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1.
Artigo em Inglês | MEDLINE | ID: mdl-34628157

RESUMO

Glutathione S-transferase (GST) is an important detoxification enzyme in organisms. GSTs play an important role in responding to environmental stresses. This study aimed to identify the GST gene superfamily in silver sillago (Sillago sihama) and analyze its expression pattern under hypoxia stress. A total of 17 GST genes were identified in silver sillago. Phylogenetic analysis showed that the GST gene family contained two subgroups (cytosolic and MAPEGs), and lacked three subgroups (i.e. Pi, Kappa, and MGST2). Phylogenetic and syntenic analysis revealed that GST genes were conserved in evolution. Eight SsGSTs were significantly differentially expressed under hypoxia stress in silver sillago by RNA-seq and qRT-PCR analysis. The expression levels of SsMGST3b, SsGSTO1, SsGSTT1b and SsGSTR2 genes were significantly up-regulated after 4 h of reoxygenation in the gill tissue. In the heart tissue, the expression of SsGSTR3 was significantly up-regulated after 1 h of hypoxia while the expression levels of SsGSTT1b and SsFLAP genes were significantly down-regulated after 4 h of hypoxia. In summary, this study provides for the first time a comprehensive analysis of the GST gene superfamily of silver sillago.

2.
Chem Commun (Camb) ; 57(73): 9284-9287, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519313

RESUMO

By virtue of α-allenols as innovative three-carbon annulation components, the Rh(III)-catalyzed redox-neutral C-H coupling of N-phenoxyacetamides with α-allenols has been realized for the assembly of 4-alkylidene chroman-2-ol frameworks via an unusual [3+3] annulation. This transformation features good functional group tolerance, specific regio-/chemoselectivity and potential synthetic utility. Mechanistic studies reveal that synergistic coordination modes between the dual directing groups (-ONHAc and -OH) and the rhodium metal center account for the observed exclusive selectivity.

3.
Ann Palliat Med ; 10(8): 8684-8691, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488357

RESUMO

BACKGROUND: The aim of this study was to observe the effect of Sacubitril/Valsartan on cardiac function and remodeling in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 120 patients with HFrEF were selected and given standard heart failure treatment according to the 2017 ACC/AHA/HFSA guidelines. Regardless of whether patients had taken Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers (ACEI/ARB) medications previously, after admission they were treated with the minimum effective dose of Sacubitril/Valsartan according to their blood pressure reading. Baseline clinical data were recorded and patients were followed up at 1, 3, 6, 9, and 12 months post discharge, during which time the dose of Sacubitril/Valsartan was gradually increased to the maximum tolerated dose (dose range 25-200 mg/twice daily). During follow-up, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and left atrium diameter (LAD) were monitored; a 6-minute walking test and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were recorded; and adverse reactions were collected. RESULTS: Over the course of the 12-month follow-up, the plasma concentrations of NT-proBNP were significantly reduced compared with the baseline, and the longer the follow-up time, the lower the NT-proBNP levels were (P<0.05). Similarly, LVEDD, LVESD and LAD were significantly smaller at 12 months than at baseline, and the longer the follow-up time, the smaller the internal diameter was (P<0.05). The LVEF, 6-minute walking distance and KCCQ scores increased significantly from baseline (P<0.05), whereas eGFR and serum potassium levels showed no significant change compared with the baseline. CONCLUSIONS: Sacubitril/Valsartan demonstrated a remarkable ability to improve cardiac function and to control cardiac remodeling with a high degree of safety in patients with HFrEF.


Assuntos
Insuficiência Cardíaca , Assistência ao Convalescente , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Alta do Paciente , Volume Sistólico , Resultado do Tratamento , Valsartana , Função Ventricular Esquerda , Remodelação Ventricular
4.
Sci Total Environ ; 802: 149905, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34525710

RESUMO

Immobilizing heavy metals (HMs) from municipal solid waste incineration fly ash (MSWIFA) using shell coal gasification fly ash (SFA)-based geopolymer can solve the energy and environmental challenges simultaneously. In this study, we synthesized a geopolymer with SFA, metakaolin (MK), and steel slag (SS) to solidify and stabilize HMs (Pb, Cr, and Zn) and investigated the early immobilization mechanisms. The results show that the prepared geopolymer possessed high early-age mechanical strength and immobilization efficiency to HMs (>90%), even under the effect of excess HMs. The early immobilization mechanism of the geopolymer for the HMs could be described as follows. (1) Most of HMs were remained in the aluminosilicate. (2) The presence of amorphous zeolite precursor and clay minerals may contribute to restrain the HMs leaching; (3) Pb and Zn were trapped by the gel structure in M-O-Al and M-O-Si forms (M = Pb or Zn), whereas Cr (VI) was reduced to Cr (III). (4) Cr might involve in the geopolymerization of [SiO4] and [AlO4]- units. (5) The immobilization process of Pb and Zn in the geopolymer could be described as crystal growth (NG) - phase boundary reaction (I) - NG - I - diffusion (D), whereas that of Cr is prolonged to NG-I-NG-I-NG-I-D.

5.
Sci Total Environ ; 803: 149866, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34525768

RESUMO

Heavy metal (HM) soil pollution has become an increasingly serious problem with the development of industries. Application of biochar in HMs remediation from contaminated environment has attracted considerable research attention during the past decade. Although the mechanism of HMs passivation with biochar has been investigated, effects and mechanisms of interaction among soil-indigenous microbes and novel carbon matrix composites for HMs adsorption and passivation are still unclear. Four different biochar-loaded aerogels, namely, BNCA-1-600, BNCA-1-900, BNCA-2-600, and BNCA-2-900, were synthesized in this study. Adsorption capacity of four kinds of synthetic materials and two types of contrast biochars (BC600 and BC900) to HMs in aqueous solution, passivation capacity of HMs in soil, and effects on soil organic matter and microbial community were explored. Results showed that BNCA-2-900 exhibits excellent adsorption property and a maximum removal capacity of 205.07 mg·g-1 at 25 °C for Pb(II), 105.56 mg·g-1 for Cd(II), and 137.89 mg·g-1 for Zn(II). Leaching concentration of HMs in contaminated soil can meet the national standard of China (GB/T 5085.3-2007) within 120 days. Results of this study confirmed that the additive BNCA-2-900 and coexistence of indigenous microorganisms can effectively reduce bioavailability of HMs. Another potential mechanism may be to remove the passivation of HMs by porous structure and surface functional groups as well as improve the content of organic matter and microbial abundance. The research results may provide a novel perceptive for the development of functional materials and strategies for eco-friendly and sustainable multiple HMs remediation in contaminated soil and water by using a combination of carbon matrix composites and soil-indigenous microorganisms.

6.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3980-3989, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472275

RESUMO

To systematically review the efficacy of Xuebijing Injection combined with western medicine in the treatment of systemic inflammatory response syndrome(SIRS). In this study, CBM, CNKI, Wanfang, VIP, PubMed and EMbase databases were retrieved for clinical randomized controlled trials on the effect of Xuebijing Injection combined with western medicine in the treatment of SIRS from the establishment of the database to July 31, 2020. After screening, Meta-analysis was conducted by RevMan 5.3 software, trial sequential analysis was conducted by TSA 0.9.5.10 beta software, and the evidence quality level was evaluated by GRADEprofiler 3.6.1 software. Meta-analysis showed that Xuebijing Injection combined with western medicine could reduce white blood cell count(MD=-2.32, 95%CI[-2.44,-2.21], P<0.000 01), C-reactive protein count(MD=-22.70, 95%CI[-29.61,-15.79], P<0.000 01), APACHE Ⅱ score(MD=-2.15, 95%CI[-2.43,-1.87], P<0.000 01), tumor necrosis factor alpha count(SMD=-1.23, 95%CI[-1.48,-0.99], P<0.000 01) and interleukin-6 count(SMD=-0.92, 95%CI[-1.15,-0.69], P<0.000 01), improve treatment efficiency(RR=1.39, 95%CI[1.23, 1.56], P<0.000 01), reduce incidence of multiple organ dysfunction(RR=0.47, 95%CI[0.35, 0.64], P<0.000 01) and mortality(RR=0.22, 95%CI[0.13, 0.37], P<0.000 01), which were better than western medicine treatment alone. Trial sequential analysis showed that in terms of reducing the incidence of multiple organ dysfunction and C-reactive protein count, the cumulative Z value passed through the traditional threshold, TSA threshold and expected information value, and reached the required number of cases. GRADE evaluation showed that the level of evidence was low or very low. According to the findings, Xuebijing Injection combined with western medicine is effective in treating SIRS. However, as the low quality of the included studies may affect the reliability of the conclusion, more high-quality studies shall be included for further verification in the future, so as to provide better suggestions for clinical medication.


Assuntos
Medicamentos de Ervas Chinesas , Humanos , Injeções , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico
7.
Sci Rep ; 11(1): 19022, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561473

RESUMO

Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpoint was unveiled in leukemic patient cells and cell lines. Transient downregulation or ablation of PIGN resulted in impaired mitotic checkpoint activation due to the dysregulated expression of spindle assembly checkpoint-related proteins including MAD1, MAD2, BUBR1, and MPS1. Moreover, ectopic overexpression of PIGN restored the expression of MAD2. PIGN regulated the spindle assembly checkpoint by forming a complex with the spindle assembly checkpoint proteins MAD1, MAD2, and the mitotic kinase MPS1. Thus, PIGN could play a vital role in the spindle assembly checkpoint to suppress chromosomal instability associated with leukemic transformation and progression.

8.
Mol Syst Biol ; 17(8): e10239, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34339582

RESUMO

Understanding the mechanism of SARS-CoV-2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID-19. These were deduced from the gene expression signature of SARS-CoV-2-infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral-host interactome. We also identified immuno-modulating compounds aiming at suppressing hyperinflammatory responses in severe COVID-19 patients, based on the transcriptome of ACE2-overexpressing A549 cells. Experiments with Vero-E6 cells infected by SARS-CoV-2, as well as independent syncytia formation assays for probing ACE2/SARS-CoV-2 spike protein-mediated cell fusion using HEK293T and Calu-3 cells, showed that several predicted compounds had inhibitory activities. Among them, salmeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero-E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. These novel findings provide new paths for broadening the repertoire of compounds pursued as therapeutics against COVID-19.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Internalização do Vírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , COVID-19/genética , COVID-19/virologia , Chlorocebus aethiops , Reposicionamento de Medicamentos , Células HEK293 , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Imidazóis/farmacologia , Pirazinas/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Xinafoato de Salmeterol/farmacologia , Células Vero
9.
J Org Chem ; 86(17): 11998-12007, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34404211

RESUMO

A visible-light photoredox-catalyzed sulfonyl lactonization of unsaturated carboxylic acids with sulfonyl chlorides is described. This reaction features good functional group tolerance and a broad substrate scope, providing a simple and efficient protocol to access a wide range of sulfonyl lactones in high to excellent yields. Preliminary mechanistic investigations suggested that a free-radical pathway should be involved in the process.

10.
Pharmacol Res ; 173: 105860, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34461220

RESUMO

In this study, SB-VHTS of the old drug library was conducted to seek for novel PPARγ ligand. In the end, an antifungal drug, FN, was identified in vitro and in vivo as a new and potent PPARγ-modulating ligand to demonstrate significantly anti-diabetic and anti-NAFLD efficacies with minimized side effects induced by PPARγ full agonists TZDs drugs. Further mechanistic investigations revealed that FN showed such desired pharmacological properties mainly through selectively activating the expressions of Adiponectin and GLUT4, effectively promoting the Akt Ser473 phosphorylation, inhibiting the expressions of proinflammatory genes including TNF-α, IL-1ß and IL-6 and blocking the PPARγ Ser273 phosphorylation mediated by CDK5 without leading to adipogenesis and increasing the expressions of key adipogenic genes CD36, AP2, LPL, C/EBPα, FASN and PPARγ. Subsequently, a molecular docking study revealed an interesting binding mode between FN and PPARγ LBD including the hydrogen-bonding network among oxygen atom, sulfur atom and nitrogen atom in FN respectively with the PPARγ residues Cys285, Tyr327 and Ser342, which gave proof of concept for the above anti-diabetic action mechanism. Taken together, our findings not only suggest that FN can serve as the new, safe and highly efficacious anti-diabetic and anti-NAFLD agents for clinical use, they can also provide a molecular basis for the future development of PPARγ modulators with a high therapeutic index and the possibility to explore new uses of old drugs for immediate drug discovery.

11.
J Org Chem ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314188

RESUMO

A copper-catalyzed intermolecular electrophilic amination of benzamides with O-benzoyl hydroxylamines was achieved with the assistance of an 8-aminoquinolyl group. With this protocol, good compatibility was observed for a variety of aryl amides and heteroaryl amides, and excellent tolerance with various functional groups was achieved. Significantly, the monoaminated product was overwhelmingly delivered under the simple reaction conditions. Preliminary mechanistic investigations suggested that a radical pathway should be excluded and C-H activation be potentially the rate-determining step.

12.
Sci Total Environ ; 794: 148719, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34214821

RESUMO

Phthalic acid esters (PAEs) are a class of biologically accumulated carcinogenic and teratogenic toxic chemicals that exist widely in the environment. This study, Pseudarthrobacter defluvii E5 was isolated from agricultural soils and showed efficient PAEs-degradation and -mineralization abilities for five PAEs, and encouraging PAEs tolerance and bioavailable range for dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) (0.25-1200 mg/L). The complete catalytic system in E5 genome enables PAEs to be degraded into monoester, phthalate (PA) and Protocatechuic acid (PCA), which eventually enter the tricarboxylic acid cycle (TCA cycle). The preferred PAEs-metabolic pathway in soil by E5 is the metabolism induced by enzymes encoded by pehA, mehpH, pht Operon and pca Operon. For the first time, two para-homologous pht gene clusters were found to coexist on the plasmid and contribute to PAEs degradation. Further study showed that P. defluvii E5 has a broad application prospect in microplastics-contaminated environments.


Assuntos
Ácidos Ftálicos , Plásticos , Dibutilftalato , Ésteres , Micrococcaceae , Ácidos Ftálicos/toxicidade
13.
Artigo em Inglês | MEDLINE | ID: mdl-34035977

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a global crisis, and medical systems in many countries are overwhelmed with supply shortages and increasing demands to treat patients due to the surge in cases and severe illnesses. This study aimed to assess COVID-19-related essential clinical resource demands in China, based on different scenarios involving COVID-19 outbreaks and interventions. We used a susceptible-exposed-infectious-hospitalized/isolated-removed (SEIHR) transmission dynamics model to estimate the number of COVID-19 infections and hospitalizations with corresponding essential healthcare resources needed. We found that, under strict non-pharmaceutical interventions (NPIs) or mass vaccination of the population, China would be able to contain community transmission and local outbreaks rapidly. However, under scenarios involving a low intensity of implemented NPIs and a small proportion of the population vaccinated, the use of a peacetime-wartime transition model would be needed for medical source stockpiles and preparations to ensure a normal functioning healthcare system. The implementation of COVID-19 vaccines and NPIs in different periods can influence the transmission of COVID-19 and subsequently affect the demand for clinical diagnosis and treatment. An increased proportion of asymptomatic infections in simulations will not reduce the demand for medical resources; however, attention must be paid to the increasing difficulty in containing COVID-19 transmission due to asymptomatic cases. This study provides evidence for emergency preparations and the adjustment of prevention and control strategies during the COVID-19 pandemic. It also provides guidance for essential healthcare investment and resource allocation.

14.
J Endocrinol ; 250(1): 1-12, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33970125

RESUMO

Our previous study has demonstrated maternal high-fat diet (HFD) caused sex-dependent cardiac hypertrophy in adult male, but not female offspring. The present study tested the hypothesis that estrogen normalizes maternal HFD-induced cardiac hypertrophy by regulating angiotensin II receptor (ATR) expression in adult female offspring. Pregnant rats were divided into the normal diet (ND) and HFD (60% kcal fat) groups. Ovariectomy (OVX) and 17ß-estradiol (E2) replacement were performed on 8-week-old female offspring. Maternal HFD had no effect on left ventricular (LV) wall thickness, cardiac function and molecular markers of cardiac hypertrophy function in sham groups. However, maternal HFD caused cardiac hypertrophy of offspring in OVX groups, which was abrogated by E2 replacement. In addition, maternal HFD had no effect on ERα and ERß in sham groups. In contrast, HFD significantly decreased ERα, but not ERß in OVX groups. In sham groups, there was no difference in the cardiac ATR type 1 (AT1R) and ATR type 2 (AT2R) between ND and HFD offspring. HFD significantly increased AT2R, but not AT1R in OVX groups. Furthermore, maternal HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the AT2R promoter, which was due to decreased GRs in hearts from OVX offspring. These HFD-induced changes in OVX groups were abrogated by E2 replacement. These results support a key role of estrogen in the sex difference of maternal HFD-induced cardiac hypertrophy in offspring, and suggest that estrogen protects female offspring from cardiac hypertrophy in adulthood by regulating AT2R.


Assuntos
Cardiomegalia/etiologia , Dieta Hiperlipídica/efeitos adversos , Estrogênios/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Receptor Tipo 2 de Angiotensina/metabolismo , Animais , Estradiol , Receptor alfa de Estrogênio/metabolismo , Feminino , Masculino , Miocárdio/metabolismo , Gravidez , Distribuição Aleatória , Ratos Sprague-Dawley , Fatores Sexuais
15.
Huan Jing Ke Xue ; 42(6): 2966-2974, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032096

RESUMO

Migration characteristics of the heavy metals Fe, Zn, Mn, and Ni during the preparation of biochar from municipal sludge were studied, and the optimal pyrolysis temperature for the preparation of biochar was determined based on potential environmental risks. Four heavy metals (Fe, Zn, Mn, and Ni) with high total contents in the biochar were selected to determine their species and content changes under different pyrolysis temperatures using the BCR extraction method. An environmental risk assessment for sludge-based biochar was also carried out using the potential ecological risk index (PERI) and risk assessment code (RAC). The results showed that the volatility of the four metals is ranked as follows:Zn>Mn>Fe>Ni. The distribution and transformation of the four metal species were different, but their migration paths shared similar characteristics. In the pyrolysis stage at low temperatures (<500℃), unstable fractions gradually changed into more stable species; under high temperatures (>500℃), some of the oxidizable and residual fractions were broken, which transformed into reducible fractions, and other fractions escaped into the atmosphere. In the environmental risk assessment, biochar prepared under high pyrolysis temperatures (>500℃) showed lower environmental risks, with the best outcomes at 500℃.

16.
J Ethnopharmacol ; 276: 114208, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34010697

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Premna microphylla turcz is traditionally used as a folk remedy. Its roots, stems and leaves can be invoked as medicines, which have the functions of detoxification, swelling and hemostasis. It belongs to the Premna in the Verbenaceae and is mainly distributed in the mountains of southeastern China. However, there are few reports of in-depth studies on the anti-inflammatory effects of polysaccharide, which was the main component in Premna microphylla turcz. MATERIALS AND METHODS: The flies were fed with standard corn flour-yeast medium to cause inflammation by sodium lauryl sulfate (SDS). The treatment group contained Premna microphylla turcz polysaccharide (pPMTLs) extract. The survival rate was obtained by feeding a vial containing five layers of filter paper, which was infiltrated with the 5% sucrose solution contaminated with SDS or SDS polysaccharide. The microvilli and nucleus of the midgut epithelial cells of different treatments were observed by transmission electron microscope, and the expression of inflammation-related genes was detected by real-time quantitative PCR (qRT-PCR). Finally, 16S rDNA analysis was conducted on the differences in the composition of the intestinal microbes of Drosophila. RESULTS: In the current study, we showed that pPMTLs significantly prolonged the life span of SDS-inflamed flies from 5 days to 6 days. And pPMTLs reduced the rupture of microvilli in the midgut and restored the nuclear structure. In addition, pPMTLs significantly improved expression level of immune-related genes in Inflammation Drosophila especially the defensin (4.32 ± 0.75 vs 9.97 ± 0.52 SDS-polysaccharide group: SDS group, p < 0.001). The analysis of intestinal microbiota showed that pPMTLs decreased the relative abundance of Raoultella while Wolbachia increased (p < 0.05). CONCLUSIONS: Collectively, our results revealed the potential application of pPMTLs in enhancing inflammation defense, which would be enormous significance for the inflammation-related disorders treatment.

17.
JAMA Netw Open ; 4(4): e216322, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856473

RESUMO

Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published. Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer. Design, Setting, and Participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system. Exposures: Sentinel lymph node biopsy and adjuvant RT. Main Outcomes and Measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%). Conclusions and Relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.


Assuntos
Neoplasias da Mama/terapia , Radioterapia Adjuvante/estatística & dados numéricos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Procedimentos Desnecessários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde , Intervalo Livre de Progressão , Receptor ErbB-2 , Receptores de Estrogênio , Sistema de Registros , Estudos Retrospectivos
18.
J Environ Sci (China) ; 103: 268-278, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33743908

RESUMO

In this work, the waste biomass lotus leaf was converted into N-doped porous carbonaceous CO2 adsorbents. The synthesis process includes carbonization of lotus leaf, melamine post-treatment and KOH activation. For the resultant sorbents, high nitrogen content can be contained due to the melamine modification and advanced porous structure were formed by KOH etching. These samples were carefully characterized by different techniques and their CO2 adsorption properties were investigated in detail. These sorbents hold good CO2 adsorption abilities, up to 3.87 and 5.89 mmol/g at 25 and 0°C under 1 bar, respectively. By thorough investigation, the combined interplay of N content and narrow microporous volume was found to be responsible for the CO2 uptake for this series of sorbents. Together with the high CO2 adsorption abilities, these carbons also display excellent reversibility, high CO2/N2 selectivity, applicable heat of adsorption, fast CO2 adsorption kinetics and good dynamic CO2 adsorption capacity. This study reveals a universal method of obtaining N-doped porous carbonaceous sorbents from leaves. The low cost of raw materials accompanied by easy synthesis procedure disclose the enormous potential of leaves-based carbons in CO2 capture as well as many other applications.


Assuntos
Lotus , Nitrogênio , Dióxido de Carbono , Folhas de Planta , Porosidade
19.
Hypertens Res ; 44(1): 36-46, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32719462

RESUMO

A maternal high-fat diet (HFD) is a risk factor for cardiovascular diseases in offspring. The aim of the study was to determine whether maternal HFD causes the epigenetic programming of vascular angiotensin II receptors (ATRs) and leads to heightened vascular contraction in adult male offspring in a sex-dependent manner. Pregnant rats were treated with HFD (60% kcal fat). Aortas were isolated from adult male and female offspring. Maternal HFD increased phenylephrine (PE)-and angiotensin II (Ang II)-induced contractions of the aorta in male but not female offspring. NG-nitro-L-arginine (ʟ-NNA; 100 µM) abrogated the maternal HFD-induced increase in PE-mediated contraction. HFD caused a decrease in endothelium-dependent relaxations induced by acetylcholine in male but not female offspring. However, it had no effect on sodium nitroprusside-induced endothelium-independent relaxations of aortas regardless of sex. The AT1 receptor (AT1R) antagonist losartan (10 µM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 µM), blocked Ang II-induced contractions in both control and HFD offspring in both sexes. Maternal HFD increased AT1R but decreased AT2R, leading to an increased ratio of AT1R/AT2R in HFD male offspring, which was associated with selective decreases in DNA methylation at the AT1aR promoter and increases in DNA methylation at the AT2R promoter. The vascular ratio of AT1R/AT2R was not significantly different in HFD female offspring compared with the control group. Our results indicated that maternal HFD caused a differential regulation of vascular AT1R and AT2R gene expression through a DNA methylation mechanism, which may be involved in HFD-induced vascular dysfunction and the development of a hypertensive phenotype in adulthood in a sex-dependent manner.

20.
Cancer Res ; 81(2): 268-281, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33148662

RESUMO

Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única/métodos , Transcriptoma , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias da Mama/genética , Caderinas/antagonistas & inibidores , Caderinas/genética , Caderinas/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Feminino , Humanos , Mutação , Prognóstico , Células Tumorais Cultivadas
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