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1.
J Hazard Mater ; 416: 126177, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492951

RESUMO

Previous study showed that lead (Pb) could induce ATM-dependent mitophagy. However, whether Pb has any impact on mitochondrial fusion and fission, the upstream events of mitophagy, and how ATM connects to these processes remain unclear. In this study, we found that Pb can disrupt mitochondrial network morphology as indicated by increased percentage of shortened mitochondria and by decreased mitochondrial footprints. Correspondingly, the expression of fission protein Drp1 and its association with mitochondrial marker Hsp60 were significantly increased, while those of fusion proteins Mfn2 and Opa1 and their co-localization with Hsp60 were drastically attenuated. Notably, the expression of p-Drp1 (Ser616) and its translocation to mitochondria were dramatically elevated. Moreover, a small amount of ATM could be detected in the cytoplasm around mitochondria in response to Pb, and the co-localization of p-ATM (Ser1981) with Drp1 and p-Drp1 (Ser616) was obviously increased while its co-localization with Mfn2 and Opa1 was dramatically decreased. Furthermore, siRNA silencing of ATM evidently promoted greater fission in response to Pb stress, indicating that ATM is involved in mitochondrial fragmentation. Our results suggest that cytoplasmic ATM is an important regulator of Pb-induced mitochondrial fission.

2.
Bioresour Technol ; 341: 125851, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34523577

RESUMO

Targeted options to reduce nitrous oxide (N2O) emission from composting is scarce due to challenges in disentangling the complex N2O production pathways. Here, combined approaches of nitrogen form analysis, isotopocule mapping, quantitative PCR, and Illumina MiSeq sequencing were used to differentiate N2O production pathways and decipher the underlying biochemical mechanisms. Results suggested that most N2O was produced at the latter stage through nitrifier denitrification. The bioelectrochemical assistance through applying an electric potential reduced N2O emissions by 28.5-75.5%, and the underlying mitigation mechanism was ammonia oxidation repression, as evidenced by the observed reduction in the proportion of the amoA containing family Nitrosomonadaceae from 99% to 83% at the lower voltage and to a negligible level at the higher voltage assessed, which was attributed to their depressed competitiveness for oxygen with heterotrophs. The findings provide evidence that the bioelectrochemical assistance could function as a nitrification inhibitor to minimize compost derived N2O emissions.

3.
Adv Mater ; : e2104849, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536044

RESUMO

Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of macrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.

4.
Sci Total Environ ; 804: 150125, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34520912

RESUMO

Phosphorus (P) from detergents contributes to water pollution and eutrophication. Understanding the impacts of detergent use on P inputs to surface waters and their main drivers is vital for supporting Sustainable Development Goals on clean water. This study aims to quantify past and future trends in P inputs to surface waters from detergent use in China. We modify the Model to Assess River Input of Nutrient to seAs (MARINA) model to assess the effects of past policies and explore options for the future on mitigating detergents P losses in China. The total consumption of detergents tripled from 2000 to 2018. However, P inputs to surface waters from detergent use decreased by 35% during these years. Although P losses vary across regions, most losses occurred in rural areas. Clearly, the P-free detergent policy which was initiated in the year 2000 has been effective. Without this policy, the detergent P losses would likely have increased fourfold during 2000-2018. In the future, detergent P inputs to surface waters in China may be further reduced to very low levels (95% reduction relative to 2018) by a combination of completely P-free detergents, an increasing urbanized population connected to sewage systems, and improving P removal in sewage treatment systems. Our results enhance the understanding of P pollution in surface waters from detergents and, illustrate the effectiveness of measures to control detergent P losses.

5.
J AOAC Int ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519786

RESUMO

BACKGROUND: At present, PGRs are widely used in agricultural and forestry production in the world, PGRs, like the traditional pesticides have certain toxicity, naively excessive applied them will cause the acute and chronic poisoning of humans and animals, potential harm to human health. OBJECTIVES: In order to assess, prevent and control the residues of plant growth regulators (PGRs) in fruits and vegetables, a set of easy, sensitive, quick, cheap, effective, reliable and safe analytical method that simultaneously detects multiple PGRs residues is urgently needed for the inspection departments of agricultural product's quality safety. METHODS: In this study, grape (representative of fruit) and cabbage (representative of vegetable) were used as the detected objects. The 30 commercial products residues of PGRs in both were detected with the ultra-high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method based on the optimized chromatographic conditions, mass spectrometry and preparation conditions (extraction solvent and cleanup conditions). Grape and cabbage samples were extracted by acetonitrile containing 5% (v/v) acetic acid, dehydrated by salt package, purified by QuEChERS method, ionized by electrospray (ESI) under positive and negative ion switching mode, detected by multi-reactions monitoring (MRM) and quantification by external standard method of matrix matching standard curve. RESULTS: The results showed that methanol was selected as the strong elution phase. The methanol-0.1% formic acid-5 mmol/L ammonium acetate solution was selected as the best mobile phase. The optimal extraction solvent was acetonitrile containing 5% acetic acid. PSA cleanup could meet the determination requirements of PGRs residues. The developed method for 30 commercial products of PGRs such as betaine showed excellent linearity in 1∼500 µg/kg, 10∼1000 µg/kg, ∼500 µg/kg, ∼2000 µg/kg, and 100∼10000 µg/kg (R ≥ 0.98). At the 0.001 mg/kg (0.01 mg/kg), 0.05 mg/kg, 0.20 mg/kg and 1.00 mg/kg additive concentrations, the average addition standard recovery of 30 commercial products of PGRs were 61%∼132% with the relative standard deviations (RSD) of 1%∼14%, the LOQwere confirmed 1.0-100 µg/kg through the actual addition values of samples. CONCLUSIONS: The results demonstrated that the optimized "QuEChERS-UHPLC-MS/MS method" is a set of simple, rapid, sensitive, accurate, efficient, economical and safe detection method that simultaneously detected the residues of more PGRs in fruits and vegetables through one time sample preparation for their high-throughput rapid quantitative screening and confirmation; it is characterized by wide coverage of detecting PGRs types, simple and convenient preparation and small amount of solvent, and which can provide the technical supports for the supervision of PGRs residues in fruits and vegetables. HIGHLIGHTS: Based on the facts mentioned above, the optimizations of extraction solvent screening, different ratio of various purification packings in QuEChERS method and UPLC-MS conditions were conducted and the indexes of method such as precision, sensitivity and recovery rate were investigated in order to establish an simple, quick, sensitive, cheap, efficient, reliable and safe QuEChERS-UPLC-MS/MS method for simultaneously detecting the 30 kinds of PGRs residues in fruits and vegetables a set of method with simultaneously detecting 30 kinds of PGRs; which shall meet the high throughput determination of multiple PGRs residues in fruits and vegetables and can also provide the technical references for related compounds residues detection of other matrix.

6.
J Hazard Mater ; 416: 126085, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492900

RESUMO

The usage of triclosan (TCS) may rise rapidly due to the COVID-19 pandemic. TCS usually sinks in the activated sludge. However, the effects of TCS in activated sludge remain largely unknown. The changes in nitrogen cycles and the abundances of antibiotic resistance genes (ARGs) caused by TCS were investigated in this study. The addition of 1000 µg/L TCS significantly inhibited nitrification since the ammonia conversion rate and the abundance of nitrification functional genes decreased by 12.14%. The other nitrogen cycle genes involved in nitrogen fixation and denitrification were also suppressed. The microbial community shifted towards tolerance and degradation of phenols. The addition of 100 µg/L TCS remarkably increased the total abundance of ARGs and mobile genetic elements by 33.1%, and notably, the tetracycline and multidrug resistance genes increased by 54.75% and 103.42%, respectively. The co-occurrence network revealed that Flavobacterium might have played a key role in the spread of ARGs. The abundance of this genus increased 92-fold under the addition of 1000 µg/L TCS, indicating that Flavobacterium is potent in the tolerance and degradation of TCS. This work would help to better understand the effects of TCS in activated sludge and provide comprehensive insight into TCS management during the pandemic era.


Assuntos
COVID-19 , Triclosan , Antibacterianos , Resistência Microbiana a Medicamentos/genética , Humanos , Nitrificação , Pandemias , SARS-CoV-2 , Esgotos
7.
Neurol Sci ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480243

RESUMO

OBJECTIVE: To evaluate whether shorter door-to-needle times (DNT) with intravenous tissue plasminogen activator (tPA) for acute ischemic stroke are associated with improved 1-year outcomes in Chinese patients. METHODS: From August to September 2019, all first-ever ischemic stroke patients who were treated with intravenous tPA within 4.5 h of the time they were last known to be well from 232 hospitals in China were included. Patients were divided into four groups according to DNT time (≤ 45 min; 45-60 min; 60-90 min; > 90 min). All discharged patients would receive a telephone follow-up at 12-month after admission. Death and disability events were recorded. RESULTS: Finally, 2370 patients were analyzed. The median age was 65 years, 66.6% were male, and 2.4% were of ethnic minorities. In the 1-year follow-up, 211 patients died (8.9%; 95%CI: 7.8-10.0%). The patients (53.1%) had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year mortality (8.9% vs 8.9% [absolute difference, 0.03% {95% CI, - 0.05% to - 0.10%}, odd ratio {OR}, 1.00 {95% CI, 0.75 to 1.33}]). In addition, 385 patients (16.2%; 14.8-17.3%) out of those survivors had disability events. The patients had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year disability rate (18.9% vs 16.7% [absolute difference, 1.9% {95% CI, 1.1% to 3.0%}, odd ratio {OR}, 1.22 {95% CI, 0.89 to 1.43}]). CONCLUSIONS: The results did not show that shorter DNT for tPA administration was significantly associated with better 1-year outcomes.

8.
Environ Pollut ; 290: 118045, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34488163

RESUMO

Ammonia (NH3) emissions, the majority of which arise from livestock production, are linked to high concentration of PM2.5 and lower air quality in China. NH3 mitigation options were well studied at the small-scale (laboratory or pilot), however, they lack of a large-scale test in China. This study fills this crucial gap by evaluating the cost-benefit of pioneering NH3 mitigation projects carried out for a whole county - Sheyang, Jiangsu province, China. Measures were implemented in 2019 following two distinct strategies, improved manure treatment for industrial livestock farms, and collection and central treatment for traditional livestock farms. Emission reductions of 16% were achieved in a short time. While this is remarkable, it falls short of expectations from small-scale studies. If measures were fully implemented according to purpose and meet expectations from the small scale, higher emission reductions of 42% would be possible. The cost benefit analysis presented in this study demonstrated advantages of central manure treatment over in-farm facilities. With improved implementation of mitigation strategies in industrial livestock farms, traditional livestock farms may play an increasing role in total NH3 emissions, which means such farms either need to be included in future NH3 mitigation policies or gradually replaced by industrial livestock farms. The study found an agricultural NH3 reduction technology route suitable for China's national conditions (such as the "Sheyang Model").

9.
Artigo em Inglês | MEDLINE | ID: mdl-34472030

RESUMO

Resource integration of coal enterprises is conducive to reducing pollution and carbon emissions, thus alleviating environmental problems such as global warming. Government regulation has a great influence on enterprise behavior. Therefore, it is necessary to analyze the strategies of government and coal enterprises in resource integration. Based on the perspective of government regulation, this paper discusses how to guide and restrict coal enterprises to conduct resource integration behavior, and whether the government supervises this behavior. First, through empirical research, government regulations of coal enterprises are given practical policy implications. Second, using evolutionary game and simulation technology, from the perspective of government regulation, we explore the complex behavioral interaction mechanism between the dominant and inferior coal enterprises, the mechanism between the government and coal enterprises, and analyze the impact of key factors on the dynamic evolution process. Finally, the sensitivity analysis of the selected parameters is discussed in details, which provides useful decision-making suggestions for the government and enterprises. In addition, this paper further analyzes the impact of different government policies on coal enterprises' green innovation strategies. Results demonstrate that (1) when the power gap between enterprises is large, the probability of dominant enterprises choosing resource integration converges to 1, while the probability of inferior enterprises converges to 0. Therefore, government regulations are invalid for inferior enterprises; (2) the combination of government regulations can help improve the efficiency of coal enterprises' strategic choices. With the increase in the intensity of government rewards and punishments, the probability of enterprise resource integration evolves from 0 to 1; (3) excessive government regulations make the choice between the government and coal companies tend to swing, because the probability of the two is between 0 and 1. Therefore, excessive government regulations cannot effectively achieve resource integration and government regulation. (4) The government subsidy strategy is less effective than the government's pollution penalty strategy in promoting the green innovation of enterprises. Our research shows that the government should choose different policy combinations and intensities to regulate resource integration according to the market power of coal enterprises, which provides theoretical reference and practical guidance for the government to regulate corporate resource integration behavior.

10.
Genome Biol ; 22(1): 230, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404453

RESUMO

BACKGROUND: Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis. RESULTS: In this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment. CONCLUSIONS: In conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.

11.
Eur J Pharmacol ; 910: 174450, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34454927

RESUMO

This study aims to investigate the effects of ß-elemene on a mouse model of heart failure (HF) and to elucidate the underlying mechanisms in vitro approaches. In this study, left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were leveraged to assess the therapeutic effects of ß-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of ß-elemene in lipid-induced inflammation. Results showed that ß-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, ß-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, ß-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-ß (PPARß). In vitro, treatment of ß-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor κB (NF-κB) and the degradation of inhibitory κBα (IκBα) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNFα) in ß-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between ß-elemene and PPARß protein. Furthermore, ß-elemene increased the expression of PPARß, which was validated by antagonist of PPARß and siRNA for PPARß.

12.
Cancer Biomark ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34334381

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide. The collection of exhaled breath condensate (EBC) is a non-invasive method that may have enormous potential as a biomarker for the early detection of lung cancer. OBJECTIVE: To investigate the proteomic differences of EBC between lung cancer and CT-detected benign nodule patients, and determine whether these proteins could be potential biomarkers. METHODS: Proteomic analysis was performed on individual samples from 10 lung cancer patients and 10 CT-detected benign nodule patients using data-independent acquisition (DIA) mass spectrometry. RESULTS: A total of 1,254 proteins were identified, and 21 proteins were differentially expressed in the lung adenocarcinoma group compared to the benign nodule group (p< 0.05). The GO analysis showed that most of these proteins were involved in neutrophil-related biological processes, and the KEGG analysis showed these proteins were mostly annotated to pyruvate and propanoate metabolism. Through protein-protein interactions (PPIs) analysis, ME1 and LDHB contributed most to the interaction-network of these proteins. CONCLUSION: Significantly differentially expressed proteins were detected between lung cancer and the CT-detected benign nodule group from EBC samples, and these proteins might serve as potential novel biomarkers of EBC for early lung cancer detection.

13.
J Oleo Sci ; 70(9): 1261-1274, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34373408

RESUMO

As a valuable natural antioxidant, sesaminol can be used in food and medicine industries, but it is trace in sesame seeds and oil, and it is feasible to prepare sesaminol from sesaminol triglucoside (STG) which is abundant in defatted sesame cake. Therefore, in order to establish an effective enzymatic preparation method and elucidate the antioxidant structure-activity relationship of sesaminol, a suitable glycosidase for preparing sesaminol from STG were screened, enzymatic hydrolysis was optimized by single-factor test and response surface methodology, and finally, the structure-activity relationship of sesaminol was illustrated by comparative molecular field analysis (CoMFA). These results suggested that ß-galactosidase was the optimal glycosidase for enzymatic hydrolysis of STG to prepare sesaminol. Under the optimal conditions of a reaction temperature of 50°C, reaction time of 4.0 h, pH of 5.5, substrate concentration of 1.0 mg/mL, and enzyme dosage of 20 mg/mL, the conversion rate of sesaminol was 98.88±0.67%. Sesaminol displayed excellent antioxidant ability in 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 0.0011 mg/mL), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonate) (ABTS, IC50 = 0.0021 mg/mL) radical scavenging activities and Ferric reducing antioxidant power (FRAP, 103.2998 mol/g) compared to other sesaminol derivatives. According to -log (IC50 of DPPH) and -log (IC50 of ABTS), CoMFA models were successfully established based on Q2 >0.5 (QDPPH 2 = 0.558, QABTS 2 = 0.534). The active site of sesaminol tended to be located on the hydroxyl group of the benzene ring (R1 position). A positive correlation between the bulky and positively charged groups at the 1H, 3H-furo [3, 4-c] furan group, the small, negatively charged groups at the R1 position and the antioxidant activity of sesaminol. This study provides an effective method to prepare sesaminol, reveals the structure-activity relationship of sesaminol and provides theoretical basis to design the novel compound.

14.
Pharmacol Res ; 171: 105574, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34419228

RESUMO

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.

15.
Circ Res ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34384247

RESUMO

Rationale: Anthracycline-induced cardiotoxicity (AIC) is a major side effect that limits the use of anthracyclines as effective chemotherapeutics. No mechanism-based therapy is available when cardiac function deteriorates.Objective: We aim to elucidate the dynamic autophagic defects in AIC, and to identify a mechanism-based therapy via both genetic and pharmacological studies. Methods and Results: Through phenotyping an adult AIC (aAIC) zebrafish model, we detected a biphasic response in autophagy: activation in the early stage and suppression in the later phase that is characterized by a decline in cardiac function. We conducted conditional genetic studies with atg7, which encodes a rate-limiting autophagy core protein, and found that atg7 overexpression (OE) leads to therapeutic effects in the late phase but deleterious effects in the early phase of aAIC. We then assessed the therapeutic effects of 37 FDA-approved autophagy activators (FAAs) using an embryonic AIC (eAIC) zebrafish model and identified spironolactone, pravastatin, and minoxidil as top-ranking drugs. We demonstrated the therapeutic efficacy of these FAAs in the aAIC model and confirmed that these drugs exert therapeutic effects in the late phase but not in the early AIC phase. Finally, we demonstrated that the time-dependent therapeutic effects are conserved in a mouse AIC model and that spironolactone and rapamycin activated autophagy in an Atg7-dependent fashion. Conclusions: Our findings suggest that atg7-based autophagy activation is an effective therapeutic avenue to reversing the decline in cardiac function in AIC, highlighting the time dependent nature of autophagy-based therapy.

16.
Oxid Med Cell Longev ; 2021: 6634718, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367464

RESUMO

The mechanism underlying the role of oxidative stress and advanced oxidation protein products (AOPPs) in the aetiology of premature ovarian insufficiency (POI) is poorly understood. Here, we investigated the plasma AOPP level in POI patients and the effects of AOPPs on granulosa cells both in vitro and in vivo. KGN cells were treated with different AOPP doses, and cell cycle distribution, intracellular reactive oxygen species (ROS), and protein expression levels were measured. Sprague-Dawley (SD) rats were treated daily with PBS, rat serum albumin, AOPP, or AOPP+ N-acetylcysteine (NAC) for 12 weeks to explore the effect of AOPPs on ovarian function. Plasma AOPP concentrations were significantly higher in both POI and biochemical POI patients than in controls and negatively correlated with anti-Müllerian hormone and the antral follicle count. KGN cells treated with AOPP exhibited G1/G0-phase arrest. AOPP induced G1/G0-phase arrest in KGN cells by activating the ROS-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)-p21 pathway. Pretreatment with NAC, SP600125, SB203580, and si-p21 blocked AOPP-induced G1/G0-phase arrest. In SD rats, AOPP treatment increased the proportion of atretic follicles, and NAC attenuated the adverse effects of AOPPs in the ovary. In conclusion, we provide mechanistic evidence that AOPPs may induce cell cycle arrest in granulosa cells via the ROS-JNK/p38 MAPK-p21 pathway and thus may be a novel biomarker of POI.

18.
ACS Nano ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347432

RESUMO

The two key problems for the industrialization of Li-S batteries are the dendrite growth of lithium anode and the shuttle effect of lithium polysulfides (LiPSs). Herein, we report the Janus separator prepared by coating anionic Bio-MOF-100 and its derived single-atom zinc catalyst on each side of the Celgard separator. The anionic metal-organic framework (MOF) coating induces the uniform and rapid deposition of lithium ions, while its derived single-atom zinc catalyzes the rapid transformation of LiPSs, thus inhibiting the lithium dendrite and shuttle effect simultaneously. Consequently, compared with other reported Li-S batteries assembled with single-atomic catalysts as separator coatings, our SAZ-AF Janus separator showed stable cyclic performance (0.05% capacity decay rate at 2 C with 1000 cycles), outstanding performance in protecting lithium anode (steady cycle 2800 h at 10 mAh cm-2), and equally excellent cycling performance in Li-SeS2 or Li-Se batteries. Our work provides an effective separator coating design to inhibit shuttle effect and lithium dendrite.

19.
Environ Toxicol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402589

RESUMO

Cadmium (Cd) at low concentrations has a potential to promote cell proliferation. However, the molecular mechanisms of Cd-induced proliferation are not well understood. Here, we reported that Cd (0-500 nM) significantly promoted the proliferation of HepG2 cells as demonstrated by elevated cell viability, more EdU-positive cells and increased gene expression of KI-67 and COX-2. Meanwhile, the gene expression of DNA methyltransferases was found to be elevated while that of tumor suppressor genes DAPK1 and RASSF1A were decreased under Cd exposure. Correspondingly, the methylation level of promoters in DAPK1 and RASSF1A were increased. Specifically, the CpG sites at -461 (Chr3:50, 374, 481) of RASSF1A promoter, and that at -260 (Chr9:90, 113, 207), -239 (Chr9:90, 113, 228), and -68 (Chr9:90, 113, 399) of DAPK1 promoter, were significantly hypermethylated. Moreover, 5-azacytidine (an inhibitor of DNA methyltransferase) partly impaired Cd-induced promoter hypermethylation of RASSF1A and DAPK1 genes, increased their expressions and slowed down Cd-induced cell proliferation, suggesting that DNA methylation play an essential part in Cd-boosted proliferation. The study showed that Cd caused promoter hypermethylation of RASSF1A and DAPK1, decreasing their expression and leading to higher level of cell proliferation. Furthermore, Cd at low concentrations could influence DNA methylation, which may serve as the proliferative mechanism of Cd.

20.
Neurosci Bull ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34460072

RESUMO

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of ß-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after ß-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of ß-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

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