RESUMO
The need for photosensors and gas sensors arises from their pivotal roles in various technological applications, ensuring enhanced efficiency, safety, and functionality in diverse fields. In this paper, interlinked PbS/Sb2O5thin film has been synthesized by a magnetron sputtering method. We control the temperature to form the nanocomposite by using their different nucleation temperature during the sulfonation process. A nanostructured PbS/Sb2O5with cross-linked morphology was synthesized by using this fast and efficient method. This method has also been used to grow a uniform thin film of nanocomposite. The photo-sensing and gas-sensing properties related to the PbS/Sb2O5compared with those of other nanomaterials have also been investigated. The experimental and theoretical calculations reveal that the PbS/Sb2O5exhibits extraordinarily superior photo-sensing and gas-sensing properties in terms of providing a pathway for electron transport to the electrode. The attractive highly sensitive photo and gas sensing properties of PbS/Sb2O5make them applicable for many different kinds of applications. The responsivity and detectivity of PbS/Sb2O5are 0.28 S/mWcm-2and 1.68 × 1011Jones respectively. The sensor response towards NO2gas was found to be 0.98 at 10 ppb with an limit of detection (LOD) of 0.083 ppb. The PbS/Sb2O5exhibits high selectivity towards the NO2gas. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were used to analyze the geometries, electronic structure, and electronic absorption spectra of a light sensor fabricated by PbS/Sb2O5. The results are very analogous to the experimental results. Both photosensors and gas sensors are indispensable tools that contribute significantly to the evolution of technology and the improvement of various aspects of modern life.
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Learned resourcefulness is a broad and abstract concept that refers to the ability to use self-observation and self-control to change internal negative feelings, emotions, or thoughts to reduce the adverse effects of stress on emotions and behavior. Excessive stress negatively affects the physical and mental health of individuals, and learned resourcefulness can help alleviate the effects of stress. Nursing measures implemented in a timely manner to enhance patients' self-regulation ability and improve their mental and physical stability are important. In this article, based on the concept analysis method of Walker and Avant (2019), the defining characteristics of learned resourcefulness are summarized as: (1) self-control ability, (2) problem-solving skills, and (3) belief in one's ability to cope effectively with adverse situations. These characteristics are illustrated in case examples, providing empirical reference indicators and introducing the application of nursing research and practice. It is hoped that this article will help nursing colleagues understand learned resourcefulness and provide a reference for clinical assessment and the development of related intervention measures.
Assuntos
Adaptação Psicológica , Aprendizagem , Humanos , Formação de Conceito , EmoçõesRESUMO
We evaluated the ability of extracorporeal shock wave (ECSW)-assisted melatonin (Mel) therapy to offer an additional benefit for alleviating the neuropathic pain (NP) in rats. Left sciatic nerve was subjected to chronic constriction injury (CCI) to induce NP. Animals (n = 30) were randomized into group 1 (sham-operated control), group 2 (CCI only), group 3 (CCI + ECSW), group 4 (CCI + Mel) and group 5 (CCI + ECSW + Mel). By days 15, 22 and 29 after CCI, the thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but they showed no difference between the later two groups (all p < 0.0001). The protein expressions of inflammatory (TNF-α, NF-κB, MMP-9, IL-1ß), oxidative-stress (NOXs-1, -2, -4, oxidized protein), apoptotic (cleaved-caspase3, cleaved-PARP), DNA/mitochondrial-damaged (γ-H2AX/cytosolic-cytochrome C), microglia/astrocyte activation (ox42/GFAP), and MAPKs [phosphorylated (p)-p38, p-JNK, p-ERK] biomarkers in dorsal root ganglia neurons (DRGs) and in spinal dorsal horn were exhibited an opposite pattern of TPWL among the five groups (all p < 0.0001). Additionally, protein expressions of Nav.1.3, Nav.1.8 and Nav.1.9 in sciatic nerve exhibited an identical pattern to inflammation among the five groups (all p < 0.0001). The numbers of cellular expressions of MAPKs (p-ERK1/2+/peripherin + cells, p-ERK1/2+/NF200 + cells and p-JNK+/peripherin + cells, p-JNK+/NF200 + cells) and voltage-gated sodium channels (Nav.1.8+/peripherin + cells, Nav.1.8+/NF200 + cells, Nav.1.9+/peripherin + cells, Nav.1.9+/NF200 + cells) in small and large DRGs displayed an identical pattern to inflammation among the five groups (all p < 0.0001). In conclusion, the synergistic effect of combined ECSW-Mel therapy is superior to either one alone for long-term improvement of mononeuropathic pain-induced by CCI in rats.
Assuntos
Antioxidantes/administração & dosagem , Tratamento por Ondas de Choque Extracorpóreas/métodos , Melatonina/administração & dosagem , Neuralgia/metabolismo , Neuralgia/terapia , Limiar da Dor/efeitos dos fármacos , Animais , Masculino , Neuralgia/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Limiar da Dor/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Resultado do TratamentoRESUMO
The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Polissacarídeos/farmacologia , Xantofilas/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Insulina/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Camundongos , Peso Molecular , PPAR gama/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Helicobacter pylori inhabits the gastric mucosa where it senses and responds to various stresses via a two-component systems (TCSs) that enable its persistent colonization. The aim of this study was to investigate whether any of the three paired TCSs (ArsRS, FleRS and CrdRS) in H. pylori respond to nitrosative stress. The results showed that the expression of crdS was significantly increased upon exposure to nitric oxide (NO). crdS-knockout (ΔcrdS) and crdR/crdS-knockout (ΔcrdRS) H. pylori, but not arsS-knockout (ΔarsS) or fleS-knockout (ΔfleS) H. pylori, showed a significant loss of viability upon exposure to NO compared with wild-type strain. Knockin crdS (ΔcrdS-in) significantly restored viability in the presence of NO. Global transcriptional profiling analysis of wild-type and ΔcrdS H. pylori in the presence or absence of NO showed that 101 genes were differentially expressed, including copper resistance determinant A (crdA), transport, binding and envelope proteins. The CrdR binding motifs were investigated by competitive electrophoretic mobility shift assay, which revealed that the two AC-rich regions in the crdA promoter region are required for binding. These results demonstrate that CrdR-crdA interaction enables H. pylori to survive under nitrosative stress.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Helicobacter pylori/metabolismo , Óxido Nítrico/metabolismo , Estresse Fisiológico , Sequência de Bases , Cobre/metabolismo , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Helicobacter pylori/genética , Dados de Sequência Molecular , Regiões Promotoras GenéticasRESUMO
The amount of monocyte chemoattractant protein-1 (MCP-1/CCL2) produced by a transitional cell carcinoma is directly correlated with high recurrence and poor prognosis in bladder cancer. However, the mechanisms underlying the effects of CCL2 on tumor progression remain unexplored. To investigate the role played by CCL2, we examined cell migration in various bladder cancer cell lines. We found that high-grade cancer cells expressing high levels of CCL2 showed more migration activity than low-grade bladder cancer cells expressing low levels of the chemokine. Although the activation of CCL2/CCR2 signals did not appreciably affect cell growth, it mediated cell migration and invasion via the activation of protein kinase C and phosphorylation of tyrosine in paxillin. Blocking CCL2 and CCR2 with small hairpin RNA (shCCL2) or a specific inhibitor reduced CCL2/CCR2-mediated cell migration. The antagonist of CCR2 promoted the survival of mice bearing MBT2 bladder cancer cells, and CCL2-depleted cells showed low tumorigenicity compared with shGFP cells. In addition to observing high-levels of CCL2 in high-grade human bladder cancer cells, we showed that the CCL2/CCR2 signaling pathway mediated migratory and invasive activity, whereas blocking the pathway decreased migration and invasion. In conclusion, high levels of CCL2 expressed in bladder cancer mediates tumor invasion and is involved with advanced tumorigenesis. Our findings suggest that this CCL2/CCR2 pathway is a potential candidate for the attenuation of bladder cancer metastases.
Assuntos
Comunicação Autócrina , Movimento Celular , Quimiocina CCL2/metabolismo , Paxilina/metabolismo , Fosfotirosina/metabolismo , Proteína Quinase C/metabolismo , Neoplasias da Bexiga Urinária/patologia , Animais , Comunicação Autócrina/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Quimiocina CCL2/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Receptores CCR2/antagonistas & inibidores , Receptores CCR2/metabolismo , Neoplasias da Bexiga Urinária/enzimologiaRESUMO
BACKGROUND: Little is known about the characteristics of patients needing palliative care consultation in the emergency department (ED). This study aimed to investigate the impacts of initiating screening in acute critically ill patients needing palliative care on mortality, health care resources, and end-of-life (EOL) care in the intensive care unit in ED (EICU). METHODS: We conducted an analysis study in Taipei Veterans General Hospital. From February 1 to July 31, 2018, acute critically ill patients in EICU were recruited. The primary outcomes were inhospital mortality and EOL care. The secondary outcomes included clinical characteristics and health care utilization. RESULTS: A total of 796 patients were screened, with 396 eligible and 400 noneligible patients needing palliative care consultations. The mean age was 74.8 ± 17.1 years, and 62.6% of the patients were male. According to logistic regression analysis, clinical predictors, including age (adjusted odds ratio [AOR], 1.028; 95% CI, 1.015-1.042), respiratory distress and/or respiratory failure (AOR, 2.670; 95% CI, 1.829-3.897), the Acute Physiology and Chronic Health Evaluation II score (AOR, 1.036; 95% CI, 1.009-1.064), Charlson Comorbidity Index score (AOR, 1.212; 95% CI, 1.125-1.306), and Glasgow Coma Scale (AOR, 0.843; 95% CI, 0.802-0.885), were statistically more significant in eligible patients than in noneligible patients. The inhospital mortality rate was significantly higher in eligible patients than that in noneligible patients (40.7% vs 11.5%, p < 0.01). Eligible patients have a higher ratio in both vasopressor and narcotic use and withdrawal of endotracheal tube than noneligible patients (p < 0.05). CONCLUSION: Our study results demonstrated that initiating palliative consultation for acute critically ill patients in ED had an impact on the utilization of health care resources and quality of EOL care. Further assessments of the viewpoints of ED patients and their family on palliative care consultations and hospice care are required.
Assuntos
Estado Terminal , Serviço Hospitalar de Emergência , Unidades de Terapia Intensiva , Cuidados Paliativos , Encaminhamento e Consulta , Idoso , Idoso de 80 Anos ou mais , Feminino , Cuidados Paliativos na Terminalidade da Vida , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The aim of this study was to explore the relationship between changes in prehospital blood pressure (BP) and the incidence of early neurological deterioration (END) after spontaneous intracerebral hemorrhage (SICH) in patients who arrive at the emergency department (ED) with a normal Glasgow Coma Scale (GCS) score. Records of consecutive adults with SICH transported by ambulance and treated in our ED from January 2015 to December 2017 were retrospectively reviewed. The study cohort included all patients with SICH occurring within the previous 6 hr who had a normal GCS score on ED arrival. Detailed information was retrieved from our hospital's intracerebral hemorrhage databank and then cross-checked in the medical and nursing charts to confirm completeness and accuracy. Early neurological deterioration was defined as a decrease of 2 or more points in the GCS score within 6 hr after ED arrival. The change in prehospital BP was defined as the BP on ED arrival minus the initial on-scene BP. An association between a change in prehospital BP and the occurrence of END was assessed by univariate and multivariate analyses (multiple logistic regression analysis). Of the 168 patients evaluated, 36 (21.4%) developed END. Factors associated with END on univariate analysis were regular antiplatelet agent use, shorter elapsed time, on-scene systolic blood pressure (SBP), prehospital SBP increase of 15 mmHg or more, intraventricular extension of the hematoma, and the presence of 3 or more noncontrast computed tomographic signs of hematoma expansion. After adjusting for other covariates, an increase in prehospital SBP of 15 mmHg or more was significantly associated with a higher risk of END. In patients with SICH who arrive at the ED with a normal GCS score, an increase in the prehospital SBP of more than 15 mmHg is associated with a higher incidence of END.
Assuntos
Pressão Sanguínea/fisiologia , Hemorragia Cerebral/fisiopatologia , Idoso , Determinação da Pressão Arterial , Progressão da Doença , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Estudos RetrospectivosRESUMO
Bioconversion is useful to produce optically pure enantiomers in the pharmaceutical industry, thereby avoiding problems with side reactions during organic synthesis processes. A short-chain dehydrogenase/reductase from Serratia marcescens BCRC 10948 (SmSDR) can stereoselectively convert 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) into (R)-phenylephrine [(R)-PE], which is marketed medically as a nasal decongestant agent. The whole-cell conversion process for the synthesis of (R)-PE using SmSDR was reported to have an unexpectedly low conversion rate. We reported the crystal structure of the SmSDR and designed profitable variants to improve the enzymatic activity by structure-guided approach. Several important residues in the structure were observed to form hydrophobic clusters that stabilize the mobile loops surrounding the pocket. Of these, Phe98 and Phe202 face toward each other and connect the upper curvature from the two arms (i.e., the α7 helix and loopß4-α4). The mutant structure of the double substitutions (F98YF202Y) exhibited a hydrogen bond between the curvatures that stabilizes the flexible arms. Site-directed mutagenesis characterization revealed that the mutations (F98Y, F98YF202Y, and F98YF202L) of the flexible loops that stabilize the region exhibited a higher transformation activity toward HPMAE. Together, our results suggest a robust structure-guided approach that can be used to generate a valuable engineered variant for pharmaceutical applications.
Assuntos
Fenilefrina/metabolismo , Serratia marcescens/enzimologia , Redutases-Desidrogenases de Cadeia Curta/química , Redutases-Desidrogenases de Cadeia Curta/metabolismo , Biotransformação , Cristalografia por Raios X , Análise Mutacional de DNA , Engenharia Metabólica , Modelos Moleculares , Conformação Proteica , Serratia marcescens/genética , Redutases-Desidrogenases de Cadeia Curta/genética , Simpatomiméticos/metabolismoRESUMO
Proinflammatory responses eliciting the microglial production of cytokines and nitric oxide (NO) have been reported to play a crucial role in the acute and chronic pathogenic effects of neurodegeneration. Chemical inhibitors of cyclin-dependent kinases (CDKs) may prevent the progression of neurodegeneration by both limiting cell proliferation and reducing cell death. However, the mechanism underlying the protective effect of CDK inhibitors on microglia remains unexplored. In this study, we found that olomoucine, a CDK inhibitor, alleviated lipopolysaccharide (LPS)-induced BV2 microglial cell death by reducing the generation of NO and inhibiting the gene expression of proinflammatory cytokines. In addition, olomoucine reduced inducible NO synthase promoter activity and alleviated NF-κB- and E2F-mediated transcriptional activation. NO-induced cell death involved mitochondrial disruptions such as cytochrome c release and loss of mitochondrial membrane potential, and pretreatment with olomoucine prior to NO exposure reduced these disruptions. Microarray analysis revealed that olomoucine treatment induced prominent down-regulation of Bcl2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a pro-apoptotic Bcl-2 family protein that is involved in mitochondrial disruption. As BNIP3 knock-down significantly increased the viability of LPS- and NO-treated BV2 cells, we conclude that olomoucine may protect cells by limiting proinflammatory responses, thereby reducing NO generation. Simultaneously, down-regulation of BNIP3 prevents NO stimulation from inducing mitochondrial disruption.
Assuntos
Apoptose/efeitos dos fármacos , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inflamação/metabolismo , Cinetina/administração & dosagem , Proteínas de Membrana/metabolismo , Microglia/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Óxido Nítrico/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Regulação para Baixo , Fatores de Transcrição E2F/metabolismo , Inibidores Enzimáticos/administração & dosagem , Inflamação/induzido quimicamente , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Camundongos , Microglia/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
A feature of allergic airway disease is the observed increase of nitric oxide (NO) in exhaled breath. Gram-negative bacterial infections have also been linked with asthma exacerbations. However, the role of NO in asthma exacerbations with gram-negative bacterial infections is still unclear. In this study, we examined the role of NO in lipopolysaccharide (LPS)-induced inflammation in an ovalbumin (OVA)-challenged mouse asthma model. To determine whether NO affected the LPS-induced response, a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) or a selective inhibitor of NO synthase (1400W) was injected intraperitoneally into the mice before the LPS stimulation. Decreased levels of proinflammatory cytokines were demonstrated in the bronchoalveolar lavage fluid from mice treated with SNAP, whereas increased levels of cytokines were found in the 1400W-treated mice. To further explore the molecular mechanism of NO-mediated inhibition of proinflammatory responses in macrophages, RAW 264.7 cells were treated with 1400W or SNAP before LPS stimulation. LPS-induced inflammation in the cells was attenuated by the presence of NO. The LPS-induced IκB kinase (IKK) activation and the expression of IKK were reduced by NO through attenuation of the interaction between Hsp90 and IKK in the cells. The IKK decrease in the lung immunohistopathology was verified in SNAP-treated asthma mice, whereas IKK increased in the 1400W-treated group. We report for the first time that NO attenuates the interaction between Hsp90 and IKK, decreasing the stability of IKK and causing the down-regulation of the proinflammatory response. Furthermore, the results suggest that NO may repress LPS-stimulated innate immunity to promote pulmonary bacterial infection in asthma patients.
Assuntos
Asma/prevenção & controle , Proteínas de Choque Térmico HSP90/fisiologia , Quinase I-kappa B/fisiologia , Inflamação/prevenção & controle , Óxido Nítrico/farmacologia , Óxido Nítrico/uso terapêutico , Transdução de Sinais/fisiologia , Animais , Asma/induzido quimicamente , Asma/fisiopatologia , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Iminas/farmacologia , Iminas/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase/antagonistas & inibidores , Ovalbumina/efeitos adversos , S-Nitroso-N-Acetilpenicilamina/farmacologia , S-Nitroso-N-Acetilpenicilamina/uso terapêutico , Transdução de Sinais/efeitos dos fármacosRESUMO
A series of lithium and sodium iminophenoxide complexes have been successfully synthesized and characterized by X-ray crystallography and investigated as catalysts for the ring opening polymerization of L-lactide. The nature and steric bulk of the ligands coordinated to the central metal ions greatly influence the catalytic properties. Complexes with bidenate ligands exhibit higher catalytic activity than tridentate counterparts because the third coordination atom contends with L-lactide, which decreases activity. Oxygen is the third atom in the tridentate ligand, providing stronger chelation ability with Li and Na than nitrogen or sulfur and occupies the space with which L-lactide is coordinated.