Single‐crystalline Ni‐rich cathodes are promising candidates for the next‐generation high‐energy Li‐ion batteries. However, they still suffer from poor rate capability and low specific capacity due ...to the severe kinetic hindrance at the nondilute state during Li+ intercalation. Herein, combining experiments with density functional theory (DFT) calculations, we demonstrate that this obstacle can be tackled by regulating the oxidation state of nickel via injecting high‐valence foreign Ta5+. The as‐obtained single‐crystalline LiNi0.8Co0.1Mn0.1O2 delivers a high specific capacity (211.2 mAh g−1 at 0.1 C), high initial Coulombic efficiency (93.8 %), excellent rate capability (157 mAh g−1 at 4 C), and good durability (90.4 % after 100 cycles under 0.5 C). This work provides a strategy to mitigate the Li+ kinetic hindrance of the appealing single‐crystalline Ni‐rich cathodes and will inspire peers to conduct an intensive study.
The Ta doping created some low‐valence Ni, decreasing the electrostatic repulsion between transition metal and Li+, thus the Li+ diffusion energy barrier has been decreased and the kinetic hindrance was mitigated.
Background
NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain ...unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non‐apoptotic form of cell death induced by iron‐dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression.
Method
Mice were fed on MCD‐diet to mimic NASH progression and gene expression in liver was analysed by RNA‐seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture.
Results
RNA‐seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD‐diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD‐fed mice. Scavenging of ferroptosis‐linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD‐diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation.
Conclusion
Our results demonstrate an important role of ferroptosis in the progression of MCD‐diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.
The ability of cells to respond to changes in nutrient availability is essential for the maintenance of metabolic ho- meostasis and viability. One of the key cellular responses to nutrient withdrawal ...is the upregulation of autophagy. Recently, there has been a rapid expansion in our knowledge of the molecular mechanisms involved in the regula- tion of mammalian autophagy induction in response to depletion of key nutrients. Intracellular amino acids, ATP, and oxygen levels are intimately tied to the cellular balance of anabolic and catabolic processes. Signaling from key nutrient-sensitive kinases mTORC1 and AMP-activated protein kinase （AMPK） is essential for the nutrient sensing of the autophagy pathway. Recent advances have shown that the nutrient status of the cell is largely passed on to the autophagic machinery through the coordinated regulation of the ULK and VPS34 kinase complexes. Identification of extensive crosstalk and feedback loops converging on the regulation of ULK and VPS34 can be attributed to the im- portance of these kinases in autophagy induction and maintaining cellular homeostasis.
Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made ...remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies.
This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method.
1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952–0·957) in the internal validation set, 0·927 (0·925–0·929) in the prospective set, and ranged from 0·915 (0·913–0·917) to 0·977 (0·977–0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 95% CI 0·924–0·957 vs 0·945 0·927–0·959; p=0·692) and superior sensitivity compared with competent (0·858 0·832–0·880, p<0·0001) and trainee (0·722 0·691–0·752, p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788–0·838) for GRAIDS, 0·932 (0·913–0·948) for the expert endoscopist, 0·974 (0·960–0·984) for the competent endoscopist, and 0·824 (0·795–0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971–0·984) for GRAIDS, 0·980 (0·974–0·985) for the expert endoscopist, 0·951 (0·942–0·959) for the competent endoscopist, and 0·904 (0·893–0·916) for the trainee endoscopist.
GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses.
The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.
High‐nickel (Ni ≥ 90%) cathodes with high specific capacity hold great potential for next‐generation lithium‐ion batteries (LIBs). However, their practical application is restricted by the high ...interfacial reactivity under continuous air erosion and electrolyte assault. Herein, a stable high‐nickel cathode is rationally designed via in situ induction of a dense amorphous Li2CO3 on the particle surface by a preemptive atmosphere control. Among the residual lithium compounds, Li2CO3 is the most thermodynamically stable one, so a dense Li2CO3 coating layer can serve as a physical protection layer to isolate the cathode from contact with moist air. Furthermore, amorphous Li2CO3 can be transformed into a robust F‐rich cathode electrolyte interphase (CEI) during cycling, which reinforces the cathode's interfacial stability and improves the electrochemical performance. The assembled coin cell with this modified cathode delivers a high discharge capacity of 232.4 mAh g–1 with a superior initial Coulombic efficiency (CE) of 95.1%, and considerable capacity retention of 90.4% after 100 cycles. Furthermore, no slurry gelation occurs during the large‐scale electrode fabrication process. This work opens a valuable perspective on the evolution of amorphous Li2CO3 in LIBs and provides guidance on protecting unstable high‐capacity cathodes for energy‐storage devices.
A high‐nickel cathode (Ni ≥ 90%) is developed through controlling the surface residual lithium composition with a formed amorphous Li2CO3 protective layer. This cathode can resist corrosion by air, and will be converted into a stable cathode electrolyte interphase during the electrochemical process, resulting in enhanced storage performance and extended cycle life for high‐nickel cathodes.
Summary Background Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose ...dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. Methods We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn , number ChiCTR-TRC-10000802. Findings Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 9% of 350 patients) than in the placebo group (79 23% of 350 patients; odds ratio OR 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 18% of 350 patients) than with dexmedetomidine (34 10% of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 14% of 350 patients) than in patients given dexmedetomidine (23 7% of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. Interpretation For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Funding Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.
•LTM, industrial structure optimization and green TFP are integrated into a unified framework.•LTM, industrial structure rationalization and optimization all can improve green TFP, while their ...interactions would inhibit it in China.•There exist regional differences of the impact of LTM and industrial structure on green TFP across the regions in China.
Market-oriented allocation of land resources is one of the main economic reforms in China. However, the influence of land transfer marketization (LTM) on green total factor productivity (green TFP) and its mechanisms remain unknown. Based on panel data of 30 provincial administrative regions in China from 2004 to 2016, this study attempts to establish mechanism among LTM, industrial structure and green TFP, which is measured by the Slack Based Measure DEA (SBM-DEA) model containing undesirable output, and empirically estimates the impact of LTM, the rationalization and optimization of industrial structure and their interactions on green TFP further. The results show that: 1) LTM has a significant promoting effect on the improvement of green TFP in China, and the effect is also significant in the eastern, central and western regions as well, indicating that the application of land transfer policy to regulate regional economic development is widespread in China. 2) The rationalization of industrial structure has significantly promoted the development of green TFP in China, as well as at the regional levels, and the effect decreases from the western region to the central and eastern regions. The optimization of industrial structure also has a promoting effect on green TFP in China and all the regions, but the regional differences of the effect are contrary to that of the rationalization of industrial structure, with a decreasing trend from the eastern region to the central and western regions. 3) The interaction between LTM and the rationalization of industrial structure has significantly inhibited the improvement of green TFP in China, and the regional variations of the restraining effect are higher in the western region, followed by the central and eastern regions. The interaction between LTM and the optimization of industrial structure also has a negative effect on green TFP in China, and the regional variations of the effect showing the decreasing trend from the eastern region to the western and central regions. Therefore, China should continue to adhere to the market-oriented urban land transfer system reform, actively play the role of the government in the industrial upgrading and industrial transfer, and formulate a differentiated land transfer system and industrial development policies based on the economic development and industrial characteristics of various regions, so as to achieve the sustainable development of China’s economy and society.
Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 ...(PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion. Mechanistically, cisplatin induces PFKFB3 acetylation at lysine 472 (K472), which impairs activity of the nuclear localization signal (NLS) and accumulates PFKFB3 in the cytoplasm. Cytoplasmic accumulation of PFKFB3 facilitates its phosphorylation by AMPK, leading to PFKFB3 activation and enhanced glycolysis. Inhibition of PFKFB3 sensitizes tumor to cisplatin treatment in a xenograft model. Our findings reveal a mechanism for cells to stimulate glycolysis to protect from DNA damage and potentially suggest a therapeutic strategy to sensitize tumor cells to genotoxic agents by targeting PFKFB3.
PDF
