A Novel Quantization and Model Compression Approach for Hardware Accelerators in Edge Computing

Massive computational complexity and memory requirement of artificial intelligence models impede their deploy-ability on edge computing devices of the Internet of Things(IoT).While Power-of-Two(PoT)quantization is pro-posed to improve the efficiency for edge inference of Deep Neural Networks(DNNs),existing PoT schemes require a huge amount of bit-wise manipulation and have large memory overhead,and their efficiency is bounded by the bottleneck of computation latency and memory footprint.To tackle this challenge,we present an efficient inference approach on the basis of PoT quantization and model compression.An integer-only scalar PoT quantization(IOS-PoT)is designed jointly with a distribution loss regularizer,wherein the regularizer minimizes quantization errors and training disturbances.Additionally,two-stage model compression is developed to effectively reduce memory requirement,and alleviate bandwidth usage in communications of networked heterogenous learning systems.The product look-up table(P-LUT)inference scheme is leveraged to replace bit-shifting with only indexing and addition operations for achieving low-latency computation and implementing efficient edge accelerators.Finally,comprehensive experiments on Residual Networks(ResNets)and efficient architectures with Canadian Institute for Advanced Research(CIFAR),ImageNet,and Real-world Affective Faces Database(RAF-DB)datasets,indicate that our approach achieves 2×∼10×improvement in the reduction of both weight size and computation cost in comparison to state-of-the-art methods.A P-LUT accelerator prototype is implemented on the Xilinx KV260 Field Programmable Gate Array(FPGA)platform for accelerating convolution operations,with performance results showing that P-LUT reduces memory footprint by 1.45×,achieves more than 3×power efficiency and 2×resource efficiency,compared to the conventional bit-shifting scheme.

Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma:Retrospective study

BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.

基于SSR标记的江西省枫香古树遗传多样性评价

采用14对SSR引物对江西省9个枫香古树群体的222个单株进行毛细管电泳测序,利用GenAIEx、CERVUS和Structure软件,进行遗传多样性与聚类分析。结果表明14个SSR位点平均观测等位基因数(Na)为8.143个,平均有效等位基因数(Ne)为2.819个,Shannon信息指数(I)平均值为1.009,平均期望杂合度(He)和观测杂合度(Ho)分别为0.504和0.470,多态信息含量(PIC)平均值为0.513。宁都(ND)群体具有最高的遗传多样性(He=0.551),湾里(WL)群体的遗传多样性最低(He=0.394)。在地区水平,赣南(He=0.534,n=8)和赣北(He=0.505,n=14)地区具有较高的遗传多样性和特有等位基因;赣中地区具有最低的遗传多样性(He=0.473)和最少的特有等位基因(n=2)。分子方差分析(AMOVA)结果表明枫香群体内变异为92%,显著高于群体间变异8%,与遗传分化系数(Fst=0.133)一致,有可能是较高的基因流造成的(Nm=2.995)。主成分分析和聚类分析表明9个群体可分成3大类群,不同枫香古树群体间存在较为强烈的基因渐渗。研究结果为枫香古树的利用及保护提供科学依据,在今后的枫香育种工作中,要加强对枫香古树个体的保护,可以加强在赣北、赣南地区群体内开展优树选择,有可能含有特定的基因类型资源,可以获得更大的遗传增益。

The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Evaluation of Benzamide Derivatives as New Influenza A Nucleoprotein Inhibitors

Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC50 values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.

常绿阔叶林米槠叶片功能性状对不同海拔梯度的响应与适应

【目的】植物对温度变化的响应与适应一直是科学家研究的热点问题,不同海拔所带来的温度差异为研究植物对低温环境的适应提供了先决条件。目前,对常绿阔叶林不同海拔下优势种米槠(Castanopsis carlesii)叶片功能性状的种内变异知之甚少,对米槠应对低温环境采取何种生理生态策略的认识非常有限。研究海拔尺度米槠叶片性状的变化,有助于了解植物对环境变化的生存策略,可为预测未来气候变化下植物的空间分布提供科学依据。【方法】以江西省九连山自然保护区不同海拔(低、中、高)的米槠天然林为对象,测定其叶片的形态性状(叶面积、叶长、叶宽、长宽比、比叶重、叶干物质含量)与生理性状(叶绿素a、叶绿素b、叶绿素、淀粉、可溶性糖、NSC),揭示不同海拔梯度下米槠叶片性状的变异规律,检验不同海拔梯度下各叶片性状间的差异,探讨米槠对低温环境的适应策略。【结果】(1)叶面积、叶长、叶宽、长宽比、叶绿素a、叶绿素b、叶绿素随海拔梯度的升高呈下降的趋势,而比叶重、淀粉、可溶性糖、NSC沿海拔梯度的增加呈上升的趋势,叶干物质含量随海拔梯度的增加没有发生明显的变异趋势;(2)叶面积、长宽比、比叶重、叶绿素a、叶绿素、可溶性糖在高海拔与低海拔之间呈显著差异,叶长、比叶重、叶绿素b、叶干物质含量在不同海拔梯度差异不显著,中高海拔间的淀粉与NSC含量差异不显著,但与低海拔处的含量呈显著差异;(3)12个叶功能性状总体的变异由大到小依次为淀粉、可溶性糖、NSC、叶面积、叶绿素b、叶绿素a、总叶绿素、叶宽、叶长、比叶重、叶长宽比和干物质含量,淀粉、可溶性糖、NSC、叶面积具有较高的变异系数,变异系数为20%~50%,属于中等变异,干物质含量变异系数最小,仅为6.73%。【结论】米槠对不同海拔梯度的生理生态适应策略差异显著,通过一系列形态、光合和生理上的调节反应来适应高海拔的低温环境,主要表现为增加比叶重以提高机械抗性,减少叶面积和叶绿素的含量来降低因捕捉过度的光能对叶面造成的伤害,同时积累可溶性糖、淀粉提高抗旱能力,而低海拔米槠主要通过增大叶面积、光合速率、降低抗旱性来快速获取资源。研究表明米槠在应对环境变化存在高效和安全的适应策略,可用作南方混交林栽培的目标树种。

Niclosamide,an old antihelminthic agent,demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells

Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several groups have independently discovered that niclosamide is also active against cancer cells,but its precise mechanism of antitumor action is not fully understood.Evidence supports that niclosamide targets multiple signaling pathways (NF-κB,Wnt/β-catenin,Notch,ROS,mTORC1,and Stat3),most of which are closely involved with cancer stem cells.The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed.A method for synthesizing a phosphate pro-drug of niclosamide is provided.Given its potential antitumor activity,clinical trials for niclosamide and its derivatives are warranted for cancer treatment.

Bioreductive prodrugs as cancer therapeutics:targeting tumor hypoxia

Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygensensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.

Clinical study of ultrasound and microbubbles for enhancing chemotherapeutic sensitivity of malignant tumors in digestive system

Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.

A Flow-Based Authentication Handover Mechanism for Multi-Domain SDN Mobility Environment

The long authentication handover delay is the greatest challenge in multi-domain SDN environment. In order to solve this problem, an authentication handover mechanism under multi-SDN domain(AHMMD) is proposed in this paper. In AHMMD, firstly, when the mobility entity accesses the network for the first time, its identity and service attributes are authenticated by the flow authentication protocol, which is designed based on the asymmetric encryption key; secondly, when the mobility entity moves to the neighbor domain, the authentication information will be delivered from the current controller to the neighborhood controller through a security communication channel. In order to promote the efficiency, a handover time prediction algorithm is adopted in AHMMD. Experimental results based on our AHMMD prototype have shown that the handover delay decreases by 50% while the handover cost decreases by 60%.

Torque and Topology of Braided DNAs under Tension

Double helix DNAs become intertwined around one another during replication and recombination.Here we used magnetic tweezers to make braided DNA molecules and measured their torques under various catenations(Ca)at forces ranging from 0.3 to 8 pN.Images of braided DNA constructs under tensions were captured by scanning electron microscopy which showed major and minor grooves of DNAs and plectonemes of the braids.When the two DNA molecules were braided,the extension decreased as the catenation increased from 0 to 50 turns.We used a thermodynamic Maxwell relation to deduce the torque by integrating the change in the braid extension as a function of the force.The torque increased with the catenation,force and intertether distance until the catenation reached a buckling point.Under the condition of 2 pN force and Ca=20,the torque was computed to be 31,21 and 15 pN nm for the braids of which the intertether distances were 54%,31%and 26%of the DNA contour length,respectively.At an 8.03 pN holding force,the torque was computed to be 76 pN nm as the catenation increased from 0 to 30 turns,or as the catenation density varied from 0 to 0.053.The torque reached a plateau when the catenation increased above 20,indicating formation of braid-plectonemes.The twist modulus increased with the catenation prior to reaching a peak.Before reaching the peak,the moduli were higher than those of a single twisted DNA under the same catenation and applied force.Our experimental data agrees well with the calculation results by a recently developed semiflexible polymer model.Our measurements of the nonlinear torque of the braid establish new fundamental properties of DNA intertwining,which is key to understanding DNA replication and gene expression.The speaker will also introduce briefly other projects in the Xiao group including direct measurements of theforce spectrum of single unlabeled proteins such as adhesive nano-fibers for biofilm,the screening of integrin-targeted peptides drugs by single cell approaches,and the micromechanical approach for determining the survival rate of stem cells.

Force Spectrum of Single CsgA Nanofiber Reveal Surprising Properties

CsgA protein monomers consist of aβ-helix of five repeat units possessing several conservative residues and thus,inherently fibrillate.CsgA protein monomers could self-assemble into hierarchical nanofiber structure cross multiple scales after expression and secretion by E.Coli cells.Previous researches show that CsgA nanofibers could provide adhesion,stiffness,and mechanical homogeneity for the biofilms,host cells’fibronectin binding for internalization,or protection against phage attack.CsgA nanofibers have obtained various applications in material science and synthetic biology.To illustrate,CsgA nanofibers have characteristics of intrinsic hierarchical structures across multiple scales,robustness in harsh environments and programmable functionality via biological tools.Studying the force spectrum or mechanical properties of the nanofiber can provide fundamental information of self-assembly process and ultra-stability in extreme conditions.Single molecule techniques such as atomic force microscopy,optical tweezers,and magnetic tweezers have been widely applied to study proteins.In these studies,proteins are usually chemically conjugated or genetically constructed to have a tag such as histidine,cysteine or biotin.Genetic engineering requires modification of the plasmids encoding the specific protein,and also involve special protein expression and purification.Such study needs collaboration from multi-disciplinary.It normally studies one protein at a time which gives out clear signal but lacks throughput and efficiency.Here we have established a simple method to measure all kinds of proteins without labels.The carboxyl terminus of a protein is attached to the amine group on a magnetic bead,and the amine terminus of the protein is attached to glutaraldehyde on the glass slide.Then we used magnetic tweezers to manipulate and stretched the bead and protein.Extension versus rotation relation was used to identify a single protein or protein fibril.The fiber under tension is also observed by Scanning Electronic Microcopy which convinces that single CsgA-His fibril is linked to a microbead.The peak of diameter distribution is around 15 nm.The fracture of fibers was observed in real time on SEM.Force-extension curves of single fibers are obtained in real time.The force-extension curves generally agree with the worm like chain model.The persistence lengths from the fitting are from 0.9 to 49.8 nm.The elongation ratio increases gradually with force until reaches a plateau.The maximum elongation ratio of 78 nanofibers were made into an elongation ratio distribution diagram,more than half of CsgA-His nanofibers has an elongation ratio from 0 to 2,some are distributed in 2~10,and a few are distributed in 10~18.The maximum elongation ratio of CsgA-His nanofibers is 17.1,indicating that the fibril’s flexibility is much higher than DNA or silk fiber.For forces less than 20 pN,the extension was reversible.With a 42.1 pN holding force,the extension jumped in steps of from 30 to 365 nm and was irreversible.At the scale tested,the jumps corresponded to the unfolding of multiple beta sheets in the fiber.Work for CsgA-His nanofibers during stretching increase with the normalized strain fractions.The experimental data agree with a theoretical prediction for a single CsgA protein from a SMD calculation.Therefore,our results provide key information for the understandings of CsgA protein nanofiber assembly and biofilm robustness.

Force-Regulated Adhesion and Activation Study of Integrin Targeting Polypeptides

Integrins are heterodimeric cell surface receptors that bind to ligands on another cell,e.g.intercellular adhesion molecule 1(ICAM-1),or the extracellular matrix.Integrins play an important role in immune system,and they participate in inflammation,thrombosis,and proliferation,migration and apoptosis of tumor cells.They mediate adhesion and transduce signals across the membrane usually under the influence of forces.A recent study has shown that integrins bind and activate transforming growth factorβisoform(TGF-β)which is involved in tumor suppression and growth,and blocking the binding of TGF-βto integrin can inhibit tumor growth.RGD(arginine-glycine-aspartate)small peptide,which competitively inhibits ligand binding to integrins,has been approved as an injectable drug.However,when the RGD is used to block cancer-related extracellular signaling pathways,it will also cause activation of integrins for a period,and stimulate the transduction of intracellular signals constantly.Therefore,it is necessary to explore for new drugs that can selectively control conformational state of integrins without activating or blocking all of them.In this study,we selected two small peptides,KQAGDV and RTDLDSLRT,that combined with integrins and do not contain an RGD sequence.The non-RGD polypeptide RTDLDSLRT has been reported to have a binding site with integrins and the binding affinity is on nanomolar scale.For the motif of the fibrinogen y chain C-terminal KQAGDV,it can adhere to the head of the integrins.The micropipette aspiration technique and electron microscopy techniques were used to study the adhesion and activation of integrins by peptides,respectively.Micropipette aspiration technique was used to investigate the adhesion frequency of peptide and integrin on Jurkat cell.The pressure system was used to supply a controllable negative pression to the microtube,and two micropipettes were used to absorb red blood cells and Jurkat cells,respectively.The red blood cells were coated with small peptides and can serve as a force sensor after being sucked when two cells were connected.The binding kinetics of integrin and peptides interactions was determined by fitting the curves constructed using adhesion probability between two cells as a function of time.The curves were fitted using a small system probabilistic kinetic model to estimate a pair of kinetic parameters,including the zero force reverse rate kr0,and the cellular binding affinity Acmrm1Ka0.The adhesion frequency yielded P(t)=75%and 57%for RGD and KQAG DV peptides,respectively.We obtained Acmrm1Ka0=1.40 and kr0=0.32 s-1,for RGD,and Acmrm1Ka0=0.85 and kr0=0.54 s-1 for KQAGDV.The RGD peptide has a higher adhesion frequency and lower dissociation rate than the KQAGDV peptide.Electron microscopy techniques was used to observe the activation of integrins by peptides.Jurkat cell expressing integrins was bound to a magnetic bead and bottom plate which were coated with different integrin-binding peptides.Then,we manipulated the beads in a controlled direction by changing the magnetic field nearby,and the forces were applied to the cell.The target cells were fixed and then observed by scanning electron microscope or transmission electron microscope.Jurkat cells contain abundant flexible microvilli of which there are many parallel bundles of actin filaments inside.By electron microscopy analysis,the cell connected with magnetic bead coated with RGD were found to be protruded and the size of microvilli increased up to#-fold of the length of the KQAGDV sample.The microvilli exhibited a curved agglomerate structure under a force-free condition.Moreover,a higher proportion of cells were activated in the presence of RGD than KQAGDV.In conclusion,the binding affinity of KQAGDV to integrin is weaker than RGD,and KQAGDV can bind with integrins effectively with a lower activated proportion.Our results indicate the peptides may selectively bind to integrins without activating them.

Study on the Mechanism of Salt-induced Osmotic Pressure Promoting Lipid Accumulation of Chlorella

Salt-induced osmotic pressure has been drawing increasing attention in the field of microalgal biomechanics because it can enhance the lipids accumulation of microalgae.Studies have shown that osmotic stress can affect the synthesis of phospholipids by activating different phospholipid signaling pathways.However,there is little research about the mechanism of action of osmotic stress in neutral lipids synthesis.In this work,the effects of different salt-induced osmotic pressure on oil synthesis and potential mechanismwere studied.First,effect of various salt4nduced osmotic pressure of 64,112,191,453 and 1304 mOsm/kg on Chlorella pyrenoidosa oil synthesis were studied and optimal salt-induced osmotic pressure of 453 mOsm/kg was acquired.Then the content of key signaling chemicals in the Cyclic Adenosine monophosphate(cAMP)signaling pathway and the key enzyme activities in the lipid synthesis pathway were determined under salt-induced osmotic pressure of 453 mOsm/kg.It was found that the cAMP signaling pathway were up-regulated under salt osmotic pressure conditions of 453 mOsm/kg;in addition,the key enzymes related to lipid synthesis increased,while those related to protein synthesis decreased,enabling the increase of the lipid content.Finally,the effects of inhibitor atropine and promoter IBMX of cAMP signal pathway were also investigated.Results showed that atropine inhibits the cAMP signaling pathway and the lipid contents decreased;in contrast,IBMX activated thecAMP signaling pathway and the lipids content increased.These observations further confirm that salt-induced osmotic pressure had the same function as the signal promoter to regulate lipid synthesis by adjusting cAMP signaling pathway regulating lipid synthesis.This study preliminarily revealed the mechanism that salt-induced osmotic pressure affected lipid synthesis pathway through cAMP signaling pathway to regulate lipid synthesis in microalgae.

Towards Incremental Deployment of Diverse Network Architectures on the Internet

In the past decades, many cleanslate future network architectures have gained limited deployment in current Internet, due to the stability and rigidity of TCP/IP, the narrow waist of the Internet. We first propose three principles that the future Internet architecture should obey to be well-defined network architecture, i.e. supporting service innovation and enabling evolvability. By abstracting different modes from TCP/IP network and SDN technology, we argue that the centric-distributed-centric(CDC) mode has great potential for the well-defined future network architecture in which diverse network architectures could be incrementally deployed and coexist with each other. Prototype system regulated by CDC mode was developed. Experimental results reveal that CDC can support diverse architectures to coexist in the current Internet and thus enables the Internet to evolve.

Isolation and Purification of Enzymatic Hydrolysates of Yam(Dioscorea opposita Thunb.)Proteins

Using yam （Dioscorea opposita Thunb. ） as the experimental material, enzymatic hydrolysates of yam proteins were prepared with alkaline protease, which were then isolated and purified by cellulose DE-52 anion exchange chromatography Sephadex G-50 gel chromatography. According to the results, four absorp- tion peaks were obtained by cellulose DE-52 anion exchange chromatography, and fractions at each absorption peak were collected. Specifically, the reducing ability of four peaks demonstrated a descending order of peak 2 （P2） 〉 peak I （ P1 ） 〉 peak 3 （P3） 〉 peak 4 （P4）. By Sephadex G-50 gel chmmatography, P1 and P2 were isolated and purified with distilled water and Tris-HC1 buffer, and two absorption peaks were obtained, respectively.

Content Authentication Based on JPEG-to-JPEG Watermarking

A content authentication technique based on JPEG-to-JPEG watermarking is proposed in this paper. In this technique, each 8x8 block in a JPEG compressed image is first processed by entropy decoding, and then the quantized discrete cosine transform （DCT） is applied to generate DCT coefficients： one DC coefficient and 63 AC coefficients in frequency coefficients. The DCT AC coefficients are used to form zero planes in which the watermark is embedded by a chaotic map. In this way, the watermark information is embedded into JPEG compressed domain, and the output watermarked image is still a JPEG format. The proposed method is especially applicable to content authentication of JPEG image since the quantized coefficients are modified for embedding the watermark and the chaotic system possesses an important property with the high sensitivity on initial values. Experimental results show that the tamper regions are localized accurately when the watermarked JPEG image is maliciously tampered.

机器人手术系统辅助下的结直肠癌经自然腔道取标本手术与常规辅助切口取标本手术的近期疗效对比研究

目的比较机器人无辅助切口NOSES组(R-NOSES)和机器人常规辅助切口组(R-LA)在结直肠癌治疗中的近期疗效差异。方法纳入203例于哈尔滨医科大学附属第二医院肿瘤中心行机器人辅助下结直肠癌根治术的患者的病例资料,包括患者的术前一般资料、手术相关资料、病理资料以及术后相关资料。对比分析R-NOSES和R-LA的近期疗效差异。结果本研究共纳入R-NOSES患者36例,R-LA患者167例。通过倾向性评分后,R-NOSES患者36例,R-LA患者25例,R-NOSES组的平均手术时间长于R-LA组(267.64±57.23 min vs. 239.80±33.68 min,t=-2.181,P=0.033)。R-NOSES组的平均术后住院时间(t=2.860,P=0.006)、平均术后进食流质食物时间(t=2.929,P=0.005)和平均术后首次排气时间(t=3.046,P=0.003)均短于R-LA组,R-NOSES组并发症比例较R-LA组少(χ^(2)=4.164,P=0.041),术后第一日疼痛评分低于R-LA组(t=2.994,P=0.005)。R-NOSES组术后躯体功能(t=-7.530,P<0.001)、角色功能(t=-6.359,P<0.001)、情绪功能(t=-4.812,P<0.001)恢复更好,整体健康情况优于R-LA组(t=-4.288,P<0.001)。结论与R-LA组相比,R-NOSES组虽然平均手术时间略有延长,但术后首次排气时间、术后首次进流食时间、术后住院时间均更短,术后并发症少,功能恢复更快,术后疼痛更少。

靶向难成药蛋白——蛋白质降解剂的力量

Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted,but are of great clinical significance.According to statistics,over 80%of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods.In recent years,with the advancement of basic research and new technologies,the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets.Among them,targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets.This technology can specifically identify target proteins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation pathways within cells.This new form of drug development includes various types such as proteolysis targeting chimera(PROTAC),molecular glue,lysosome-targeting Chimaera(LYTAC),autophagosometethering compound(ATTEC),autophagy-targeting chimera(AUTAC),autophagy-targeting chimera(AUTOTAC),degrader-antibody conjugate(DAC).This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets.Finally,the article looks forward to the future development direction and application prospects of targeted protein degradation technology.

K_(2)S_(2)O_(8)-mediated acylarylation of unactivated alkenes via acyl radical addition/C–H annulation cascade of N-allyl-indoles with silver cocatalysis

A silver-catalyzed,K_(2)S_(2)O_(8)-mediated protocol to access regioselective acylarylation of unactivated alkenes was developed.The reaction between N-allyl-indoles andα-oxocarboxylic acids proceeded smoothly and involved an acyl radical addition/C–H cyclization cascade.The protocol showed a broad substrate scope and good tolerance of functional groups.The reaction proceeded with both internal and terminal alkenes to furnish many functional pyrrolo[1,2-a]indoles bearing the ketone carbonyl group,and this feature also provides the potential to construct structurally complex N-containing heterocycles.