Abstract EphrinB–EphB receptor signaling plays diverse roles during development, but recently has been implicated in synaptic plasticity in the matured nervous system and in pain processes. The ...present study investigated the correlation between expression of ephrinB and EphB receptor proteins and chronic constriction injury (CCI) of the sciatic nerve and dorsal rhizotomy (DR) in dorsal root ganglion (DRG) and spinal cord (SC); and interaction of CCI and DR on expression of these signals. Adult, male Sprague–Dawley rats were employed and thermal sensitivity was determined in the sham operated CCI and DR rats. Western blot and immunobiochemistry analysis and immunofluorescence staining techniques were used to detect the expression and location of the ephrinB–EphB receptor proteins in DRG and SC. The results showed that expression of ephrinB1 and EphB1 receptor proteins was significantly upregulated in DRG and SC in a time-dependent manner corresponding to the development of thermal hyperalgesia after CCI. The increased expression is predominately located in the medium- and small-sized DRG neurons, the superficial layers of spinal dorsal horn (DH) neurons, and the IB4 positive nociceptive terminals. DR increases ephrinB1 in DRG, not SC and EphB receptor in SC, not DRG. DR suppressed CCI-induced upregulation of ephrinB1 in SC and EphB1 receptor in DRG and SC. These findings indicate that ephrinB–EphB receptor activation and redistribution in DRG and DH neurons after nerve injury could contribute to neuropathic pain. This study may also provide a new mechanism underlying DR-induced analgesia in clinic.
Conspectus Because of their unique biological, physical, and chemical properties, organofluorine compounds play an increasingly important role in numerous areas of chemistry and everyday life. ...However, although fluorine is the most abundant halogen in the earth’s crust and ranks 13th in abundance among all elements, naturally occurring organofluorine compounds are rare. Consequently, there is a growing demand for the development of safe and efficient reagents and selective synthetic methodologies for the introduction of fluorine or fluorine-containing groups into organic compounds. A wide variety of shelf-stable electrophilic fluorinating and fluoroalkylating reagents have been developed in the past decades. Some of them have also been shown to act as radical sources. These versatile reagents have promoted revolutionary advances in synthetic fluorine chemistry. These developments of novel reagents and the choice of suitable reagents for new reactions have relied largely on the traditional trial-and-error approach because (i) structure–reactivity relationships and mechanisms of reactions of these reagents are sparse and (ii) the rules that govern the synthesis of non-fluorinated analogues cannot necessarily be transposed to fluorinated compounds ( Cahard, D. ; et al. Chem. Soc. Rev. 2014, 43, 135 ), since organic fluorine compounds often exhibit unusual properties. Over the past several years, our studies have aimed at establishing comprehensive cation and radical donor scales of electrophilic F, CF3, and SCF3 transfer reagents. We have also developed detailed structure–reactivity relationships. We used density functional theory calculations to systematically investigate the energies required to heterolytically cleave the Y–F/CF3/SCF3 bonds to donate electrophilic F/CF3/SCF3 groups. We found that these energies can be used as convenient indicators of the relative electrophilic fluorinating/trifluoromethylating/trifluoromethylthiolating strengths of these reagents. We have constructed the first comprehensive cation donor scales for electrophilic F, CF3, and SCF3 transfer reagents. In collaboration with Mayr group, we experimentally determined the electrophilicity parameters of SCF3 transfer reagents and demonstrated the importance of intrinsic barriers for predicting their kinetic reactivity. The recognition of the novel application of a few traditional electrophilic reagents as radical sources prompted us further to construct comprehensive radical donor scales of electrophilic F, CF3, and SCF3 transfer reagents. We identified a series of potential new radical F, CF3, and SCF3 donors. Single electron transfer was found to exhibit a substantial effect on activation of the Y–CF3/SCF3 bonds, significantly facilitating the release of CF3/SCF3 radicals. This Account summarizes computational and experimental accomplishments from our group and others to establish the missing links between structure and reactivity for these reagents. Our results pave the way toward the rational optimization, design, and prediction of novel electrophilic fluorinating and fluoroalkylating reagents and new reactions.
Supercritical carbon dioxide (S-CO2) cycle is proven to be one promising alternative to provide high efficiency and has been developed for a wide range of energy conversion applications. Thermal ...efficiency of the S-CO2 cycle can be further improved by incorporating an appropriate bottoming cycle utilizing the residual heat. In this paper, an Organic Rankine Cycle (ORC) is added to the S-CO2 cycle for heat recovery. Different recuperative ratios of the topping S-CO2 cycle are considered and the influence of heat source initial temperature and total heat load on the bottoming ORC is evaluated. Two configurations of the S-CO2-ORC combined cycle system are presented, one without a pre-cooler and the other still with a pre-cooler, corresponding to total and partial residual heat recovery respectively. Though the entire residual heat recovery by the bottoming cycle could definitely increase the system thermal efficiency, the low ORC evaporation temperature and mediocre ORC performance leads to a limited improvement. While in the combined cycle system with a pre-cooler, higher ORC evaporation temperature could be attained and it has a remarkable effect on the ORC performance, even though part of the topping cycle residual heat is discharged to the ambient. The simulation results reveal that the S-CO2-ORC combined cycle system performance could be significantly improved through this parametric optimization. The recompression S-CO2 cycle with bottoming ORC is then analyzed and thermal performance is improved based on the previous optimization results. The bottoming ORC could effectively recover the residual heat of the topping S-CO2 cycle and increase the system thermal efficiency, thus it can be considered and applied in similar practical cases.
•An ORC is added to the S-CO2 cycle for residual heat recovery.•Different recuperative ratios of the topping cycle is considered.•Influence of the heat source conditions on the bottoming ORC is evaluated.•Parametric optimization of the combined cycle system is conducted.
Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first ...genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.
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•Ore geology, distribution, magmatic affinity, and relations to porphyry, high-sulfidation, and low-sulfidation deposits of intermediate sulfidation epithermal (IS) deposits are ...reviewed.•Deep and slow fluids exsolving is favorable for the occurrence of IS deposits.•An empirical subclassification (NC-type IS in neutral-compressive settings and E-type IS in extensional settings) of IS deposits is proposed.•The subtypes of IS are mainly controlled by the source of parental magma.
Intermediate sulfidation (IS) veins is one of the subtypes of epithermal deposits formed in subduction-related arc settings or post-collisional orogenic belts. The economic and scientific significance of IS deposits has been highlighting importance in Ag-Au-Pb-Zn exploration and study of porphyry-epithermal systems. This epithermal clan of deposits typically have a close relationship with andesitic-dacitic volcanic-subvolcanic rocks, and formed at a depth of ∼0.3 to as much as 1 + km. IS deposits are typically related to oxidized calcic to calc-alkaline magmatism. Fluid homogenization temperatures and salinities range between 150 and 350 °C, and 0 and 23 wt% NaCl equivalent, respectively. The O and H isotope compositions are consistent with a mixture of magmatic and meteoric water, with an increase in meteoric diluent as the hydrothermal system wanes. Most of the IS deposits in the world, particularly those in Circum-Pacific metallogenic belts, formed during Cenozoic time. Several Mesozoic and Paleozoic IS deposits in the Central Asian Orogenic Belt imply great exploration potential for pre-Cenozoic IS deposits in this area.
The presence of Mn-carbonate such as rhodochrosite and manganocalcite (locally Mn-silicate, e.g., rhodonite, helvite) typically in mid to late hydrothermal stages is a common diagnostic feature to discern IS from low-sulfidation (LS) deposits. In addition, the occurrence of intermediate-sulfidation state sulfides such as pyrite, chalcopyrite, sphalerite, galena, and tetrahedrite/tennantite associations are another indicator of the IS type; light-colored (Fe-poor) sphalerite is typical of IS deposits, consistent with relatively oxidized fluids. Elevated fluid salinity is another characteristic, with maximum salinity values of base metal-rich IS veins usually >5 wt% NaCl equiv.
The reported IS deposits worldwide show that they develop in compressional volcanic arcs as well as in some extensional settings. In this review, IS deposits are subdivided into “NC (Neutral-Compressional)-type IS” with a low Ag/Au ratio (<60), formed in neutral to compressive stress state volcanic arcs, and “E (Extensional)-type IS”, on the contrary, with a high Ag/Au ratio (>60), formed in extensional settings such as extensional intra-arc, post-collisional orogenic belts, and back-arc settings. Another notable feature of E-type IS deposits is their large Ag endowment compared to NC-type IS. NC-type IS (Au ± Ag) deposits can be associated with porphyry Cu-Au and/or high sulfidation (HS) Au-Cu deposits, and their economic metals are mainly gold and/or silver. By contrast, some E-type IS deposits can occur on the flanks of porphyry molybdenum deposits; E-type IS veins can also occur together with LS precious metal veins in back arcs or extensional continental margins, the most representative examples occurring in Mexico. The occurrence of the two subtypes of IS are largely controlled by the parent magma, with parent magma of NC-type IS primarily derived from depleted mantle or juvenile crust, while parent magma of E-type IS mainly from (ancient?) continental crust.
The occurrence of IS deposits is presumably controlled by tectono-magmatic settings and fluid evolution paths. Neutral to compressive stress regime, relatively great depth to an exsolving magma (>4 km) and low exsolution rate of magmatic fluids, plus the presence of syn-ore dikes in conjunction with the development of interconnected fracture networks above the porphyry stock could be conducive for the occurrence of IS (and also HS) Au veins upon porphyry copper deposits (PCDs). Confirmation of sub-types and variations of IS veins can aid in exploration for spatially and genetic-related mineralization types, such as porphyry and HS deposits.
•Preheating S-CO2 cycle system is used for engine waste heat recovery.•Influence of the preheating temperature is evaluated.•A regeneration branch is added to achieve a sufficient regeneration ...process.•Performance improvement is achieved.
Due to the compact structure in addition to the system safety level and environmental friendly characteristics, supercritical CO2 (S-CO2) cycle has emerged as a promising method to be used in engine waste heat recovery. This paper explores the potential of using a preheating S-CO2 cycle based system to recover the waste heat of a diesel engine. An original preheating system is presented, in which the high temperature engine exhaust gas is firstly utilized in the evaporator and then it is further cooled through preheating process together with the low temperature jacket cooling water. Though the entire heat load from these two heat sources could be entirely recovered, the high preheating temperature suppresses the heat transfer in the regenerator. An improved preheating S-CO2 cycle based system with a regeneration branch is then presented. S-CO2 flow from the compressor is divided into two parts, one of which is still preheated by the jacket cooling water and the cooled engine exhaust gas in series while the other is heated in a low temperature regenerator. The two flows converge and then continues to be heated in the high temperature regenerator and in the evaporator. The simulation results reveal that the improved system could achieve a deeper utilization of the regeneration heat load hence improve the system performance. The maximum net power output of the improved system reaches 68.4 kW, which is 7.4% higher than that of the original system, 63.7 kW. Adopting the improved preheating S-CO2 cycle based system for waste heat recovery, the engine power output (996 kW) can be increased by 6.9%.
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•Eight types of functional materials in the field of chiral CE are covered.•The application modes of these materials are systematically classified.•Parallel comparisons of different ...types of functional materials are presented.•A technical summary of functional materials in chiral CE is given.•A literature database on this topic is provided for readers to use.
Researchers in the field of chiral science have been endeavoring to develop high-performance analytical methods for enantioseparations. The inherent flexibility of capillary electrophoresis (CE) provides a unique platform for scientists to come up with innovative ideas. In reviewing the literature of the past years, it is not difficult to notice that the application of various functional materials in chiral CE has attracted considerable attention of researchers. A search performed using databases (Web of Science, Scopus and Google Scholar) for journal reports using the terms “Chiral CE” & “Materials” returned approximately 300 publications (since 2010). The aim of this article is to provide an overview of the development and state-of-the-art of various advanced functional materials in chiral CE. Rather than exhaustively listing all the applications, this review concentrates on innovative concepts, and highlights significant progress and issues in this field, especially in the past decade. Coverage includes the most representative types of advanced functional materials such as ionic liquids (ILs), deep-eutectic solvents (DESs), nanoparticles (NPs), molecularly imprinted polymers (MIPs), metal organic frameworks (MOFs), covalent organic frameworks (COFs) and some other advanced porous organic materials.
Abstract
Complex biomedical data generated during clinical, omics and mechanism-based experiments have increasingly been exploited through cloud- and visualization-based data mining techniques. ...However, the scientific community still lacks an easy-to-use web service for the comprehensive visualization of biomedical data, particularly high-quality and publication-ready graphics that allow easy scaling and updatability according to user demands. Therefore, we propose a community-driven modern web service, Hiplot (https://hiplot.org), with concise and top-quality data visualization applications for the life sciences and biomedical fields. This web service permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be conducted by senior bioinformatics or biostatistics researchers. It covers most of the daily demands of biomedical researchers with its equipped 240+ biomedical data visualization functions, involving basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modelling, etc. Moreover, to improve the efficiency in use and development of plugins, we introduced some core advantages on the client-/server-side of the website, such as spreadsheet-based data importing, cross-platform command-line controller (Hctl), multi-user plumber workers, JavaScript Object Notation-based plugin system, easy data/parameters, results and errors reproduction and real-time updates mode. Meanwhile, using demo/real data sets and benchmark tests, we explored statistical parameters, cancer genomic landscapes, disease risk factors and the performance of website based on selected native plugins. The statistics of visits and user numbers could further reflect the potential impact of this web service on relevant fields. Thus, researchers devoted to life and data sciences would benefit from this emerging and free web service.
The transition metal‐catalyzed cross‐coupling reaction with Fischer metal carbene intermediates bearing an electron‐rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily ...available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer‐type copper carbene species bearing a α‐siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox‐neutral conditions. The side‐arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.
The coupling of alkynes with the Fischer‐type copper carbene species has been achieved, by harnessing α‐siloxyl carbene intermediates that were in situ generated from acylsilanes. Mechanistic studies suggested that the side‐arm modified bisoxazoline (SaBox) ligands are crucial for this coupling reaction.
To explore the prognostic significance of preoperative prognostic nutritional index (PNI) in bladder cancer after radical cystectomy and compare the prognostic ability of inflammation-based indices.
...We retrospectively analyzed data for 516 patients with bladder cancer who underwent radical cystectomy in our institution between 2006 to 2012. Clinicopathologic characteristics and inflammation-based indices (PNI, neutrophil/lymphocyte ratio NLR, platelet/lymphocyte ratio PLR, lymphocyte/monocyte ratio LMR) were evaluated by pre-treatment measurements. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method and compared by log-rank test. Multivariate analysis with a Cox proportional hazards model was used to confirm predictors identified on univariate analysis. The association between clinicopathological characteristics and PNI or NLR was tested.
Among the 516 patients, the median follow-up was 37 months (interquartile range 20 to 56). On multivariate analysis, PNI and NLR independently predicted OS (PNI: hazard ratio HR = 1.668, 95% CI: 1.147-2.425, P = 0.007; NLR: HR = 1.416, 95% CI:1.094-2.016, P = 0.0149) and PFS (PNI: HR = 1.680, 95% CI:1.092-2.005, P = 0.015; NLR: HR = 1.550, 95% CI:1.140-2.388, P = 0.008). Low PNI predicted worse OS for all pathological stages and PFS for T1 and T2 stages. Low PNI was associated with older age (>65 years), muscle-invasive bladder cancer, high American Society of Anesthesiologists grade and anemia.
PNI and NLR were independent predictors of OS and PFS for patients with bladder cancer after radical cystectomy and PNI might be a novel reliable biomarker for bladder cancer.
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