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1.
Org Lett ; 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114465

RESUMO

A metal- and base-free C(sp2)-H direct arylsulfonylation of secondary and tertiary enamides with aryldiazonium salts and ex situ generated SO2 (from SOgen) is presented. This method runs smoothly to produce ß-amidovinyl sulfones with excellent stereoselectivities in moderate to excellent yields. Moreover, this strategy features good functional group tolerance and environmentally benign reaction conditions. Mechanistic experiments indicate that this sulfonylation may proceed in a radical pathway.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34078642

RESUMO

BACKGROUND: Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL). METHODS: Seven cytokines - interleukin 1ß (IL1ß), IL4, IL6, IL8, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα), and vascular endothelial growth factor (VEGF) - were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. Odds ratios (ORs) and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression adjusting for sociodemographic and birth characteristics. RESULTS: We found that ALL patients were born with higher levels of a group of correlated cytokines than controls [IL1ß: OR of 1.18 (95% CI: 1.03, 1.35); IL8: 1.19 (1.03, 1.38); TNFα: 1.15 (1.01, 1.30); VEGF: 1.16 (1.01, 1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk. CONCLUSIONS: We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL. IMPACT: This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.

3.
Cell Chem Biol ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34107297

RESUMO

The generation of a library of variant genes is a prerequisite of directed evolution, a powerful tool for biomolecular engineering. As the number of all possible sequences often far exceeds the diversity of a practical library, methods that allow efficient library diversification in living cells are essential for in vivo directed evolution technologies to effectively sample the sequence space and allow hits to emerge. While traditional whole-genome mutagenesis often results in toxicity and the emergence of "cheater" mutations, recent developments that exploit the targeting and editing abilities of genome editors to facilitate in vivo library diversification have allowed for precise mutagenesis focused on specific genes of interest, higher mutational density, and reduced the occurrence of cheater mutations. This minireview summarizes recent advances in genome editor-directed in vivo library diversification and provides an outlook on their future applications in chemical biology.

4.
J Phys Chem B ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133190

RESUMO

Although the interaction mechanism between shock waves and cells is critical for advancing the medical applications of shock waves, we still have little understanding about it. This work aims to study the response of diseased cells subjected to lipid peroxidation to the nanojet from shock wave-induced bubble collapse by using the coarse-grained molecular dynamics simulation. Factors considered in the simulations include the shock velocity (up), movement time of piston (τp), bubble size (R), and peroxidation level of membranes. Here, we mainly focus on the role of peroxidation levels, that is, the degree (%) and the distribution of oxidized lipids in membranes. The results indicate that the shock damage threshold (up at which the pore in membranes is formed) of peroxidation membranes is less than that of normal membranes and decreases with the peroxidation degree. Importantly, the distribution of oxidized lipids has more effect on the damage threshold than the peroxidation degree. The threshold of membrane with 33% localized oxidized lipids is lower than that of membrane with 50% average oxidized lipids. The results can be explained by the stretching modulus (κs) and bending modulus (κb) of cell membranes. For example, the κb value (4.3 × 10-20 J) of 100% peroxidation membrane is about half of that (8.4 × 10-20 J) of a membrane without peroxidation. A lower modulus means high deformation under the same impact. Further analysis shows that peroxidation introduces a polar hydrophobic group to the tail of phospholipids that increases the hydrophilicity of tails and warps the tail of phospholipids toward the membrane-water interface, resulting in looser accumulation. This can be confirmed by the increased average phospholipid area with peroxidation levels. Indeed, most of the pores formed during the shock can heal. However, the permeation of water molecules across the healing membrane still increased. All these membrane-level information obtained from this study will be useful for improving the biomedical applications of shock waves.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34139674

RESUMO

Being a best-known prototype of phase-change materials, GeTe was reported to possess many high-pressure phases, whose structural evolution and superconductivity remain under debate for decades. Herein, we systematically investigated the pressure dependence of electrical transport and the structural evolution of the GeTe via in situ angle-dispersive synchrotron X-ray diffraction and resistance measurements up to 55 GPa. At room temperature, the structural phase transitions from the initial rhombohedral phase to the Fm 3m phase, and then to an orthorhombic Pnma phase, were observed at pressures of about 4 and 13.4 GPa, respectively. Furthermore, the metallization occurred at around 11 GPa, where the superconductivity could also be observed. With increasing pressure, the superconducting transition temperature increases monotonically from 5.7 to 6.4 K and then is independent of pressure above 23 GPa in the pure Pnma phase. These results provide insights into the pressure-dependent evolution of the structure and superconductivity in GeTe and have implications for the understanding of other IV-VI semiconductors at high pressure.

6.
Chem Commun (Camb) ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075947

RESUMO

We report a heterogeneous postassembly modification (PAM) to synthesize a zirconium metal-organic cage decorated with acrylate functional groups, ZrT-1-AA, which cannot be synthesized by direct coordination-driven self-assembly owing to the reactivity and instability of the ligand. The PAM process is carried out in a single-crystal-to-single-crystal transformation under mild reaction conditions with high efficiency, which is confirmed by ESI-TOF-MS and 1H NMR. In addition, ZrT-1-AA is crosslinked into shaped materials to demonstrate its potential applications. The proposed PAM strategy sheds light on the development of Zr-MOCs decorated with reactive functional groups, whose introduction is challenging or impossible via direct self-assembly.

7.
Nano Lett ; 21(10): 4437-4446, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33955221

RESUMO

A failure in immune tolerance leads to autoimmune destruction of insulin-producing ß-cells, leading to type 1 diabetes (T1D). Inhibiting autoreactive T cells and inducing regulatory T cells (Tregs) to re-establish immune tolerance are promising approaches to prevent the onset of T1D. Here, we investigated the ability of tetrahedral framework nucleic acids (tFNAs) to induce immune tolerance and prevent T1D in nonobese diabetic (NOD) mice. In prediabetic NOD mice, tFNAs treatment led to maintenance of normoglycemia and reduced incidence of diabetes. Moreover, the tFNAs (250 nM) treatment preserved the mass and function of ß-cells, increased the frequency of Tregs, and suppressed autoreactive T cells, leading to immune tolerance. Collectively, our results demonstrate that tFNAs treatment aids glycemic control, provides ß-cell protection, and prevents the onset of T1D in NOD mice by immunomodulation. These results highlight the potential of tFNAs for the prevention of autoimmune T1D.

8.
Int J Cardiol ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33961944

RESUMO

BACKGROUND: Late gadolinium enhancement (LGE) derived from cardiac magnetic resonance (CMR) represents myocardial fibrosis (MF) and is associated with prognosis in hypertrophic cardiomyopathy (HCM). However, it cannot be evaluated when CMR is unavailable. Hence, we aimed to investigate the ability of radiomic features derived from coronary computed tomography angiography (CCTA) to detect the presence and extent of MF in HCM, with LGE as references. METHODS: 161 patients with HCM who underwent CCTA and CMR were retrospectively enrolled and randomly divided into training (107 patients, 1712 segments) and testing cohorts (54 patients, 864 segments). Segments were obtained according to AHA 17-segment method. Radiomic features were extracted from per-segment and entire myocardium regions, and multiple machine-learning algorithms were used for radiomic signatures (Rad-sig) generation and model building. Four models were established by multivariable logistic regression using Rad-sig (R-model), clinical characteristic (C-model), echocardiography parameters (E-model), and all features integrated (Integ-model) to identify LGE/left ventricular mass ≥ 15%. RESULTS: The model achieved good diagnostic accuracy in both training (area under the curve [AUC]:0.81, 95% confidence interval [CI]: 0.78-0.83) and testing cohort (AUC: 0.78, 95%CI: 0.75-0.81) on a per-segment basis for the presence of MF. The Integ-model owned the highest discriminative ability for patients with LGE/left ventricular mass ≥ 15% in both training and testing cohorts with AUC of 0.94 (95%CI: 0.89-0.98) and 0.92 (95%CI: 0.85-0.99), respectively. CONCLUSIONS: Our radiomic models were considered as useful and complementary biomarkers for the evaluation of the presence and extent of MF on CCTA, facilitating clinical decision-making and risk stratification in HCM patients.

9.
Environ Microbiol ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891359

RESUMO

Understanding how soil microorganisms influence the direction and magnitude of soil carbon feedback to global warming is vital to predict future climate change. Although microbial activities are major contributors to soil respiration (RS ) and its temperature sensitivity (Q10 ), the mechanisms underpinning microbial influence on RS and Q10 remain unclear. Coupling variation partitioning analysis (VPA), correlation analysis and multiple stepwise linear regression analysis, we illustrate that bacteria mainly affect RS and its temperature sensitivity (Q10 ) by shifting bacterial community composition (denoted by principal coordinates analysis). We also found that soil water content (SWC) and available nutrient (AN) were the factor key to changing bacterial community composition (P < 0.05). Co-occurrence network demonstrated that Mod 0 ecological cluster composed of copiotrophic taxa groups was significantly associated with RS and Q10 (P < 0.01, R > 0.5), including Proteobacteria, Actinobacteria, and Bacteroidetes. Illuminating the mechanisms underpinning the influence of soil microbes on RS and Q10 values is fundamental to understanding mechanistic soil-climate carbon cycles.

10.
Mol Neurodegener ; 16(1): 25, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853653

RESUMO

BACKGROUND: Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain. METHODS: AIF splicing induction in brain was determined by multiple approaches including 5' RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration. RESULTS: We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2-4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice. CONCLUSIONS: We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.

11.
Drug Deliv ; 28(1): 844-855, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33928829

RESUMO

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3ß1 not αvß3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

12.
Health Promot Int ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33880518

RESUMO

More than one-third of American Millennial adults have obesity, and a significant amount of their household budget is spent on purchasing energy-dense and nutrient-poor food and beverage products. Consumers' brand awareness and purchasing behaviors are influenced by celebrity credibility measured by trustworthiness, expertise and attractiveness; and celebrity 'fit' between products, brands and consumer' self-image. This empirical mixed-methods study combined Q methodology with questionnaires to explore the shared and distinct viewpoints of demographically diverse Millennial adults about celebrity endorsement of food and beverage products or marketing campaigns in the United States (USA). Millennials (n = 40; aged 26-39 years) sorted photo images (n = 48) of US celebrities associated with branded food and beverage product endorsements on a 9-point normal distribution scale from 'most trusted' (+4) to 'most distrusted' (-4). Participants also completed a 4-item post Q-sort questionnaire to interpret their thoughts during the card sorting process, and a 3-item questionnaire to examine their views about celebrity credibility, 'fit' and multiple brand and product endorsements. Three distinct viewpoints were identified that included: (i) healthy lifestyle champions who trusted celebrities associated with healthy products or campaigns; (ii) female role-model admirers who trusted female celebrities associated with positive social impacts and (ii) African-American celebrity fans who trusted African-American celebrities who endorsed any brand or products. Qualitative analysis of the questionnaire identified the potential negative influence of celebrity endorsement for unhealthy products on Millennials' dietary behaviors. Businesses and organizations should carefully select credible celebrities trusted by Millennials to encourage food and beverage products associated with a healthy diet.

13.
J Med Syst ; 45(5): 61, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847850

RESUMO

In recent years, artificial intelligence-based computer aided diagnosis (CAD) system for the hepatitis has made great progress. Especially, the complex models such as deep learning achieve better performance than the simple ones due to the nonlinear hypotheses of the real world clinical data. However,complex model as a black box, which ignores why it make a certain decision, causes the model distrust from clinicians. To solve these issues, an explainable artificial intelligence (XAI) framework is proposed in this paper to give the global and local interpretation of auxiliary diagnosis of hepatitis while retaining the good prediction performance. First, a public hepatitis classification benchmark from UCI is used to test the feasibility of the framework. Then, the transparent and black-box machine learning models are both employed to forecast the hepatitis deterioration. The transparent models such as logistic regression (LR), decision tree (DT)and k-nearest neighbor (KNN) are picked. While the black-box model such as the eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), random forests (RF) are selected. Finally, the SHapley Additive exPlanations (SHAP), Local Interpretable Model-agnostic Explanations (LIME) and Partial Dependence Plots (PDP) are utilized to improve the model interpretation of liver disease. The experimental results show that the complex models outperform the simple ones. The developed RF achieves the highest accuracy (91.9%) among all the models. The proposed framework combining the global and local interpretable methods improves the transparency of complex models, and gets insight into the judgments from the complex models, thereby guiding the treatment strategy and improving the prognosis of hepatitis patients. In addition, the proposed framework could also assist the clinical data scientists to design a more appropriate structure of CAD.

14.
Medicine (Baltimore) ; 100(14): e25371, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832122

RESUMO

INTRODUCTION: Early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery is one of the most fatal surgical complications. It is often accompanied by shock and hypotension, with high mortality rate. Due to surgical wounds, patients with early acute massive PTE after lung cancer surgery have a high risk of thrombolytic bleeding, which renders treatment more challenging and there is currently no standard protocol on how to safely and effectively treat these patients in the clinic. PATIENT CONCERNS: A 66-year-old woman after video-assisted thoracoscopic surgery for lung cancer, experienced sudden severe dyspnea, shock and hypotension with high D-Dimer, changed electrocardiogram (ECG), right ventricular dilatation, severe tricuspid regurgitation, and raised pulmonary arterial pressure on ultrasonic cardiogram (UCG), thromboses found on Ultrasonography of lower extremity vein. DIAGNOSIS: Because of her clinical manifestations and results of bedside auxiliary examinations, the patient was finally diagnosed with acute high-risk PTE after lung cancer surgery. INTERVENTIONS: 1.5 hours after onset of symptoms, thrombolysis using a continuous micropump infusion of 20,000 units/kg urokinase into the peripheral vein for 2 hours was initiated for this patient. OUTCOMES: The patient died of massive hemorrhage after thrombolysis. LESSONS: Treatment for patients with early acute PTE after lung cancer surgery is challenging due to a high risk of thrombolytic bleeding at the surgical site. Real-time monitoring of vital signs during thrombolysis and catheter-directed thrombolysis are recommended for these patients, in order to use the minimum drug dosage for quick curative effects and a low risk of bleeding.


Assuntos
Neoplasias Pulmonares/cirurgia , Embolia Pulmonar/diagnóstico , Terapia Trombolítica/efeitos adversos , Trombose/diagnóstico por imagem , Doença Aguda , Idoso , Evolução Fatal , Feminino , Hemorragia/induzido quimicamente , Humanos , Complicações Pós-Operatórias , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Cirurgia Torácica Vídeoassistida/métodos , Terapia Trombolítica/métodos , Trombose/complicações , Ultrassonografia/métodos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico
15.
Clin Sci (Lond) ; 135(8): 1053-1063, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33851706

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.

16.
Environ Res ; 197: 111138, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33844970

RESUMO

Sediments are the major sinks for Cd(Ⅱ) in the aquatic environment. Here, the detailed binding mechanisms and effects of environmental factors on Cd(Ⅱ) adsorption onto lake sediment were tested by a batch of adsorption and characteristic experiments. Sediment samples and sediment-Cd complexes were characterized using Scanning electron microscopy, Energy dispersive spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction spectral analyses. The interactive and main effect of parameters such as pH, flow velocity, Cd(II) concentration, sediment particle size, humic acid, fulvic acid and adsorption time involved in the adsorption process were determined using two models based on response surface methodology (RSM) and a back-propagation neural network with genetic algorithm (GABP). Results showed that Cd(II) adsorption onto sediment was mainly achieved through surface complexation with O-containing groups and precipitation with carbonate and sulfide. RSM was favorable for modeling Cd(II) adsorption in lake systems because it intuitively reflected the influence of the factors and had a good fitting precision (R2 = 0.8838, RSME = 2.5496) close to that of the GABP model (R2 = 0.8959, RSME = 2.5410). pH, sediment particle size, and humic acid exerted strong influences on Cd(II) immobilized by the sediment. Overall, our findings facilitate a better understanding of Cd(II) mobility in lakes and provide a reference for controlling heavy metals derived from both aqueous and sediment sources.

17.
J Occup Environ Med ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33883533

RESUMO

OBJECTIVES: To explore the circulating metabolites and related pathways in silicosis and asbestosis exposure to different mineral dusts. METHODS: Plasma of 30 silicosis, 30 asbestosis, and 20 healthy controls was analyzed using liquid chromatography-mass spectrometry. Metabolic networks and the relevance of the identified metabolic derangements were explored. RESULTS: Compared with healthy controls, 37 and 39 dysregulated plasma metabolites were found in silicosis and asbestosis respectively, of which the levels of 22 metabolites differed. Three major pathways were identified, among which arginine and proline metabolism was identified as the most closely related metabolic pathway. CONCLUSIONS: The types and quantities of up-regulated metabolites including lipids, amino acids, and carnitines were differed between silicosis and asbestosis. Pathways inducing lung fibrosis were common to mineral dusts exposure, while pathways related to oxidative stress and tumorigenesis differed between silicosis and asbestosis.

18.
Front Cell Infect Microbiol ; 11: 634505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732664

RESUMO

Cattle have been suggested as the primary reservoirs of E. coli O157 mainly as a result of colonization of the recto-anal junction (RAJ) and subsequent shedding into the environment. Although a recent study reported different gene expression at RAJ between super-shedders (SS) and non-shedders (NS), the regulatory mechanisms of altered gene expression is unknown. This study aimed to investigate whether bovine non-coding RNAs play a role in regulating the differentially expressed (DE) genes between SS and NS, thus further influencing E. coli O157 shedding behavior in the animals through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 (duodenum) to 413 ± 49 (descending colon). Comparison between SS and NS revealed the number of differentially expressed (DE) miRNAs ranged from one (in descending colon) to eight (in distal jejunum), and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (eight and seven, respectively). The miRNAs, bta-miR-378b, bta-miR-2284j, and bta-miR-2284d were down-regulated in both distal jejunum and rectum of SS (log2fold-change: -2.7 to -3.8), bta-miR-2887 was down-regulated in the rectum of SS (log2fold-change: -3.2), and bta-miR-211 and bta-miR-29d-3p were up-regulated in the rectum of SS (log2fold-change: 4.5 and 2.2). Functional analysis of these miRNAs indicated their potential regulatory role in host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that altered expression of miRNA in the gut of SS may lead to differential regulation of immune functions involved in E. coli O157 super-shedding in cattle.

19.
Adv Mater ; : e2006042, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749910

RESUMO

Electrochemical water splitting has attracted significant attention as a key pathway for the development of renewable energy systems. Fabricating efficient electrocatalysts for these processes is intensely desired to reduce their overpotentials and facilitate practical applications. Recently, metal-organic framework (MOF) nanoarchitectures featuring ultrahigh surface areas, tunable nanostructures, and excellent porosities have emerged as promising materials for the development of highly active catalysts for electrochemical water splitting. Herein, the most pivotal advances in recent research on engineering MOF nanoarchitectures for efficient electrochemical water splitting are presented. First, the design of catalytic centers for MOF-based/derived electrocatalysts is summarized and compared from the aspects of chemical composition optimization and structural functionalization at the atomic and molecular levels. Subsequently, the fast-growing breakthroughs in catalytic activities, identification of highly active sites, and fundamental mechanisms are thoroughly discussed. Finally, a comprehensive commentary on the current primary challenges and future perspectives in water splitting and its commercialization for hydrogen production is provided. Hereby, new insights into the synthetic principles and electrocatalysis for designing MOF nanoarchitectures for the practical utilization of water splitting are offered, thus further promoting their future prosperity for a wide range of applications.

20.
Nat Prod Res ; : 1-10, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648391

RESUMO

One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.

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