Showing papers by "Sichuan University published in 2016"
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The annual estimates of child mortality by cause to 2000–15 are updated to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival.
2,252 citations
TL;DR: This review focuses on how miRNAs regulate the development of human tumors by acting as tumor suppressors or oncogenes.
Abstract: MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that function in regulation of gene expression. Compelling evidences have demonstrated that miRNA expression is dysregulated in human cancer through various mechanisms, including amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes and defects in the miRNA biogenesis machinery. MiRNAs may function as either oncogenes or tumor suppressors under certain conditions. The dysregulated miRNAs have been shown to affect the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, activating invasion and metastasis, and inducing angiogenesis. An increasing number of studies have identified miRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools, which needs further investigation and validation. In this review, we focus on how miRNAs regulate the development of human tumors by acting as tumor suppressors or oncogenes.
1,535 citations
TL;DR: A computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells is developed and may inform effective cancer vaccine and checkpoint blockade therapies.
Abstract: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor–immune interactions in cancers. We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER
. We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies.
1,485 citations
Lars G. Fritsche1, Wilmar Igl2, Jessica N. Cooke Bailey3, Felix Grassmann2 +182 more•Institutions (58)
TL;DR: The results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
1,088 citations
TL;DR: The Jiangmen Underground Neutrino Observatory (JUNO) as mentioned in this paper is a 20kton multi-purpose underground liquid scintillator detector with the determination of neutrino mass hierarchy (MH) as a primary physics goal.
Abstract: The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy (MH) as a primary physics goal. The excellent energy resolution and the large fiducial volume anticipated for the JUNO detector offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. In this document, we present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. Following an introduction summarizing the current status and open issues in neutrino physics, we discuss how the detection of antineutrinos generated by a cluster of nuclear power plants allows the determination of the neutrino MH at a 3–4σ significance with six years of running of JUNO. The measurement of antineutrino spectrum with excellent energy resolution will also lead to the precise determination of the neutrino oscillation parameters ${\mathrm{sin}}^{2}{\theta }_{12}$, ${\rm{\Delta }}{m}_{21}^{2}$, and $| {\rm{\Delta }}{m}_{{ee}}^{2}| $ to an accuracy of better than 1%, which will play a crucial role in the future unitarity test of the MNSP matrix. The JUNO detector is capable of observing not only antineutrinos from the power plants, but also neutrinos/antineutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, and solar neutrinos. As a result of JUNO's large size, excellent energy resolution, and vertex reconstruction capability, interesting new data on these topics can be collected. For example, a neutrino burst from a typical core-collapse supernova at a distance of 10 kpc would lead to ∼5000 inverse-beta-decay events and ∼2000 all-flavor neutrino–proton ES events in JUNO, which are of crucial importance for understanding the mechanism of supernova explosion and for exploring novel phenomena such as collective neutrino oscillations. Detection of neutrinos from all past core-collapse supernova explosions in the visible universe with JUNO would further provide valuable information on the cosmic star-formation rate and the average core-collapse neutrino energy spectrum. Antineutrinos originating from the radioactive decay of uranium and thorium in the Earth can be detected in JUNO with a rate of ∼400 events per year, significantly improving the statistics of existing geoneutrino event samples. Atmospheric neutrino events collected in JUNO can provide independent inputs for determining the MH and the octant of the ${\theta }_{23}$ mixing angle. Detection of the (7)Be and (8)B solar neutrino events at JUNO would shed new light on the solar metallicity problem and examine the transition region between the vacuum and matter dominated neutrino oscillations. Regarding light sterile neutrino topics, sterile neutrinos with ${10}^{-5}\,{{\rm{eV}}}^{2}\lt {\rm{\Delta }}{m}_{41}^{2}\lt {10}^{-2}\,{{\rm{eV}}}^{2}$ and a sufficiently large mixing angle ${\theta }_{14}$ could be identified through a precise measurement of the reactor antineutrino energy spectrum. Meanwhile, JUNO can also provide us excellent opportunities to test the eV-scale sterile neutrino hypothesis, using either the radioactive neutrino sources or a cyclotron-produced neutrino beam. The JUNO detector is also sensitive to several other beyondthe-standard-model physics. Examples include the search for proton decay via the $p\to {K}^{+}+\bar{
u }$ decay channel, search for neutrinos resulting from dark-matter annihilation in the Sun, search for violation of Lorentz invariance via the sidereal modulation of the reactor neutrino event rate, and search for the effects of non-standard interactions. The proposed construction of the JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics in a timely and cost-effective fashion. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.
807 citations
TL;DR: An extended TOPSIS method and an aggregation-based method respectively for multi-attribute group decision making (MAGDM) with probabilistic linguistic information, and apply them to a practical case concerning strategy initiatives.
807 citations
TL;DR: In this article, the authors demonstrated that K-doped graphitic carbon nitride (g-C3N4) with a unique electronic structure possessed highly enhanced visible-light photocatalytic performance for NO removal.
Abstract: Graphitic carbon nitride (g-C3N4) has been widely investigated and applied in photocatalysis and catalysis, but its performance is still unsatisfactory. Here, we demonstrated that K-doped g-C3N4 with a unique electronic structure possessed highly enhanced visible-light photocatalytic performance for NO removal, which was superior to Na-doped g-C3N4. DFT calculations revealed that K or Na doping can narrow the bandgap of g-C3N4. K atoms, intercalated into the g-C3N4 interlayer via bridging the layers, could decrease the electronic localization and extend the π conjugated system, whereas Na atoms tended to be doped into the CN planes and increased the in-planar electron density. On the basis of theoretical calculation results, we synthesized K-doped g-C3N4 and Na-doped g-C3N4 by a facile thermal polymerization method. Consistent with the theoretical prediction, it was found that K was intercalated into the space between the g-C3N4 layers. The K-intercalated g-C3N4 sample showed increased visible-light absor...
796 citations
Fudan University1, Nanchang University2, Nanjing Medical University3, Harbin Medical University4, Hebei Medical University5, Peking Union Medical College6, China Medical University (PRC)7, Sun Yat-sen University8, Qingdao University9, Fujian Medical University10, Sichuan University11, Bengbu Medical College12, Fourth Military Medical University13, Tianjin Medical University Cancer Institute and Hospital14, Shanghai Jiao Tong University15, Third Military Medical University16, Zhejiang University17, Shantou University18
TL;DR: These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy.
Abstract: PurposeThere is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed.Patients and MethodsThis was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS).ResultsBetween January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with t...
711 citations
TL;DR: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity.
Abstract: Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m 2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m 2 on day 1), intravenous cisplatin (60 mg/m 2 on day 1), and continuous intravenous fluorouracil (600 mg/m 2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
Haidong Wang1, Zulfiqar A Bhutta2, Zulfiqar A Bhutta3, Matthew M Coates1 +610 more•Institutions (263)
TL;DR: The Global Burden of Disease 2015 Study provides an analytical framework to comprehensively assess trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time and decomposed the changes in under- 5 mortality to changes in SDI at the global level.
TL;DR: This study reports on the development of self-standing ternary FexCo1-xP nanowire array on carbon cloth as a Pt-free HER catalyst with activities being strongly related to Fe substitution ratio, and reveals that Fe substitution of Co in CoP leads to more optimal free energy of hydrogen adsorption to the catalyst surface.
Abstract: Replacement of precious Pt with earth-abundant electrocatalysts for the hydrogen evolution reaction (HER) holds great promise for clean energy devices, but the development of low-cost and durable HER catalysts with Pt-like activity is still a huge challenge. In this communication, we report on the development of self-standing ternary FexCo1–xP nanowire array on carbon cloth (FexCo1–xP/CC) as a Pt-free HER catalyst with activities being strongly related to Fe substitution ratio. Electrochemical tests show that Fe0.5Co0.5P/CC not only possesses Pt-like activity with the need of overpotential of only 37 mV to drive 10 mA cm–2, outperforming all non-noble-metal HER catalysts reported to date, but demonstrates superior long-term durability in 0.5 M H2SO4. Density functional theory calculations further reveal that Fe substitution of Co in CoP leads to more optimal free energy of hydrogen adsorption to the catalyst surface. This study offers us a promising flexible monolithic catalyst for practical applications.
TL;DR: Ternary KNN-based ceramics demonstrate the potential for applications and can be ascribed to the co-existence of "nano-scale strain domains" and a high density of ferroelectric domain boundaries.
Abstract: A superior piezoelectric coefficient (d33 = 570 ± 10 pC N"1 ), the highest value reported to date in potassium-sodium niobate-based ceramics, is obtained in (1-x-y)K1-w Naw Nb1-z Sbz O3-y BaZrO3-x - Bi0.5 K0.5 HfO3 ceramics. This high d33 value can be ascribed to the co-existence of "nano-scale strain domains" (1-2 nm) and a high density of ferroelectric domain boundaries. Therefore, ternary KNN-based ceramics demonstrate the potential for applications.
TL;DR: The prevailing 3D printing techniques and their most recent applications in building tissue constructs are discussed and 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation.
01 May 2016
TL;DR: This paper first extends the TODIM approach to solve the MCDM problems with Pythagorean fuzzy information, and conducts simulation tests to analyze how the risk attitudes of the decision makers exert the influence on the results of M CDM under uncertainty.
Abstract: Develop the Pythagorean fuzzy TODIM approach to multi-criteria decision making.The developed approach can portray the uncertainty and risk simultaneously.Conduct the simulation tests to verify risk attitude's influence on the ranking orders.Provide a case study to show the practicality and effectiveness of the proposed approach.Demonstrate the superiority of our approach by comparing it with the existing ones. Recently, the TODIM (an acronym in Portuguese for Interactive Multi-criteria Decision Making) approach, which can characterize the decision makers' psychological behaviours under risk, has been introduced to handle multi-criteria decision making (MCDM) problems. Moreover, Pythagorean fuzzy set is an effective tool for depicting uncertainty of the MCDM problems. In this paper, based on the prospect theory, we first extend the TODIM approach to solve the MCDM problems with Pythagorean fuzzy information. Then, we conduct simulation tests to analyze how the risk attitudes of the decision makers exert the influence on the results of MCDM under uncertainty. Finally, a case study on selecting the governor of Asian Infrastructure Investment Bank is made to show the applicability of the proposed approach.
Southern Medical University1, Sun Yat-sen University2, Fujian Medical University3, Fudan University4, Shanghai Jiao Tong University5, Peking University6, Sichuan University7, Harbin Medical University8, Jilin University9, Huazhong University of Science and Technology10, Fourth Military Medical University11
TL;DR: Experienced surgeons can safely perform LG with D2 lymphadenectomy for AGC, and the morbidity and mortality within 30 days after surgery between the LG and OG groups were compared on the basis of the modified intention-to-treat principle.
Abstract: PurposeThe safety and efficacy of radical laparoscopic distal gastrectomy (LG) with D2 lymphadenectomy for the treatment of advanced gastric cancer (AGC) remain controversial. We conducted a randomized controlled trial to compare laparoscopic and conventional open distal gastrectomy with D2 lymph node dissections for AGC.Patients and MethodsBetween September 2012 and December 2014, 1,056 patients with clinical stage T2-4aN0-3M0 gastric cancer were eligible for inclusion. They were randomly assigned to either the LG with D2 lymphadenectomy group (n = 528) or the open gastrectomy (OG) with D2 lymphadenectomy group (n = 528). Fifteen experienced surgeons from 14 institutions in China participated in the study. The morbidity and mortality within 30 days after surgery between the LG (n = 519) and the OG (n = 520) groups were compared on the basis of the modified intention-to-treat principle. Postoperative complications were stratified according to the Clavien-Dindo classification.ResultsThe compliance rates of...
TL;DR: In this article, a very simple and low-cost approach is proposed to fabricate versatile pressure sensors based on microcrack-designed carbon black (CB)@polyurethane (PU) sponges via natural polymer-mediated water-based layer-by-layer assembly.
Abstract: It is a challenge to manufacture pressure-sensing materials that possess flexibility, high sensitivity, large-area compliance, and capability to detect both tiny and large motions for the development of artificial intelligence products. Herein, a very simple and low-cost approach is proposed to fabricate versatile pressure sensors based on microcrack-designed carbon black (CB)@polyurethane (PU) sponges via natural polymer-mediated water-based layer-by-layer assembly. These sensors are capable of satisfying the requirements of ultrasmall as well as large motion monitoring. The versatility of these sensors benefits from two aspects: microcrack junction sensing mechanism for tiny motion detecting (91 Pa pressure, 0.2% strain) inspired by the spider sensory system and compressive contact of CB@PU conductive backbones for large motion monitoring (16.4 kPa pressure, 60% strain). Furthermore, these sensors exhibit excellent flexibility, fast response times (<20 ms), as well as good reproducibility over 50 000 cycles. This study also demonstrates the versatility of these sensors for various applications, ranging from speech recognition, health monitoring, bodily motion detection to artificial electronic skin. The desirable comprehensive performance of our sensors, which is comparable to the recently reported pressure-sensing devices, together with their significant advantages of low-cost, easy fabrication, especially versatility, makes them attractive in the future of artificial intelligence.
TL;DR: A novel bit-level image encryption algorithm that is based on piecewise linear chaotic maps (PWLCM) that is both secure and reliable for image encryption.
TL;DR: In this paper, a copper/bronze laminates with varying interface spacing were fabricated by accumulative roll bonding and subsequent annealing to systematically study the interface effect on mechanical properties.
TL;DR: A comprehensive review on the progress of BFO-based materials made in the past fifteen years in the different forms of ceramic bulks, thin films and nanostructures, focusing on the pathways to modify different structures and to achieve enhanced physical properties and new functional behavior is provided in this paper.
Capital Medical University1, Samsung Medical Center2, The Chinese University of Hong Kong3, Hong Kong University of Science and Technology4, Mongolian National University5, Fudan University6, Peking Union Medical College Hospital7, Sichuan University8, Nanjing Medical University9, Harbin Medical University10, Tianjin Medical University General Hospital11, Chinese PLA General Hospital12, Central South University13, China Medical University (PRC)14, Sun Yat-sen University15, Zhengzhou University16, Third Military Medical University17, Fourth Military Medical University18, Soochow University (Suzhou)19
TL;DR: The recommendations will provide a framework and assurance for the strategy of diagnostic and therapeutic measures to reduce complications from unnecessary treatment and cost and should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also as a source of knowledge for insurance companies and other institutionsinvolved in the cost regulation of cancer care in China.
TL;DR: The findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21-rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment.
Abstract: Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor patient outcomes. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. However, the mechanisms underlying the association between exosomes and hypoxia during cancer progression remain poorly understood. In this study, we found that exosomes derived from hypoxic oral squamous cell carcinoma (OSCC) cells increased the migration and invasion of OSCC cells in a HIF-1α and HIF-2α-dependent manner. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we performed miRNA sequencing of normoxic and hypoxic OSCC-derived exosomes. Of the 108 miRNAs that were differentially expressed, miR-21 stood out as one of the most significantly upregulated miRNAs under hypoxic conditions. miR-21 depletion in hypoxic OSCC cells led to decreased miR-21 levels in exosomes and significantly reduced cell migration and invasion. Conversely, restoration of miR-21 expression in HIF-1α and HIF-2α-depleted exosomes rescued OSCC cell migration and invasion. Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo Finally, circulating exosomal miR-21 levels were closely associated with HIF-1α/HIF-2α expression, T stage, and lymph node metastasis in patients with OSCC. In conclusion, our findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21-rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment. Cancer Res; 76(7); 1770-80. ©2016 AACR.
TL;DR: The definition and basic properties of the different types of fuzzy sets that have appeared up to now in the literature are reviewed and the relationships between them are analyzed.
Abstract: In this paper, we review the definition and basic properties of the different types of fuzzy sets that have appeared up to now in the literature. We also analyze the relationships between them and enumerate some of the applications in which they have been used.
TL;DR: The results demonstrate that the NiCo2S4@PPy-50 core-shell heterostructure nanotube array is promising as electrode material for supercapacitors in energy storage.
Abstract: In this paper, a hierarchical NiCo2S4@polypyrrole core–shell heterostructure nanotube array on Ni foam (NiCo2S4@PPy/NF) was successfully developed as a bind-free electrode for supercapacitors. NiCo2S4@PPy-50/NF obtained under 50 s PPy electrodeposition shows a low charge-transfer resistance (0.31 Ω) and a high area specific capacitance of 9.781 F/cm2 at a current density of 5 mA/cm2, which is two times higher than that of pristine NiCo2S4/NF (4.255 F/cm2). Furthermore, an asymmetric supercapacitor was assembled using NiCo2S4@PPy-50/NF as positive electrode and activated carbon (AC) as negative electrode. The resulting NiCo2S4@PPy-50/NF//AC device exhibits a high energy density of 34.62 Wh/kg at a power density of 120.19 W/kg with good cycling performance (80.64% of the initial capacitance retention at 50 mA/cm2 over 2500 cycles). The superior electrochemical performance can be attributed to the combined contribution of both component and unique core–shell heterostructure. The results demonstrate that the ...
TL;DR: In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier (BBTB), and nose-to-brain barrier, and delivery strategies are focused on overcoming theBBB, directly targeting diseased cells in the brain, and dual- targeted delivery.
TL;DR: Hybrid graphene aerogels (HGA) consisting of graphene oxide (GO) and graphene nanoplatelets (GNP) were prepared and introduced into polyethylene glycol (PEG) via vacuum impregnation, aiming at obtaining composite phase change materials (PCMs) with high thermal conductivity, outstanding shape-stabilization, high energy storage density, commendable thermal repeatability and the ability to light-to-heat energy storage.
TL;DR: Based on the existing binary phase diagrams with eutectic points, a strategy of designing EHEAs with desired high strength and ductility is proposed in this article, which is composed of a ductile face centered cubic (FCC) phase and a hard Laves phase with fine laminar structures.
TL;DR: This work has shown that deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases.
Abstract: Ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological processes, including different aspects of immune functions. Ubiquitination regulates pattern-recognition receptor signaling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Ubiquitination also regulates the development, activation, and differentiation of T cells, thereby maintaining efficient adaptive immune responses to pathogens and immunological tolerance to self-tissues. Like phosphorylation, ubiquitination is a reversible reaction tightly controlled by the opposing actions of ubiquitin ligases and deubiquitinases. Deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases.
TL;DR: To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium, a large number of patients with a history of psychosis are treated with these medications.
Abstract: Objectives
To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium.
Design
Systematic review and meta-analysis.
Setting
PubMed, EMBASE, CINAHL, and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013.
Participants
Adult surgical and medical inpatients.
Intervention
Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies.
Measurements
Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi-square P 50%. Using a random-effects model (I2 > 50%) or a fixed-effects model (I2 < 50%), odds ratios (ORs) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit (ICU) length of stay (LOS)). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics.
Results
Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence (OR = 0.56, 95% confidence interval (CI) = 0.23–1.34, I2 = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected (OR = 0.90, 95% CI = 0.62–1.29, I2 = 0%).
Conclusion
Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed.