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1.
Chemistry ; 25(33): 7815-7819, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30934137

RESUMO

The first example of one single crystal (NTOU-5) containing two different organic-inorganic hybrid open-framework structures was obtained using a hydro(solvo)thermal method and structurally characterized by single-crystal X-ray diffraction. Remarkably, under the same synthetic conditions, the zinc ions are respectively coordinated by oxalic acid (OX) and 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene (TIMB) linkers to form two significantly different frameworks: anionic [Zn2 (OX)3 ]2- and cationic [Zn(TIMB)]2+ networks that interweave with each other to give an unprecedented interpenetrating structure with two differently-bonded open-frameworks. From the inorganic chemistry perspective, it is extremely difficult to control to which metal center the oxygen-donor linkers or/and nitrogen-donor ligands bind. A mixed Co/Zn analogue was also obtained by a similar method. The single-crystal XRD and EDS analyses indicate that the octahedral Zn ions of the anionic framework are replaced by cobalt cations, whereas the Zn ions in the tetrahedral positions of the cationic networks remain intact. This leads to the formation of the interpenetrating analogue with a mixed metal composition. Furthermore, NTOU-5 shows structural stability and efficiently removes organic dyes from aqueous solutions at concentrations of 10 ppm.

2.
Biomacromolecules ; 20(6): 2305-2314, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31091092

RESUMO

Selective release of small interfering RNA (siRNA) payloads in response to intracellular substances is a prerequisite for the smart design of siRNA carriers. In this context, we developed a molecular program that allows reactivity with pyruvate for siRNA release in the cell on the basis of polyionic-complex- (PIC-) based siRNA carriers. Hydrazide can react with the α-keto acid structure of anionic pyruvate to form α-oxohydrazone, resulting in the reduction of the cationic net charge of the cationic polymer bearing a hydrazide moiety, which in turn leads to an inefficient electrostatic interaction with anionic siRNA and the consequent destabilization of the PIC (i.e., PGlu [DET/hydrazide]) in pyruvate-enriched environments, such as the cytoplasm, thus achieving effective siRNA release from the PIC and its associated gene-silencing activity. The present study provides the rationale for an α-oxohydrazone-formation-based smart design of pyruvate-responsive materials in the cell.


Assuntos
Portadores de Fármacos , Hidrazonas/metabolismo , Ácido Pirúvico/metabolismo , RNA Interferente Pequeno , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/farmacologia
3.
Chemistry ; 22(45): 16099-16102, 2016 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-27723143

RESUMO

A new 3D tubular zinc phosphite, Zn2 (C22 H22 N8 )0.5 (HPO3 )2 ⋅H2 O (1), incorporating a tetradentate organic ligand was synthesized under hydro(solvo)thermal conditions and structurally characterized by single-crystal X-ray diffraction. Compound 1 is the first example of inorganic zincophosphite chains being interlinked through 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene to form a tubular porous framework with unusual organic-inorganic hybrid channels. The thermal and chemical stabilities, high capacity for CO2 adsorption compared to that for N2 adsorption, and interesting optical properties of LED devices fabricated using this compound were also studied.

4.
Biosens Bioelectron ; 236: 115403, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37271096

RESUMO

Water is one of the most indispensable elements for human beings. People can live without food for a couple of weeks but cannot live without water for a couple of days. Unfortunately, drinking water is not always safe around the world; in many areas, the water for drinking could be contaminated with various microbes. However, the total viable microbe count in water still relies on culture-based methods in laboratories. Therefore, in this work, we report a novel, simple, and highly efficient strategy to detect live bacteria in water via a nylon membrane-integrated centrifugal microfluidic device. A handheld fan and a rechargeable hand warmer were utilized as the centrifugal rotor and the heat resource for reactions, respectively. The bacteria in water can be rapidly concentrated >500-fold by our centrifugation system. After incubation with water-soluble tetrazolium-8 (WST-8), the color change of the nylon membranes can be visually interpreted directly by the naked eye or recorded with a smartphone camera. The whole process can be finished in 3 h, and the detection limit can reach 102 CFU/mL. The detection range ranges from 102 CFU/mL to 105 CFU/mL. The cell counting results of our platform are highly positively correlated with the results of cell counting by the conventional lysogeny broth (LB) agar plate approach or the commercial 3 M Petrifilm™ cell counting plate. Our platform provides a convenient and sensitive strategy for rapid monitoring. We highly anticipate that this platform can improve water quality monitoring in resource-poor countries in the near future.


Assuntos
Técnicas Biossensoriais , Microfluídica , Humanos , Nylons , Bactérias , Smartphone
5.
Cell Metab ; 35(6): 996-1008.e7, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37146607

RESUMO

Aging results in a decline in neural stem cells (NSCs), neurogenesis, and cognitive function, and evidence is emerging to demonstrate disrupted adult neurogenesis in the hippocampus of patients with several neurodegenerative disorders. Here, single-cell RNA sequencing of the dentate gyrus of young and old mice shows that the mitochondrial protein folding stress is prominent in activated NSCs/neural progenitors (NPCs) among the neurogenic niche, and it increases with aging accompanying dysregulated cell cycle and mitochondrial activity in activated NSCs/NPCs in the dentate gyrus. Increasing mitochondrial protein folding stress results in compromised NSC maintenance and reduced neurogenesis in the dentate gyrus, neural hyperactivity, and impaired cognitive function. Reducing mitochondrial protein folding stress in the dentate gyrus of old mice improves neurogenesis and cognitive function. These results establish the mitochondrial protein folding stress as a driver of NSC aging and suggest approaches to improve aging-associated cognitive decline.


Assuntos
Hipocampo , Células-Tronco Neurais , Camundongos , Animais , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Envelhecimento/fisiologia , Resposta a Proteínas não Dobradas , Proliferação de Células
6.
Cell Rep ; 41(11): 111803, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36516757

RESUMO

Nonalcoholic fatty liver disease (NAFLD) can be ameliorated by calorie restriction, which leads to the suppressed somatotroph axis. Paradoxically, the suppressed somatotroph axis is associated with patients with NAFLD and is correlated with the severity of fibrosis. How the somatotroph axis becomes dysregulated and whether the repressed somatotroph axis impacts liver damage during the progression of NAFLD are unclear. Here, we identify a regulatory branch of the hepatic integrated stress response (ISR), which represses the somatotroph axis in hepatocytes through ATF3, resulting in enhanced cell survival and reduced cell proliferation. In mouse models of NAFLD, the ISR represses the somatotroph axis, leading to reduced apoptosis and inflammation but decreased hepatocyte proliferation and exacerbated fibrosis in the liver. NAD+ repletion reduces the ISR, rescues the dysregulated somatotroph axis, and alleviates NAFLD. These results establish that the hepatic ISR suppresses the somatotroph axis to control cell fate decisions and liver damage in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Somatotrofos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/patologia , Hepatócitos/patologia , Cirrose Hepática/patologia
7.
Curr Stem Cell Rep ; 6(4): 119-125, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33777658

RESUMO

PURPOSE OF REVIEW: Diet has profound impacts on health and longevity. Evidence is emerging to suggest that diet impinges upon the metabolic pathways in tissue-specific stem cells to influence health and disease. Here, we review the similarities and differences in the metabolism of stem cells from several tissues, and highlight the mitochondrial metabolic checkpoint in stem cell maintenance and aging. We discuss how diet engages the nutrient sensing metabolic pathways and impacts stem cell maintenance. Finally, we explore the therapeutic implications of dietary and metabolic regulation of stem cells. RECENT FINDINGS: Stem Cell transition from quiescence to proliferation is associated with a metabolic switch from glycolysis to mitochondrial OXPHOS and the mitochondrial metabolic checkpoint is critically controlled by the nutrient sensors SIRT2, SIRT3, and SIRT7 in hematopoietic stem cells. Intestine stem cell homeostasis during aging and in response to diet is critically dependent on fatty acid metabolism and ketone bodies and is influenced by the niche mediated by the nutrient sensor mTOR. SUMMARY: Nutrient sensing metabolic pathways critically regulate stem cell maintenance during aging and in response to diet. Elucidating the molecular mechanisms underlying dietary and metabolic regulation of stem cells provides novel insights for stem cell biology and may be targeted therapeutically to reverse stem cell aging and tissue degeneration.

8.
Food Funct ; 10(1): 125-139, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30600821

RESUMO

Loss of skeletal muscle mass and strength is often associated with disability and poor quality of life. Selective Androgen Receptor Modulators (SARMs) are under development as potential treatment. This study aims at examining the potential of wild bitter gourd (BG) as a SARM and its effects on the muscle decline induced by orchiectomy. In the cell-based androgen receptor (AR) transactivation assay, the BGP extract showed weak agonistic and antagonistic activities, resembling those of some SARMs. Male C57BL/6J mice were sham-operated (Sham group) or castrated (Cast groups) and fed a modified AIN-93G high sucrose diet supplemented without (Cast group) or with 5% lyophilized BG powder (Cast + BGP) or with testosterone propionate (7 mg TP per kg diet, Cast + TP) for 23 weeks. In contrast to the Cast + TP group, the BGP supplementation did not affect the serum testosterone concentration, and prostate and seminal vesicle mass. Both TP and BGP supplementation increased the weight of androgen responsive muscles, bulbocavernosus (BC) and levator ani (LA) (p < 0.05). The grip strength and the performance on a rotarod of the Cast + BGP group were comparable to those of the Cast + TP group (p > 0.05). The number of succinate dehydrogenase (SDH)-positive fibers of the Cast + BGP group was not significantly different from that of the Sham and Cast + TP groups (p > 0.05). The BGP supplementation up-regulated the Pgc1α, Ucp2 or Ucp3 gene expressions in skeletal muscles of castrated mice (p < 0.05). BGP showed some characteristics of the SARM and might improve skeletal muscle function through the up-regulation of mitochondrial biogenic genes and oxidative capacity, and ameliorated the castration-induced decline of skeletal muscle function in mice.


Assuntos
Androgênios/metabolismo , Momordica charantia/metabolismo , Músculo Esquelético/fisiopatologia , Atrofia Muscular/dietoterapia , Orquiectomia , Receptores Androgênicos/metabolismo , Androgênios/química , Animais , Dietoterapia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Momordica charantia/química , Força Muscular , Músculo Esquelético/cirurgia , Testosterona/sangue
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