Lactam Triterpenoids from the Bark of Toona sinensis

Three new limonoid-type triterpenoids,namely toonasins A–C(1–3)with a rare lactam E ring,along with six known compounds(4–9)were isolated from the barks of Toona sinensis.The structures of new compounds were elucidated by interpretation of spectroscopic data,and the relative configuration of compound 1 was further characterized by X-ray crystallographic analyses.The isolated compounds were evaluated for their cytotoxic activities against five human tumor cell lines(HL-60,SMMC-7721,A-549,MCF-7 and SW480),and compounds 3 and 5 showed weak cytotoxicities.

Characterization of New Ent-kaurane Diterpenoids of Yunnan Arabica Coffee Beans

Five new ent-kaurane diterpenoids,named mascaroside Ⅲ–Ⅴ(1–3),and 20-nor-cofaryloside Ⅰ–Ⅱ(4–5),together with seven known diterpenoids,were isolated from methanol extracts of the green coffee beans of Yunnan Arabica Coffee.Their chemical structures were elucidated by extensive spectroscopic analyses.Meanwhile,cytotoxicity assay against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cell lines showed that they have not evident inhibition of cytotoxicity.

GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

Hyperplasia and migration of fibroblast-like synoviocytes(FLSs)are the key drivers in the pathogenesis of rheumatoid arthritis(RA)and joint destruction.Abundant Yes-associated protein(YAP),which is a powerful transcription co-activator for proliferative genes,was observed in the nucleus of inflammatory FLSs with unknown upstream mechanisms.Using Gene Expression Omnibus database analysis,it was found that Salvador homolog-1(SAV1),the pivotal negative regulator of the Hippo-YAP pathway,was slightly downregulated in RA synovium.However,SAV1 protein expression is extremely reduced.Subsequently,it was revealed that SAV1 is phosphorylated,ubiquitinated,and degraded by interacting with an important serine-threonine kinase,G protein-coupled receptor(GPCR)kinase 2(GRK2),which was predominately upregulated by GPCR activation induced by ligands such as prostaglandin E2(PGE2)in RA.This process further contributes to the decreased phosphorylation,nuclear translocation,and transcriptional potency of YAP,and leads to aberrant FLSs proliferation.Genetic depletion of GRK2 or inhibition of GRK2 by paroxetine rescued SAV1 expression and restored YAP phosphorylation and finally inhibited RA FLSs proliferation and migration.Similarly,paroxetine treatment effectively reduced the abnormal proliferation of FLSs in a rat model of collagen-induced arthritis which was accompanied by a significant improvement in clinical manifestations.Collectively,these results elucidate the significance of GRK2 regulation of Hippo-YAP signaling in FLSs proliferation and migration and the potential application of GRK2 inhibition in the treatment of FLSs-driven joint destruction in RA.

Optimizing guest swapping using elastic and transparent memory provisioning on virtualization platform

On virtualization platforms, peak memory de- mand caused by hotspot applications often triggers page swapping in guest OS, causing performance degradation in- side and outside of this virtual machine （VM）. Even though host holds sufficient memory pages, guest OS is unable to utilize free pages in host directly due to the semantic gap between virtual machine monitor （MM） and guest operat- ing system （OS）. Our work aims at utilizing the free memory scattered in multiple hosts in a virtualization environment to improve the performance of guest swapping in a transparent and implicit way. Based on the insightful analysis of behav- ioral characteristics of guest swapping, we design and im- plement a distributed and scalable framework HybridSwap. It dynamically constructs virtual swap pools using various policies, and builds up a synthetic swapping mechanism in a peer-to-peer way, which can adaptively choose different vir- tual swap pools. We implement the prototype of HybridSwap and evaluate it with some benchmarks in different scenar- ios. The evaluation results demonstrate that our solution has the ability to promote the guest swapping efficiency indeed and shows a double performance promotion in some cases. Even in the worst case, the system overhead brought by Hy- bridSwap is acceptable.

Socioeconomic disparities of patients with acute kidney injury:subgroup analysis of local hospitals in China from a national survey

To the Editor:Acute kidney injury(AKI)is a common public health problem worldwide,which can adversely affect patients’quality of life and even lead to death.^([1])Academic hospitals play an important role in admitting and providing treatment for patients with AKI,but limited data exist regarding the characteristics of patients in county-level local hospitals.Our research group initiated a comprehensive survey as part of the International Society of Nephrology’s"0 by 25"project(eliminating all deaths related to untreated AKI by 2025)for investigating the disease burden of AKI and its associated risk factors and prognosis through 22 province-level regions of China in 2013.