AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Interacting topological magnons in a checkerboard ferromagnet

This work is devoted to studying the magnon-magnon interaction effect in a two-dimensional checkerboard ferromagnet with the Dzyaloshinskii-Moriya interaction.Using a first-order Green function method,we analyze the influence of magnon-magnon interaction on the magnon band topology.We find that Chern numbers of two renormalized magnon bands are different above and below the critical temperature,which means that the magnon band gap-closing phenomenon is an indicator for one topological phase transition of the checkerboard ferromagnet.Our results show that the checkerboard ferromagnet possesses two topological phases,and its topological phase can be controlled either via the temperature or the applied magnetic field due to magnon-magnon interactions.Interestingly,it is found that the topological phase transition can occur twice with the increase in the temperature,which is different from the results of the honeycomb ferromagnet.

Generation and regulation of electromagnetic pulses generated by femtosecond lasers interacting with multitargets

Ultrashort and powerful laser interactions with a target generate intense wideband electromagnetic pulses(EMPs).In this study,we report EMPs generated by the interactions between petawatt(30 fs,1.4×10^(20) W/cm^(2))femtosecond(fs)lasers with metal flat,plastic flat,and plastic nanowire-array(NWA)targets.Detailed analyses are conducted on the EMPs in terms of their spatial distribution,time and frequency domains,radiation energy,and protection.The results indicate that EMPs from metal targets exhibit larger amplitudes at varying angles than those generated by other types of targets and are enhanced significantly for NWA targets.Using a plastic target holder and increasing the laser focal spot can significantly decrease the radiation energy of the EMPs.Moreover,the composite shielding materials indicate an effective shielding effect against EMPs.The simulation results show that the NWA targets exert a collimating effect on thermal electrons,which directly affects the distribution of EMPs.This study provides guidance for regulating EMPs by controlling the laser focal spot,target parameters,and target rod material and is beneficial for electromagnetic-shielding design.

Visualization of hydraulic fracture interacting with pre-existing fracture

Hydraulic fracturing is considered the main stimulation method to develop shale gas reservoirs. Due to its strong heterogeneity, the shale gas formation is typically embedded with geological discontinuities such as bedding planes and natural fractures. Many researchers realized that the interaction between natural fractures and hydraulic fractures plays a crucial role in generating a complex fracture network. In this paper, true tri-axial hydraulic fracturing tests were performed on polymethyl methacrylate (PMMA), on which pre-existing fracture was pre-manufactured to simulate natural fracture. A cohesive model has been developed to verify the results of the experimental tests. The key findings demonstrate that the experimental results agreed well with the numerical simulation outcomes where three main interaction modes were observed: crossing;being arrested by opening the pre-existing fracture;being arrested without dilating the pre-existing fracture. Crossing behavior is more likely to occur with the approaching angle, horizontal stress difference, and injection rate increase. Furthermore, the higher flow rate might assist in reactivating the natural fractures where both sides of the pre-existing fractures were reactivated as the injection rate increased from 5 to 20 mL/min. Additionally, hydraulic fractures show a tendency to extend vertically rather than along the direction of maximum horizontal stress when they are first terminated at the interface. This research may contribute to the field application of hydraulic fracturing in shale gas formation.

Calcium/calmodulin modulates salt responses by binding a novel interacting protein SAMS1 in peanut(Arachis hypogaea L.)

The Ca^(2+)/CaM signal transduction pathway helps plants adapt to environmental stress. However, our knowledge on the functional proteins of C^(2+)/CaM pathway in peanut(Arachis hypogeae L.) remains limited. In the present study, a novel calmodulin 4(CaM4)-binding protein S-adenosyl-methionine synthetase 1(SAMS1) in peanut was identified using a yeast two-hybrid assay. Expression of AhSAMS1was induced by Ca^(2+), ABA, and salt stress. To elucidate the function of AhSAMS1, physiological and phenotypic analyses were performed with wild-type and transgenic materials. Overexpression of AhSAMS1increased spermidine and spermidine synthesis while decreased the contents of ethylene, thereby eliminating excessive reactive oxygen species(ROS) in transgenic lines under salt stress. AhSAMS1 reduced uptake of Na+and leakage of K+from mesophyll cells, and was less sensitive to salt stress during early seedling growth, in agreement with the induction of SOS and NHX genes Transcriptomics combined with epigenetic regulation uncovered relationships between differentially expressed genes and differentially methylated regions, which raised the salt tolerance and plants growth. Our findings support a model in which the role of AhSAMS1 in the ROS-dependent regulation of ion homeostasis was enhanced by Ca^(2+)/CaM while AhSAMS1-induced methylation was regulated by CaM, thus providing a new strategy for increasing the tolerance of plants to salt stress.

OsSPL10 controls trichome development by interacting with OsWOX3B at both transcription and protein levels in rice(Oryza sativa L.)

Plant trichomes are a specialized cellular tissue that functions in resistance to biotic and abiotic stresses.In rice,three transcription-factor genes:OsWOX3B,HL6,and OsSPL10,have been found to control trichome development.Although studies have shown interactions between the three genes,their full relationship in trichome development is unclear.We found that the expression levels of OsWOX3B and HL6 were both reduced in OsSPL10-knockout plants but increased in OsSPL10-overexpression plants,suggesting that OsSPL10 positively regulates their expression.Physical interaction between OsSPL10 and OsWOX3B was found both in vivo and in vitro and attenuated their abilities to bind to the promoter of HL6 to activate its transcription.This mechanism may regulate trichome length by adjusting the expression of HL6.A rice gene network regulating trichome development is proposed.

Mismatched effects of receptor interacting protein kinase-3 on hepatic steatosis and inflammation in nonalcoholic fatty liver disease

AIM To validate the effects of receptor interacting protein kinase-3(RIP3) deletion in non-alcoholic fatty liver disease(NAFLD) and to clarify the mechanism of action.METHODS Wild-type(WT) and RIP3 knockout(KO) mice werefed normal chow and high fat(HF) diets for 12 wk. The body weight was assessed once weekly. After 12 wk, the liver and serum samples were extracted. The liver tissue expression levels of RIP3, microsomal triglyceride transfer protein, protein disulfide isomerase, apolipoprotein-B, X-box binding protein-1, sterol regulatory element-binding protein-1c, fatty acid synthase, cluster of differentiation-36, diglyceride acyltransferase, peroxisome proliferator-activated receptor alpha, tumor necrosis factor-alpha(TNF-α), and interleukin-6 were assessed. Oleic acid treated primary hepatocytes from WT and RIP3 KO mice were stained with Nile red. The expression of inflammatory cytokines, including chemokine(C-X-C motif) ligand(CXCL) 1, CXCL2, and TNF-α, in monocytes was evaluated.RESULTS RIP3 KO HF diet fed mice showed a significant gain in body weight, and liver weight, liver to body weight ratio, and liver triglycerides were increased in HF diet fed RIP3 KO mice compared to HF diet fed WT mice. RIP3 KO primary hepatocytes also had increased intracellular fat droplets compared to WT primary hepatocytes after oleic acid treatment. RIP3 overexpression decreased hepatic fat content. Quantitative real-time polymerase chain reaction analysis showed that the expression of very-low-density lipoproteins secretion markers(microsomal triglyceride transfer protein, protein disulfide isomerase, and apolipoprotein-B) was significantly suppressed in RIP3 KO mice. The overall NAFLD Activity Score was the same between WT and RIP3 KO mice; however, RIP3 KO mice had increased fatty change and decreased lobular inflammation compared to WT mice. Inflammatory signals(CXCL1/2, TNF-α, and interleukin-6) increased after lipopolysaccharide and pancaspase inhibitor(necroptotic condition) treatment in monocytes. Neutrophil chemokines(CXCL1, and CXCL2) were decreased, and TNF-α was increased after RIP3 inhibitor treatment in monocytes.CONCLUSION RIP3 deletion exacerbates steatosis, and partially inhibits inflammation in the HF diet induced NAFLD model.

MicroRNA-760 acts as a tumor suppressor in gastric cancer development via inhibiting G-protein-coupled receptor kinase interacting protein-1 transcription

BACKGROUND Gastric cancer(GC)has become a serious threat to people's health.Accumulative evidence reveals that dysregulation of numerous microRNAs(miRNAs)has been found during malignant formation.So far,the role of microRNA-760(miR-760)in the development of GC is largely unknown.AIM To measure the expression level of miR-760 in GC and investigate its role in gastric tumorigenesis.METHODS Real-time quantitative polymerase chain reaction and Western blot analysis were used to measure the expression of miR-760 and G-protein-coupled receptor kinase interacting protein-1(GIT1).Cell growth was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)and cell colony formation assays.Apoptosis was assessed by flow cytometric analysis.The relationship between miR-760 and GIT1 was verified by luciferase reporter assay.RESULTS The results showed that the expression of miR-760 was decreased in GC and associated with poor clinical outcomes in GC patients.Furthermore,miR-760 restrained cell proliferation and cell colony formation and induced apoptosis in GC cells.In addition,miR-760 directly targeted GIT1 and negatively regulated its expression in GC.GIT1 was upregulated in GC and predicted a worse prognosis in GC patients.We also found that upregulation of GIT1 weakened the inhibitory CONCLUSION In conclusion,miR-760 targets GIT1 to inhibit cell growth and promote apoptosis in GC cells.Our data demonstrate that miR-760 may be a potential target for the treatment of GC.

VANISHING VISCOSITY FOR NON-ISENTROPIC GAS DYNAMICS WITH INTERACTING SHOCKS

In this paper, we study the vanishing viscosity limit for non-isentropic gas dy- namics with interacting shocks. Given any entropy solution of non-isentropic gas dynamics which consists of two different families of shocks interacting at some positive time, we show that such solution is the vanishing viscosity limit of a family of smooth global solutions for a viscous system of conservation law. We remark that, after the interacting time, not only shocks but also contact discontinuity are generated.

Thioredoxin interacting protein,a key molecular switch between oxidative stress and sterile inflammation in cellular response

Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.

An application of interacting shear flows theory: exact solution for unsteady oblique stagnation point flow

An analytical solution of the governing equations of the interacting shear flows for unsteady oblique stagnation point flow is obtained. It has the same form as that of the exact solution obtained from the complete NS equations and physical analysis and relevant discussions are then presented.

Aircraft Trajectory Prediction Based on Modified Interacting Multiple Model Algorithm

In order to realize the aircraft trajectory prediction,a modified interacting multiple model(M-IMM) algorithm is proposed,which is based on the performance analysis of the standard interacting multiple model(IMM) algorithm.In the proposed M-IMM algorithm,a new likelihood function is defined for the sake of updating flight mode probabilities,in which the influences of interacting to residual's mean error are taken into account and the assumption of likelihood function being a zero mean Gaussian function is discarded.Finally,the proposed M-IMM algorithm is applied to the simulation of the aircraft trajectory prediction,and the comparative studies are conducted to existing algorithms.The simulation results indicate the proposed M-IMM algorithm can predict aircraft trajectory more quickly and accurately.

Effects of ethanol on the proteasome interacting proteins

Proteasome dysfunction has been repeatedly reported in alcoholic liver disease. Ethanol metabolism endproducts affect the structure of the proteasome, and, therefore, change the proteasome interaction with its regulatory complexes 19S and PA28, as well as its interacting proteins. Chronic ethanol feeding alters the ubiquitin-proteasome activity by altering the interaction between the 19S and the 20S proteasome interaction. The degradation of oxidized and damaged proteins is thus decreased and leads to accumulation of insoluble protein aggregates, such as Mallory-Denk bodies. Ethanol also affects the immunoproteasome formation. PA28a/b interactions with the 20S proteasome are decreased in the proteasome fraction isolated from the liver of rats fed ethanol chronically, thus affecting the cellular antigen presentation and defense against pathogenic agents. Recently, it has been shown that ethanol also affects the proteasome interacting proteins (PIPs). Interaction of the proteasome with Ecm29 and with deubiquitinating enzymes Rpn11, UCH37, and Usp14 has been found to decrease. However, the two UBL-ubiquitin-associated domain (UBA) PIPs p62 and valosin-containing protein are upregulated when the proteasome is inhibited. The increase of these UBL-UBA proteins, as well as the increase in Hsp70 and Hsp25 levels, compensated for the proteasome failure and helped in the unfolding/docking of misfolded proteins. Chronic alcohol feeding to rats causes a significant inhibition of the proteasome pathway and this inhibition results from a decreases of the interaction between the 20S proteasome and the regulatory complexes, PIPs, and the ubiquitin system components.

A Novel Interacting Multiple-Model Method and Its Application to Moisture Content Prediction of ASP Flooding

In this paper,an interacting multiple-model(IMM)method based on datadriven identification model is proposed for the prediction of nonlinear dynamic systems.Firstly,two basic models are selected as combination components due to their proved effectiveness.One is Gaussian process(GP)model,which can provide the predictive variance of the predicted output and only has several optimizing parameters.The other is regularized extreme learning machine(RELM)model,which can improve the overfitting problem resulted by empirical risk minimization principle and enhances the overall generalization performance.Then both of the models are updated continually using meaningful new data selected by data selection methods.Furthermore,recursive methods are employed in the two models to reduce the computational burden caused by continuous renewal.Finally,the two models are combined in IMM algorithm to realize the hybrid prediction,which can avoid the error accumulation in the single-model prediction.In order to verify the performance,the proposed method is applied to the prediction of moisture content of alkali-surfactant-polymer(ASP)flooding.The simulation results show that the proposed model can match the process very well.And IMM algorithm can outperform its components and provide a nice improvement in accuracy and robustness.

Single Photon Scattering in a Pair of Waveguides Coupled by a Whispering-Gallery Resonator Interacting with a Semiconductor Quantum Dot

The single photon scattering properties in a pair of waveguides coupled by a whispering-gallery resonator in- teracting with a semiconductor quantum dot are investigated theoretically. The two waveguides support four possible ports for an incident single photon. The quantum dot is considered a V-type system. The incident direction-dependent single photon scattering properties are studied and equal-output probability from the four ports for a single photon incident is discussed. The influences of backscattering between the two modes of the whispering-gallery resonator for incident direction-dependent single photon scattering properties are also pre- sented.

A new analytical-numerical method for calculating interacting stresses of a multi-hole problem under both remote and arbitrary surface stresses

Based on the elementary solutions and new integral equations,a new analytical-numerical method is proposed to calculate the interacting stresses of multiple circular holes in an infinite elastic plate under both remote stresses and arbitrarily distributed stresses applied to the circular boundaries.The validity of this new analytical-numerical method is verified by the analytical solution of the bi-harmonic stress function method,the numerical solution of the finite element method,and the analytical-numerical solutions of the series expansion and Laurent series methods.Some numerical examples are presented to investigate the effects of the hole geometry parameters(radii and relative positions)and loading conditions(remote stresses and surface stresses)on the interacting tangential stresses and interacting stress concentration factors(SCFs).The results show that whether the interference effect is shielding(k<1)or amplifying(k>1)depends on the relative orientation of holes(α)and remote stresses(σ^∞x,σ^∞y).When the maximum principal stress is aligned with the connecting line of two-hole centers andσ^∞y<0.5σ^∞x,the plate containing two circular holes has greater stability than that containing one circular hole,and the smaller circular hole has greater stability than the bigger one.This new method not only has a simple formulation and high accuracy,but also has an advantage of wide applications over common analytical methods and analytical-numerical methods in calculating the interacting stresses of a multi-hole problem under both remote and arbitrary surface stresses.

Applying the New Extended Direct Algebraic Method to Solve the Equation of Obliquely Interacting Waves in Shallow Waters

In this study,the potential Kadomtsev-Petviashvili(pKP)equation,which describes the oblique interaction of surface waves in shallow waters,is solved by the new extended direct algebraic method.The results of the study show that by applying the new direct algebraic method to the pKP equation,the behavior of the obliquely interacting surface waves in two dimensions can be analyzed.This article fairly clarifies the behaviors of surface waves in shallow waters.In the literature,several mathematical models have been developed in attempt to study these behaviors,with nonlinear mathematics being one of the most important steps;however,the investigations are still at a level that can be called‘baby steps’.Therefore,every study to be carried out in this context is of great importance.Thus,this study will serve as a reference to guide scientists working in this field.

Screening of Proteins Interacting with Nonstructural 1 Protein of H5N1 Avian Influenza Virus from T7-phage Display Library

Avian influenza virus（AIV） nonstructural 1（NS1） gene was amplified by real-time polymerse chain reac tion（RT-PCR） and inserted into pET28a, then transformed into E. coli BL21（DE3） competent cell. With the induction of isopropyl-β-D-thiogalactoside（IPTG） and the purification of Ni-NTA column, we finally obtained purified NS1 protein. T7-phage display system was used to screen the proteins that interacted with NS1 from lung cell cDNA li brary. The selected positive clones were identified by DNA sequencing and analyzed by BLAST program in Gene Bank. Two proteins were obtained as NS1 binding proteins, Homo sapiens nucleolar and coiled-body phosphoprotein 1（NOLC1） and Homo sapiens similar to colon cancer-associated antigen. By co-immunoprecipitation and other me thods, Homo sapiens NOLC1 was found to interact with the NS1 protein, the results would provide the basis for fur ther studying biological function of NS1 protein.

Microscopic Calculation of Parameters of the sdg Interacting Boson Model for ^(104-110)Pd Isotopes

The parameters of the sdg interacting boson model Hamiltonian are calculated for the 104-110Pdisotopes.The calculations utilize the microscopic procedure based on the Dyson boson mapping proposedby Yang-Liu-Qi and extended to include the g boson effects.The calculated parameters reproduce thosevalues from the phenomenological fits.The resulting spectra are compared with the experimental spectra.

Preferable Orientations of Interacting C_(60) Molecules inside Single Wall Boron Nitride Nanotubes

This work focuses on the preferable orientation analysis of the hybrid system where the C60 molecules are encap- sulated inside the boron nitride nanotubes by using the two-molecule model. The low-energy state can be acquired in the contour map, which provides the visual information of the systematical van der Waals interaction potential for the C60 molecules adopting different orientations. Our results show that the C60 molecules exhibit the pre- ferred pentagon and hexagon orientations with the tube＇s diameter smaller and larger than 13.55A, respectively. The preferred two-bond orientation obtained in the single-molecule model is absent in this study, indicating that the intermolecular interaction of adjacent C60 molecules plays an important role in the orientational behaviors of this peapod structure.