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1.
ACS Omega ; 6(45): 30656-30665, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34805693

RESUMO

Energy-saving membrane separation for water purification is increasingly desired, which requires appropriate nanofiltration membranes enabling to reject undesired solutes efficiently and allows high permeation of water. Herein, we report the fabrication of three-dimensional lamellar reduced graphene oxide (rGO) hydrogel membranes with a one-step, environment-friendly and water/vapor interfacial hydrothermal assembly process and the corresponding aerogel membranes by the freeze-drying method. The structures of the aerogel membranes can be tuned from lamellar to porously interconnected morphologies by controlling the volume of GO suspensions during the hydrothermal process. The rGO aerogel membrane was extremely flexible, which can be bent in liquid nitrogen and boiling water without any deformation, and highly stable in various solvents for at least 2 months. When used as nanofiltration membranes, the rGO aerogel membranes showed ∼100% rejection of organic dyes and a moderate water flux (up to 53 L m-2 h-1) only under the gravity of organic dye aqueous solutions of a 30 cm height. This water self-purification property of our flexible and stable aerogel membranes without extra energy consumption provides a possibility to make cheap, portable water purification devices for utilization in emergency and home-used water purification systems in the areas with electricity unavailable or inconvenient.

2.
PLoS One ; 16(11): e0260510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34843562

RESUMO

In actual farms, individual livestock identification technology relies on large models with slow recognition speeds, which seriously restricts its practical application. In this study, we use deep learning to recognize the features of individual cows. Alexnet is used as a skeleton network for a lightweight convolutional neural network that can recognise individual cows in images with complex backgrounds. The model is improved for multiple multiscale convolutions of Alexnet using the short-circuit connected BasicBlock to fit the desired values and avoid gradient disappearance or explosion. An improved inception module and attention mechanism are added to extract features at multiple scales to enhance the detection of feature points. In experiments, side-view images of 13 cows were collected. The proposed method achieved 97.95% accuracy in cow identification with a single training time of only 6 s, which is one-sixth that of the original Alexnet. To verify the validity of the model, the dataset and experimental parameters were kept constant and compared with the results of Vgg16, Resnet50, Mobilnet V2 and GoogLenet. The proposed model ensured high accuracy while having the smallest parameter size of 6.51 MB, which is 1.3 times less than that of the Mobilnet V2 network, which is famous for its light weight. This method overcomes the defects of traditional methods, which require artificial extraction of features, are often not robust enough, have slow recognition speeds, and require large numbers of parameters in the recognition model. The proposed method works with images with complex backgrounds, making it suitable for actual farming environments. It also provides a reference for the identification of individual cows in images with complex backgrounds.

3.
Appl Opt ; 60(29): 9146-9150, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624007

RESUMO

In this work, we report on the preparation and characterization of the planar and ridge optical waveguides in the Er3+-doped germanate glass by combining hydrogen ion implantation and precise diamond blade dicing. The nuclear energy loss and the implantation depth were calculated by the SRIM 2013 software. The refractive index profile was obtained by the reflectivity calculation method. The dark-mode spectrum and the near-field intensity distribution were measured by the prism coupling system and end-face coupling technique, respectively. This work has important reference significance for the development of Er3+-doped germanate glass active devices in the optical communication field.

4.
J Hazard Mater ; 424(Pt B): 127425, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34634705

RESUMO

Hydrogen peroxide (H2O2) is an important active oxygen species that plays a major role in redox balance and in physiological and pathological processes of various diseases of biological systems. As H2O2 is an endogenous active molecule, fluctuations in H2O2 content are not only affected by the state of biological system itself but also easily affected by Bisphenol A (BPA, a typical estrogenic environmental pollutant) in the external environment. Here, the near-infrared fluorescent probe Cy-NOH2 (λem = 750 nm) as a tool was synthesized to detect fluctuations in H2O2 content in cells and organisms induced by BPA. High sensitivity and excellent selectivity were found when the probe Cy-NOH2 was used to monitor endogenous H2O2 in vitro. In addition, the expression of H2O2 induced by different concentrations of BPA was able to be detected by the probe. Zebrafish and mice models were induced with different concentrations of BPA, and the H2O2 content showed significant increasing trends in zebrafish and livers of mice with increasing BPA concentrations. This study reveals that the probe Cy-NOH2 can be used as an effective tool to monitor the redox state in vivo under the influence of BPA, which provides a basis for clarifying the mechanisms of BPA in a variety of physiological and pathological processes.

5.
Int J Nurs Pract ; : e13011, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472156

RESUMO

AIM: This study was conducted to identify and compare the levels of compassion fatigue and job satisfaction among haemodialysis nurses in public and private hospitals in China and explore explanatory factors based on sociodemographic and occupational characteristics. METHODS: A descriptive study was conducted using a self-designed demographic questionnaire, the Professional Quality of Life Scale and the Minnesota Satisfaction Questionnaire, with responses from 283 haemodialysis nurses working at six public and private hospitals in China between June and November 2018. RESULTS: The compassion fatigue score of public hospital nurses was significantly higher than that of private hospital nurses. Univariate analysis showed that there were significant differences in compassion fatigue among nurses based on the number of years worked, nature of employment, and education level. Correlational analysis showed a negative correlation between overall job satisfaction and compassion fatigue in both public and private hospitals. Multiple regression analysis showed that compassion fatigue among haemodialysis nurses in public hospitals was associated with years worked, type of employment, and intrinsic and extrinsic satisfaction, whereas in private hospitals, education level, years worked, and intrinsic and extrinsic satisfaction were significant. CONCLUSION: Haemodialysis nurses in public hospitals are more likely to develop compassion fatigue than those in private hospitals.

6.
Nat Commun ; 12(1): 5404, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518526

RESUMO

Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca2+) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca2+-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , DNA Helicases/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Mitocôndrias/metabolismo , Mutação , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , DNA Helicases/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Transporte de Íons/genética , Masculino , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
7.
J Cell Mol Med ; 25(20): 9597-9608, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34551202

RESUMO

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by uncontrolled renal cyst formation, and few treatment options are available. There are many parallels between ADPKD and clear-cell renal cell carcinoma (ccRCC); however, few studies have addressed the mechanisms linking them. In this study, we aimed to investigate their convergences and divergences based on bioinformatics and explore the potential of compounds commonly used in cancer research to be repurposed for ADPKD. We analysed gene expression datasets of ADPKD and ccRCC to identify the common and disease-specific differentially expressed genes (DEGs). We then mapped them to the Connectivity Map database to identify small molecular compounds with therapeutic potential. A total of 117 significant DEGs were identified, and enrichment analyses results revealed that they are mainly enriched in arachidonic acid metabolism, p53 signalling pathway and metabolic pathways. In addition, 127 ccRCC-specific up-regulated genes were identified as related to the survival of patients with cancer. We focused on the compound NS398 as it targeted DEGs and found that it inhibited the proliferation of Pkd1-/- and 786-0 cells. Furthermore, its administration curbed cystogenesis in Pkd2 zebrafish and early-onset Pkd1-deficient mouse models. In conclusion, NS398 is a potential therapeutic agent for ADPKD.

8.
Vaccine ; 39(41): 6050-6056, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34521552

RESUMO

The development of an effective vaccine to control the global coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) is of utmost importance. In this study, a synthetic DNA-based vaccine candidate, known as pSV10-SARS-CoV-2, expressing the SARS-CoV-2 spike protein was designed and tested in 39 BALB/c mice with BC01, an adjuvant derived from unmethylated CpG motif-containing DNA fragments from the Bacillus Calmette-Guerin genome. Mice vaccinated with pSV10-SARS-CoV-2 with BC01 produced early neutralizing antibodies and developed stronger humoral and cellular immune responses compared to mice that received the DNA vaccine only. Moreover, sera from mice vaccinated with pSV10-SARS-CoV-2 with BC01 can neutralize certain variants, including 614G, 614G + 472 V, 452R, 483A, 501Y.V2, and B.1.1.7. The results of this study demonstrate that the addition of BC01 to a DNA-vaccine for COVID-19 could elicit more effective neutralizing antibody titers for disease prevention.


Assuntos
COVID-19 , Vacinas de DNA , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BCG , Vacinas contra COVID-19 , DNA , Genômica , Humanos , Imunidade Celular , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
9.
Int J Gynecol Pathol ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380971

RESUMO

A variety of unusual tumors are associated with both germline and somatic DICER1 pathogenic variants (PVs), including, in the female genital tract, embryonal rhabdomyosarcoma at various sites and ovarian Sertoli-Leydig cell tumor. There have been occasional reported cases of ovarian germ cell tumors [mainly yolk sac tumor (YST)] harboring DICER1 PVs but, as far as we are aware, none of these has been proven to have a germline provenance. We report an unusual enteric variant of ovarian YST in a 28-yr-old woman associated with a germline PV c.901C>T (p.Gln301Ter) in exon 7 of DICER1, accompanied by a somatic (YST-only) hotspot mutation: c.5437G>A, p.E1813K. To our knowledge, this is the first report of an ovarian germ cell tumor associated with a germline DICER1 PV. We review other reported cases of ovarian germ cell tumor with DICER1 PVs and discuss the differential diagnosis of this unusual variant of YST which was originally diagnosed as a mucinous adenocarcinoma.

10.
Nat Commun ; 12(1): 4210, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244522

RESUMO

Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Receptores Virais/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Sítios de Ligação/imunologia , COVID-19/imunologia , Cricetinae , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Humanos , Masculino , Testes de Neutralização , Receptores de Antígenos de Linfócitos B/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Front Immunol ; 12: 697074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262569

RESUMO

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


Assuntos
Vacinas contra Adenovirus/administração & dosagem , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Esquemas de Imunização , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Vacinação/métodos , Vacinas contra Adenovirus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Cricetinae , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pan troglodytes , RNA Viral/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Transfecção , Resultado do Tratamento
12.
Hemodial Int ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34227223

RESUMO

INTRODUCTION: The current study aims to elucidate the relationships of depression of caregivers with depression of hemodialysis patients and determine predictors of hospitalization of hemodialysis patients. METHODS: The single-center, cross-sectional study consisted of 200 pairs of eligible hemodialysis patients and caregivers from January 2019 to January 2020. Depression was evaluated using Hospital Anxiety and Depression Scale (HADS) questionnaire. FINDINGS: There were 89 hemodialysis patients with depression (44.5%) and 74 caregivers with depression (37.0%). In multi-variable logistic regression analysis, the hemodialysis patients with depressed caregivers were at increased risk of depression after adjusting for potential confounders (OR = 2.36, p = 0.04). Depression of hemodialysis patients (ß = 0.51, p = 0.00) and depression of caregivers (ß = 0.36, p = 0.04) were predictors of hospitalization of hemodialysis patients. DISCUSSION: Depression was prevalent among hemodialysis patients and their caregivers. Depression of caregivers was a risk factor for depression and hospitalization of hemodialysis patients. Implementation of appropriate screening programs and specific interventions for depression of hemodialysis patients and their caregivers is required.

13.
Anal Chem ; 93(29): 10378-10387, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34275284

RESUMO

Pantetheinase (also known as Vanin-1) is highly expressed in the liver, kidneys, and intestine and is closely associated with a number of diseases. Vanin-1 can hydrolyze pantetheine to pantothenic acid (vitamin B5) and cysteamine and participate in the synthesis of glutathione (GSH). GSH is highly expressed in tumor cells and plays a major role in the resistance of tumor cells to cisplatin. Therefore, we urgently need a method to monitor the activity level of Vanin-1 in tumor cells and tissues and elucidate the relationship between the role of Vanin-1 in GSH synthesis and tumor resistance. Herein, we report a Cy-Pa fluorescent probe for imaging Vanin-1 in cells and in vivo that can qualitatively and quantitatively detect the fluctuation of Vanin-1 concentrations in HepG2 and HepG2/DDP cells or tumor tissues of tumor-bearing mice. This probe shows excellent potential in in situ real-time monitoring of endogenous Vanin-1. Moreover, we proved that Vanin-1 can inhibit GSH synthesis using the probe. When the Vanin-1 inhibitor RR6 was used in combination with cisplatin, HepG2 and HepG2/DDP cells showed increased resistance to cisplatin, while the therapeutic efficiency of cisplatin was reduced in HepG2 and HepG2/DDP xenografts. In this study, Vanin-1 was shown to play an important role in the treatment of cancer, and the study of Vanin-1 may provide an idea for the treatment of cancer in the future.


Assuntos
Cisteamina , Corantes Fluorescentes , Amidoidrolases , Animais , Proteínas Ligadas por GPI , Glutationa , Humanos , Camundongos , Panteteína , Ácido Pantotênico
14.
Food Chem ; 365: 130389, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34256228

RESUMO

Leafy vegetables have high nutritional value and are very popular in China. However, the long-term variation in residues and integrated risks of synthetic pyrethroids (SPs) in these vegetables have not been well examined. In this study, a total of 1005 samples were collected from 55 markets during 2017-2019. The cumulative exposure to nine kinds of SPs in Zhejiang, China, through the consumption of nine leafy vegetables was analyzed, and the potential integrated risk was assessed by the relative potency factor. A total of 191 samples were detected with SPs residues. The most frequently detected SPs were λ-cyhalothrin and cypermethrin. The integrated risk assessment results revealed that the dietary risk for these SPs via leafy vegetable exposure is acceptable for children, adults and elderly individuals. The data provided here will be helpful for the government to formulate food policies in China.


Assuntos
Piretrinas , Verduras , Idoso , Criança , China , Contaminação de Alimentos/análise , Humanos , Folhas de Planta , Medição de Risco
15.
Toxicol Appl Pharmacol ; 428: 115648, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34280409

RESUMO

Acute lung injury (ALI) is a diffuse lung dysfunction disease characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Therefore, anti-inflammation may be a potential therapy strategy for ALI. Indazole-containing derivatives, representing one of the most important heterocycles in drug molecules, are endowed with a broad range of biological properties, such as anti-cancer and anti-inflammation. In the current study, we investigated the biological effects of Cyy-272, a newly synthesized indazole compound, on LPS-induced ALI both in vivo and in vitro. Results show that Cyy-272 can inhibit the release of inflammatory cytokines in LPS-stimulated macrophage and alleviate LPS induced ALI. Further experiment revealed that Cyy-272 exhibit anti-inflammation activity by inhibiting JNK phosphorylation. Overall, our studies show that an indazole derivative, Cyy-272, is effective in suppressing LPS-induced JNK activation and inflammatory signaling.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Indazóis/uso terapêutico , Lipopolissacarídeos/toxicidade , MAP Quinase Quinase 4/antagonistas & inibidores , Lesão Pulmonar Aguda/metabolismo , Animais , Relação Dose-Resposta a Droga , Indazóis/química , Indazóis/farmacologia , MAP Quinase Quinase 4/química , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Estrutura Terciária de Proteína , Células RAW 264.7
16.
Front Immunol ; 12: 651656, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936072

RESUMO

Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14+ cells expressed higher levels of glycolysis-related genes (PKM, LDHA and PKM) and PPP-related genes (PGD and TKT) in severe patients than in mild patients. These genes may contribute to the hyperinflammation in mono-CD14+ cells of patients with severe COVID-19. The mono-CD16+ cell population in COVID-19 patients showed reduced transcription levels of genes related to lysine degradation (NSD1, KMT2E, and SETD2) and elevated transcription levels of genes involved in OXPHOS (ATP6V1B2, ATP5A1, ATP5E, and ATP5B), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene ATP13A3 in COVID-19 patients, which was positively associated with antibody secretion and survival of PCs. Moreover, enhanced glycolysis or OXPHOS was positively associated with the differentiation of memory B cells into plasmablasts or plasma cells. This study comprehensively investigated the metabolic features of peripheral immune cells and revealed that metabolic changes exacerbated inflammation in monocytes and promoted antibody secretion and cell survival in PCs in COVID-19 patients, especially those with severe disease.


Assuntos
COVID-19/imunologia , Glicólise/genética , Lisina/metabolismo , Monócitos/metabolismo , Análise de Célula Única/métodos , Adenosina Trifosfatases/sangue , Adenosina Trifosfatases/genética , Anticorpos/metabolismo , COVID-19/metabolismo , COVID-19/fisiopatologia , Bases de Dados Genéticas , Proteínas Ligadas por GPI/metabolismo , Ontologia Genética , Hematopoese/genética , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Receptores de Lipopolissacarídeos/metabolismo , Lisina/genética , Proteínas de Membrana Transportadoras/sangue , Proteínas de Membrana Transportadoras/genética , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/fisiologia , Monócitos/imunologia , Monócitos/patologia , Fosforilação Oxidativa , RNA-Seq , Receptores de IgG/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma/genética
17.
Acta Neuropathol ; 141(6): 929-944, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33644822

RESUMO

Pituitary blastoma (PitB) has recently been identified as a rare and potentially lethal pediatric intracranial tumor. All cases that have been studied molecularly possess at least one DICER1 pathogenic variant. Here, we characterized nine pituitary samples, including three fresh frozen PitBs, three normal fetal pituitary glands and three normal postnatal pituitary glands using small-RNA-Seq, RNA-Seq, methylation profiling, whole genome sequencing and Nanostring® miRNA analyses; an extended series of 21 pituitary samples was used for validation purposes. These analyses demonstrated that DICER1 RNase IIIb hotspot mutations in PitBs induced improper processing of miRNA precursors, resulting in aberrant 5p-derived miRNA products and a skewed distribution of miRNAs favoring mature 3p over 5p miRNAs. This led to dysregulation of hundreds of 5p and 3p miRNAs and concomitant dysregulation of numerous mRNA targets. Gene expression analysis revealed PRAME as the most significantly upregulated gene (500-fold increase). PRAME is a member of the Retinoic Acid Receptor (RAR) signaling pathway and in PitBs, the RAR, WNT and NOTCH pathways are dysregulated. Cancer Hallmarks analysis showed that PI3K pathway is activated in the tumors. Whole genome sequencing demonstrated a quiet genome with very few somatic alterations. The comparison of methylation profiles to publicly available data from ~ 3000 other central nervous system tumors revealed that PitBs have a distinct methylation profile compared to all other tumors, including pituitary adenomas. In conclusion, this comprehensive characterization of DICER1-related PitB revealed key molecular underpinnings of PitB and identified pathways that could potentially be exploited in the treatment of this tumor.

18.
Mitochondrial DNA B Resour ; 6(1): 15-16, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33659644

RESUMO

Chlorella vulgaris ITBBA3-12 has a role in the purification of the rubber processing wastewater. Its complete chloroplast genome contains 168369 bp, with a G + C content of 33.0%. A total of 147 genes were annotated, including 113 protein-coding genes, three rRNA (rrn23, rrn16, and rrn5) genes, and 31 tRNA genes. The significant feature of the chloroplast genome is that the genes encoding subunit V (petG), VI (petL), and apocytochrome f (petA) of the cytochrome b6/f complex are in triplicate, which was not observed in the other C. vulgaris strains. Phylogenetic analysis using the chloroplast genomes of Chlorophyta species indicated that ITBBA3-12 is closely related to C. vulgaris strain UTEX259 and NJ-7, and they clustered in the Chlorella lineage.

19.
J Hazard Mater ; 414: 125389, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33677314

RESUMO

Despite the ubiquity of cypermethrin (CYP) stereoisomers in environment biota, the stereoisomeric selectivity of endocrine-disrupting potency of α-CYP, ß-CYP, and θ-CYP has not been well studied. In this study, dual-luciferase reporter gene assays were adopted to analyze their potential endocrine-disrupting effects via four receptors (ERα, GRα, MR and RXR). The results showed that α-CYP was antagonistic to ERα, GRα, and MR with RIC20 of 9.1 × 10-7, 7.6 × 10-7, and 1.0 × 10-6 M, respectively. ß-CYP exhibited only ERα-mediated agonistic activity with a REC20 of 2.1 × 10-6 M. None of the CYP stereoisomers interacted with RXR. Molecular docking indicated that α-CYP had the strongest binding capacity to GRα among the compounds. The expression levels of steroid hormone-related genes in human adrenocortical carcinoma (H295R) cells displayed that all three compounds inhibited the transcription of 3-ßHSD, indicating the block of turning cholesterol into different hormones. Both α-CYP and ß-CYP upregulated genes encoding estrogen- and aldosterone-forming enzymes including 17-ßHSD, CYP19, STAR, and CYP11B2. Mortality and malformation toxicity assays in zebrafish embryos revealed that the order of toxicity was α-CYP > ß-CYP > θ-CYP. Our results indicated that α-CYP may pose the strongest endocrine-disrupting effects. The data provided here will be helpful to systematically understand stereoisomeric selectivity in the endocrine-disrupting effects of cypermethrin.


Assuntos
Disruptores Endócrinos , Animais , Disruptores Endócrinos/toxicidade , Humanos , Simulação de Acoplamento Molecular , Piretrinas , Estereoisomerismo , Peixe-Zebra
20.
J Toxicol ; 2021: 6290524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505465

RESUMO

The objective of this work was to explore the ability of lactic acid bacteria strains to bind benzo(a)pyrene (B(a)P) existing in PM2.5. In this study, we examined the ability of Lactobacillus acidophilus NCFM to bind B(a)P in the simulated PM2.5 environment. Among the tested 5 strains, Lactobacillus acidophilus NCFM exhibited the best capacity to bind B(a)P, and its B(a)P binding percentage was 60.00%. Simulations of organic and inorganic systems which represent PM2.5 indicated that B(a)P could be absorbed by strain L. acidophilus NCFM. For the inorganic system of pH 5, L. acidophilus NCFM bound 92.74% B(a)P with a cell concentration of 1 × 1010 cfu/mL at 37°C for 8 hr. Regarding the organic system with pH 6, 73.00% B(a)P was bound by strain L. acidophilus NCFM after this bacterium was incubated at 37°C for 10 min. A quick B(a)P binding by this probiotic bacterium took place in the organic system. The removal of B(a)P from PM2.5 was significantly related to incubation time, cultivation temperature, pH, and cell concentration. Thus, our finding shows that long-term consumption of L. acidophilus NCFM is beneficial for the reduction of B(a)P towards the population who are exposed to PM2.5, although the ability of this bacterium to adsorb B(a)P is partly affected by the differences in the origin of PM2.5.

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