Discovery and structure-activity relationship studies of novel tetrahydro-β-carboline derivatives as apoptosis initiators for treating bacterial infections

Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.

Recent progress on fabrication and flat-band physics in 2D transition metal dichalcogenides moiré superlattices

Moiré superlattices are formed when overlaying two materials with a slight mismatch in twist angle or lattice constant. They provide a novel platform for the study of strong electronic correlations and non-trivial band topology, where emergent phenomena such as correlated insulating states, unconventional superconductivity, and quantum anomalous Hall effect are discovered. In this review, we focus on the semiconducting transition metal dichalcogenides(TMDs) based moiré systems that host intriguing flat-band physics. We first review the exfoliation methods of two-dimensional materials and the fabrication technique of their moiré structures. Secondly, we overview the progress of the optically excited moiré excitons, which render the main discovery in the early experiments on TMD moiré systems. We then introduce the formation mechanism of flat bands and their potential in the quantum simulation of the Hubbard model with tunable doping, degeneracies, and correlation strength. Finally, we briefly discuss the challenges and future perspectives of this field.

Morphological Development of Sambong (Blumea balsamifera (L.) DC.) Leaf Studied by Frozen Section and Thin Section

The sambong (Blumea balsamifera (L.) DC.) leaf was investigated by applying frozen section and thin section technology, and observed through optical microscope. The results showed that the sambong leaf was firstly originated nearby the apical bud at the stem tip. The first leaf grows fast, that the mitosis happens frequently and the cytoplasm manufacture rapidly. The cells in the first few leaves have not yet differentiated into the spongy parenchyma and palisade parenchyma. In the mature leaf, the spongy parenchyma and palisade parenchyma were fully developed. The epidermal hairs were firstly developed on the abaxial side of the first leaf.

Some Identities Involving the High-Order Cauchy Polynomials

In this paper, we consider the Cauchy numbers and polynomials of order k and give some relation between Cauchy polynomials of order k and special polynomials by using generating functions and the Riordan matrix methods. In addition, we establish some new equalities and relations involving high-order Cauchy numbers and polynomials, high-order Daehee numbers and polynomials, the generalized Bell polynomials, the Bernoulli numbers and polynomials, high-order Changhee polynomials, high-order Changhee-Genocchi polynomials, the combinatorial numbers, Lah numbers and Stirling numbers, etc.

Bo Bs技术在智力障碍遗传学病因诊断中的应用

目的探讨BoBs技术在智力障碍遗传学病因诊断中的应用价值。方法应用BoBs技术对2017年7月至2018年10月就诊我科门诊的200例智力障碍患儿进行外周血检测。结果异常检出率为14.5%,染色体非整倍体检出率6%;染色体微缺失综合征检出率7.5%;微重复检出率1%。结论智力障碍是儿童康复科常见神经发育障碍性疾病。研究显示染色体微缺失是遗传性病因之一。BoBs技术是唯一同时进行常见染色体非整倍体和9种常见微缺失综合征的检测方法,可进行遗传学病因诊断,还具有指导康复治疗、遗传咨询及优生优育的重要意义。

美国0~3岁婴幼儿照护服务体系及借鉴

美国目前已形成政府主导、社会各类组织积极响应的婴幼儿照护服务体系,它包括中心式和家庭式两大服务模式,家庭可以获得政府财政和社会资金的支持,用于支付获得婴幼儿照护服务的成本。美国的婴幼儿照护服务体系具有因地制宜、公私结合、财政支持灵活多样、服务对象覆盖广的特点。借鉴美国的经验,我国在建设0~3岁婴幼儿照护服务体系时应注意建立健全政府在该领域的工作和管理机制,完善相关法律制度和规范标准,加强对家庭的支持、援助和指导,重视社区服务建设,鼓励社会力量积极参与,努力满足不同家庭和人群的各类照护需求。

In vivo mice brain microcirculation monitoring based on contrast-enhanced SD-OCT

In this paper,we proposed a contrast-enhanced homemade spectral domain optical coherence tomography(SD-OCT)method for monitoring of brain microcirculation.We used the polyethylene glycol(PEG)-ylated gold nanorods(GNRs)as a contrast-enhanced agent,obtained clearly 2D and 3D OCT images of blood vessels and dynamic changes of probes in mouse blood vessels.Owing to high scattering of the PEG-GNRs,more tiny blood vessels can be imaged and the OCT signal can be enhanced by 5.87 dB after injection of PEG-GNRs for 20 min,the enhancement then declined gradually for 60 min.Our results demonstrate an effective technique for the enhanced imaging of blood vessels in vivo,especially for studies of the brain microcirculation,which could be serviced for disease mechanism research and therapeutic drug monitoring.

Recent advances in nonlinear optics for bio‐imaging applications

Nonlinear optics,which is a subject for studying the interaction between intense light and materials,has great impact on various research fields.Since many structures in biological tissues exhibit strong nonlinear optical effects,nonlinear optics has been widely applied in biomedical studies.Especially in the aspect of bio-imaging,nonlinear optical techniques can provide rapid,label-free and chemically specific imaging of biological samples,which enable the investigation of biological processes and analysis of samples beyond other microscopy techniques.In this review,we focus on the introduction of nonlinear optical processes and their applications in bio-imaging as well as the recent advances in this filed.Our perspective of this field is also presented.

Monitoring microenvironment of Hep G2 cell apoptosis using two-photon fluorescence lifetime imaging microscopy

Apoptosis is very important for the maintenance of cellular homeostasis and is closely related to the occurrence and treatment of many diseases.Mitochondria in cells play a crucial role in programmed cell death and redox processes.Nicotinamide adenine dinucleotide(NAD(P)H)is the primary producer of energy in mitochondria,changing NAD(P)H can directly reflect the physiological state of mitochondria.Therefore,NAD(P)H can be used to evaluate metabolic response.In this paper,we propose a noninvasive detection method that uses two-photon fluorescence lifetime imaging microscopy(TP-FLIM)to characterize apoptosis by observing the binding kinetics of cellular endogenous NAD(P)H.The result shows that the average fluorescence lifetime of NAD(P)H and the fluorescence lifetime of protein-bound NAD(P)H will be affected by the changing pH,serum content,and oxygen concentration in the cell culture environment,and by the treatment with reagents such as H2O2 and paclitaxel.Taxol(PTX).This noninvasive detection method realized the dynamic detection of cellular endogenous substances and the assessment of apoptosis.

Preparation of chitosan-Epigallocatechin-3-O-gallate nanoparticles and their inhibitory effect on the growth of breast cancer cells

In this paper,we prepared the nanoparticle drug carrier system between nanoparticles chitosan and Epigallocatechin-3 O-gallate(EGCG)for breast cancer cell inhibiting application.For this drug carrier system,chitosan acts as a carrier and EGOG as a drug.Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility.We also did a cell scratch test and the result indicated that the chitosan EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells.The inhibition rate could reach up to 21.91%.This work revealed that the modification of nanopartidles paved a way for specific biomedical applications.

Fast fluorescence lifetime imaging techniques:A review on challenge and development

Fluorescence lifetime imaging microscopy(FLIM)is increasingly used in biomedicine,material science,chemistry,and other related research fields,because of its advantages of high specificity and sensitivity in monitoring cellular microenvironments,studying interaction between proteins,metabolic state,screening drugs and analyzing their efficacy,characterizing novel materials,and diagnosing early cancers.Understandably,there is a large interest in obtaining FLIM data within an acquisition time as short as possible.Consequently,there is currently a technology that advances towards faster and faster FLIM recording.However,the maximum speed of a recording technique is only part of the problerm.The acquisition time of a FLIM image is a complex function of many factors.These include the photon rate that can be obtained from the sample,the amount of information a technique extracts from the decay functions,the fficiency at which it determines fluorescence decay parameters from the recorded photons,the demands for the accuracy of these parameters,the number of pixels,and the lateral and axial resolutions that are obtained in biological materials.Starting from a discussion of the parameters which determine the acquisition time,this review will describe existing and emerging FLIM techniques and data analysis algo-rithms,and analyze their performance and recording speed in biological and biomedical applications.

Development of a hydrogen peroxide-responsive and oxygen-carrying nanoemulsion for photodynamic therapy against hypoxic tumors using phase inversion composition method

Photodynamic therapy(PDT)has become an attractive tumor treatment modality because of its noninvasive feature and low side effects.However,extreme hypoxia inside solid tumors severely impedes PDT therapeutic outcome.To overcome this obstacle,various strategies have been developed recently.Among them,in situ oxygen generation,which relies on the decom-position of tumor endogenous H_(2)O_(2),and oxygen delivery tactic using high oxygen loading capacity of hemoglobin or perfluorocarbons,have been widely studied.The in situ oxygen generation strategy has high specificity to tumors,but its oxygen-generating efficiency is lim-ited by the intrinsically low tumor H_(2)O_(2)level.In contrast,the oxygen delivery approach holds advantage of high oxygen loading efficiency,nevertheless lacks tumor specificity.In this work,we prepared a nanoemulsion system containing H_(2)O_(2)-responsive catalase,highly efficient ox-ygen carrier perfiuoropolyether(PFPE),and a near-infrared(NIR)light activatable photo-sensitizer IR780,to combine the high tumor specificity of the in situ oxygen generation strategy and the high efficiency of the oxygen delivery strategy.This concisely prepared nanoplatform exhibited enhanced and H_(2)O_(2)-controllable production of singlet oxygen under light excitation,satisfactory cytocompatibility,and ability to kill cancer cells under NIR light excitation.This highlights the potential of this novel nanoplatform for highly efficient and selective NIR light mediated PDT against hypoxic tumors.This research provides new insight into the design of intelligent nanoplatform for relieving tumor hypoxia and enhancing the oxygen-dependent PDT effects in hypoxic tumors.

Enhancement of refresh time in quasi-nonvolatile memory by the density of states engineering

The recently reported quasi-nonvolatile memory based on semi-floating gate architecture has attracted extensive attention thanks to its potential to bridge the large gap between volatile and nonvolatile memory.However,the further extension of the refresh time in quasi-nonvolatile memory is limited by the charge leakage through the p-n junction.Here,based on the density of states engineered van der Waals heterostructures,the leakage of electrons from the floating gate to the channel is greatly suppressed.As a result,the refresh time is effectively extended to more than 100 s,which is the longest among all previously reported quasi-nonvolatile memories.This work provides a new idea to enhance the refresh time of quasi-nonvolatile memory by the density of states engineering and demonstrates great application potential for high-speed and low-power memory technology.

Implementation and application of FRET-FLIM technology

With the development of the new detection methods and the function of fluorescent molecule,researchers hope to further explore the internal mechanisms of organisms,monitor changes in the intracellular microenvironment,and dynamic processes of molecular interactions in cells.Fluo-rescence resonance energy transfer(FRET)describes the energy transfer process between donor fluorescent molecules and acceptor fluorescent molecules.It is an important means to detect protein-protein interactions and protein conformation changes in cells.Fluorescence lifetime imaging microscopy(FLIM)enables noninvasive measurement of the fAuorescence lifetime of fluorescent particles in vivo.The FRET-FLIM technology,which is use FLIM to quantify and analyze FRET,enables real-time monitoring of dynamic changes of proteins in biological cells and analysis of protein interaction mechanisms.The distance between donor and acceptor and their respective fAuorescent lifetime,which are of great importance for studying the mechanism of intracellular activity can be obtained by data analysis and algorithm ftting.

Brain regional changes of guanine nucleotide binding protein-inhabitant 2 in acute and chronic morphine-tolerant and-dependent rats

BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, the hippocampus, and the locus coeruleus. OBJECTIVE： To investigate regional changes of guanine nucleotide binding protein-inhabitant 2 （Gi2） in dopaminergic and noradrenergic neurons in brains of morphine-tolerant and -dependent rats. DESIGN, TIME, AND SETTING： A randomized control study was performed at the Department of Neurobiology in the Second Military Medical University of Chinese PLA （Shanghai, China） between September 2002 and March 2004. MATERIALS： Thirty-six, healthy, male, Sprague-Dawley （SD） rats were used to establish morphine-dependent models. Morphine hydrochloride was a product of Shenyang First Pharmaceutical Factory （China）; naloxone hydrochloride was a product of Beijing Four-Ring Pharmaceutical Factory （China）; and α subunit of Gi2 antibody was offered by Santa Cruz Biotechnology, lnc （USA）. METHODS： Thirty-six SD rats were randomly divided into six groups （n = 6）： （1） acute morphine-dependent group, （2） acute abstinent group, （3） acute control group, （4） chronic morphine-dependent group, （5） chronic abstinent group, and （6） chronic control group. Rats in the acute morphine-dependent and the acute groups were injected with morphine （5 mg/kg）, one injection every two hours, for a total of eight injections. In the acute and chronic morphine-dependent rat models, morphine withdrawal syndrome was precipitated by an injection of naloxone （5 mg/kg）. Rats in the acute control group were given a peritoneal injection of physiological saline at the same administration time as the above two groups. Rats in the chronic morphine-dependent and chronic abstinent groups were injected with morphine three times per day. The administration dose on day 1 was initially 5 mg/kg at 20：00, which increased by 5 mg/kg at 8：00, 12：00, and 20：00 until day 7. On day 13, the dose continuously increased by 10 mg/kg until a chronic morphine-dependent rat model was successfully induced. Afterwards, the rats presented with withdrawal syndromes on naloxone （5 mg/kg） at 8：00 on the same day. Rats in the chronic control group were injected with physiological saline at the same time of the two chronic groups. MAIN OUTCOME MEASURES： The concentration of Gi2 protein in the five brain regions （ventral tegmental area, nucleus accumbens, prefrontal cortex, locus coeruleus, and hippocampus） was detected by immunohistochemistry. RESULTS： In the acute morphine-dependent and acute abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, compared to the acute control group （P 〈 0.01）, while no obvious changes were detected in other brain regions. In the chronic morphine-dependent and chronic abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, but significantly increased in the locus coeruleus （P 〈 0.01 ） compared to the chronic control group. CONCLUSION： Morphine dependence and tolerance may induce obvious reductions of Gi2 protein levels in the nucleus accumbens of rats. Chronic morphine dependence desensitizes the homologous neurons.

Recent progress in 2D group-V elemental monolayers:fabrications and properties

A large number of two-dimensional(2D)monoelemental materials with huge application potentials have been developed,since graphene was reported as a monoelemental material with unique properties.As cousins of graphene,2D group-V elemental monolayers have gained tremendous interest due to their electronic properties with significant fundamental bandgap.In this review,we extensively summarize the latest theoretical and experimental progress in group-V monoelemental materials,including the latest fabrication methods,the properties and potential applications of these 2D monoelementals.We also give a perspective of the challenges and opportunities of 2D monoelemental group-V monolayer materials and related functional nanodevices.

Influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein in primary hippocampal neurons

BACKGROUND： The pharmacological action of opioid drugs is related to signal transduction of inhibitory guanine nucleotide binding protein. OBJECTIVE： To quantitatively and qualitatively analyze the influence of morphine on levels of type Ⅱ inhibitory guanine nucleotide binding protein （Gi2 protein） in primary cultured hippocampal neurons at different time points. DESIGN, TIME AND SETTING： A randomized controlled study, which was performed at the Department of Neurobiology, Changzheng Hospital, Second Military Medical University of Chinese PLA between September 2002 and March 2004. MATERIALS： Cerebral hippocampal neurons were obtained from newborn SD rats at 1 2 days of age. Biotin-antibody Ⅱ-avidin fluorescein isothiocyanate （Avidin-FITC） was purchased from Sigma Company （USA） and the Gi2 protein polyclonal antibody from Santa Cruz Biochemistry Company （USA）. METHODS： Seven days after culture, mature hippocampal neurons were randomly divided into six groups： 4-, 8-, 16-, 24-, and 48-hour morphine groups, and a blank control group. Neurons in the morphine groups received morphine （10 μ mol/L）, which could cause alterations of G-protein mRNA and cAMP expression in the prefrontal cortex. Neurons in the blank control group were given the same volume of saline. MAIN OUTCOME MEASURES： Gi2 protein levels were detected by an immunofluorescence technique, and were analyzed by the image analytic system with the use of green fluorescence intensity. RESULTS： Gi2 protein levels in hippocampal neurons gradually decreased in the 4-, 8-, 16-, 24-, and 48-hour morphine groups. In particular, Gi2 protein levels in the 16-, 24-, and 48-hour morphine groups were significantly lower than that in the blank control group （P 〈 0.05 0.01）. CONCLUSION： Morphine may decrease Gi2 protein level in primary hippocampal neurons, and the decreasing trend is positively related to morphine-induced time.

Progress on 2D topological insulators and potential applications in electronic devices

Two-dimensional topological insulators(2DTIs)have attracted increasing attention during the past few years.New 2DTIs with increasing larger spin-orbit coupling(SOC)gaps have been predicted by theoretical calculations and some of them have been synthesized experimentally.In this review,the 2DTIs,ranging from single element graphene-like materials to bi-elemental transition metal chalcogenides(TMDs)and to multi-elemental materials,with different thicknesses,structures,and phases,have been summarized and discussed.The topological properties(especially the quantum spin Hall effect and Dirac fermion feature)and potential applications have been summarized.This review also points out the challenge and opportunities for future 2DTI study,especially on the device applications based on the topological properties.

█████

The recently reported quasi-nonvolatile memory based on semi-floating gate architecture has attracted extensive attention thanks to its potential to bridge the large gap between volatile and nonvolatile memory.However,the further extension of the refresh time in quasi-nonvolatile memory is limited by the charge leakage through the p-n junction.Here,based on the density of states engineered van der Waals heterostructures,the leakage of electrons from the floating gate to the channel is greatly suppressed.As a result,the refresh time is effectively extended to more than 100 s,which is the longest among all previously reported quasi-nonvolatile memories.This work provides a new idea to enhance the refresh time of quasi-nonvolatile memory by the density of states engineering and demonstrates great application potential for high-speed and low-power memory technology.

Introduction to the Special Issue on Fluorescence Lifetime Imaging Microscopy(FLIM)

Fluorescence Lifetime Imaging Microscopy(FLIM)is an advanced tool that enables the description of exponential decay rate distribution of fuorescent molecules in the samples.This technique has been broadly used in biomedicine,material science,chemistry,and other related research fields,due to its ability to illustrate both localization of specific fuorophores and fuorophores'local microenvironment,and it is superior to fluorescence intensity based imaging.