The reversible effects of free fatty acids on sulfonylurea-stimulated insulin secretion are related to the expression and dynamin-mediated endocytosis of KATP channels in pancreatic β cells

Objective: Lipotoxicity-induced pancreatic β cell-dysfunction results in decreased insulin secretion in response to multiple stimulus. In this study, we i nvestigated the reversible effects of palmitate (PA) or oleate (OA) on insulin secretion and the relationship with pancreatic β-cell ATP-sensitive potassium (KATP) channels. Methods: MIN6 cells were treated with PA and OA for 48 h and then washed out for 24 h to determine the changes in expression and endocytosis of the KATP channels and glucose-stimulated insulin secretion (GSIS) and sulfonylurea-stimulated insulin secretion (SU-SIS). Results: MIN6 cells exposed to PA or OA showed both impaired GSIS and SU -SIS; the former was not restorable, while the latter was reversible with washout of PA or OA. Decreased expressions of both total and surface Kir6.2 and SUR1 and endocytosis of KATP channels were observed, which were also recoverable after wash out. When MIN6 cells exposed to free fatty acids (FFAs) were cotreated wi th 5-aminoimidazole- 4-carboxamide ribonucleotide (AICAR) or dynasore, we found that endocytosis of KATP channels did not change significantly by AICAR but was almost co mpletely blocked by dynasore. Meanwhile, the inhibition of endocytosis of K ATP channels after washout could be activated by PIP2. The recovery of SU-SIS after washout was significantly weakened by PIP2, but the decrease of SU-SIS induced by FFAs was not allevi ated by dynasore. Conclusions: FFAs can cause reversible impairment of SU-SIS on pancreatic β cells. The reversibility of the effects is partial because of the changes o f expression and endocytosis of Kir6.2 and SUR1 which was mediated by dynamin

Functional profile of perilesional gray matter in focal cortical dysplasia: an fMRI study

ObjectivesWe aim to investigate the functional profiles of perilesional gray matter (GM) in epileptic patients with focal cortical dysplasia (FCD) and to correlate these profiles with FCD II subtypes, surgical outcomes, and different antiseizure medications (ASMs) treatment response patterns.MethodsNine patients with drug-responsive epilepsy and 30 patients with drug-resistant epilepsy (11 were histologically confirmed FCD type IIa, 19 were FCD type IIb) were included. Individual-specific perilesional GM and contralateral homotopic GM layer masks were generated. These masks underwent a two-voxel (2 mm) dilation from the FCD lesion and contralateral homotopic region, resulting in 10 GM layers (20 mm). Layer 1, the innermost, progressed to Layer 10, the outermost. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analyses were conducted to assess the functional characteristics of ipsilateral perilesional GM and contralateral homotopic GM.ResultsCompared to the contralateral homotopic GM, a significant reduction of ALFF was detected at ipsilateral perilesional GM layer 1 to 6 in FCD type IIa (after Bonferroni correction p < 0.005, paired t-test), whereas a significant decrease was observed at ipsilateral perilesional GM layer 1 to 2 in FCD type IIb (after Bonferroni correction p < 0.005, paired t-test). Additionally, a significant decrease of the ReHo was detected at ipsilateral perilesional GM layer 1 compared to the CHRs in FCD type IIb. Notably, complete resection of functional perilesional GM alterations did not correlate with surgical outcomes. Compared to the contralateral homotopic GM, a decreased ALFF in the ipsilateral perilesional GM layer was detected in drug-responsive patients, whereas decreased ALFF in the ipsilateral perilesional GM layer 1–6 and decreased ReHo at ipsilateral perilesional GM layer 1 were observed in drug-resistant patients (after Bonferroni correction p < 0.005, paired t-test).ConclusionOur findings indicate distinct functional profiles of perilesional GM based on FCD histological subtypes and ASMs’ response patterns. Importantly, our study illustrates that the identified functional alterations in perilesional GM may not provide sufficient evidence to determine the epileptogenic boundary required for surgical resection

Looking under the hood: A comparison of techno-economic assumptions across national and global integrated assessment models

Integrated assessment models are extensively used in the analysis of climate change mitigation and are informing national decision makers as well as contribute to international scientific assessments. This paper conducts a comprehensive review of techno-economic assumptions in the electricity sector among fifteen different global and national integrated assessment models. Particular focus is given to six major economies in the world: Brazil, China, the EU, India, Japan and the US. The comparison reveals that techno-economic characteristics are quite different across integrated assessment models, both for the base year and future years. It is, however, important to recognize that techno-economic assessments from the literature exhibit an equally large range of parameters as the integrated assessment models reviewed. Beyond numerical differences, the representation of technologies also differs among models, which needs to be taken into account when comparing numerical parameters. While desirable, it seems difficult to fully harmonize techno-economic parameters across a broader range of models due to structural differences in the representation of technology. Therefore, making techno-economic parameters available in the future, together with of the technology representation as well as the exact definitions of the parameters should become the standard approach as it allows an open discussion of appropriate assumptions. © 2019 The Author

Emission scenario analysis for China under the global 1.5 °C target

In the Paris Agreement, there are targets set up for 2100 to be well below 2 °C. A more ambitious target of 1.5 °C also appears in the agreement. In order to address whether this target is achievable or not, studies about the 1.5 °C target's emission pathway are essential. Recently a few studies have presented modelling results of the global emission pathway for the 1.5 °C target. This paper presents an analysis for China under the global 1.5 °C pathway and budget, by looking at key options to go beyond the 2 °C target pathway. Similar to the global emission pathway, China's CO2 emissions have to be reduced quickly and reach zero emission between 2050 and 2060. China's energy system needs to make a rapid transition to much greater reduction in fossil fuel use from now on. End-use sectors need to increase electricity use significantly. Power generation will achieve negative emission before 2050. CCS will be widely used, and biomass energy with CCS (BECCS) must be adopted on a large scale by 2040. This is doable in China, but very near-term changes in policy are needed to make such a pathway happen

Transition scenarios of power generation in China under global 2 °C and 1.5 °C targets

Under the Paris Agreement, targets implemented for 2100 specify temperature increases well below 2 °C, with an ambitious target of 1.5 °C. China signed this agreement and will support these global targets. The question remains whether they are possible, especially considering the slow progress in recent decades, despite the fact that the Kyoto Protocol implemented these targets in 2010. The Intergovernmental Panel on Climate Change (IPCC) required modeling research teams to analyze possible pathways, policy options, and cost benefit analyses for GHG mitigation. China’s CO2 emissions from the energy and cement industries already accounted for almost 29% of global emissions in 2017, and this trend is expected to continue increasing. The role of China in global GHG mitigation is therefore crucial. This study presents a scenario analysis for China’s power generation against the background of the global 2 °C and 1.5 °C targets. We discuss the possibility of a lower CO2 emission power generation scenario in China in order to evaluate the national emission pathway towards these targets. Our findings suggest that China can accomplish rapid transition in the power generation sector, reaching its emission peak before 2025. This would make the global 2 °C target possible because energy system development is a key factor. Furthermore, the recent progress of key power generation technologies, potential for further investment in the power generation sector, and recent policy implementation all significantly contribute to China following a low carbon emission development pathway. Keywords: GHG mitigation, Emission scenarios, Global target, China, Modelin

High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

After reconstructing the anterior cruciate ligament (ACL), unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage. With good biological features and high formability, Magnesium-Zinc-Gadolinium (ZG21) wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation. Microstructure, tensile strength, degradation, and cytotoxicity of ZG21 wire are evaluated. The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT, histology, and mechanical test. The SEM/EDS, immunochemistry, and in vitro assessments are performed to investigate the underlying mechanism. Material tests demonstrate the high formability of ZG21 wire as surgical suture. Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation, and histologically with earlier and more fibrocartilage regeneration at the healing interface. The mechanical test shows higher ultimate load in the ZG21 group. The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate (Ca-P) deposition. IHC results demonstrate upregulation of Wnt3a, BMP2, and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing. In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a, β catenin, ocn and opn to stimulate osteogenesis. Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue. In conclusion, the ZG21 wire is feasible for tendon graft bunching. Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction