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1.
Mol Biol Evol ; 40(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37341536

RESUMO

Three prevalent SARS-CoV-2 variants of concern (VOCs) emerged and caused epidemic waves. It is essential to uncover advantageous mutations that cause the high transmissibility of VOCs. However, viral mutations are tightly linked, so traditional population genetic methods, including machine learning-based methods, cannot reliably detect mutations conferring a fitness advantage. In this study, we developed an approach based on the sequential occurrence order of mutations and the accelerated furcation rate in the pandemic-scale phylogenomic tree. We analyzed 3,777,753 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata using the Coronavirus GenBrowser. We found that two noncoding mutations at the same position (g.a28271-/u) may be crucial to the high transmissibility of Alpha, Delta, and Omicron VOCs although the noncoding mutations alone cannot increase viral transmissibility. Both mutations cause an A-to-U change at the core position -3 of the Kozak sequence of the N gene and significantly reduce the protein expression ratio of ORF9b to N. Using a convergent evolutionary analysis, we found that g.a28271-/u, S:p.P681H/R, and N:p.R203K/M occur independently on three VOC lineages, suggesting that coordinated changes of S, N, and ORF9b proteins are crucial to high viral transmissibility. Our results provide new insights into high viral transmissibility co-modulated by advantageous noncoding and nonsynonymous changes.


Assuntos
COVID-19 , COVID-19/genética , SARS-CoV-2/genética , Evolução Biológica , Mutação , Pandemias
2.
Eur J Neurosci ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044332

RESUMO

Post-traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD's underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the central nervous system, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body's response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart-brain axis interactions relevant to the development of PTSD. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD's prophylaxis and therapy.

3.
Small ; : e2311086, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459647

RESUMO

Despite the low competitive cost and high theoretical capacity of lithium-sulfur (Li-S) batteries, their practical application is severely hindered by the lithium polysulfide (LiPS) shuttling and low conversion efficiency. Herein, the electronic structure of hollow Titanium dioxide nanospheres is tunned by single Iron atom dopants that can cooperatively enhance LiPS absorption and facilitate desired redox reaction in practical Li-S batteries, further suppressing the notorious shuttle effect, which is consistent with theoretical calculations and in situ UV/vis investigation. The obtained electrode with massive active sites and lower energy barrier for sulfur conversions exhibits exceptional cycling stability after 500 cycles and high capacity under the sulfur loading of 10.53 mg cm-2 . In particular, an Ah-level Li-S pouch cell is fabricated, further demonstrating that the synthetic strategy based on atomic-level design offers a promising route toward practical high-energy-density Li-S batteries.

4.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35043153

RESUMO

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Vigilância em Saúde Pública/métodos , SARS-CoV-2/genética , Software , Navegador , Biologia Computacional/métodos , Análise Mutacional de DNA , Bases de Dados Genéticas , Genoma Viral , Genômica , Humanos , Epidemiologia Molecular/métodos , Anotação de Sequência Molecular , Mutação
5.
Drug Metab Dispos ; 52(7): 654-661, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38729662

RESUMO

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel. Our approaches were grounded in the molecular framework of clopidogrel and incorporated the C2-pharmacophore design from prasugrel. The selection of ester or carbamate substituents at the C2-position facilitated the generation of the 2-oxointermediate through hydrolysis, akin to prasugrel, thereby bypassing the issue of CYP2C19 dependency. The bulky C2-pharmacophore in our approach distinguishes itself from prasugrel's acetyloxy substituent by exhibiting a moderated hydrolysis rate, resulting in a more gradual formation of the active metabolite. Excessive and rapid release of the active metabolite, believed to be linked with an elevated risk of bleeding, is thus mitigated. Our proposed structural modification retains the hydrolysis-sensitive methyl ester of clopidogrel but substitutes it with a deuterated methyl group, shown to effectively reduce metabolic deactivation. Three promising compounds demonstrated a pharmacokinetic profile similar to that of clopidogrel at four times the dose, while also augmenting its antiplatelet activity. SIGNIFICANCE STATEMENT: Inspired by the structure-pharmacokinetic relationship of clopidogrel and prasugrel, a range of clopidogrel derivatives were designed, synthesized, and assessed. Among them, three promising compounds have been identified, striking a delicate balance between efficacy and safety for antiplatelet therapy. Additionally, the ozagrel prodrug conjugate was discovered to exert a synergistic therapeutic effect alongside clopidogrel.


Assuntos
Clopidogrel , Inibidores da Agregação Plaquetária , Cloridrato de Prasugrel , Clopidogrel/farmacocinética , Clopidogrel/farmacologia , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/química , Humanos , Cloridrato de Prasugrel/farmacocinética , Cloridrato de Prasugrel/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Relação Estrutura-Atividade , Ativação Metabólica , Masculino , Hidrólise , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos
6.
BMC Cancer ; 24(1): 582, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741069

RESUMO

BACKGROUND: Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. AIM: To find potential biomarkers of tumors for predicting postoperative recurrence. METHODS: In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. RESULTS: The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. CONCLUSIONS: This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Biomarcadores Tumorais , Proteínas de Ciclo Celular , Quimiorradioterapia , Recidiva Local de Neoplasia , PTEN Fosfo-Hidrolase , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Biomarcadores Tumorais/metabolismo , Idoso , Prognóstico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Fosfoproteínas/metabolismo , Adulto , Estadiamento de Neoplasias
7.
Phys Chem Chem Phys ; 26(28): 19207-19216, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38957083

RESUMO

The discovery of novel two-dimensional (2D) half-metallic materials with a robust ferromagnetic (FM) order and a high Curie temperature (Tc) is attractive for the advancement of next-generation spintronic devices. Here, we propose a monolayer with stable 2D intrinsic FM half-metallicity, i.e., the CrSc2Te4 monolayer, which was constructed by intercalating a monolayer of 1T-CrTe2-type sandwiched between two layers of 2H-ScTe2 monolayers. Our calculations reveal that it exhibits exceptional dynamical, thermal, and mechanical stabilities accompanied by a robust half-metallicity characterized by a wide bandgap of 1.02 eV and FM ordering with a high Tc of 326 K. Notably, these properties remain intact in almost the entire range of the biaxial strain from -5% to 5%. Furthermore, our investigations demonstrate excellent spin transport capabilities, including an outstanding spin-filtering effect, and a remarkably high tunneling magnetoresistance ratio peaking at 6087.07%. The remarkable magnetic features of the 2D CrSc2Te4 monolayer with room temperature FM, intrinsic half-metallicity, and 100% spin-polarization make it a promising candidate for the next-generation high-performance spintronic nanodevices as well as high-density magnetic recording and sensors.

8.
Nature ; 551(7679): 198-203, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29120414

RESUMO

The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Variação Genética , Neuroglia/metabolismo , Neurônios/metabolismo , Transdução de Sinais/genética , Alelos , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Neurônios Dopaminérgicos/metabolismo , Feminino , Genética Populacional , Locomoção/genética , Locomoção/fisiologia , Longevidade/genética , Longevidade/fisiologia , Masculino , Faringe/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas G/metabolismo , Neurônios Serotoninérgicos/metabolismo , Comportamento Sexual Animal/fisiologia , Sirtuínas/metabolismo , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/fisiologia
9.
Angew Chem Int Ed Engl ; 62(10): e202217839, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631412

RESUMO

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

10.
BMC Genomics ; 23(1): 387, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35596128

RESUMO

BACKGROUND: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). RESULTS: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. CONCLUSIONS: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle.


Assuntos
Músculo Esquelético , Transcriptoma , Animais , Bovinos , Ácidos Graxos/metabolismo , Carne/análise , Músculo Esquelético/metabolismo
11.
Hum Genet ; 141(2): 273-281, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35048190

RESUMO

Recombination is a major force that shapes genetic diversity. Determination of recombination rate is important and can theoretically be improved by increasing the sample size. However, it is nearly impossible to estimate recombination rates using traditional population genetics methods when the sample size is large because these methods are highly computationally demanding. In this study, we used a refined machine learning approach to estimate the recombination rate of the human genome using the UK10K human genomic dataset with 7,562 genomic sequences and its three subsets with 200, 400 and 2,000 genomic sequences. The estimation was performed under the human Out-of-Africa demographic model. We not only obtained an accurate human genetic map, but also found that the fluctuation of estimated recombination rate is reduced along the human genome when the sample size increases. The estimated UK10K recombination rate heterogeneity is less than that estimated from its subsets. Our results demonstrate how the sample size affects the estimated recombination rate, and analyses of a larger number of genomes result in a more precise estimation of recombination rate. The accurate genetic map based on UK10K data set is also expected to benefit other human biology researches.


Assuntos
Mapeamento Cromossômico/métodos , Genoma Humano , Mapeamento Cromossômico/estatística & dados numéricos , Bases de Dados Genéticas/estatística & dados numéricos , Genética Populacional , Humanos , Aprendizado de Máquina , Modelos Genéticos , Recombinação Genética , Tamanho da Amostra , Software , Reino Unido
12.
Appl Environ Microbiol ; 88(9): e0034122, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35442081

RESUMO

Isopropanol dehydrogenase (IPADH) is one of the most attractive options for nicotinamide cofactor regeneration due to its low cost and simple downstream processing. However, poor thermostability and strict cofactor dependency hinder its practical application for bioconversions. In this study, we simultaneously improved the thermostability (433-fold) and catalytic activity (3.3-fold) of IPADH from Brucella suis via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H) by 1.23 × 106-fold. When these variants were employed in three typical bioredox reactions to drive the synthesis of important chiral pharmaceutical building blocks, they outperformed the commonly used cofactor regeneration systems (glucose dehydrogenase [GDH], formate dehydrogenase [FDH], and lactate dehydrogenase [LDH]) with respect to efficiency of cofactor regeneration. Overall, our study provides two promising IPADH variants with complementary cofactor specificities that have great potential for wide applications. IMPORTANCE Oxidoreductases represent one group of the most important biocatalysts for synthesis of various chiral synthons. However, their practical application was hindered by the expensive nicotinamide cofactors used. Isopropanol dehydrogenase (IPADH) is one of the most attractive biocatalysts for nicotinamide cofactor regeneration. However, poor thermostability and strict cofactor dependency hinder its practical application. In this work, the thermostability and catalytic activity of an IPADH were simultaneously improved via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H). The resultant variants show great potential for regeneration of nicotinamide cofactors, and the engineering strategy might serve as a useful approach for future engineering of other oxidoreductases.


Assuntos
NAD , Niacinamida , 2-Propanol , Formiato Desidrogenases/genética , NADP , Regeneração
13.
Chaos ; 32(6): 063132, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35778118

RESUMO

Symbolic dynamics is a powerful tool to describe topological features of a nonlinear system, where the required partition, however, remains a challenge for some time due to the complications involved in determining the partition boundaries. In this article, we show that it is possible to carry out interesting symbolic partitions for chaotic maps based on properly constructed eigenfunctions of the finite-dimensional approximation of the Koopman operator. The partition boundaries overlap with the extrema of these eigenfunctions, the accuracy of which is improved by including more basis functions in the numerical computation. The validity of this scheme is demonstrated in well-known 1D and 2D maps.

14.
Sensors (Basel) ; 22(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35408286

RESUMO

Breast density has been recognised as an important biomarker that indicates the risk of developing breast cancer. Accurate classification of breast density plays a crucial role in developing a computer-aided detection (CADe) system for mammogram interpretation. This paper proposes a novel texture descriptor, namely, rotation invariant uniform local quinary patterns (RIU4-LQP), to describe texture patterns in mammograms and to improve the robustness of image features. In conventional processing schemes, image features are obtained by computing histograms from texture patterns. However, such processes ignore very important spatial information related to the texture features. This study designs a new feature vector, namely, K-spectrum, by using Baddeley's K-inhom function to characterise the spatial distribution information of feature point sets. Texture features extracted by RIU4-LQP and K-spectrum are utilised to classify mammograms into BI-RADS density categories. Three feature selection methods are employed to optimise the feature set. In our experiment, two mammogram datasets, INbreast and MIAS, are used to test the proposed methods, and comparative analyses and statistical tests between different schemes are conducted. Experimental results show that our proposed method outperforms other approaches described in the literature, with the best classification accuracy of 92.76% (INbreast) and 86.96% (MIAS).


Assuntos
Densidade da Mama , Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Mamografia/métodos , Análise Espacial
15.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499383

RESUMO

Carcass yield traits are of considerable economic importance for farm animals, which act as a major contributor to the world's food supply. Genome-wide association studies (GWASs) have identified many genetic variants associated with carcass yield traits in beef cattle. However, their functions are not effectively illustrated. In this study, we performed an integrative analysis of gene-based GWAS with expression quantitative trait locus (eQTL) analysis to detect candidate genes for carcass yield traits and validate their effects on bovine skeletal muscle satellite cells (BSCs). The gene-based GWAS and cis-eQTL analysis revealed 1780 GWAS and 1538 cis-expression genes. Among them, we identified 153 shared genes that may play important roles in carcass yield traits. Notably, the identified cis-eQTLs of PON3 and PRIM2 were significantly (p < 0.001) enriched in previous GWAS loci for carcass traits. Furthermore, overexpression of PON3 and PRIM2 promoted the BSCs' proliferation, increased the expression of MYOD and downregulated the expression of MYOG, which indicated that these genes may inhibit myogenic differentiation. In contrast, PON3 and PRIM2 were significantly downregulated during the differentiation of BSCs. These findings suggested that PON3 and PRIM2 may promote the proliferation of BSCs and inhibit them in the pre-differentiation stage. Our results further contribute to the understanding of the molecular mechanisms of carcass yield traits in beef cattle.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Bovinos/genética , Animais , Polimorfismo de Nucleotídeo Único , Fenótipo , Expressão Gênica
16.
Molecules ; 27(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35268655

RESUMO

In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate.


Assuntos
Fosfatidilinositol 3-Quinases
17.
Inorg Chem ; 60(23): 18473-18482, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34797628

RESUMO

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

18.
Nanotechnology ; 33(11)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34844218

RESUMO

Lithium-sulfur (Li-S) batteries with tremendous energy density possess great promise for the next-generation energy storage devices. Even though, the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) seriously restrict practical applications of Li-S batteries. Herein, a three-dimensionally ordered macro/mesoporous TiN (3DOM TiN) nanostructure is established via using poly (methyl methacrylate) PMMA spheres as template. The interconnected macro/mesoporous channels are constructed to effectively alleviate the stacking of composite materials and render a large portion of inherent active sites exposed on the surface region. Moreover, TiN exhibits high electrical conductivity, which efficiently enhances charge-transfer kinetics and guarantees the favorable electrochemical performance of sulfur cathode. More importantly, the as-prepared 3DOM TiN suppresses the shuttle effect and improves the redox kinetics significantly due to strong affinity toward LiPSs. Attributed to these unique features, the S/3DOM TiN electrode achieves an ultrahigh initial discharge capacity of 1187 mAh g-1at 0.2 C, and stable cycling performance of 552 mAh g-1over 500 cycles at 1 C. Meanwhile, the discharge capacity retention of 701 mAh g-1(3.5 mAh cm-2) can be endowed for the S/3DOM TiN electrode under high sulfur loading of 5 mg cm-2after 100 cycles at 0.1 C. Therefore, the 3DOM TiN nanostructure electrocatalyst provides a promising path for developing practically useable Li-S batteries.

19.
Proc Natl Acad Sci U S A ; 115(22): E5056-E5065, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760079

RESUMO

Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation.


Assuntos
Anuros/genética , Anuros/fisiologia , Fluxo Gênico/genética , Especiação Genética , Animais , Hibridização Genética , Metagenômica , Filogenia , Seleção Genética , Tibet
20.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640891

RESUMO

To construct circular barrier coverage (CBC) with multistatic radars, a deployment optimization method based on equipartition strategy is proposed in this paper. In the method, the whole circular area is divided into several sub-circles with equal width, and each sub-circle is blanketed by a sub-CBC that is built based on the multistatic radar deployment patterns. To determine the optimal deployment patterns for each sub-CBC, the optimization conditions are firstly studied. Then, to optimize the deployment of the whole circular area, a model based on minimum deployment cost is proposed, and the proposed model is divided into two sub-models to solve the optimization issue. In the inner model, it is assumed that the width of a sub-circle is given. Based on the optimization conditions of the deployment pattern, integer linear programming (ILP) and exhaustive method (EM) are jointly adopted to determine the types and numbers of deployment patterns. Moreover, a modified formula is introduced to calculate the maximum valid number of receivers in a pattern, thus narrowing the search scope of the EM. In the outer model, the width of a sub-circle is assumed to be a variable, and the EM is adopted to determine the minimum total deployment cost and the optimal deployment patterns on each sub-circle. Moreover, the improved formula is exploited to determine the range of width for a sub-circle barrier and reduce the search scope of the EM. Finally, simulations are conducted in different conditions to verify the effectiveness of the proposed method. The simulation results indicate that the proposed method can spend less deployment cost and deploy fewer transmitters than the state-of-the-artwork.

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