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This study successfully designed and synthesized two nonfused ring electron acceptors, 412-6F and 412-6Cl, modified with fluorine and chlorine substituents, respectively. Single-crystal analysis revealed that 412-6F possesses a planar molecular backbone and exhibits pronounced dipole-dipole interactions between the fluorine atoms on the lateral phenyl groups and the carbonyl oxygen atoms on the end groups. This specific interaction promotes dense end-group stacking, leading to a reduced interlayer spacing. Improved crystallinity and coherence length are observed in the D18:412-6F blend film. Conversely, 412-6Cl adopts a more distorted configuration and lacks these interactions. As a result, the organic solar cell (OSC) based on D18:412-6F achieved a remarkable power conversion efficiency of 18.03%, surpassing the performance of the D18:412-6Cl OSC. This underscores the importance of designing novel acceptors with beneficial intermolecular interactions to enhance OSC efficiency, thus providing a new direction for organic photovoltaic advancement.
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Motivated by simplifying the synthesis of nonfullerene acceptor and establishing the relation between molecular structure and photovoltaic performance, two isomeric nonfused ring electron acceptors (o-TT-Cl and m-TT-Cl), whose properties can be adjusted by changing the side chains, are designed and synthesized with several high-yield steps. o-TT-Cl with V-shaped side chain induces a dominated J-aggregation and displays much better solubility and more ordered packing than m-TT-Cl with linear side chain. Thus, the o-TT-Cl-based blend film generates better phase morphology and charge transport than m-TT-Cl-based one. Finally, the power conversion efficiency of o-TT-Cl-based devices is 12.84%, which is much higher than that of m-TT-Cl-based ones (6.54%). This work highlights the importance of side chains engineering on improving photovoltaic performance of nonfused ring electron acceptors.
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BACKGROUND: To date, universally accepted preventive measures for contrast-induced acute kidney injury (CI-AKI) do not exist, and they warrant further research. OBJECTIVE: The purpose of this study was to evaluate the efficacy of vitamins, including vitamin C and E, for prevention of CI-AKI. METHODS: We electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome of interest was the incidence of CI-AKI. RESULTS: A total of 19 studies were included in this meta-analysis. Pooled analysis showed that vitamin C plus saline [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49-0.82, p = 0.0005] and vitamin E plus saline (RR = 0.39, 95% CI 0.24-0.62, p < 0.0001) significantly reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C plus saline was further confirmed by trial sequential analysis (TSA). However, TSA indicated that more trials are required to confirm the efficacy of vitamin E plus saline. There was no significant difference in preventing CI-AKI between vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47-1.71, p = 0.75), between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30-1.30, p = 0.20), as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49-1.92, p = 0.93). CONCLUSIONS: Vitamin C plus saline administration is effective at reducing the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context is encouraging, but more trials are required. Furthermore, this meta-analysis and TSA indicated insufficient power to draw a definitive conclusion on the effect of vitamin C plus NAC, versus saline or NAC alone, which needs to be explored further.
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Injúria Renal Aguda/prevenção & controle , Ácido Ascórbico/administração & dosagem , Meios de Contraste/efeitos adversos , Vitamina E/administração & dosagem , Acetilcisteína/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Humanos , Incidência , Cloreto de Sódio/uso terapêuticoRESUMO
PTPRA is reported to be involved in cancer development and progression through activating the Src family kinase (SFK) signaling pathways, however, the roles of PTPRA in the squamous cell lung cancer (SCC) development are unclear. The purpose of this study was to clarify the clinical relevance and biological roles of PTPRA in SCC. We found that PTPRA was upregulated in squamous cell lung cancer compared to matched normal tissues at the mRNA (N=20, P=0.004) and protein expression levels (N=75, P<0.001). Notably, high mRNA level of PTPRA was significantly correlated with poorer prognosis in 675 SCC patients from the Kaplan-Meier plotter database. With 75 cases, we found that PTPRA protein expression was significantly correlated with tumor size (P=0.002), lymph node metastasis (P=0.008), depth of tumor invasion (P<0.001) and clinical stage (P<0.001). The Kaplan-Meier plot suggested that high expression of PTPRA had poorer overall survival in SCC patients (P=0.009). Multivariate Cox regression analysis suggested that PTPRA expression was an independent prognostic factor in SCC patients. In the cellular models, PTPRA promotes SCC cell proliferation through modulating Src activation as well as cell cycle progression. In conclusion, higher PTPRA level was associated with worse prognosis of SCC patients and PTPRA could promote the cell cycle progression through stimulating the c-Src signaling pathways.
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Neoplasias Pulmonares/genética , Neoplasias de Células Escamosas/genética , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores/genética , Quinases da Família src/genética , Idoso , Proteína Tirosina Quinase CSK , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/patologia , Prognóstico , RNA Mensageiro/genética , Transdução de SinaisRESUMO
The traditional method to establish a cardiovascular disease model induced by high fat and high cholesterol diets is time consuming and laborious and may not be appropriate in all circumstances. A suitable pig model to study metabolic disorders and subsequent atherosclerosis is not currently available. For this purpose, we applied the CRISPR/Cas9 system to Bama minipigs, targeting apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) gene simultaneously. Six biallelic knockout pigs of these two genes were obtained successfully in a single step. No off-target incidents or mosaic mutations were detected by an unbiased analysis. Serum biochemical analyses of gene-modified piglets showed that the levels of low density lipoprotein choleserol (LDL-C), total cholesterol (TC) and apolipoprotein B (APOB) were elevated significantly. This model should prove valuable for the study of human cardiovascular disease and related translational research.
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Apolipoproteínas E/genética , Sistemas CRISPR-Cas/genética , Eletroforese em Gel de Ágar/métodos , Técnicas de Inativação de Genes/métodos , Hipercolesterolemia/metabolismo , Lipoproteínas LDL/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Animais , Modelos Animais de Doenças , Humanos , Suínos , TransfecçãoRESUMO
BACKGROUND: The effects of early renal replacement therapy (RRT) on mortality and renal recovery in patients with acute kidney injury (AKI) remain controversial. A systematic review and meta-analysis of randomized-controlled trials (RCTs) was performed. METHODS: MEDLINE, EMBASE and the Cochrane Library database (Cochrane Central Register of Controlled Trials) were searched to identify RCTs, investigating the effects of early RRT on patients with AKI. RESULTS: Six studies with a total of 1257 participants were included in this meta-analysis. Compared to late RRT, early RRT did not reduce the risk of mortality (RR 0.93, 95 % CI 0.68-1.26) or affect renal recovery (RR 0.88, 95 % CI 0.48-1.62) or composite endpoint (death or dialysis dependence) (RR 0.91, 95 % CI 0.71-1.17). There was no significant difference in adverse events in the analysis, between the early RRT and late RRT arms. CONCLUSIONS: Early initiation of RRT for patients with AKI is not associated with decreased overall mortality or a delayed renal recovery rate. The optimal time to initiate RRT remains uncertain. Large scale and adequately powered RCTs are needed to detect the effects of early initiation of RRT in AKI patients.
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Injúria Renal Aguda/terapia , Rim/fisiopatologia , Terapia de Substituição Renal , Tempo para o Tratamento , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Terapia de Substituição Renal/efeitos adversos , Terapia de Substituição Renal/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The aims of this study were to determine if Thioredoxin reductase (TR) is detected in the serum, and to establish the sensitivity and specificity of serum TR for diagnosing prostate cancer (PC). We assessed serum TR in 380 participants in the training cohort: 160 patients with PC, 120 with benign prostatic hyperplasia and 100 healthy individuals. The validation cohort comprised 320 participants: 120 with PC, 100 with BPH and 100 healthy individuals. TR was measured in serum by ELISA by independent researchers. The patients with PC were graded using the Gleason system. Receiver operating characteristic (ROC) curves were utilized to evaluate the accuracy of biomarkers to diagnose PC. The influence of serum levels of TR on tumor grade and metastasis was performed by binary logistic regression analysis. The median levels of serum TR in PC were significantly higher than that of healthy subjects and patients with BPH (P < 0.0001). Based on the ROC curve, the optimal cutoff value of serum TR levels as an indicator for auxiliary diagnosis of PC from BPH was projected to be 8.2 U/ml, which yielded a sensitivity of 81.8% and a specificity of 68.9%, with the area under the curve at 0.862 (95% CI, 0.821-0.903). Combined model (TR and PSA) showed a significantly greater discriminatory ability as compared with those markers alone. In regression analysis, after adjusting for other significant predictors, TR remained an independent metastasis predictor with an adjusted OR of 4.99 (95% CI, 2.64-8.09). Similarly, TR also was an independent High-grade tumors (HGT) predictor with an adjusted OR of 5.15 (95% CI, 2.52-9.14). Our study has demonstrated the additional benefit of TR measurement in the diagnosis of PC in the Chinese population. Further studies of the application of TR in this region may be beneficial.
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Although there is more evidence that shows that IFNs (interferons) plays a very important role in the early development of the embryo, the mechanism of IFNs is still unclear. Our study showed that IFRG is expressed from oocytes- through to the preimplantation embryo in rabbits. This finding provides some clues for better understanding the role of IFNs in the development of the embryo. The full length of rabbit IFRG cDNA (Accession No. AJ584672), with a 2794bp encoding 131 amino acid sequence, was cloned IFRG expression can be detected in 8 different tissues: ovary, heart, lung, liver, kidney, spleen, cerebra, and the 18-day whole-body embryo. Whole-mount in situ hybridization showed that IFRG was highly expressed in the inner-cell mass of rabbit blastula. IFRG may play an important role in embryo development and tissue differentiation.
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Blastocisto/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genes Controladores do Desenvolvimento/efeitos dos fármacos , Interferons/farmacologia , Oócitos/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Sequência de Bases , Blastocisto/metabolismo , Clonagem Molecular , DNA Complementar/isolamento & purificação , Dados de Sequência Molecular , Oócitos/metabolismo , RNA Mensageiro/metabolismo , CoelhosRESUMO
OBJECTIVE: To explore the expression of transforming growth factor-beta(1) (TGF-beta1) in penile tissue from rats after bilateral cavernosal nerve (CN) ablation, mimicking patients who have had no nerve-sparing during prostatectomy. MATERIALS AND METHODS: Ten adult male rats (neurectomy group) had a bilateral CN resection aseptically under an operating microscope, with six sham-operated rats as controls. Fifteen weeks after surgery an apomorphine test was used in all rats to assess penile erection. The penile specimens were then collected and prepared for detecting the expression of TGF-beta1 by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry, and for quantitative analysis of the ratio of smooth muscle to collagen fibres in the corpus cavernosum with confocal microscopy. RESULTS: All rats in the sham-operated group but none after neurectomy had an erectile response after subcutaneous injection with apomorphine (100 micro g/kg). Immunohistochemistry, RT-PCR and western blot analyses showed a significantly higher expression of TGF-beta1 in the penile tissues after neurectomy than after sham surgery. Smooth muscle cells (fluorescing red) and collagen fibres (green autofluorescence) after paraformaldehyde fixation, were clearly identified by confocal microscopy. The fluorescence intensity expressed as the mean (sem) ratio of smooth muscle to collagen fibres in the corpus cavernosum after neurectomy was 0.265 (0.125), significantly lower than that in the sham-operated group, at 0.760 (0.196) (P < 0.01). CONCLUSION: An increased expression of TGF-beta1 in penile tissue which promotes the synthesis of collagen may be one of the important factors for the erectile dysfunction caused by bilateral CN ablation. Similar pathophysiological processes may occur in the corpus cavernosum of patients after radical prostatectomy.