The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phase...The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated.Cell cycle proteins enhance the activity of CDKs,while natural CDK inhibitors(CDKIs)suppress them.The cell cycle continues in cycles under normal conditions,but when conditions change,cells halt or terminate the cell cycle.Tumors are tissues that grow out of control,and the mechanisms of various types of tumors are different;however,almost all tumor cells share several common characteristics,including proliferation,prevention of apoptosis and genomic instability.Cellular division is essential in the progression of cancer.A key characteristic of cancer is the uncontrolled growth of tumor cells,which is due to the erratic behavior of several proteins during the cell cycle.Therefore,cell cycle regulators are considered attractive targets for the treatment of cancer.The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle,such as CDKs,and provides a brief overview of checkpoint kinases.The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.展开更多
The microbial-induced calcite precipitation(MICP)technique has been developed as a sustainable methodology for the improvement of the engineering characteristics of sandy soils.However,the efficiency of MICP-treated s...The microbial-induced calcite precipitation(MICP)technique has been developed as a sustainable methodology for the improvement of the engineering characteristics of sandy soils.However,the efficiency of MICP-treated sand has not been well established in the literature considering cyclic loading under undrained conditions.Furthermore,the efficacy of different bacterial strains in enhancing the cyclic properties of MICP-treated sand has not been sufficiently documented.Moreover,the effect of wetting-drying(WD)cycles on the cyclic characteristics of MICP-treated sand is not readily available,which may contribute to the limited adoption of MICP treatment in field applications.In this study,strain-controlled consolidated undrained(CU)cyclic triaxial testing was conducted to evaluate the effects of MICP treatment on standard Ennore sand from India with two bacterial strains:Sporosarcina pasteurii and Bacillus subtilis.The treatment durations of 7 d and 14 d were considered,with an interval of 12 h between treatments.The cyclic characteristics,such as the shear modulus and damping ratio,of the MICP-treated sand with the different bacterial strains have been estimated and compared.Furthermore,the effect of WD cycles on the cyclic characteristics of MICP-treated sand has been evaluated considering 5–15 cycles and aging of samples up to three months.The findings of this study may be helpful in assessing the cyclic characteristics of MICP-treated sand,considering the influence of different bacterial strains,treatment duration,and WD cycles.展开更多
In cold regions,slope rocks are inevitably impacted by freeze-thaw,dry-wet cycles and their alternating actions,leading to strength weakening and pore degradation.In this study,the mechanical and microstructural prope...In cold regions,slope rocks are inevitably impacted by freeze-thaw,dry-wet cycles and their alternating actions,leading to strength weakening and pore degradation.In this study,the mechanical and microstructural properties of schist subjected to four conditions were investigated:freeze-thaw cycles in air(FTA),freeze-thaw cycles in water(FTW),dry-wet cycles(DW),and dry-wet-freeze-thaw cycles(DWFT).Uniaxial compressive strength(UCS),water absorption,ultrasonication,low-field nuclear magnetic resonance,and scanning electron microscopy analyses were conducted.The integrity attenuation characteristics of the longitudinal wave velocity,UCS,and elastic modulus were analyzed.The results showed that liquid water emerged as a critical factor in reducing the brittleness of schist.The attenuation function model accurately described the peak stress and static elastic modulus of schist in various media(R2>0.97).Different media affected the schist deterioration and half-life,with the FTW-immersed samples having a half-life of 28 cycles.Furthermore,the longitudinal wave velocity decreased as the number of cycles increased,with the FTW showing the most significant reduction and having the shortest half-life of 208 cycles.Moreover,the damage variables of compressive strength and elastic modulus increased with the number of cycles.After 40 cycles,the schist exposed to FTW exhibited the highest damage variables and saturated water content.展开更多
The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not...The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not been approved.A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market.Subsequently,resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment.In this review,we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors.Moreover,we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors,which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.展开更多
In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a to...In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.展开更多
Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets it...Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets itself apart from existing research by applying a novel optimization technique to a basic ideal Rankine cycle,focusing on a specific power plant that has not been previously analyzed.Currently,this cycle operates at 41%efficiency and a steam quality of 76%,constrained by fixed operational parameters.The primary objectives are to increase thermal efficiency beyond 46%and raise steam quality above 85%,while adhering to operational limits:a boiler pressure not exceeding 15 MPa,condenser pressure not dropping below 10 kPa,and turbine temperature not surpassing 500℃.This study utilizes numerical simulations to model the effects of varying boiler pressure(Pb)and condenser pressure(Pc)within the ranges of 12MPa<Pb<15 MPa and 5 kPa<Pc<10 kPa.By systematically adjusting these parameters,the proposed aimto identify optimal conditions that maximize efficiency and performance within specified constraints.The findings will provide valuable insights for power plant operators seeking to optimize performance under real-world conditions,contributing to more efficient and sustainable power generation.展开更多
With the increasingly serious environmental problems,the use of sustainable materials is particularly important.This study focuses on the greenhouse gas emissions and economic costs of wood over its life cycle as a su...With the increasingly serious environmental problems,the use of sustainable materials is particularly important.This study focuses on the greenhouse gas emissions and economic costs of wood over its life cycle as a sustainable resource.We use a systematic life cycle assessment(LCA)approach to assess the entire process from raw material collection,processing,use to disposal.The study found that using wood can significantly reduce greenhouse gas emissions compared to traditional building materials such as steel and concrete.In addition,although the initial procurement costs of wood may be higher,its maintenance costs are lower in the long run,making the life cycle costs generally more economical.The results of this study highlight the environmental and economic advantages of wood in the selection of sustainable building materials,and provide a scientific basis for promoting the use of wood.展开更多
Under many aspects Italy would be ideal for cycling:the weather is favourable for a good part of the year and many historic centres are characterized by roads which would mainly be suitable for bicycle traffic.The pos...Under many aspects Italy would be ideal for cycling:the weather is favourable for a good part of the year and many historic centres are characterized by roads which would mainly be suitable for bicycle traffic.The positive aspects relating to cycling are well known,but unfortunately,the use of bicycles in Italy is still poor and the main cause of this phenomenon is certainly relating to a general lack of safety in cycling.In the last decade,in Italy the trend of road accidents and victims is generally decreasing,but,at the same time,the number of cyclists involved in road accidents increased by 24,5%,therefore,more attention to cyclists as Vulnerable Road Users is absolutely needed.The causes of this high accident rate is mainly relating to a lack of national legislation or to standards which are old,often overlapped to regional guidelines,uneven,confusing and in some case also contradictory.In terms of cycle network planning,it should be reminded that in Italy there is no regulation that establishes the criteria for a functional classification of bicycle paths.As a consequence,the infrastructure geometry and facilities(bicycle parking,places of refreshments,cycle repair shops,etc.)are not properly put in relation to the role played by the cycle path in the territory.In the course of time,we assisted to the realization of isolated cycle path trunks,generally out of a planning strategy and characterized by their own geometry.Therefore,taking also inspiration by the standards developed in other European Countries,this research tries to provide guidelines for pre-normative functional classification of cycle paths,for their design and planning,in order to obtain safe and homogeneous cycling routes in Italy.It should be noted that the technical solutions,devices and traffic regulations,adopted in other countries,are very effective for a safe cycle mobility,but need to be revised in relation to the existing Italian law.展开更多
Dear Editor,This letter presents a latent-factorization-of-tensors(LFT)-incorporated battery cycle life prediction framework.Data-driven prognosis and health management(PHM)for battery pack(BP)can boost the safety and...Dear Editor,This letter presents a latent-factorization-of-tensors(LFT)-incorporated battery cycle life prediction framework.Data-driven prognosis and health management(PHM)for battery pack(BP)can boost the safety and sustainability of a battery management system(BMS),which relies heavily on the quality of the measured BP data like the voltage(V),current(I),and temperature(T).展开更多
Under the background of resource shortage and global warming,it is of great significance to explore the status,influencing factors and carbon emission reduction effect of waste recycling in China after the implementat...Under the background of resource shortage and global warming,it is of great significance to explore the status,influencing factors and carbon emission reduction effect of waste recycling in China after the implementation of new waste classification policy for guiding waste classification and carbon emission accounting.In this research,the temporal and spatial changes and influencing factors of waste recycling were studied from subdistrict level,life-cycle carbon emission reduction was predicted and policy suggestions for waste recycling were proposed.The results showed that after the implementation of new waste classification policy,the amount of recycled waste and the proportion of low-value recycled waste increased by 420.93 t and 2.29%per month on average,respectively.The district center has the largest amount of recycled waste.Income was the main factors affecting waste recycling,and online shopping and takeout could become important sources of recyclable waste.Accounting cradle-to-grave life cycle carbon footprint,waste plastics takes up the most contribution,accounting for 39.11%,and nearly 391.68 Mt CO_(2eq) would be reduced by waste recycling in China by 2030.Therefore,in the process of waste classification,refining waste classification to increase the amount of low-value recyclables,and rationally deploying collection and transportation vehicles to ensure efficient waste recycling are of great significance to achieve the goal of“carbon peaking and carbon neutrality”.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleoti...BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase(GTPase)and is implicated in various cancers.However,the role of RCC1 in HCC remains unex-plored.AIM To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.METHODS Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy.The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells.Furthermore,quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.RESULTS Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients.Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells,especially the proliferation of HCC cells,whereas RCC1 knockdown had the opposite effect.Mechanistically,we identied cell division cycle-associated(CDCA)8 as a downstream target of RCC1 in HCC.RCC1 overexpression markedly increased CDCA8 levels,consequently enhancing cell proliferation and survival in HCC cells.Additionally,we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.CONCLUSION Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been lin...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.展开更多
With a three-dimensional semiclassical ensemble method, we theoretically investigated the nonsequential double ionization of Ar driven by the spatially inhomogeneous few-cycle negatively chirped laser pulses. Our resu...With a three-dimensional semiclassical ensemble method, we theoretically investigated the nonsequential double ionization of Ar driven by the spatially inhomogeneous few-cycle negatively chirped laser pulses. Our results show that the recollision time window can be precisely controlled within an isolated time interval of several hundred attoseconds, which is useful for understanding the subcycle correlated electron dynamics. More interestingly, the correlated electron momentum distribution (CEMD) exhibits a strong dependence on laser intensity. That is, at lower laser intensity, CEMD is located in the first quadrant. As the laser intensity increases,CEMD shifts almost completely to the second and fourth quadrants, and then gradually to the third quadrant.The underlying physics governing the CEMD's dependence on laser intensity is explained.展开更多
China is the most important steel producer in the world,and its steel industry is one of themost carbon-intensive industries in China.Consequently,research on carbon emissions from the steel industry is crucial for Ch...China is the most important steel producer in the world,and its steel industry is one of themost carbon-intensive industries in China.Consequently,research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals.We constructed a carbon dioxide(CO_(2))emission model for China’s iron and steel industry froma life cycle perspective,conducted an empirical analysis based on data from2019,and calculated the CO_(2)emissions of the industry throughout its life cycle.Key emission reduction factors were identified using sensitivity analysis.The results demonstrated that the CO_(2)emission intensity of the steel industry was 2.33 ton CO_(2)/ton,and the production and manufacturing stages were the main sources of CO_(2)emissions,accounting for 89.84%of the total steel life-cycle emissions.Notably,fossil fuel combustion had the highest sensitivity to steel CO_(2)emissions,with a sensitivity coefficient of 0.68,reducing the amount of fossil fuel combustion by 20%and carbon emissions by 13.60%.The sensitivities of power structure optimization and scrap consumption were similar,while that of the transportation structure adjustment was the lowest,with a sensitivity coefficient of less than 0.1.Given the current strategic goals of peak carbon and carbon neutrality,it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies,increase the ratio of scrap steel to steelmaking,and build a new power system.展开更多
GH4169 joints manufactured by Linear Friction Welding(LFW)are subjected to tensile test and stair-case method to evaluate the High Cycle Fatigue(HCF)performance at 650℃.The yield and ultimate tensile strengths are 58...GH4169 joints manufactured by Linear Friction Welding(LFW)are subjected to tensile test and stair-case method to evaluate the High Cycle Fatigue(HCF)performance at 650℃.The yield and ultimate tensile strengths are 582 MPa and 820 MPa,respectively.The HCF strength of joint reaches 400 MPa,which is slightly lower than that of Base Metal(BM),indicating reliable quality of this type of joint.The microstructure observation results show that all cracks initiate at the inside of specimens and transfer into deeper region with decrease of external stress,and the crack initiation site is related with microhardness of matrix.The Electron Backscattered Diffraction(EBSD)results of the observed regions with different distances to fracture show that plastic deformation plays a key role in HCF,and the Schmid factor of most grains near fracture exceeds 0.4.In addition,the generation of twins plays a vital role in strain concentration release and coordinating plastic deformation among grains.展开更多
Approximately 3.44 billion tons of copper mine tailings(MT)were produced globally in 2018 with an increase of 45%from 2010.Significant efforts are being made to manage these tailings through storage facilities,recycli...Approximately 3.44 billion tons of copper mine tailings(MT)were produced globally in 2018 with an increase of 45%from 2010.Significant efforts are being made to manage these tailings through storage facilities,recycling,and reuse in different industries.Currently,a large portion of tailings are managed through the tailing storage facilities(TSF)where these tailings undergo hydro-thermal-mechanical stresses with seasonal cycles which are not comprehensively understood.This study presents an investigative study to evaluate the performance of control and cement-stabilized copper MT under the influence of seasonal cycles,freeze-thaw(F-T)and wet-dry(W-D)conditions,representing the seasonal variability in the cold and arid regions.The control and cement-stabilized MT samples were subjected to a maximum of 12 F-T and 12 W-D cycles and corresponding micro-and-macro behavior was investigated through scanning electron microscope(SEM),volumetric strain(εvT,wet density(r),moisture content loss,and unconfined compressive strength(UCS)tests.The results indicated the vulnerability of Copper MT to 67%and 75%strength loss reaching residual states with 12 F-T and 8 W-D cycles,respectively.Whereas the stabilized MT retained 39%-55%and 16%-34%strength with F-T and W-D cycles,demonstrating increased durability.This research highlights the impact of seasonal cycles and corresponding strength-deformation characteristics of control and stabilized Copper MT in cold and arid regions.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.展开更多
Mining and tailings deposition can cause serious heavy metal(loids)pollution to the surrounding soil environment.Soil microorganisms adapt their metabolism to such conditions,driving alterations in soil function.This ...Mining and tailings deposition can cause serious heavy metal(loids)pollution to the surrounding soil environment.Soil microorganisms adapt their metabolism to such conditions,driving alterations in soil function.This study aims to elucidate the response patterns of nitrogen-cycling microorganisms under long-term heavy metal(loids)exposure.The results showed that the diversity and abundance of nitrogen-cyclingmicroorganisms showed negative feedback to heavy metal(loids)concentrations.Denitrifying microorganisms were shown to be the dominant microorganisms with over 60%of relative abundance and a complex community structure including 27 phyla.Further,the key bacterial species in the denitrification process were calculated using a random forest model,where the top three key species(Pseudomonas stutzei,Sphingobium japonicum and Leifsonia rubra)were found to play a prominent role in nitrite reduction.Functional gene analysis and qPCR revealed that nirK,which is involved in nitrite reduction,significantly accumulated in the most metal-rich soil with the increase of absolute abundance of 63.86%.The experimental results confirmed that the activity of nitrite reductase(Nir)encoded by nirK in the soil was increased at high concentrations of heavy metal(loids).Partial least squares-path model identified three potential modes of nitrite reduction processes being stimulated by heavy metal(loids),the most prominent of which contributed to enhanced nirK abundance and soil Nir activity through positive stimulation of key species.The results provide new insights and preliminary evidence on the stimulation of nitrite reduction processes by heavy metal(loids).展开更多
The roughness of the fracture surface directly affects the strength,deformation,and permeability of the surrounding rock in deep underground engineering.Understanding the effect of high temperature and thermal cycle o...The roughness of the fracture surface directly affects the strength,deformation,and permeability of the surrounding rock in deep underground engineering.Understanding the effect of high temperature and thermal cycle on the fracture surface roughness plays an important role in estimating the damage degree and stability of deep rock mass.In this paper,the variations of fracture surface roughness of granite after different heating and thermal cycles were investigated using the joint roughness coefficient method(JRC),three-dimensional(3D)roughness parameters,and fractal dimension(D),and the mechanism of damage and deterioration of granite were revealed.The experimental results show an increase in the roughness of the granite fracture surface as temperature and cycle number were incremented.The variations of JRC,height parameter,inclination parameter and area parameter with the temperature conformed to the Boltzmann's functional distribution,while the D decreased linearly as the temperature increased.Besides,the anisotropy index(Ip)of the granite fracture surface increased as the temperature increased,and the larger parameter values of roughness characterization at different temperatures were attained mainly in directions of 20°–40°,60°–100°and 140°–160°.The fracture aperture of granite after fracture followed the Gauss distribution and the average aperture increased with increasing temperature,which increased from 0.665 mm at 25℃to 1.058 mm at 800℃.High temperature caused an uneven thermal expansion,water evaporation,and oxidation of minerals within the granite,which promoted the growth and expansion of microfractures,and reduced interparticle bonding strength.In particular,the damage was exacerbated by the expansion and cracking of the quartz phase transition after T>500℃.Thermal cycles contributed to the accumulation of this damage and further weakened the interparticle bonding forces,resulting in a significant increase in the roughness,anisotropy,and aperture of the fracture surface after five cycles.展开更多
文摘The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated.Cell cycle proteins enhance the activity of CDKs,while natural CDK inhibitors(CDKIs)suppress them.The cell cycle continues in cycles under normal conditions,but when conditions change,cells halt or terminate the cell cycle.Tumors are tissues that grow out of control,and the mechanisms of various types of tumors are different;however,almost all tumor cells share several common characteristics,including proliferation,prevention of apoptosis and genomic instability.Cellular division is essential in the progression of cancer.A key characteristic of cancer is the uncontrolled growth of tumor cells,which is due to the erratic behavior of several proteins during the cell cycle.Therefore,cell cycle regulators are considered attractive targets for the treatment of cancer.The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle,such as CDKs,and provides a brief overview of checkpoint kinases.The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.
基金the financial support provided by the Ministry of Education(MoE),Government of IndiaThe second author acknowledges Coal India Limited for providing financial assistance for the research(Project No.CIL/R&D/01/73/2021).
文摘The microbial-induced calcite precipitation(MICP)technique has been developed as a sustainable methodology for the improvement of the engineering characteristics of sandy soils.However,the efficiency of MICP-treated sand has not been well established in the literature considering cyclic loading under undrained conditions.Furthermore,the efficacy of different bacterial strains in enhancing the cyclic properties of MICP-treated sand has not been sufficiently documented.Moreover,the effect of wetting-drying(WD)cycles on the cyclic characteristics of MICP-treated sand is not readily available,which may contribute to the limited adoption of MICP treatment in field applications.In this study,strain-controlled consolidated undrained(CU)cyclic triaxial testing was conducted to evaluate the effects of MICP treatment on standard Ennore sand from India with two bacterial strains:Sporosarcina pasteurii and Bacillus subtilis.The treatment durations of 7 d and 14 d were considered,with an interval of 12 h between treatments.The cyclic characteristics,such as the shear modulus and damping ratio,of the MICP-treated sand with the different bacterial strains have been estimated and compared.Furthermore,the effect of WD cycles on the cyclic characteristics of MICP-treated sand has been evaluated considering 5–15 cycles and aging of samples up to three months.The findings of this study may be helpful in assessing the cyclic characteristics of MICP-treated sand,considering the influence of different bacterial strains,treatment duration,and WD cycles.
基金supported by the National Natural Science Foundation of China(Nos.42171108 and 42101136)Sichuan Science and Technology Program(Nos.2024NSFSC2007 and2025YFHZ0273)Natural Science Starting Project of SWPU(No.2024QHZ029)。
文摘In cold regions,slope rocks are inevitably impacted by freeze-thaw,dry-wet cycles and their alternating actions,leading to strength weakening and pore degradation.In this study,the mechanical and microstructural properties of schist subjected to four conditions were investigated:freeze-thaw cycles in air(FTA),freeze-thaw cycles in water(FTW),dry-wet cycles(DW),and dry-wet-freeze-thaw cycles(DWFT).Uniaxial compressive strength(UCS),water absorption,ultrasonication,low-field nuclear magnetic resonance,and scanning electron microscopy analyses were conducted.The integrity attenuation characteristics of the longitudinal wave velocity,UCS,and elastic modulus were analyzed.The results showed that liquid water emerged as a critical factor in reducing the brittleness of schist.The attenuation function model accurately described the peak stress and static elastic modulus of schist in various media(R2>0.97).Different media affected the schist deterioration and half-life,with the FTW-immersed samples having a half-life of 28 cycles.Furthermore,the longitudinal wave velocity decreased as the number of cycles increased,with the FTW showing the most significant reduction and having the shortest half-life of 208 cycles.Moreover,the damage variables of compressive strength and elastic modulus increased with the number of cycles.After 40 cycles,the schist exposed to FTW exhibited the highest damage variables and saturated water content.
基金supported by the National Key R&D Program of China(No.2023YFC2706303)the National Natural Science Foundation of China(Nos.82373738 and 82304293)Natural Science Foundation of Jiangsu Province(Nos.SBK2024090146 and BK20221040).
文摘The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not been approved.A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market.Subsequently,resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment.In this review,we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors.Moreover,we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors,which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.
文摘In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.
文摘Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets itself apart from existing research by applying a novel optimization technique to a basic ideal Rankine cycle,focusing on a specific power plant that has not been previously analyzed.Currently,this cycle operates at 41%efficiency and a steam quality of 76%,constrained by fixed operational parameters.The primary objectives are to increase thermal efficiency beyond 46%and raise steam quality above 85%,while adhering to operational limits:a boiler pressure not exceeding 15 MPa,condenser pressure not dropping below 10 kPa,and turbine temperature not surpassing 500℃.This study utilizes numerical simulations to model the effects of varying boiler pressure(Pb)and condenser pressure(Pc)within the ranges of 12MPa<Pb<15 MPa and 5 kPa<Pc<10 kPa.By systematically adjusting these parameters,the proposed aimto identify optimal conditions that maximize efficiency and performance within specified constraints.The findings will provide valuable insights for power plant operators seeking to optimize performance under real-world conditions,contributing to more efficient and sustainable power generation.
文摘With the increasingly serious environmental problems,the use of sustainable materials is particularly important.This study focuses on the greenhouse gas emissions and economic costs of wood over its life cycle as a sustainable resource.We use a systematic life cycle assessment(LCA)approach to assess the entire process from raw material collection,processing,use to disposal.The study found that using wood can significantly reduce greenhouse gas emissions compared to traditional building materials such as steel and concrete.In addition,although the initial procurement costs of wood may be higher,its maintenance costs are lower in the long run,making the life cycle costs generally more economical.The results of this study highlight the environmental and economic advantages of wood in the selection of sustainable building materials,and provide a scientific basis for promoting the use of wood.
文摘Under many aspects Italy would be ideal for cycling:the weather is favourable for a good part of the year and many historic centres are characterized by roads which would mainly be suitable for bicycle traffic.The positive aspects relating to cycling are well known,but unfortunately,the use of bicycles in Italy is still poor and the main cause of this phenomenon is certainly relating to a general lack of safety in cycling.In the last decade,in Italy the trend of road accidents and victims is generally decreasing,but,at the same time,the number of cyclists involved in road accidents increased by 24,5%,therefore,more attention to cyclists as Vulnerable Road Users is absolutely needed.The causes of this high accident rate is mainly relating to a lack of national legislation or to standards which are old,often overlapped to regional guidelines,uneven,confusing and in some case also contradictory.In terms of cycle network planning,it should be reminded that in Italy there is no regulation that establishes the criteria for a functional classification of bicycle paths.As a consequence,the infrastructure geometry and facilities(bicycle parking,places of refreshments,cycle repair shops,etc.)are not properly put in relation to the role played by the cycle path in the territory.In the course of time,we assisted to the realization of isolated cycle path trunks,generally out of a planning strategy and characterized by their own geometry.Therefore,taking also inspiration by the standards developed in other European Countries,this research tries to provide guidelines for pre-normative functional classification of cycle paths,for their design and planning,in order to obtain safe and homogeneous cycling routes in Italy.It should be noted that the technical solutions,devices and traffic regulations,adopted in other countries,are very effective for a safe cycle mobility,but need to be revised in relation to the existing Italian law.
文摘Dear Editor,This letter presents a latent-factorization-of-tensors(LFT)-incorporated battery cycle life prediction framework.Data-driven prognosis and health management(PHM)for battery pack(BP)can boost the safety and sustainability of a battery management system(BMS),which relies heavily on the quality of the measured BP data like the voltage(V),current(I),and temperature(T).
基金supported by the Construction of Environmental Science and Engineering Discipline for the Goal of Carbon Peaking and Carbon Neutrality Funding comes from Beijing Forestry University(No.2022XKJS0207).
文摘Under the background of resource shortage and global warming,it is of great significance to explore the status,influencing factors and carbon emission reduction effect of waste recycling in China after the implementation of new waste classification policy for guiding waste classification and carbon emission accounting.In this research,the temporal and spatial changes and influencing factors of waste recycling were studied from subdistrict level,life-cycle carbon emission reduction was predicted and policy suggestions for waste recycling were proposed.The results showed that after the implementation of new waste classification policy,the amount of recycled waste and the proportion of low-value recycled waste increased by 420.93 t and 2.29%per month on average,respectively.The district center has the largest amount of recycled waste.Income was the main factors affecting waste recycling,and online shopping and takeout could become important sources of recyclable waste.Accounting cradle-to-grave life cycle carbon footprint,waste plastics takes up the most contribution,accounting for 39.11%,and nearly 391.68 Mt CO_(2eq) would be reduced by waste recycling in China by 2030.Therefore,in the process of waste classification,refining waste classification to increase the amount of low-value recyclables,and rationally deploying collection and transportation vehicles to ensure efficient waste recycling are of great significance to achieve the goal of“carbon peaking and carbon neutrality”.
基金Supported by the National Natural Science Foundation of China,No.82002940 and No.82203336Shaanxi Natural Science Foundation,No.2023-JC-YB-166.
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase(GTPase)and is implicated in various cancers.However,the role of RCC1 in HCC remains unex-plored.AIM To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.METHODS Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy.The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells.Furthermore,quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.RESULTS Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients.Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells,especially the proliferation of HCC cells,whereas RCC1 knockdown had the opposite effect.Mechanistically,we identied cell division cycle-associated(CDCA)8 as a downstream target of RCC1 in HCC.RCC1 overexpression markedly increased CDCA8 levels,consequently enhancing cell proliferation and survival in HCC cells.Additionally,we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.CONCLUSION Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY22H160005。
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.
基金supported by the National Natural Science Foundation of China (Grant No. 12074329)Nanhu Scholars Program for Young Scholars of Xinyang Normal University。
文摘With a three-dimensional semiclassical ensemble method, we theoretically investigated the nonsequential double ionization of Ar driven by the spatially inhomogeneous few-cycle negatively chirped laser pulses. Our results show that the recollision time window can be precisely controlled within an isolated time interval of several hundred attoseconds, which is useful for understanding the subcycle correlated electron dynamics. More interestingly, the correlated electron momentum distribution (CEMD) exhibits a strong dependence on laser intensity. That is, at lower laser intensity, CEMD is located in the first quadrant. As the laser intensity increases,CEMD shifts almost completely to the second and fourth quadrants, and then gradually to the third quadrant.The underlying physics governing the CEMD's dependence on laser intensity is explained.
基金supported by Ningbo’s major scientific and technological breakthrough project“Research and Demonstration on the Technology of Collaborative Disposal of Secondary Ash in Typical Industrial Furnaces” (No.20212ZDYF020047)the central balance fund project“Research on Carbon Emission Accounting and Emission Reduction Potential Assessment for the Whole Life Cycle of Iron and Steel Industry” (No.2021-JY-07).
文摘China is the most important steel producer in the world,and its steel industry is one of themost carbon-intensive industries in China.Consequently,research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals.We constructed a carbon dioxide(CO_(2))emission model for China’s iron and steel industry froma life cycle perspective,conducted an empirical analysis based on data from2019,and calculated the CO_(2)emissions of the industry throughout its life cycle.Key emission reduction factors were identified using sensitivity analysis.The results demonstrated that the CO_(2)emission intensity of the steel industry was 2.33 ton CO_(2)/ton,and the production and manufacturing stages were the main sources of CO_(2)emissions,accounting for 89.84%of the total steel life-cycle emissions.Notably,fossil fuel combustion had the highest sensitivity to steel CO_(2)emissions,with a sensitivity coefficient of 0.68,reducing the amount of fossil fuel combustion by 20%and carbon emissions by 13.60%.The sensitivities of power structure optimization and scrap consumption were similar,while that of the transportation structure adjustment was the lowest,with a sensitivity coefficient of less than 0.1.Given the current strategic goals of peak carbon and carbon neutrality,it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies,increase the ratio of scrap steel to steelmaking,and build a new power system.
基金supported by the National Natural Science Foundation of China(Nos.52074228,52305420,and 51875470)the China Postdoctoral Science Foundation(No.2023M742830)。
文摘GH4169 joints manufactured by Linear Friction Welding(LFW)are subjected to tensile test and stair-case method to evaluate the High Cycle Fatigue(HCF)performance at 650℃.The yield and ultimate tensile strengths are 582 MPa and 820 MPa,respectively.The HCF strength of joint reaches 400 MPa,which is slightly lower than that of Base Metal(BM),indicating reliable quality of this type of joint.The microstructure observation results show that all cracks initiate at the inside of specimens and transfer into deeper region with decrease of external stress,and the crack initiation site is related with microhardness of matrix.The Electron Backscattered Diffraction(EBSD)results of the observed regions with different distances to fracture show that plastic deformation plays a key role in HCF,and the Schmid factor of most grains near fracture exceeds 0.4.In addition,the generation of twins plays a vital role in strain concentration release and coordinating plastic deformation among grains.
基金the W.M.Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona(Grant No.RRID:SCR_022884),with funding from the W.M.Keck Foundation Grant.
文摘Approximately 3.44 billion tons of copper mine tailings(MT)were produced globally in 2018 with an increase of 45%from 2010.Significant efforts are being made to manage these tailings through storage facilities,recycling,and reuse in different industries.Currently,a large portion of tailings are managed through the tailing storage facilities(TSF)where these tailings undergo hydro-thermal-mechanical stresses with seasonal cycles which are not comprehensively understood.This study presents an investigative study to evaluate the performance of control and cement-stabilized copper MT under the influence of seasonal cycles,freeze-thaw(F-T)and wet-dry(W-D)conditions,representing the seasonal variability in the cold and arid regions.The control and cement-stabilized MT samples were subjected to a maximum of 12 F-T and 12 W-D cycles and corresponding micro-and-macro behavior was investigated through scanning electron microscope(SEM),volumetric strain(εvT,wet density(r),moisture content loss,and unconfined compressive strength(UCS)tests.The results indicated the vulnerability of Copper MT to 67%and 75%strength loss reaching residual states with 12 F-T and 8 W-D cycles,respectively.Whereas the stabilized MT retained 39%-55%and 16%-34%strength with F-T and W-D cycles,demonstrating increased durability.This research highlights the impact of seasonal cycles and corresponding strength-deformation characteristics of control and stabilized Copper MT in cold and arid regions.
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
基金supported by the National Natural Science Foundation of China(No.41977029).
文摘Mining and tailings deposition can cause serious heavy metal(loids)pollution to the surrounding soil environment.Soil microorganisms adapt their metabolism to such conditions,driving alterations in soil function.This study aims to elucidate the response patterns of nitrogen-cycling microorganisms under long-term heavy metal(loids)exposure.The results showed that the diversity and abundance of nitrogen-cyclingmicroorganisms showed negative feedback to heavy metal(loids)concentrations.Denitrifying microorganisms were shown to be the dominant microorganisms with over 60%of relative abundance and a complex community structure including 27 phyla.Further,the key bacterial species in the denitrification process were calculated using a random forest model,where the top three key species(Pseudomonas stutzei,Sphingobium japonicum and Leifsonia rubra)were found to play a prominent role in nitrite reduction.Functional gene analysis and qPCR revealed that nirK,which is involved in nitrite reduction,significantly accumulated in the most metal-rich soil with the increase of absolute abundance of 63.86%.The experimental results confirmed that the activity of nitrite reductase(Nir)encoded by nirK in the soil was increased at high concentrations of heavy metal(loids).Partial least squares-path model identified three potential modes of nitrite reduction processes being stimulated by heavy metal(loids),the most prominent of which contributed to enhanced nirK abundance and soil Nir activity through positive stimulation of key species.The results provide new insights and preliminary evidence on the stimulation of nitrite reduction processes by heavy metal(loids).
基金funding support from the National Natural Science Foundation of China(Grant No.52274082)the Program of Qingjiang Excellent Young Talents,Jiangxi University of Science and Technology(Grant No.JXUSTQJBJ2020003)the Innovation Fund Designated for Graduate Students of Jiangxi Province(Grant No.YC2023-B215).
文摘The roughness of the fracture surface directly affects the strength,deformation,and permeability of the surrounding rock in deep underground engineering.Understanding the effect of high temperature and thermal cycle on the fracture surface roughness plays an important role in estimating the damage degree and stability of deep rock mass.In this paper,the variations of fracture surface roughness of granite after different heating and thermal cycles were investigated using the joint roughness coefficient method(JRC),three-dimensional(3D)roughness parameters,and fractal dimension(D),and the mechanism of damage and deterioration of granite were revealed.The experimental results show an increase in the roughness of the granite fracture surface as temperature and cycle number were incremented.The variations of JRC,height parameter,inclination parameter and area parameter with the temperature conformed to the Boltzmann's functional distribution,while the D decreased linearly as the temperature increased.Besides,the anisotropy index(Ip)of the granite fracture surface increased as the temperature increased,and the larger parameter values of roughness characterization at different temperatures were attained mainly in directions of 20°–40°,60°–100°and 140°–160°.The fracture aperture of granite after fracture followed the Gauss distribution and the average aperture increased with increasing temperature,which increased from 0.665 mm at 25℃to 1.058 mm at 800℃.High temperature caused an uneven thermal expansion,water evaporation,and oxidation of minerals within the granite,which promoted the growth and expansion of microfractures,and reduced interparticle bonding strength.In particular,the damage was exacerbated by the expansion and cracking of the quartz phase transition after T>500℃.Thermal cycles contributed to the accumulation of this damage and further weakened the interparticle bonding forces,resulting in a significant increase in the roughness,anisotropy,and aperture of the fracture surface after five cycles.
