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1.
J Am Chem Soc ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602882

RESUMEN

Hydrogen peroxide (H2O2) holds significance as a vital chemical with the potential to serve as an energy carrier. Compared with the conventional anthraquinone process, photocatalytic H2O2 production has emerged as an appealing alternative because of its energy efficiency and environmental sustainability. However, the existing photocatalysts suffer from low catalytic efficiency, limited tunability of optical properties, and reliance on sacrificial agents due to high energy loss caused by inefficient charge separation. Therefore, developing catalysts with tunable optical properties and efficient charge separation is desirable. In this work, we introduce postsynthetic functionalization into an electrically conductive metal-organic framework, namely, DPT-MOF. Leveraging DPT (3,6-di(4-pyridyl)-1,2,4,5-tetrazine) as a pillar ligand, we exploited click-type chemistry to manipulate band position and charge separation efficiency, allowing for photocatalytic nonsacrificial H2O2 production. Notably, the fluorine-functionalized MOF exhibited the highest H2O2 production rate of 1676 µmol g-1 h-1 under visible light in O2-saturated water among our other samples. This high production rate is attributed to the tuned electronic structure and prolonged charge lifetime facilitated by the fluorine groups. This work highlights the effectiveness of postsynthetic methodology in tuning optical properties, opening a promising avenue for advancing the field of semiconductive MOF-based photocatalysis.

2.
Ann Pharmacother ; 57(7): 776-786, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36314281

RESUMEN

BACKGROUND: No study has yet systematically evaluated the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate the effect of different antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. METHODS: We comprehensively retrieved the published research which examined the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. The odds ratio (OR) and its 95% confidence interval (95% CI) for clinical outcomes were calculated using the random-effects model, and meta-regression was adopted to evaluate the potential sources of heterogeneity between studies. RESULTS: A total of 54 studies were included in this study. We found that the use of metformin (OR = 0.66, 95% CI: 0.58-0.75), SGLT-2i (OR = 0.80, 95% CI: 0.73-0.88), and GLP-1ra (OR = 0.83, 95% CI: 0.70-0.98) were significantly associated with lower mortality risk in COVID-19 patients with T2D, while insulin use might unexpectedly increase the ICU admission rate (OR = 2.32, 95% CI: 1.34-4.01) and risk of death (OR = 1.52, 95% CI: 1.32-1.75). No statistically significant associations were identified for DPP-4i, SUs, AGIs, and TZDs. CONCLUSION AND RELEVANCE: We demonstrated that the usage of metformin, SGLT-2i, and GLP-1ra could significantly decrease mortality in COVID-19 patients with T2D. The heterogeneity across the studies, baseline characteristics of the included patients, shortage of dosage and the duration of antidiabetic drugs and autonomy of drug selection might limit the objectivity and accuracy of results. Further adequately powered and high-quality randomized controlled trials are warranted for conclusive findings.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Metformina , Humanos , Hipoglucemiantes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Metformina/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón
3.
J Environ Manage ; 331: 117307, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36652878

RESUMEN

Microorganisms in anaerobic digestion (AD) are essential for wastes/pollutants treatment and energy recovery. Due to microbial enormous diversity, developing effective perspectives to understand microbial roles therein is urgent. This study conducted AD of swine manure, used an ensemble-based network analysis to distinguish interconnected, unconnected, copresence (positively interconnected) and mutual-exclusion (negatively interconnected) microorganisms within microbial communities, and explored their importance towards AD performances, using amplicon sequencing of 16S rRNA and 16S rRNA gene. Our analyses revealed greater importance of interconnected than unconnected microorganisms towards CH4 production and AD multifunctionality, which was attributed to higher niche breadth, deterministic community assembly, community stability and phylogenetic conservatism. The diversity was higher in unconnected than interconnected microorganisms, but was not linked to AD performances. Compared to copresence microorganisms, mutual-exclusion microorganisms showed greater and equal importance towards CH4 production and AD multifunctionality, which was attributed to their roles in stabilizing microbial communities. The increased feedstock biodegradability, by replacing part of manure with fructose or apple waste, hardly affected the relative importance of interconnected versus unconnected microorganisms towards CH4 production or AD multifunctionality. Our findings develop a new framework to understand microbial roles, and have important implications in targeted manipulation of critical microorganisms in waste-treatment systems.


Asunto(s)
Estiércol , Microbiota , Animales , Porcinos , Anaerobiosis , Filogenia , ARN Ribosómico 16S/genética , Metano , Reactores Biológicos , Biocombustibles
4.
Angew Chem Int Ed Engl ; 62(11): e202217054, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36571433

RESUMEN

Uncovering differences between crystalline and amorphous states in molecular solids would both promote the understanding of their structure-property relationships, as well as inform development of multi-functional materials based on the same compound. Herein, for the first time, we report an approach to leverage crystalline and amorphous states of a zero-dimensional metal-organic complex, which exhibited negative and positive photochromism, due to the competitive chemical routes between photocycloaddition and photogenerated radicals. Furthermore, different polymorphs lead to the on/off toggling of photo-burst movement (photosalient effect), indicating the controllable light-mechanical conversion. Three demos were further constructed to support their application in information encryption and anti-counterfeiting. This work provides the proof-of-concept of a state- and polymorph-dependent photochemical route, paving an effective way for the design of new dynamically responsive systems.

5.
Respir Res ; 23(1): 6, 2022 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-35016680

RESUMEN

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. METHODS: Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. RESULTS: In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. CONCLUSIONS: These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.


Asunto(s)
Regulación de la Expresión Génica , Hipertensión Pulmonar/genética , Hipoxia/complicaciones , Miocitos del Músculo Liso/metabolismo , Receptor Notch4/genética , Remodelación Vascular/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipoxia/genética , Hipoxia/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Miocitos del Músculo Liso/patología , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptor Notch4/biosíntesis , Transducción de Señal , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesis
6.
Inorg Chem ; 61(41): 16477-16483, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36190957

RESUMEN

Metal-organic hybrids with ultralong room-temperature phosphorescence (RTP) have potential applications in many fields, including optical communications, anticounterfeiting, encryption, bioimaging, and so on. Herein, we report two isostructural one-dimensional zinc-organic halides as coordination polymers ZnX2(bpp) (X = Cl, 1; Br, 2; bpp = 1,3-di(4-pyridyl)propane) with excitation wavelength- and time-dependent ultralong RTP properties. The dynamic multicolor afterglow can be assigned to the emission of the pristine ligand bpp and its interactions with halogen atoms. Experiments and theoretical calculations both suggest that ZnX2 is crucial for ultralong RTP: (a) the metal coordination and X...π bonds in coordination polymers fix the bpp molecules and suppress the nonradiative transitions; (b) the spin-orbital coupling of coordination polymers is largely enhanced relative to the bpp because of the heavy atom effect; and (c) the charge transfer exists between halogens and bpp ligand. Therefore, this work not only presents metal-halide coordination polymers with excitation wavelength- and time-dependent RTP properties, but also provides a facile method for the new types of dynamic multicolor afterglow materials.

7.
J Opt Soc Am A Opt Image Sci Vis ; 39(11): 2110-2123, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36520708

RESUMEN

Fringe patterns' denoising in electronic speckle pattern interferometry (ESPI) is an important step in phase extraction. In this study, we propose a new denoising method for ESPI fringe patterns based on a convolutional neural network (CNN). The proposed model which combines the attention mechanism and CNN is defined as attention-denoising CNN. In this model, owing to the attention mechanism, more attention will be paid to fringe information, and better filtering results will be achieved. The experimental results show that our proposed method can obtain excellent results, especially with high and large variation density ESPI fringe patterns.


Asunto(s)
Interferometría , Redes Neurales de la Computación , Interferometría/métodos , Electrónica
8.
Angew Chem Int Ed Engl ; 61(2): e202114100, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34747088

RESUMEN

Photo-controllable persistent luminescence at the single crystal level can be achieved by the integration of long-lived room temperature phosphorescence (RTP) and photochromism within metal-organic frameworks (MOFs) for the first time. Moreover, the multiblock core-shell heterojunctions have been prepared utilizing the isostructural MOFs through an epitaxial growth process, in which the shell exhibits bright yellow afterglow emission that gradually disappears upon further irradiation, but the core does not show such property. Benefitting from combined persistent luminescence and photochromic behavior, a multiple encryption demo can be facilely designed based on the dynamic manipulating RTP via reversible photochromism. This work not only develops new types of dynamically photo-controllable afterglow switch, but also provides a method to obtain MOFs-based optical heterojunctions towards potential space/time-resolved information encryption and anti-counterfeiting applications.

9.
Biochem Biophys Res Commun ; 557: 40-47, 2021 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-33862458

RESUMEN

Hypoxic pulmonary vascular remodeling is a pathological feature of pulmonary hypertension (PH). Our results showed that centromere-associated protein E (CENPE) expression in PH patients and hypoxia-induced PH rats was significantly higher than that in normal controls. In addition, CENPE deficiency significantly inhibited the development of pulmonary vascular remodeling and right ventricular hypertrophy. Moreover, knocking out CENPE effectively inhibited the proliferation and induced the apoptosis of primary pulmonary artery smooth muscle cells (PASMCs) in vivo. Furthermore, CENPE silencing by small interference significantly inhibited abnormal proliferation, apoptosis resistance, migration, and cell cycle arrest in hypoxia-induced PASMCs. Interestingly, we found that CENPE might exert its biological effect by targeting the transcription of CDK1 proteins.


Asunto(s)
Proteína Quinasa CDC2/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Hipertensión Pulmonar/patología , Hipertrofia Ventricular Derecha/patología , Arteria Pulmonar/patología , Remodelación Vascular/fisiología , Animales , Proteína Quinasa CDC2/genética , Células Cultivadas , Proteínas Cromosómicas no Histona/genética , Modelos Animales de Enfermedad , Femenino , Humanos , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertrofia Ventricular Derecha/genética , Hipertrofia Ventricular Derecha/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Hipoxia/patología , Masculino , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal
10.
Respir Res ; 22(1): 312, 2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34906150

RESUMEN

BACKGROUND: Hypoxic pulmonary hypertension (PH) is a refractory pulmonary vascular remodeling disease, and the efficiency of current PH treatment strategies is unsatisfactory. Tribbles homolog 3 (TRB3), a member of the pseudokinase family, is upregulated in diverse types of cellular stresses and functions as either a pro-proliferative or pro-apoptotic factor depending on the specific microenvironment. The regulatory mechanisms of TRB3 in hypoxic PH are poorly understood. METHODS: We performed studies using TRB3-specific silencing and overexpressing lentiviral vectors to investigate the potential roles of TRB3 on hypoxic pulmonary artery smooth muscle cells (PASMCs). Adeno-associated virus type 1(AVV1) vectors encoding short-hairpin RNAs against rat TRB3 were used to assess the role of TRB3 on hypoxic PH. TRB3 protein expression in PH patients was explored in clinical samples by western blot analysis. RESULTS: The results of whole-rat genome oligo microarrays showed that the expression of TRB3 and endoplasmic reticulum stress (ERS)-related genes was upregulated in hypoxic PASMCs. TRB3 protein expression was significantly upregulated by hypoxia and thapsigargin. In addition, 4-PBA and 4µ8C, both inhibitors of ERS, decreased the expression of TRB3. TRB3 knockdown promoted apoptosis and damaged the proliferative and migratory abilities of hypoxic PASMCs as well as inhibited activation of the MAPK signaling pathway. TRB3 overexpression stimulated the proliferation and migration of PASMCs but decreased the apoptosis of PASMCs, which was partly reversed by specific inhibitors of ERK, JNK and p38 MAPK. The Co-IP results revealed that TRB3 directly interacts with ERK, JNK, and p38 MAPK. Knockdown of TRB3 in rat lung tissue reduced the right ventricular systolic pressure and decreased pulmonary medial wall thickness in hypoxic PH model rats. Further, the expression of TRB3 in lung tissues was higher in patients with PH compared with those who have normal pulmonary artery pressure. CONCLUSIONS: TRB3 was upregulated in hypoxic PASMCs and was affected by ERS. TRB3 plays a key role in the pathogenesis of hypoxia-induced PH by binding and activating the ERK, JNK, and p38 MAPK pathways. Thus, TRB3 might be a promising target for the treatment of hypoxic PH.


Asunto(s)
Estrés del Retículo Endoplásmico/genética , Regulación de la Expresión Génica , Hipertensión Pulmonar/genética , Hipoxia/complicaciones , Sistema de Señalización de MAP Quinasas/genética , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Remodelación Vascular/genética , Animales , Apoptosis , Comunicación Celular , Modelos Animales de Enfermedad , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Masculino , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Serina-Treonina Quinasas/genética , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Regulación hacia Arriba
11.
Respir Res ; 22(1): 216, 2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344357

RESUMEN

BACKGROUND: Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. METHODS: Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1ß, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1ß in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1ß mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. RESULTS: NA had increased baseline sputum cell IL-1ß expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1ß mRNA was positively correlated with protein expression. Sputum IL-1ß mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1ß mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1ß augmenting TGF-ß1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors. CONCLUSIONS: IL-1ß level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1ß augmenting TGF-ß1-induced steroid-resistant EMT through MAPK signaling pathways. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).


Asunto(s)
Asma/inmunología , Transición Epitelial-Mesenquimal/inmunología , Interleucina-1beta/inmunología , Neutrófilos/inmunología , Mucosa Respiratoria/inmunología , Factor de Crecimiento Transformador beta/administración & dosificación , Células A549 , Adulto , Asma/genética , Asma/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Estudios de Seguimiento , Humanos , Interleucina-1beta/genética , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Adulto Joven
12.
Mikrochim Acta ; 188(6): 204, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-34043073

RESUMEN

A molecularly imprinted ratiometric fluorescent sensor was synthesized for the detection of 4-bromophenoxybenzene (BDE-3) based on perovskite quantum dots and metal organic framework. First, aspartic acid (Asp) was introduced during the synthesis of perovskite CsPbX3 for the formation of a core-shell structure of CsPbX3@Asp-Cs4PbX6. Due to the protection of the shell layer Cs4PbX6, the stability of the core CsPbX3 was improved significantly. Compared to CsPb(BrI)3, the ultraviolet and thermal stabilities of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 were increased by 26 times and 32 times, respectively, and, compared to CsPbBr3, these stabilities of CsPbBr3@Asp-Cs4PbBr6 were increased by 3 times and 13 times, respectively. The water stabilities of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 and CsPbBr3@Asp-Cs4PbBr6 were greatly improved too. Then, a ratiometric fluorescence sensor was constructed by in situ growth of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 in metal organic framework (NH2-MIL-53) for the detection of BDE-3, in which the orange fluorescence of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 (614 nm) was regarded as the reference signal and the cyan fluorescence of NH2-MIL-53 (494 nm) was used as the fluorescence response signal. To improve the selectivity of the sensor, the molecular imprinting polymer (MIP) was modified on the NH2-MIL-53 and an imprinting factor of 3.17 was obtained. Under 365 nm light excitation, the fluorescent response signal at 494 nm was quenched gradually by BDE-3 in the range 11.4 to 68.5 nmol/L, while the reference signal at 614 nm remained unchanged. The limit of detection and limit of quantification were 3.35 and 11.2 nmol/L, respectively, and the fluorescent color of the sensor changed gradually from cyan to green to orange, which illustrated that the developed sensor has an ability to recognize BDE-3 specifically, a good anti-interference ability, and a sensitively visual detection ability. Moreover, the sensor was successfully applied to the BDE-3 detection in polyethylene terephthalate plastic bottle, polyvinyl chloride plastic bag, and circuit board with satisfactory recoveries (96.3-108.1%) and low relative standard deviations (5%). The preparation processes of NH2-MIL-53, NH2-MIL-53-CsPb(BrI)3@Asp-Cs4Pb(BrI)6, and the MIP-NH2-MIL-53-CsPb(BrI)3@Asp-Cs4Pb(BrI)6 composites.

13.
J Cell Physiol ; 235(1): 538-547, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31256425

RESUMEN

Tribbles homolog 3 (TRB3) has been accounted for regulation of a few cell processes through interaction with other significant proteins. The molecular mechanisms underlying TRB3 in tumorigenesis in lung adenocarcinoma have not been entirely elucidated. The present study is aimed at determining the function and fundamental mechanisms of TRB3 in lung adenocarcinoma progression. TRB3 was highly expressed in A549 and H1299 cells and lung adenocarcinoma tissues compared with human bronchial epithelial cells (HBEpC) and adjacent normal lung tissues. Hypoxia significantly upregulated the expression of TRB3 protein in A549 and H1299 cells in a time-dependent way. Gene expression profiling interactive analysis data analysis indicated that patients with lung adenocarcinoma with excessive expression of TRB3 mRNA had fundamentally shorter survival time. TRB3 knockdown in A549 cells can inhibit cell proliferation and migration, and promote cell apoptosis. TRB3 knockdown reduced the expression of p-ERK and p-JNK, but did not affect the expression of p-P38 MAPK. TRB3 overexpression enhances the malignant transformation abilities of HBEpC such as cell proliferation, migration and colony formation, which could be reversed by U0126 and SP600125. TRB3 overexpression promotes the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) but was not affected by U0126 and SP600125. The results of coimmunoprecipitation experiments indicated that TRB3 binds directly to ERK and JNK. This study suggests that TRB3 has a potentially carcinogenic role in lung adenocarcinoma by binding to ERK and JNK and promoting the phosphorylation of ERK and JNK. TRB3 can be a possible therapeutic focus for lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Proteínas de Ciclo Celular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Neoplasias Pulmonares/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Represoras/genética , Células A549 , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Transformación Celular Neoplásica/genética , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Sistema de Señalización de MAP Quinasas , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
14.
Angew Chem Int Ed Engl ; 59(50): 22623-22630, 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-32875702

RESUMEN

Smart molecular crystals with light-driven mechanical responses have received interest owing to their potential uses in molecular machines, artificial muscles, and biomimetics. However, challenges remain in control over both the dynamic photo-mechanical behaviors and static photonic properties of molecular crystals based on the same molecule. Herein, we show the construction of isostructural co-crystals allows their light-induced cracking and jumping behaviors (photosalient effect) to be controlled. Hydrogen-bonded co-crystals from 4-(1-naphthylvinyl)pyridine (NVP) with co-formers (tetrafluoro-4-hydroxybenzoic acid (THA) and tetrafluorobenzoic acid (TA)) crystallize as isostructural crystals, but have different static and dynamic photo-mechanical behaviors. These differences are due to alternations in the orientation of NVP and hydrogen-bonding modes of the co-formers. After light activation, the 1D NVP-TA crystal splits and shears off within 1 s. For NVP-THA, its photostability and high quantum yield give novel photonic properties, including low optical waveguide loss, highly polarized anisotropy, and efficient up-conversion fluorescence.

15.
Bioorg Med Chem ; 27(15): 3390-3395, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31221612

RESUMEN

Aberrant activation of B cell receptor (BCR) signal transduction cascade contributes to the propagation and maintenance of B cell malignancies. The discovery of mall molecules with high potency and selectivity against Bruton's tyrosine kinase (BTK), a key signaling molecule in this cascade, is particularly urgent in modern treatment regimens. Herein, a series of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives were reported as potent BTK inhibitors. Compounds 17 and 18 displayed strong BTK inhibitory activities in the enzymatic inhibition assay, with the IC50 values of 1.2 and 0.8 nM, respectively, which were comparable to that of ibrutinib (IC50 = 0.6 nM). Additionally, compound 17 had a more selective profile over EGFR than ibrutinib. According to the putative binding poses, the molecular basis of this series of compounds with respect to potency against BTK and selectivity over EGFR was elucidated. In further experiments at cellular level, compounds 17 and 18 significantly inhibited the proliferation of Ramos and TMD8 cells. And they arrested 75.4% and 75.2% of TMD8 cells in G1 phase, respectively, at the concentration of 1 µM.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Antineoplásicos/farmacología , Descubrimiento de Drogas , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Agammaglobulinemia Tirosina Quinasa/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
Appl Microbiol Biotechnol ; 101(19): 7303-7316, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28828628

RESUMEN

Methanosarcina barkeri (DSM 800) is a metabolically versatile methanogen and shows distinct metabolic status under different substrate regimes. However, the mechanisms underlying distinct transcriptional profiles under different substrate regimes remain elusive. In this study, based on transcriptional analysis, the growth performances and gene expressions of M. barkeri fed on acetate, H2 + CO2, and methanol, respectively, were investigated. M. barkeri showed higher growth performances under methanol, followed by H2 + CO2 and acetate, which corresponded well with the variations of gene expressions. The α diversity (evenness) of gene expressions was highest under the acetate regime, followed by H2 + CO2 and methanol, and significantly and negatively correlated with growth performances. The gene co-expression analysis showed that "Energy production and conversion," "Coenzyme transport and metabolism," and "Translation, ribosomal structure, and biogenesis" showed deterministic cooperation patterns of intra- and inter-functional classes. However, "Posttranslational modification, protein turnover, chaperones" showed exclusion with other functional classes. The gene expressions and especially the relationships among them potentially drove the shifts of metabolic status under different substrate regimes. Consequently, this study revealed the diversity-related ecological strategies that a high α diversity probably provided more fitness and tolerance under natural environments and oppositely a low α diversity strengthened some specific physiological functions, as well as the co-responses of gene expressions to different substrate regimes.


Asunto(s)
Medios de Cultivo/química , Euryarchaeota/genética , Methanosarcina barkeri/genética , Transcriptoma , Ácido Acético/química , Dióxido de Carbono/química , Euryarchaeota/metabolismo , Regulación de la Expresión Génica Arqueal , Hidrógeno/química , Concentración de Iones de Hidrógeno , Metanol/química , Methanosarcina barkeri/metabolismo , ARN de Archaea/genética , Análisis de Secuencia de ARN , Especificidad por Sustrato
17.
Microb Cell Fact ; 15: 96, 2016 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-27260194

RESUMEN

BACKGROUND: Temperature is an important factor determining the performance and stability of the anaerobic digestion process. However, the microorganism-regulated mechanisms of temperature effects on the performance of anaerobic digestion systems remain further elusive. To address this issue, we investigated the changes in composition, diversity and activities of microbial communities under temperature gradient from 25 to 55 °C using 16S rRNA gene amplicon sequencing approach based on genomic DNA (refer to as "16S rDNA") and total RNA (refer to as "16S rRNA"). RESULTS: Microbial community structure and activities changed dramatically along the temperature gradient, which corresponded to the variations in digestion performance (e.g., daily CH4 production, total biogas production and volatile fatty acids concentration). The ratios of 16S rRNA to 16S rDNA of microbial taxa, as an indicator of the potentially relative activities in situ, and whole activities of microbial community assessed by the similarity between microbial community based on 16S rDNA and rRNA, varied strongly along the temperature gradient, reflecting different metabolic activities. The daily CH4 production increased with temperature from 25 to 50 °C and declined at 55 °C. Among all the examined microbial properties, the whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities showed highest correlations to the performance. CONCLUSIONS: The whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities were sensitive indicators for the performance of anaerobic digestion systems under temperature gradient, while beta-diversity could predict functional differences. Microorganism-regulated mechanisms of temperature effects on anaerobic digestion performance were likely realized through increasing alpha-diversity of both microbial communities and potentially relative activities to supply more functional pathways and activities for metabolic network, and increasing the whole activities of microbial community, especially methanogenesis, to improve the strength and efficiency in anaerobic digestion process.


Asunto(s)
Bacterias/genética , Anaerobiosis , Bacterias/metabolismo , ADN Bacteriano/genética , Análisis de Componente Principal , ARN Ribosómico 16S/genética , Temperatura
18.
Chem Sci ; 15(10): 3625-3632, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38455006

RESUMEN

Color-tunable room temperature phosphorescent (RTP) materials have raised wide interest due to their potential application in the fields of encryption and anti-counterfeiting. Herein, a series of CdX2-organic hybrid perovskitoids, (H-apim)CdX3 and (apim)CdX2 (denoted as CdX-apim1 and CdX-apim2, apim = 1-(3-aminopropyl)imidazole, X = Cl, Br), were synthesized using apim with both rigid and flexible groups as ligands, which exhibit naked-eye detectable RTP with different durations and colors (from cyan to red) by virtue of different halogen atoms, coordination modes and the coplanar configuration of flexible groups. Interestingly, CdCl-apim1 and CdX-apim2 both exhibit excitation wavelength-dependent RTP properties, which can be attributed to the multiple excitation of imidazole/apim, the diverse interactions with halogen atoms, and aggregated state of imidazoles. Structural analysis and theoretical calculations confirm that the aminopropyl groups in CdCl-apim1 do not participate in luminescence, while those in CdCl-apim2 are involved in luminescence including both metal/halogen to ligand charge transfer and twisted intramolecular charge transfer. Furthermore, we demonstrate that these perovskitoids can be applied in multi-step anti-counterfeiting, information encryption and smart ink fields. This work not only develops a new type of perovskitoid with full-color persistent luminescence, but also provides new insight into the effect of flexible ligands and halogen engineering on the wide-range modulation of RTP properties.

19.
Nanoscale ; 16(23): 11187-11202, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38771650

RESUMEN

This research introduces a method to enhance the mechanical properties of elastomers by grafting polymer chains onto single-chain flexible nanoparticles (SCNPs) and incorporating dynamic functional groups. Drawing on developments in grafting polymers onto hard nanoparticle fillers, this method employs the distinct flexibility of SCNPs to diminish heterogeneity and enhance core size control. We use molecular dynamics (MD) simulations for a mesoscale analysis of structural properties, particularly the effects of dynamic functional group quantities and their distribution. The findings demonstrate that increased quantities of functional groups are correlated with enhanced mechanical strength and toughness, showing improved stress-strain responses and energy dissipation capabilities. Moreover, the uniformity in the distribution of these functional groups is crucial, promoting a more cohesive and stable dynamic bonding network. The insights gained from MD simulations not only advance our understanding of the microstructural control necessary for optimizing macroscopic properties, but also provide valuable guidance for the design and engineering of advanced polymer nanocomposites, thereby enhancing the material performance through strategic molecular design.

20.
ISA Trans ; 136: 428-441, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36371262

RESUMEN

In avionics and industrial electronic systems, analog circuits are one of the most commonly used components. Intermittent faults (IFs) are a no fault found (NFF) state in analog circuits that are difficult to detect. In addition, the presence of noise may obscure critical information about the state of the circuit. Considering these challenges, this paper proposes an adaptive multiscale and dual subnet convolutional auto-encoder (AMDSCAE) to detect IFs. The proposed method can adaptively assign different attention to each scale and then fuse the multiscale information, which has better noise robustness. Then, the fault reconstruction error is amplified by the dual subnet structure to enhance the IF detection ability and find weaker faults. Considering the difficulty of obtaining fault sample labels, the proposed model requires only fault-free samples in the training process. In three typical analog filter circuit experiments, AMDSCAE has better noise immunity and can detect weaker IFs.

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