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1.
J Hazard Mater ; : 127614, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34740510

RESUMO

The coastal area is one of the key zones for transport and fate of microplastics (MPs). This study investigated the transport behaviors of different sized MPs in three water-saturated coastal soils, with the aim to explore effects of properties of three different coastal soils on the dispersion and migration of three-sized MPs (0.3, 0.5, and 1 µm). All three-sized MPs had the strongest dispersion in Soil 3 solution, followed by that in Soil 1 solution and then that in Soil 2 solution. The strongest dispersion of MPs in Soil 3 solution was attributed to the lowest ionic strength. Such a high dispersion favored MPs movement in soil solution but readily be sorbed and fixed by rich Fe and Al oxides in Soil 3 solid through strong electrostatic attraction, leading to the lowest transport rate (20.5-41.2%). The high ionic strength in the Soil 1 solution decreased the dispersion of MPs, but the presence of high content of humic acid enhanced the electrostatic repulsion and steric hindrance between MPs and soil particles, resulting in the highest transport ability of MPs in Soil 1 (39.4-72.5%). The large amount of dissolved Ca2+ and Mg2+ in Soil 2 solution favored MPs bridged with fulvic acid, resulting in the highest aggregation of MPs and relatively lower transport ability (34.1-49.6%). Large-sized MPs had higher electrostatic repulsion between the particles, thus increasing the dispersion and transport capacity of MPs in soil. Modeling showed the experiment-consistent results that Soil 3 had the lowest MPs transport after 600 mm of heavy rainfall, with the maximum migration distance of 7.50-10.5 cm, which was smaller than that in Soil 2 (8.10-12.0 cm) and that in Soil 1 (9.00-18.3 cm). These results indicated that MPs transport in coastal soil is significant and soil solution and solid composition plays an important role in the dispersion and transport of MPs, respectively. These findings afforded a great basis for the assessment of the fate and risk of MPs in coastal areas.

2.
Adv Sci (Weinh) ; : e2103030, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719884

RESUMO

Detection of biomarkers associated with body conditions provides in-depth healthcare information and benefits to disease management, where the key challenge is to develop a minimally invasive platform with the ability to directly detect multiple biomarkers in body fluid. Dermal tattoo biosensor holds the potential to simultaneously detect multiple health-related biomarkers in skin interstitial fluid because of the features of minimal invasion, easy operation, and equipment-free result reading. Herein, a colorimetric dermal tattoo biosensor fabricated by a four-area segmented microneedle patch is developed for multiplexed detection of health-related biomarkers. The biosensor exhibits color changes in response to the change of biomarker concentration (i.e., pH, glucose, uric acid, and temperature), which can be directly read by naked eyes or captured by a camera for semi-quantitative measurement. It is demonstrated that the colorimetric dermal tattoo biosensor can simultaneously detect multiple biomarkers in vitro, ex vivo, and in vivo, and monitor the changes of the biomarker concentration for at least 4 days, showing its great potential for long-term health monitoring.

3.
J Hepatol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793870

RESUMO

BACKGROUND & AIMS: Primary liver tumors contain distinct subtypes. A subset of iCCAs can arise from cell fate reprogramming of mature hepatocytes in mouse models. However, the underpinning of cell fate plasticity during hepatocarcinogenesis is still poorly understood, hampering therapeutic development to treat HCC and iCCA. As YAP activation induces liver tumor formation and cell fate plasticity, we investigated the role of Sox9, a transcription factor downstream of Yap activation and expressed in biliary epithelial cells (BECs), in Yap-induced cell fate plasticity during hepatocarcinogenesis. METHODS: To evaluate the function of Sox9 in YAP-induced hepatocarcinogenesis in vivo, we performed inducible hepatocyte-specific YAP activation with simultaneous Sox9 removal in several mouse genetic models. Cell fate reprogramming was determined by lineage tracing and immunohistochemistry. The molecular mechanism underlying Yap and Sox9 function in hepatocyte plasticity was investigated by transcription and transcriptomic analyses of mouse and human liver tumors. RESULTS: Sox9, a marker of liver progenitor cells (LPCs) and BECs, is differentially required in YAP-induced stepwise hepatocyte programming. While Sox9 has limited function in hepatocyte dedifferentiation to LPCs, it is required for BEC differentiation from LPCs. YAP activation in Sox9-deficient hepatocytes resulted in more aggressive HCC with enhanced Yap activity at the expense of iCCA-like tumors. Furthermore, we showed that 20% of primary human liver tumors were associated with a YAP activation signature, and tumor plasticity is highly correlated with YAP activation and SOX9 expression. CONCLUSION: Our data demonstrated that Yap-Sox9 signaling determines hepatocyte plasticity and tumor heterogeneity in hepatocarcinogenesis in both mouse and human liver tumors. We identified Sox9 as a critical transcription factor required for Yap-induced hepatocyte cell fate reprogramming during hepatocarcinogenesis. LAY SUMMARY: Sox9, a marker of liver progenitor cells and bile duct lining cells, is a downstream target of YAP protein activation. Here we found that YAP activation in hepatocytes leads to a transition from mature hepatocytes to first liver progenitor cells and then the formation of the bile duct lining cells and Sox9 is required in the second step during mouse hepatocarcinogenesis. We also found that human YAP and SOX9 may play similar roles in liver cancers.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34826077

RESUMO

The widespread usage of per- and polyfluoroalkyl substances (PFASs) has led to their ubiquitous co-existence with hydrocarbon surfactants in the subsurface environment. In this study, column experiments were conducted to investigate the effect of an anionic hydrocarbon surfactant (sodium dodecylbenzene sulfonate, SDBS, 1 and 10 mg/L) on the transport of perfluorooctanoic acid (PFOA) in two saturated natural soils under different cation type (Na+ and Ca2+) conditions. Results showed that SDBS (10 mg/L) significantly enhanced the transport of PFOA in two soils. This was likely because SDBS had a stronger adsorption affinity to the soils than PFOA, and can outcompete PFOA for the finite adsorption sites on the soil surface. The effect of SDBS on PFOA transport varied greatly in the two soils. More negatively charged soil surface and greater soil particle size likely contributed to the more noticeable transport-enhancement of PFOA resulting from the presence of SDBS. Also, the enhancement effect of SDBS (10 mg/L) with Ca2+ on PFOA transport was more significantly than that with Na+. This was possibly due to the blocking effect of SDBS to the more positively charged soil surface induced by Ca2+. Findings of this study point out the importance of anionic hydrocarbon surfactants on PFOA transport when assessing its environmental risks and implementing remediation efforts.

5.
Theor Appl Genet ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811574

RESUMO

KEY MESSAGE: Rf candidate genes were related to the super D05_PPR-cluster and verified to be individually nonfunctional. Restorer of fertility (Rf) genes of cytoplasmic male sterility (CMS) is commonly found to be PPR (pentatricopeptide repeat) genes, which are mostly located in a cluster of PPR genes with high similarity. Here, Homocap-seq was applied to analyze PPR clusters in 'three lines,' and we found broad variations within the D05_PPR-cluster in a restorer line and deduced that the D05_PPR-cluster was associated with fertility restoration. Genetic mapping of Rf and Homocap-seq analysis of three genotypes in the F2 population validated that the D05_PPR-cluster was the origin of Rf. Three Rf candidates were cloned that were the most actively expressed genes in the D05_PPR-cluster in the restorer line as revealed by their high-depth amplicons. However, further transgenic experiments showed that none of the candidates could restore fertility of the CMS line independently. Then, the members of the brand-new super D05_PPR-cluster in the restorer line, containing 14 full-length PPRs and at least 13 PPR homologous sequences, were identified by long-read resequencing, which validated the effectiveness of variation and expression prediction of Homocap-seq. Additionally, we found that several PPR duplications, including 2 of the 3 Rf candidates, had undergone site-specific selection as potentially important anther development-associated genes. Finally, we proposed that multiple PPRs were coordinately responsible for the fertility restoration of the CMS line.

6.
Kidney Blood Press Res ; : 1-12, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34818247

RESUMO

OBJECTIVE: Kidney renal clear cell carcinoma (KIRC) is a common cancer with high morbidity and mortality in renal cancer. Thus, the transcriptome data of KIRC patients in The Cancer Genome Atlas (TCGA) database were analyzed and drug candidates for the treatment of KIRC were explored through the connectivity map (CMap) database. METHODS: The transcriptome data of KIRC patients were downloaded from TCGA database, and KIRC-associated hub genes were screened out through differential analysis and protein-protein interaction (PPI) network analysis. Afterward, the CMap database was used to select drug candidates for KIRC treatment, and the drug-targeted genes were obtained through the STITCH database. A PPI network was constructed by combining drug-targeted genes with hub genes that affected the pathogenesis of KIRC to obtain final hub genes. Finally, combining hub genes and KIRC-associated hub genes, the pathways affected by drugs were explored by pathway enrichment analysis. RESULTS: A total of 2,312 differentially expressed genes were found in patients, which were concentrated in immune cell activity, cytokine, and chemokine secretion pathways. Drug screening disclosed 5 drug candidates for KIRC treatment: fedratinib, Ly344864, geldanamycin, AS-605240, and luminespib. Based on drug-targeted genes and KIRC-associated hub genes, 16 hub genes were screened out. Pathway enrichment analysis revealed that drugs mainly affected pathways such as neuroactive ligand pathways, cell adhesion, and chemokines. CONCLUSION: The above results indicated that fedratinib, LY 344864, geldanamycin, AS-605240, and luminespib could be used as candidates for KIRC therapy. The findings from this study will make contributions to the treatment of KIRC in the future.

7.
Mater Horiz ; 8(2): 619-629, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821279

RESUMO

Biological neurons exhibit dynamic excitation behavior in the form of stochastic firing, rather than stiffly giving out spikes upon reaching a fixed threshold voltage, which empowers the brain to perform probabilistic inference in the face of uncertainty. However, owing to the complexity of the stochastic firing process in biological neurons, the challenge of fabricating and applying stochastic neurons with bio-realistic dynamics to probabilistic scenarios remains to be fully addressed. In this work, a novel CuS/GeSe conductive-bridge threshold switching memristor is fabricated and singled out to realize electronic stochastic neurons, which is ascribed to the similarity between the stochastic switching behavior observed in the device and that of biological ion channels. The corresponding electric circuit of a stochastic neuron is then constructed and the probabilistic firing capacity of the neuron is utilized to implement Bayesian inference in a spiking neural network (SNN). The application prospects are demonstrated on the example of a tumor diagnosis task, where common fatal diagnostic errors of a conventional artificial neural network are successfully circumvented. Moreover, in comparison to deterministic neuron-based SNNs, the stochastic neurons enable SNNs to deliver an estimate of the uncertainty in their predictions, and the fidelity of the judgement is drastically improved by 81.2%.

8.
World Neurosurg ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648989

RESUMO

OBJECTIVE: To develop and validate a nomogram for predicting the risk of venous thromboembolism in critically ill patients with primary intracerebral hemorrhage. METHODS: Patients ≥18 years old with primary intracerebral hemorrhage were screened within 24 hours of onset from January 2019 to April 2021. Univariate and multivariate logistic regression analyses were performed to screen out independent predictors that were significantly associated with venous thromboembolism. A nomogram was constructed based on the results of a multivariate regression analysis. Discrimination and calibration were used to evaluate performance of the nomogram. A decision curve analysis was used to assess its clinical utility. RESULTS: This study enrolled 369 patients. The nomogram included 3 predictors from the regression analysis: D-dimer, National Institutes of Health Stroke Scale score, and Glasgow Coma Scale score on admission. The area under the receiver operating characteristic curve was 0.794, indicating good discrimination of the nomogram. The nomogram demonstrated calibration curves with slight deviation from the ideal predictions. Decision curve analysis showed that the prediction nomogram was clinically useful. CONCLUSIONS: This nomogram comprising D-dimer, National Institutes of Health Stroke Scale score and Glasgow Coma Scale score on admission can accurately predict the risk of venous thromboembolism in critically ill patients with intracerebral hemorrhage.

9.
BMC Ecol Evol ; 21(1): 194, 2021 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689746

RESUMO

BACKGROUND: The boreal forest is one of the largest biomes on earth, supporting thousands of species. The global climate fluctuations in the Quaternary, especially the ice ages, had a significant influence on the distribution of boreal forest, as well as the divergence and evolution of species inhabiting this biome. To understand the possible effects of on-going and future climate change it would be useful to reconstruct past population size changes and relate such to climatic events in the past. We sequenced the genomes of 32 individuals from two forest inhabiting bird species, Hazel Grouse (Tetrastes bonasia) and Chinese Grouse (T. sewerzowi) and three representatives of two outgroup species from Europe and China. RESULTS: We estimated the divergence time of Chinese Grouse and Hazel Grouse to 1.76 (0.46-3.37) MYA. The demographic history of different populations in these two sibling species was reconstructed, and showed that peaks and bottlenecks of effective population size occurred at different times for the two species. The northern Qilian population of Chinese Grouse became separated from the rest of the species residing in the south approximately 250,000 years ago and have since then showed consistently lower effective population size than the southern population. The Chinese Hazel Grouse population had a higher effective population size at the peak of the Last Glacial Period (approx. 300,000 years ago) than the European population. Both species have decreased recently and now have low effective population sizes. CONCLUSIONS: Combined with the uplift history and reconstructed climate change during the Quaternary, our results support that cold-adapted grouse species diverged in response to changes in the distribution of palaeo-boreal forest and the formation of the Loess Plateau. The combined effects of climate change and an increased human pressure impose major threats to the survival and conservation of both species.


Assuntos
Mudança Climática , Galliformes , Animais , Ecossistema , Galliformes/genética , Humanos , Densidade Demográfica , Sequenciamento Completo do Genoma
10.
Analyst ; 146(22): 6960-6969, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34657942

RESUMO

Digital PCR has shown great potential for quantitative nucleic acid testing (NAT), but most existing platforms are dependent on large auxiliary equipment (e.g., vacuum pump, amplification instrument, fluorescence microscope) to achieve target dispersion, amplification, signal capture and result analysis. Such complex, expensive and bulky NAT platforms have limited their applications in resource-limited areas, especially for point-of-care testing (POCT). In this work, we designed a digital isothermal NAT platform based on a pump-free open droplet array microfluidic chip. A pump-free microfluidic chip was developed based on an open microdroplet array in the form of thousands of independent microdroplets for spontaneous sample dispersion, without the need for external power. Combined with a handheld fluorescent signal reader based on a smartphone, this digital NAT platform can accurately quantify as low as 1 copy per µL of λDNA. Therefore, our integrated NAT platform, as a potable, robust and low-cost tool for highly accurate NA quantitative analysis, holds great potential for POCT applications.


Assuntos
Técnicas Analíticas Microfluídicas , Ácidos Nucleicos , Dispositivos Lab-On-A-Chip , Microfluídica , Técnicas de Amplificação de Ácido Nucleico
11.
Front Endocrinol (Lausanne) ; 12: 751802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707573

RESUMO

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of liver disorders, from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Compared with fatty liver, NASH is characterized by increased liver injury and inflammation, in which liver-infiltrating immune cells, with neutrophil infiltration as a hallmark of NASH, play a critical role in promoting the progression of fatty liver to NASH. Neutrophils are the first responders to injury and infection in various tissues, establishing the first line of defense through multiple mechanisms such as phagocytosis, cytokine secretion, reactive oxygen species production, and neutrophil extracellular trap formation; however, their roles in the pathogenesis of NASH remain obscure. The current review summarizes the roles of neutrophils that facilitate the progression of fatty liver to NASH and their involvement in inflammation resolution during NASH pathogenesis. The notion that neutrophils are potential therapeutic targets for the treatment of NASH is also discussed.

12.
Front Med (Lausanne) ; 8: 712205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708051

RESUMO

Background: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for critically ill patients. Portable ECMO devices can be applied in both in-hospital and out-of-hospital emergency conditions. We evaluated the safety and biocompatibility of a novel centrifugal pump and ECMO device of the OASSIST ECMO System (Jiangsu STMed Technologies Co., Suzhou, China) in a 168-h ovine ECMO model. Methods: The portable OASSIST ECMO system consists of the control console, the pump drive, and the disposable centrifugal pump. Ten healthy sheep were used to evaluate the OASSIST ECMO system. Five were supported on veno-venous ECMO and five on veno-arterial ECMO, each for 168 h. The systemic anticoagulation was achieved by continuous heparin infusion to maintain the activated clotting time (ACT) between 220 and 250 s. The rotary speed was set at 3,200-3,500 rpm. The ECMO configurations and ACT were recorded every 6 hours (h). The free hemoglobin (fHb), complete blood count, and coagulation action test were monitored, at the 6th h and every 24 h after the initiation of the ECMO. The dissection of the pump head and oxygenator were conducted to explore thrombosis. Results: Ten sheep successfully completed the study duration without device-related accidents. The pumps ran stably, and the ECMO flow ranged from 1.6 ± 0.1 to 2.0 ± 0.11 L/min in the V-V group, and from 1.8 ± 0.1 to 2.4 ± 0.14 L/min in the V-A group. The anticoagulation was well-performed. The ACT was maintained at 239.78 ± 36.31 s, no major bleeding or thrombosis was observed during the ECMO run or in the autopsy. 3/5 in the V-A group and 4/5 in the V-V group developed small thrombus in the bearing pedestal. No obvious thrombus formed in the oxygenator was observed. The hemolytic blood damage was not significant. The average fHb was 0.17 ± 0.12 g/L. Considering hemodilution, the hemoglobin, white blood cell, and platelets didn't reduce during the ECMO runs. Conclusions: The OASSIST ECMO system shows satisfactory safety and biocompatibility for the 168-h preclinical evaluation in the ovine model. The OASSIST ECMO system is promising to be applied in clinical conditions in the future.

14.
J Clin Invest ; 131(20)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651578

RESUMO

Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease, affecting 1.5%-6.5% of the world population. Currently, there are no FDA-approved drugs to treat this disease. Accumulating evidence suggests that metabolically hazardous visceral fat contributes to NASH progression by releasing fatty acids and proinflammatory mediators. Therefore, targeting adipose tissue to reduce adipose inflammation may provide an effective strategy to treat NASH. Another strategy is to target specific inflammatory mediators that are produced by adipose tissue and contribute to NASH progression. In this issue of the JCI, Liu, Xiang, et al. demonstrate that secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) was highly upregulated in adipose tissue and played a role in exacerbating NASH progression in a mouse model of NASH. Thus, inhibition of SPARCL1 may provide another attractive strategy to tackle NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Tecido Adiposo , Animais , Proteínas de Ligação ao Cálcio , Cisteína , Proteínas da Matriz Extracelular , Gordura Intra-Abdominal , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Osteonectina
15.
BMJ Open ; 11(10): e045530, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697109

RESUMO

INTRODUCTION: Inferior vena cava (IVC) filters are commonly used in patients with venous thromboembolism to prevent fatal pulmonary embolism, but the thrombosis risk increases after filter placement. Warfarin is a widely anticoagulant, but long-term monitoring and dose adjustments are required. Anticoagulation with rivaroxaban is more straightforward as it dose not require laboratory monitoring. This study compares the efficacy and safety of rivaroxaban and warfarin as an in anticoagulation therapy for patients with IVC filter placement. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial. In total, 200 patients with deep vein thrombosis (DVT) with IVC filter implantation from 10 hospitals will be recruited. The patients will be randomised to the experimental group (rivaroxaban) or the control group (nadroparin overlapped with warfarin). The primary outcomes include death of any cause, pulmonary embolism (PE)-related death, bleeding and recurrent PE/DVT. The secondary outcomes include the percentage of other vascular events, IVC filter retrieval failure and net clinical benefits. This study aims to provide reliable, verification for the efficacy and safety of rivaroxaban antithrombotic therapy after IVC filter placement. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval number: (2019) 295). The results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04066764.


Assuntos
Embolia Pulmonar , Filtros de Veia Cava , Anticoagulantes/efeitos adversos , Contraindicações , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/efeitos adversos , Resultado do Tratamento
16.
Nat Commun ; 12(1): 6229, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711824

RESUMO

Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell's mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed "mechanical memory" in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.

17.
J Hazard Mater ; 416: 125714, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492774

RESUMO

In the present work, the removal of fast sulphon black (FSB) dye from water was executed by using chitin-cl-poly(itaconic acid-co-acrylamide)/zirconium tungstate nanocomposite hydrogel (Ch-cl-poly(IA-co-AAm)-ZrW NCH). The Ch-cl-poly(IA-co-AAm)-ZrW NCH was fabricated proficiently by microwave-induced sol-gel/copolymrization method. The zirconium tungstate (ZrW) photocatalyst was prepared by co-precipitation method using sodium tungstate and zirconium oxychloride in ratio (2:1). The polymeric hydrogel part has been used to support the ZrW, and it acted as an adsorbent for adsorptive removal of FSB dye. The band gap for nanocomposite hydrogel was found about 4.18 eV by using Tauc equation. The Ch-cl-poly(IA-co-AAm)-ZrW NCH was characterized by various techniques as FTIR (Fourier-transform infrared spectroscopy), X-ray diffraction (XRD), transmittance electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The adsorptional-photocatalytic remediation experiment of FSB dye was optimized for reaction parameters as FSB dye and Ch-cl-poly(IA-co-AAm)-ZrW NCH concentration, and pH. The maximum percentage removal for FSB dye was observed at 92.66% in 120 min under adsorptional-photocatalysis condition.


Assuntos
Quitina , Nanocompostos , Acrilamida , Concentração de Íons de Hidrogênio , Nanogéis , Espectroscopia de Infravermelho com Transformada de Fourier , Succinatos , Compostos de Tungstênio , Zircônio
18.
J Hazard Mater ; 416: 126229, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492983

RESUMO

The groundwater table fluctuation zone is the main interface for contaminants to transport between the unsaturated soil and saturated aquifers which still lacks of concern. In this study, we explored the interactions of Cr(VI) in this specific zone during water table fluctuation through laboratory experiment and numerical modeling. The higher reduction of Cr(VI) was found in the lower soil layer due to the lower Eh at the bottom layer of the unsaturated zone and the Cr(III) concentration increased with rise in water level and fluctuation amplitudes. After twice water fluctuation, nevertheless, there was still about 42.2% Cr retained in the soil and dominantly present as Cr(III) form. The model coupling reaction network with hydrodynamic field showed the cumulative Cr(III) in the unsaturated soil zone had a faster increase at the higher water level rise speed compared with lower rise speed. The cumulative Cr(VI) decreases over time in the saturated aquifers, whereas the cumulative Cr(III) increased with the increase of fluctuation amplitude. Reduction of Cr(VI) into Cr(III) was accompanied with Fe(II) and organic carbon oxidation. The results indicate that the hydrodynamic conditions have impacts on the redox environment of soil which could further affect the transformation and transport of Cr.

19.
Hepatology ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510484

RESUMO

OBJECTIVES: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. DESIGN: Young and aged mice, myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking presented with acute intoxication were analyzed. RESULTS: Neutrophilic Sirt1 and miR-223 expression were downregulated in aged mice compared to young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and downregulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, downregulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared to those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients. CONCLUSIONS: Aging increases the susceptibility of alcohol-induced liver injury in mice and humans via the downregulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a novel therapeutic target for the prevention and/or treatment of ALD.

20.
J Fungi (Basel) ; 7(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34356932

RESUMO

Coronavirus Disease 2019 (COVID-19) elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is calling for novel targeted drugs. Since the viral entry into host cells depends on specific interactions between the receptor-binding domain (RBD) of the viral Spike protein and the membrane-bound monocarboxypeptidase angiotensin converting enzyme 2 (ACE2), the development of high affinity RBD binders to compete with human ACE2 represents a promising strategy for the design of therapeutics to prevent viral entry. Here, we report the discovery of such a binder and its improvement via a combination of computational and experimental approaches. The binder micasin, a known fungal defensin from the dermatophytic fungus Microsporum canis with antibacterial activity, can dock to the crevice formed by the receptor-binding motif (RBM) of RBD via an extensive shape complementarity interface (855.9 Å2 in area) with numerous hydrophobic and hydrogen-bonding interactions. Using microscale thermophoresis (MST) technique, we confirmed that micasin and its C-terminal γ-core derivative with multiple predicted interacting residues exhibited a low micromolar affinity to RBD. Expanding the interface area of micasin through a single point mutation to 970.5 Å2 accompanying an enhanced hydrogen bond network significantly improved its binding affinity by six-fold. Our work highlights the naturally occurring fungal defensins as an emerging resource that may be suitable for the development into antiviral agents for COVID-19.

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