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1.
Nature ; 617(7962): 717-723, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37225883

RESUMO

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

2.
Proc Natl Acad Sci U S A ; 121(6): e2314309121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38285943

RESUMO

Mucins are large, highly glycosylated extracellular matrix proteins that line and protect epithelia of the respiratory, digestive, and urogenital tracts. Previous work has shown that mucins form large, interconnected polymeric networks that mediate their biological functions once secreted. However, how these large matrix molecules are compacted and packaged into much smaller secretory granules within cells prior to secretion is largely unknown. Here, we demonstrate that a small cysteine-rich adaptor protein is essential for proper packaging of a secretory mucin in vivo. This adaptor acts via cysteine bonding between itself and the cysteine-rich domain of the mucin. Loss of this adaptor protein disrupts mucin packaging in secretory granules, alters the mobile fraction within granules, and results in granules that are larger, more circular, and more fragile. Understanding the factors and mechanisms by which mucins and other highly glycosylated matrix proteins are properly packaged and secreted may provide insight into diseases characterized by aberrant mucin secretion.


Assuntos
Cisteína , Mucinas , Mucinas/metabolismo , Cisteína/metabolismo , Transporte Biológico , Vesículas Secretórias/metabolismo
3.
Proc Natl Acad Sci U S A ; 119(35): e2116655119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994643

RESUMO

The Mediterranean region has been identified as a climate hot spot, with models projecting a robust warming and rainfall decline in response to increasing greenhouse gases. The projected rainfall decline would have impacts on agriculture and water resources. Can such changes be reversed with significant reductions in greenhouse gases? To explore this, we examine large ensembles of a high-resolution climate model with various future radiative forcing scenarios, including a scenario with substantial reductions in greenhouse gas concentrations beginning in the mid-21st century. In response to greenhouse gas reductions, the Mediterranean summer rainfall decline is reversed, but the winter rainfall decline continues. This continued winter rainfall decline results from a persistent atmospheric anticyclone over the western Mediterranean. Using additional numerical experiments, we show that the anticyclone and continued winter rainfall decline are attributable to greenhouse gas-induced weakening of the Atlantic Meridional Overturning Circulation (AMOC) that continues throughout the 21st century. The persistently weak AMOC, in concert with greenhouse gas reductions, leads to rapid cooling and sea ice growth in the subpolar North Atlantic. This cooling leads to a strong cyclonic atmospheric circulation anomaly over the North Atlantic subpolar gyre and, via atmospheric teleconnections, to the anticyclonic circulation anomaly over the Mediterranean. The failure to reverse the winter rainfall decline, despite substantial climate change mitigation, is an example of a "surprise" in the climate system. In this case, a persistent AMOC change unexpectedly impedes the reversibility of Mediterranean climate change. Such surprises could complicate pathways toward full climate recovery.


Assuntos
Mudança Climática , Conservação dos Recursos Naturais , Gases de Efeito Estufa , Chuva , Movimentos da Água , Oceano Atlântico , Gases de Efeito Estufa/efeitos adversos , Gases de Efeito Estufa/análise , Camada de Gelo , Região do Mediterrâneo , Estações do Ano
4.
Proc Natl Acad Sci U S A ; 119(43): e2209750119, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36252017

RESUMO

Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (Vha16-1), Ca2+ ions (fwe) and Cl- ions (Clic and ClC-c). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of mucins through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct mucins are efficiently packaged into and secreted from secretory granules may provide insight into diseases resulting from defects in mucin secretion.


Assuntos
Mucinas , Vesículas Secretórias , Grânulos Citoplasmáticos/metabolismo , Glicosilação , Mucinas/metabolismo , Vesículas Secretórias/metabolismo
5.
J Am Chem Soc ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842938

RESUMO

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of natural products. The enzyme mechanism for the biaryl phenol coupling reaction of the bicyclic CCNPs remains unclear. Herein, we report the discovery of two new arabinofuranosylated bicyclic CCNPs cihanmycins (CHMs) A (1) and B (2) from Amycolatopsis cihanbeyliensis DSM 45679 and the identification of the CHM biosynthetic gene cluster (cih BGC) by heterologous expression in Streptomyces lividans SBT18 to afford CHMs C (3) and D (4). The structure of 1 was confirmed by X-ray diffraction analysis. Three cytochrome P450 enzyme (CYP)-encoding genes cih26, cih32, and cih33 were individually inactivated in the heterologous host to produce CHMs E (5), F (6), and G (7), respectively. The structures of 5 and 6 indicated that Cih26 was responsible for the hydroxylation and epoxidation of the cinnamoyl moiety, and Cih32 should catalyze the ß-hydroxylation of three amino acid residues. Cih33 and its homologues DmlH and EpcH were biochemically verified to convert CHM G (7) with a monocyclic structure to a bicyclic skeleton of CHM C (3) through an intramolecular C-O phenol coupling reaction. The substrate 7-bound crystal structure of DmlH not only established the structure of 7, which was difficult for NMR analysis for displaying anomalous splitting signals, but also provided the binding mode of macrocyclic peptides recognized by these intramolecular C-O coupling CYPs. In addition, computational studies revealed a water-mediated diradical mechanism for the C-O phenol coupling reaction. These findings have shed important mechanistic insights into the CYP-catalyzed phenol coupling reactions.

6.
J Am Chem Soc ; 146(18): 12556-12564, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38660792

RESUMO

Transition metal nitride (TMN)-based nanostructures have emerged as promising materials for diverse applications in electronics, photonics, energy storage, and catalysis due to their highly desirable physicochemical properties. However, synthesizing TMN-based nanostructures with designed compositions and morphologies poses challenges, especially in the solution phase. The cation exchange reaction (CER) stands out as a versatile postsynthetic strategy for preparing nanostructures that are otherwise inaccessible through direct synthesis. Nevertheless, exploration of the CER in TMNs lags behind that in metal chalcogenides and metal phosphides. Here, we demonstrate cation exchange in colloidal metal nitride nanocrystals, employing Cu3N nanocrystals as starting materials to synthesize Ni4N and CoN nanocrystals. By controlling the reaction conditions, Cu3N@Ni4N and Cu3N@CoN core@shell heterostructures with tunable compositions can also be obtained. The Ni4N and CoN nanocrystals are evaluated as catalysts for the electrochemical oxygen evolution reaction (OER). Remarkably, CoN nanocrystals demonstrate superior OER performance with a low overpotential of 286 mV at 10 mA·cm-2, a small Tafel slope of 89 mV·dec-1, and long-term stability. Our CER approach in colloidal TMNs offers a new strategy for preparing other metal nitride nanocrystals and their heterostructures, paving the way for prospective applications.

7.
Small ; : e2310664, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342707

RESUMO

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl2 ·2H2 O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S4 -Sn-N2 , with electron pathways of SnS2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS2 -TCN is increased significantly, promoting the formation of S4 -Sn-N2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h-1 , which is 3.15 times greater than that of bare TCN.

8.
BMC Microbiol ; 24(1): 231, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951812

RESUMO

BACKGROUND: Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris. Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis. RESULTS: The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects. CONCLUSIONS: This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.


Assuntos
Afídeos , Bacillus , Inseticidas , Lipopeptídeos , Animais , Afídeos/efeitos dos fármacos , Bacillus/genética , Bacillus/metabolismo , Lipopeptídeos/farmacologia , Lipopeptídeos/química , Lipopeptídeos/metabolismo , Lipopeptídeos/isolamento & purificação , Inseticidas/farmacologia , Inseticidas/metabolismo , Inseticidas/química , Família Multigênica , Metabolismo Secundário , Controle Biológico de Vetores , Sequenciamento Completo do Genoma , Genoma Bacteriano/genética
9.
Hepatology ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37983829

RESUMO

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (IR) injury is the most common complication that occurs in liver surgery and hemorrhagic shock. ATP citrate lyase (Acly) plays a pivotal role in chromatin modification via generating acetyl-CoA for histone acetylation to influence biological processes. We aim to examine the roles of Acly, which is highly expressed in hepatocytes, in liver IR injury. APPROACH AND RESULTS: The functions of Acly in hepatic IR injury were examined in the mouse model with a hepatocyte-specific knockout of Acly . The Acly target genes were analyzed by CUT&RUN assay and RNA sequencing. The relationship between the susceptibility of the steatotic liver to IR and Acly was determined by the gain of function studies in mice. Hepatic deficiency of Acly exacerbated liver IR injury. IR induced Acly nuclear translocation in hepatocytes, which spatially fueled nuclear acetyl-CoA. This alteration was associated with enhanced acetylation of H3K9 and subsequent activation of the Foxa2 signaling pathway. Nuclear localization of Acly enabled Foxa2-mediated protective effects after hypoxia-reperfusion in cultured hepatocytes, while cytosolic Acly demonstrated no effect. The presence of steatosis disrupted Acly nuclear translocation. In the steatotic liver, restoration of Acly nuclear localization through overexpression of Rspondin-1 or Rspondin-3 ameliorated the IR-induced injury. CONCLUSIONS: Our results indicate that Acly regulates histone modification by means of nuclear AcCoA production in hepatic IR. Disruption of Acly nuclear translocation increases the vulnerability of the steatotic liver to IR. Nuclear Acly thus may serve as a potential therapeutic target for future interventions in hepatic IR injury, particularly in the context of steatosis.

10.
Plant Physiol ; 192(1): 154-169, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36721922

RESUMO

Flowering transition is tightly coordinated by complex gene regulatory networks, in which AGAMOUS-LIKE 16 (AGL16) plays important roles. Here, we identified the molecular function and binding properties of AGL16 and demonstrated its partial dependency on the SUPPRESSOR OF CONSTANS 1 (SOC1) function in regulating flowering. AGL16 bound to promoters of more than 2,000 genes via CArG-box motifs with high similarity to that of SOC1 in Arabidopsis (Arabidopsis thaliana). Approximately 70 flowering genes involved in multiple pathways were potential targets of AGL16. AGL16 formed a protein complex with SOC1 and shared a common set of targets. Intriguingly, only a limited number of genes were differentially expressed in the agl16-1 loss-of-function mutant. However, in the soc1-2 knockout background, AGL16 repressed and activated the expression of 375 and 182 genes, respectively, with more than a quarter bound by AGL16. Corroborating these findings, AGL16 repressed the flowering time more strongly in soc1-2 than in the Col-0 background. These data identify a partial inter-dependency between AGL16 and SOC1 in regulating genome-wide gene expression and flowering time, while AGL16 provides a feedback regulation on SOC1 expression. Our study sheds light on the complex background dependency of AGL16 in flowering regulation, thus providing additional insights into the molecular coordination of development and environmental adaptation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Flores
11.
Plant Cell Environ ; 47(5): 1782-1796, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38315745

RESUMO

Alternative splicing (AS) is an important regulatory mode at the post-transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a-4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above-mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering-related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Sulfeto de Hidrogênio , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Processamento de RNA/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sulfeto de Hidrogênio/metabolismo , Processamento Alternativo/genética , Precursores de RNA/genética , Regulação da Expressão Gênica de Plantas , Flores/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Opt Express ; 32(7): 12449-12461, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571067

RESUMO

In this paper, we introduce a new type of controllable auto-focusing vortex beam array named annular quasi-Airy vortex beam array (QAVBA), which can reduce the crosstalk among different orbital angular momentum (OAM) modes of optical vortex. The effects of initial beam parameters of annular QAVBA and propagation conditions on the OAM mode propagation performance are investigated. The results indicate that the topological angle θ, the topological charge m, and the decay parameter α could manipulate the auto-focusing characteristics of annular QAVBA and regulate the crosstalk of OAM modes. The crosstalk among OAM modes increases with the turbulence strength. Interestingly, the annular QAVBA with obtuse topological angle is favorable for the OAM mode transmitting at far propagation distance or in strong atmospheric turbulence when the decay parameter α is large enough for the energy of annular QAVBA mainly concentrating on the main light ring. Our research provides a reference for optimizing the design of light sources and free-space optical communication system with annular QAVBA.

13.
Opt Lett ; 49(10): 2681-2684, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748135

RESUMO

A type of circular Airyprime function of complex-variable Gaussian vortex (AFCGV) wave packets in a strongly nonlocal nonlinear medium is introduced numerically, combining the properties of helicity states and abrupt autofocusing. We investigate the effects of the chirp factor, distribution parameter, and decay factor on the AFCGV wave packets in the strongly nonlocal nonlinear medium. Interestingly, by adjusting the distribution parameter, the AFCGV wave packets can exhibit stable rotational motions in various shapes, such as symmetric lobes and doughnuts. In addition, the Poynting vector and the gradient force of the AFCGV wave packets are also discussed. Our research not only explains the theoretical model for controlling AFCGV wave packets but also advances fundamental research on self-bending and autofocusing structured light fields.

14.
Cell Commun Signal ; 22(1): 45, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233864

RESUMO

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Ligação a Retinoblastoma/genética , Proteína Smad4/genética , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Ubiquitina-Proteína Ligases/genética
15.
AIDS Care ; 36(2): 153-164, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37995747

RESUMO

A clear and accurate assessment of depressive symptoms among people living with HIV/AIDS (PLWHA) in the past five years is essential to help develop reasonable and sound interventions to improve their depressive symptoms. PubMed, Web of Science, MEDLINE, Cochrane, Embase, CINAHL, and APA were searched from 1 January 2017 to 12 April 2022. The data were analyzed using STATA 15 Software to pool the global prevalence of depressive symptoms in PLWHA. Ultimately, 103785 PLWHA from 81 original studies were included. The pooled analysis showed that the global prevalence of depressive symptoms in PLWHA over the past five years was 0.35 (95% CI: 0.31-0.38), with differences in depressive symptoms in PLWHA by geographic location, gender, assessment instruments, alcohol use, smoking, marriage, co-morbid disease, financial situation, and educational level. Scientific and timely public health interventions should be developed among PLWHA to improve their depressive symptoms and thereby improve mental health and clinical outcomes.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Prevalência , Depressão/epidemiologia , Depressão/psicologia , Comorbidade
16.
Inorg Chem ; 63(27): 12624-12634, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38910548

RESUMO

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.


Assuntos
Antineoplásicos , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Mefenâmico , Prata , Humanos , Prata/química , Prata/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ligantes , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Ácido Mefenâmico/farmacologia , Ácido Mefenâmico/química , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Proliferação de Células/efeitos dos fármacos , Nitrogênio/química , Estrutura Molecular , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Linhagem Celular Tumoral
17.
J Nat Prod ; 87(6): 1591-1600, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38862138

RESUMO

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain Streptomyces sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A-D (1-4) and two known analogues FD-594 (5) and the aglycon (6). The structures of 1-6 were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. 1-3 featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster (keb) was identified in Streptomyces sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar-O-methyltransferase, leading to a proposed biosynthetic route to 1-6. This study paves the way to further investigate 1 as a potential lead compound.


Assuntos
Antibacterianos , Streptomyces , Streptomyces/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Estrutura Molecular , Testes de Sensibilidade Microbiana , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Família Multigênica , Ensaios de Seleção de Medicamentos Antitumorais , Rhizophoraceae/microbiologia
18.
J Nat Prod ; 87(2): 371-380, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38301035

RESUMO

Thiazole scaffold-based small molecules exhibit a range of biological activities and play important roles in drug discovery. Based on bioinformatics analysis, a putative biosynthetic gene cluster (BGC) for thiazole-containing compounds was identified from Streptomyces sp. SCSIO 40020. Heterologous expression of this BGC led to the production of eight new thiazole-containing compounds, grisechelins E, F, and I-N (1, 2, 5-10), and two quinoline derivatives, grisechelins G and H (3 and 4). The structures of 1-10, including their absolute configurations, were elucidated by HRESIMS, NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Grisechelin F (2) is a unique derivative, distinguished by the presence of a salicylic acid moiety. The biosynthetic pathway for 2 was proposed based on bioinformatics analysis and in vivo gene knockout experiments. Grisechelin E (1) displayed moderate antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MIC of 8 µg mL-1).


Assuntos
Streptomyces , Streptomyces/genética , Streptomyces/química , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética , Ácido Salicílico , Tiazóis
19.
BMC Psychiatry ; 24(1): 475, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937737

RESUMO

BACKGROUND: This study aimed to explore discrepancies in adolescents with chronic illness and their parents' perceptions of family resilience, as well as the relationship between these differences and the psychological adjustment of adolescents with chronic illness. METHODS: A cross-sectional study was conducted. A total of 264 dyads of parents (77.7% mothers, mean age 41.60 years, SD = 6.17) and adolescents (48.5% girls, mean age 12.68 years, SD = 2.11) with chronic illness were recruited through convenience sampling from three children's hospitals in Wenzhou, Hangzhou, and Shanghai, China between June 2022 and May 2023. The Chinese version of the Family Resilience Scale and the Psychological Adjustment Scale, which are commonly used measures with good reliability and validity, were employed to assess family resilience and psychological adaption, respectively. The data were analyzed using polynomial regression and response surface analysis. RESULTS: Adolescents with chronic illness reported higher family resilience than their parents (t=-2.80, p < 0.05). The correlations between family resilience and adolescents' psychological adjustment reported by the adolescents (r = 0.45-0.48) were higher than parents (r = 0.18-0.23). In the line of congruence, there were positive linear (a1 = 1.09-1.60, p < 0.001) and curvilinear (a2=-1.38∼-0.72, p < 0.05) associations between convergent family resilience and adolescents' psychological adjustment. In the line of incongruence, when adolescents reported lower family resilience than parents, adolescents had a lower level of psychological adjustment (a3=-1.02∼-0.45, p < 0.05). Adolescents' sociability decreased when the perceived family resilience of parent-adolescent dyads converged (a4 = 1.36, p < 0.01). CONCLUSION: The findings highlighted the importance of considering the discrepancies and congruence of family resilience in the parent-child dyads when developing interventions to improve the psychological adjustment of adolescents with chronic illness. Interventions aimed at strengthening family communication to foster the convergence of perceptions of family resilience in parent-adolescent dyads were warranted.


Assuntos
Ajustamento Emocional , Pais , Resiliência Psicológica , Humanos , Feminino , Adolescente , Masculino , Doença Crônica/psicologia , Estudos Transversais , Pais/psicologia , Adulto , Criança , China , Adaptação Psicológica , Família/psicologia , Pessoa de Meia-Idade
20.
Compr Psychiatry ; 133: 152487, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38714144

RESUMO

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.


Assuntos
Regulação Emocional , Imageamento por Ressonância Magnética , Comportamento Autodestrutivo , Humanos , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/fisiopatologia , Masculino , Feminino , Regulação Emocional/fisiologia , Adulto , Adulto Jovem , Adolescente , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Inquéritos e Questionários
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