Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
1.
Materials (Basel) ; 17(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39124470

RESUMO

Optimizing the design of the top compression ring holds immense importance in reducing friction across both traditional Internal Combustion (IC) engines and hybrid power systems. This study investigates the impact of alternative fuels, specifically hydrogen and CNG, on the behavior of top piston rings within internal combustion (IC) engines. The goal of this approach is to understand the complex interplay between blow-by, fuel type, material behavior, and their effects on ring friction, energy losses, and resulting ring strength. Two types of IC engines were analyzed, taking into account flow conditions derived from in-cylinder pressures and piston geometry. Following ISO 6622-2:2013 guidelines, thick top compression rings made from varying materials (steel, cast iron, and silicon nitride) were investigated and compared. Through a quasi-static ring model within Computational Fluid Dynamics (CFD), critical tribological parameters such as the minimum film and ring friction were simulated, revealing that lighter hydrogen-powered engines with higher combustion pressures could potentially experience approximately 34.7% greater power losses compared to their heavier CNG counterparts. By delving into the interaction among the fuel delivery system, gas blow-by, and material properties, this study unveils valuable insights into the tribological and structural behavior of the top piston ring conjunction. Notably, the silicon nitride material demonstrates promising strength improvements, while the adoption of Direct Injection (DI) is associated with approximately 10.1% higher energy losses compared to PFI. Such findings carry significant implications for enhancing engine efficiency and promoting sustainable energy utilization.

2.
FASEB J ; 38(17): e70021, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39215566

RESUMO

Cone photoreceptor cyclic nucleotide-gated (CNG) channels play an essential role in phototransduction and cellular Ca2+ homeostasis. Mutations in genes encoding the channel subunits CNGA3 and CNGB3 are associated with achromatopsia, progressive cone dystrophy, and early-onset macular degeneration. Cone loss in patients with achromatopsia and cone dystrophy associated with CNG channel mutations has been documented by optical coherence tomography and in mouse models of CNG channel deficiency. Cone death in CNG channel-deficient retinas involves endoplasmic reticulum (ER) stress-associated apoptosis, dysregulation of cellular/ER Ca2+ homeostasis, impaired protein folding/processing, and impaired ER-associated degradation (ERAD). The E3 ubiquitin-protein ligase synoviolin 1 (SYVN1) is the primary component of the SYVN1/SEL1L ER retrotranslocon responsible for ERAD. Previous studies have shown that manipulations that protect cones and reduce ER stress/cone death in CNG channel deficiency, such as increasing ER Ca2+ preservation or treatment with an ER chaperone, increase the expression of SYVN1 and other components of the ER retrotranslocon. The present work investigated the effects of SYVN1 overexpression. Intraocular injection of AAV5-IRBP/GNAT2-Syvn1 resulted in overexpression of SYVN1 in cones of CNG channel-deficient mice. Following treatment, cone density in Cnga3-/- mice was significantly increased, compared with untreated controls, outer segment localization of cone opsin was improved, and ER stress/apoptotic cell death was reduced. Overexpression of SYVN1 also led to increased expression levels of the retrotranslocon components, degradation in ER protein 1 (DERL1), ERAD E3 ligase adaptor subunit (SEL1L), and homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1). Moreover, overexpression of SYVN1 likely enhanced protein ubiquitination/proteasome degradation in CNG channel-deficient retinas. This study demonstrates the role of SYVN1/ERAD in cone preservation in CNG channel deficiency and supports the strategy of promoting ERAD for cone protection.


Assuntos
Canais de Cátion Regulados por Nucleotídeos Cíclicos , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Células Fotorreceptoras Retinianas Cones , Ubiquitina-Proteína Ligases , Animais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Camundongos , Retículo Endoplasmático/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Degradação Associada com o Retículo Endoplasmático , Camundongos Knockout , Camundongos Endogâmicos C57BL
3.
Heliyon ; 10(15): e35010, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170269

RESUMO

The main objective of the paper is to reveal a few aspects related to combustion quality of a diesel engine fueled in diesel-gas mode with diesel fuel and compressed natural gas. The total amount of heat released per cycle will be higher when the engine is fueled in dual-fuel mode due to higher LHV and because of the gaseous state of CNG. For low and medium loads the total quality of heat released per cycle will increase with 10 % and for higher loads it will reach levels with 25 % higher. The heat release rate of the preformed mixture will double its value for low and medium loads and will reach thresholds up to 3.5 times higher (interval -15; -5°CA); admitting CNG into cylinder will help the preformed mixture to reach stoichiometric values and thus improving the fast combustion phase. Fueling the engine in dual fuel mode with diesel fuel and CNG will have a negative effect on the maximum heat release rate; there will be a 10 % drop in maximum HRR for low loads when the energetic substitution coefficient reaches 36 % and 14 % at high loads when the xc is 26 %. The gaseous state and a higher LHV of CNG will have a good impact on indicated mean effective pressure for all studied regimes when the engine is fueled in DG mode: for low and medium loads 30 % and for high loads 20 % increase will be recorded. Gaseous state of CNG will lead to a higher percentage of preformed mixture and thus the fast combustion phase will extend for longer periods for all studied regimes when the engine is fueled in DG mode (20 % longer for low and medium loads and 30 % for high loads). The diffusive combustion phase will become shorter due to a lower quantity of the main dose when CNG is injected into the intake manifold (10-15 % shorter for low loads and 7 % at high loads).

4.
Environ Int ; 190: 108945, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39151268

RESUMO

Vehicle exhaust is one of the major organic sources in urban areas. Old taxis equipped with failed three-way catalysts (TWCs) have been regarded as "super emitters". Compressed natural gas (CNG) is a regular substitution fuel for gasoline in taxis. The relative effect of fuel substitution and TWC failure has not been thoroughly investigated. In this work, vehicle exhausts from gasoline and CNG taxis with optimally functioning and malfunctioning TWCs are sampled by Tenax TA tubes and then analyzed by a comprehensive two-dimensional gas chromatography-mass spectrometer (GC×GC-MS). A total of 216 organics are quantified, including 80 volatile organic compounds (VOCs) and 132 intermediate volatility organic compounds (IVOCs). Failure of TWC introduces super emitters with 30 - 70 times emission factors (EFs), 60 - 112 times ozone formation potentials (OFPs), and 34 - 92 times secondary organic aerosols (SOAs) more than normal vehicles. Specifically, for the taxi with failed TWC, the total organic EF of CNG is 16 times that of gasoline, indicating that the failure of TWC exceeds the emission reduction achieved by CNG-gasoline substitution. A significant but unbalanced reduction of ozone and SOA is observed after TWC, whereas a notable "enrichment" in IVOCs was observed. Naphthalene is a typical IVOC component strongly associated with CNG-gasoline substitution and TWC failure, which is lacking in current VOC measurement. We especially emphasize that there is an urgent need to scrap vehicles with failed TWCs in order to significantly reduce air pollution.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Gasolina , Gás Natural , Emissões de Veículos , Compostos Orgânicos Voláteis , Emissões de Veículos/análise , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , Gasolina/análise , Monitoramento Ambiental/métodos , Gás Natural/análise , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Ozônio/química , Ozônio/análise , Poluição do Ar/prevenção & controle , Aerossóis/análise
5.
Sci Rep ; 14(1): 16617, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026008

RESUMO

Gas stations distributed around densely populated areas are responsible for toxic pollutant emissions such as volatile organic compounds (VOCs). This study aims to measure VOCs emission from three different kinds of gas stations to determine the extent of pollution from the gas stations and the most frequent type of VOC compound emitted. The concentrations of ambient VOCs at three refueling stations with a different type of fuels in Mashhad were monitored. The result of this study showed that CNG fuel stations are less polluting than petrol stations. In all the studied sites, the highest concentrations were related to xylene isomers, irrespective of the fuel type. Total VOCs at the supply of both compressed natural gas (CNG) and gasoline stations was 482.36 ± 563.45 µg m-3. At a CNG station and a gasoline station, total VOC concentrations were 1363.4 ± 1975 µg m-3 and 410.29 ± 483.37 µg m-3, respectively. The differences in concentrations of toluene and m,p-xylene between the fuel stations can be related to the quality and type of fuel, vapor recovery technology, fuel reserves, dripless nozzles, traffic density in these stations, meteorological conditions and the location of sampling sites. The combination of a sine function and a quadratic function could model the fluctuation behavior of air pollutants like m,p-xylene. In all the sites, the highest concentrations were related to xylene isomers, irrespective of the type of fuel. The changing rate of m,p-xylene pollutant in each station was also modeled in this study.

6.
Proc Natl Acad Sci U S A ; 121(25): e2321228121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857399

RESUMO

Ciliary defects are linked to ciliopathies, but impairments in the sensory cilia of Caenorhabditis elegans neurons extend lifespan, a phenomenon with previously unclear mechanisms. Our study reveals that neuronal cilia defects trigger the unfolded protein response of the endoplasmic reticulum (UPRER) within intestinal cells, a process dependent on the insulin/insulin-like growth factor 1 (IGF-1) signaling transcription factor and the release of neuronal signaling molecules. While inhibiting UPRER doesn't alter the lifespan of wild-type worms, it normalizes the extended lifespan of ciliary mutants. Notably, deactivating the cyclic nucleotide-gated (CNG) channel TAX-4 on the ciliary membrane promotes lifespan extension through a UPRER-dependent mechanism. Conversely, constitutive activation of TAX-4 attenuates intestinal UPRER in ciliary mutants. Administering a CNG channel blocker to worm larvae activates intestinal UPRER and increases adult longevity. These findings suggest that ciliary dysfunction in sensory neurons triggers intestinal UPRER, contributing to lifespan extension and implying that transiently inhibiting ciliary channel activity may effectively prolong lifespan.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cílios , Longevidade , Resposta a Proteínas não Dobradas , Animais , Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Intestinos/citologia , Transdução de Sinais , Neurônios/metabolismo , Retículo Endoplasmático/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/metabolismo
7.
Ophthalmic Res ; 67(1): 301-310, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38705136

RESUMO

INTRODUCTION: Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively, accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study was to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations. METHODS: The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs, and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (low and high group). RESULTS: In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between low and high groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between low and high groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients. CONCLUSION: Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.


Assuntos
Canais de Cátion Regulados por Nucleotídeos Cíclicos , Genótipo , Fenótipo , Retinose Pigmentar , Acuidade Visual , Humanos , Retinose Pigmentar/genética , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/fisiopatologia , Masculino , Feminino , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Adulto Jovem , Adolescente , Eletrorretinografia , Tomografia de Coerência Óptica/métodos , Idoso , Mutação , Criança , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Angiofluoresceinografia/métodos , Estudos de Associação Genética , Análise Mutacional de DNA , Linhagem , DNA/genética
8.
ACS Chem Neurosci ; 15(8): 1652-1668, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38579109

RESUMO

In treating retinitis pigmentosa, a genetic disorder causing progressive vision loss, selective inhibition of rod cyclic nucleotide-gated (CNG) channels holds promise. Blocking the increased Ca2+-influx in rod photoreceptors through CNG channels can potentially delay disease progression and improve the quality of life for patients. To find inhibitors for rod CNG channels, we investigated the impact of 16 cGMP analogues on both rod and cone CNG channels using the patch-clamp technique. Although modifications at the C8 position of the guanine ring did not change the ligand efficacy, modifications at the N1 and N2 positions rendered cGMP largely ineffective in activating retinal CNG channels. Notably, PET-cGMP displayed selective potential, favoring rod over cone, whereas Rp-cGMPS showed greater efficiency in activating cone over rod CNG channels. Ligand docking and molecular dynamics simulations on cyclic nucleotide-binding domains showed comparable binding energies and binding modes for cGMP and its analogues in both rod and cone CNG channels (CNGA1 vs CNGA3 subunits). Computational experiments on CNGB1a vs CNGB3 subunits showed similar binding modes albeit with fewer amino acid interactions with cGMP due to an inactivated conformation of their C-helix. In addition, no clear correlation could be observed between the computational scores and the CNG channel efficacy values, suggesting additional factors beyond binding strength determining ligand selectivity and potency. This study highlights the importance of looking beyond the cyclic nucleotide-binding domain and toward the gating mechanism when searching for selective modulators. Future efforts in developing selective modulators for CNG channels should prioritize targeting alternative channel domains.


Assuntos
Canais de Cátion Regulados por Nucleotídeos Cíclicos , Qualidade de Vida , Humanos , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Ligantes , Retina/metabolismo , Nucleotídeos Cíclicos , GMP Cíclico/metabolismo
9.
Sci Rep ; 14(1): 4266, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383548

RESUMO

As one of the potential explosions and inflammation, compressed natural gas (CNG) stations in urban areas cause irreparable losses and casualties. Estimating risk assessment in gas stress based on coherent uses can reduce accidents in urban areas. The purpose of the present study was to estimate a small risk estimation at one of the CNG multipurpose stations, LPG, using combined models of the Fuzzy Bayesian Network, Bow-tie Diagram, and consequence modeling. This study was conducted based on the basic and 25 intermediate events. This study formed a seven-person safety team to identify the primary events and build the Bow-tie diagram. Then, because of the lack of a proper database, fuzzy theory was used to determine the probability of significant events. Bayesian networks were drawn based on the Bow-tie model using GeNLe software. Finally, the main events of the two Bow-tie, Bayesian network modeling, and risk estimation were performed with the help of PHAST/SAFETI (V8.22). The geographical information system software was used to zone the explosion effects. The Risk assessment result showed that the social risks and the Bayesian network model are more than Bow-tie, and the Bow-tie diagram is unacceptable. Therefore, using incompatible land uses in the vicinity of the CNG stations gives rise to the effects of accident scenarios in particular residential and administrative land uses, which decision-makers and city managers should consider. Based on the findings of this study, the obtained results can be utilized to implement effective control measures. These measures encompass devising a response plan tailored to address specific emergency conditions and conducting comprehensive training programs for the individuals and residents residing within the study area.

10.
Channels (Austin) ; 17(1): 2273165, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37905307

RESUMO

Recent years have seen an outpouring of atomic or near atomic resolution structures of cyclic nucleotide-gated (CNG) channels, captured in closed, transition, pre-open, partially open, and fully open states. These structures provide unprecedented molecular insights into the activation, assembly, architecture, regulation, and channelopathy of CNG channels, as well as mechanistic explanations for CNG channel biophysical and pharmacological properties. This article summarizes recent advances in CNG channel structural biology, describes key structural features and elements, and illuminates a detailed conformational landscape of activation by cyclic nucleotides. The review also correlates structures with findings and properties delineated in functional studies, including nonselective monovalent cation selectivity, Ca2+ permeation and block, block by L-cis-diltiazem, location of the activation gate, lack of voltage-dependent gating, and modulation by lipids and calmodulin. A perspective on future research is also offered.


Assuntos
Canalopatias , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Humanos , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/química , Canalopatias/genética , Nucleotídeos Cíclicos , Calmodulina , GMP Cíclico
11.
Adv Exp Med Biol ; 1415: 269-276, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37440044

RESUMO

Photoreceptors (PRs) in the neural retina convert photon capture into an electrical signal that is communicated across a chemical synapse to second-order neurons in the retina and on through the rest of the visual pathway. This information is decoded in the visual cortex to create images. The activity of PRs depends on the concerted action of several voltage-gated ion channels that will be discussed in this chapter.


Assuntos
Células Fotorreceptoras , Retina , Células Fotorreceptoras/metabolismo , Retina/metabolismo , Transdução de Sinais , Sinapses/metabolismo , Canais Iônicos/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Células Fotorreceptoras Retinianas Cones/fisiologia
12.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37446378

RESUMO

Photoreceptors in the retina are highly specialized neurons with photosensitive molecules in the outer segment that transform light into chemical and electrical signals, and these signals are ultimately relayed to the visual cortex in the brain to form vision. Photoreceptors are composed of rods and cones. Rods are responsible for dim light vision, whereas cones are responsible for bright light, color vision, and visual acuity. Photoreceptors undergo progressive degeneration over time in many hereditary and age-related retinal diseases. Despite the remarkable heterogeneity of disease-causing genes, environmental factors, and pathogenesis, the progressive death of rod and cone photoreceptors ultimately leads to loss of vision/blindness. There are currently no treatments available for retinal degeneration. Cyclic guanosine 3', 5'-monophosphate (cGMP) plays a pivotal role in phototransduction. cGMP governs the cyclic nucleotide-gated (CNG) channels on the plasma membrane of the photoreceptor outer segments, thereby regulating membrane potential and signal transmission. By gating the CNG channels, cGMP regulates cellular Ca2+ homeostasis and signal transduction. As a second messenger, cGMP activates the cGMP-dependent protein kinase G (PKG), which regulates numerous targets/cellular events. The dysregulation of cGMP signaling is observed in varieties of photoreceptor/retinal degenerative diseases. Abnormally elevated cGMP signaling interferes with various cellular events, which ultimately leads to photoreceptor degeneration. In line with this, strategies to reduce cellular cGMP signaling result in photoreceptor protection in mouse models of retinal degeneration. The potential mechanisms underlying cGMP signaling-induced photoreceptor degeneration involve the activation of PKG and impaired Ca2+ homeostasis/Ca2+ overload, resulting from overactivation of the CNG channels, as well as the subsequent activation of the downstream cellular stress/death pathways. Thus, targeting the cellular cGMP/PKG signaling and the Ca2+-regulating pathways represents a significant strategy for photoreceptor protection in retinal degenerative diseases.


Assuntos
Degeneração Retiniana , Camundongos , Animais , Degeneração Retiniana/patologia , Transdução de Sinais , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , GMP Cíclico/metabolismo
13.
Polymers (Basel) ; 15(11)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37299277

RESUMO

The new generation presented for CNG fuel tanks of vehicles (type-IV) is made entirely of composites. The reason for that is to prevent the sudden explosion of metal tanks and to use the advantage of gas leakage in composite materials. Previous research has shown that type-IV CNG fuel tanks also have challenges such as variable wall thickness in outer shell parts, which are prone to failure under cyclic refueling loading. The optimization of this structure is on the agenda of many scholars and automakers, and in this regard, there are many standards for strength assessment. Despite reporting injury events, it seems that another parameter should be included in these calculations. In this article, the authors have attempted to numerically investigate the effect of drivers' refueling habits on the service life of type-IV CNG fuel tanks. For this purpose, a 34-L CNG tank made of glass/epoxy composite, polyethylene, and Al-7075T6, respectively, for the outer shell parts, liner, and flanges was considered as a case study. Moreover, a real-size measurement-based finite element model validated in the corresponding author's previous research was used. The loading history was applied as internal pressure according to the standard statement. Furthermore, considering different behavior of drivers for refueling, several loading histories with asymmetric details were applied. Eventually, the results obtained for different cases were compared to experimental data in symmetrical loading. The results showed that, based on the car's mileage, the driver's behavior in the refueling process can significantly reduce the service life of the tank (up to 78% of the predicted life based on the standard methodology).

14.
Phytomedicine ; 115: 154826, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37167846

RESUMO

BACKGROUND: Chronic non-atrophic gastritis (CNG) is the most common type of chronic gastritis. If not actively treated, it may induce gastric cancer (GC). Western medicine is effective in CNG, but there are more adverse reactions after long-term medication, and it is easy to relapse after treatment, which affects patients' health and life. Tibetan medicine Liuwei Muxiang Pills (LWMX pills) is a traditional Tibetan medicine compound, which has a unique curative effect in the treatment of gastric inflammation, especially chronic non-atrophic gastritis. However, the mechanisms of LWMX pills for treatment CNG still remain poor known. PURPOSE: The aim of this study was to evaluate the therapeutic intervention potential of Tibetan medicine LWMX pills on CNG and explore its potential mechanisms in mice models. METHODS: The mice models was established to evaluate the therapeutic effect of LWMX pills on CNG. The main components of LWMX pills were analyzed by GC-MS. HE staining, immunohistochemistry, proteomics and Western Blot were used to analyze the potential mechanism of LWMX pills for CNG treatment. RESULTS: In the present study, LWMX pills containing costunolide, dehydrocostuslactone and antioxidants were found. IF results showed that the expression of ALDH1B1 in the control group was significantly lower than that in the model group in the gastric mucosa tissue, and the expression of ALDH1B1 was significantly lower in the 25 mg/ml LWMX Pills group (one month) and 25 mg/ml LWMX Pills group (two months) than in the model group. IHC revealed that model group samples expressed higher levels of Furin than 25 mg/ml LWMX Pills group samples, as evidenced by very strong staining of Furin in gastric mucosal cells. However, AMY2 staining in gastric mucosal cells did not differ significantly between the treated and control groups. the protein expression levels of these proteins were decreased in 25 mg/mL LWMX pills. Meanwhile, we found that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths).Western blotting showed that the protein expression levels of Furin, AMY2A, CPA3, ALDH1B1, Cam1, COXII, IL-6, IL-1ß were decreased in 25 mg/mL LWMX pills. Meanwhile, that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths). CONCLUSION: 25mg/ml LWMX pill treatment for one month had better therapeutic effect on mice CNG. Further proteomic results showed that LWMX pills maintain gastric function by inhibiting inflammation and oxidative stress, and we also found that LWMX pills regulate the expression of proteins associated with cancer development (Amy2, Furin).


Assuntos
Gastrite Atrófica , Gastrite , Camundongos , Animais , Medicina Tradicional Tibetana/métodos , Furina , Proteômica , Recidiva Local de Neoplasia , Gastrite Atrófica/tratamento farmacológico , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Mucosa Gástrica/metabolismo , Inflamação
15.
Vision Res ; 208: 108232, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37054604

RESUMO

The genes CNGA1 and CNGB1 encode the alpha and beta subunits of the rod CNG channel, a ligand-gated cation channel whose activity is controlled by cyclic guanosine monophosphate (cGMP). Autosomal inherited mutations in either of the genes lead to a progressive rod-cone retinopathy known as retinitis pigmentosa (RP). The rod CNG channel is expressed in the plasma membrane of the outer segment and functions as a molecular switch that converts light-mediated changes in cGMP into a voltage and Ca2+ signal. Here, we will first review the molecular properties and physiological role of the rod CNG channel and then discuss the characteristics of CNG-related RP. Finally, we will summarize recent activities in the field of gene therapy aimed at developing therapies for CNG-related RP.


Assuntos
Canais de Cátion Regulados por Nucleotídeos Cíclicos , Retinose Pigmentar , Humanos , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Retinose Pigmentar/genética , Células Fotorreceptoras de Vertebrados
16.
J Mol Model ; 29(4): 119, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36988725

RESUMO

CONTEXT: In this research, CO2 and NO2 adsorption on doped nanographene (NG) sheets with transition metals (Fe, Ni, Zn) and (Mn, Co, Cu), respectively, have been applied for scavenging of these toxic gases as the environmental pollutants. The values of changes of atomic charge density have illustrated a more significant charge transfer for Ni-doped C-NG through CO2 adsorption and a more remarkable charge transfer for Co-doped C-NG through NO2 adsorption. The data of NMR spectroscopy has depicted several fluctuations around the graph of Zn-doped on the nanographene surface. The thermodynamic results from IR spectroscopy have indicated that [Formula: see text] values are almost similar for doped metal transitions of Mn, Co, and Cu on the C-NG nanosheet, while [Formula: see text] has the largest gap of Gibbs free energy adsorption with dipole moment. METHODS: The Langmuir adsorption model with a three-layered ONIOM using CAM-B3LYP functional accompanying LANL2DZ, EPR-III and 6-31 + G (d,p) basis sets due to Gaussian 16 revision C.01 program on the complexes of CO2 → (Fe, Ni, Zn) and NO2 → (Mn, Co, Cu) doped on the C-NG has been accomplished. Then, NMR and IR spectroscopy, nuclear quadrupole resonance, and natural bond orbital analysis have been accomplished for evaluating chemical shielding tensors, thermodynamic properties, electric potential, and occupancy fluctuation through bond orbitals, respectively. In addition, frontier orbitals of LUMO, HOMO, and also a series of chemical reactivity parameters have been calculated. Finally, time-dependent-DFT method due to UV-VIS spectrums has been accomplished to discern the low-lying excited states of CO2 and NO2 adsorption on the (Fe, Ni, Zn) and (Mn, Co, Cu), respectively, doped C-NG sheet.

17.
Biomedicines ; 11(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36830806

RESUMO

The visual process begins with the absorption of photons by photopigments of cone and rod photoreceptors in the retina. In this process, the signal is first amplified by a cyclic guanosine monophosphate (cGMP)-based signaling cascade and then converted into an electrical signal by cyclic nucleotide-gated (CNG) channels. CNG channels are purely ligand-gated channels whose activity can be controlled by cGMP, which induces a depolarizing Na+/Ca2+ current upon binding to the channel. Structurally, CNG channels belong to the superfamily of pore-loop cation channels and share structural similarities with hyperpolarization-activated cyclic nucleotide (HCN) and voltage-gated potassium (KCN) channels. Cone and rod photoreceptors express distinct CNG channels encoded by homologous genes. Mutations in the genes encoding the rod CNG channel (CNGA1 and CNGB1) result in retinitis-pigmentosa-type blindness. Mutations in the genes encoding the cone CNG channel (CNGA3 and CNGB3) lead to achromatopsia. Here, we review the molecular properties of CNG channels and describe their physiological and pathophysiological roles in the retina. Moreover, we summarize recent activities in the field of gene therapy aimed at developing the first gene therapies for CNG channelopathies.

18.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36834527

RESUMO

Porcine spermatozoa are stored in the oviductal isthmus after natural mating, and the number of spermatozoa is increased in the oviductal ampulla when the mature cumulus-oocyte complexes (COCs) are transferred into the ampulla. However, the mechanism is unclear. Herein, natriuretic peptide type C (NPPC) was mainly expressed in porcine ampullary epithelial cells, whereas its cognate receptor natriuretic peptide receptor 2 (NPR2) was located on the neck and the midpiece of porcine spermatozoa. NPPC increased sperm motility and intracellular Ca2+ levels, and induced sperm release from oviduct isthmic cell aggregates. These actions of NPPC were blocked by the cyclic guanosine monophosphate (cGMP)-sensitive cyclic nucleotide-gated (CNG) channel inhibitor l-cis-Diltiazem. Moreover, porcine COCs acquired the ability to promote NPPC expression in the ampullary epithelial cells when the immature COCs were induced to maturation by epidermal growth factor (EGF). Simultaneously, transforming growth factor-ß ligand 1 (TGFB1) levels were dramatically increased in the cumulus cells of the mature COCs. The addition of TGFB1 promoted NPPC expression in the ampullary epithelial cells, and the mature COC-induced NPPC was blocked by the transforming growth factor-ß type 1 receptor (TGFBR1) inhibitor SD208. Taken together, the mature COCs promote NPPC expression in the ampullae via TGF-ß signaling, and NPPC is required for the release of porcine spermatozoa from the oviduct isthmic cells.


Assuntos
Oócitos , Motilidade dos Espermatozoides , Feminino , Humanos , Masculino , Suínos , Animais , Oócitos/metabolismo , Sêmen , Oviductos , Espermatozoides , Fatores de Crescimento Transformadores/metabolismo , Peptídeos Natriuréticos/metabolismo
19.
Environ Monit Assess ; 195(3): 369, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36749427

RESUMO

Methane is an important greenhouse gas, which constitutes minimum 90% of automotive grade compressed natural gas (CNG) used in India. The use of CNG as automotive fuel has been implemented in almost all major tier I to tier III cities of the country. Delhi, the capital city of India, has world largest CNG-fuelled public transport system. The cylinders fitted to the CNG-fuelled vehicles are required to be subjected to hydrostatic stretch test every 3 years at Government of India approved CNG cylinder testing stations, as mandated under Rule 35 of Gas Cylinders Rules, 2016. During the testing of cylinders, CNG present in the cylinders are discharged in the atmosphere at the degassing point of CNG testing stations. This study estimates annual methane emissions from the CNG cylinder testing stations of Delhi. The annual average methane emission from the CNG cylinder testing stations of Delhi was found to be 30.8 tons during the year 2019. The uncertainties in the emission estimate are also identified and discussed.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Aquecimento Global , Metano , Monitoramento Ambiental , Gás Natural/análise
20.
Sci Total Environ ; 858(Pt 2): 159966, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36347281

RESUMO

In China, natural gas (NG) is the main vehicle fuel after gasoline and diesel, and the number of NG vehicles ranks first in the world. At present, there are many studies on the conventional gaseous pollutants and particulate matter of NG vehicles, but very few studies on their VOCs. In this study, the chassis dynamometer is used to test CNG/E10 bi-fuel light-duty vehicles, analyze the advantages of CNG in CO2, fuel thermal efficiency, and cost, and discuss its disadvantages in NOx emission. Most importantly, the emission characteristics and ozone formation potential of VOCs in the exhaust of CNG vehicles were analyzed in the study. Compared with E10, CNG fuel can reduce CO2 emission by about 20 %, improve thermal efficiency by about 13 %, and save fuel costs by about 50 %. However, it will increase NOx and NO2 emissions by about 10 % and 13 % respectively. As for VOCs, the emission factor of VOCs from CNG fuel is about 54 % of E10 fuel. The VOCs group with the highest proportion in the exhaust of CNG-fueled vehicles is alkanes, >80 %. while the alkanes and alkenes with the highest proportion in E10 fuel are 30 % and 23 % respectively. C2 VOCs emitted by CNG account for >70 %, while C2 VOCs emitted by E10 are <60 %, followed by C4 VOCs, about 10 % - 30 %. The OFPs of VOCs in CNG exhaust is about 13.7 % of E10. Alkenes contribute the most to ozone, and the OFPs of alkenes in CNG and E10 vehicle exhaust accounts for about 55.3 % and 78.8 % of TVOCs respectively. The results of this study are helpful to improve people's understanding of the environmental value of using NG vehicles.


Assuntos
Poluentes Atmosféricos , Ozônio , Humanos , Poluentes Atmosféricos/análise , Dióxido de Carbono , Emissões de Veículos/análise , Gasolina , Gás Natural , Alcanos , Alcenos , Veículos Automotores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA