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1.
Chem Commun (Camb) ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146179

RESUMO

Here, a new strategy is reported for the preparation of a new class of nanocomposite anode materials consisting of ppm-level phosphorus-doped Si nanoparticles (P-Si) wrapped in a network of poly-γ-glutamate and graphene. The network produces not only a conductivity-enhanced conduit but also a mechanical stress buffer. The incorporation of poly-γ-glutamate in the nanocomposite enables self-healing capability and maintains the electrode structural integrity. This multifunctionality has significant implications for advancing the design of stable Si-based nanomaterials as high-performance anodes in Li-ion batteries.

2.
Int J Mol Sci ; 21(21)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171818

RESUMO

Immune evasion and altered metabolism, where glucose utilization is diverted to increased lactic acid production, are two fundamental hallmarks of cancer. Although lactic acid has long been considered a waste product of this alteration, it is now well accepted that increased lactic acid production and the resultant acidification of the tumor microenvironment (TME) promotes multiple critical oncogenic processes including angiogenesis, tissue invasion/metastasis, and drug resistance. We and others have hypothesized that excess lactic acid in the TME is responsible for suppressing anticancer immunity. Recent studies support this hypothesis and provide mechanistic evidence explaining how lactic acid and the acidic TME impede immune cell functions. In this review, we consider lactic acid's role as a critical immunoregulatory molecule involved in suppressing immune effector cell proliferation and inducing immune cell de-differentiation. This results in the inhibition of antitumor immune responses and the activation of potent, negative regulators of innate and adaptive immune cells. We also consider the role of an acidic TME in suppressing anticancer immunity. Finally, we provide insights to help translate this new knowledge into impactful anticancer immune therapies.

3.
Biosens Bioelectron ; 172: 112757, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33129074

RESUMO

MicroRNAs (miRNAs) are important biomarkers for the diagnosis, prognosis, and treatment of human diseases. Sensitive and selective detection of multiple miRNAs simultaneously will greatly facilitate the early and accurate diagnosis of cancers. Herein, a novel entropy-driven amplification system-templated silver nanoclusters sensing platform was developed for the multiplexed analysis of tumor-associated miRNAs. The sensing platform was constructed by coupling target-triggered entropy-driven catalysis with luminescence adjustable DNA-templated silver nanoclusters (Ag NCs). In the presence of target miRNA, the sensing platform initiates the branch migration and strand displacement of the complex, which has a six-base cytosine loop for stabilizing the luminous Ag NCs. The target is cyclically generated for new catalysis while turning off the fluorescence of Ag NCs; this is accompanied by a significantly amplified optical readout. In this study, two different complex-stabilized Ag NCs systems were proposed, the yellow-emitting Ag NCs and red-emitting Ag NCs biosensors enabled the analysis of miRNA-141 and miRNA-155 with detection limits of 6.1 pM and 8.7 pM, respectively. Impressively, owing to the excellent selectivity, flexibility, and narrow-band excitation of the platform, the multiplexed synchronous detection of miRNA-141 and miRNA-155 were achieved in buffer, biological cell lysates and human serum samples with satisfactory results. The simple, flexible, and convenient strategy provides a powerful tool for multiple biomarkers analysis and related clinical applications.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33074566

RESUMO

BACKGROUND AND AIM: Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD. METHODS: The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954). RESULTS: In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively. CONCLUSIONS: This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.

5.
Nat Prod Res ; : 1-7, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32954869

RESUMO

The chemical investigation of the fruits of Xanthium strumarium (Asteraceae) led to the isolation of two new ent-kauranoid glucosides named 2-O-(6-O-isocaleryl-ß-D-glucopyranosyl) atractyligenin (1) and 2-O-(2-O-isovaleryl-ß-D-glucopyranosyl) atractyligenin (2), together with one known compound. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction and electronic circular dichroism data. All compounds and their aglycone were evaluated for their anti-proliferative activities in vitro against three human cancer cell lines.

6.
Fitoterapia ; 146: 104728, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32949648

RESUMO

Phytochemical investigation of Physalis minima led to the isolation of six new withanolides, including physaminilides HK (1-4), two artificial withanolides (5-6), and 19 known ones (7-25). Their structures were elucidated on the basis of spectroscopic analysis, including NMR and electronic circular dichroism (ECD) data. The isolates were evaluated for their cytotoxic activities against A375 human melanoma cells. Compounds 1, 8-9, 12-13, 15-17 and 19 exhibited significant cytotoxic activities with IC50 values in the range of 1.2-7.5 µM.

7.
Epigenomics ; 12(16): 1457-1476, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32938196

RESUMO

Immunotherapies are revolutionizing the clinical management of a wide range of cancers. However, intrinsic or acquired unresponsiveness to immunotherapies does occur due to the dynamic cancer immunoediting which ultimately leads to immune escape. The evolutionarily conserved histone modifier enhancer of zeste 2 (EZH2) is aberrantly overexpressed in a number of human cancers. Accumulating studies indicate that EZH2 is a main driver of cancer cells' immunoediting and mediate immune escape through downregulating immune recognition and activation, upregulating immune checkpoints and creating an immunosuppressive tumor microenvironment. In this review, we overviewed the roles of EZH2 in cancer immunoediting, the preclinical and clinical studies of current pharmacologic EZH2 inhibitors and the prospects for EZH2 inhibitor and immunotherapy combination for cancer treatment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32776372

RESUMO

Substitutional doping provides an effective strategy to tailor the properties of 2D materials, but it remains an open challenge to achieve tunable uniform doping, especially at high doping level. Here, uniform lattice substitution of a 2D Mo2 C superconductor by magnetic Cr atoms with controlled concentration up to ≈46.9 at% by chemical vapor deposition and a specifically designed Cu/Cr/Mo trilayer growth substrate is reported. The concentration of Cr atoms can be easily tuned by simply changing the thickness of the Cr layer, and the samples retain the original structure of 2D Mo2 C even at a very high Cr concentration. The controlled uniform Cr doping enables the tuning of the competition of the 2D superconductor and the Kondo effect across the whole sample. Transport measurements show that with increasing Cr concentration, the superconductivity of the 2D Cr-doped Mo2 C crystals disappears along with the emergence of the Kondo effect, and the Kondo temperature increases monotonously. Using scanning tunneling microscopy/spectroscopy, the mechanism of the doping level effect on the interplay and evolution between superconductivity and the Kondo effect is revealed. This work paves a new way for the synthesis of 2D materials with widely tunable doping levels, and provides new understandings on the interplay between superconductivity and magnetism in the 2D limit.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32752166

RESUMO

Promoting the use of green space is a fundamental way to improve physical and mental health and to enhance the quality of life of urban residents. In response to increasing demand for green space in cities, the impact of perception of green space for health promotion on willingness to use parks and actual use among young urban residents was investigated in this study. A total of 1135 young residents (ages 18-35) in three cities in China were surveyed by online questionnaire. A group of multiple regression models was constructed to investigate the influencing perception factors of participants' willingness to use parks and actual use. The results revealed that the young residents' perception of green space components for health promotion (green space access, types, sizes, plants, water, sensory features, microclimate environments and amenity facilities) had a greater effect on their willingness to use parks and to promote health, while it was less influential with respect to their actual park use behavior (frequency and duration). Among these variables, green space access is a critical concern for willingness to use toward parks. The disparities of perception of green space for health promotion effect on willingness to use a park and actual use provide a better understanding of the psychological factors affecting park use among young residents. The findings also provided some implications for public health policymakers, urban planners and landscape architects in designing parks to encourage visitation by young people.


Assuntos
Exercício Físico , Promoção da Saúde , Parques Recreativos , Qualidade de Vida , Adolescente , Adulto , China , Cidades , Feminino , Humanos , Masculino , População Urbana , Adulto Jovem
10.
Ann Palliat Med ; 9(4): 1404-1412, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692208

RESUMO

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has outbreak in the world. Little is known about the clinical characteristics of patients with SARS-CoV-2 infection in the high-altitude region of China. We reported the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Gansu province, China. METHODS: In this retrospective study, patients with laboratory-confirmed SARS-CoV-2 infection were consecutively enrolled from January 21, 2020 to February 11, 2020. The information on the epidemiological, clinical characteristics, laboratory tests, radiological features on admission, treatment and outcome were obtained with the final follow-up of March 13, 2020. On the basis of the median length of hospital stay, patients were further analyzed in two groups (long- vs. short-hospital stay). RESULTS: Of the 86 patients of COVID-19 in 11 cities of Gansu Province, the median hospital stay was 14.0 days (interquartile rang, 11.0-19.0 days). In the overall cohort, the median age was 41.0 years (interquartile rang, 31.0-54.3 years), and 48 (55.8%) patients were female. Forty (46.5%) had a history of exposure to epidemic regions, but none exposed to the Huanan seafood market in Wuhan. Common symptoms included fever (41, 47.7%), and cough (37, 43.0%). On admission, 30 (34.9%) and 58 (67.4%) patients had leukopenia and lymphopenia. According to chest CT scans, 53 (66.3%) of 80 patients showed bilateral pneumonia, and 19 (23.8%) of 80 patients showed unilateral pneumonia. Of the 15 asymptomatic cases, 10 (66.6%) cases were found CT findings of pneumonia. Besides, there were 65 (75.6%) patients with mild and moderate type of COVID-19. All 86 patients received antiviral and traditional Chinese medicine therapy, 53 (61.6%) received antibacterial therapy, and 3 (3.5%) patients received invasive ventilator mechanical ventilation. The proportion of patients received antibiotic treatment in long-hospital stay group was significantly higher than that in the short-hospital stay group (P=0.045). As of March 13, 2020, 84 (97.7%) patients were discharged, and two (2.3%) cases died. CONCLUSIONS: In the Gansu province cohort of 86 patients of COVID-19, most patients were with mild or moderate type, and most asymptomatic cases showed CT imaging findings of SARS-CoV-2 related pneumonia.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
ACS Nano ; 14(9): 11670-11676, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32701270

RESUMO

Lead halide perovskite materials have recently received considerable attention for achieving an economic and tunable laser owing to their solution-processable feature and promising optical properties. However, most reported perovskite-based lasers operate with a large lasing-mode volume, resulting in a high lasing threshold due to the inefficient coupling between the optical gain medium and cavity. Here, we demonstrate a continuous-wave nanolasing from a single lead halide perovskite (CsPbBr3) quantum dot (PQD) in a plasmonic gap-mode nanocavity with an ultralow threshold of 1.9 Wcm-2 under 120 K. The calculated ultrasmall mode volume (∼0.002 λ3) with a z-polarized dipole and the significantly large Purcell enhancement at the corner of the nanocavity inside the gap dramatically enhance the light-matter interaction in the nanocavity, thus facilitating lasing. The demonstration of PQD nanolasing with an ultralow-threshold provides an approach for realizing on-chip electrically driven lasing and integration into on-chip plasmonic circuitry for ultrafast optical communication and quantum information processing.

12.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2626-2633, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627498

RESUMO

This study aims to reveal the pharmacokinetics of Shuganning Injection in normal rats. In this experiment,ultra-high performance liquid chromatography-electrospray-tandem mass spectrometry( UPLC-ESI-MS/MS) was used to establish an analytical method for simultaneous determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma. Then,the non-compartmental model( NCA) in Phoenix WinN onL in 6. 4 software was used to fit pharmacokinetic parameters. The methodological validation showed that the linear relationship of the components in rat plasma samples were good( r>0. 995). The recovery rate and matrix effect of plasma samples with low,middle and high concentration were 79. 14%-101. 4%. The intra-day and inter-day precision,accuracy and stability meet the requirements of biological sample analysis. The half-life( t1/2) of chlorogenic acid,gardenioside,oroxylin A did not change significantly and the area under blood concentration-time curve( AUC0-t) is proportional to the dose,which suggested that three components showed a linear kinetic characteristics,but baicalin showed nonlinear kinetic characteristics. Moreover,the retention time of each component in rats was short. The established UPLC-MS/MS quantitative analysis method is rapid,sensitive and accurate,which can be used for the determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma and pharmacokinetic study of Shuganning Injection.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Animais , Ácido Clorogênico , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
13.
Artigo em Inglês | MEDLINE | ID: mdl-32705728

RESUMO

Fibrous materials serve as an intriguing class of 3D materials to meet the growing demands for flexible, foldable, biocompatible, biodegradable, disposable, inexpensive, and wearable sensors and the rising desires for higher sensitivity, greater miniaturization, lower cost, and better wearability. The use of such materials for the creation of a fibrous sensor substrate that interfaces with a sensing film in 3D with the transducing electronics is however difficult by conventional photolithographic methods. Here, a highly effective pathway featuring surface-mediated interconnection (SMI) of metal nanoclusters (NCs) and nanoparticles (NPs) in fibrous materials at ambient conditions is demonstrated for fabricating fibrous sensor substrates or platforms. Bimodally distributed gold-copper alloy NCs and NPs are used as a model system to demonstrate the semiconductive-to-metallic conductivity transition, quantized capacitive charging, and anisotropic conductivity characteristics. Upon coupling SMI of NCs/NPs as electrically conductive microelectrodes and surface-mediated assembly (SMA) of the NCs/NPs as chemically sensitive interfaces, the resulting fibrous chemiresistors function as sensitive and selective sensors for gaseous and vaporous analytes. This new SMI-SMA strategy has significant implications for manufacturing high-performance fibrous platforms to meet the growing demands of the advanced multifunctional sensors and biosensors.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32605012

RESUMO

Urban streets are important public spaces for daily activities that play a crucial role in promoting health in the elderly. The purpose of this study was to investigate the association between perceived street walkability and mood in the elderly, and specifically, the mediating effect of environmental preference and place attachment. We surveyed a total of 269 elderly residents from six streets in Guangzhou, China. We collected assessments of the street environments, environmental preferences, place attachment, and mood status from the elderly. A serial multiple mediator model was constructed using the structural equation modeling method. The results showed that the perceived street walkability was sequentially associated first with an increased level of place attachment (ß = 0.798, SE = 0.358, p < 0.000) and then environmental preference (ß = 0.191, SE = 0.033, p = 0.038), which was in turn related to improvement of positive mood in the elderly (ß = 0.595 SE = 0.341, p < 0.000). Environmental preference alone was found to be significantly associated with positive mood (ß = 0.595, SE = 0.341, p < 0.000), while no significant effect of place attachment was found when considered individually (ß = -0.075, SE = 0.089, p = 0.395). These findings provide a greater understanding of the possible mechanism through which street environment impacts mood in the elderly. Therefore, when promoting the emotional experience of the elderly, we might consider not only physical environment factors but also psychological conditions in street environments.


Assuntos
Planejamento Ambiental , Caminhada , Idoso , China , Feminino , Humanos , Masculino , Características de Residência , Inquéritos e Questionários
15.
Eur J Med Chem ; 204: 112553, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717481

RESUMO

The SUMO (small ubiquitin-related modifier)-specific proteases (SENPs) are responsible for the cleavage of SUMO from its target proteins, thus play important roles in the dynamic SUMOylation and deSUMOylation processes. SENPs are related to a variety of human diseases including cancer and represent a new class of potential therapeutic targets with mechanism of action that is likely to be different from that of current clinically used drugs. However, potent inhibitors that are selective within the SENPs family members still remain a challenge due to their high homology. In order to demonstrate the feasibility of developing selective inhibitors within the SENPs family, we chose SENP1/2/5 as representatives, aiming to identify inhibitors with selectivity among the members. Starting from a hit compound ZCL951 from virtual screening, a series of benzothiophene-2-carboxamide inhibitors were designed based on the protein structures of SENP1, 2, and 5. First, an unoccupied hydrophobic pocket was first identified which led to IC50 as low as 0.56 µM. Furthermore, the ethylacetate 77 gave both submicromolar inhibitory activity and 33-fold selectivity for SENP2 versus SENP5. They are the most potent and selective nonpeptidic inhibitor reported so far for the SENPs family, as far as we are aware. Their structure-activity relationship was also discussed.

16.
Sci Rep ; 10(1): 9482, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514042

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32510811

RESUMO

Two dimensional (2D) nanoribbons constitute an emerging nanoarchitecture for advanced microelectronics and energy conversion due to the stronger size confinement effects compared to traditional nanosheets. Triclinic crystalline red phosphorus (cRP) composed by a layered structure is a promising 2D phosphorus allotrope and the tube-like substructure is beneficial to the construction of nanoribbons. In this work, few-layer cRP nanoribbons are synthesized and the effectiveness in the electrochemical nitrogen reduction reaction (NRR) is investigated. An iodine-assisted chemical vapor transport (CVT) method is developed to synthesize circa 10 g of bulk cRP lumps with a yield of over 99 %. With the aid of probe ultrasonic treatment, high-quality cRP microcrystals are exfoliated into few-layer nanoribbons (cRP NRs) with large aspect ratios. As non-metallic materials, cRP NRs are suitable for the electrochemical nitrogen reduction reaction. The ammonia yield is 15.4 µg h-1 mgcat. -1 at -0.4 V vs. reversible hydrogen electrode in a neutral electrolyte under ambient conditions and the Faradaic efficiency is 9.4 % at -0.2 V. Not only is cRP a promising catalyst, but also the novel strategy expands the application of phosphorus-based 2D structures beyond that of traditional nanosheets.

19.
Biomed Pharmacother ; 128: 110245, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454290

RESUMO

Berberine, an isoquinoline alkaloid from Coptidis Rhizoma, has been characterized as a potential anticancer drug due to its good anti-tumor effects. However, the molecular mechanisms involved in anti-gastric cancer remain poorly understood. Herein, the role of berberine in gastric cancer suppression by inducing cytostatic autophagy in vitro and in vivo was first investigated. Results showed that berberine induced an obvious growth inhibitory effect on gastric cancer BGC-823 cells without toxicity to human peripheral blood mononuclear cells. Treatment with berberine triggered cell autophagy, as demonstrated by the punctuate distribution of monodansylcadaverine staining and GFP-LC3, as well as the LC3-II, Beclin-1 and p-ULK1 promotion, and p62 degradation. Inhibition of autophagy by 3-MA, CQ, Baf-A1 and BECN1 siRNA obviously increased cell viability of berberine-exposed gastric cancer cells, which confirmed the anti-cancer role of autophagy induced by berberine. Mechanistic studies showed that berberine inhibited mTOR, Akt and MAPK (ERK, JNK and p38) pathways thereby inducing autophagy. Inhibition of above pathways increases berberine induced autophagy and cytotoxicity. Interestingly, mTOR/p70S6K was inhibited by the MAPK but not Akt. Furthermore, inhibition of autophagy reversed berberine down-regulated mTOR, Akt and MAPK. In xenografts, the berberine induced autophagy leads to suppression of tumor proliferation with no side-effect, and western blotting displayed an apparent attenuation of p-mTOR, p-p70S6K, p-Akt, p-ERK, p-JNK and p-p38 in tumors from berberine treated mice. Briefly, these results indicated that berberine repressed human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt, and provided a molecular basis for the treatment of gastric cancer.

20.
Toxicol In Vitro ; 67: 104885, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32407876

RESUMO

Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell carcinoma (LSCC), as been reported previously. The present work further mechanistically extended action of the synergistic effects of combination treatment. Firstly, two LSCC cells displayed higher sensitivity to oridonin, whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells were less sensitive to oridonin. Next, cetuximab/oridonin significantly enhanced the mitochondrial apoptosis through NF-κB. Meanwhile, PI3K/Akt and JAK2/STAT3 pathways are associated with the nucleus translocation of NF-κB by combination treatment. Additionally, cetuximab enhanced oridonin-promoted ER stress-related apoptosis. Interestingly, both ER stress and mitochondrial apoptosis by combination treatment are abrogated by ROS scavenger. Furthermore, oridonin/cetuximab induced ROS production after 1.5 h, followed by G2/M arrest and apoptosis, indicating that ROS generation might be an early and key event. Taken together, cetuximab enhances oridonin-induced ER stress and mitochondrial apoptotic pathway, which contributes to the synergistic antitumor effects of cetuximab/oridonin.

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