α-Vitamin E derivative, RRR-α-tocopheryloxybutyric acid inhibits the proliferation of prostate cancer cells

Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.

Development and validation of an LC-MS/MS method for tyrphostin A9

Here we have presented a sensitive and selective LC-MS/MS method for the quantification of tyrphostin A9, which is a selective inhibitor for platelet derived growth factor receptor tyrosine kinase and has been investigated in vitro as a potent oxidative phosphorylation uncoupler. The murine analytical method was developed for three biological matrices: cell culture media, 3T3-L1 cell lysate, and murine plasma. For each matrix the limit of detection and the limit of quantification were found to be 0.5 ng/mL and 1.0 ng/ mL, respectively. The range of standard curve for each matrix was 1.0-100 ng/mL, linearity was >0.99, and the precision and accuracy were within 20%. 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoic acid was found to be the most suitable internal standard. The validated LC-MS/MS method was used to investigate stability and in vitro pharmacokinetics of tyrphostin A9. It was found that tyrphostin A9 is susceptible to hydrolysis, and the degradation product was identified as 3,5-di-tert-butyl-4- hydroxybenzaldehyde. Tyrphostin A9 was not stable in biological matrices, and the rate of its degradation in murine plasma was faster than that in cell culture media. In vitro pharmacokinetic studies revealed that tyrphostin A9 concentrations in the cell culture media declined in a bi-exponential manner and the concentrations inside the adipocytes remained constant, suggesting tyrphostin A9 has an intracellular binding site and is retained within the cell. The LC-MS/MS method presented here paves the way for further quantitative investigations involving tyrphostin A9.

Secure Model of Medical Data Sharing for Complex Scenarios

In order to secure the massive heterogeneous medical data for the complex scenarios and improve the information sharing efficiency in healthcare system,a distributed medical data ledger model(DMDL)is proposed in this paper.This DMDL model has adopted the blockchain technology including the function decoupling,the distributed consensus,smart contract as well as multi-channel communication structure of consortium blockchain.The DMDL model not only has high adaptability,but also meets the requirements of the medical treatment processes which generally involve multientities,highly private information and secure transaction.The steps for processing the medical data are also introduced.Additionally,the methods for the definition and application of the DMDL model are presented for three specific medical scenarios,i.e.,the management of the heterogeneous data,copyright protection for medical data and the secure utilization of sensitive data.The advantage of the proposed DMDL model is demonstrated by comparing with the models which are being currently adopted in healthcare system.

S4A-2 Role of Trace Amine-Associated Receptor 1(TAAR 1)in Nicotine Addiction

Background and Purpose:Nicotine addiction and abuse remains a global health issue.To date,the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood.Trace amine-associated receptor 1(TAAR1)is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictivelike behaviors.We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors.Experimental Approach:TAAR1 expression after nicotine treatment was evaluated by western blotting.c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release,respectively.We then thoroughly and systematically examined the role of TAAR1 in mediating nicotine-induced sensitization,nicotine discrimination,nicotine self-administration,nicotine demand curve,and the reinstatement of nicotine-seeking.Local pharmacological manipulation was conducted to determine the role of TAAR1 in the nucleus accumbens(NAcs)in the reinstatement of nicotine-seeking.Minipump was implanted into TAAR 1 knockout mice and their wildtype counterparts to establish physical dependence.One week after the minipump implantation,the pump was retrieved and mecamylamine was used to precipitate physical withdrawal signs including observable signs and anxiety-like behaviors(elevated plus maze).Key Results:We found that the expression of TAAR1 protein was selectively downregulated in the NAc,with no change in either dorsal striatum or prefrontal cortex.TAAR1 activation was sufficient to block nicotine-induced c-Fos expression in the NAc,while also reducing nicotine-induced dopamine release in the NAc.Systemic administration of TAAR1 agonists attenuated the expression and development of nicotine-induced sensitization,nicotine self-administration,the reinstatement of nicotine-seeking,and increased the elasticity of nicotine demand curve,while intra-NAc infusions of a TAAR1 agonist was sufficient to attenuate nicotine reinstatement.Moreover,TAAR1-knockout rats showed augmented cue-induced and druginduced reinstatement of nicotine-seeking.Mice that were physically dependent on chronic nicotine exposure demonstrated significant withdrawal signs after mecamylamine treatment,and TAAR 1 knockout mice demonstrated more severe withdrawal signs.TAAR 1 agonist reduced the withdrawal signs in the wildtype mice.Conclusions and Implications:These results indicated that modulation of TAAR1 activity regulates nicotine addictive-like behaviors and TAAR1 represents a novel target towards the treatment of nicotine addiction.

Alpha-synuclein in mitochondrial dysfunction:opportunities or obstacles

Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.

Ototoxicity of styrene

Styrene is extensively used in industry,but its ototoxicity,in particular in the pregnant female and the offspring,is still not well understood.In the current study,young adult male rats and pregnant female rats were exposed to styrene by gavage at different doses.The young adult male rats received a total of 12g/kg styrene within different periods (800 mg/kg/day for 5 days/week for 3 weeks,400 mg/kg/day for 5 days/week for 6 weeks,200 mg/kg/day for 5 days/week for 12 weeks,and 100 mg/kg/day for 5 days/week for 24 weeks) and the pregnant female rats received styrene at a dose of 400 mg/kg/day for 5 days/week for 6 weeks starting from the gestation day-4.Hearing loss and hair cell loss were assessed 5 days after the styrene treatment in the young adult male rats and in the mother rats.The cochlear impairments in the rat pups were examined 2 months after their birth.The styrene exposure caused hearing loss and hair cell loss starting from the mid-frequency region in the third row of outer hair cells (OHCs) and the impairments appeared to be related to the dosing level in each single day.Significantly,the styrene exposure to the pregnant rats interfered with auditory functional development of their fetus,leading to a deficit of cochlear amplification,although the OHCs appeared to develop well.The results indicate that a short-term high-level styrene exposure may be more ototoxic than a long-term low-level exposure for a similar total styrene dose and the styrene in the pregnant woman’s body may interfere with auditory development of their fetus.

Inter-WBAN Coexistence and Interference Mitigation

With promising applications in e-health and entertainment, wireless body area networks （WBANs） have attracted the interest of both academia and industry. If WBANs are densely deployed within a small area, serious problems may arise between the WBANs. In this paper, we discuss issues related to the coexistence of WBANs and investigate the main factors that cause inter-WBAN interference. We survey inter- WBAN interference mitigation strategies and track recent research developments. We also discuss unresolved issues related to inter-WBAN interference mitigation and propose fu- ture research directions.

芳酰胺类大环一步高效合成及其成环机理研究进展

总结了最近发现的新型芳酰胺及芳酰肼大环一步合成反应,着重探讨了由分子内三中心氢键所引导的高效一步成环反应机理.这类反应是由未成环寡聚物前体的折叠构象所构筑,不仅高效,而且反应机理新颖,提供了传统成环反应难以得到的几类刚性大环的合成方法.这些大环化合物表现出对客体识别的高度专一性,并能形成具有高通量性的跨膜孔道.

复方健耳剂对C57BL/6J小鼠AHL毛细胞的保护作用

目的探讨老年性耳蜗毛细胞损害与中药复方健耳剂两种喂药方法干预的作用。方法选择1月龄C57BL/6J小鼠22只用于本实验,其中4只小鼠每日饮用自来水直到出生后3个月作为幼龄对照组;6只小鼠每日饮用自来水直到出生后7个月作为老年性聋对照组;6只小鼠每日自动饮用中药复方健耳剂直到出生后7个月;另6只小鼠每日自动饮用同样中药至4个月后改用每日人工灌服直到出生后7个月。各组动物实验到期终止后,取耳蜗进行全耳蜗基底膜铺片,将全耳蜗内、外毛细胞计数结果输入计算机并应用耳蜗图软件进行耳蜗毛细胞密度对比分析,其中选择基底膜上重要的病变区间的毛细胞密度进行统计学分析。结果 3月龄对照组小鼠耳蜗外、内毛细胞缺损仅仅出现在耳蜗底回钩端区域;7月龄对照组外、内毛细胞缺损从底回基底膜起始端扩展到距离耳蜗顶端约40%区域;7月龄中药灌服组和自动饮用组动物的内、外毛细胞缺损范围和程度相似,均显著比7月龄对照组为轻(P<0.001)。结论中药复方健耳剂能够有效延缓C57BL/6J小鼠老年性耳蜗毛细胞损害的发生和发展,两种喂药方式所起作用相同(P>0.05),其药理机制可能与其改善微循环,清除活性氧,保护线粒体等作用相关。

酸胁迫对铜藻早期生长阶段的影响

为探究低pH胁迫对大型藻类早期生长的影响,以铜藻Sargassum horneri为研究对象,设置pH=3.5、4.5、5.5、6.5处理组和自然海水对照组,以不同处理时间分别对铜藻孢子和幼体进行胁迫实验。孢子实验中,于铜藻孢子附着前、后对其进行15、30、60、120 min的酸胁迫,以附着率和脱落率表征低pH对孢子附着的影响;幼体实验中,持续将铜藻幼体暴露于酸性条件下,以脱落死亡率表征pH对幼体的致死效应。结果显示,在短时间酸胁迫下,酸度对铜藻孢子附着的影响显著,附着率随pH值的下降而降低;胁迫时间对孢子的附着影响显著,附着率随胁迫时间的延长而降低,pH值与胁迫时间无交互作用;而当孢子已充分附着后,短期酸胁迫并没有显著影响孢子体的存活。在长时间酸胁迫下,与对照组相比,所有处理组铜藻幼体的存活率均显著降低。研究表明,低pH会对铜藻孢子、幼体的存活生长产生不利影响,并且这种影响在铜藻早期发育的不同阶段有所不同。

留园冠云峰庭院空间造园要素的量化特征及其意境研究

以苏州古典园林留园冠云峰庭院为研究对象,以造园要素的量化特征及其意境为研究目标,重点研究了我国古典庭院的造园艺术与手法特点。着重研究了冠云峰庭院建筑、峰石、水体的平立面布局在尺度上的量化数据及其特征;花木的总体布局特征;冠云峰庭院造园要素营造的实景与空间意境的联系;人与冠云峰庭院空间景境营造的关系。试图从定量和定性两方面,深入剖析我国传统庭院空间造园要素的营造手法及其量化特征;也提示观赏者在观赏具体庭院空间时,应从"切入点—路径—出口"的思考角度,来理解古代造园家营造具体空间的真正目的。旨在更好地传承和借鉴园林遗产精髓,并将其融入我国现代园林的理论与方法体系之中,逐渐形成真正蕴涵传统园林血脉的现代园林理论与方法体系。

融合多数据源的蛋白质功能模块的挖掘算法

针对蛋白质相互作用(protein-protein interaction,PPI)网络的信息不完善和高噪声问题,提出一种融合多生物数据的二分图聚类集成方法以检测网络中的功能模块.该方法结合了基因本体论(gene ontology,GO)、基因表达谱数据以及多种基础聚类算法,用一种新的二分图来组织多种基础聚类算法的中间结果,并结合对称非负矩阵分解(non-negative matrix factorization,NMF)算法挖掘其中功能意义上最一致蛋白质功能模块,同时,该算法能处理蛋白质功能重叠问题.实验结果表明:所提算法整体优于基准比较方法,是一种融合多种生物信息源和不同的聚类方法的有效途径.

药物奖赏记忆:从药物诱导的条件性位置偏爱模型中的见解（英文）

药物成瘾是一种慢性复发性脑疾病,其发生至少部分原因是由于异常的学习记忆所导致。大量的研究表明,成瘾性药物篡夺了正常记忆的神经环路,从而形成了长期维持的药物记忆,这可能是导致药物成瘾复吸的重要原因。本文综述了关联性药物奖赏记忆的模型之一药物诱导的条件性位置偏爱的相关研究结果,旨在阐述目前对于药物奖赏记忆的认识。药物奖赏记忆是一个动态的过程,包括习得、巩固、维持、唤起、再巩固和消退多个阶段,对这些药物奖赏记忆阶段进行药理学干预可以不同地调控药物奖赏记忆。最近,根据记忆阶段假说所发展的纯行为学模式,例如唤起-消退模式,展现出比药理学手段干预药物奖赏记忆更强的优越性。最后,本综述讨论了在药物奖赏记忆实验设计与相关实验结果解释时需要重点考虑2个方法学问题:模式和时间。目前为止,仍然不确定是否能发展一种药理学治疗方法,仅仅抹除药物奖赏记忆而不影响正常的记忆。我们提出,抑制药物奖赏记忆的方法仍不失一种有效降低复吸风险的手段。虽然目前关于药物奖赏记忆的研究对药物成瘾的治疗贡献并不大,但继续深入的研究将为降低成瘾复吸带来新的治疗方法。

线粒体动态相关蛋白1在阿尔茨海默病线粒体动态学中的作用机制研究进展（英文）

线粒体动态在哺乳动物细胞内发挥重要作用。在健康细胞内,线粒体保持分裂与融合的动态平衡。线粒体动态相关蛋白1(Drp1)在神经细胞轴突和树突部位线粒体分裂动态调控中发挥枢纽作用。对阿尔茨海默症患者的研究证明,Drp1表达及功能变化会破坏线粒体分裂与融合的动态平衡并导致患者海马细胞的功能损坏或缺失。因此,Drp1具有成为以调节线粒体动态为机制的阿尔茨海默病治疗新方案中的全新药物靶点蛋白。

激光与反激光共存

激光与反激光可在单个腔体中彼此共存。激光是通过辐射的受激发射实现光放大,与之相反,反激光代表着激光发射的时间反转对应物。然而,美国的研究人员采用奇偶时间对称性原理,通过实验的方式在单个腔体（即CPA（相干完美吸收）激光器）中在相同频率下实现了激光与反激光现象。

Super-Resolution Displacement Spectroscopic Sensing over a Surface“Rainbow”

Subwavelength manipulation of light waves with high precision can enable new and exciting applications in spectroscopy,sensing,and medical imaging.For these applications,miniaturized spectrometers are desirable to enable the on-chip analysis of spectral information.In particular,for imaging-based spectroscopic sensing mechanisms,the key challenge is to determine the spatial-shift information accurately(i.e.,the spatial displacement introduced by wavelength shift or biological or chemical surface binding),which is similar to the challenge presented by super-resolution imaging.Here,we report a unique"rainbow"trapping metasurface for on-chip spectrometers and sensors.Combined with super-resolution image processing,the low-setting 4×optical microscope system resolves a displacement of the resonant position within 35 nm on the plasmonic rainbow trapping metasurface with a tiny area as small as0.002 mm2.This unique feature of the spatial manipulation of efficiently coupled rainbow plasmonic resonances reveals a new platform for miniaturized on-chip spectroscopic analysis with a spectral resolution of 0.032 nm in wavelength shift.Using this low-setting 4×microscope imaging system,we demonstrate a biosensing resolution of 1.92×109exosomes per milliliter for A549-derived exosomes and distinguish between patient samples and healthy controls using exosomal epidermal growth factor receptor(EGFR)expression values,thereby demonstrating a new on-chip sensing system for personalized accurate bio/chemical sensing applications.

Connected Geomatics in the big data era

The development of global informatization and its integration with industrialization symbolizes that human society has entered into the big data era.This article covers seven new characteristics of Geomatics(i.e.ubiquitous sensor,multi-dimensional dynamics,integration via networking,full automation in real time,from sensing to recognition,crowdsourcing and volunteered geographic information,and serviceoriented science),and puts forward the corresponding critical technical challenges in the construction of integrated space-air-ground geospatial networks.Through the discussions outlined in this paper,we propose a new development stage of Geomatics entitled‘Connected Geomatics,’which is defined as a multi-disciplinary science and technology that uses systematic approaches and integrates methods of spatio-temporal data acquisition,information extraction,network management,knowledge discovery,and spatial sensing and recognition,as well as intelligent location-based services pertaining to any physical objects and human activities on the earth.It is envisioned that the advancement of Geomatics will make a great contribution to human sustainable development.

Unidirectional lasing in semiconductor microring lasers at an exceptional point [Invited]

Recent experiments demonstrated that chiral symmetry breaking at an exceptional point(EP) is a viable route to achieve unidirectional laser emission in microring lasers. By a detailed semiconductor laser rate equation model,we show here that unidirectional laser emission at an EP is a robust regime. Slight deviations from the EP condition can break preferential unidirectional lasing near threshold via a Hopf instability. However, abovea "second" laser threshold, unidirectional emission is restored.