undergoing maintenance hemodialysis who was hospitalized for arteriovenous graft thrombus complicated by acute upper limb ischemia arising from thrombus shedding to the fingertip arteries during thrombolysis. We successfully restored fingertip arterial patency, avoided amputation, and recovered the function of the arteriovenous graft by precise thrombolysis, anticoagulation, correction of arteriospasm, and percutaneous transluminal angioplasty. This case provides a basis for vascular access surgeons to treat acute upper limb ischemia caused by thromboembolism similarly.
Assuntos
Diálise Renal , Trombose , Humanos , Isquemia/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Terapia Trombolítica , Resultado do Tratamento , Grau de Desobstrução Vascular , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the effect of paclitaxel on platelet aggregation induced by adenosine diphosphate (ADP) in vitro. METHODS: Platelet suspension was incubated with paclitaxel in different concentrations (0 ng/mL, 0.01 ng/mL, 0.1 ng/mL, 1 ng/mL, 10 ng/mL, 100 ng/mL, 1 000 ng/mL), then the maximal extent of platelet aggregation was determined under the conditions of the best ADP concentration and the best incubation time. RESULTS: Under the condition of 10 micromol/L ADP and incubated for 10 min, with the increase of paclitaxel concentration, the effect of paclitaxel on platelet aggregation induced by ADP elevated accordingly, and the differences among the different concentration groups were statistically significant (P < 0.05). CONCLUSION: Paclitaxel can enhance ADP-induced platelet aggregation in a concentration-dependent manner in vitro.
Assuntos
Difosfato de Adenosina/farmacologia , Plaquetas/efeitos dos fármacos , Paclitaxel/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Adulto , Sinergismo Farmacológico , Humanos , Masculino , Adulto JovemRESUMO
Cholesteric liquid crystals (CLCs) exhibit selective reflection due to their self-assembled helical superstructures. Reconfigurable templates can achieve integration functions via inducing processes of molecular assemblies. Here we demonstrate temperature self-adaptive and color-adjustable smart windows using CLCs, which are fabricated via the templating method and exhibit simultaneous reflections in the visible and infrared spectra. Reflection bands formed by the refilled CLC materials can be adjusted reversibly both upon thermal and electrical actuation. In CLC with adjustable reflection in the infrared, the central wavelength of the infrared reflection band can be adjusted from 950 nm to 1305 nm via temperature, and from 1150 nm to 950 nm via electric field. A temperature variation of 10.3 °C within 55 s was induced by the single-layer templated CLC cell, and a comfortable temperature range could be effectively maintained by the CLC cell in a varied environment. In CLC with dynamic color in the visible spectrum, color shifts from 530 nm to 650 nm tuned by temperature and from 530 nm to 440 nm adjusted by electric field were obtained. Temperature-responsive reflection in the infrared spectrum contributes to automatic thermal management, and electric-field-induced band shift in the visible spectrum enables active dynamic color adjustment. The presented templated CLC smart windows show considerable potential in energy conservation and biological clock regulation fields.
RESUMO
OBJECTIVE: To identify profiles of nurses' perceived professional benefits as well as their predictors. DESIGN: Cross-sectional study. SETTING: The study was carried out online in China. METHODS: From 6 July to 27 July 2022, a total of 1309 registered nurses participated in the survey by convenient sampling. We collected the Nurses' Perceived Professional Benefits Questionnaire and demographic data. Using latent profile analysis (LPA), subgroups of nurses' perceived professional benefits were identified. Moreover, univariate and multinomial logistic regression analyses were conducted to find the factors that were linked with the profiles. RESULTS: The survey was validly completed by 1309 nurses, with a 92.9% effective return rate. The findings of the LPA demonstrated three unique profiles: low-perceived professional benefits (11.8%), moderate-perceived professional benefits (57.1%) and high-perceived professional benefits (31.1%). There was a correlation between marital status, the number of night shifts per month and leadership role. CONCLUSIONS: According to our research, registered nurses have three unique professional benefit profiles. In order to sustain the nursing workforce, despite the fact that nurses get a high level of professional benefits, interventions are necessary to increase nurses' perception of their professional value.
Assuntos
Esgotamento Profissional , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Recursos Humanos de Enfermagem , Humanos , Estudos Transversais , China , Inquéritos e Questionários , Satisfação no EmpregoRESUMO
An optical filter is one of the indispensable devices in massive and high-speed communication, optical signal processing, and display. Twist-structure liquid crystals, cholesteric liquid crystals, blue-phase liquid crystals, and sphere-phase liquid crystals show potential application in optical filters originating from the periodic nanostructures. Wavelength and bandwidth tuning can be controlled via temperature, electric fields, light, angle, spatial control, and templating technology. In this review, we discuss the recent developments of twist-structure liquid crystal filters.