Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.296
Filtrar
1.
Cell Death Differ ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976389

RESUMO

A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFNγ-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.

2.
Adv Sci (Weinh) ; 8(9): 2003410, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33977048

RESUMO

Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3-hydroxybutyrate (3-HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3-HB can significantly ameliorate atherosclerosis. Mechanistically, 3-HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G-protein-coupled receptor 109a (Gpr109a). 3-HB-Gpr109a signaling promotes extracellular calcium (Ca2+) influx. The elevation of intracellular Ca2+ level reduces the release of Ca2+ from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca2+ store depletion. As NLRP3 inflammasome can be activated by ER stress, 3-HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3-HB attenuates atherosclerosis in mice.

3.
J Am Med Dir Assoc ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33965405

RESUMO

OBJECTIVES: This study aimed to examine the bidirectional associations between handgrip strength and depressive symptoms in a nationally representative sample. DESIGN: Cohort study with a 4-year follow-up. SETTING AND PARTICIPANTS: A total of 13,208 participants from the China Health and Retirement Longitudinal Study were included in the analyses. METHODS: Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies-Depression Scale. Separate generalized estimating equations were used to analyze the cross-sectional and longitudinal associations between handgrip strength and depressive symptoms. Restricted cubic spline models were performed to explore the shape of the dose-response relationship. RESULTS: Decreased handgrip strength was related to subsequent increased risk of depressive symptoms, such that participants in the lowest quartile of handgrip strength were found to have an approximately 36% increased in their risk of depressive symptoms compared with those in the highest quartile [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.17, 1.58]. There was a linear dose-response relationship between handgrip strength and risk of depressive symptoms (Pnonlinearity = .25), in that a 5-unit increment in handgrip strength may lead to an 11% decrease in the risk of depressive symptoms (OR 0.89, 95% CI 0.85, 0.92). Conversely, depressive symptoms were prospectively associated with subsequent decreased handgrip strength (ß = -0.84, 95% CI -1.13, -0.55). An approximatively L-shaped dose-response pattern was found for the association between depressive symptoms level and handgrip strength (Pnonlinearity = .02). CONCLUSIONS AND IMPLICATIONS: The present study identified bidirectional associations between handgrip strength and depressive symptoms, and the associations were found to have a dose-response pattern. It provides important insights into integrated mental and physical health intervention strategies that simultaneously promote handgrip strength and depressive symptoms.

4.
Mol Cell Biochem ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970409

RESUMO

Reprogramming of energy metabolism is a hallmark of cancer which is prevalent worldwide. Octamer transcription factor-1 (OCT1) is a well-known transcription factor. However, the role of OCT1 in metabolism remodeling has not been well defined. In the present study, we found that OCT1 was up-regulated in non-small cell lung cancer (NSCLC) and correlated with poor patient survival. Further data identified that OCT1 increased glycolysis flux, promoting proliferation in lung cancer cells. Mechanistically, OCT1 facilitated the aerobic glycolysis and cell proliferation via up-regulation of hexokinase 2 (HK2), a crucial enzyme of the Warburg effect. Hence, our findings indicate that, in NSCLC, high levels of OCT1 contribute to the Warburg effect through up-regulation of HK2, linking up the OCT1/HK2 axis and cancer progression, which provide a potential biomarker and therapeutic target for NSCLC treatment.

5.
Org Biomol Chem ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960992

RESUMO

A nickel-catalyzed asymmetric Suzuki-Miyaura cross-coupling of racemic 3-bromo-phthalides and arylboronic acids was realized for the synthesis of diverse chiral 3-aryl-phthalides in moderate to excellent reaction yields. The reaction proceeded in a stereoconvergent manner and high enantioselectivities were observed for most examined examples. A number of functional groups like aldehyde, ester and bromide were well tolerated. Heteroaromatic boronic acids were also competent coupling partners in this reaction.

6.
Biophys J ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940024

RESUMO

Cell migration, which can be significantly affected by intracellular signaling pathways (ICSP) and extracellular matrix (ECM), plays a crucial role in many physiological and pathological processes. Cell migration is typically modeled as a persistent random walk (PRW), which depends on two critical motility parameters, i.e., migration speed and persistence time. It is generally very challenging to efficiently and accurately quantify the migration dynamics from noisy experimental data. Here, we introduce the normalized Shannon entropy (SE) based on the Fourier power spectrum of cellular velocity autocovariance function to quantify migration dynamics. The Shannon entropy introduced here possesses the similar physical interpretation as the Gibbs entropy for thermal systems in that SE naturally reflects the degree of order or randomness of cellular migration, attaining the maximal value of unity for purely diffusive migration (i.e., SE = 1 for the most "random" dynamics) and the minimal value of zero for purely ballistic dynamics (i.e., SE = 0 for the most "ordered" dynamics). We also find that SE is strongly correlated with the migration persistence while is less sensitive to the migration speed. Moreover, we introduce the time-varying Shannon entropy based on the wavelet power spectrum of cellular dynamics and demonstrate its superior utility to characterize the time-dependent persistence of cell migration, which is typically resulted from complex and time-varying intra or extracellular mechanisms. We employ our approach to analyze experimental data of in vitro cell migration regulated by distinct intracellular and extracellular mechanisms, exhibiting a rich spectrum of dynamic characteristics. Our analysis indicates that the Shannon entropy and wavelet transform (i.e., SE-based approach) offers a simple and efficient tool to quantify cell migration dynamics in complex microenvironment.

7.
J Mater Chem B ; 9(17): 3640-3661, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33870985

RESUMO

The excessive use of antibiotics has led to a rise in drug-resistant bacteria. These "superbugs" are continuously emerging and becoming increasingly harder to treat. As a result, new and effective treatment protocols that have minimal risks of generating drug-resistant bacteria are urgently required. Advanced nanomaterials are particularly promising due to their drug loading/releasing capabilities combined with their potential photodynamic/photothermal therapeutic properties. In this review, 0-dimensional, 1-dimensional, 2-dimensional, and 3-dimensional nanomaterial-based systems are comprehensively discussed for bacterial-based diagnostic and treatment applications. Since the use of these platforms as antibacterials is relatively new, this review will provide appropriate insight into their construction and applications. As such, we hope this review will inspire researchers to explore antibacterial-based nanomaterials with the aim of developing systems for clinical applications.

8.
Autoimmunity ; 54(3): 138-147, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33825599

RESUMO

OBJECTIVE: Asthma is a prevalent chronic inflammatory airway disease that is characterised by airway remodelling and airway hyperresponsiveness. Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) contribute to airway remodelling in asthma. However, the molecular mechanism underlying an increased ASMC mass in asthma remains elusive. Herein, we aimed at investigating the regulation of lncRNA PVT1 on ASMCs and focussing on the mechanism in the proliferation and migration. METHODS: Expression levels of lncRNA PVT1 and miR-590-5p in the serum collected from 24 children with asthma and 10 control children were determined by qRT-PCR. ASMCs proliferation and migration prior to and post platelet-derived growth factor subunit B (PDGF-BB) stimulation were examined by CCK-8 test and transwell assay. Dual-luciferase reporter assay was performed to determine miR-590-5p interaction with lncRNA PVT1 and follistatin-like 1 (FSTL1). Expression of lncRNA PVT1, miR-590-5p, FSTL1, C-Myc, cyclin D1, and cyclin-dependent kinase 1 (CDK1) was tested by quantitative real-time PCR (qRT-PCR) and immunoblotting analysis. RESULTS: The expression level of lncRNA PVT1 was higher but the expression level of miR-590-5p was lower in the serum of children with asthma than in control children. The expression level of lncRNA PVT1 was negatively correlated with the expression level of miR-590-5p in asthma. LncRNA PVT1 was upregulated upon PDGF-BB stimulation. LncRNA PVT1 knockdown by its specific shRNA repressed PDGF-BB-induced promotion of proliferation and migration in ASMCs and triggered an elevated miR-590-5p along with declined C-Myc, cyclin D1, and CDK1. The effects of lncRNA PVT1 knockdown on PDGF-BB-induced ASMCs were lost upon miR-590-5p inhibition. MiR-590-5p targeted FSTL1 gene and declined its expression, thus suppressing ASMC proliferation and migration following PDGF-BB stimulation and downregulating C-Myc, cyclin D1, and CDK1 expressions. The effects of miR-590-5p on PDGF-BB-induced ASMCs were lost upon FSTL1 overexpression. CONCLUSION: These results support the notion that the lncRNA PVT1/miR-590-5p/FSTL1 axis modulates ASMCs proliferation and migration following PDGF-BB stimulation, providing a potential therapeutic target to attenuate airway remodelling in asthma.

9.
J Int Med Res ; 49(4): 300060521999541, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33878943

RESUMO

A giant retrosternal goiter can lead to compression of vital organs in the mediastinum with high risk of acute cardiorespiratory decompensation. Additionally, patients with acromegaly are prone to developing severe airway obstruction and ventilation difficulties during anesthetic induction, leading to hypoxia and an increased partial pressure of carbon dioxide. Therefore, more comprehensive airway management strategies are needed. We herein describe a 57-year-old man with acromegaly and severe tracheal obstruction caused by a giant retrosternal goiter. He presented with a 1-week history of progressive dyspnea and was scheduled to undergo right lobe thyroidectomy and retrosternal goiter thyroidectomy. We created a comprehensive emergency plan for a difficult airway, including regional and topical anesthesia for awake endotracheal intubation, sevoflurane inhalation, small doses of midazolam and sufentanil to increase tolerance, self-made extended-length tracheostomy, video laryngoscope-assisted fiber-optic bronchoscopy, extracorporeal membrane oxygenation, and surgical tracheostomy. Importantly, tetracaine was inhaled through an atomizer, and a laryngotracheal topical anesthesia applicator was used to spray the larynx with 1% tetracaine to reduce stimulation during intubation. The giant goiter was successfully removed through the cervical approach. A carefully designed airway management strategy and close communication among a multidisciplinary operation team are the basis of perioperative anesthetic management for these patients.

10.
Genome ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852810

RESUMO

Understanding the genetic diversity of wheat is important for wheat breeding and improvement. However, there have been limited attempts to evaluate wheat diversity using fluorescence in situ hybridization (FISH). In this study, the chromosomal structures of 149 wheat accessions from 13 countries located between the latitudes of 30° and 45°N, the principal growing region for wheat, were characterized using FISH with pTa535 and pSc119.2 probes. The ranges of the numbers of FISH types in the A-, B-, and D-genomes were 2-8, 3-7, and 2-4, respectively, and the average numbers in the A- and B-genomes were greater than in the D-genome. Chromosomal translocations were detected by these probes, and previously undescribed translocations were also observed. Using the FISH, the genetic relationships among the 149 common wheat lines were divided into three groups (G1, G2, and G3). G1 mainly consisted of Southern European lines, G2 consisted of most lines from Japan and some lines from Western Asia, China, and Korea, and G3 consisted of the other lines from Southern Europe and most of the lines from Western Asia, China, and Korea. FISH karyotypes of wheat chromosomes distinguished chromosomal structural variations, revealed the genetic diversity among wheat varieties. Furthermore, these results provide valuable information for the further genetic improvement of wheat in China.

11.
Nutr Rev ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33855443

RESUMO

CONTEXT: The prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) is increasing in Asia and several countries are adopting preventive policies to reduce consumption of sugar-sweetened beverages (SSBs). However, evidence on the relation between SSB consumption and cardiometabolic health in Asian populations has not been summarized. OBJECTIVE: In this systematic review, the associations between consumption of SSBs and cardiometabolic outcomes, including obesity, T2DM, and CVD, are examined in Asian populations. DATA SOURCES: The PubMed, Scopus, and Web of Science databases, and gray literature were searched up to October, 2020 to identify relevant articles. DATA EXTRACTION: Two investigators independently extracted data from included studies. DATA ANALYSIS: When sufficient studies were available, a random-effects meta-analysis was used to calculate the pooled estimates (expressed as risk ratio [RR] and 95% confidence interval [CI]). Heterogeneity was tested and quantified using the Cochrane Q test and I2 statistic, respectively. RESULTS: Of the 17 studies included, 8 provided results about measures of adiposity (3 on weight change, 4 on body mass index (BMI), 2 on percent body fat, and 1 on abdominal obesity), 6 reported results about T2DM, and 3 reported on different CVD outcomes. High SSB consumption was significantly associated with greater weight gain and with a higher risk of selected CVD outcomes as compared with low consumption. In the meta-analysis, high SSB consumption was associated with greater T2DM risk before (RR, 1.51; 95%CI, 1.15-1.98 for highest vs lowest category; I2 = 76%) and after (RR, 1.38; 95%CI, 1.09-1.73; I2 = 56%) adjustment for BMI. CONCLUSIONS: These findings suggest that high SSB consumption is directly associated with weight gain, risk of T2DM, and, possibly, selected CVD outcomes in Asian populations. Public health strategies to reduce SSB consumption in Asian countries are warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019129456.Keywords: adiposity. cardiovascular disease, Asia, sugar-sweetened beverages, type 2 diabetes.

12.
Huan Jing Ke Xue ; 42(5): 2343-2352, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884804

RESUMO

The visible light-driven photocatalyst Ag3PO4/g-C3N4 was synthesized by a simple in-situ precipitation method. The synthesized samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. Compared with that of single Ag3PO4 and g-C3N4, the Ag3PO4/g-C3N4 composite had a higher catalytic efficiency for levofloxacin. According to the energy band analysis and free radical capture experiment, the mechanism of the Z-type heterostructure of the Ag3PO4/g-C3N4 composite was proposed.

13.
Essays Biochem ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885142

RESUMO

With the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and high salt concentration. These salt-loving microbes can partially solve the challenges of current industrial biotechnology (CIB) which requires high energy-consuming sterilization to prevent contamination as CIB is based on traditional chassis, typically, Escherichia coli, Bacillus subtilis, Pseudomonas putida and Corynebacterium glutamicum. The advantages and current status of Halomonas spp. including their molecular biology and metabolic engineering approaches as well as their applications are reviewed here. Moreover, a systematic strain engineering streamline, including product-based host development, genetic parts mining, static and dynamic optimization of modularized pathways and bioprocess-inspired cell engineering are summarized. All of these developments result in the term called next-generation industrial biotechnology (NGIB). Increasing efforts are made to develop their versatile cell factories powered by synthetic biology to demonstrate a new biomanufacturing strategy under open and continuous processes with significant cost-reduction on process complexity, energy, substrates and fresh water consumption.

14.
Proc Biol Sci ; 288(1948): 20210073, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33823666

RESUMO

Both anthropogenic impacts and historical climate change could contribute to population decline and species extinction, but their relative importance is still unclear. Emerging approaches based on genomic, climatic and anthropogenic data provide a promising analytical framework to address this question. This study applied such an integrative approach to examine potential drivers for the endangerment of the green peafowl (Pavo muticus). Several demographic reconstructions based on population genomes congruently retrieved a drastic population declination since the mid-Holocene. Furthermore, a comparison between historical and modern genomes suggested genetic diversity decrease during the last 50 years. However, climate-based ecological niche models predicted stationary general range during these periods and imply the little impact of climate change. Further analyses suggested that human disturbance intensities were negatively correlated with the green peafowl's effective population sizes and significantly associated with its survival status (extirpation or persistence). Archaeological and historical records corroborate the critical role of humans, leaving the footprint of low genomic diversity and high inbreeding in the survival populations. This study sheds light on the potential deep-time effects of human disturbance on species endangerment and offers a multi-evidential approach in examining underlying forces for population declines.

15.
Mol Hum Reprod ; 27(5)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33848337

RESUMO

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS; however, its pathogenesis remains unclear. Here, we performed whole-exome sequencing in 10 unrelated ASS and identified 2 homozygous variants, c.381delA[p.V128Sfs7*] and c.675C>A[p.Y225X], and 1 compound variant, c.88 C > T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in 4 patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C>A and c.88 C > T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a 'triplet' structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the 'triplet' structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.

16.
EMBO J ; : e106771, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909912

RESUMO

Chemical compounds have recently been introduced as alternative and non-integrating inducers of pluripotent stem cell fate. However, chemical reprogramming is hampered by low efficiency and the molecular mechanisms remain poorly characterized. Here, we show that inhibition of spleen tyrosine kinase (Syk) by R406 significantly promotes mouse chemical reprogramming. Mechanistically, R406 alleviates Syk / calcineurin (Cn) / nuclear factor of activated T cells (NFAT) signaling-mediated suppression of glycine, serine, and threonine metabolic genes and dependent metabolites. Syk inhibition upregulates glycine level and downstream transsulfuration cysteine biosynthesis, promoting cysteine metabolism and cellular hydrogen sulfide (H2 S) production. This metabolic rewiring decreased oxidative phosphorylation and ROS levels, enhancing chemical reprogramming. In sum, our study identifies Syk-Cn-NFAT signaling axis as a new barrier of chemical reprogramming and suggests metabolic rewiring and redox homeostasis as important opportunities for controlling cell fates.

17.
Phys Biol ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910180

RESUMO

Cell migration, which is regulated by intracellular signaling pathways (ICSP) and extracellular matrix (ECM), plays an indispensable role in many physiological and pathological process such as normal tissue development and cancer metastasis. However, there is a lack of rigorous and quantitative tools for analyzing the time-varying characteristics of cell migration in heterogeneous microenvironment, resulted from, e.g., the time-dependent local stiffness due to microstructural remodeling by migrating cells. Here, we develop a wavelet-analysis approach to derive the time-dependent motility parameters from cell migration trajectories, based on the time-varying persistent random walk model. In particular, the wavelet denoising and wavelet transform are employed to analyze migration velocities and obtain the wavelet power spectrum. Subsequently, the time-dependent motility parameters are derived via Lorentzian power spectrum. Our results based on synthetic data indicate the superiority of the method for estimating the intrinsic transient motility parameters, robust against a variety of stochastic noises. We also carry out a systematic parameter study and elaborate the effects of parameter selection on the performance of the method. Moreover, we demonstrate the utility of our approach via analyzing experimental data of in vitro cell migration in distinct microenvironments, including the migration of MDA-MB-231 cells in confined micro-channel arrays and correlated migration of MCF-10A cells due to ECM-mediated mechanical coupling. Our analysis shows that our approach can be as a powerful tool to accurately derive the time-dependent motility parameters, and further analyze the time-dependent characteristics of cell migration regulated by complex microenvironment.

18.
Insect Mol Biol ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837597

RESUMO

Proteins containing nuclear localization signals (NLSs) are actively transported into the nucleus via the classic importin-α/ß-mediated pathway, and NLSs are recognized by members of the importin-α family. Most studies of insect importin-αs have focused on Drosophila to date, little is known about the importin-α proteins in Lepidoptera insects. In this study, we identified four putative importin-α homologues, Spodoptera frugiperda importin-α1 (SfIMA1), SfIMA2, SfIMA4 and SfIMA7, from Sf9 cells. Immunofluorescence analysis showed that SfIMA2, SfIMA4 and SfIMA7 localized to the nucleus, while SfIMA1 distributed in cytoplasm. Additionally, SfIMA4 and SfIMA7 were also detected in the nuclear membrane of Sf9 cells. SfIMA1, SfIMA4 and SfIMA7, but not SfIMA2, were found to associate with the C terminus of AcMNPV DNA polymerase (DNApol) that harbours a typical monopartite NLS and a classic bipartite NLS. Further analysis of protein-protein interactions revealed that SfIMA1 specifically recognizes the bipartite NLS, while SfIMA4 and SfIMA7 bind to both monopartite and bipartite NLSs. Together, our results suggested that SfIMA1, SfIMA4 and SfIMA7 play important roles in the nuclear import of AcMNPV DNApol C terminus in Sf9 cells.

19.
Anal Bioanal Chem ; 413(9): 2457-2466, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33674935

RESUMO

In this study, an effective and portable method for enzyme activity detection and inhibitory activity evaluation was developed based on the alkaline phosphatase (ALP)-mediated reaction in a personal glucose meter (PGM). In this method, ALP catalyzes the hydrolysis of substrate amifostine (WR-2721) to produce ethanethiol (WR-1065), which can trigger the reduction of ferricyanide (K3[Fe(CN)6]), an electron transfer mediator in glucose test strips, to ferrocyanide ([K4Fe(CN)6]) and generate a PGM-detectable signal. Thus, WR-1065 can be directly quantified by a PGM as simply as detecting glucose in blood. After being systematically optimized, the method was applied to evaluate the inhibitory activity of ten small-molecule compounds and six Cordyceps sinensis (CS) extracts on ALP. The results showed that adenosine-5-monophosphate and theophylline had high inhibitory activity, but two CS extracts have promotion potency on ALP with the values of -20.7 ± 1.3% and -46.6 ± 2.1%, respectively. Moreover, the binding sites and modes of small-molecule compounds to ALP were investigated by molecular docking, while a new substrate competitor with theoretically good inhibitory activity against ALP was designed by scaffold hopping. Finally, the accuracy of the PGM method for enzyme activity detection was assessed by detecting ALP from milk samples, and the recovery ranged from 87.7% to 116.9%. These results indicate that it is feasible to evaluate enzyme activity and the inhibitory activity of small-molecule compounds and CS extracts on ALP using a PGM based on ALP-mediated reaction. Graphical abstract.

20.
Mol Ecol Resour ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33665976

RESUMO

Detecting genetic regions under selection in structured populations is of great importance in ecology, evolutionary biology and breeding programmes. We recently proposed EigenGWAS, an unsupervised genomic scanning approach that is similar to F ST but does not require grouping information of the population, for detection of genomic regions under selection. The original EigenGWAS is designed for the random mating population, and here we extend its use to inbred populations. We also show in theory and simulation that eigenvalues, the previous corrector for genetic drift in EigenGWAS, are overcorrected for genetic drift, and the genomic inflation factor is a better option for this adjustment. Applying the updated algorithm, we introduce the new EigenGWAS online platform with highly efficient core implementation. Our online computational tool accepts plink data in a standard binary format that can be easily converted from the original sequencing data, provides the users with graphical results via the R-Shiny user-friendly interface. We applied the proposed method and tool to various data sets, and biologically interpretable results as well as caveats that may lead to an unsatisfactory outcome are given. The EigenGWAS online platform is available at www.eigengwas.com, and can be localized and scaled up via R (recommended) or docker.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...