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Solid-state lithium-sulfur batteries have shown prospects as safe, high-energy electrochemical storage technology for powering regional electrified transportation. Owing to limited ion mobility in crystalline polymer electrolytes, the battery is incapable of operating at subzero temperature. Addition of liquid plasticizer into the polymer electrolyte improves the Li-ion conductivity yet sacrifices the mechanical strength and interfacial stability with both electrodes. In this work, we showed that by introducing a spherical hyperbranched solid polymer plasticizer into a Li+ -conductive linear polymer matrix, an integrated dynamic cross-linked polymer network was built to maintain fully amorphous in a wide temperature range down to subzero. A quasi-solid polymer electrolyte with a solid mass content >90 % was prepared from the cross-linked polymer network, and demonstrated fast Li+ conduction at a low temperature, high mechanical strength, and stable interfacial chemistry. As a result, solid-state lithium-sulfur batteries employing the new electrolyte delivered high reversible capacity and long cycle life at 25 °C, 0 °C and -10 °C to serve energy storage at complex environmental conditions.
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A simple and efficient one-pot oxidation synthesis of N-1-piperidonyl amides was successfully developed through the double oxidation of hydrazides (involving hydrazonium formation, azodioxy-carbonyl compounds generation, and α-carbon oxidation) by using meta-chloroperbenzoic acid (mCPBA). The convenient oxidation method was also extended to Rimonabant analogue. The lactam oxidized Rimonabant analogue was first successfully synthesized for demonstrating the construction and characterized by NMR spectroscopic methods and the single-crystal X-ray diffraction study (ORTEP).
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As two stable hydrogen isotopes, protium and deuterium show magnified isotope effects in physicochemical properties due to the significantly varied atomic masses. In this work, aqueous electrolytes based on heavy water (D2 O) and light water (H2 O) were prepared to reveal the electrochemical isotope effects between the hydrogen isotopes. The covalent hydrogen-oxygen bond and intermolecular hydrogen bond in D2 O are much stronger than those in H2 O, making them thermodynamically more stable. Compared with the H2 O-based electrolyte, the D2 O-based electrolyte shows a broader electrochemical window, a higher percentage of coordinated water and a longer lifetime of hydrogen bond. Because of the above electrochemical isotope effects, the D2 O-based electrolyte shows high anodic stability against operation of high-voltage layered oxide cathode materials including LiCoO2 and LiNi0.8 Co0.1 Mn0.1 O2 , which enables long cycle life and favorable rate performance of aqueous Li-ion batteries.
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Various prostanoids and peroxisome proliferator-activated receptor γ (PPARγ) ligands play an important role in gastric cancer. Previously, we demonstrated that prostaglandin reductase 2 (PTGR2) catalyzes the reduction of the PPARγ ligand 15-keto-PGE(2) into 13,14-dihydro-15-keto-PGE(2). Here, we present functional data and clinical relevance for the role of PTGR2 in gastric cancer. Using lentiviral technology in AGS and SNU-16 gastric cancer cell lines, we either down-regulated or overexpressed PTGR2. In vitro analysis showed that PTGR2 knockdown resulted in decreased proliferation rate and colony formation, and in vivo xenograft models showed slower growth of tumors. Mechanistically, PTGR2 knockdown induced cell death, altered mitochondrial function, and increased reactive oxygen species production, which led to activation of ERK1/2 and caspase 3, with increased Bcl-2 and suppressed Bax expression. PTGR2 overexpression showed the opposite outcomes. Clinically, immunopathological staining showed strong PTGR2 expression in the gastric tumor portion, relative to nearby nontumor portions, and its expression negatively correlated with survival of patients with intestinal-type gastric cancer. Finally, in contrast to PTGR2-overexpressing cells, PTGR2-knockdown cells were more sensitive to cisplatin and 5-fluorouracil. Taken together, our findings not only provide functional and mechanistic evidence of the involvement of PTGR2 in gastric cancer, but also provide clinical observations affirming the significance of PTGR2 in gastric cancer and suggesting that PTGR2-target based therapy is worth further evaluation.
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Álcool Desidrogenase/metabolismo , Transformação Celular Neoplásica/patologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , 15-Oxoprostaglandina 13-Redutase , Animais , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , Análise de SobrevidaRESUMO
An efficient synthesis method was developed for furoxan/1,2,4-triazole hybrids 5a-k from methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1 through two-steps reaction including hydrolyzation and esterification. All of the furoxan/1,2,4-triazole hybrid derivatives were characterized by spectroscopy. On the other hand, the influence of newly synthesized multi-substituted 1,2,4-triazoles on the exogenous NO release ability, in vitro and in vivo anti-inflammatory activity, and in silico predictions were experimentally evaluated. Based on the exogenous NO release ability study and SAR studies of in vitro anti-inflammatory activity, all of compounds 5a-k exhibited slightly NO release ability and potential anti-inflammatory activity on LPS-induced RAW264.7 cells (IC50 = 5.74-15.3 µM) compared to Celecoxib (IC50 = 16.5 µM) and Indomethacin (IC50 = 56.8 µM). Furthermore, compounds 5a-k were also subjected to in vitro COX-1/COX-2 inhibition assays. Particularly, compound 5f exhibited extraordinary COX-2 inhibition (IC50 = 0.0455 µM) and selectivity (SI = 209). In addition, compound 5f was also examined in vivo pro-inflammatory cytokine productions and gastric safety and possessed the better inhibition of cytokine and safety compared with Indomethacin at the same concentration. Through the molecular modeling and in silico physicochemical and pharmacokinetic properties prediction, compound 5f was stabilized in COX-2 active binding site and possessed the fundamental strong H-bond interaction with Arg499 to form the significant physicochemical and pharmacological properties as a candidate drug. Following the in vitro, in vivo, and in silico study results, compound 5f demonstrated to be a potential anti-inflammatory agent and had comparable effects with Celecoxib.
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Anti-Inflamatórios não Esteroides , Anti-Inflamatórios , Anti-Inflamatórios não Esteroides/química , Celecoxib , Ciclo-Oxigenase 2/metabolismo , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Triazóis/química , Indometacina , Citocinas , Inibidores de Ciclo-Oxigenase 2/farmacologia , Estrutura MolecularRESUMO
Primary mediastinal nonseminomatous germ cell tumor with extrathoracic metastases is associated with a very high mortality rate, and there is no consensus regarding optimal upfront therapy. Once patients fail the first-line treatment, salvage therapy often fails to effectively control the disease. Resection of the residual mediastinal mass does not appear to achieve long-term control in those who have extrathoracic metastases following conventional first-line systemic therapy. We report a case where a young man presented with symptomatic brain metastases as well as extensive visceral involvement of the liver, small intestine, and lungs. He was successfully managed with multimodality treatment including high-dose chemotherapy with hematopoietic stem cell support following standard first-line chemotherapy, resection of mediastinal disease, lung metastasectomy, and stereotactic brain radiation. He has achieved long-term survival.
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Dimensionality reduction (DR) methods are commonly used for analyzing and visualizing multidimensional data. However, when data is a live streaming feed, conventional DR methods cannot be directly used because of their computational complexity and inability to preserve the projected data positions at previous time points. In addition, the problem becomes even more challenging when the dynamic data records have a varying number of dimensions as often found in real-world applications. This paper presents an incremental DR solution. We enhance an existing incremental PCA method in several ways to ensure its usability for visualizing streaming multidimensional data. First, we use geometric transformation and animation methods to help preserve a viewer's mental map when visualizing the incremental results. Second, to handle data dimension variants, we use an optimization method to estimate the projected data positions, and also convey the resulting uncertainty in the visualization. We demonstrate the effectiveness of our design with two case studies using real-world datasets.
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Lithium-chalcogen batteries are an appealing choice for high-energy-storage technology. However, the traditional battery that employs liquid electrolytes suffers irreversible loss and shuttle of the soluble intermediates. New batteries that adopt Li+ -conductive polymer electrolytes to mitigate the shuttle problem are hindered by incomplete discharge of sulfur/selenium. To address the trade-off between energy and cycle life, a new electrolyte is proposed that reconciles the merits of liquid and polymer electrolytes while resolving each of their inferiorities. An in situ interfacial polymerization strategy is developed to create a liquid/polymer hybrid electrolyte between a LiPF6 -coated separator and the cathode. A polymer-gel electrolyte in situ formed on the separator shows high Li+ transfer number to serve as a chemical barrier against the shuttle effect. Between the gel electrolyte and the cathode surface is a thin gradient solidification layer that enables transformation from gel to liquid so that the liquid electrolyte is maintained inside the cathode for rapid Li+ transport and high utilization of active materials. By addressing the dilemma between the shuttle chemistry and incomplete discharge of S/Se, the new electrolyte configuration demonstrates its feasibility to trigger higher capacity retention of the cathodes. As a result, Li-S and Li-Se cells with high energy and long cycle lives are realized, showing promise for practical use.
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In this study we immobilized gold nanoparticles (AuNPs) onto thiol-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films as bioelectronic interfaces (BEIs) to be integrated into organic electrochemical transistors (OECTs) for effective detection of dopamine (DA) and also as surface-enhanced Raman scattering (SERS)-active substrates for the selective detection of p-cresol (PC) in the presence of multiple interferers. This novel PEDOT-based BEI device platform combined (i) an underlying layer of polystyrenesulfonate-doped PEDOT (PEDOT:PSS), which greatly enhanced the transconductance and sensitivity of OECTs for electrochemical sensing of DA in the presence of other ascorbic acid and uric acid metabolites, as well as amperometric response toward DA with a detection limit (S/N = 3) of 37 nM in the linear range from 50 nM to 100 µM; with (ii) a top interfacial layer of AuNP-immobilized three-dimensional (3D) thiol-functionalized PEDOT, which not only improved the performance of OECTs for detecting DA, due to the signal amplification effect of the AuNPs with high catalytic activity, but also enabled downstream analysis (SERS detection) of PC on the same chip. We demonstrate that PEDOT-based 3D OECT devices decorated with a high-density of AuNPs can display new versatility for the design of next-generation biosensors for point-of-care diagnostics.
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Sharing data for public usage requires sanitization to prevent sensitive information from leaking. Previous studies have presented methods for creating privacy preserving visualizations. However, few of them provide sufficient feedback to users on how much utility is reduced (or preserved) during such a process. To address this, we design a visual interface along with a data manipulation pipeline that allows users to gauge utility loss while interactively and iteratively handling privacy issues in their data. Widely known and discussed types of privacy models, i.e., syntactic anonymity and differential privacy, are integrated and compared under different use case scenarios. Case study results on a variety of examples demonstrate the effectiveness of our approach.
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Analyzing social networks reveals the relationships between individuals and groups in the data. However, such analysis can also lead to privacy exposure (whether intentionally or inadvertently): leaking the real-world identity of ostensibly anonymous individuals. Most sanitization strategies modify the graph's structure based on hypothesized tactics that an adversary would employ. While combining multiple anonymization schemes provides a more comprehensive privacy protection, deciding the appropriate set of techniques-along with evaluating how applying the strategies will affect the utility of the anonymized results-remains a significant challenge. To address this problem, we introduce GraphProtector, a visual interface that guides a user through a privacy preservation pipeline. GraphProtector enables multiple privacy protection schemes which can be simultaneously combined together as a hybrid approach. To demonstrate the effectiveness of GraphProtector, we report several case studies and feedback collected from interviews with expert users in various scenarios.
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Investigations were carried out to evaluate the therapeutic properties of the seeds and leaves of Moringa oleifera Lam as herbal medicines. Ethanol extracts showed anti-fungal activities in vitro against dermatophytes such as Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis. GC-MS analysis of the chemical composition of the essential oil from leaves showed a total of 44 compounds. Isolated extracts could be of use for the future development of anti-skin disease agents.
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Antifúngicos/farmacologia , Moringa oleifera/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Antifúngicos/química , Fungos/efeitos dos fármacos , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Óleos de Plantas/química , Sementes/químicaRESUMO
BACKGROUND: The development of technical approaches for endovascular abdominal aortic aneurysm (AAA) repair during the last decade was briefly reviewed. The role of endovascular AAA repair as a new reliable method of treatment in high-risk patients was evaluated in both the major studies reported and a preliminary result of our center. METHODS: General criteria for the selection and exclusion of high-risk patients were summarized. Six patients (mean age: 72 years) with complex infrarenal AAA underwent endovascular aneurysm repair using the bifurcated stent graft system. Routine follow-up examination included computed tomography performed periodically from the post-operative month up to one year. Patients suspected of endoleak underwent angiography and further endovascular treatment. RESULTS: Successful deployment of the endograft and exclusion of the aneurysm was achieved in all six patients (100%) in our preliminary series. None of our patients required conversion to open aneurysmal repair. Comorbidity was an important factor in the outcome of aneurysm repair in high-risk patients, with cardiovascular disease and chronic obstructive pulmonary disease being the major comorbid conditions. Cardiac events were the most common complications, followed by transient renal failure, wound infection and endoleaks, which were corrected with endovascular treatment. CONCLUSIONS: The long-term results and efficacy of endovascular repair of infrarenal AAA remain to be demonstrated, but the procedure is believed to provide a safe and effective alternative treatment for high-risk patients suffering from AAA.
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Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Idoso , HumanosRESUMO
Filamentous phage display systems have been developed successfully to generate functional Fab antibody fragments. In this study, a recombinant Fab antibody fragment was successfully cloned from a murine monoclonal antibody 2H2 that can effectively neutralize Japanese encephalitis virus (JEV) in vitro. The recombinant Fab 2H2 antibody fragment expressed in Escherichia coli using the pComb3H phage vector resulted in a dose-dependent neutralization response using plaque reduction neutralization test. Molecular modeling of the Fab 2H2 indicated that the rational contact residues of the Fab 2H2 were targeted to the lateral surface of domain III of the JEV E protein. The combining sites of Fab 2H2 were mostly located at the variable region of the heavy chain genes. In vitro shuffling of the heavy-chain variable genes using pCom3H phage technology indicated that the sequence analysis of 10 high-affinity clones selected from the self-shuffling libraries presented no change in their amino acid sequences in 6CDRs, suggesting that the Fab 2H2 had evolved to be highly matured in the combining sites to the lateral surface of domain III. The information gained from this study may benefit the design of vaccines and therapeutic antibodies against JEV infection.