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1.
Front Med (Lausanne) ; 8: 753295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651003

RESUMO

Objective: This study aimed to assess the status of intrinsic capacity (IC)-a novel function-centered construct proposed by the WHO and examine whether impairment in IC predicts subsequent 1-year activities of daily living (ADL) disability better than a disease-based approach, i. e., multimorbidity status. Methods: This study included data of community-dwelling older adults from the Beijing Longitudinal Study on Aging II aged 65 years or older who were followed up at 1 year. Multivariate logistic regressions were performed to estimate the odds of ADL disability at baseline and 1-year follow-up. Results: A total of 7,298 older participants aged 65 years or older were included in the current study. About 4,742 older adults were followed up at 1 year. At baseline, subjects with a higher impairment in IC domains showed higher odds of ADL disability [adj. odds ratio (OR) = 9.51 for impairment in ≥3 domains, area under the curve (AUC) = 0.751] compared to much lower odds of ADL disability in subjects with a higher number (≥3) of chronic diseases (adj. OR 3.92, AUC = 0.712). At 1-year follow-up, the overall incidence of ADL disability increased with the impairment in IC domains higher than the increase in multimorbidity status. A higher impairment in IC domains showed higher odds of incidence ADL disability for impairment in 2 or ≥3 IC domains (adj. OR 2.32 for impairment in ≥3 domains, adj. OR 1.43 for impairment in two domains, AUC = 0.685). Only subjects who had ≥3 chronic diseases had higher odds of 1-year incident ADL disability (adj. OR 1.73, AUC = 0.681) that was statistically significant. Conclusion: Our results imply that a function-centered construct could have higher predictability of disability compared to the multimorbidity status in community older people. Our results need to be confirmed by studies with longer follow-up.

2.
J Neuroinflammation ; 18(1): 230, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645472

RESUMO

BACKGROUND: Astrocytic glycogen works as an essential energy reserve for surrounding neurons and is reported to accumulate excessively during cerebral ischemia/reperfusion (I/R) injury. Our previous study found that accumulated glycogen mobilization exhibits a neuroprotective effect against I/R damage. In addition, ischemia could transform astrocytes into A1-like (toxic) and A2-like (protective) subtypes. However, the underlying mechanism behind accumulated glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury and its relationship with the astrocytic A1/A2 paradigm is unknown. METHODS: Astrocytic glycogen phosphorylase, the rate-limiting enzyme in glycogen mobilization, was specifically overexpressed and knocked down in mice and in cultured astrocytes. The I/R injury was imitated using a middle cerebral artery occlusion/reperfusion model in mice and an oxygen-glucose deprivation/reoxygenation model in cultured cells. Alterations in A1-like and A2-like astrocytes and the expression of phosphorylated nuclear transcription factor-κB (NF-κB) and phosphorylated signal transducer and activator of transcription 3 (STAT3) were determined by RNA sequencing, immunofluorescence and immunoblotting. Metabolites, including glycogen, NADPH, glutathione and reactive oxygen species (ROS), were analyzed by biochemical analysis. RESULTS: Here, we observed that astrocytic glycogen mobilization inhibited A1-like astrocytes and enhanced A2-like astrocytes after reperfusion in an experimental ischemic stroke model in vivo and in vitro. In addition, glycogen mobilization could enhance the production of NADPH and glutathione by the pentose phosphate pathway (PPP) and reduce ROS levels during reperfusion. NF-κB inhibition and STAT3 activation caused by a decrease in ROS levels were responsible for glycogen mobilization-induced A1-like and A2-like astrocyte transformation after I/R. The astrocytic A1/A2 paradigm is closely correlated with glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury. CONCLUSIONS: Our data suggest that ROS-mediated NF-κB inhibition and STAT3 activation are the key pathways for glycogen mobilization-induced neuroprotection and provide a promising metabolic target for brain reperfusion injury in ischemic stroke.

3.
Trends Microbiol ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600784

RESUMO

The complement system has historically been entertained as a fluid-phase, hepatically derived system which protects the intravascular space from encapsulated bacteria. However, there has been an increasing appreciation for its role in protection against non-encapsulated pathogens. Specifically, we have an improved understanding of how pathogens are recognized by specific complement proteins, as well as how they trigger and evade them. Additionally, we have an improved understanding of locally derived complement proteins, many of which promote host defense. Moreover, intracellular complement proteins have been identified that facilitate local protection and barrier function despite pathogen invasion. Our review aims to summarize these advances in the field as well as provide an insight into the pathophysiological changes occurring when the system is dysregulated in infection.

4.
Ageing Res Rev ; 72: 101483, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610479

RESUMO

Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles, is the most common form of dementia worldwide. However, currently, there are no satisfying curative therapies for AD. The blood-brain barrier (BBB) acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. BBB dysfunction as an upstream or downstream event promotes the onset and progression of AD. Moreover, the pathogenesis of AD caused by BBB injury hasn't been well elucidated. Glial cells, BBB compartments and neurons form a minimal functional unit called the neurovascular unit (NVU). Emerging evidence suggests that glial cells are regulators in maintaining the BBB integrity and neuronal function. Illustrating the regulatory mechanism of glial cells in the BBB assists us in drawing a glial-vascular coupling diagram of AD, which may offer new insight into the pathogenesis of AD and early intervention strategies for AD. This review aims to summarize our current knowledge of glial-BBB interactions and their pathological implications in AD and to provide new therapeutic potentials for future investigations.

5.
Behav Neurol ; 2021: 2962792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34580600

RESUMO

Background: Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene polymorphisms are related to a growing risk of Alzheimer's disease; however, whether this association applies to mild cognitive impairment (MCI) remains unclear. Objective: We conducted this meta-analysis to evaluate the contribution of MTHFR C677T (rs1801133) gene variants to the risk of MCI. Methods: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched from their inception to March 21, 2021, with language restricted to English or Chinese. We used fixed or random effects to examine the association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility. Forest plots of pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated. Results: Eight articles with 2,175 participants were included in the present meta-analysis. There was no significant association between MTHFR C677T (rs1801133) gene variants and MCI susceptibility under the allelic (OR, 1.318; 95% CI, 0.964-1.801; p = 0.084), dominant (OR, 1.296; 95% CI, 0.925-1.817; p = 0.132), recessive (OR, 1.397; 95% CI, 0.845-2.312; p = 0.193), heterozygous (OR, 1.031; 95% CI, 0.855-1.243; p = 0.749), or homozygous (OR, 1.506; 95% CI, 0.850-2.667; p = 0.160) models. Conclusion: The results suggest that MTHFR C677T (rs1801133) gene polymorphisms are not associated with MCI susceptibility. However, large-scale studies covering various factors are required.


Assuntos
Disfunção Cognitiva , Metilenotetra-Hidrofolato Redutase (NADPH2) , Disfunção Cognitiva/genética , Predisposição Genética para Doença , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Razão de Chances , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
6.
Front Nutr ; 8: 731356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552957

RESUMO

Frailty is an age-related clinical syndrome that may increase the risk of falls, disability, hospitalization, and death in older adults. Delaying the progression of frailty helps improve the quality of life in older adults. Caloric restriction (CR) may extend lifespan and reduce the risk of age-related diseases. However, few studies have explored the relationship between CR and frailty. In this review, we focused on the impact of CR on frailty and aimed to identify potential associated mechanisms. Although CR may help prevent frailty, further studies are required to determine the underlying mechanisms and specific CR regimens suitable for use in humans.

7.
Percept Mot Skills ; : 315125211044051, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490797

RESUMO

How people encode numbers in the context of multiple overlapping encoded cues remains unclear. In this study, we explored Chinese finger numbers, which contain both a numerical magnitude cue and a left-right hand cue offered by the expressing hand, to investigate the number encoding mechanism in the context of multiple overlapping cues. Chinese finger numbers expressed by the left or right hand were randomly and centrally presented on a computer screen to participants who were asked to perform a hand classification task (Experiment 1), a magnitude classification task (Experiment 2), a parity classification task (Experiment 3) and a magnitude classification or ring classification task (Experiment 4). We discovered (a) only an association effect between the pressed key and the expressing hand in hand classification and parity classification tasks, (b) the SNARC effect only on the magnitude classification task, (c) the association effect between the pressed key and the expressing hand on the larger, Chinese finger number, magnitude classification task in Experiment 2, and (d) the SNARC effect and the association between the pressed key and the expressing hand were reversed on the ring classification task. From these results, we concluded that people can flexibly choose appropriate number encoding cues and how numbers are encoded in the context of multiple overlapping cues depending on (a) which cognition task individuals perform and (b) the character of the numbers involved.

8.
Epigenomics ; 13(18): 1443-1458, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34528440

RESUMO

Aim: The aim of this study was to identify the long noncoding RNAs (lncRNAs) associated with schizophrenia (SZ) and the relationships among their expression, antipsychotic efficacy and SZ severity. Method: The diagnostic and predictive value of nine lncRNAs, Gomafu, DISC2, PSZA11, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2, was investigated in 48 patients with SZ before and after antipsychotic treatment. Results: Gomafu, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2 were individually and collectively associated with, and predictive of, SZ pathogenesis. Moreover, increased expression of plasma AK123097, uc011dma.1 and ENST00000509804-1 levels was reversed after 12 weeks of antipsychotic treatment, which was associated with SZ severity. Conclusion: Seven lncRNAs serve as novel biomarkers for SZ diagnosis and prognosis and three lncRNAs are potential therapeutic targets.

9.
Plant Direct ; 5(9): e343, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34514289

RESUMO

Plant oil production has been increasing continuously in the past decade. There has been significant investment in the production of high biomass plants with elevated oil content. We recently showed that the expression of Arabidopsis thaliana WRI1 and DGAT1 genes increase oil content by up to 15% in leaf dry weight tissue. However, triacylglycerols in leaf tissue are subject to degradation during senescence. In order to better package the oil, we expressed a series of lipid droplet proteins isolated from bacterial and plant sources in Nicotiana benthamiana leaf tissue. We observed further increases in leaf oil content of up to 2.3-fold when we co-expressed Sesamum indicum Oleosin L with AtWRI1 and AtDGAT1. Biochemical assays and lipid droplet visualization with confocal microscopy confirmed the increase in oil content and revealed a significant change in the size and abundance of lipid droplets.

10.
Medicine (Baltimore) ; 100(31): e26736, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397814

RESUMO

BACKGROUND: To explore the effects of psychological nursing on improving the mental health status of young patients with lung cancer surgery during the perioperative period. METHODS: seventy-eight young patients (From February 2018 to February 2019) underwent lung cancer operation were selected. All these patients were randomly allocated to intervention group and control group. The patients in the control group were treated with general routine care. The patients in the intervention group were treated with a comprehensive and systematic family participation psychological nursing. The mental health status of the patients in the 2 groups were compared and analyzed. RESULTS: The self-rating anxiety scale scores and self-rating depression scale scores of patients were significantly reduced in the intervention group compared with the control group (P < .05). The scores of somatization, obsessive symptoms, interpersonal relationship, depression, anxiety, hostile, phobic neurosis, stubborn, paranoia and psychosis were also significantly reduced in the intervention group compared with the control group (P < .05). CONCLUSION: the comprehensive and systematic psychological nursing intervention improved the mental health status of young patients with lung cancer surgery during the perioperative period.


Assuntos
Neoplasias Pulmonares/cirurgia , Saúde Mental/normas , Período Perioperatório/enfermagem , Adulto , Feminino , Humanos , Neoplasias Pulmonares/psicologia , Masculino , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Período Perioperatório/estatística & dados numéricos , Inquéritos e Questionários
11.
Gut Liver ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34446613

RESUMO

Background/Aims: To investigate postpartum hepatic flares and associated factors in highly viremic pregnant patients in the immune tolerance phase who adopted telbivudine (LdT) treatment in the last trimester to reduce vertical transmission of hepatitis B virus. Methods: Hepatitis B e antigen (HBeAg)-positive, highly viremic pregnant women were recruited for this prospective study. Treatment with LdT was started from 28 weeks of gestation. Virological and biochemical markers were examined before LdT treatment, antepartum and postpartum. Serial blood samples at the same time were collected to detect cytokines and cortisol (COR). Results: Fifty-six of 153 patients (36.6%) had postpartum hepatic flares, defined as a 2-fold increase in alanine aminotransferase 6 weeks after delivery. Age and the antepartum alanine aminotransferase and postpartum HBeAg levels were independent influencing factors of postpartum hepatic flares. Cytokines showed no regularity during or after pregnancy. Compared with the patients with no postpartum flares, the patients with flares had lower baseline interferon γ and COR levels (p=0.022 and p=0.028) and higher postpartum interferon γ levels (p=0.026). Conclusions: A high proportion of highly viremic and immune-tolerant pregnant patients treated with LdT in the last trimester had postpartum hepatic flares, which implied that these patients entered the immune clearance phase after delivery. Thus, this may create an appropriate opportunity for re-antiviral therapy.

12.
Front Cell Dev Biol ; 9: 707268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395435

RESUMO

Tau is a protein that associates with microtubules (MTs) and promotes their assembly and stability. The protein loses its ability to bind MTs in tauopathies, and detached tau can misfold and induce the pathological changes that characterize Alzheimer's disease (AD). A growing body of evidence indicates that tauopathies can spread between cells or connected regions. Pathological tau transmission in the brain of patients with AD and other tauopathies is due to the spread of various tau species along neuroanatomically connected regions in a "prion-like" manner. This complex process involves multiple steps of secretion, cellular uptake, transcellular transfer, and/or seeding, but the precise mechanisms of tau pathology propagation remain unclear. This review summarizes the current evidence on the nature of propagative tau species and the possible steps involved in the process of tau pathology spread, including detachment from MTs, degradations, and secretion, and discusses the different mechanisms underlying the spread of tau pathology.

13.
Int J Med Sci ; 18(14): 3309-3317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34400900

RESUMO

Background: Frailty is known to be highly prevalent in older hemodialysis (HD) patients. We studied the prevalence of frailty and its associated factors in Chinese HD patients. We further studied if frailty could predict survival in HD patients. Methods: This is a prospective study involving patients receiving maintenance HD in the dialysis center of Xuanwu Hospital, Beijing. Study subjects were enrolled from October to December, 2017 and followed up for two years. Demographic data, comorbidities and biological parameters were collected. Frailty was assessed using the Fried frailty phenotype at baseline. Cox regression analysis was performed to identify the relationship between frailty and mortality in HD patients. Kaplan-Meier was plotted using the cutoff value obtained by ROC curve to evaluate survival rates in different frailty status. Results: Total of 208 HD patients were enrolled with a mean age of 60.5±12.7 years. According to the frailty criteria, at baseline the prevalence of robust, pre-frail and frail in HD patients was 28.7%, 45.9%, and 25.4%, respectively. The two-year all-cause mortality was 18.8% (39/207) and underlying causes of death included coronary artery disease (CAD), cerebrovascular disease (CVD), hyperkalemia, severe infection, malignant tumor and others. Survival curve showed the patients with frailty score ≥4 to have significantly shorter survival time as compared to patients with frailty score ≤ 3. Frailty predicted two-year mortality when frailty score ≥4 with a sensitivity of 70% and a specificity of 83.67% with an AUC of 0.819. Frailty score was positively associated with age and ratio of ultrafiltration volume to dry weight, while negatively associated with levels of serum albumin, uric acid and diastolic blood pressure after HD. Conclusions: Our results confirm frailty to be very common among HD patients and severity of frailty was a significant predictor of mortality for HD patients. Factors such as age, malnutrition and low blood pressure are the factors to be associated with frailty. Interdialytic weight gain inducing excessive ultrafiltration volume is an important risk factor.

14.
Nat Commun ; 12(1): 4785, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373459

RESUMO

The implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties. One variant, termed THOR-707, selectively engages the IL-2 receptor beta/gamma complex without engagement of the IL-2 receptor alpha. In mice, administration of THOR-707 results in large-scale activation and amplification of CD8+ T cells and NK cells, without Treg expansion characteristic of IL-2. In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating CD8+ T and NK cells, and leads to a dose-dependent reduction of tumor growth. These results support further characterization of the immune modulatory, anti-tumor properties of THOR-707 and represent a fundamental advance in the application of synthetic biology to medicine, leveraging engineered semi-synthetic organisms as cellular factories to facilitate discovery and production of differentiated classes of chemically modified biologics.


Assuntos
Antineoplásicos/uso terapêutico , Interleucina-2/química , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Descoberta de Drogas , Engenharia Genética , Humanos , Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2 , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Linfócitos/efeitos dos fármacos , Camundongos , Biologia Sintética
15.
Front Pediatr ; 9: 707452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336746

RESUMO

Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations. Pathogenic genes are a result of mutations in AVPR2 on chromosome Xq28 and in AQP2 on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by an AVPR2 mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C > T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.

16.
Int J Biol Sci ; 17(9): 2181-2192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239348

RESUMO

Extracellular neuritic plaques composed of amyloid­ß (Aß) protein and intracellular neurofibrillary tangles containing phosphorylated tau protein are the two hallmark proteins of Alzheimer's disease (AD), and the separate neurotoxicity of these proteins in AD has been extensively studied. However, interventions that target Aß or tau individually have not yielded substantial breakthroughs. The interest in the interactions between Aß and tau in AD is increasing, but related drug investigations are in their infancy. This review discusses how Aß accelerates tau phosphorylation and the possible mechanisms and pathways by which tau mediates Aß toxicity. This review also describes the possible synergistic effects between Aß and tau on microglial cells and astrocytes. Studies suggest that the coexistence of Aß plaques and phosphorylated tau is related to the mechanism by which Aß facilitates the propagation of tau aggregation in neuritic plaques. The interactions between Aß and tau mediate cognitive dysfunction in patients with AD. In summary, this review summarizes recent data on the interplay between Aß and tau to promote a better understanding of the roles of these proteins in the pathological process of AD and provide new insights into interventions against AD.

17.
Hum Pathol ; 116: 49-62, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34273395

RESUMO

Severe COVID-19 results in a glucocorticoid responsive form of acute respiratory distress (ARDS)/diffuse alveolar damage (DAD). Herein we compare the immunopathology of lung tissue procured at autopsy in patients dying of SARS-CoV-2 with those dying of DAD prior to the COVID-19 pandemic. Autopsy gross and microscopic features stratified by duration of illness in twelve patients who tested positive for SARS-CoV-2 viral RNA, as well as seven patients dying of DAD prior to the COVID-19 pandemic were evaluated with multiplex (5-plex: CD4, CD8, CD68, CD20, AE1/AE3) and SARS-CoV immunohistochemistry to characterize the immunopathologic stages of DAD. We observed a distinctive pseudopalisaded histiocytic hyperplasia interposed between the exudative and proliferative phase of COVID-19 associated DAD, which was most pronounced at the fourth week from symptom onset. Pulmonary macrothrombi were seen predominantly in cases with pseudopalisaded histiocytic hyperplasia and/or proliferative phase DAD. Neither pseudopalisaded histiocytic hyperplasia nor pulmonary macrothrombi was seen in non-COVID-19 DAD cases, whereas microthrombi were common in DAD regardless of etiology. The inflammatory pattern of pseudopalisaded histiocytic hyperplasia may represent the distinctive immunopathology associated with the dexamethasone responsive form of DAD seen in severe COVID-19.


Assuntos
COVID-19/patologia , Histiócitos/patologia , Pulmão/patologia , Alvéolos Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/fisiologia , Feminino , Humanos , Hiperplasia/patologia , Masculino , Pessoa de Meia-Idade
18.
Inorg Chem ; 60(14): 10698-10706, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34232028

RESUMO

The new indium-based organic framework {(Me2NH2)[In(BDPO)]·DMF·2H2O}n (1) was successfully constructed by using the oxalamide group modified ligand N,N'-bis(isophthalic acid)oxalamide (H4BDPO). This framework presents a 2-fold interpenetrating structural characteristic, and the unique polar pore environment leads to a high capture ability for CO2, C2Hn and CH3OH and good separation ability for CO2 and C2Hn over CH4 as well as for CH3OH over C2H5OH, which was further verified by an ideal adsorbed solution theory (IAST) calculation. Theoretical simulations pointed out the possible adsorption sites of different adsorbed gases in 1. In addition, the excellent chemical stability and strong luminescence of 1 give it an effective selective detection ability for 2,6-dichloro-4-nitroaniline (DCN) in water with a low detection limit of 3.85 ppm, and the detection mechanism is discussed in detail.

19.
Aging (Albany NY) ; 13(14): 18191-18222, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289449

RESUMO

This investigation attempted to discern whether formononetin restrained progression of triple-negative breast cancer (TNBC) by blocking lncRNA AFAP1-AS1-miR-195/miR-545 axis. We prepared TNBC cell lines (i.e. MDA-MB-231 and BT-549) and normal human mammary epithelial cell line (i.e. MCF-10A) in advance, and the TNBC cell lines were, respectively, transfected by pcDNA3.1-lncRNA AFAP1-AS1, si-lncRNA AFAP1-AS1, pcDNA6.2/GW/EmGFP-miR-545 or pcDNA6.2/GW/EmGFP-miR-195. Resistance of TNBC cells in response to 5-Fu, adriamycin, paclitaxel and cisplatin was evaluated through MTT assay, while potentials of TNBC cells in proliferation, migration and invasion were assessed via CCK8 assay and Transwell assay. Consequently, silencing of lncRNA AFAP1-AS1 impaired chemo-resistance, proliferation, migration and invasion of TNBC cells (P<0.05), and over-expression of miR-195 and miR-545, which were sponged and down-regulated by lncRNA AFAP1-AS1 (P<0.05), significantly reversed the promoting effect of pcDNA3.1-lncRNA AFAP1-AS1 on proliferation, migration, invasion and chemo-resistance of TNBC cells (P<0.05). Furthermore, CDK4 and Raf-1, essential biomarkers of TNBC progression, were, respectively, subjected to target and down-regulation of miR-545 and miR-195 (P<0.05), and they were promoted by pcDNA3.1-lncRNA AFAP1-AS1 at protein and mRNA levels (P<0.05). Additionally, formononetin significantly decreased expressions of lncRNA AFAP1-AS1, CDK4 and Raf-1, while raised miR-195 and miR-545 expressions in TNBC cells (P<0.05), and exposure to it dramatically contained malignant behaviors of TNBC cells (P<0.05). In conclusion, formononetin alleviated TNBC malignancy by suppressing lncRNA AFAP1-AS1-miR-195/miR-545 axis, suggesting that molecular targets combined with traditional Chinese medicine could yield significant clinical benefits in TNBC.

20.
BMC Health Serv Res ; 21(1): 656, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225721

RESUMO

OBJECTIVES: The aim of this study is to address the difficulties encountered by public health workers in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. METHODS: Using multi-stage sampling, a survey of public health workers involved in the prevention and control of COVID-19 was conducted from 18 February to 1 March 2020 through a self-administered questionnaire. These public health workers were from the primary health care center (defined as "primary-urban" and "primary-rural" for those in urban and rural areas, respectively) and the center for disease control and prevention (defined as "non-primary") in five provinces including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, China. RESULTS: A total of 9,475 public health workers were surveyed, of which 40.0 %, 27.0 % and 33.0 % were from the primary-rural, primary-urban and non-primary, respectively. The resources shortage were reported by 27.9 % participants, with the primary-rural being the worst affected (OR = 1.201, 95 %CI: 1.073-1.345). The difficulties in data processing were reported by 31.5 % participants, with no significant differences among institutions. The difficulties in communication and coordination were reported by 29.8 % participants, with the non-primary being the most serious (primary-rural: OR = 0.520, 95 %CI: 0.446-0.606; primary-urban: OR = 0.533, 95 %CI: 0.454-0.625). The difficulties with target audiences were reported by 20.2 % participants, with the primary-urban being the worst (OR = 1.368, 95 %CI: 1.199-1.560). The psychological distress were reported by 48.8 % participants, with no significant differences among institutions. CONCLUSIONS: Psychological distress is the most serious problem in the prevention and control of COVID-19. Resources shortage in primary-rural, difficulties in communication and coordination in non-primary, and difficulties with target audiences in the primary-urban deserve attention. This study will provide scientific evidences for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.


Assuntos
COVID-19 , Saúde Pública , China/epidemiologia , Estudos Transversais , Surtos de Doenças/prevenção & controle , Humanos , SARS-CoV-2 , Inquéritos e Questionários
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