Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis It was approved by the FDA for the treatment of advanced renal ...cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma （HCC） in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems. Recent studies to the primary resistance, mechanisms are underying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Here, we briefly describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for HCC patients.
Potassium‐ion batteries (PIBs) are promising alternatives to lithium‐ion batteries because of the advantage of abundant, low‐cost potassium resources. However, PIBs are facing a pivotal challenge to ...develop suitable electrode materials for efficient insertion/extraction of large‐radius potassium ions (K+). Here, a viable anode material composed of uniform, hollow porous bowl‐like hard carbon dual doped with nitrogen (N) and phosphorus (P) (denoted as N/P‐HPCB) is developed for high‐performance PIBs. With prominent merits in structure, the as‐fabricated N/P‐HPCB electrode manifests extraordinary potassium storage performance in terms of high reversible capacity (458.3 mAh g−1 after 100 cycles at 0.1 A g−1), superior rate performance (213.6 mAh g−1 at 4 A g−1), and long‐term cyclability (205.2 mAh g−1 after 1000 cycles at 2 A g−1). Density‐functional theory calculations reveal the merits of N/P dual doping in favor of facilitating the adsorption/diffusion of K+ and enhancing the electronic conductivity, guaranteeing improved capacity, and rate capability. Moreover, in situ transmission electron microscopy in conjunction with ex situ microscopy and Raman spectroscopy confirms the exceptional cycling stability originating from the excellent phase reversibility and robust structure integrity of N/P‐HPCB electrode during cycling. Overall, the findings shed light on the development of high‐performance, durable carbon anodes for advanced PIBs.
A viable anode material composed of nitrogen/phosphorus co‐doped hollow porous bowl‐like hard carbon is developed for potassium ion batteries. The resulting anode manifests prominent merits in structure, endowing it with extraordinary K+ storage capability. The K+ storage mechanisms are revealed through in‐depth studies by combining in situ TEM studies, ex situ microscopic, and Raman spectroscopy in conjunction with DFT calculations.
Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly ...desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.
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•lncARSR promotes sunitinib resistance and predicts poor response of RCC patients•Intercellular transfer of lncARSR by exosomes disseminates sunitinib resistance•lncARSR acts as a ceRNA for miR-34 and miR-449 to promote AXL and c-MET expression•Targeting lncARSR or AXL/c-MET in sunitinib-resistant RCC restores drug sensitivity
Qu et al. identify lncARSR as a mediator of sunitinib resistance in renal cell carcinoma by acting as a competing endogenous RNA for miR-34 and miR-449, thereby increasing expression of their targets AXL and c-MET, and show that exosome-mediated transmission of lncARSR can confer resistance to sensitive cells.
The increasing demands of energy storage require the significant improvement of current Li‐ion battery electrode materials and the development of advanced electrode materials. Thus, it is necessary ...to gain an in‐depth understanding of the reaction processes, degradation mechanism, and thermal decomposition mechanisms under realistic operation conditions. This understanding can be obtained by in situ/operando characterization techniques, which provide information on the structure evolution, redox mechanism, solid‐electrolyte interphase (SEI) formation, side reactions, and Li‐ion transport properties under operating conditions. Here, the recent developments in the in situ/operando techniques employed for the investigation of the structural stability, dynamic properties, chemical environment changes, and morphological evolution are described and summarized. The experimental approaches reviewed here include X‐ray, electron, neutron, optical, and scanning probes. The experimental methods and operating principles, especially the in situ cell designs, are described in detail. Representative studies of the in situ/operando techniques are summarized, and finally the major current challenges and future opportunities are discussed. Several important battery challenges are likely to benefit from these in situ/operando techniques, including the inhomogeneous reactions of high‐energy‐density cathodes, the development of safe and reversible Li metal plating, and the development of stable SEI.
Recent developments of the five important in situ/operando characterization categories for lithium battery research are summarized, including X‐ray, electron, neutron, optical, and scanning probe techniques. For each technique, the operating principles and in situ cell design are described in detail, including representative studies of typical electrode materials and related processes summarized in tables for easy comparison and cross reference.
Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus HBV), nonalcoholic fatty liver disease, and ...alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV‐infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second‐most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western‐trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver‐related research in China. (Hepatology 2014;60:2098–2107)
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA ...sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.
Accelerated conversion by catalysis is a promising way to inhibit shuttling of soluble polysulfides in lithium–sulfur (Li–S) batteries, but most of the reported catalysts work only for one direction ...sulfur reaction (reduction or oxidation), which is still not a root solution since fast cycled use of sulfur species is not finally realized. A bidirectional catalyst design, oxide–sulfide heterostructure, is proposed to accelerate both reduction of soluble polysulfides and oxidation of insoluble discharge products (e.g., Li2S), indicating a fundamental way for improving both the cycling stability and sulfur utilization. Typically, a TiO2–Ni3S2 heterostructure is prepared by in situ growing TiO2 nanoparticles on Ni3S2 surface and the intimately bonded interfaces are the key for bidirectional catalysis. For reduction, TiO2 traps while Ni3S2 catalytically converts polysulfides. For oxidation, TiO2 and Ni3S2 both show catalytic activity for Li2S dissolution, refreshing the catalyst surface. The produced sulfur cathode with TiO2–Ni3S2 delivers a low capacity decay of 0.038% per cycle for 900 cycles at 0.5C and specially, with a sulfur loading of 3.9 mg cm−2, achieves a high capacity retention of 65% over 500 cycles at 0.3C. This work unlocks how a bidirectional catalyst works for boosting Li–S batteries approaching practical uses.
A lithium–sulfur battery with long cycling stability is assembled with a specially designed bidirectional catalyst. The TiO2–Ni3S2 heterostructured catalyst realizes the smooth trapping–diffusion–conversion of polysulfides in the reduction process. The two components show catalytic activity toward the oxidation of Li2S. Thus, the shuttle effect and the formation of dead sulfides are effectively suppressed.
Seeking an electrochemical catalyst to accelerate the liquid‐to‐solid conversion of soluble lithium polysulfides to insoluble products is crucial to inhibit the shuttle effect in lithium–sulfur ...(Li–S) batteries and thus increase their practical energy density. Mn‐based mullite (SmMn2O5) is used as a model catalyst for the sulfur redox reaction to show how the design rules involving lattice matching and 3d‐orbital selection improve catalyst performance. Theoretical simulation shows that the positions of Mn and O active sites on the (001) surface are a good match with those of Li and S atoms in polysulfides, resulting in their tight anchoring to each other. Fundamentally, dz2 and dx2−y2 around the Fermi level are found to be crucial for strongly coupling with the p‐orbitals of the polysulfides and thus decreasing the redox overpotential. Following the theoretical calculation, SmMn2O5 catalyst is synthesized and used as an interlayer in a Li–S battery. The resulted battery has a high cycling stability over 1500 cycles at 0.5 C and more promisingly a high areal capacity of 7.5 mAh cm−2 is achieved with a sulfur loading of ≈5.6 mg cm−2 under the condition of a low electrolyte/sulfur (E/S) value ≈4.6 µL mg−1.
Lattice matching and 3d‐orbital selection are proposed as two rules for the rational design of sulfur redox electrocatalysts. The former promotes the tight anchoring of polysulfides onto the SmMn2O5 catalyst, while the latter reduces the overpotential of the sulfur redox reaction, fundamentally accelerating the conversion of liquid‐phase polysulfides to solid‐phase discharge product and thus suppressing the shuttling.
Water electrolysis offers a promising energy conversion and storage technology for mitigating the global energy and environmental crisis, but there still lack highly efficient and pH-universal ...electrocatalysts to boost the sluggish kinetics for both cathodic hydrogen evolution reaction (HER) and anodic oxygen evolution reaction (OER). Herein, we report uniformly dispersed iridium nanoclusters embedded on nitrogen and sulfur co-doped graphene as an efficient and robust electrocatalyst for both HER and OER at all pH conditions, reaching a current density of 10 mA cm
with only 300, 190 and 220 mV overpotential for overall water splitting in neutral, acidic and alkaline electrolyte, respectively. Based on probing experiments, operando X-ray absorption spectroscopy and theoretical calculations, we attribute the high catalytic activities to the optimum bindings to hydrogen (for HER) and oxygenated intermediate species (for OER) derived from the tunable and favorable electronic state of the iridium sites coordinated with both nitrogen and sulfur.
Their chemical stability, high specific surface area, and electric conductivity enable porous carbon materials to be the most commonly used electrode materials for electrochemical capacitors (also ...known as supercapacitors). To further increase the energy and power density, engineering of the pore structures with a higher electrochemical accessible surface area, faster ion‐transport path and a more‐robust interface with the electrolyte is widely investigated. Compared with traditional porous carbons, two‐dimensional (2D) porous carbon sheets with an interlinked hierarchical porous structure are a good candidate for supercapacitors due to their advantages in high aspect ratio for electrode packing and electron transport, hierarchical pore structures for ion transport, and short ion‐transport length. Recent progress on the synthesis of 2D porous carbons is reported here, along with the improved electrochemical behavior due to enhanced ion transport. Challenges for the controlled preparation of 2D porous carbons with desired properties are also discussed; these require precise tuning of the hierarchical structure and a clarification of the formation mechanisms.
Two‐dimensional (2D) porous carbon sheets, which can be synthesized by templating approaches, biomass carbonization, biomass carbonization–activation, in situ activation, etc, are good candidates for supercapacitors due to their advantages in their short ion‐transport length and high aspect ratio for electrode packing and electron transport.
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