p53-expressing conditionally replicative adenovirus CNHK500-p53 against hepatocellular carcinoma in vitro

AIM： To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma （HCC）. METHODS： CNHK500-p53 was constructed by using human telomerase reverse transcriptase （hTERT） promoter to drive adenovirus E1a gene and hypoxia response element （HRE） promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect （CPE） and methyl thiazolyl tetrazolium （MTT） assay were performed to test the selective replication and oncolytic efficacy of CNHK500-p53. RESULTS： Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factordependent HCC cells, p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro （388 ± 34.6 μg/L vs 76.3 ± 13.17 μg/L）. Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and H1-F assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected. CONCLUSION： A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells.

Generating of Conditionally Exactly Soluble Potentials by Method of Supersymmetric Quantum Mechanics

This paper suggests a systematic method based on supersymmetric quantum mechanics for generating conditionally exactly soluble potentials, and uses the variational supersymmetric WKB method to obtain the approximate values of the energy spectrum of the whole class.

Conditionally Teleported States Using Optical Squeezers and Photon Counting

By virtue of the neat expression of the two-mode squeezing operator in the Einstein, Podolsky and Rosen entangled state representation, we provide a new approach for discussing the teleportation scheme using optical squeezers and photon counting devices. We derive the explicit form of the teleported states, so that the conditional property of teleportation and teleportation fidelity of this protocol can be seen more clearly. The derivation is concise.

Preliminary Evaluation of Safety of Conditionally Replication Adenovirus M4

Conditionally replication adenovirus M4, which was constructed in our lab, was proved to have good clinical application prospect for its good antitumor and antimetastasis effect. However, clinically applying M4 faces many problems. One of the most important is the safety of M4. In this study, we investigated the safety of M4 by comparing with Adv-TK, which was proved to be safe in Ⅰ–Ⅲ phase clinical trials. M4 and Adv-TK were injected into mice via the tail vein separately, and the mice were sacrificed at the indicated time. Blood was collected for biochemical tests, the liver was harvested for hematoxylin and eosin (H&E) staining and viral quantification, and splenic lymphocytes were separated for adenovirus specific cellular immune response. Our results showed that M4 had no obvious effect on mouse general symptoms. A transient reversible infiltration of inflammatory cells in collect abbacy was only observed in M4 group, and a transient slight increase in Cr level was detected both after M4 and Adv-TK injection. The adenovirus specific cellular immune response induced by M4 was similar to that by Adv-TK, and the distribution and metabolism of M4 in the mouse liver were also similar to those of Adv-TK. It was concluded that conditionally replication adenovirus M4 had the same safety as Adv-TK. The study provides safety basis for the coming clinical trials of M4.

The study of RNAi-mediated by conditionally replicating adenovirus silencing on Survivin gene in colon cancer cell lastingly

Objective： To investigate the effect of RNAj-mediated Survivin gene with conditionally replicating adenovirus silencing on Survivin gene in colon carcinoma cell lines HT-29 lastingly. Methods： We transfected Ad-delE1655KD-shRNA / Survivin-EGFP to HT-29 （control was replication defective adenovirus and liposome vector which was contained the same shRNA as Ad-delE1b55KD-shRNA / Survivin-EGFP）. The expressions of EGFP, Survivin mRNA and Survivin protein in HT- 29 were detected at the 1st, 7th, 14th and 28th days alter transfection. Results： The expression of EGFP, the inhibition of Survivin mRNA and Survivin protein in HT-29 were high in each group at the 7th day alter transfection, among the total, the effect of Ad-delE1655KD-shRNA/Survivin-EGFP group was the highest; at the 14th day, the effects of replication defective adenovirus group and liposome vector group were decreased obviously, and it was still high in Ad-delE1655KD-shRNA / Survivin-EGFP group; at the 28th day, the effects of control groups were disappeared, and it was still high in Ad-delE1b55KD- shRNA/Survivin-EGFP group like before （P 〈 0.05）. Conclusion： RNAi-mediated Survivin gene with conditionally replicating adenovirus can silence Survivin gene in colon carcinoma cell lines HT-29 lastingly.

A Conditionally Anonymous Linkable Ring Signature for Blockchain Privacy Protection

In recent years,the issue of preserving the privacy of parties involved in blockchain transactions has garnered significant attention.To ensure privacy protection for both sides of the transaction,many researchers are using ring signature technology instead of the original signature technology.However,in practice,identifying the signer of an illegal blockchain transaction once it has been placed on the chain necessitates a signature technique that offers conditional anonymity.Some illegals can conduct illegal transactions and evade the lawusing ring signatures,which offer perfect anonymity.This paper firstly constructs a conditionally anonymous linkable ring signature using the Diffie-Hellman key exchange protocol and the Elliptic Curve Discrete Logarithm,which offers a non-interactive process for finding the signer of a ring signature in a specific case.Secondly,this paper’s proposed scheme is proven correct and secure under Elliptic Curve Discrete Logarithm Assumptions.Lastly,compared to previous constructions,the scheme presented in this paper provides a non-interactive,efficient,and secure confirmation process.In addition,this paper presents the implementation of the proposed scheme on a personal computer,where the confirmation process takes only 2,16,and 24ms for ring sizes of 4,24 and 48,respectively,and the confirmation process can be combined with a smart contract on the blockchain with a tested millisecond level of running efficiency.In conclusion,the proposed scheme offers a solution to the challenge of identifying the signer of an illegal blockchain transaction,making it an essential contribution to the field.

Conditionally Suboptimal Filtering in Nonlinear Stochastic Differential System

This paper presents a novel conditionally suboptimal filtering algorithm on estimation problems that arise in discrete nonlinear time-varying stochastic difference systems. The suboptimal state estimate is formed by summing of conditionally nonlinear filtering estimates that their weights depend only on time instants, in contrast to conditionally optimal filtering, the proposed conditionally suboptimal filtering allows parallel processing of information and reduce online computational requirements in some nonlinear stochastic difference system. High accuracy and efficiency of the conditionally suboptimal nonlinear filtering are demonstrated on a numerical example.

Some conditional results for conditionally strong mixing sequences of random variables

The relation between strong mixing and conditionally strong mixing is answered by examples,that is,the strong mixing property of random variables does not imply the conditionally strong mixing property,and the opposite implication is also not true.Some equivalent definitions and basic properties of conditional strong mixing random variables are derived,and several conditional covariance inequalities are obtained.By means of these properties and conditional covariance inequalities,a conditional central limit theorem stated in terms of conditional characteristic functions is established,which is a conditional version of the earlier result under non-conditional case.

CONDITIONALLY PERIODIC SOLUTIONS TO NONLINEAR SCHRDINGER EQUATIONS——INVERSE SPECTRAL PROBLEM OF DIRAC OPERATORS

We introduce a kind of spectrum coordinates to study the inverse spectral problem of Dirac operators of a certain finite-band spectrum and obtain conditionally periodic solutions of the Cauchy problems of defocusing NLS equation.

On Conditionally Positive Definite Dot Product Kernels

Let m and n be fixed, positive integers and P a space composed of real polynomials in m variables. The authors study functions f ： R →R which map Gram matrices, based upon n points of R^m, into matrices, which are nonnegative definite with respect to P Among other things, the authors discuss continuity, differentiability, convexity, and convexity in the sense of Jensen, of such functions

Optimal consumption–investment under partial information in conditionally log-Gaussian models

Certain Merton type consumption−investment problems under partial information are reduced to the ones of full information and within the framework of a complete market model.Then,specializing to conditionally log−Gaussian diffusion models,concrete analysis about the optimal values and optimal strategies is performed by using analytical tools like Feynman−Kac formula,or HJB equations.The explicit solutions to the related forward-backward equations are also given.

Conditional mean convergence theorems of conditionally dependent random variables under conditions of integrability

We give the conditionally residual h-integrability with exponent r for an array of random variables and establish the conditional mean convergence of conditionally negatively quadrant dependent and conditionally negative associated random variables under this integrability. These results generalize and improve the known ones.

Organic Matter Accumulation in the Upper Permian Dalong Formation from the Lower Yangtze Region,South China

The Late Permian was marked by a series of important geological events and widespread organic-rich black shale depositions,acting as important unconventional hydrocarbon source rocks.However,the mechanism of organic matter(OM)enrichment throughout this period is still controversial.Based on geochemical data,the marine redox conditions,paleogeographic and hydrographic environment,primary productivity,volcanism,and terrigenous input during the Late Permian in the Lower Yangtze region have been studied from the Putaoling section,Chaohu,to provide new insights into OM accumulation.Five Phases are distinguished based on the TOC and environmental variations.In Phase I,anoxic conditions driven by water restriction enhanced OM preservation.In Phase II,euxinic and cycling hydrological environments were the two most substantial controlling factors for the massive OM deposition.During Phase III,intensified terrestrial input potentially diluted the OM in sediment and the presence of oxygen in bottom water weakened the preservation condition.Phase IV was characterized by a relatively higher abundance of mercury(Hg)and TOC(peak at 16.98 wt%),indicating that enhanced volcanism potentially stimulated higher productivity and a euxinic environment.In Phase V,extremely lean OM was preserved as a result of terrestrial dilutions and decreasing primary productivity.Phases I,II and IV are characterized as the most prominent OM-rich zones due to the effective interactions of the controlling factors,namely paleogeographic,hydrographic environment,volcanism,and redox conditions.

Genesis of LCT Pegmatites during Early Paleozoic Orogeny of the North Qinling Orogenic Belt,China:Emplacement Conditions and Structural Control

The Guanpo pegmatite field in the North Qinling orogenic belt(NQB),China,hosts the most abundant LCT pegmatites.However,their emplacement conditions and structural control remain unexplored.In this contribution,we investigated it combining pegmatite orientation measurement with oxygen isotope geothermometry and fluid inclusion study.The orientations of type A1 pegmatites(P_(f)<σ_(2))are predominantly influenced by P-and T-fractures due to simple shearing in Shiziping dextral thrust shear zone during D_(2)deformation,whereas type A2 pegmatites(contemporaneous with D_(4))are governed by hydraulic fractures aligned with S_(0)and S_(0+1)stemming from fluid pressure(P_(f)<σ_(2)).Additionally,type B pegmatites(P_(f)≤σ_(2))exhibit orientations shaped by en echelon extensional fractures in local ductile shear zones(contemporaneous with D_(3)).The albite-quartz oxygen isotope geothermometry and microthermometric analysis of fluid inclusions in elbaites from the latest pegmatites(including types B and A2)suggest that the crystallization P-T for late magmatic and hydrothermal stages are 527.5-559.2℃,320℃,3.1-3.6 kbar and 2.0 kbar,respectively.Our observations along with previous studies suggest that the genesis of the LCT pegmatites was a long-term,multi-stage event during early Paleozoic orogeny(including the collision stage)of the NQB,and was facilitated by various local fractures.

Ambient-Condition Strategy for Production of Hollow Ga_(2)O_(3)@rGO Crystalline Nanostructures Toward Efficient Lithium Storage

Crystallineγ-Ga_(2)O_(3)@rGO core-shell nanostructures are synthesized in gram scale,which are accomplished by a facile sonochemical strategy under ambient condition.They are composed of uniformγ-Ga_(2)O_(3)nanospheres encapsulated by reduced graphene oxide(rGO)nanolayers,and their formation is mainly attributed to the existed opposite zeta potential between the Ga_(2)O_(3)and rGO.The as-constructed lithium-ion batteries(LIBs)based on as-fabricatedγ-Ga_(2)O_(3)@rGO nanostructures deliver an initial discharge capacity of 1000 mAh g^(-1)at 100 mA g^(-1)and reversible capacity of 600 mAh g^(-1)under 500 mA g^(-1)after 1000 cycles,respectively,which are remarkably higher than those of pristineγ-Ga_(2)O_(3)with a much reduced lifetime of 100 cycles and much lower capacity.Ex situ XRD and XPS analyses demonstrate that the reversible LIBs storage is dominant by a conversion reaction and alloying mechanism,where the discharged product of liquid metal Ga exhibits self-healing ability,thus preventing the destroy of electrodes.Additionally,the rGO shell could act robustly as conductive network of the electrode for significantly improved conductivity,endowing the efficient Li storage behaviors.This work might provide some insight on mass production of advanced electrode materials under mild condition for energy storage and conversion applications.

Aero-Hydro-Elastic-Servo Modeling and Dynamic Response Analysis of A Monopile Offshore Wind Turbine Under Different Operating Scenarios

This paper constructs a coupled aero-hydro-elastic-servo simulation framework for a monopile offshore wind turbine(OWT).In this framework,a detailed multi-body dynamics model of the monopile OWT including the gearbox,blades,tower and other components(nacelle,hub,bedplate,etc.)has been explicitly established.The effects of pile−soil interaction,controller and operational conditions on the turbine dynamic responses are studied systematically in time domain and frequency domain.The results show that(1)a comprehensive drivetrain model has the capability to provide a more precise representation of the complex dynamic characteristics exhibited by drivetrain components,which can be used as the basis for further study on the dynamic characteristics of the drivetrain.(2)The pile−soil interaction can influence the wind turbine dynamic responses,particularly under the parked condition.(3)The effect of the pile−soil interaction on tower responses is more significant than that on blade responses.(4)The use of the controller can substantially affect the rotor characteristics,which in turn influences the turbine dynamic responses.(5)The tower and blade displacements under the operational condition are much larger than those under the parked condition.The model and methodology presented in this study demonstrate potential for examining complex dynamic behaviors of the monopile OWTs.To ensure accuracy and precision,it is imperative to construct a detailed model of the wind turbine system,while also taking into account simulation efficiency.

Role of outdoor trees on pedestrian wind and thermal conditions around a pre-education building for sustainable energy management

Finding sustainable energy resources is essential to face the increasing energy demand.Trees are an important part of ancient architecture but are becoming rare in urban areas.Trees can control and tune the pedestrian-level wind velocity and thermal condition.In this study,a numerical investigation is employed to assess the role of trees planted in the windward direction of the building complex on the thermal and pedestrian wind velocity conditions around/inside a pre-education building located in the center of the complex.Compared to the previous studies(which considered only outside buildings),this work considers the effects of trees on microclimate change both inside/outside buildings.Effects of different parameters including the leaf area density and number of trees,number of rows,far-field velocity magnitude,and thermal condition around the main building are assessed.The results show that the flow velocity in the spacing between the first-row buildings is reduced by 30%-40% when the one-row trees with 2 m height are planted 15 m farther than the buildings.Furthermore,two rows of trees are more effective in higher velocities and reduce the maximum velocity by about 50%.The investigation shows that trees also could reduce the temperature by about 1℃around the building.

Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition:Harnessing the power of nanotheranostics

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

Dynamic Vision-Based Machinery Fault Diagnosis With Cross-Modality Feature Alignment

Intelligent machinery fault diagnosis methods have been popularly and successfully developed in the past decades,and the vibration acceleration data collected by contact accelerometers have been widely investigated.In many industrial scenarios,contactless sensors are more preferred.The event camera is an emerging bio-inspired technology for vision sensing,which asynchronously records per-pixel brightness change polarity with high temporal resolution and low latency.It offers a promising tool for contactless machine vibration sensing and fault diagnosis.However,the dynamic vision-based methods suffer from variations of practical factors such as camera position,machine operating condition,etc.Furthermore,as a new sensing technology,the labeled dynamic vision data are limited,which generally cannot cover a wide range of machine fault modes.Aiming at these challenges,a novel dynamic vision-based machinery fault diagnosis method is proposed in this paper.It is motivated to explore the abundant vibration acceleration data for enhancing the dynamic vision-based model performance.A crossmodality feature alignment method is thus proposed with deep adversarial neural networks to achieve fault diagnosis knowledge transfer.An event erasing method is further proposed for improving model robustness against variations.The proposed method can effectively identify unseen fault mode with dynamic vision data.Experiments on two rotating machine monitoring datasets are carried out for validations,and the results suggest the proposed method is promising for generalized contactless machinery fault diagnosis.

Debaryomyces hansenii supplementation in low fish meal diets promotes growth,modulates microbiota and enhances intestinal condition in juvenile marine fish

Background The development of a sustainable business model with social acceptance,makes necessary to develop new strategies to guarantee the growth,health,and well-being of farmed animals.Debaryomyces hansenii is a yeast species that can be used as a probiotic in aquaculture due to its capacity to i)promote cell proliferation and differen-tiation,ii)have immunostimulatory effects,iii)modulate gut microbiota,and/or iv)enhance the digestive function.To provide inside into the effects of D.hansenii on juveniles of gilthead seabream(Sparus aurata)condition,we inte-grated the evaluation of the main key performance indicators coupled with the integrative analysis of the intestine condition,through histological and microbiota state,and its transcriptomic profiling.Results After 70 days of a nutritional trial in which a diet with low levels of fishmeal(7%)was supplemented with 1.1%of D.hansenii(17.2×10^(5) CFU),an increase of ca.12%in somatic growth was observed together with an improve-ment in feed conversion in fish fed a yeast-supplemented diet.In terms of intestinal condition,this probiotic modu-lated gut microbiota without affecting the intestine cell organization,whereas an increase in the staining intensity of mucins rich in carboxylated and weakly sulphated glycoconjugates coupled with changes in the affinity for certain lectins were noted in goblet cells.Changes in microbiota were characterized by the reduction in abundance of several groups of Proteobacteria,especially those characterized as opportunistic groups.The microarrays-based transcrip-tomic analysis found 232 differential expressed genes in the anterior-mid intestine of S.aurata,that were mostly related to metabolic,antioxidant,immune,and symbiotic processes.Conclusions Dietary administration of D.hansenii enhanced somatic growth and improved feed efficiency param-eters,results that were coupled to an improvement of intestinal condition as histochemical and transcriptomic tools indicated.This probiotic yeast stimulated host-microbiota interactions without altering the intestinal cell organization nor generating dysbiosis,which demonstrated its safety as a feed additive.At the transcriptomic level,D.hansenii pro-moted metabolic pathways,mainly protein-related,sphingolipid,and thymidylate pathways,in addition to enhance antioxidant-related intestinal mechanisms,and to regulate sentinel immune processes,potentiating the defensive capacity meanwhile maintaining the homeostatic status of the intestine.