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SLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

China's electricity demand has grown rapidly over only two decades and is currently the largest in the world. This was largely owing to a framework of regulation in which governments regulated prices and quantities, and there was ample incentive for investment. As the growth in electricity demand has slowed and the use of renewable energy has been impeded by integration-related challenges, China has embarked on a new round of power sector reform, with a focus on market construction. Considering four years of market experiments at the provincial level, we review the backgrounds and goals of the reforms, as well as the current progress toward meeting the initial targets. Then, we discuss the key challenges to be overcome to achieve complete implementation of the reforms, with special emphasis on the system of dispatch. We recommend that China's reforms, in order to achieve the goal of market-based competition, must embrace short-term markets, a greater role for independent regulation, compatibility with renewable energy, and inter-provincial coordination.

China's electricity system is the world's largest, in terms of installed generating capacity, and is also the world's largest single source of greenhouse gas emissions. In 2015, China embarked on reforms in its electricity sector that aim to introduce market mechanisms in wholesale pricing. This study provides a quantitative assessment of the economic and carbon dioxide (CO2) emission impacts of transitioning to electricity markets in China, focusing on Guangdong Province. We find that market reforms deliver significant annual cost savings (21 to 63 billion yuan, 9%–27% reduction in total costs in a base case) to consumers in Guangdong, with smaller production cost savings (12 billion yuan, 13% reduction in production costs in a base case). Savings for consumers are accompanied by a large reduction in net revenues for coal and natural gas generators, raising concerns about generator solvency, longer-term resource adequacy, and the need for transition mechanisms. Market reforms increase CO2 emissions in Guangdong, as a result of gas-to-coal switching, though higher hydropower imports from neighboring provinces could offset these emissions. CO2 pricing has a limited impact on CO2 emissions in the short run and has the potential to lead to significant wealth transfers. The most important benefit of market reforms will be in providing an economic framework for longer-term operations and investment.

In order to achieve low cost and high stability metal oxide-based inverted planar perovskite solar cells (IPSCs), we designed Al-doped NiOx (ANO) films as the hole transport layer (HTL) to prepare a solar cell with ITO/ANO/CsPbBr3/ZnO/carbon structure. The results showed that compared to the pristine NiOx film, ANO-8 (8% Al doping) film could not only provide higher conductivity and carrier mobility, but also form a good interfacial band alignment with the CsPbBr3 perovskite layer. Additionally, a better crystallization quality and larger grain size of CsPbBr3 films could be obtained on the ANO-8 HTL. Therefore, the champion efficiency based on this optimization strategy reached 6.72%, where the open circuit voltage (Voc) was 1.33 V and the short circuit current (Jsc) was 8.11 mA/cm2. After 28 days, the photoelectric conversion efficiency still retained 96.73% of the original efficiency in an air environment with 80% relative humidity and temperature of 25 °C, demonstrating considerable stability. These results provide a promising approach for achieving stable and reliable IPSCs with low-cost inorganic HTLs. [ABSTRACT FROM AUTHOR]

Super‐resolution imaging techniques, such as structured illumination microscopy (SIM), have enabled researchers to obtain nanoscale organelle‐level outputs in living systems, but they impose additional stringent requirements on fluorescence probes. However, high‐performance, custom‐designed SIM probes that can explain underlying biological processes remain unavailable. Herein, a customizable engineering toolkit is developed for the facile assembly of SIM probes suitable for subcellular component detection. This toolkit is used to customize a fluorescent molecule, CPC (coumarin–phenylhydrazine–carboxyl), capable of simultaneously monitoring peroxynitrite (ONOO−) and polarity distribution in mitochondria and lipid droplets (LDs), respectively, through functional ON–OFF mechanisms. The customized CPC molecule demonstrated excellent imaging capabilities under SIM, enabled the successful localization of multiple organelles, and reliably tracked the distribution of different components, thus facilitating the study of the interplay between organelles. Using CPC, the physical transition of intracellular LDs is demonstrated from heterogeneity to homogeneity. This was specifically observed during ferroptosis where the polarity of the LDs increased and their morphology became more contracted. Furthermore, the loss of LDs functionality could not counteract the accumulation of ONOO− within the mitochondria, leading to the decoupling of mitochondrial LDs during ferroptosis. These results confirmed the potential mechanism of LDs dysfunction and decoupling triggered via cumulative mitochondrial oxidative stress during ferroptosis. To summarize, this toolkit will be a powerful tool for examining subtle variations among components during the interplay between different organelles, thus offering novel avenues for understanding and treating related diseases. [ABSTRACT FROM AUTHOR]

Background: Skeleton involvement is one of the most significant aspects of Gaucher disease (GD). However, the treatment for spinal involvement in GD among patients undergoing enzyme replacement therapy (ERT) is poorly characterized. We present a case of progressive kyphotic spinal deformity in a young child caused by vertebral involvement, which was managed by posterior spinal fusion without anterior spinal release under ERT. Case presentation: This is a retrospective study. A 10-year-old boy presenting with progression kyphosis (thoracic kyphotic angle of 113°) associated with type-IIIb GD had undergone posterior spinal fusion with segmental pedicle screw fixation (from T6-L3) and Ponte osteotomy. The patient went back to school without further brace protection. Proximal junctional kyphosis (PJK) was observed at 4 months postoperatively. Revision surgery was performed to prevent neurological impairment. Additional posterior spinal fusion from T2–T6 and decompressive laminectomy were performed during the revision surgery. A 2-year follow-up showed no recurrence of PJK and solid fusion was achieved in the patient under ERT and brace protection. Conclusions: Posterior spinal fusion without anterior spinal release is a good treatment option for severe spinal deformity in patients with GD. However, the fusion level and reinforced fixation require careful consideration. Revision surgery and brace protection is needed as long as PJK is observed. [ABSTRACT FROM AUTHOR]

In this paper, the problem of direct data-driven control is studied for a class of discrete-time switched systems with input saturation. For unknown switched systems, a data-driven approach is adopted to parameterize the controller directly from the input-state data of the system, which does not depend on the exact mathematical model. In addition, the input saturation problem is addressed by using the polyhedral convex hull method, and the data representation is given for the closed-loop system. By using Lyapunov theory and dwell time method, the exponential stability conditions of linear matrix inequalities (LMIs) form are obtained, and the desired attractive domain is estimated. Moreover, considering the data polluted by process noise, a robust data-driven state feedback controller is designed and the performance of $ \mathcal{L}_{2} $ gain is guaranteed. Finally, the advantage of the proposed data-driven based control method is verified by two numerical examples. [ABSTRACT FROM AUTHOR]