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1.
Int J Biol Macromol ; 274(Pt 1): 133105, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876240

RESUMO

To effectively utilize the photodynamic antibacterial ability of vitamin K3 (VK3), by solving the photothermal instability of VK3, it was combined with natural polymers to apply the preservation of chilled mutton. We encapsulated VK3 in the (2-Hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) to construct VK3-HP-ß-CD complex and then introduced the complex to chitosan (CS) and polyvinyl alcohol (PVA) to fabricate an antibacterial film (CS/PVA-VK3-HP-ß-CD film). Through the packaging performance test of the film, the content of VK3-HP-ß-CD was an important factor determining the properties of film including tensile strength, elongation at break, water vapor permeability, water content and water contact angle. Meanwhile, CS/PVA-VK3-HP-ß-CD films could continuously release ROS under light and suspended in dark, thus realizing >99 % antibacterial rate for Escherichia coli and Staphylococcus aureus. In the application experiment of chilled mutton, CS/PVA-VK3-1-HP-ß-CD film could significantly inhibit the increase of total viable count (TVC), pH value (pH) and total volatile base nitrogen (TVB-N) of chilled mutton, and extended its shelf life for at least 12 days. These results indicated that the CS/PVA film with the VK3-HP-ß-CD complex might have promising potential as an antibacterial material for packaging and preserving food.

2.
Cancer Cell ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38942026

RESUMO

KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. We further observed that the proteasome inhibitor, carfilzomib, improved the anti-tumor efficacy of HRS-4642. Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.

3.
Ecotoxicol Environ Saf ; 278: 116397, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38714088

RESUMO

The soil pollution caused by cadmium (Cd) poses a significant threat to the environment. Therefore, identifying plants that can effectively remediate Cd-contaminated soils is urgently needed. In this study, physiological, cytological, and transcriptome analyses were performed to comprehensively understand the changes in Artemisia argyi under Cd stress. Physiological and cytological analyses indicated that A. argyi maintained normal growth with intact cell structure under Cd stress levels up to 10 mg/kg. Cytological analysis showed that Cd precipitation in leaf cells occurred in the cytoplasm and intercellular spaces. As the levels of Cd stress increased, proline accumulation in leaves increased, whereas soluble protein and soluble sugar initially increased, followed by a subsequent decline. The translocation factor was above 1 under 0.6 mg/kg Cd stress but decreased when it exceeded this concentration. Transcriptome analyses revealed several crucial Cd-influenced pathways, including amino acid, terpenoid, flavonoid, and sugar metabolisms. This study not only proved that A. argyi could enrich Cd in soil but also revealed the response of A. argyi to Cd and its resistance mechanisms, which provided insight into the cleaner production of A. argyi and the remediation of Cd-contaminated soil.


Assuntos
Artemisia , Cádmio , Poluentes do Solo , Artemisia/genética , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Folhas de Planta , Perfilação da Expressão Gênica , Adaptação Fisiológica/genética , Transcriptoma/efeitos dos fármacos , Biodegradação Ambiental , Solo/química
4.
J Thorac Dis ; 16(2): 911-923, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505063

RESUMO

Background: Programmed cell death (PCD) plays a critical role in tumor progression and malignancy, and exploring its relationship with lung adenocarcinoma (LUAD)'s survival outcomes is important for personalized diagnosis and treatment. This study aimed to identify survival-related genes and construct an effective prognostic indicator for LUAD based on 12 forms of PCD. Methods: A total of 1,933 candidate genes related to PCD were collected from published studies and public data center. A prognostic gene signature, called the cell death index (CDI), was established based on RNA-Seq and immunohistochemistry (IHC). IHC staining on tissue microarray was applied for the validation of protein level. Moreover, GSE42127, GSE72094 were used as validation datasets. Results: The CDI based on expression level of nine genes (CCNB2, HMGA1, CACNA2D2, BUB1B, BTG2, KIF14, PTGDS, SERPINB5, BRCA1) was highly predictive for overall survival (OS) of LUAD in our cohort [36-month area under the curve (AUC): 0.750, 60-month AUC: 0.809]. The CDI was further validated in independent cohorts (GSE72094, 36-month AUC: 0.717, 60-month AUC: 0.737; GSE42127, 12-month AUC: 0.829, 60-month AUC: 0.663). And the CDI was found to be an independent prognostic factor after adjusting for other clinical characteristics. Furthermore, the high-CDI group was associated with upregulated tumor immune infiltration compared to the low-CDI group. Conclusions: This study identified a 9-gene signature (CDI) based on PCD-related genes that accurately predicted the prognosis of LUAD patients. The CDI could serve as a valuable prognostic indicator and guide personalized therapeutic strategies for LUAD.

5.
Cell Res ; 33(11): 835-850, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37726403

RESUMO

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Serina/metabolismo , Linhagem Celular Tumoral
6.
Sensors (Basel) ; 23(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37448006

RESUMO

This paper verified through experiments that change in ambient temperature are the main cause of dark output noise drift. Additionally, the impact of dark output noise drift in fiber optic spectrometers on emissivity measurements has been investigated in this work. Based on an improved fiber optic spectrometer, two methods were proposed for characterizing and correcting the dark output noise offset in fiber optic spectrometers: the mean correction scheme and the linear fitting correction scheme. Compared to the mean correction scheme, the linear fitting correction scheme is more effective in solving the problem of dark output noise drift. When the wavelength is greater than 1600 nm, the calibration relative error of silicon carbide (SIC) emissivity is less than 0.8% by the mean correction scheme, while the calibration relative error of silicon carbide emissivity is less than 0.62% by the linear fitting correction scheme. This work solves the problem of dark output noise drift in prolonged measurement based on fiber optic spectrometers, improving the accuracy and reliability of emissivity and quantitative radiation measurement.


Assuntos
Tecnologia de Fibra Óptica , Reprodutibilidade dos Testes
7.
Artigo em Inglês | MEDLINE | ID: mdl-37030776

RESUMO

We present a novel framework to efficiently acquire anisotropic reflectance in a pixel-independent fashion, using a deep gated mixture-of-experts. While existing work employs a unified network to handle all possible input, our network automatically learns to condition on the input for enhanced reconstruction. We train a gating module that takes photometric measurements as input and selects one out of a number of specialized decoders for reflectance reconstruction, essentially trading generality for quality. A common pre-trained latent-transform module is also appended to each decoder, to offset the burden of the increased number of decoders. In addition, the illumination conditions during acquisition can be jointly optimized. The effectiveness of our framework is validated on a wide variety of challenging near-planar samples with a lightstage. Compared with the state-of-the-art technique, our quality is improved with the same number of input images, and our input image number can be reduced to about 1/3 for equal-quality results. We further generalize the framework to enhance a state-of-the-art technique on non-planar reflectance scanning.

8.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362290

RESUMO

Potassium (K+) is essential for plant growth and stress responses. A deficiency in soil K+ contents can result in decreased wheat quality and productivity. Thus, clarifying the molecular mechanism underlying wheat responses to low-K+ (LK) stress is critical. In this study, a tandem mass tag (TMT)-based quantitative proteomic analysis was performed to investigate the differentially abundant proteins (DAPs) in roots of the LK-tolerant wheat cultivar "KN9204" at the seedling stage after exposure to LK stress. A total of 104 DAPs were identified in the LK-treated roots. The DAPs related to carbohydrate and energy metabolism, transport, stress responses and defense, and post-translational modifications under LK conditions were highlighted. We identified a high-affinity potassium transporter (TaHAK1-4A) that was significantly up-regulated after the LK treatment. Additionally, TaHAK1-4A was mainly expressed in roots, and the encoded protein was localized in the plasma membrane. The complementation assay in yeast suggested that TaHAK1-4A mediates K+ uptake under extreme LK conditions. The overexpression of TaHAK1-4A increased the fresh weight and root length of Arabidopsis under LK conditions and improved the growth of Arabidopsis athak5 mutant seedlings, which grow poorly under LK conditions. Moreover, silencing of TaHAK1-4A in wheat roots treated with LK stress decreased the root length, dry weight, K+ concentration, and K+ influx. Accordingly, TaHAK1-4A is important for the uptake of K+ by roots exposed to LK stress. Our results reveal the protein metabolic changes in wheat induced by LK stress. Furthermore, we identified a candidate gene potentially relevant for developing wheat lines with increased K+ use efficiency.


Assuntos
Arabidopsis , Deficiência de Potássio , Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Potássio/metabolismo , Deficiência de Potássio/metabolismo , Proteômica , Plântula/genética , Plântula/metabolismo , Triticum/genética , Triticum/metabolismo
9.
Nat Metab ; 4(10): 1369-1401, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36217034

RESUMO

The activity of 5'-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.


Assuntos
Insulinas , Inanição , Humanos , Masculino , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Lisossomos/metabolismo , Inanição/metabolismo , Adenosina Trifosfatases/metabolismo , Caenorhabditis elegans , Monofosfato de Adenosina/metabolismo , Frutose/metabolismo , Insulinas/metabolismo
10.
Environ Sci Technol ; 56(7): 4262-4271, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35258949

RESUMO

We developed an infrared (IR)-based real-time online monitoring device (US Patent No: US 10,571,448 B2) to quantify heart electrocardiogram (ECG) signals to assess the water quality based on physiological changes in fish. The device is compact, allowing us to monitor cardiac function for an extended period (from 7 to 30 days depending on the rechargeable battery capacity) without function injury and disturbance of swimming activity. The electrode samples and the biopotential amplifier and microcontroller process the cardiac-electrical signals. An infrared transceiver transmits denoised electrocardiac signals to complete the signal transmission. The infrared receiver array and biomedical acquisition signal processing system send signals to the computer. The software in the computer processes the data in real time. We quantified ECG indexes (P-wave, Q-wave, R-wave, S-wave, T-wave, PR-interval, QRS-complex, and QT-interval) of carp precisely and incessantly under the different experimental setup (CuSO4 and deltamethrin). The ECG cue responses were chemical-specific based on CuSO4 and deltamethrin exposures. This study provides an additional technology for noninvasive water quality surveillance.


Assuntos
Eletrocardiografia , Coração , Animais , Peixes , Processamento de Sinais Assistido por Computador , Qualidade da Água
11.
Nature ; 603(7899): 159-165, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35197629

RESUMO

Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.


Assuntos
Hipoglicemiantes , Metformina , ATPases Vacuolares Próton-Translocadoras , Proteínas Quinases Ativadas por AMP/metabolismo , Adenosina Trifosfatases/metabolismo , Secretases da Proteína Precursora do Amiloide , Animais , Caenorhabditis elegans/metabolismo , Diabetes Mellitus/tratamento farmacológico , Glucose/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Lisossomos/metabolismo , Proteínas de Membrana , Metformina/agonistas , Metformina/metabolismo , Metformina/farmacologia , ATPases Vacuolares Próton-Translocadoras/metabolismo
12.
Environ Sci Pollut Res Int ; 29(27): 41849-41862, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35098459

RESUMO

Eco-toxicity profiles for commonly used disinfectants were lacking. Available traditional toxicity techniques have some limitations (assessments and ethical issues). Behaviour toxicology is a promising research area towards early warning and non-invasive approaches. We studied the potential eco-toxic effects of sodium hypochlorite (NaOCl) on the swimming behaviour of zebrafish. Zebrafish were exposed to different concentrations (Treatment I, Treatment II, Treatment III, and Treatment IV) of NaOCl for 360 h. Recovery study (144 h) was conducted for NaOCl treatment groups. The swimming behaviour of zebrafish was quantified efficiently using an online monitoring system (OMS). OMS dataset was processed for determination of behavioural differences by MATLAB and SPSS. Compared to the control group, the swimming strength of zebrafish under NaOCl treatments declined significantly (p < 0.001). Avoidance behaviour has occurred on zebrafish under NaOCl exposure periods. Furthermore, NaOCl toxicity also adjusted circadian rhythms on zebrafish. Zebrafish swimming strength was significantly (p < 0.001) improved under-recovery periods. Moreover, normal diurnal patterns have occurred. NaOCl could cause behavioural abnormalities in non-target organisms. Continuous exposure to common disinfectants could cause external and internal stress on non-target organisms, resulting in behavioural changes and circadian rhythm adjustments. Continuous changes in behavioural and circadian rhythms might reduce organisms' fitness and adaptation capacity. This study highlights (1) the importance of computer-based toxicity assessments, and (2) swimming behaviour is an early warning biomarker for eco-toxicity studies.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Animais , Comportamento Animal , Biomarcadores , Desinfetantes/toxicidade , Natação , Água , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
13.
Micromachines (Basel) ; 12(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34832749

RESUMO

In order to meet the requirements of having a small structure, a wide frequency band, and high sensitivity for acoustic signal measurement, an acoustic sensor based on a silicon-based grooved microring resonator is proposed. In this paper, the effective refractive index method and the finite element method are used to analyze the optical characteristics of a grooved microring resonator, and the size of the sensor is optimized. The theoretical analysis results show that, when the bending radius reaches 10 µm, the theoretical quality factor is about 106, the sensitivity is 3.14 mV/Pa, and the 3 dB bandwidth is 430 MHz, which is three orders of magnitude larger based on the sensitivity of the silicon-based cascaded resonator acoustic sensor. The sensor exhibits high sensitivity and can be used in hydrophones. The small size of the sensor also shows its potential application in the field of array integration.

14.
Micromachines (Basel) ; 12(11)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34832771

RESUMO

To reduce the loss of the metal-insulator-metal waveguide structure in the near-infrared region, a plasmonic nanosensor structure based on a racetrack resonant cavity is proposed herein. Through finite element simulation, the transmission spectra of the sensor under different size parameters were analyzed, and its influence on the sensing characteristics of the system was examined. The analysis results show that the structure can excite the double Fano resonance, which has a distinctive dependence on the size parameters of the sensor. The position and line shape of the resonance peak can be adjusted by changing the key parameters. In addition, the sensor has a higher sensitivity, which can reach 1503.7 nm/RIU when being used in refractive index sensing; the figure of merit is 26.8, and it can reach 0.75 nm/°C when it is used in temperature sensing. This structure can be used in optical integrated circuits, especially high-sensitivity nanosensors.

15.
Curr Biol ; 31(4): 840-852.e5, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33340458

RESUMO

In the germarium of the Drosophila ovary, developing germline cysts are surrounded by a population of somatic escort cells that are known to function as the niche cells for germline differentiation;1 however, the underlying molecular mechanisms of this niche function remain poorly understood. Through single-cell gene expression profiling combined with genetic analyses, we here demonstrate that the escort cells can be spatially and functionally divided into two successive domains. The anterior escort cells (aECs) specifically produce ecdysone, which acts on the cystoblast to promote synchronous cell division, whereas the posterior escort cells (pECs) respond to ecdysone signaling and regulate soma-germline cell adhesion to promote the transition from 16-cell cyst-to-egg chamber formation. The patterning of the aEC and pEC domains is independent of the germline but is dependent on JAK/STAT signaling activity, which emanates from the posterior. Thus, a heterogeneous population of escort cells constitutes a stepwise niche environment to orchestrate cystoblast division and differentiation toward egg chamber formation.


Assuntos
Cistos , Proteínas de Drosophila , Ecdisona , Animais , Diferenciação Celular , Drosophila , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Ecdisona/metabolismo , Feminino , Células Germinativas , Ovário , Células-Tronco
16.
Nucleic Acids Res ; 48(19): 10877-10889, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33010153

RESUMO

The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II , Regulação Fúngica da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Fatores de Elongação da Transcrição/metabolismo , Proteínas de Transporte/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Histona Acetiltransferases/metabolismo , Nucleossomos/metabolismo , Regiões Promotoras Genéticas , Proteínas de Saccharomyces cerevisiae/genética
17.
Sci Adv ; 6(16): eaaz2386, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32494612

RESUMO

Materials exhibiting reversible changes in optical properties upon light irradiation have shown great potential in diverse optoelectronic areas. In particular, the modulation of photochromic behavior on demand for such materials is of fundamental importance, but it remains a formidable challenge. Here, we report a facile and effective strategy to engineer controllable photochromic properties by varying the counterions in a series of zinc complexes consisting of a spirolactam-based photochromic ligand. Colorability and coloration rate can be finely tuned by conveniently changing their counterions. Through utilization of the reversible feature of the metal-ligand coordination bond between Zn2+ and the spirolactam-based ligand, dynamic manipulation of photochromic behavior was achieved. Furthermore, we demonstrated the practical applications of the tunable photochromic properties for these complexes by creating photochromic films and developing multilevel security printing. These findings show opportunities for the development of smart materials with dynamically controllable responsive behavior in advanced optoelectronic applications.

18.
Genetics ; 215(2): 407-420, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32327563

RESUMO

Mediator is an essential, multisubunit complex that functions as a transcriptional coactivator in yeast and other eukaryotic organisms. Mediator has four conserved modules, Head, Middle, Tail, and Kinase, and has been implicated in nearly all aspects of gene regulation. The Tail module has been shown to recruit the Mediator complex to the enhancer or upstream activating sequence (UAS) regions of genes via interactions with transcription factors, and the Kinase module facilitates the transition of Mediator from the UAS/enhancer to the preinitiation complex via protein phosphorylation. Here, we analyze expression of the Saccharomyces cerevisiaeHO gene using a sin4 Mediator Tail mutation that separates the Tail module from the rest of the complex; the sin4 mutation permits independent recruitment of the Tail module to promoters without the rest of Mediator. Significant increases in recruitment of the SWI/SNF and SAGA coactivators to the HO promoter UAS were observed in a sin4 mutant, along with increased gene activation. These results are consistent with recent studies that have suggested that the Kinase module functions negatively to inhibit activation by the Tail. However, we found that Kinase module mutations did not mimic the effect of a sin4 mutation on HO expression. This suggests that at HO the core Mediator complex (Middle and Head modules) must play a role in limiting Tail binding to the promoter UAS and gene activation. We propose that the core Mediator complex helps modulate Mediator binding to the UAS regions of genes to limit coactivator recruitment and ensure proper regulation of gene transcription.


Assuntos
Regulação Fúngica da Expressão Gênica , Complexo Mediador/metabolismo , RNA Polimerase II/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transcrição Gênica , Ativação Transcricional , Complexo Mediador/genética , Regiões Promotoras Genéticas , RNA Polimerase II/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética
19.
Sci Rep ; 9(1): 15998, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690787

RESUMO

Our aim is to assess the optimal cutoff value of fasting plasma glucose (FPG) in Chinese women at 24-28 weeks' gestation by performing oral glucose tolerance test (OGTT) to improve diagnostic rate of gestational diabetes mellitus (GDM). Data were derived from the Medical Birth Registry of Xiamen. A FPG cutoff value of 5.1 mmol/L confirmed the diagnosis of GDM in 4,794 (6.10%) pregnant women. However, a FPG cutoff value of 4.5 mmol/L should rule out the diagnosis of GDM in 35,932 (45.73%) pregnant women. If we use this cutoff value, the diagnosis of GDM to about 27.3% of pregnant women will be missed. Additionally, a 75-g OGTT was performed in pregnant women with FPG values between 4.5 and 5.1 mmol/L, avoiding the performance of formal 75-g OGTT in about 50.37% pregnant women. Meanwhile, according to maternal age and pre-pregnancy BMI categories, with FPG values between 4.5 mmol/L and 5.1 mmol/L, which had high sensitivity, to improve the diagnostic rate of GDM in all groups. Further researches are needed to present stronger evidences for the screening value of FPG in establishing the diagnosis of GDM in pregnant women.


Assuntos
Glicemia/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Jejum/sangue , Adulto , China , Diabetes Gestacional/etnologia , Feminino , Teste de Tolerância a Glucose , Humanos , Gravidez , Adulto Jovem
20.
J Diabetes Investig ; 10(5): 1358-1364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30869198

RESUMO

AIMS/INTRODUCTION: Diabetes prevalence in China has increased, but the trend in gestational diabetes mellitus prevalence is unclear. The objective of the present study was to examine the prevalence of gestational diabetes in Xiamen, China, and its association with maternal risk factors. MATERIALS AND METHODS: This linked-database cohort study used the Medical Birth Registry of Xiamen. Between 1 March 2011 and 30 March 2018, 78,572 women who were diagnosed with gestational diabetes mellitus (GDM) were enrolled in the study. Maternal factors associated with the prevalence of GDM were examined using multivariate logistic regression. RESULTS: A total of 13,738 (17.6%) pregnant women were diagnosed with GDM according to the International Association of Diabetes and Pregnancy Study Groups criteria. GDM prevalence ranged from 15.5% (2012) to 19.9% (2017). Increasing age was associated with GDM; women aged >40 years versus those aged >25 years had an adjusted odds ratio (OR) of 5.91 (95% confidence interval [CI] 4.202-8.314). A positive correlation was observed between weight and GDM risk; obese women versus normal-weight women had an adjusted OR of 2.508 (95% CI 2.253-2.792). Family history of diabetes and hypertension were more commonly observed among women with GDM. Multivariate analysis showed that family history of diabetes (OR 1.101, 90% CI 1.028-1.180), weight gain during early pregnancy (OR 1.087, 90% CI 1.052-1.124) and systolic blood pressure (OR 1.015, 90% CI 1.011-1.020) were risk factors associated with GDM incidence. CONCLUSIONS: GDM affects 17.6% of all pregnant women in Xiamen. Age and maternal obesity were major contributors to GDM. The trend of GDM risk remained stable during the study.


Assuntos
Diabetes Gestacional/epidemiologia , Idade Materna , Obesidade/fisiopatologia , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Gravidez , Prevalência , Prognóstico
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