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.

Superior Mechanical Behavior and Flame Retardancy FRP via a Distribution Controllable 1D/2D Hybrid Nanoclay Synergistic Toughening Strategy

The incorporation of commercial flame retardants into fiber-reinforced polymer(FRP)composites has been proposed as a potential solution to improve the latter’s poor flame resistance.However,this approach often poses a challenge,as it can adversely affect the mechanical properties of the FRP.Thus,balancing the need for improved flame resistance with the preservation of mechanical integrity remains a complex issue in FRP research.Addressing this critical concern,this study introduces a novel additive system featuring a combination of one-dimensional(1D)hollow tubular structured halloysite nanotubes(HNTs)and two-dimensional(2D)polygonal flake-shaped nano kaolinite(NKN).By employing a 1D/2D hybrid kaolinite nanoclay system,this research aims to simultaneously improve the flame retardancy and mechanical properties.This innovative approach offers several advantages.During combustion and pyrolysis processes,the 1D/2D hybrid kaolinite nanoclay system proves effective in reducing heat release and volatile leaching.Furthermore,the system facilitates the formation of reinforcing skeletons through a crosslinking mechanism during pyrolysis,resulting in the development of a compact char layer.This char layer acts as a protective barrier,enhancing the material’s resistance to heat and flames.In terms of mechanical properties,the multilayered polygonal flake-shaped 2D NKN plays a crucial role by impeding the formation of cracks that typically arise from vulnerable areas,such as adhesive phase particles.Simultaneously,the 1D HNT bridges these cracks within the matrix,ensuring the structural integrity of the composite material.In an optimal scenario,the homogeneously distributed 1D/2D hybrid kaolinite nanoclays exhibit remarkable results,with a 51.0%improvement in mode II fracture toughness(GIIC),indicating increased resistance to crack propagation.In addition,there is a 34.5%reduction in total heat release,signifying improved flame retardancy.This study represents a significant step forward in the field of composite materials.The innovative use of hybrid low-dimensional nanomaterials offers a promising avenue for the development of multifunctional composites.By carefully designing and incorporating these nanoclays,researchers can potentially create a new generation of FRP composites that excel in both flame resistance and mechanical strength.

T-PBFT: An EigenTrust-Based Practical Byzantine Fault Tolerance Consensus Algorithm

Blockchain with these characteristics of decentralized structure, transparent and credible, time-series and immutability, has been considering as a promising technology. Consensus algorithm as one of the core techniques of blockchain directly affects the scalability of blockchain systems. Existing probabilistic finality blockchain consensus algorithms such as PoW, PoS, suffer from power consumptions and low efficiency;while absolute finality blockchain consensus algorithms such as PBFT, HoneyBadgerBFT, could not meet the scalability requirement in a largescale network. In this paper, we propose a novel optimized practical Byzantine fault tolerance consensus algorithm based on EigenTrust model, namely T-PBFT, which is a multi-stage consensus algorithm. It evaluates node trust by the transactions between nodes so that the high quality of nodes in the network will be selected to construct a consensus group. To reduce the probability of view change, we propose to replace a single primary node with a primary group. By group signature and mutual supervision, we can enhance the robustness of the primary group further. Finally, we analyze T-PBFT and compare it with the other Byzantine fault tolerant consensus algorithms. Theoretical analysis shows that our T-PBFT can optimize the Byzantine fault-tolerant rate,reduce the probability of view change and communication complexity.

Effects of pore structure and distribution on strength of porous Cu-Sn-Ti alumina composites

Porous Cu-Sn-Ti alumina composites were fabricated by sintering Cu-Sn-Ti alloy powders, graphite particles, and alumina hollow particles agent. The effects of the pore structure and distribution on the composites strength were evaluated. Different pore distributions were modeled by using finite element analysis to investigate the tensile strength of the composites. Furthermore, a fractal analysis-based box-covering algorithm was used on the Cu-Sn-Ti alumina composites topology graphs to better investigate the pore structure and distribution. Results obtained show that different sizes and concentrations of alumina hollow particles could result in different porosities from20% to 50%. A larger pore size and a higher pore concentration reduce the strength, but provide more space for chip formation as a bonding material of a grinding wheel. The body-centered pore structure of the composites shows the highest stress under a tension load. The original composites topology graphs have been transformed to ordered distributed pore graphs based on the total pore area conservation. The information dimension magnitude difference between the original topology graphs and the ordered distributed circulars graphs is found to be linear with the Cu-Sn-Ti alumina composites strength. A larger difference renders a lower flexural strength, which indicates that uniform ordered distributed pores could benefit the composites strength.

Experimental and numerical study of deposition mechanisms for cold spray additive manufacturing process

Cold spray is an attractive and rapidly developing process for additive manufacturing with high efficiency and precision,repairing and coating,especially in aircraft and aerospace applications.Cold spray additive manufacturing deposits micro-particles with large plastic deformation below their melting point,eliminating heat effect zone which could deteriorate the quality of repairing zone.The particle deposition in cold spray is a complex process which involves high strain rate,high contact pressure and high temperature.Here we develop,utilize and validate a thermomechanical model to provide a definitive way to predict deposition mechanics and surface deformation evolution for particle deposition process in cold spray additive manufacturing.Both a single particle and dual particles models were developed to investigate the contact interaction between particle/substrate and particle/particle.Different combinations of particle/substrate materials(Cu/Cu,Al/Al,steel/steel,and nickel/nickel)and process parameters were considered in this study.The experimental study was conducted to validate simulation results,providing useful information for understanding the limitations and challenges associated with cold spray additive manufacturing.The framework provides insights into improving the quality and precision of stress/strain formation,particle interactions and particle deposition in cold spray additive manufacturing process.

高龄急性肾损伤患者连续性肾脏替代治疗的预后及影响因素

目的探讨高龄老年急性肾损伤(AKI)患者连续性肾脏替代治疗(CRRT)后的预后及影响因素。方法回顾性分析中日友好医院肾病科2016年1月至2023年1月的≥80岁高龄AKI患者接受CRRT治疗90 d后的生存情况,及其治疗剂量、急性生理和慢性健康状况评估Ⅱ(APACHEⅡ)和序贯器官衰竭评估(SOFA)评分。结果43例年龄(91.3±6.6)岁的AKI患者CRRT 90 d后,生存12例、死亡31例,总死亡率72.1%。APACHEⅡ评分死亡患者(27.2±4.2)明显高于生存患者(24.0±5.0)(P<0.05)。CRRT治疗15 d、30 d和45 d的累积生存率分别为71.8%、56.8%和43.2%。Logistic回归分析显示APACHEⅡ评分和SOFA评分是患者预后的独立影响因素(P<0.05)。结论高龄AKI患者CRRT治疗后的死亡率随APACHEⅡ评分增高而升高。APACHEⅡ评分和SOFA评分是高龄AKI患者开始CRRT治疗和预后的影响因素。

Experimental and modeling study of surface topography generation considering tool-workpiece vibration in high-precision turning

High-precision turning(HPT)is a main processing method for manufacturing rotary high-precision components,especially for metallic parts.However,the generated vibration between tool tip and workpiece during turning may seriously deteriorate the surface integrity.Therefore,exploring the effect of vibration on turning surface morphology and quality of copper parts using 3D surface topography regeneration model is crucial for predicting HPT performance.This developed model can update the machined surface topology in real time.In this study,the effects of tool arc radius,feed rate,radial vibration,axial vibration and tangential vibration on the surface topography and surface roughness were explored.The results show that the effect of radial vibration on surface topography is greater than that of axial vibration and tangential vibration.The radial vibration frequency is also critical.When vibration frequency changes,the surface topography profile presents three different types:the standard sinusoidal curve,the sinusoidal curve whose lowfrequency signal envelopes high-frequency signal,and the oscillation curve whose low-frequency signal superimposes high-frequency signal.In addition,HPT experiment was carried out to validate the developed model.The surface roughness obtained in the experiment was Ra=53 nm,while the roughness obtained by the simulation was Ra=46 nm,achieving a prediction accuracy of 86.7%.Received 4 September 2022;revised 3 October 2022;accepted 17 October 2022.

Synthesis of sponge-like TiO_(2) with surface-phase junctions for enhanced visible-light photocatalytic performance

Maximizing adsorption and catalytic active sites and promoting the photo-excited charge separation are two key factors to achieve excellent photocatalytic performance.In this study,we report a sol-gel synthesis approach to obtain non-metal doped TiO_(2)with sponge-like structure and surface-phase junctions all at once.While doping of carbon and nitrogen shifted the activation wavelength to the visible-light region,the innovative use of perchloric acid as a pore-making agent led to the formation of three-dimensional lamellar and porous structure with surface-phase junctions.High surface area with catalytic active sites rendered by the sponge-like structure and surface-phase junctions contributed to the much improved photocatalytic degradation efficiency toward rhodamine B,tetracycline and Disperse Red 60 with excellent reusability and stability.The improved gen eration and separati on efficie ncy of the photo-induced charge carriers of the as-prepared TiO_(2)were supported by electrochemical impedance measurements and transient photocurrent responses.This method could also be applied to other photocatalysts to achieve structural alteration and element doping simultaneously.

Regional Sampling of Forest Canopy Covers Using UAV Visible Stereoscopic Imagery for Assessment of Satellite-Based Products in Northeast China

Canopy cover is an important parameter affecting forest succession,carbon fluxes,and wildlife habitats.Several global maps with different spatial resolutions have been produced based on satellite images,but facing the deficiency of reliable references for accuracy assessments.The rapid development of unmanned aerial vehicle(UAV)equipped with consumer-grade camera enables the acquisition of high-resolution images at low cost,which provides the research community a promising tool to collect reference data.However,it is still a challenge to distinguish tree crowns and understory green vegetation based on the UAV-based true color images(RGB)due to the limited spectral information.In addition,the canopy height model(CHM)derived from photogrammetric point clouds has also been used to identify tree crowns but limited by the unavailability of understory terrain elevations.This study proposed a simple method to distinguish tree crowns and understories based on UAV visible images,which was referred to as BAMOS for convenience.The central idea of the BAMOS was the synergy of spectral information from digital orthophoto map(DOM)and structural information from digital surface model(DSM).Samples of canopy covers were produced by applying the BAMOS method on the UAV images collected at 77 sites with a size of about 1.0 km^(2) across Daxing’anling forested area in northeast of China.Results showed that canopy cover extracted by the BAMOS method was highly correlated to visually interpreted ones with correlation coefficient(r)of 0.96 and root mean square error(RMSE)of 5.7%.Then,the UAV-based canopy covers served as references for assessment of satellite-based maps,including MOD44B Version 6 Vegetation Continuous Fields(MODIS VCF),maps developed by the Global Land Cover Facility(GLCF)and by the Global Land Analysis and Discovery laboratory(GLAD).Results showed that both GLAD and GLCF canopy covers could capture the dominant spatial patterns,but GLAD canopy cover tended to miss scattered trees in highly heterogeneous areas,and GLCF failed to capture non-tree areas.Most important of all,obvious underestimations with RMSE about 20%were easily observed in all satellite-based maps,although the temporal inconsistency with references might have some contributions.