Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson's disease

Parkinson’s disease is a neurodegenerative disorder,and fe rroptosis plays a significant role in the pathological mechanism underlying Parkinson’s disease.Rapamycin,an autophagy inducer,has been shown to have neuroprotective effects in Parkinson’s disease.However,the link between rapamycin and ferroptosis in Parkinson’s disease is not entirely clear.In this study,rapamycin was administe red to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson’s disease PC12 cell model.The results showed that rapamycin improved the behavioral symptoms of Parkinson’s disease model mice,reduced the loss of dopamine neurons in the substantia nigra pars compacta,and reduced the expression of ferroptosis-related indicators(glutathione peroxidase 4,recombinant solute carrier family 7,member 11,glutathione,malondialdehyde,and reactive oxygen species).In the Parkinson’s disease cell model,rapamycin improved cell viability and reduced ferro ptosis.The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer(methyl(1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate)and an autophagy inhibitor(3-methyladenine).Inhibiting ferro ptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects.Therefo re,the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson’s disease.

Radar style transfer for metric robot localisation on lidar maps

Lidar and visual data are affected heavily in adverse weather conditions due to sensing mechanisms,which bring potential safety hazards for vehicle navigation.Radar sensing is desirable to build a more robust navigation system.In this paper,a cross-modality radar localisation on prior lidar maps is presented.Specifically,the proposed workflow consists of two parts:first,bird's-eye-view radar images are transferred to fake lidar images by training a generative adversarial network offline.Then with online radar scans,a Monte Carlo localisation framework is built to track the robot pose on lidar maps.The whole online localisation system only needs a rotating radar sensor and a pre-built global lidar map.In the experimental section,the authors conduct an ablation study on image settings and test the proposed system on Oxford Radar Robot Car Dataset.The promising results show that the proposed localisation system could track the robot pose successfully,thus demonstrating the feasibility of radar style transfer for metric robot localisation on lidar maps.

高固相含量浆料浸渍结合PIP法制备C/C–ZrB2–SiC复合材料及其性能（英文）

往C/C复合材料中加入超高温陶瓷,以满足其在高温有氧环境中的应用。采用高固相含量浆料浸渍结合前驱体浸渍裂解工艺制备C/C-ZrB2-SiC复合材料,研究ZrB2浆料的分散性和流变行为,以及C/C-ZrB2-SiC复合材料的显微组织、力学性能和烧蚀性能。结果表明:硼化锆浆料在分散剂聚乙烯胺含量为0.40 wt.%、pH值为5的条件下具有良好的分散性和较低的黏度。陶瓷相均匀地分布在C/C复合材料的网胎层和针刺区;C/C-ZrB2-SiC复合材料的抗弯强度为309.30MPa,其在2500℃氧乙炔火焰烧蚀条件下显示出优异的烧蚀性能,质量烧蚀率和线烧蚀率分别为0.40 mg/s和0.91μm/s。此外,在烧蚀过程中,复合材料表面形成连续、致密的二氧化锆层,能有效地降低氧气向材料内部的扩散速率,对复合材料形成良好的保护。

Detection of Salmonella and several common Salmonella serotypes in food by loop-mediated isothermal amplification method

Salmonella Choleraesuis,S.Enteritidis and S.Typhimurium are the main pathogens that contaminate animal products and cause human Salmonella food poisoning.To establish the loop-mediated isothermal amplification(LAMP)method for the rapid detection of Salmonella and 3 common Salmonella serotypes,inner and outer primer sets targeting Salmonella invE gene and 3 serotype-specific genes fliC,lygD and STM4495 were designed.The LAMP reaction conditions were optimized.The specificity of LAMP primers was identified by testing 10 different bacterial strains including S.Choleraesuis,S.Enteritidis and S.Typhimurium.Take S.Choleraesuis as example,the detection limit of LAMP assay was 1.33×10^1 CFU/mL for bacteria culture and 2.0×10^1 CFU/mL for simulated pork sample.The results show that LAMP is a rapid,sensitive and specific method for Salmonella detection and can be used for the rapid detection of Salmonella in food.

Mechano-Sensing by Endothelial Primary Cilium

Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.

Hexagonally ordered microbowl arrays decorated with ultrathin CuInS_(2) nanosheets for enhanced photoelectrochemical performance

This paper demonstrates the design and fabrication of three-dimensional(3 D) hexagonally ordered microbowl arrays(MBAs) decorated with Cu In S2 nanosheets for enhanced photoelectrochemical(PEC) performance. The 3 D MBAs are fabricated by a micro-fabrication technique. The ultrathin CuInS2 nanosheets are grown on the 3 D electrodes by solvothermal transformation of Cu film. The photocurrent density of 3 D photocathode(CuInS2@MBAs) is about two times higher than that of the planar counterpart(CuInS2@Planar). The improved PEC performance can be ascribed to the elevated light trapping ability and the increased surface area for loading photocatalysts. In addition, CdS quantum dots as cocatalysts are modified onto the Cu In S2 nanosheets to further enhance the PEC activity because the formed p-n heterojunction can accelerate the separation of photogenerated carriers. As a result, the 3 D photocathode of CuInS2/CdS@MBAs shows an optimal incident photon to current efficiency of 10% at the wavelength of400 nm. It is believed that this work can be generalized to design other hierarchical 3 D photoelectrodes for improved solar water splitting.

Mechano-Sensing and shear stress-shielding by endothelial primary cilia:structure,composition,and function

Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.

酚妥拉明对脓毒症心肌损伤患者心功能、心肌损伤指标及血流动力学的影响

目的:观察酚妥拉明治疗脓毒症心肌损伤(SMD)的效果,并分析其对患者心功能、心肌损伤指标及血流动力学的影响。方法:回顾性分析鄂东医疗集团黄石市中心医院2017年2月至2020年2月收治的SMD患者79例的临床资料,以是否联合酚妥拉明治疗分为对照组41例、观察组38例,比较两组临床效果及治疗前后心功能、心肌损伤指标及血流动力学指标。结果:两组28 d病死率差异无统计学意义(P>0.05)。观察组重症监护病房(ICU)入住时间、机械通气时间分别为(9.33±3.52)d、83.00(28.50,138.00)h,均显著短于对照组的(12.17±4.15)d、111.00(47.50,169.00)h(t=3.26,Z=-2.27,均P<0.05)。观察组有效率为81.58%(31/38),显著高于对照组的60.98%(25/41)(χ^(2)=4.05,P<0.05)。治疗后7 d,两组左心室射血分数(LVEF)均显著高于治疗前(均P<0.05),左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)均显著低于治疗前(均P<0.05);观察组LVEF显著高于对照组(t=3.29,P<0.05),LVEDD、LVESD均显著低于对照组(t=5.94、11.21,均P<0.05)。两组患者N-末端原脑利钠肽(NT-proBNP)、心肌肌钙蛋白I(cTnI)均随着时间的延长而显著下降(均P<0.05);治疗后24 h、治疗后72 h、治疗后7 d,观察组NT-proBNP、cTnI水平均显著低于对照组(均P<0.05)。治疗后7 d,两组心率(HR)均显著低于治疗前(均P<0.05),平均动脉压(MAP)、心脏指数(CI)、每搏输出量指数(SVI)均显著高于治疗前(均P<0.05);观察组HR显著低于对照组(t=4.90,P<0.05),MAP、CI、SVI均显著高于对照组(t=4.37、3.23、6.01,均P<0.05)。结论:酚妥拉明可改善SMD患者血流动力学,减轻心肌损伤,提高心功能。