MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Effect of hydrogen fluoride and magnesium oxide on AZ31 Mg alloy/carbon fiber-reinforced plastic composite by thermal laser joining technique

Although hydrofluoric acid(HF)surface treatment is known to enhance the joining of metals with polymers,there is limited information on its effect on the joining of AZ31 alloy and carbon-fiber-reinforced plastics(CFRPs)through laser-assisted metal and plastic direct joining(LAMP).This study uses the LAMP technique to produce AZ31-CFRP joints.The joining process involves as-received AZ31,HFpretreated AZ31,and thermally oxidized HF-pretreated AZ31 alloy sheets.Furthermore,the bonding strength of joints prepared with thermally oxidized AZ31 alloy sheets is examined to ascertain the combined effect of HF treatment and thermal oxidation on bonding strength.The microstructures,surface chemical interactions,and mechanical performances of joints are investigated under tensile shear loading.Various factors,such as bubble formation,CFRP resin decomposition,and mechanical interlocking considerably affect joint strength.Additionally,surface chemical interactions between the active species on metal parts and the polar amide along with carbonyl groups of polymer play a significant role in improving joint strength.Joints prepared with surface-pretreated AZ31 alloy sheets show significant improvements in bonding strength.

Study on Key Joining Technology and Test Method of Steel/Al Hybrid Structure Body-in-White

Green and low carbon promote the application and development of light-weight materials in body-in-white. Large-scale die-casting Al alloy (DCAA) and high-strength thermo-formed steel sheet (TFSS) have put forward higher requirements for the application of joining technology of high-strength steel/Al dissimilar materials. Taking the new die-casting Al alloy body as an example, this paper systematically studies the progress of the latest joining methods of steel/Al dissimilar material with combination of two-layer plate and three-layer plate. By analyzing the joining technologies such as FSPR, RES, FDS and SPR, the technology and process characteristics of steel/Al dissimilar material joining are studied, and the joining technical feasibility and realization means of different material combination of the body are analyzed. The conditions of material combination, material thickness, material strength, flange height, preformed holes and joint spacing for achieving high-quality joining are given. The FSPR joining technology is developed and tested in order to meet with the joining of parts with DCAA and TFSS, especially for the joining of three-layer plates with them. It finds the method and technical basis for the realization of high quality joining of dissimilar materials, provides the early conditions for the application of large DCAA and TFSS parts in body-in-white, and meets the design requirements of new energy body. .

Challenge to Welding and Joining Technology for Applying Multi-material in Electric Vehicle Production

Advanced high strength steel,aluminum alloy and plastic materials are used in the right places for the purpose of reducing the weight of EV(electric vehicle)bodies and in-vehicle parts,and multi-material structures are advancing.Therefore,it is difficult to handle the welding and joining processes of automobile structures by the conventional arc welding and resistance spot welding,which have been applied to steel joining,and various joining processes are being applied depending on the material.Under above mentioned background,the authors have developed some unique joining processes for multi-materials that are used in the right place.This paper introduces the dissimilar metal joining between the galvanized steel and aluminum alloy by laser arc hybrid process,the metal/thermoplastic dissimilar material joining using laser process and the solid-state resistance spot joining process of advanced high strength steel for EV body structural parts.Moreover,the authors describe the high-speed plasma jet GTA(Gas Tungusten Arc)welding process of copper applied to electrical components such as motors.

Progress in Joining Ceramics to Metals

The research and development of joining methods of ceramics to metals, especially brazing, diffusion bonding and partial transition liquid phase bonding, were introduced. Some opinions were put forward. For new composites emerging, it is necessary to develop new joining methods, particularly in the field of high temperature technique for joining ceramics to superalloys.

Semisolid joining of aluminum A356 alloy by partial remelting and mechanical stirring

A method to reach the globular weld structure of A356 aluminum alloy using stirring the localized semisolid zone during butt-joining is developed.Since the heat conductivity of this alloy is very high, the accurate controlling of temperature during joining must be considered.A gas heating system was used to heat up the nitrogen gas up to the required temperature.A dried and free oxygen gas was prepared when a stream of nitrogen gas could pass closely around a hot element.Hot and pure nitrogen gas flow through a precise ceramic nozzle was used to create a localized semisolid pool.At this stage a fine stirrer was introduced into the weld seam in order to mix the two sides into a single uniform joint.Substrates were moved in direction of joint line by a small trolley to avoid the deviation of nozzle from the joint line and its distance and angle from the substrate.A fixture system was used to hold two substrates together on the trolley.A narrow hot plate was located on the trolley to heat up the joint line due to high heat conductivity of aluminum.Effect of gas temperature was investigated on the microstructure and mechanical properties of weld seam.Results showed that increase in temperature promoted the final welding properties, and also at liquid fractions less than 50% joining was not fully practical.The best mechanical properties were achieved with liquid fraction of about 70%.

Joining Performance and Microstructure of the 2024/7075 Aluminium Alloys Welded Joints by Vaporizing Foil Actuator Welding

Vaporizing foil actuator welding(VFAW) was used for joining 2024-T3 and 7075-T6 aluminum alloy sheets, and the resulting joint microstructure was analyzed. 2024/7075 aluminum alloy pairs with suitable processing parameters can be prepared by using VFAW. Dynamic preform addresses the poor formability problem of target material and advantage of VFAW on dissimilar materials in some conditions. But with standoff sheet inserting in the flyer and target, 2024/7075 welded pairs gets the better weld strength, compared with flyer preformed method. The microstructure of the circular weld area of the welded joint showed a wave interface, in which a thin melt layer formed at the center and edge parts. The crystal grains near the bonding interface were remarkably elongated and refined. Therefore, the joining of the 2024/7075 pairs was facilitated through plastic forming and melting.

Kinematics Analysis and Optimization of the Fast Shearing-extrusion Joining Mechanism for Solid-state Metal

Dynamical Joining of the solid-state metal is the key technology to realize endless hot rolling. The heating and laser welding method both require long joining time. Based on super deformation method, a 7-bar and 2-slider mechanism was developed in Japan, and the joining time is less than 0.5 s, however the length of each bar are not reported and this mechanism is complex. A relatively simple 6-bar and 1-slider mechanism is put forward, which can realize the shearing and extrusion motion of the top and bottom blades with a speed approximately equal to the speed of the metal plates. In order to study the kinematics property of the double blades, based on complex vector method, the multi-rigid-body model is built, and the displacement and speed functions of the double blades, the joining time and joining thickness are deduced, the kinematics analysis shows that the initial parameters can＇t satisfy the joining process. Hence, optimization of this mechanism is employed using genetic algorithm（GA） and the optimization parameters of this mechanism are obtained, the kinematics analysis show that the joining time is less than 0.1 s, the joining thickness is more than 80% of the thickness of the solid-state metal, and the horizontal speeds of the blades are improved. A new mechanism is provided for the joining of the solid-state metal and a foundation is laid for the design of the device.

Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining： relevance to cancer, aging, and the immune system

Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.

Study of joining mechanism of ABS polymer and steel/aluminum by resistance spot welding

The joining of metal and polymer is an increasingly important method to get lightweight components in the development of manufacturing industry- nowadays. In this artiele, metal and polymer lap joint was achieved by means of resistance spot welding （RSW） and ultrasonic assistance welding （UAW）. The joining mechanism of lap joint was analyzed by OM, TEM on microstructure at the interface of lap joints and XPS and IR spectra was discussed based on the following different ones： mechanical-interlocking, diffusion bond and coordination bond. The results showed that it was the combined action that played an important role in the effective joining work. Besides, ultrasonic assistance was used in the study to aid welding process based on its high-frequency ultrasonic vibration, which made joints shaping better and improved tensile strength visibly contrast to joints with the same lower heat input parameters.

Climatological Characteristics of the Moisture Budget and Their Anomalies over the Joining Area of Asia and the Indian-Pacific Ocean

The climatological characteristics of the moisture budget over the joining area of Asia and the IndianPacific Ocean （AIPO） and its adjacent regions as well as their anomalies have been estimated in this study. The main results are as follows. In the winter, the northeasterly moisture transport covers the extensive areas at the lower latitudes of the AIPO. The westerly and northerly moisture transport is the major source and the South Indian Ocean （SIO） is the moisture sink. In the summer, influenced by the southwesterly monsoonal wind, the crossequatorial southwesterly moisture transport across Somali originating from the SIO is transported through the Arabian Sea （AS）, the Bay of Bengal （BOB）, and the South China Sea （SCS） to eastern China. The AIPO is controlled by the southwesterly moisture transport. The net moisture influx over the AIPO has obvious interannual and interdecadal variations. From the mid- or late 1970s, the influxes over the SIO, the AS, the northern part of the western North Pacific （NWNP）, and North China （NC） as well as South China （SC） begin to decrease abruptly, while those over Northeast China （NEC） and the Yangtze River-Huaihe River basins （YHRB） have increased remarkably. As a whole, the net moisture influxes over the BOB and the southern part of the western North Pacific （SWNP） in the recent 50 years take on a linear increasing trend. However, the transition timing for these two regions is different with the former being at the mid- or late 1980s and the latter occurring earlier, approximately at the early stage of the 1970s. The anomalous moisture source associated with the precipitation anomalies is different from the normal conditions of the summer precipitation. For the drought or flood years or the years of E1 Nifio and its following years, the anomalous moisture transport originating from the western North Pacific （WNP） is the vital source of the anomalous precipitation over eastern China, which is greatly related with the variation of the subtropical Pacific high.

MICROWAVE JOINING OF ALUMINA CERAMIC AND HYDROXYLAPATITE BIOCERAMIC

Microwave joining is a rapid developmental new technique in recent years. This paper introduces a new microwave joining equipment which was made by our lab, succeeds in alumina ceramic - hydroxylapatite bioceramic join in the equipment, and analyzes the join situation of join boundary by using scanning electron microscope (SEM), this paper analyzes the mechanism of microwave joining also. (Author abstract) 4 Refs.

Joining of AZ31 and AZ91 Mg alloys by friction stir welding

Two dissimilar magnesium(Mg)alloy sheets,one with low aluminium(AZ31)and another with high aluminium(AZ91)content,were successfully joined by friction stir welding(FSW).The effect of process parameters on the formation of hot cracks was investigated.A sound metallurgical joint was obtained at optimized process parameters(1400 rpm with 25 mm/min feed)which contained fine grains and distributed β(Mg_(17)Al_(12))phase within the nugget zone.An increasing trend in the hardness measurements has also confirmed more amount of dissolution of aluminium within the nugget zone.A sharp interface between nugget zone and thermo mechanical affected zone(TMAZ)was clearly noticed at the AZ31 Mg alloy side(advancing)but not on the AZ91 Mg alloy side(retreating).From the results it can be concluded that FSW can be effectively used to join dissimilar metals,particularly difficult to process metals such as Mg alloys,and hot cracking can be completely eliminated by choosing appropriate process parameters to achieve sound joint.

Thermal fatigue behaviors of SiC power module by Ag sinter joining under harsh thermal shock test

The excellent properties of SiC bring new challenges for the device packaging.In this study,the bonding strength,fracture behaviors and microstructural evolution of micron-porous Ag joint were elevated during thermal cycling(–50 ℃–250 ℃) in SiC/DBC(direct bonding copper) die attachment structure for different time.During harsh thermal shock test,the strength of sintered joint deceased gradually with the increase of cycling number,and the value just was half of the value of as-sintered after 1 000 cycles.Coarsening of Ag grains was observed in micron-porous joint with the structure inhomogeneity and defects increasing,which were the reasons of the strength decease.In addition,it was also found that the fracture behavior of sintered joints was changed from ductile deformation of Ag grain to brittle fracture of crack propagation after 1 000 cycles.This study will add the understanding in the mechanical properties of Ag sinter joining and its applications at high temperature.

Green State Joining of ZrO_2(8YSZ)-Al_2O_3 Ceramics Using Slurry Containing PLS Nanocomposites

Joining of ZrO_2 (containing 8% (mol fraction) Y_2O_3,as the composition used in oxygen sensors) to 95Al_2O_3 (widely used at elevated temperature) in green state was described using polymer/layered silicate (PLS) nanocomposites contained slurry,without applied pressure. Microstructure of the joined section was investigated. The effects of interlayer and PLS on joining qualities were analysed. The results show that interface cracks are easily produced because of mismatch of both thermal expansion and/or sintering shrinkage between joined samples. With an optimized condition of joining layer composition and solid contents,a fine joint could be obtained without obvious cracks,pores and other defects. This process is suitable for joining of various kinds of advanced ceramics.

Influences of tool plunge speed and tool plunge depth on friction spot joining of AA5454-O aluminum alloy plates with different thicknesses

AA5454-O aluminum alloy plates with the thicknesses of 1.4 and 1.0 mm were friction-spot-joined (FSJed).The plunge speed of the joining tool was changed in a range of 100 500 mm/min under a constant rotation speed of 500 r/min.The plunge depth was ranged from 1.6 mm to 2.2 mm.The tool plunge speed did not make a remarkable effect on the surface appearance and macro-structure of the FSJed zone.The average hardness of the FSJed zone was greater than or equal to that of the base metal.However,there was no remarkable tendency in the average hardness change of the FSJed zone in spite of the variation in the tool plunge speed and tool plunge depth.The increase of the tool plunge depth resulted in the increase of the tensile shear load.However,the change of the tool plunge speed did not lead to the remarkable variation in the tensile shear load of the FSJed plates.It was noteworthy that the FSJed plate exhibited the highest tensile shear load of about 4.0 kN.

JOINING OF TiAl BASEDALLOYS BY HOT PRESSING

By hot pressing in an inert atmosphere, the joining interface between coarse lamellar structures and that between a coarse lamellar structure and a fine duplex structure of a Ti 33Al 3Cr(%, mass fraction) alloy, and the effect of heat treatment on the microstructure at the interfaces have been studied. The results showed that the microstructure at the interface between two coarse lamellar structures depends on the orientations of lamellae. And microcavities are found at such interfaces. After heat treatment at 1 250 ℃, the recrystallization structure widened. As to the interface between a coarse lamellar structure and a fine duplex structure, a new duplex structure formed within the original duplex structure at the interface and further widened after subsequent heat treatment at 1 250 ℃ for 4 h. Microcavities are rare at such interfaces, and the joining appears better than that between two coarse lamellar structures.

Forces and Stresses During Friction Stir Joining of 2024 Aluminum Alloy

An attempt is made to measure three direction forces using octagonal ring dynamometer in the 2024 aluminum alloy friction stir joining(FSJ)process.A test is made to measure the specific area stress and stress distributions in the specific area of the workpiece are obtained.The workpiece stresses in the FSJ process are analyzed by numerical simulation method.It is found that,in the downward stage of the process,feed force and lateral force in the tool are small,almost zero,and the maximum axial force can reach 12.5kN.In the stable joining stage,the forces acting on the tool become stabilized.Compared with the low speed,high feed speed results in small feed force and small lateral force,but large feed force in the stable joining stage.The stresses in three directions of feed direction,direction that perpendicular to butt face and direction perpendicular to the surface are obtained.The simulation stress value of measure point is obtained.Test and numerical simulation can authenticate each other.Both experimental stress values and numerical simulation stress values are credible.

Precise assembly and joining of silver nanowires in three dimensions for highly conductive composite structures

Three-dimensional(3D)electrically conductive micro/nanostructures are now a key component in a broad range of research and industry fields.In this work,a novel method is developed to realize metallic 3D micro/nanostructures with silver-thiol-acrylate composites via two-photon polymerization followed by femtosecond laser nanojoining.Complex 3D micro/nanoscale conductive structures have been successfully fabricated with∼200 nm resolution.The loading of silver nanowires(AgNWs)and joining of junctions successfully enhance the electrical conductivity of the composites from insulating to 92.9 Sm^−1 at room temperature.Moreover,for the first time,a reversible switching to a higher conductivity is observed,up to∼10^5Sm^−1 at 523 K.The temperature-dependent conductivity of the composite is analyzed following the variable range hopping and thermal activation models.The nanomaterial assembly and joining method demonstrated in this study pave a way towards a wide range of device applications,including 3D electronics,sensors,memristors,micro/nanoelectromechanical systems,and biomedical devices,etc.

A study on joining magnesium alloy high pressure die casting components with thread forming fasteners

With tremendous weight saving potential,magnesium alloy high pressure die casting components have been widely used for automotive applications.Magnesium fastening technology is thus becoming increasingly important to design engineers.Joining as-cast holes of magnesium high pressure die casting components with thread forming fasteners provides significant advantages for the assembly process,overall cost benefit and joint integrity.This type of joint is thus preferred for structural applications.Designing the thread forming fasteners with as-cast holes follows the general rules for designing for the machined holes,including carefully designing the variables such as the assembly torque range,the length of thread engagement,the hole diameter and required failure mode.In addition,special attention needs to be paid to the draft angles of the magnesium cast components that are required for the die casting process.In this paper,the effects of above key factors,individually and combined,on the joint performance of thread forming fasteners with as-cast blind holes of AM60B magnesium components are studied.A joint design philosophy was proposed to optimize both joint performance(the prevailing torque,the failure torque and the failure mode)and manufacturing easiness(the hole diameter and corresponding draft angle).The detailed design considerations for as-cast holes of magnesium HPDC are discussed and explained through a hypothetical example.