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The metabolic rewiring of tumor cells and immune cells has been viewed as a promising source of novel drug targets. Many of the molecular pathways implicated in rheumatoid arthritis (RA) directly modify synovium metabolism and transform the resident cells, such as the fibroblast-like synoviocytes (FLS), and the synovial tissue macrophages (STM), toward an overproduction of enzymes, which degrade cartilage and bone, and cytokines, which promote immune cell infiltration. Recent studies have shown metabolic changes in stromal and immune cells from RA patients. Metabolic disruption in the synovium provide the opportunity to use in vivo metabolism-based imaging techniques for patient stratification and to monitor treatment response. In addition, these metabolic changes may be therapeutically targetable. Thus, resetting metabolism of the synovial membrane offers additional opportunities for disease modulation and restoration of homeostasis in RA. In fact, rheumatologists already use the antimetabolite methotrexate, a chemotherapy agent, for the treatment of patients with inflammatory arthritis. Metabolic targets that do not compromise systemic homeostasis or corresponding metabolic functions in normal cells could increase the drug armamentarium in rheumatic diseases for combination therapy independent of systemic immunosuppression. This article summarizes what is known about metabolism in synovial tissue cells and highlights chemotherapies that target metabolism as potential future therapeutic strategies for RA.

How macrophages are programmed to respond to monosodium urate crystals (MSUc) is incompletely understood partly due to the use of a toll-like receptor-induced priming step. Here, using genome wide transcriptomic analysis and biochemical assays we demonstrate that MSUc alone induces an in vitro metabolic and inflammatory transcriptional program in both human and murine macrophages markedly distinct from that induced by LPS. Genes uniquely up-regulated in response to MSUc belonged to lipids, glycolysis, and transport of small molecules via SLC transporters pathways. Sera from individuals and mice with acute gouty arthritis provided further evidence for this metabolic rewiring. This distinct macrophage activation may explain the initiating mechanisms in acute gout flares and is regulated through JUN binding to the promoter of target genes through activation of JNK (but not by P38) in a process that is independent of inflammasome activation. Finally, pharmacological JNK inhibition limited MSUc-induced inflammation in animal models of acute gouty inflammation. Competing Interest Statement The authors have declared no competing interest.

In this work, a selective wet etching process of Si to Si 0.7 Ge 0.3 with TMAH solution to fabricate SiGe nanowires is systematically investigated. Initially, the 2.3% TMAH solution at 20 °C is applied for the as grown Si 0.7 Ge 0.3 /Si multilayers stack and a “rectangular” profile is achieved at the Si 0.7 Ge 0.3 extremity due to its high selectivity. However, the reduction of Ge concentration due to the Ge interdiffusion caused by the high temperature anneal treatment will attain a reduced selectivity of Si to Si 0.7 Ge 0.3 and a “rounding” Si 0.7 Ge 0.3 extremity profile. Moreover, the profile of the upper Si 0.7 Ge 0.3 extremity is clearly worse than the bottom one. This is because the Ge concentration of upper Si 0.7 Ge 0.3 is 1.5% lower and the Ge interdiffusion of the upper Si 0.7 Ge 0.3 is slightly worse. After increasing the TMAH concentration to 25%, both the upper and bottom Si 0.7 Ge 0.3 extremity can achieve a “rectangular” extremity profile with an almost the same Si 0.7 Ge 0.3 loss ~ 1.5 nm per side. Compared with 2.3% TMAH concentration, the Ge concentration of the etching off SiGe film can be reduced from lower than 29% to lower than 24% using the 25% TMAH solution at 20 °C. Therefore, the 25% TMAH solution at 20 °C is chosen as the optimal selective etching condition for the thermal treated Si 0.7 Ge 0.3 /Si multilayers stack samples. Finally, a vertical stacked double SiGe nanowire structure is successfully prepared by utilizing this optimal process condition. This indicates that it is a practicable technique for the selective wet etching of Si in fabricating SiGe nanowires.

Background and objectiveThe injury of the cholinergic white matter pathway underlies cognition decline in patients with silent cerebrovascular disease (SCD) with white matter hyperintensities (WMH) of vascular origin. However, the evaluation of the cholinergic white matter pathway is complex with poor consistency. We established an intelligent algorithm to evaluate WMH in the cholinergic pathway.MethodsPatients with SCD with WMH of vascular origin were enrolled. The Cholinergic Pathways Hyperintensities Scale (CHIPS) was used to measure cholinergic white matter pathway impairment. The intelligent algorithm used a deep learning model based on convolutional neural networks to achieve WMH segmentation and CHIPS scoring. The diagnostic value of the intelligent algorithm for moderate-to-severe cholinergic pathway injury was calculated. The correlation between the WMH in the cholinergic pathway and cognitive function was analysed.ResultsA number of 464 patients with SCD were enrolled in internal training and test set. The algorithm was validated using data from an external cohort comprising 100 patients with SCD. The sensitivity, specificity and area under the curve of the intelligent algorithm to assess moderate and severe cholinergic white matter pathway injury were 91.7%, 87.3%, 0.903 (95% CI 0.861 to 0.952) and 86.5%, 81.3%, 0.868 (95% CI 0.819 to 0.921) for the internal test set and external validation set. for the. The general cognitive function, execution function and attention showed significant differences among the three groups of different CHIPS score (all p<0.05).DiscussionWe have established the first intelligent algorithm to evaluate the cholinergic white matter pathway with good accuracy compared with the gold standard. It helps more easily assess the cognitive function in patients with SCD.

In this work, SiGe Fin formation technique using shallow trench isolation (STI) first or STI last strategy for the high mobility channel FinFET device is systematically investigated. A 20 nm width and 35 nm height high crystalline quality of the Si 0.7 Ge 0.3 Fin formation for STI first scheme is demonstrated by utilizing a new developed Si Fin etching, Si Fin recess and SiGe selective epitaxial growth process. For the STI last strategy, a novel chemical mechanical planarization (CMP) treated three-layer SiGe strain relaxed buffer (SRB) is successfully fabricated and a 50 nm high crystal quality and atomically smooth surface Si 0.5 Ge 0.5 layer on this SRB is attained. Moreover, a spike annealing is employed to avoid the Si 0.5 Ge 0.5 Fin oxidation during STI densification with an acceptable STI etching rate. However, both a spike annealing and a lower temperature of traditional furnace at 850 °C or 750 °C suffer micro-trench issue during the Fin reveal process. Therefore, a new developed process, named as STI recess first, is developed to resolve both thermal instability and micro-trench issue at the same time. A minor Si 0.5 Ge 0.5 Fin loss with a sharp Si 0.7 Ge 0.3 SRB/Si 0.5 Ge 0.5 interfaces for STI last scheme is realized by utilizing this new developed STI recess first process.

利用美国国家海洋大气管理局2007年发布的全球海域温度数据库资料和美国国家地球物理数据中心2006年发布的海底地形数据库资料,对东海黑潮热核(即高温区)的时空分布进行了分析。结果显示:从表层到250m深,东海黑潮热核的分布区域由表层的靠近中轴线附近逐渐偏向黑潮的东部边缘,分布范围由表层占黑潮流幅的30%以上缩减到250m深度的10%左右,250m以下热核的分布范围和区域再没有明显的变化;从表层到水深200m,从东海黑潮的入口到出口,热核的温度与深度呈下降的趋势,在200m以下呈上升的趋势,2月份上层下降的趋势最明显;热核在台湾东北部和30°N附近进入吐噶喇海峡处均出现明显的转弯点,随着深度的增加热核的转弯点逐渐偏向东南,在台湾东北部200m水深以上热核转弯点分布还存在明显的季节变化。

通过对近10年来中国近海海平面变化研究成果的分析得出:(1)中国海域海平面变化时空差异明显,沿海海平面高值出现在8-9月,最低值出现在2-3月,季节最大差值可达20.75 cm;黄海和东海海区东南高、西北低;南海夏季西低东高,冬季东低西高;从辽宁到广西海平面上升速率差异大,范围在-2.1~10 mm/a之间;相对海平面上升较快区域主要是黄河三角洲、长江三角洲和珠江三角洲,2050年3个地区海平面预计分别上升980、720、520 mm。(2)地面沉降已经成为中国东部沿海相对海平面上升速率高的重要影响因素,在黄河三角洲和长江三角洲人口密集地区尤为突出。(3)每年8-9月为我国一年中的海平面最高月份,此时也正是热带气旋影响中国东南沿海的高峰时段,在季风、热带气旋等共同作用下,东南沿海高海平面将对东南沿海城市安全构成严重威胁。