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.

AN URGENT JOINT CAUSE

COP29-the 29th session of the Conference of the Parties to the United Nations Framework Convention on Climate Change-has accentuated the urgency of jointly addressing climate change,our common global threat,by pushing for a fair and ambitious new climate financing target.It has also brought into the global spotlight China’s progress in green transition and carbon emission reduction and its commitment to international cooperation.

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. .

A Market for All

CIIE plays key role in further opening up of China Tanzanian exhibitors were in the spotlight at the seventh China International Import Expo(CIIE)held in Shanghai,east China,from 5 to 10 November.Participating in the expo for the seventh time,the country was among one of the six guests of honour for this year and saw more Tanzanian firms joining in.

Uncovering the Memories Sealed in Stones

Do stones havememories?Can theytalk?ForGewang,a conservatorwhohas dedicated tenyears toTibetan stone carvingart,theanswer is yes.Heis thrilled to witness the increasing efforts in the preservation and study of stone carvings and the growing number of peoplejoining this cause.

Study of galvanic corrosion and mechanical joint properties of AZ31B and carbon-fiber–reinforced polymer joined by friction self-piercing riveting

A new testing methodology was developed to quantitively study galvanic corrosion of AZ31B and thermoset carbon-fiber–reinforced polymer spot-joined by a friction self-piercing riveting process.Pre-defined areas of AZ31B in the joint were exposed in 0.1 M NaCl solution over time.Massive galvanic corrosion of AZ31B was observed as exposure time increased.The measured volume loss was converted into corrosion current that was at least 48 times greater than the corrosion current of AZ31B without galvanic coupling.Ninety percent of the mechanical joint integrity was retained for corroded F-SPR joints to 200 h and then decreased because of the massive volume loss of AZ31B。

Fabrication and Life Prediction of SSiC Ceramic Joint Joined with Silicon Resin YR3370

Joints between sintered silicon carbide （SSiC） were produced using a polysiloxane silicon resin YR3370 （GE Toshiba Silicones） as joining material. Samples were heat treated in a 99.99% nitrogen flux at temperatures ranging from 1 100 ℃ to 1 300 ℃. Three point bending strength of the joint reached the maximum of 179 MPa as joined at 1 200℃. The joining layer is continuous, homogeneous and densified and has a thickness of 2 μm -5μm. The joining mechanism is that the amorphous silicon oxycarbide （SixOyCz） ceramic pyrolyzed from silicon resin YR3370 acts as an inorganic adhesive to SSiC substrate, which means the formation of the continuous Si-C bond structure between SixOyCz structure and SSiC substrate. Life prediction of the ceramic joint can be realized through the measurement of the critical time of the joint after the cyclic loading test.

New insights into tumor dormancy:Targeting DNA repair pathways

Over the past few decades, major strides have advanced the techniques for early detection and treatment of cancer. However, metastatic tumor growth still accounts for the majority of cancer-related deaths worldwide. In fact, breast cancers are notorious for relapsing years or decades after the initial clinical treatment, and this relapse can vary according to the type of breast cancer. In estrogen receptor-positive breast cancers, late tumor relapses frequently occur whereas relapses in estrogen receptor-negative cancers or triple negative tumors arise early resulting in a higher mortality risk. One of the main causes of metastasis is tumor dormancy in which cancer cells remain concealed, asymptomatic, and untraceable over a prolonged period of time. Under certain conditions, dormant cells can re-enter into the cell cycle and resume proliferation leading to recurrence. However, the molecular and cellular regulators underlying this transition remain poorly understood. To date, three mechanisms have been identified to trigger tumor dormancy including cellular, angiogenic, and immunologic dormancies. In addition, recent studies have suggested that DNA repair mechanisms may contribute to the survival of dormant cancer cells. In this article, we summarize the recent experimental and clinical evidence governing cancer dormancy. In addition, we will discuss the role of DNA repair mechanisms in promoting the survival of dormant cells. This information provides mechanistic insight to explain why recurrence occurs, and strategies that may enhance therapeutic approaches to prevent disease recurrence.

Quantum search of many vertices on the joined complete graph

The quantum search on the graph is a very important topic.In this work,we develop a theoretic method on searching of single vertex on the graph[Phys.Rev.Lett.114110503(2015)],and systematically study the search of many vertices on one low-connectivity graph,the joined complete graph.Our results reveal that,with the optimal jumping rate obtained from the theoretical method,we can find such target vertices at the time O(√N),where N is the number of total vertices.Therefore,the search of many vertices on the joined complete graph possessing quantum advantage has been achieved.

TiC Particle Reinforced Silicon Nitride Composite Joined With Y_2O_3-Al_2O_3-SiO_2 Mixture

Silicon nitride composite is joined to itself by heating interlayer of Y2 O3 -AL2O3 -SiO2 mixtures above their liquidus temperatures in flowing nitrogen. The joined specimens are tested in four point flexure from room temperature to 1373 K. The interface microstruclure and fractured surfaces after testing are observed and analyzed by SEM, EPMA and XRD respectively. The results show that F2 O3 -A12 O3 -SiO2 glass reacts with Si3 N4 at interface, forming the Si3 N4/Si2 N2 O( Y-AlrSi-O-N glass/ Y-Al- Si-O glass gradient interface. With the increase of bonding temperature and holding time, the joint strength first increases, reaching a peak, and then decreases . According to interfacial analyses , the bonding strength depends on joint thickness .

Conceptual Design and Aerodynamic Study of Joined-Wing Business Jet Aircraft

The concept of joined-wing aircraft with nonplanar wings as conceived and patented by Wolkovitch is attractive due to various advantages such as light weight, high stiffness, low induced drag, high trimmed CLmax, reduced wetted area and parasite drag and good stability and control, which have been supported by independent analyses, design studies and wind tunnel tests. With such foreseen advantages, the present work is carried out to design joined-wing business-jet aircraft and study and investigate its advantages and benefits as compared to the current available conventional business jet of similar size, passenger and payload capacity. In particular, the work searches for a conceptual design of joined-wing configured business-jet aircraft that possesses more superior characteristics and better aerodynamic performance in terms of increased lift and reduced drag, and lighter than the conventional business jet of similar size. Another significant objective of this work is to prove that the added rigidity possessed by the joined wing configuration can contribute to weight reduction.

CNOOC Joined Hands with WorleyParsons

On Aug. 25, China National Offshore Oil Corporation （CNOOC） and WorleyParsons, a world famous project construction company, signed an agreement for jointly setting up Huizhou Refinery Project Construction Team in Beijing KEMPINSKI Hotel. Zheng Changbo, assistant president of CNOOC, Dong Xiaoli, general manager of Huizhou Refinery Project Team, and Lynn C. Fister, deputy general manager of WorleyParsons attended the signing ceremony.

基于Fork/Join的事务日志伴随模式挖掘方法

信息系统产生的大量事务日志数据蕴含着潜在的伴随模式,伴随模式是指在时空上频繁共现的一组对象.由于传统的滑动窗口算法和FP-Growth算法只能调用单一线程进行计算,随着数据规模的扩张,会导致挖掘伴随模式的时间急剧增加.为此本文提出了一种基于Fork/Join并行技术的伴随模式挖掘框架,其能够实现从单线程到多线程的迁移,充分利用多核配置的加速性能.该框架由划定伴随数据集、频繁项集挖掘和关联规则挖掘三部分组成.首先,提出了基于Fork/Join的多核并行滑动窗口算法,以缩短从事务日志中划定伴随数据集的时间;然后,提出基于Fork/Join的多核并行FP-Growth算法,以并行地挖掘伴随数据集中的频繁项集;最后,引入支持度、置信度和提升度3个参数,对伴随模式中各对象间的关联规则进行挖掘.基于门禁刷卡数据的实验结果表明,相比传统算法,本文所提出的框架能够挖掘出更多的伴随模式,同时挖掘效率较高.

Mechanically Joined Extrusion Profiles for Battery Trays

In the context of electromobility,ensuring the leak tightness of assemblies is of paramount importance,particularly in bat-tery housings.Current battery housings,often featuring base assemblies crafted from extruded aluminum profiles,address the challenge of leak tightness at joints through methods like friction stir welding,a process known for its time and cost intensiveness.The aim of this study is to develop and implement a new type of extruded profile concept to produce tight base assemblies for battery housings by a longitudinal mechanical single stroke joining process.The geometry,the process and the properties of the aluminum profiles are investigated to get a joint that meets the tightness requirements and achieve high load-bearing capacities in agreement with the high homologation requirements set to vehicles with high-voltage systems.The joint is formed by means of a single stage press stroke,which eliminates the need for complex tool designs that are neces-sary for continuous joining(roll joining).Flat steel contact surfaces are used as joining tools.To evaluate the joint quality,force curves from the joining process are analyzed and the resulting joint geometries are assessed using micrographs.The resulting leak tightness of the linear joints is measured by a helium sniffer leak detector and the load-bearing capacities are investigated by shear lap and bending tests and fatigue strength test.The study also explores whether a difference in strength between the two joining partners has a positive effect on the joint properties.

大规模电力系统潮流转移比多核并行批处理方法

实现各类预想故障下潮流转移比快速仿真分析是电网安全稳定运行的重要保证。针对现有实际运行方式中潮流转移分析困难问题,提出大规模电力系统潮流转移比多核并行批处理方法。该方法基于广泛使用的商业大系统分析工具,在参数解析分类、故障自动设置及结果解析的基础上,引入深度优先搜索(depth first search,DFS)算法进行孤立节点和孤岛区域检测以保证网络完整性,结合潮流计算合理性的自动判别以实现潮流转移比的批处理分析;同时在多核环境下,构建基于Fork/Join的并行框架,采用"分治模式"递归分解计算任务,从而实现分析方法的多核并行。算例仿真和在云南电网的实际应用验证了所提方法的有效性和快速性。

Microstructure and mechanical properties of friction welds between TiA l alloy and 40Cr steel rods

Direct friction welding of Ti Al alloy to 40 Cr steel rods was conducted, and the microstructure and mechanical properties of the resultant joints in as-welded and post-weld heat treatment（PWHT） states were investigated. The martensitic transformation occurred and brittle Ti C phase formed near the interface due to C agglomeration, which degraded the joint strength and increased the microhardness at the interface in as-welded state. Feathery and Widmanstatten structure generated near the interface on Ti Al alloy side. After PWHT at 580 °C and 630 °C for 2 h, the sorbite formed and C dispersed at the interface, leading to the increase of the joint strength from 86 MPa in as-welded state to 395 MPa and 330 MPa, respectively. The heat-treated specimen fractured with quasi-cleavage features through the zone 1 mm away from the interface on TiA l alloy side, but the as-welded specimen failed through the interface.

基于任务复制的调度算法

任务调度是并行分布式计算系统中最具挑战性的NP完全问题之一。基于任务复制的调度是一种有效的调度方法。在通信开销较小的情况下,现已有许多算法能产生最优调度。但其最优条件要么比较苛刻,要么比较复杂。因此,针对这些算法存在的问题,提出一个新的基于任务复制的聚集调度(TDCS)算法,不仅其最优条件简单、宽松,而且该算法具有更小的时间复杂度O(log),其中,和分别表示任务集中任务的个数和最大入度。

并行数据库的改进Hash划分方法及并行Join算法

文中提出了Ｈａｓｈ 划分的改进方法——ＩＨ 划分． ＩＨ划分为结点扩充时数据的重新划分提供了方便．在论述ＩＨ 划分的基础上，给出了基于该数据划分方法的并行Ｊｏｉｎ 算法．利用已有的数据分布，文中提出的并行Ｊｏｉｎ 算法提高了算法的效率．最后，从理论上对以上并行算法的计算复杂性进行了分析．