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1.
Nano Lett ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029994

RESUMO

The structural and mechanical properties of low-dimensional nanostructured metals have been attracting tremendous interest in the fast-growing fields of nanosciences and nanotechnologies. However, it still remains a challenge today to develop strong yet ductile low-dimensional metals that can support the further development of nanodevices. Here, through the polymer-assisted assembly of gold nanocrystals, we successfully fabricated the freestanding, ultrathin gold nanomaterial. Unlike conventional bulk gold or other low-dimensional gold nanostructures (i.e., nanowires and nanosheets), these gold nanosheets are composed of highly distorted gold nanocrystals that are 3-5 nm in size, which are joined together through nanosized amorphous carbon interphases. As a result, the gold nanosheets exhibit superb strength (up to 1.2 GPa), excellent ductility (>50%), and superior fracture toughness (>100 J/m2), outperforming various gold nanostructures hitherto reported.

2.
Zool Res ; 43(1): 52-63, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821086

RESUMO

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.


Assuntos
Quirópteros , Temperatura Alta , Estações do Ano , Canais de Cátion TRPC , Animais , Quirópteros/genética , Feminino , Hibernação/genética , Masculino , Camundongos , Canais de Cátion TRPC/genética , Canais de Cátion TRPV/genética
3.
Hepatobiliary Pancreat Dis Int ; 20(5): 452-459, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34256994

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. METHODS: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson's trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score (NAS) was analyzed. RESULTS: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine (PC) (P-22:0/18:1), sphingomyelin (SM) (d14:0/18:0), SM (d14:0/24:0), SM (d14:0/22:0), phosphatidylethanolamine (PE) (18:0/22:5), PC (O-22:2/12:0), and PC (26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC (14:0/18:2), PE (18:0/22:5) and PC (26:1/11:0)] or plasmalogens [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC (14:0/18:2), phosphatidic acid (18:2/24:4) were positively correlated with NAS; whereas PC (18:0/0:0) was correlated positively with fibrosis score. CONCLUSIONS: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

4.
mBio ; 12(4): e0110021, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34225495

RESUMO

Most bacteria employ a two-step indirect tRNA aminoacylation pathway for the synthesis of aminoacylated tRNAGln and tRNAAsn. The heterotrimeric enzyme GatCAB performs a critical amidotransferase reaction in the second step of this pathway. We have previously demonstrated in mycobacteria that this two-step pathway is error prone and translational errors contribute to adaptive phenotypes such as antibiotic tolerance. Furthermore, we identified clinical isolates of the globally important pathogen Mycobacterium tuberculosis with partial loss-of-function mutations in gatA, and demonstrated that these mutations result in high, specific rates of translational error and increased rifampin tolerance. However, the mechanisms by which these clinically derived mutations in gatA impact GatCAB function were unknown. Here, we describe biochemical and biophysical characterization of M. tuberculosis GatCAB, containing either wild-type gatA or one of two gatA mutants from clinical strains. We show that these mutations have minimal impact on enzymatic activity of GatCAB; however, they result in destabilization of the GatCAB complex as well as that of the ternary asparaginyl-transamidosome. Stabilizing complex formation with the solute trehalose increases specific translational fidelity of not only the mutant strains but also of wild-type mycobacteria. Therefore, our data suggest that alteration of GatCAB stability may be a mechanism for modulation of translational fidelity. IMPORTANCE Most bacteria use a two-step indirect pathway to aminoacylate tRNAGln and tRNAAsn, despite the fact that the indirect pathway consumes more energy and is error prone. We have previously shown that the higher protein synthesis errors from this indirect pathway in mycobacteria allow adaptation to hostile environments such as antibiotic treatment through generation of novel alternate proteins not coded by the genome. However, the precise mechanisms of how translational fidelity is tuned were not known. Here, we biochemically and biophysically characterize the critical enzyme of the Mycobacterium tuberculosis indirect pathway, GatCAB, as well as two mutant enzymes previously identified from clinical isolates that were associated with increased mistranslation. We show that the mutants dysregulate the pathway via destabilizing the enzyme complex. Importantly, increasing stability improves translational fidelity in both wild-type and mutant bacteria, demonstrating a mechanism by which mycobacteria may tune mistranslation rates.

5.
Chem Asian J ; 16(16): 2249-2252, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34101360

RESUMO

Morphologically and dimensionally controlled growth of Ag nanocrystals has long been plagued by surfactants or capping agents that complicate downstream applications, unstable Ag salts that impaired the reproducibility, and multistep seed injection that is troublesome and time-consuming. Here, we report a one-pot electro-chemical method to fast (∼2 min) produce Ag nanoparticles from commercial bulk Ag materials in a nitric acid solution, eliminating any need for surfactants or capping agents. Their size can be easily manipulated in an unprecedentedly wide range from 35 to 660 nm. Furthermore, the Ag nanoparticles are directly grown on the Ag substrate, highly desirable for promising applications such as catalysis and plasmonics. The mechanistic studies reveal that the concentration of Ag+ in the diffusion layer nearby the surface, controlled by the magnitude and duration of voltage, is critical in governing the nanoparticle formation (<1.3 mM) and its dimensional adjustability.


Assuntos
Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Compostos de Prata/química , Tensoativos
6.
Plant Physiol ; 186(3): 1706-1720, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-33871656

RESUMO

In plants, reactive oxygen species (ROS) produced following the expression of the respiratory burst oxidase homolog (Rboh) gene are important regulators of stress responses. However, little is known about how plants acclimate to salt stress through the Rboh-derived ROS signaling pathway. Here, we showed that a 400-bp fragment of the tobacco (Nicotiana tabacum) NtRbohE promoter played a critical role in the salt response. Using yeast one-hybrid (Y1H) screens, NtbHLH123, a bHLH transcription factor, was identified as an upstream partner of the NtRbohE promoter. These interactions were confirmed by Y1H, electrophoretic mobility assay, and chromatin immunoprecipitation assays. Overexpression of NtbHLH123 resulted in greater resistance to salt stress, while NtbHLH123-silenced plants had reduced resistance to salt stress. We also found that NtbHLH123 positively regulates the expression of NtRbohE and ROS production soon after salt stress treatment. Moreover, knockout of NtRbohE in the 35S::NtbHLH123 background resulted in reduced expression of ROS-scavenging and salt stress-related genes and salt tolerance, suggesting that NtbHLH123-regulated salt tolerance is dependent on the NtbHLH123-NtRbohE signaling pathway. Our data show that NtbHLH123 is a positive regulator and acts as a molecular switch to control a Rboh-dependent mechanism in response to salt stress in plants.

7.
Neurosci Bull ; 37(5): 597-610, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33900570

RESUMO

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.


Assuntos
Dor Crônica , Nociceptividade , Animais , Neurônios Dopaminérgicos , Camundongos , Núcleo Accumbens , Recompensa , Área Tegmentar Ventral
8.
J Hepatobiliary Pancreat Sci ; 28(7): 593-603, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33908180

RESUMO

BACKGROUND: The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers. METHODS: We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n = 278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n = 275). Significant fibrosis was defined as fibrosis stage F ≥ 2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. RESULTS: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95% CI 0.869-0.904) for identifying fibrosis F ≥ 2. The LRM AUROC was 0.764, 95% CI 0.710-0.816 and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95% CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95% CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470-0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. CONCLUSIONS: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy-confirmed NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Algoritmos , Biomarcadores , Biópsia , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Aprendizado de Máquina , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Valor Preditivo dos Testes , Curva ROC , Índice de Gravidade de Doença
9.
Br J Pharmacol ; 178(11): 2351-2369, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33645631

RESUMO

BACKGROUND AND PURPOSE: It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. EXPERIMENTAL APPROACH: Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18α overexpression were analysed in ATG5high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29atg5 and SW480atg5 cancer cells. KEY RESULTS: In ATG5high colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5+/- and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5-Mis18α complex and MMR-D/MSI-H. CONCLUSIONS AND IMPLICATIONS: Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18α in ATG5high colorectal cancer cells. We suggest that ATG5-Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteína 5 Relacionada à Autofagia , Neoplasias Colorretais , Instabilidade de Microssatélites , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias Encefálicas , Proteínas Cromossômicas não Histona , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , DNA , Metilação de DNA , Humanos , Camundongos , Proteína 1 Homóloga a MutL/genética , Síndromes Neoplásicas Hereditárias
10.
Am J Addict ; 30(4): 389-397, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33738888

RESUMO

BACKGROUND AND OBJECTIVES: COVID-19-related quarantine and stress have likely escalated the crisis of Internet addiction. This study aimed to determine the impact of the COVID-19 pandemic on Internet use and related risk factors among the general public in China. METHODS: A large-sample cross-sectional online survey was conducted from March 24 to April 30, 2020, in China, and 20,472 participants completed the survey. We investigated the prevalence and severity of Internet addiction based on the Internet Addiction Test (IAT), and explored the risk factors related to increases in time spent on Internet use and severity of Internet addiction, as well as severe Internet addiction. RESULTS: The overall prevalence of Internet addiction was 36.7% among the general population during the pandemic, and that of severe Internet addiction was 2.8%, according to IAT scores. Time spent on recreational Internet use had significantly increased during the pandemic, and almost half of participants reported increases in the severity of Internet addiction. Risk factors for increases in time spent on Internet use and severity of Internet addiction and severe Internet addiction included having fewer social supporters, perceiving pressure and impact on mental health status due to COVID-19, and being over-engaged in playing videogames. DISCUSSION AND CONCLUSIONS: The COVID-19 pandemic adversely impacted Internet use and increased the prevalence and severity of Internet addiction among the general population in China, especially in vulnerable populations. SCIENTIFIC SIGNIFICANCE: This study provides evidence for policymakers to refine public health policies to control the pandemic and make efforts to provide population-specific prevention and interventions for people at risk of developing Internet addiction. (Am J Addict 2021;00:00-00).


Assuntos
Comportamento Aditivo/psicologia , COVID-19/psicologia , Transtorno de Adição à Internet/epidemiologia , Adolescente , Adulto , Comportamento Aditivo/epidemiologia , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Internet , Transtorno de Adição à Internet/psicologia , Masculino , Pessoa de Meia-Idade , Pandemias , Prevalência , Fatores de Risco , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
11.
Small ; 17(8): e2006373, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33522133

RESUMO

Up to now, the silicon-graphite anode materials with commercial prospect for lithium batteries (LIBs) still face three dilemmas of the huge volume effect, the poor interface compatibility, and the high resistance. To address the above challenges, micro-nano structured composites of graphite coating by ZnO-incorporated and carbon-coated silicon (marked as Gr@ZnO-Si-C) are reasonably synthesized via an efficient and convenient method of liquid phase self-assembly synthesis combined with annealing treatment. The designed composites of Gr@ZnO-Si-C deliver excellent lithium battery performance with good rate performance and stable long-cycling life of 1000 cycles with reversible capacities of 1150 and 780 mAh g-1 tested at 600 and 1200 mA g-1 , respectively. The obtained results reveal that the incorporated ZnO effectively improve the interface compatibility between electrolyte and active materials, and boost the formation of compact and stable surface solid electrolyte interphase layer for electrodes. Furthermore, the pyrolytic carbon layer formed from polyacrylamide can directly improve electrical conductivity, decrease polarization, and thus promote their electrochemical performance. Finally, based on the scalable preparation of Gr@ZnO-Si-C composites, the pouch full cells of Gr@ZnO-Si-C||NCM523 are assembled and used to evaluate the commercial prospects of Si-graphite composites, offering highly useful information for researchers working in the battery industry.

12.
Front Cell Dev Biol ; 9: 635728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33604343

RESUMO

RBM14 is an RNA-binding protein that regulates spindle integrity in mitosis; however, its functions during meiosis are still unclear. In this study, we discovered that RBM14 expression was down-regulated in oocytes from old mice. The RBM14 distribution at different stages of meiosis was explored, while it presents overlapped localization patterns with α-tubulin in MI- and MII-stage oocytes. Treatment of MI-stage oocytes with spindle-perturbing agents revealed that RBM14 was co-localized with microtubules. RBM14 knockdown with RBM14-specific morpholino showed that RBM14-depleted oocytes underwent symmetric division compared to the controls. RBM14 knockdown also resulted in spindle defects and chromosome abnormalities during oocyte maturation, presumably due to α-tubulin hyperacetylation. Co-immunoprecipitation analysis demonstrated that RBM14 is interacted with endogenous α-tubulin in mammalian cells. These findings indicate that RBM14 is an essential modulator of oocyte meiotic maturation by regulating α-tubulin acetylation to affect spindle morphology and chromosome alignment. Consequently, RBM14 represents a potential biomarker of oocyte quality and a novel therapeutic target in women with oocyte maturation failure.

13.
iScience ; 24(2): 101982, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33521596

RESUMO

Plasmonic metal nanostructures (PMNs) are characterized by the plasmon oscillation of conduction band electron in response to external radiation, enabling strong light absorption and scattering capacities and near-field amplification. Owing to these enhanced light-matter interactions, PMNs have garnered extensive research interest in the past decades. Notably, a growingly large number of reports show that the energetics and kinetics of chemical transformations on PMNs can be modified upon photoexcitation of their plasmons, giving rise to a new paradigm of manipulating the reaction rate and selectivity of chemical reactions. On the other hand, there is urgent need to achieve clear understanding of the mechanism underlying the photo-mediated chemical transformations on PMNs for unleashing their full potential in converting solar energy to chemicals. In this perspective, we review current fundamental concepts of photo-mediated chemical transformations executed at PMNs. Three pivotal mechanistic questions, i.e., thermal and nonthermal effects, direct and indirect charge transfer processes, and the specific impacts of plasmon-induced potentials, are explored based on recent studies. We highlight the critical aspects in which major advancements should be made to facilitate the rational design and optimization of photo-mediated chemical transformations on PMNs in the future.

14.
Br J Nutr ; 126(6): 813-824, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33198849

RESUMO

The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

15.
Eur J Gastroenterol Hepatol ; 33(3): 430-435, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32398489

RESUMO

OBJECTIVE: FibroTouch is a newly developed device to assess ultrasound attenuation parameter (UAP) and liver stiffness measurement to quantify hepatic steatosis and fibrosis, respectively. However, there is currently a lack of defined thresholds of UAP to diagnose different stages of hepatic steatosis. We aimed to assess the optimal thresholds of UAP for hepatic steatosis in individuals with biopsy-proven fatty liver disease (FLD). METHODS: We enrolled 497 adults with FLD undergoing FibroTouch and liver biopsy. Area under the receiver operating characteristic curve (AUROC) was performed to calculate the performance of UAP in staging hepatic steatosis. Hepatic steatosis >33% was defined as significant steatosis. We determined the optimal cutoff values of UAP and the sensitivity or specificity higher than 90%. Sensitivity, specificity, positive predictive value and negative predictive value were subsequently calculated. RESULTS: The median UAP for the enrolled patients was 308 dB/m. Multivariable logistic regression analysis showed that UAP was associated with significant steatosis [adjusted-odds ratio 1.05, 95% confidence interval (CI), 1.02-1.09; P = 0.001]. The AUROCs for S ≥ 1, S ≥ 2 and S = 3 were 0.88 (95% CI, 0.84-0.91), 0.77 (95% CI, 0.73-0.81), and 0.70 (95% CI, 0.63-0.77), respectively. The optimal UAP cutoffs were 295 dB/m for S ≥ 1, 314 dB/m for S ≥ 2, and 324 dB/m for S = 3. Almost identical results were observed in the subgroup of patients with biopsy-confirmed nonalcoholic fatty liver disease (n = 435). CONCLUSION: We found that the AUROC values of UAP by FibroTouch were ranging from 0.70 to 0.88 for assessing hepatic steatosis severity. These UAP cutoffs could be applicable for clinical use.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Adulto , Área Sob a Curva , Biópsia , Humanos , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Curva ROC
16.
Artigo em Inglês | MEDLINE | ID: mdl-33133218

RESUMO

The gut microbiota is important in metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with inflammation caused by ionizing radiation (IR). Guiqi Baizhu decoction (GQBZD) is a medicinal compound used in traditional Chinese medicine with anti-inflammatory and antioxidation effects, especially in the process of radiotherapy. However, the effect of GQBZD on reducing the damage to the normal immune system in radiotherapy remains unclear. Here, we show that GQBZD reduces body weights, water intake, food intake, diarrhea level and quality of life score, and inflammation and enhances immunity function in rats treated with X-ray radiation. Meanwhile, our data indicate that GQBZD not only reverses IR-induced gut dysbiosis as indicated change of α-diversity and ß-diversity of microbiota, the composition of Desulfovibrio, Bacteroides, and Parabacteroides, except for Roseburia and Lachnoclostridium, but also maintains intestinal barrier integrity and promoting the formation of short-chain fatty acids (SCFAs). GQBZD can also reduce the level of phosphorylation P65 (p-P65). Our results demonstrate that GQBZD can significantly alleviate the inflammatory responses and improve the immune damage against IR, and may be used as prebiotic agents to prevent gut dysbiosis and radiation-related metabolic disorders in radiotherapy.

17.
Chem Commun (Camb) ; 56(92): 14467-14470, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33147303

RESUMO

Unique Fe and N co-doped multi-walled carbon nanotubes are designed to efficiently catalyze the oxygen reduction reaction (ORR). The preparation processes involve surface functionalization, subsequent wet impregnation and final thermal fixation of Fe-Nx species. The catalyst achieved outstanding alkaline ORR performance with a very positive half-wave potential (∼0.91 V). Theoretical calculations show that the carbon layer below the active Fe-Nx sites is beneficial to the ORR.

18.
Med Sci Monit ; 26: e926323, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206632

RESUMO

BACKGROUND Previous studies have implicated reduced brain-derived neurotrophic factor (BDNF) expression and BDNF-TrkB receptor signaling as well as microglial activation and neuroinflammation in poststroke depression (PSD). However, the contributions of microglial BDNF-TrkB signaling to PSD pathogenesis are unclear. MATERIAL AND METHODS We compared depression-like behaviors as well as neuronal and microglial BDNF and TrkB expression levels in the amygdala, a critical mood-relating limbic structure, in rat models of stroke, depression, and PSD. Depression-like behaviors were assessed using the sucrose preference test, open-field test, and weight measurements, while immunofluorescence double staining was employed to estimate BDNF and TrkB expression by CD11b-positive amygdala microglia and NeuN-positive amygdala neuron. Another group of PSD model rats were examined following daily intracerebroventricular injection of proBDNF, tissue plasminogen activator (t-PA), or normal saline (NS) for 7 days starting 4 weeks after chronic unpredictable mild stress (CUMS). RESULTS The numbers of BDNF/CD11b- and TrkB/CD11b-immunofluorescence-positive cells were lowest in the PSD group at 4 and 8 weeks after CUMS (P0.05). Injection of t-PA increased BDNF/CD11b- and TrkB/CD11b-positive cells in the amygdala of PSD rats and normalized behavior compared with NS or proBDNF injection (P<0.05). In contrast, proBDNF injection reduced BDNF and TrkB expression compared with NS (P<0.05). CONCLUSIONS These results suggest that decreased BDNF and TrkB expression by amygdala microglia may contribute to PSD pathogenesis and depression-like behaviors.


Assuntos
Tonsila do Cerebelo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/etiologia , Depressão/metabolismo , Microglia/metabolismo , Receptor trkB/metabolismo , Acidente Vascular Cerebral/complicações , Animais , Comportamento Animal , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Injeções Intraventriculares , Atividade Motora , Neuraminidase/metabolismo , Ratos Sprague-Dawley , Ativador de Plasminogênio Tecidual/metabolismo
19.
Front Microbiol ; 11: 577756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072044

RESUMO

Most bacteria, including mycobacteria, utilize a two-step indirect tRNA aminoacylation pathway to generate correctly aminoacylated glutaminyl and asparaginyl tRNAs. This involves an initial step in which a non-discriminatory aminoacyl tRNA synthetase misacylates the tRNA, followed by a second step in which the essential amidotransferase, GatCAB, amidates the misacylated tRNA to its correct, cognate form. It had been previously demonstrated that mutations in gatA can mediate increased error rates specifically of glutamine to glutamate or asparagine to aspartate in protein synthesis. However, the role of mutations in gatB or gatC in mediating mistranslation are unknown. Here, we applied a forward genetic screen to enrich for mistranslating mutants of Mycobacterium smegmatis. The majority (57/67) of mutants had mutations in one of the gatCAB genes. Intriguingly, the most common mutation identified was an insertion in the 3' of gatC, abolishing its stop codon, and resulting in a fused GatC-GatA polypeptide. Modeling the effect of the fusion on GatCAB structure suggested a disruption of the interaction of GatB with the CCA-tail of the misacylated tRNA, suggesting a potential mechanism by which this mutation may mediate increased translational errors. Furthermore, we confirm that the majority of mutations in gatCAB that result in increased mistranslation also cause increased tolerance to rifampicin, although there was not a perfect correlation between mistranslation rates and degree of tolerance. Overall, our study identifies that mutations in all three gatCAB genes can mediate adaptive mistranslation and that mycobacteria are extremely tolerant to perturbation in the indirect tRNA aminoacylation pathway.

20.
Cell Cycle ; 19(22): 3195-3207, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33121344

RESUMO

The purpose of this study was to investigate the effects of astragalus polysaccharides (APS) on the proliferation and apoptosis of bone marrow mesenchymal stem cells (BMSCs) induced by X-ray radiation-induced A549 cells bystander effect (RIBE), and to explore their mechanisms. In this study, APS increased the reduced cell proliferation rate induced by RIBE and inhibiting the apoptosis of bystander cells. In terms of mechanism, APS up-regulates the proteins Bcl-2, Bcl-xl, and down-regulates the proteins Bax and Bak, which induces a decrease in mitochondrial membrane potential, which induces the release of Cyt-c and AIF, which leads to caspase-dependent and caspase-independent pathway to cause apoptosis. In addition, we believe that ROS may be the main cause of these protein changes. APS can inhibit the generation of ROS in bystander cells and thus inhibit the activation of the mitochondrial pathway, further preventing cellular damage caused by RIBE.

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