Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response.

Adipocytes promote cancer progression and impair treatment, and have been shown to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we investigate whether this protection is mediated by changes in oxidative stress. Co-culture experiments showed that adipocytes protect ALL cells from oxidative stress induced by drugs or irradiation. We demonstrated that ALL cells induce intracellular ROS and an oxidative stress response in adipocytes. This adipocyte oxidative stress response leads to the secretion of soluble factors which protect ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL cells elicit an oxidative stress response in adipocytes, leading to adipocyte protection of ALL cells against DNR

Present-day activity and seismic potential of the north Qinling fault, southern ordos block, central China, as revealed from GPS data and seismicity

The North Qinling Fault, located at the boundary of the North China Block and the South China Block, represents an important tectonic structure between the Weihe Basin and the Qinling Mountains, and controls the subsidence and expansion of the Weihe Basin. This fault has been highly active and has caused strong earthquakes since the Holocene and in a pre-seismic stage currently, as indicated by the many paleoearthquake traces found along it. To determine the present-day activity and seismic potential of the North Qinling Fault, by inverting GPS data, we produced fault locking depth, slip rate, and regional strain fields maps; moreover, based on seismicity, we produced a seismic b-value map. Combining this information with modern seismicity, we were able to comprehensively analyze the seismic potential of different fault segments. Our inversion of GPS data showed that the slip rate of the western segment of the fault (Qingjiangkou–Xitangyu) and the correspondent locking depth are 1.33 mm/a and 13.54 km, respectively, while the slip rate of the middle segment (Xitangyu–Fengyukou) and the correspondent locking depth are 0.45 mm/a and 8.58 km, respectively; finally, the slip rate of the eastern segment (Xitangyu–Daiyu) and the correspondent locking depth are 0.36 mm/a and 21.46 km, respectively. The locking depths of the western and middle segments of the fault are shallower than 90% of the seismic cutoff depth, while the locking depth of the eastern segment of the fault is similar to 90% of the seismic cutoff depth, indicating that “deep creep” occurs in the western and middle segments, while the eastern segment is locked. Modern small earthquakes have involved the western and middle segments of the fault, while the eastern segment has acted as a seismic gap with weak seismicity, characterized by a higher shear strain value and a lower b-value. These characteristics reflect the relationship between the locking depth and seismicity distribution. The results of our comprehensive analysis, combined with field geological surveys, show that the eastern segment of the North Qinling Fault has a strong seismic potential and is presently locked

Present-day kinematics and seismic potential of the Ganzi-Yushu fault, eastern Tibetan plateau, constrained from InSAR

In recent years, earthquakes have occurred frequently on the southeastern edge of the Tibetan Plateau, and the seismic hazard is high. However, because of the remote location of the Ganzi-Yushu fault zone, no high-resolution geodetic measurements of this region have been made. The radar line-of-sight deformation field of the Ganzi-Yushu fault was obtained using seven-track ascending and descending Sentinel-A/B interferometric synthetic aperture radar (InSAR) data from 2014 to 2020. Using the InSAR and published Global Navigation Satellite System (GNSS) data, we calculated the 3D deformation field in the study area, investigated the segment-specific fault slip rate, and inverted the fault slip distribution pattern using the steepest descent method. We then evaluated the seismic hazard using the strain rate field and slip deficit rate. The main findings of this study include the following. 1) The slip rate of the Ganzi-Yushu fault gradually increases from 2.5 to 6.8 mm/yr from northwest to southeast. 2) A high-resolution strain rate map shows high-value anomalies in the Yushu and Dangjiang areas. 3) Our comprehensive analysis suggests that the seismic hazard of the Dangjiang and Dengke segments with high slip deficits cannot be ignored

Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications

This was the first study to use genipin to cross-link collagen and chitosan.In this study, genipin-cross-linked collagen/chitosan biodegradable porous scaffolds were prepared for articular cartilage regeneration. The influence of chitosan amount and genipin concentration on the scaffolds physicochemical properties was evaluated. The morphologies of the scaffolds were characterized by scanning electron microscope (SEM) and cross-linking degree was investigated by ninhydrin assay. Additionally, the mechanical properties of the scaffolds were assessed under dynamic compression. To study the swelling ratio and the biostability of the collagen/chitosan scaffold, in vitro tests were also carried out by immersion of the scaffolds in PBS solution or digestion in collagenase, respectively. The results showed that the morphologies of the scaffolds underwent a fiber-like to a sheet-like structural transition by increasing chitosan amount. Genipin cross-linking remarkably changed the morphologies and pore sizes of the scaffolds when chitosan amount was less than 25%. Either by increasing the chitosan ratio or performing cross-linking treatment, the swelling ratio of the scaffolds can be tailored. The ninhydrin assay demonstrated that the addition of chitosan could obviously increase the cross-linking efficiency. The degradation studies indicated that genipin cross-linking can effectively enhance the biostability of the scaffolds. The biocompatibility of the scaffolds was evaluated by culturing rabbit chondrocytes in vitro. This study demonstrated that a good viability of the chondrocytes seeded on the scaffold was achieved. The SEM analysis has revealed that the chondrocytes adhered well to the surface of the scaffolds and contacted each other. These results suggest that the genipin-cross-linked collagen/chitosan matrix may be a promising formulation for articular cartilage scaffolding.Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-year Plan Period. Grant Number: 2006BA116B04Guangdong Natural Science Foundation. Grant Number: 07300602Natural Science Foundation Team Project of Guangdong. Grant Number: 4205786State Key Program of National Natural Science of China. Grant Number: 50732003National Basic Research Program of China. Grant Number: 2005CB62390

Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine ( 131 I-MIBG) therapy for neuroblastoma.

Background 131 I-Metaiodobenzylguanidine ( 131 I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and 131 I-MIBG is concentrated in the liver after 131 I-MIBG therapy. The aim of our study was to analyze the effects of 131 I-MIBG therapy on thyroid and liver function. Procedure Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131 I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined. Results In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after 131 I-MIBG therapy. At 2 years post- 131 I-MIBG therapy, 76 ± 4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23 ± 5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. Conclusion The prophylactic regimen of potassium iodide and potassium perchlorate with 131 I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131 I-MIBG therapy were primarily reversible and did not result in late toxicity. 131 I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction. Pediatr Blood Cancer 2011;56:191–201. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78497/1/22767_ftp.pd

Metal–organic layers stabilize earth-abundant metal–terpyridine diradical complexes for catalytic C–H activation

Metal–organic layers stabilize Fe II or Co II -terpyridine diradical complexes to catalyze alkylazide C sp3 –H amination and benzylic C–H borylation, respectively

Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast

Although many prokaryotes have glycolysis alternatives, it\u27s considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs