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1.
Environ Int ; 155: 106594, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940395

RESUMO

Antibiotics contamination is an emerging environmental concern, owing to its potential risks to ecosystems and human health. Microalgae-based technology has been widely reported as a promising alternative to conventional wastewater treatment, since it is a solar-power driven, ecologically friendly, cost-effective, and sustainable reclamation strategy. This review provides fundamental insights into the major mechanisms underpinning microalgae-based antibiotics removal, including bioadsorption, bioaccumulation, and biodegradation. The critical role of extracellular polymeric substances on bioadsorption and extracellular biodegradation of antibiotics are also covered. Moreover, this review sheds light on the important factors affecting the removal of antibiotics by microalgae, and summarizes several novel approaches to improve the removal efficiency, including acclimation, co-metabolism and microbial consortium. Besides, hybrid systems (such as, microalgae-based technologies combined with the conventional activated sludge, advanced oxidation processes, constructed wetlands, and microbial fuel cells), and genetic engineering are also recommended, which will be feasible for enhanced removal of antibiotics. Finally, this review also highlights the need for further studies aimed at optimizing microalgae-based technology, with emphasis on improving performance and expanding its application in large-scale settings, especially in terms of technical, environmental-friendly and economically competitiveness. Overall, this review summarizes current understanding on microalgae-based technologies for removal of antibiotics and outlines future research directions.

2.
ACS Chem Neurosci ; 12(9): 1480-1486, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33899470

RESUMO

Postoperative recovery for patients (particularly elderly) will be commonly encountered for postoperative neurocognitive disorders. Although effort has been undertaken to better understand and prevent these disorders, little improvement has been observed, due to largely unknown mechanisms. Emerging evidence indicates that noncoding RNAs including microRNA(s), long noncoding RNA(s), and circular RNA(s) are promising biomarkers for diagnosis, prognosis, and novel pathways to reveal mechanisms of postoperative neurocognitive disorders. However, there has been little crosstalk between noncoding RNA biology and development of postoperative neurocognitive disorders. We discuss the major noncoding RNAs in mechanisms, diagnosis, risk-stratification, prognosis, and treatment in postoperative neurocognitive disorders in a novel approach.

3.
Ann Med ; 53(1): 639-646, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33855907

RESUMO

OBJECTIVE: Little is known about the therapeutic relationship between coblation discoplasty and cervicogenic dizziness (CGD). CGD can be caused by abnormal proprioceptive inputs from compressed nerve roots, intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc. The aim was to analyze the efficacy of coblation discoplasty in CGD through intradiscal nerve ablation and disc decompression in a 12-month follow-up retrospective study. METHODS: From 2015 to 2019, 42 CGD patients who received coblation discolplasty were recruited as the surgery group, and 22 CGD patients who rejected surgery were recruited as the conservative group. Using intent-to-treat (ITT) analysis, we retrospectively analyzed the CGD visual analogue scale (VAS), neck pain VAS, CGD frequency score, and the CGD alleviation rating throughout a 12-month follow-up period. RESULTS: Compared with conservative intervention, coblation discoplasty revealed a better recovery trend with effect sizes of 1.76, 2.15, 0.92, 0.78 and 0.81 in CGD VAS, and effect sizes of 1.32, 1.54, 0.93, 0.86 and 0.76in neck pain VAS at post-operative 1 week, and 1, 3, 6, 12 months, respectively. The lower CGD frequency score indicated fewer attacks of dizziness until postoperative 3 months (p < 0.01). At post-operative 12 months, the coblation procedure showed increased satisfactory outcomes of CGD alleviation rating (p < .001, -1.00 of effect size). CONCLUSIONS: Coblation discoplasty significantly improves the severity and frequency of CGD, which is important inbridging unresponsive conservative intervention and open surgery.Key messagesThere is a correlation between the degenerative cervical disc and cervicogenic dizziness (CGD).CGD can be caused by abnormal proprioceptive inputs from a compressed nerve root and intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc.Cervical coblation discoplasty can alleviate CGD through ablating intradiscal nerve endings and decompressing the nerve root.

4.
Carbohydr Polym ; 263: 117981, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33858576

RESUMO

The existence of hydroxyl and carboxyl groups makes the photothermal stability of cellulose nanofibers (CNFs) poor and thus limits its scale application. This problem could be solved by doping layered double hydroxides (LDHs) nanopowders with opposite charge on the surface of CNFs. This work mainly focused on investigation of the influence of the crystal morphology of the inorganic ultraviolet shielding agent (i.e. ZnAl-LDHs) on the thermal stability of CNFs/ZnAl-LDHs composited films. The results showed that the morphology of LDHs was positively correlated with the photothermal stability of CNFs-based films. Specially, the ZnAl-LDHs with uniform crystal morphology could be prepared by controlling the molar ratio of Zn/Al at 3:1 and thus enhance the photothermal stability of CNFs-based films without any serious light transmittance deteriorating after doping. This work provided a practical and effective way for preparation of photothermal-stable CNFs-based transparent films for industrial application in the fields of photonics and electronics.

5.
Infect Genet Evol ; : 104831, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798758

RESUMO

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global pandemic with alarming speed, comprehensively analyzing the mutation and evolution of early SARS-CoV-2 strains contributes to detect and prevent such virus. Here, we explored 1962 high-quality genomes of early SARS-CoV-2 strains obtained from 42 countries before April 2020. The changing trends of genetic variations in SARS-CoV-2 strains over time and country were subsequently identified. In addition, viral genotype mapping and phylogenetic analysis were performed to identify the variation features of SARS-CoV-2. Results showed that 57.89% of genetic variations involved in ORF1ab, most of which (68.85%) were nonsynonymous. Haplotype maps and phylogenetic tree analysis showed that amino acid variations in ORF1ab (p.5828P > L and p.5865Y > C, also NSP13: P504L and NSP13: Y541C) were the important characteristics of such clade. Furthermore, these variants showed more significant aggregation in the United States (P = 2.92E-66, 95%) than in Australia or Canada, especially in strains from Washington State (P = 1.56E-23, 77.65%). Further analysis demonstrated that the report date of the variants was associated with the date of increased infections and the date of recovery and fatality rate change in the United States. More importantly, the fatality rate in Washington State was higher (4.13%) and showed poorer outcomes (P = 4.12E-21 in fatality rate, P = 3.64E-29 in death and recovered cases) than found in other states containing a small proportion of strains with such variants. Using sequence alignment, we found that variations at the 504 and 541 sites had functional effects on NSP13. In this study, we comprehensively analyzed genetic variations in SARS-CoV-2, gaining insights into amino acid variations in ORF1ab and COVID-19 outcomes.

6.
Phys Rev Lett ; 126(7): 070502, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33666457

RESUMO

The ability to efficiently simulate random quantum circuits using a classical computer is increasingly important for developing noisy intermediate-scale quantum devices. Here, we present a tensor network states based algorithm specifically designed to compute amplitudes for random quantum circuits with arbitrary geometry. Singular value decomposition based compression together with a two-sided circuit evolution algorithm are used to further compress the resulting tensor network. To further accelerate the simulation, we also propose a heuristic algorithm to compute the optimal tensor contraction path. We demonstrate that our algorithm is up to 2 orders of magnitudes faster than the Schrödinger-Feynman algorithm for verifying random quantum circuits on the 53-qubit Sycamore processor, with circuit depths below 12. We also simulate larger random quantum circuits with up to 104 qubits, showing that this algorithm is an ideal tool to verify relatively shallow quantum circuits on near-term quantum computers.

7.
Environ Sci Technol ; 55(8): 5272-5281, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33764736

RESUMO

In addition to a rise in global air and water mean temperatures, extreme climate events such as heat waves are increasing in frequency, intensity, and duration in many regions of the globe. Developing a mechanistic understanding of the impacts of heat waves on key ecosystem processes and how they differ from just an increase in mean temperatures is therefore of utmost importance for adaptive management against effects of global change. However, little is known about the impact of extreme events on freshwater ecosystem processes, particularly the decomposition of macrophyte detritus. We performed a mesocosm experiment to evaluate the impact of warming and heat waves on macrophyte detrital decomposition, applied as a fixed increment (+4 °C) above ambient and a fluctuating treatment with similar energy input, ranging from 0 to 6 °C above ambient (i.e., simulating heat waves). We showed that both warming and heat waves significantly accelerate dry mass loss of the detritus and carbon (C) release but found no significant differences between the two heated treatments on the effects on detritus dry mass loss and C release amount. This suggests that moderate warming indirectly enhanced macrophyte detritus dry mass loss and C release mainly by the amount of energy input rather than by the way in which warming was provided (i.e., by a fixed increment or in heat waves). However, we found significantly different amounts of nitrogen (N) and phosphorus (P) released between the two warming treatments, and there was an asymmetric response of N and P release patterns to the two warming treatments, possibly due to species-specific responses of decomposers to short-term temperature fluctuations and litter quality. Our results conclude that future climate scenarios can significantly accelerate organic matter decomposition and C, N, and P release from decaying macrophytes, and more importantly, there are asymmetric alterations in macrophyte-derived detrital N and P release dynamic. Therefore, future climate change scenarios could lead to alterations in N/P ratios in the water column via macrophyte decomposition processes and ultimately affect the structure and function of aquatic ecosystems, especially in the plankton community.


Assuntos
Ecossistema , Temperatura Alta , Mudança Climática , Água Doce , Nitrogênio , Nutrientes
8.
J Colloid Interface Sci ; 593: 434-446, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33765625

RESUMO

With the increased awareness of reusing solid wastes for higher sustainability and the concern of water pollution associated with phosphorus over-emission, there are strong interests in developing solid waste based adsorbents for purifying phosphorus-containing wastewater. As a rich calcium resource, paper mill sludge (i.e., a major solid waste from pulping industry) can be used as phosphorus removal adsorbent after calcination. Thus, in this work, a simple and clean thermally treating route has been proposed for preparing calcium-containing biochar from paper mill sludge. The effect of the physicochemical properties of paper mill sludge and its carbonization condition on phosphorus adsorption has been analyzed. Moreover, the influence of some key adsorption parameters, e.g., biochar dosage, initial pH of solution, co-existing anions, initial phosphorus concentration and contact time has also been investigated. The results showed that the phosphorus adsorption data could be fitted well with pseudo-second-order kinetic and Langmuir isothermal models. The calculated maximum adsorption capacity of the as-prepared optimal calcium-containing biochar could reach to 68.49 mg·g-1 at 25 °C. Combined with the characterization results, it can be reasonably inferred that the adsorption process was chemisorption-dominated. Lastly, the application of this spent adsorbent in agriculture field has also been discussed. In brief, this work provided a feasible strategy for converting paper mill solid waste to an environmental functional material (i.e., calcium-rich biochar) for remediation of eutrophic water.

9.
Langmuir ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725445

RESUMO

In this study, the behaviors of water droplets on hydrophobic surfaces with different cavities are studied by molecular dynamics. Hydrophobic surfaces with different cavities are designed and simulated: trapezoidal cavity with the same lower width, upside down trapezoidal cavity with the same lower width, and so on. The results show that the influence of the upper width and the depth of the cavity on the contact state and contact angle is different for different trapezoidal cavities. For example, for the trapezoidal cavity with the same lower width, the upper width decreases with the increase of the cavity depth. In such a scenario, the upper width and depth of the cavity collectively promote the droplet transition into the Cassie state from the Wenzel state, but the effect of the upper width and depth on the contact angle is opposite, and the decrease of the upper width of the cavity is the dominant factor, which leads to a decrease in the contact angle. Then, we have built trapezoidal cavities with different base angles. The influence of different base angles on wettability is also discussed, and it is found that an increase in base angle can significantly delay the transition from Cassie state into the Wenzel state.

11.
Sci Transl Med ; 13(583)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658354

RESUMO

The E4 allele of the apolipoprotein E gene (APOE) has been established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer's disease (AD), yet its mechanism of action remains poorly understood. APOE is a lipid transport protein, and the dysregulation of lipids has recently emerged as a key feature of several neurodegenerative diseases including AD. However, it is unclear how APOE4 perturbs the intracellular lipid state. Here, we report that APOE4, but not APOE3, disrupted the cellular lipidomes of human induced pluripotent stem cell (iPSC)-derived astrocytes generated from fibroblasts of APOE4 or APOE3 carriers, and of yeast expressing human APOE isoforms. We combined lipidomics and unbiased genome-wide screens in yeast with functional and genetic characterization to demonstrate that human APOE4 induced altered lipid homeostasis. These changes resulted in increased unsaturation of fatty acids and accumulation of intracellular lipid droplets both in yeast and in APOE4-expressing human iPSC-derived astrocytes. We then identified genetic and chemical modulators of this lipid disruption. We showed that supplementation of the culture medium with choline (a soluble phospholipid precursor) restored the cellular lipidome to its basal state in APOE4-expressing human iPSC-derived astrocytes and in yeast expressing human APOE4 Our study illuminates key molecular disruptions in lipid metabolism that may contribute to the disease risk linked to the APOE4 genotype. Our study suggests that manipulating lipid metabolism could be a therapeutic approach to help alleviate the consequences of carrying the APOE4 allele.

12.
Small ; : e2007791, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33749128

RESUMO

Miniaturized energy storage device (MESD) is the core module in microscale electronic equipment, yet its electrochemical performance is far away from the actual requirements. The extensive research efforts have improved the performance of MESD via the fabrication techniques and material construction, while ignoring the expansion of optimization strategy in the combination of energy storage mechanism. Herein, the Prussian blue/Zn microbattery is reported with the regulation of lattice-water-adsorbed intercalated ion. The optimal charge transport of cathode is achieved via the optimization of 3D structure of microelectrode to maximize the electrochemical performance. Also, lattice-water-adsorbed ion storage mechanism is further investigated to guide the design of differential energy storage for cathode and anode. The Cu3 (Fe(CN)6 )2 /Zn microbattery, with K+ inter/deintercalation in the cathode and Zn2+ deplating/plating in the anode, displays high capacity (0.281 mAh cm-2 at 2.5 mA cm-2 ), rate performance (0.181 mAh cm-2 at 25 mA cm-2 ), and cycling stability (77.6% capacity retention after 1500 cycles) enhanced by Cu2+ in the electrolyte. This highly efficient combination of fabrication process, active material, and multi-ion storage for microelectrode shows a high tolerance for optimization strategies, expanding the compatibility of optimization path for high-performance MESD.

13.
Medicine (Baltimore) ; 100(3): e24273, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546048

RESUMO

ABSTRACT: The exact dose of cytarabine still remain controversial for the management of patients with acute myeloid leukemia (AML) after complete remission (CR), but recent studies favor lower doses. This study aimed to investigate the toxic effects of single-intermediate dose (ID) cytarabine in patients with AML after achieving CR, compared with standard-dose cytarabine.In this retrospective study, AML patients who achieved CR after consolidation therapy before enrollment between 07/2008 and 05/2019 were included. All patients were divided into single-ID cytarabine and standard-dose cytarabine. The Kaplan-Meier method was used to compare overall survival (OS) and relapse-free time (RFS). Cox regression models were used to assess factors independently associated with OS and RFS. The toxic side effects of hematology and non-hematology were observed.52 patients were enrolled. There were 33 in ID group, 19 in Standard dose group. The 3-year RFS rate (40.4% vs 22.2%, P = .031) was better in the ID group than in the standard-dose group, while the 3-year OS rate was not different between the 2 groups (50.2% vs 27.8%, P = .074). Treatment stratage of ID cytarabine chemotherapy significantly improve the prognosis of AML regardless of patient age, risk grade, WBC count. There were no significant differences between the 2 groups in grade 3 to 4 bone marrow suppression, gastrointestinal symptoms, blood transfusion, infections.Patients with AML receiving ID cytarabine showed better survival and similar toxicity profiles compared with patients who received standard-dose cytarabine.


Assuntos
Quimioterapia de Consolidação/normas , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia de Consolidação/métodos , Quimioterapia de Consolidação/estatística & dados numéricos , Citarabina/farmacologia , Citarabina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
14.
Transl Psychiatry ; 11(1): 146, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637690

RESUMO

Despite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer's disease (AD), its underlying biological mechanisms are still elusive. The discovery of novel AD-associated genetic variants, particularly in coding regions and from APOE ε4 non-carriers, is critical for understanding the pathology of AD. In this study, we carried out an exome-wide association analysis of age-of-onset of AD with ~20,000 subjects and placed more emphasis on APOE ε4 non-carriers. Using Cox mixed-effects models, we find that age-of-onset shows a stronger genetic signal than AD case-control status, capturing many known variants with stronger significance, and also revealing new variants. We identified two novel variants, rs56201815, a rare synonymous variant in ERN1, and rs12373123, a common missense variant in SPPL2C in the MAPT region in APOE ε4 non-carriers. Besides, a rare missense variant rs144292455 in TACR3 showed the consistent direction of effect sizes across all studies with a suggestive significant level. In an attempt to unravel their regulatory and biological functions, we found that the minor allele of rs56201815 was associated with lower average FDG uptake across five brain regions in ADNI. Our eQTL analyses based on 6198 gene expression samples from ROSMAP and GTEx revealed that the minor allele of rs56201815 was potentially associated with elevated expression of ERN1, a key gene triggering unfolded protein response (UPR), in multiple brain regions, including the posterior cingulate cortex and nucleus accumbens. Our cell-type-specific eQTL analysis using ~80,000 single nuclei in the prefrontal cortex revealed that the protective minor allele of rs12373123 significantly increased the expression of GRN in microglia, and was associated with MAPT expression in astrocytes. These findings provide novel evidence supporting the hypothesis of the potential involvement of the UPR to ER stress in the pathological pathway of AD, and also give more insights into underlying regulatory mechanisms behind the pleiotropic effects of rs12373123 in multiple degenerative diseases including AD and Parkinson's disease.

15.
Sci Total Environ ; 772: 145516, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571766

RESUMO

Mining activities are known to generate a large amount of mine tailings and acid mine drainage which contain varieties of heavy metals. Heavy metals play an important role in co-selection for bacterial antibiotic resistance. However, the characteristics of antibiotic resistance genes (ARGs) in mining-affected water environments are still unclear. Here we investigated the pollution of metals, profiles of ARGs, mobile genetic elements (MGEs) and microbial community in mining-affected surface water and groundwater. The results showed that in the tested water samples, the concentrations of Zn and Mn were the highest, and Ni was the lowest. Higher abundances of ARGs with great proportion of sulfonamides, chloramphenicols and tetracyclines resistance genes were found in mining-affected water when compared with those without mining activities. Additionally, there were positive correlations between heavy metals (especially Ni, Zn and Mn) and these ARGs. Linear regression analysis suggested that MGEs were positively correlated with ARGs. In addition, total phosphorus was correlated with ARGs (p < 0.05). The microbial community was different between the mining-affected water and the reference (p < 0.05). Proteobacteria, Bacteroidetes and Actinobacteria were dominant phyla in the surface water and groundwater. Network analysis showed that many ARGs were significantly associated with these dominant bacteria, which suggested they might be potential hosts for these ARGs. These findings provide a clear evidence that the mining activities in the study area had a significant impact on surface water and groundwater to different degrees.


Assuntos
Antibacterianos , Água Subterrânea , Antibacterianos/análise , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Água
16.
J Food Biochem ; 45(4): e13668, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33605461

RESUMO

The fruits of Swietenia macrophylla King have been processed commercially to a variety of health foods and healthcare products and exhibited antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. This study was aimed to examine the glucose consumption in human hepatoma HepG2 cells and the expression of PPARγ of limonoids isolated from the fruits of S. macrophylla. The phytochemical investigation of the fruits led to the isolation of ten limonoids which structures were elucidated by spectroscopic analysis as swietenine (1), khayasin T (2), 6-deoxyswietenine (3), 3-O-tigloylswietenolide (4), swietenolide (5), 3,6-O,O-diacetylswietenolide (6), 7-deacetoxy-7-oxogedunin (7), fissinolide (8), proceranolide (9), 7-deacetoxy-7α-hydroxygedunin (10), and compound 10 was isolated from this plant for the first time. The glucose consumption assay revealed that compounds 1, 2, 3, 5, and 9 could promote glucose consumption significantly in normal hyperglycemia-induced HepG2 cells, furthermore, compounds 1, 5, and 9 had a better effect on promoting glucose consumption in insulin-resistant HepG2 cells. In addition, compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells according to the western blotting analysis result. PRACTICAL APPLICATIONS: Swietenia macrophylla King belongs to the family Meliaceae and the fruits have been exhibited a wide range of biological activities, such as antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. Phytochemical investigations of S. macrophylla have revealed that limonoids and triterpenoids were effective antidiabetic agents. However, the mechanism of these limonoids to antidiabetic activity is unclear. In this study, limonoids were isolated from the fruit of S. macrophylla and their effects on the glucose consumption of insulin-resistant HepG2 cells were studied. The results showed that compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells, which will give aid to explore the mechanism of these limonoids in the treatment of type 2 diabetes. Therefore, this research might facilitate further research and development of S. macrophylla.

17.
Sci Rep ; 11(1): 810, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436721

RESUMO

Maize (Zea mays L.) production in Northeast China is vulnerable to climate change. Thus, exploring future adaptation measures for maize is crucial to developing sustainable agriculture to ensure food security. The current study was undertaken to evaluate the impacts of climate change on maize yield and partial factor productivity of nitrogen (PFPN) and explore potential adaptation strategies in Northeast China. The Decision Support System for Agrotechnology Transfer (DSSAT) model was calibrated and validated using the measurements from nine maize experiments. DSSAT performed well in simulating maize yield, biomass and N uptake for both calibration and validation periods (normalized root mean square error (nRMSE) < 10%, -5% < normalized average relative error (nARE) < 5% and index of agreement (d) > 0.8). Compared to the baseline (1980-2010), the average maize yields and PFPN would decrease by 7.6-32.1% and 3.6-14.0 kg N kg-1 respectively under future climate scenarios (2041-2070 and 2071-2100) without adaptation. Optimizing N application rate and timing, establishing rotation system with legumes, adjusting planting dates and breeding long-season cultivars could be effective adaptation strategies to climate change. This study demonstrated that optimizing agronomic crop management practices would assist to make policy development on mitigating the negative impacts of future climate change on maize production.

18.
Int J Biol Macromol ; 171: 550-559, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33444654

RESUMO

Larch arabinogalactan (AG), extracted from Larix gmelinii sawdust, was depolymerized by H2O2 oxidation and purified by gel column to yield a novel degraded fraction (AGD2). The structural analysis indicated AGD2 had lower arabinose content and molecular weight compared with AG, in which the ratio of galactose and arabinose was changed from 7:3 to 16:1, the molecular weight was decreased from 50.2 kDa to 3.7 kDa, and the chain conformation spread from highly branched structure to flexible strand. It was one kind of ß-D-(1 â†’ 3)-galactan with fewer ß-D-(1 â†’ 6)-Galp side branches at O-6 position. Further, the results of the Gal-3 binding and immunomodulatory assay suggested that the unbinding force of AGD2 onto Gal-3 was as twice as AG to be 76 ± 11 pN at the loading rate of 0.15 µm/s. It could better promote the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) than AG in a dose-dependent manner.


Assuntos
Galactanos/isolamento & purificação , Larix/química , Madeira/química , Animais , Arabinose/análise , Proteínas Sanguíneas/antagonistas & inibidores , Configuração de Carboidratos , Relação Dose-Resposta a Droga , Galactanos/química , Galactanos/farmacologia , Galactose/análise , Galectinas/antagonistas & inibidores , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Metilação , Camundongos , Microscopia de Força Atômica , Ressonância Magnética Nuclear Biomolecular , Células RAW 264.7 , Fator de Necrose Tumoral alfa/biossíntese
19.
Eur J Med Chem ; 213: 113182, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33486198

RESUMO

In this paper, two new Cu(II) complexes, [Cu(Gluc)(HPB)(H2O)]Gluc (CuG1) and [Cu(Gluc)(HPBC)(H2O)]Gluc (CuG2) (where HPB = 2-(2'-pyridyl)benzimidazole, HPBC = 5-chloro-2-(2'-pyridyl)benzimidazole, Gluc = d-Gluconic acid), with good water solubility were synthesized and characterized. These complexes exhibited a five-coordinated tetragonal pyramidal geometry. The DNA binding and cleavage properties of the complexes were investigated using multi-spectroscopy, viscosity measurement, molecular docking and gel electrophoresis analysis methods. The results showed that the complexes could interact with DNA by insertion and groove binding, and cleave CT-DNA through a singlet oxygen-dependent pathway in the presence of ascorbic acid. The studies on antibacterial and anticancer activities in vitro demonstrated that both complexes had good inhibitory activity against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes) and one Gram-negative bacterium (Escherichia coli) and good cytotoxic activity toward the tested cancer cells (A549, HeLa and SGC-7901). CuG2 showed higher antimicrobial and cytotoxic activities than CuG1, which was consistent with their binding strength and cleavage ability to DNA, indicating that their antimicrobial and cytotoxic activities may be related to the DNA interaction. Moreover, the cell-based mechanism studies have indicated that CuG1 and CuG2 could arrest the cell cycle at G2/M phase, elevate the levels of intracellular reactive oxygen species (ROS) and decrease the mitochondrial membrane potential (MMP). The results showed that the complexes could induce apoptosis through DNA-damaged and ROS-mediated mitochondrial dysfunction pathways. Finally, the in vivo antitumor study revealed that CuG2 inhibited tumor growth by 50.44%, which is better than that of cisplatin (40.94%).


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , DNA/efeitos dos fármacos , Gluconatos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Bacillus subtilis/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Gluconatos/química , Humanos , Listeria monocytogenes/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Solubilidade , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Água/química
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