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1.
BMC Psychiatry ; 23(1): 826, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951892

RESUMO

BACKGROUND: Depressive symptoms associated with schizophrenia are closely related to stigma and quality of life(QOL). There is, however, no thorough research on the connection between the three. This study sought to investigate the possible factors influencing depressive symptoms in people with schizophrenia (PWS) in rural Chaohu, China, and to further explore the role of depression severity in stigma and lifestyle quality. METHODS: Eight hundred twenty-one schizophrenia patients accomplished the entire scale, including the 9-item Patient Health Questionnaire (PHQ-9), the Social Impact Scale (SIS), and the World Health Organization on Quality of Life Brief Scale(WHOQOL-BREF). A straightforward mediation model was employed to determine if the intensity of the depression could act as a mediator between stigma and QOL. RESULTS: Two hundred seventy-nine schizophrenia patients (34%) had depressive symptoms (PHQ ≥ 10), and 542 patients (66%) did not (PHQ < 10). Logistic regression showed that marital status, job status, physical exercise, standard of living, and stigma contributed to the depressed symptoms of schizophrenia. Depression severity partially mediated the effect between stigma and QOL, with a mediating effect of 48.3%. CONCLUSIONS: This study discovered a significant incidence of depressed symptoms associated with schizophrenia, with depression severity serving as a mediator variable connecting stigma and QOL and partially moderating the association.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Depressão/epidemiologia , Qualidade de Vida , Estigma Social , China
2.
Cell Mol Biol Lett ; 28(1): 35, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101253

RESUMO

BACKGROUND: Heart failure is a common complication of sepsis with a high mortality rate. It has been reported that melatonin can attenuate septic injury due to various properties. On the basis of previous reports, this study will further explore the effects and mechanisms of melatonin pretreatment, posttreatment, and combination with antibiotics in the treatment of sepsis and septic myocardial injury. METHODS AND RESULTS: Our results showed that melatonin pretreatment showed an obvious protective effect on sepsis and septic myocardial injury, which was related to the attenuation of inflammation and oxidative stress, the improvement of mitochondrial function, the regulation of endoplasmic reticulum stress (ERS), and the activation of the AMPK signaling pathway. In particular, AMPK serves as a key effector for melatonin-initiated myocardial benefits. In addition, melatonin posttreatment also had a certain degree of protection, while its effect was not as remarkable as that of pretreatment. The combination of melatonin and classical antibiotics had a slight but limited effect. RNA-seq detection clarified the cardioprotective mechanism of melatonin. CONCLUSION: Altogether, this study provides a theoretical basis for the application strategy and combination of melatonin in septic myocardial injury.


Assuntos
Melatonina , Sepse , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Miocárdio/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico
3.
Molecules ; 28(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36770988

RESUMO

The photosynthetic tetrapyrroles share a common structural feature comprised of a ß-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1-3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences.


Assuntos
Pirróis , Tetrapirróis , Pirróis/química , Clorofila/química , Bacterioclorofilas/química , Fotossíntese
4.
Inorg Chem ; 61(31): 12308-12317, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35892197

RESUMO

The monoanionic tetrapyrrolic macrocycle B,C-tetradehydrocorrin (TDC) resides chemically between corroles and corrins. This chemical space remains largely unexplored due to a lack of reliable synthetic strategies. We now report the preparation and characterization of Co(II)- and Ni(II)-metalated TDC derivatives ([Co-TDC]+ and [Ni-TDC]+, respectively) with a combination of crystallographic, electrochemical, computational, and spectroscopic techniques. [Ni-TDC]+ was found to undergo primarily ligand-centered electrochemical reduction, leading to hydrogenation of the macrocycle under cathodic electrolysis in the presence of acid. Transient absorption (TA) spectroscopy reveals that [Ni-TDC]+ and the two-electron-reduced [Ni-TDC]- possess long-lived excited states, whereas the excited state of singly reduced [Ni-TDC] exhibits picosecond dynamics. The Co(I) compound [Co-TDC] is air stable, highlighting the notable property of the TDC ligand to stabilize low-valent metal centers in contradistinction to other tetrapyrroles such as corroles, which typically stabilize metals in higher oxidation states.

5.
J Nanobiotechnology ; 20(1): 405, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064371

RESUMO

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.


Assuntos
Insuficiência Cardíaca , Traumatismos Cardíacos , Nanopartículas , Sepse , Animais , Insuficiência Cardíaca/metabolismo , Ferro , Camundongos , Miocárdio/metabolismo , Sepse/metabolismo
6.
Phytother Res ; 36(6): 2628-2640, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35583809

RESUMO

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti-inflammatory, anti-vitiligo, anti-bacterial, and anti-viral effects. Growth arrest-specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor-related factor 2 (Nrf-2), NAD(P)H dehydrogenase quinone-1 (NQO1), heme oxygenase-1 (HO-1), silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B-cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR-induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling.


Assuntos
Hipóxia Encefálica , Fármacos Neuroprotetores , Benzofuranos , Cumarínicos/farmacologia , Humanos , Hipóxia , Peptídeos e Proteínas de Sinalização Intercelular , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo
7.
Nucleic Acids Res ; 47(9): 4449-4461, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30838422

RESUMO

HMGN proteins localize to chromatin regulatory sites and modulate the cell-type specific transcription profile; however, the molecular mechanism whereby these ubiquitous nucleosome binding proteins affect gene expression is not fully understood. Here, we show that HMGNs regulate the expression of Rex1, one of the most highly transcribed genes in mouse embryonic stem cells (ESCs), by recruiting the transcription factors NANOG, OCT4 and SOX2 to an ESC-specific super enhancer located in the 5' region of Rex1. HMGNs facilitate the establishment of an epigenetic landscape characteristic of active chromatin and enhancer promoter interactions, as seen by chromatin conformation capture. Loss of HMGNs alters the local epigenetic profile, increases histone H1 occupancy, decreases transcription factors binding and reduces enhancer promoter interactions, thereby downregulating, but not abolishing Rex1 expression. ChIP-seq analyses show high colocalization of HMGNs and of REX1, a zinc finger protein, at promoters and enhancers. Loss of HMGNs preferentially reduces the specific binding of REX1 to these chromatin regulatory sites. Thus, HMGNs affects both the expression and the chromatin binding specificity of REX1. We suggest that HMGNs affect cell-type specific gene expression by modulating the binding specificity of transcription factors to chromatin.


Assuntos
Cromatina/genética , Epigênese Genética , Proteínas HMGN/genética , Fatores de Transcrição/genética , Animais , Sítios de Ligação/genética , Regulação da Expressão Gênica/genética , Proteínas HMGN/química , Histonas/genética , Camundongos , Células-Tronco Embrionárias Murinas , Proteína Homeobox Nanog/genética , Nucleossomos/genética , Fator 3 de Transcrição de Octâmero/genética , Regiões Promotoras Genéticas , Ligação Proteica/genética , Sequências Reguladoras de Ácido Nucleico/genética , Fatores de Transcrição SOXB1/genética
8.
Chemistry ; 26(44): 9883-9888, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32348001

RESUMO

Boronic acid catalysis has emerged as a mild method for promoting a wide variety of reactions. It has been proposed that the mode of catalysis involves Lewis acid or covalent activation of hydroxyl groups by boron, but limited mechanistic evidence exists. In this work, representative boronic acid catalyzed reactions of alcohols and oximes have been reinvestigated. A series of control experiments with boronic and Brønsted acids were interpreted along with correlations between their reactivity and their acidity measured by the Gutmann-Beckett method. Overall, it was concluded that the major modes of catalysis involve either dual H-bond catalysis or Brønsted acid catalysis. Strong Brønsted acids were shown to be generated in situ from covalent assembly of the boronic acids with hexafluoroisopropanol, explaining why the solvent had such a major impact on the reactivity. This new insight should guide the future development of boronic acid catalysis, where the diverse and solvent-specific nature of catalytic modes has been overlooked.

9.
Nucleic Acids Res ; 45(6): 3031-3045, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-27923998

RESUMO

An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the presence of HMGN proteins is required for proper expression of neural differentiation genes during embryonic stem cell differentiation. Specifically, we demonstrate that the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular/genética , Epigênese Genética , Proteínas HMGN/fisiologia , Histonas/metabolismo , Proteínas do Tecido Nervoso/genética , Oligodendroglia/citologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Células-Tronco Embrionárias/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Proteína HMGN1/genética , Proteína HMGN1/fisiologia , Proteína HMGN2/genética , Proteína HMGN2/fisiologia , Masculino , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos
10.
Nat Prod Rep ; 35(9): 879-901, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-29845995

RESUMO

Covering: up to 2018 Chlorophylls, bacteriochlorophylls and related hydroporphyrins constitute invaluable natural products but have largely remained outside the scope of viable syntheses. The campaign toward chlorophyll a by Woodward and coworkers is a deservedly celebrated landmark in organic synthesis yet the route entailed 49 steps, relied on semisynthetic replenishment of advanced intermediates, and then pointed to (but did not implement) uncertain literature procedures for the final transformations. Indeed, the full synthesis at any scale of any (bacterio)chlorophylls - conversion of small-molecule starting materials to the product - has never been accomplished. Herein, the reported syntheses of (±)-bonellin dimethyl ester (0.93 mg) and tolyporphin A O,O-diacetate (0.38 mg), as well as the never-fully traversed route to chlorophyll a, have been evaluated in a quantitative manner. Bonellin and tolyporphin A are naturally occurring chlorin and bacteriochlorin macrocycles, respectively, that lack the characteristic fifth ring of (bacterio)chlorophylls. A practical assessment is provided by the cumulative reaction mass efficiency (cRME) of the entire synthetic process. The cRME for the route to chlorophyll a would be 4.3 × 10-9 (230 kg of all reactants and reagents in total would yield 1.0 mg of chlorophyll a), whereas that for (±)-bonellin dimethyl ester or tolyporphin A O,O-diacetate is approximately 6.4 × 10-4 or 3.6 × 10-5, respectively. Comparison of the three syntheses reveals insights for designing hydroporphyrin syntheses. Development of syntheses with cRME > 10-5 (if not 10-4), as required to obtain 10 mg quantities of hydroporphyrin for diverse physicochemical, biochemical and medicinal chemistry studies, necessitates significant further advances in tetrapyrrole chemistry.


Assuntos
Clorofila/síntese química , Porfirinas/síntese química , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/química , Estrutura Molecular , Porfirinas/química
11.
Genome Res ; 25(9): 1295-308, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26156321

RESUMO

DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHS landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome-wide mapping of the DHSs in Hmgn1(-/-), Hmgn2(-/-), and Hmgn1(-/-)n2(-/-) MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHS landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress-responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHS landscape, and the transcription fidelity and is necessary to retain wild-type phenotypes. Our study provides insight into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins.


Assuntos
Sítios de Ligação , Desoxirribonuclease I/metabolismo , Elementos Facilitadores Genéticos , Proteínas HMGN/metabolismo , Animais , Linhagem Celular , Cromatina/metabolismo , Análise por Conglomerados , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Proteínas HMGN/genética , Proteína HMGN1/genética , Proteína HMGN1/metabolismo , Proteína HMGN2/genética , Proteína HMGN2/metabolismo , Humanos , Camundongos , Camundongos Knockout , Nucleossomos/metabolismo , Fenótipo , Regiões Promotoras Genéticas , Ligação Proteica , Isoformas de Proteínas , Estresse Fisiológico/genética
12.
Macromol Rapid Commun ; 39(4)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29250847

RESUMO

Herein, the report on a new class of self-healing and pH/temperature responsive mixed solvent (ethanol and water) gels shows unusual mechanical properties to resist slicing, sustain high compression, and withstand stretching as evidenced by the cutting breaking stress, the fracture compressive stress, and the stretching ratio of one of the gels as obtained can reach or exceed 26.4 MPa, 9.2 MPa, and ≈5 times, respectively. The gels are designed by introducing dynamic covalent bond, acylhydrazone, which is believed to combine the merits of conventional chemical bonds and those of supramolecular interactions. Specifically, a hydrazide-modified calix[4]arene derivative and linear benzaldehyde-terminated poly(ethylene glycol)s are synthesized and used as reactive components to build gel networks. Interestingly, acid-degradable hydrogel can be obtained via natural drying of the mixed solvent gel first and then swelling in pure water.


Assuntos
Calixarenos/síntese química , Géis/síntese química , Hidrazonas/química , Benzaldeídos/síntese química , Benzaldeídos/química , Calixarenos/química , Etanol/química , Géis/química , Concentração de Íons de Hidrogênio , Polietilenoglicóis/química , Solventes/química , Temperatura , Água/química
13.
Nucleic Acids Res ; 44(15): 7144-58, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27112571

RESUMO

The activation of naïve B lymphocyte involves rapid and major changes in chromatin organization and gene expression; however, the complete repertoire of nuclear factors affecting these genomic changes is not known. We report that HMGN proteins, which bind to nucleosomes and affect chromatin structure and function, co-localize with, and maintain the intensity of DNase I hypersensitive sites genome wide, in resting but not in activated B cells. Transcription analyses of resting and activated B cells from wild-type and Hmgn(-/-) mice, show that loss of HMGNs dampens the magnitude of the transcriptional response and alters the pattern of gene expression during the course of B-cell activation; defense response genes are most affected at the onset of activation. Our study provides insights into the biological function of the ubiquitous HMGN chromatin binding proteins and into epigenetic processes that affect the fidelity of the transcriptional response during the activation of B cell lymphocytes.


Assuntos
Linfócitos B/metabolismo , Cromatina/genética , Cromatina/metabolismo , Regulação da Expressão Gênica , Proteínas HMGN/metabolismo , Ativação Linfocitária/genética , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Desoxirribonuclease I/metabolismo , Epigênese Genética , Proteínas HMGN/deficiência , Proteínas HMGN/genética , Proteína HMGN1/metabolismo , Proteína HMGN2/metabolismo , Masculino , Camundongos , Nucleossomos/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Baço/citologia , Baço/imunologia
14.
J Org Chem ; 82(5): 2489-2504, 2017 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-28225270

RESUMO

Bacteriochlorophylls contain a bacteriochlorin macrocycle bearing an annulated fifth ring. The fifth ring, termed the isocyclic ring or ring E, is equipped with 131-oxo and 132-carbomethoxy substituents. Herein, a general route to stable, synthetic bacteriochlorophyll analogues is described. Knoevenagel condensation (∼40 mM, rt, CH2Cl2, piperidine/AcOH/molecular sieves) of a dihydrodipyrrin-carboxaldehyde (AD half) and a dihydrodipyrrin substituted with a ß-ketoester (BC half) forms a propenone bearing the two halves (a hydrobilin analogue). Subsequent treatment (0.2 mM) with acid (Yb(OTf)3, CH3CN, 80 °C) promotes a double ring-closure process: (i) condensation between the α-position of pyrrole ring A and the α-acetal unit attached to pyrroline ring B forms the bacteriochlorin macrocycle, and (ii) Nazarov cyclization of the ß-(propenoyl)-substituted ring C forms the isocyclic ring (E). Five new bacteriochlorins bearing various substituents (alkyl/alkyl, aryl, and alkyl/ester) at positions 2 and 3 (ß-pyrrole sites, ring A) and 132 carboalkoxy groups (R = Me or Et) were constructed in 37-61% yield from the hydrobilin analogues. The BC half and AD half are available in five and eight steps, respectively, from the corresponding pyrrole-2-carboxaldehyde and unsaturated ketone. The bacteriochlorins exhibit absorption spectra typical of bacteriopheophytins (free base bacteriochlorophylls), with a strong near-infrared absorption band (707-751 nm).


Assuntos
Bacterioclorofila A/química , Compostos Macrocíclicos/química , Porfirinas/química , Análise Espectral/métodos
15.
Molecules ; 22(4)2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28420113

RESUMO

Synthetic bacteriochlorins-analogues of bacteriochlorophylls, Nature's near-infrared absorbers-are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin-carbinol or dihydrodipyrrin-acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline ring to ensure stability toward oxidation. The two routes differ in the location of the gem-dimethyl group at the respective 3- or 2-position in the dihydrodipyrrin, and the method of synthesis of the dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1-carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1-(aryl)carbinol, and upon subsequent acetylation, the corresponding dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin-acetate). Self-condensation of the dihydrodipyrrin-acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2-dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case, the aromatization process entails a 2e-/2H⁺ (aerobic) dehydrogenative oxidation following the dihydrodipyrrin self-condensation. Comparison of a tetrahydrodipyrrin-acetal (0%) versus a dihydrodipyrrin-acetal (41%) in bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins revealed the importance of resonance stabilization of the reactive hydrodipyrrin intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins have been prepared. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 726-743 nm.


Assuntos
Estrutura Molecular , Porfirinas/química , Análise Espectral , Técnicas de Química Sintética , Porfirinas/síntese química
16.
J Biol Chem ; 288(25): 18104-9, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23673662

RESUMO

The interactions of nuclear lamins with the chromatin fiber play an important role in regulating nuclear architecture and chromatin function; however, the full spectrum of these interactions is not known. We report that the N-terminal domain of the nucleosome-binding protein HMGN5 interacts with the C-terminal domain of the lamin-binding protein LAP2α and that these proteins reciprocally alter their interaction with chromatin. Chromatin immunoprecipitation analysis of cells lacking either HMGN5 or LAP2α reveals that loss of either protein affects the genome-wide distribution of the remaining partner. Our study identifies a new functional link between chromatin-binding and lamin-binding proteins.


Assuntos
Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Genoma Humano , Proteínas HMGN/metabolismo , Proteínas de Membrana/metabolismo , Transativadores/metabolismo , Sítios de Ligação/genética , Western Blotting , Núcleo Celular/metabolismo , Cromatina/genética , Imunoprecipitação da Cromatina , Proteínas de Ligação a DNA/genética , Recuperação de Fluorescência Após Fotodegradação , Células HEK293 , Proteínas HMGN/genética , Células HeLa , Humanos , Cinética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Membrana/genética , Ligação Proteica , Interferência de RNA , Transativadores/genética
17.
Nano Lett ; 13(11): 5437-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24074440

RESUMO

We have examined the carrier injection process of axial nanowire light-emitting diode (LED) structures and identified that poor carrier injection efficiency, due to the large surface recombination, is the primary cause for the extremely low output power of phosphor-free nanowire white LEDs. We have further developed InGaN/GaN/AlGaN dot-in-a-wire core-shell white LEDs on Si substrate, which can break the carrier injection efficiency bottleneck, leading to a massive enhancement in the output power. At room temperature, the devices can exhibit an output power of ~1.5 mW, which is more than 2 orders of magnitude stronger than nanowire LEDs without shell coverage. Additionally, such phosphor-free nanowire white LEDs can deliver an unprecedentedly high color rendering index of ~92-98 in both the warm and cool white regions, with the color rendering capability approaching that of an ideal light source, i.e. a blackbody.

18.
J Cardiovasc Transl Res ; 17(3): 723-731, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38622370

RESUMO

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.


Assuntos
Dissecção Aórtica , Eosinófilos , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Fatores de Tempo , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Medição de Risco , Doença Aguda , Resultado do Tratamento , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/cirurgia , Contagem de Leucócitos
19.
Environ Mol Mutagen ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012003

RESUMO

The detection of N-nitrosamines in drug products has raised global regulatory interest in recent years due to the carcinogenic potential of some nitrosamines in animals and a need to identify a testing strategy has emerged. Ideally, methods used would allow for the use of quantitative analysis of dose-response data from in vivo genotoxicity assays to determine a compound-specific acceptable intake for novel nitrosamines without sufficient carcinogenicity data. In a previous study we compared the dose-response relationships of N-nitrosodiethylamine (NDEA) in three in vivo genotoxicity endpoints in rats. Here we report a comparison of NDEA's genotoxicity profile in mice. Big Blue® mice were administered NDEA at doses of 0.001, 0.01, 0.1, 1 and 3 mg/kg/day by oral gavage for 28 days followed by 3 days of expression. Statistically significant increases in the NDEA induced mutations were detected by both the transgenic rodent mutation assay (TGR) using the cII endpoint and by duplex sequencing in the liver but not bone marrow of mice. In addition, administration of NDEA for two consecutive days in male C57BL/6N mice caused elevated DNA damage levels in the liver as measured by % tail DNA in comet assay. The benchmark dose (BMD) analysis shows a BMDL50 of 0.03, 0.04 and 0.72 mg/kg/day for TGR, duplex sequencing and comet endpoints, respectively. Overall, this study demonstrated a similar genotoxicity profile of NDEA between mice and rats and provides a reference that can be used to compare the potential potency of other novel nitrosamines for the induction of gene mutations.

20.
Schizophr Res ; 267: 122-129, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531159

RESUMO

Aggression in schizophrenia patients is an issue of concern. Previous studies have shown that aggression in schizophrenia patients may be related to insomnia and quality of life to different extents. This study aimed to explore the potential mediating role of quality of life in the relationship between aggression and insomnia among schizophrenia patients. Demographic factors affecting aggression in schizophrenia patients were also explored. PATIENTS AND METHODS: A total of 781 stable patients aged 18-75 who met the ICD10 diagnosis of "schizophrenia" completed the completed questionnaire. Aggression was assessed using the Modified Overt Aggression Scale (MOAS), sleep was assessed using the Insomnia Severity Index Scale (ISI), and quality of life was assessed using the five Likert options. Descriptive statistics and correlation analysis examined the correlation between aggression and other variables. The mediating role of quality of life in the association between insomnia and aggression was examined by pathway analysis. RESULTS: A total of 781 patients participated in this study, and approximately 16 % of the schizophrenia patients were aggressive. According to the mediation analysis, the direct effect of insomnia on aggression was 0.147, and the mediating effect of quality of life on insomnia and aggression was 0.021. Specifically, for the four dimensions of the MOAS, the direct effects of insomnia on verbal aggression, aggression toward property, and aggression toward oneself were 0.028, 0.032, and 0.023, respectively, with mediating effects of 0.003, 0.007, and 0.006, respectively, and no mediating effect on physical aggression was found. CONCLUSION: This study showed that insomnia significantly influenced aggression in schizophrenia patients. Quality of life significantly mediated insomnia and aggression and played a vital role in moderating aggression. Therefore, we suggest that in the future, improving aggression in schizophrenia patients, while paying attention to the importance of sleep, could start with improving quality of life to address this problem from multiple perspectives.


Assuntos
Agressão , Qualidade de Vida , Esquizofrenia , Distúrbios do Início e da Manutenção do Sono , Humanos , Agressão/fisiologia , Masculino , Feminino , Adulto , Esquizofrenia/fisiopatologia , Esquizofrenia/complicações , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Psicologia do Esquizofrênico
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