Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover...Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.展开更多
Sprouts are ready-to-eat and are recognized worldwide as functional components of the human diet.Recent advances in innovative agricultural techniques could enable an increase in the production of healthy food.The use...Sprouts are ready-to-eat and are recognized worldwide as functional components of the human diet.Recent advances in innovative agricultural techniques could enable an increase in the production of healthy food.The use of light-emitting diode(LED)in indoor agricultural production could alter the biological feedback loop,increasing the functional benefits of plant foods such as wheat and lentil sprouts and promoting the bioavailability of nutrients.The effects of white(W),red(R),and blue(B)light were investigated on the growth parameters and nutritional value of wheat and lentil sprouts.In the laboratory,seeds were sown under three different LED treat-ments:white,red,and blue light,while normal incandescent light served as a control.Percentage seed germina-tion improved by 18.34%and 12.67%for wheat and 18.34%and 12.67%for lentil sprouts under LED treatments R and B,respectively.An increase in total soluble protein and sugar by 33.4%and 9.23%in wheat and by 31.5%and 5.87%in lentils was observed under the R LED treatment.Vitamin C concentrations in wheat and lentils were significantly increased by R LED compared to all other treatments.Other parameters,including potassium and sodium concentrations,were significantly increased under red and blue light compared to the control;white light,on the other hand,significantly decreased all these parameters.According to the experimental data,red and blue LED light could be beneficial in the production of functional wheat and lentil sprouts with high nutrient concentrations.展开更多
The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could of...The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug resistance.To this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy.The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool.Expression and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA databases.Mutational,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank databases.Lastly,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in KIRC.Out of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC patients.Moreover,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes.In addition to this,hub genes were also linked with different cisplatin resistance-causing pathways.Thus,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol,Acetaminophen,Acitretin,Cyclosporine,Azacitidine,Genistein,and Resveratrol drugs.As the pathogenesis of KIRC is complex,targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance,which might uplift overall survival among KIRC patients.展开更多
Aluminum alloy is the main structural material of aircraft,launch vehicle,spaceship,and space station and is processed by milling.However,tool wear and vibration are the bottlenecks in the milling process of aviation ...Aluminum alloy is the main structural material of aircraft,launch vehicle,spaceship,and space station and is processed by milling.However,tool wear and vibration are the bottlenecks in the milling process of aviation aluminum alloy.The machining accuracy and surface quality of aluminum alloy milling depend on the cutting parameters,material mechanical properties,machine tools,and other parameters.In particular,milling force is the crucial factor to determine material removal and workpiece surface integrity.However,establishing the prediction model of milling force is important and difficult because milling force is the result of multiparameter coupling of process system.The research progress of cutting force model is reviewed from three modeling methods:empirical model,finite element simulation,and instantaneous milling force model.The problems of cutting force modeling are also determined.In view of these problems,the future work direction is proposed in the following four aspects:(1)high-speed milling is adopted for the thin-walled structure of large aviation with large cutting depth,which easily produces high residual stress.The residual stress should be analyzed under this particular condition.(2)Multiple factors(e.g.,eccentric swing milling parameters,lubrication conditions,tools,tool and workpiece deformation,and size effect)should be considered comprehensively when modeling instantaneous milling forces,especially for micro milling and complex surface machining.(3)The database of milling force model,including the corresponding workpiece materials,working condition,cutting tools(geometric figures and coatings),and other parameters,should be established.(4)The effect of chatter on the prediction accuracy of milling force cannot be ignored in thin-walled workpiece milling.(5)The cutting force of aviation aluminum alloy milling under the condition of minimum quantity lubrication(mql)and nanofluid mql should be predicted.展开更多
The application of cutting fluid in the field of engineering manufacturing has a history of hundreds of years,and it plays a vital role in the processing efficiency and surface quality of parts.Among them,water-based ...The application of cutting fluid in the field of engineering manufacturing has a history of hundreds of years,and it plays a vital role in the processing efficiency and surface quality of parts.Among them,water-based cutting fluid accounts for more than 90%of the consumption of cutting fluid.However,long-term recycling of water-based cutting fluid could easily cause deterioration,and the breeding of bacteria could cause the cutting fluid to fail,increase manufacturing costs,and even endanger the health of workers.Traditional bactericides could improve the biological stability of cutting fluids,but they are toxic to the environment and do not conform to the development trend of low-carbon manufacturing.Low-carbon manufacturing is inevitable and the direction of sustainable manufacturing.The use of nanomaterials,transition metal complexes,and physical sterilization methods on the bacterial cell membrane and genetic material could effectively solve this problem.In this article,the mechanism of action of additives and microbial metabolites was first analyzed.Then,the denaturation mechanism of traditional bactericides on the target protein and the effect of sterilization efficiency were summarized.Further,the mechanism of nanomaterials disrupting cell membrane potential was discussed.The effects of lipophilicity and the atomic number of transition metal complexes on cell membrane penetration were also summarized,and the effects of ultraviolet rays and ozone on the destruction of bacterial genetic material were reviewed.In other words,the bactericidal performance,hazard,degradability,and economics of various sterilization methods were comprehensively evaluated,and the potential development direction of improving the biological stability of cutting fluid was proposed.展开更多
The unsteady flow of an incompressible fractional Maxwell fluid between two infinite coaxial cylinders is studied by means of integral transforms. The motion of the fluid is due to the inner cylinder that applies a ti...The unsteady flow of an incompressible fractional Maxwell fluid between two infinite coaxial cylinders is studied by means of integral transforms. The motion of the fluid is due to the inner cylinder that applies a time dependent tor- sional shear to the fluid. The exact solutions for velocity and shear stress are presented in series form in terms of some generalized functions. They can easily be particularized to give similar solutions for Maxwell and Newtonian fluids. Fi- nally, the influence of pertinent parameters on the fluid motion, as well as a comparison between models, is highlighted by graphical illustrations.展开更多
The 3-D seismic dataset is a key tool to analyze and understand the mechanism of structural and stratigraphic hydrocarbon(HC)trapping in the subsurface.Conventionally used subsurface seismic characterization methods f...The 3-D seismic dataset is a key tool to analyze and understand the mechanism of structural and stratigraphic hydrocarbon(HC)trapping in the subsurface.Conventionally used subsurface seismic characterization methods for fractures are based on the theory of effective anisotropy medium.The aim of this work is to improve the structural images with dense sampling of 3-D survey to evaluate structural and stratigraphic models for reservoir development to predict reservoir quality.The present study of the Gullfaks Field,located in the Norwegian North Sea Gullfaks sector,identifies the shallowest structural elements.The steepness of westward structural dip decreases eastward during the Upper Jurassic to Lower Cretaceous deposition.Reservoir sands consist of the Middle Jurassic deltaic deposits and Lower Jurassic fluvial channel and delta plain deposits.Sediment supply steadily prevails on sea-level rise and the succession displays a regressive trend indicated by a good continuous stacking pattern.The key factor for the development of reservoirs in the Gullfaks Field is fault transmissibility with spatially distributed pressure.The majority of mapped faults with sand-to-sand contacts are non-sealing,which provide restriction for the HC flow between the fault blocks.The traps for HC accumulation occur between the post-rift and syn-rift strata,i.e.antiform set by extensional system,unconformity trap at the top of syndeposition,and structural trap due to normal faults.Overall reservoir quality in the studied area is generally excellent with average 35%porosity and permeability in the Darcy range.Our findings are useful to better understand the development of siliciclastic reservoirs in similar geological settings worldwide.展开更多
Geostatistical data plays a vibrant role for surface-based reservoir modeling through outcrop analogues,which is used to understand three-dimensional(3D)variability of petrophysical properties.The main purpose of this...Geostatistical data plays a vibrant role for surface-based reservoir modeling through outcrop analogues,which is used to understand three-dimensional(3D)variability of petrophysical properties.The main purpose of this study is to improvise the surface-based 3D geo-modeling to demonstrate petrophysical characteristics and heterogeneities of Sandakan reservoirs,NW Borneo.We used point cloud data from Light Detection and Ranging(Li DAR)to build high-resolution virtual outcrop modeling(VOM)onto which we mapped 6 different lithofacies.Porosity and permeability of core plugs were measured to determine the average variance of petrophysical properties for each lithofacies.By utilizing the integration of VOMs analogues and petrophysical properties in Petrel^(TM),we demonstrated the distribution and associations of all lithofacies in pseudo wells that have inherent thin beds heterogeneities in 3D geocellular model.The results concluded that the heterogeneity of thin beds in lithofacies is dependent on porosity and permeability with input dataset.According to the final model,cross-bedding sandstone(CBS),hummocky cross-stratified sandstone(HCSS)and trough cross-bedding sandstone(TCBS)show good reservoir quality due to high porosity ranging from:25.6%to 20.4%and,19.3%-14.5%,and permeability ranging from:74.03 mD to 66.84 mD and,64.86 mD to 21.01 mD.In contrast,massive to weak laminae sandstone(MWLS)and bioturbated sandstone(BS)show fair to poor reservoir quality,caused baffling of surrounding mud sediments in the reservoir lithofacies.Results also revealed that Li DAR based VOM with petrophysical properties can significantly reduce the risk and minimize the cost of reservoir modeling in petroleum industry.展开更多
AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation.· METHODS: A consanguineous Pakistani fa...AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation.· METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome(USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat(STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene.· RESULTS: By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them,c.1304AC was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype.This, c.1304 A C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435(p.D435A) of its protein product.Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic.·CONCLUSION:Theidentificationofc.1304ACpathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is thefirst example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.展开更多
An emerging definition of the fractal-fractional operator has been used in this study for the modeling of Casson fluid flow.The magnetohydrodynamics flow of Casson fluid has cogent in a channel where the motion of the...An emerging definition of the fractal-fractional operator has been used in this study for the modeling of Casson fluid flow.The magnetohydrodynamics flow of Casson fluid has cogent in a channel where the motion of the upper plate generates the flow while the lower plate is at a static position.The proposed model is non-dimensionalized using the Pi-Buckingham theorem to reduce the complexity in solving the model and computation time.The non-dimensional fractal-fractional model with the power-law kernel has been solved through the Laplace transform technique.The Mathcad software has been used for illustration of the influence of various parameters,i.e.,Hartman number,fractal,fractional,and Casson fluid parameters on the velocity of fluid flow.Through graphs and tables,the results have been implemented and it is shown that the boundary conditions are fully satisfied.The results reveal that the flow velocity is decreasing with the increasing values of the Hartman number and is increasing with the increasing values of the Casson fluid parameter.The findings of the fractal-fractional model have elucidated that the memory effect of the flow model has higher quality than the simple fractional and classical models.Furthermore,to show the validity of the obtained closed-form solutions,special cases have been obtained which are in agreement with the already published solutions.展开更多
This paper establishes the velocity field and the adequate shear stress corresponding to the motion of an Oldroyd-B fluid between two infinite coaxial circular cylinders by means of finite Hankel transforms. The flow ...This paper establishes the velocity field and the adequate shear stress corresponding to the motion of an Oldroyd-B fluid between two infinite coaxial circular cylinders by means of finite Hankel transforms. The flow of the fluid is produced by the inner cylinder which applies a time-dependent longitudinal shear stress to the fluid. The exact analytical solutions, presented in series form in terms of Bessel functions, satisfy all imposed initial and boundary conditions. The general solutions can be easily specialized to give similar solutions for Maxwell, second grade and Newtonian fluids performing the same motion. Finally, some characteristics of the motion as well as the influence of the material parameters on the behavior of the fluid motion are graphically illustrated.展开更多
Corundum abrasives with good chemical stability can be fabricated into various free abrasives and bonded abrasive tools that are widely used in the precision machining of various parts.However,these abrasives cannot s...Corundum abrasives with good chemical stability can be fabricated into various free abrasives and bonded abrasive tools that are widely used in the precision machining of various parts.However,these abrasives cannot satisfy the machining requirements of difficult-to-machine materials with high hardness,high strength,and strong wearing resistance.Although superhard abrasives can machine the above-mentioned materials,their dressing and manufacturing costs are high.By contrast,ceramic corundum abrasives fabricated by sol–gel method is a costeffective product between conventional and superhard abrasives.Ceramic corundum abrasives exhibit self-sharpening and high toughness.In this review,the optimization methods of ceramic corundum abrasive properties are introduced from three aspects:precursor synthesis,particle shaping,and sintering.Firstly,the functional mechanism of seeds and additives on the microstructural and mechanical properties of abrasives is analyzed.Specifically,seeds can reduce the phase transition temperature and improve fracture toughness.The grain size and uniformly dense structure can be controlled by applying an appropriate amount of multicomponent additives.Then,the urgent need of engineering application and machinability of special shape ceramic corundum abrasives is reviewed,and three methods of abrasive shaping are summarized.The micromold replication technique is highly advanced and can be used to prepare functional abrasives.Additionally,the influence of a new sintering method,namely,two-step sintering technique,on the microstructural and mechanical performance of ceramic corundum abrasives is summarized.Finally,the challenge and developmental trend of the optimization of ceramic corundum abrasives are prospected.展开更多
Cutting fluid plays a cooling-lubrication role in the cutting of metal materials.However,the substantial usage of cutting fluid in traditional flood machining seriously pollutes the environment and threatens the healt...Cutting fluid plays a cooling-lubrication role in the cutting of metal materials.However,the substantial usage of cutting fluid in traditional flood machining seriously pollutes the environment and threatens the health of workers.Environmental machining technologies,such as dry cutting,minimum quantity lubrication(MQL),and cryogenic cooling technology,have been used as substitute for flood machining.However,the insufficient cooling capacity of MQL with normal-temperature compressed gas and the lack of lubricating performance of cryogenic cooling technology limit their industrial application.The technical bottleneck of mechanical-thermal damage of difficult-to-cut materials in aerospace and other fields can be solved by combining cryogenic medium and MQL.The latest progress of cryogenic minimum quantity lubrication(CMQL)technology is reviewed in this paper,and the key scientific issues in the research achievements of CMQL are clarified.First,the application forms and process characteristics of CMQL devices in turning,milling,and grinding are systematically summarized from traditional settings to innovative design.Second,the cooling-lubrication mechanism of CMQL and its influence mechanism on material hardness,cutting force,tool wear,and workpiece surface quality in cutting are extensively revealed.The effects of CMQL are systematically analyzed based on its mechanism and application form.Results show that the application effect of CMQL is better than that of cryogenic technology or MQL alone.Finally,the prospect,which provides basis and support for engineering application and development of CMQL technology,is introduced considering the limitations of CMQL.展开更多
To eliminate the negative effect of traditional metal-working fluids and achieve sustainable manufacturing,the usage of nano-enhanced biolubricant(NEBL)is widely researched in minimum quantify lubrication(MQL)machinin...To eliminate the negative effect of traditional metal-working fluids and achieve sustainable manufacturing,the usage of nano-enhanced biolubricant(NEBL)is widely researched in minimum quantify lubrication(MQL)machining.It's improved tool wear and surface integrity have been preliminarily verified by experimental studies.The previous review papers also concluded the major influencing factors of processability including nano-enhancer and lubricant types,NEBL concentration,micro droplet size,and so on.Nevertheless,the complex action of NEBL,from preparation,atomization,infiltration to heat transfer and anti-friction,is indistinct which limits preparation of process specifications and popularity in factories.Especially in the complex machining process,in-depth understanding is difficult and meaningful.To fll this gap,this paper concentrates on the comprehensive quantitative assessment of processability based on tribological,thermal,and machined surface quality aspects for NEBL application in turning,milling,and grinding.Then it attempts to answer mechanisms systematically considering multi-factor influence of molecular structure,physicochemical properties,concentration,and dispersion.Firstly,this paper reveals advanced lubrication and heat transfer mechanisms of NEBL by quantitative comparison with biolubricant-based MQL machining.Secondly,the distinctive filmformation,atomization,and infiltration mechanisms of NEBL,as distinguished from metal-working fluid,are clarified combining with its unique molecular structure and physical properties.Furtherly,the process optimization strategy is concluded based on the synergistic relationship analysis among process variables,physicochemical properties,machining mechanisms,and performance of NEBL.Finally,the future development directions are put forward aiming at current performance limitations of NEBL,which requires improvement on preparation and jet methods respects.This paper will help scientists deeply understand effective mechanism,formulate process specifications,and find future development trend of this technology.展开更多
Owing to reliability and high strength-to-weight ratio,large thin-walled components are widely used in the aviation and aerospace industry.Due to the complex features and sequence involved in the machining process of ...Owing to reliability and high strength-to-weight ratio,large thin-walled components are widely used in the aviation and aerospace industry.Due to the complex features and sequence involved in the machining process of large thin-walled components,machining deformation of component is easy to exceed the specification.In order to address the problem,it is important to retain the appropriate finishing allowance.To find the overall machining deformation,finishing allowance-induced deformation(web finishing allowance,sidewall finishing allowance)and initial residual stress-induced deformation were considered as major factors.Meanwhile,machined surface residual stress-induced deformation,clamping stress-induced deformation,thermal deformation,gravity-induced deformation and inertial force-induced deformation were neglected in the optimization model.Six-peak Gaussian function was introduced to fit the initial residual stress.Based upon the obtained function of initial residual stress,a deformation prediction model between initial residual stress and finishing allowance was established to attain the finishing allowanceinduced deformation.In addition,linear programming optimization model based on the simplex algorithm was developed to optimize the overall machining deformation.Results have concluded that the overall machining deformation reached the minimum value when sidewall finishing allowance and web finishing allowance varied between 1 and 2 mm.Additionally,web finishing allowance-induced deformation and sidewall finishing allowance-induced deformation were1.05 mm and 0.7 mm.Furthermore,the machining deformation decreased to 0.3–0.38 mm with the application of optimized finishing allowance allocation strategy,which made 39–56%reduction of the overall machining deformation compared to that in conventional method.展开更多
It is an inevitable trend of sustainable manufacturing to replace flood and dry machining with minimum quantity lubrication(MQL)technology.Nevertheless,for aeronautical difficult-tomachine materials,MQL couldn’t meet...It is an inevitable trend of sustainable manufacturing to replace flood and dry machining with minimum quantity lubrication(MQL)technology.Nevertheless,for aeronautical difficult-tomachine materials,MQL couldn’t meet the high demand of cooling and lubrication due to high heat generation during machining.Nano-biolubricants,especially non-toxic carbon group nano-enhancers(CGNs)are used,can solve this technical bottleneck.However,the machining mechanisms under lubrication of CGNs are unclear at complex interface between tool and workpiece,which characterized by high temperature,pressure,and speed,limited its application in factories and necessitates in-depth understanding.To fill this gap,this study concentrates on the comprehensive quantitative assessment of tribological characteristics based on force,tool wear,chip,and surface integrity in titanium alloy and nickel alloy machining and attempts to answer mechanisms systematically.First,to establish evaluation standard,the cutting mechanisms and performance improvement behavior covering antifriction,antiwear,tool failure,material removal,and surface formation of MQL were revealed.Second,the unique film formation and lubrication behaviors of CGNs in MQL turning,milling,and grinding are concluded.The influence law of molecular structure and micromorphology of CGNs was also answered and optimized options were recommended by considering diverse boundary conditions.Finally,in view of CGNs limitations in MQL,the future development direction is proposed,which needs to be improved in thermal stability of lubricant,activity of CGNs,controllable atomization and transportation methods,and intelligent formation of processing technology solutions.展开更多
基金The authors would like to extend their sincere appreciation to the Researchers Supporting Project Number(RSP2023R457),King Saud University,Riyadh,Saudi Arabia.
文摘Kidney Renal Clear Cell Carcinoma(KIRC)is a malignant tumor that carries a substantial risk of morbidity and mortality.The MMP family assumes a crucial role in tumor invasion and metastasis.This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma(KIRC)through a comprehensive approach encompassing both computational and molecular analyses.STRING,Cytoscape,UALCAN,GEPIA,OncoDB,HPA,cBioPortal,GSEA,TIMER,ENCORI,DrugBank,targeted bisulfite sequencing(bisulfite-seq),conventional PCR,Sanger sequencing,and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC.By performing STRING and Cytohubba analyses of the 24 MMP gene family members,MMP2(matrix metallopeptidase 2),MMP9(matrix metallopeptidase 9),MMP12(matrix metallopeptidase 12),and MMP16(matrix metallopeptidase 16)genes were denoted as hub genes having highest degree scores.After analyzing MMP2,MMP9,MMP12,and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines,interestingly,all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls.The notable effect of the up-regulated MMP2,MMP9,MMP12,and MMP16 was also documented on the overall survival(OS)of the KIRC patients.Moreover,targeted bisulfite-sequencing(bisulfite-seq)analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes(MMP2,MMP9,MMP12,and MMP16).In addition to this,hub genes were involved in various diverse oncogenic pathways.The MMP gene family members(MMP2,MMP9,MMP12,and MMP16)may serve as therapeutic targets and prognostic biomarkers in KIRC.
基金Supported by Researchers Supporting Project Number(RSP2024R410)King Saud University,Riyadh,Saudi Arabia.
文摘Sprouts are ready-to-eat and are recognized worldwide as functional components of the human diet.Recent advances in innovative agricultural techniques could enable an increase in the production of healthy food.The use of light-emitting diode(LED)in indoor agricultural production could alter the biological feedback loop,increasing the functional benefits of plant foods such as wheat and lentil sprouts and promoting the bioavailability of nutrients.The effects of white(W),red(R),and blue(B)light were investigated on the growth parameters and nutritional value of wheat and lentil sprouts.In the laboratory,seeds were sown under three different LED treat-ments:white,red,and blue light,while normal incandescent light served as a control.Percentage seed germina-tion improved by 18.34%and 12.67%for wheat and 18.34%and 12.67%for lentil sprouts under LED treatments R and B,respectively.An increase in total soluble protein and sugar by 33.4%and 9.23%in wheat and by 31.5%and 5.87%in lentils was observed under the R LED treatment.Vitamin C concentrations in wheat and lentils were significantly increased by R LED compared to all other treatments.Other parameters,including potassium and sodium concentrations,were significantly increased under red and blue light compared to the control;white light,on the other hand,significantly decreased all these parameters.According to the experimental data,red and blue LED light could be beneficial in the production of functional wheat and lentil sprouts with high nutrient concentrations.
基金The authors would like to extend their sincere appreciation to the Researchers Supporting Project Number(RSPD2023R986)King Saud University,Riyadh,Saudi Arabia.
文摘The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug resistance.To this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy.The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool.Expression and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA databases.Mutational,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank databases.Lastly,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in KIRC.Out of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC patients.Moreover,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes.In addition to this,hub genes were also linked with different cisplatin resistance-causing pathways.Thus,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol,Acetaminophen,Acitretin,Cyclosporine,Azacitidine,Genistein,and Resveratrol drugs.As the pathogenesis of KIRC is complex,targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance,which might uplift overall survival among KIRC patients.
基金Suppo rted by National Natural Science Foundation of China(Grant Nos.51975305,51905289)Major Research Project of Shandong Province of China(Grant Nos.2019GGX104040,2019GSF108236)+2 种基金Major Science and Technology Innovation Engineering Projects of Shandong Province of China(Grant No.2019JZZY020111)the Natural Scie nce Foundation of Shandong Province(Grant Nos.ZR2020KE027 and ZR2020ME158)Applied Basic Research Youth Project of Qingdao Science and Technology Plan of China(Grant No.19-6-2-63-cg).
文摘Aluminum alloy is the main structural material of aircraft,launch vehicle,spaceship,and space station and is processed by milling.However,tool wear and vibration are the bottlenecks in the milling process of aviation aluminum alloy.The machining accuracy and surface quality of aluminum alloy milling depend on the cutting parameters,material mechanical properties,machine tools,and other parameters.In particular,milling force is the crucial factor to determine material removal and workpiece surface integrity.However,establishing the prediction model of milling force is important and difficult because milling force is the result of multiparameter coupling of process system.The research progress of cutting force model is reviewed from three modeling methods:empirical model,finite element simulation,and instantaneous milling force model.The problems of cutting force modeling are also determined.In view of these problems,the future work direction is proposed in the following four aspects:(1)high-speed milling is adopted for the thin-walled structure of large aviation with large cutting depth,which easily produces high residual stress.The residual stress should be analyzed under this particular condition.(2)Multiple factors(e.g.,eccentric swing milling parameters,lubrication conditions,tools,tool and workpiece deformation,and size effect)should be considered comprehensively when modeling instantaneous milling forces,especially for micro milling and complex surface machining.(3)The database of milling force model,including the corresponding workpiece materials,working condition,cutting tools(geometric figures and coatings),and other parameters,should be established.(4)The effect of chatter on the prediction accuracy of milling force cannot be ignored in thin-walled workpiece milling.(5)The cutting force of aviation aluminum alloy milling under the condition of minimum quantity lubrication(mql)and nanofluid mql should be predicted.
基金Supported by National Key Research and Development Program of China(Grant No.2020YFB2010500)National Natural Science Foundation of China(Grant Nos.51975305,51905289)+2 种基金Shandong Provincial Major Science and Technology Innovation Engineering Projects of China(Grant No.2019JZZY020111)Shandong Provincial Natural Science Foundation of China(Grant Nos.ZR2020KE027,ZR2020ME158,ZR2019PEE008)Applied Basic Research Youth Project of Qingdao Science and Technology Plan(Grant No.19-6-2-63-cg)。
文摘The application of cutting fluid in the field of engineering manufacturing has a history of hundreds of years,and it plays a vital role in the processing efficiency and surface quality of parts.Among them,water-based cutting fluid accounts for more than 90%of the consumption of cutting fluid.However,long-term recycling of water-based cutting fluid could easily cause deterioration,and the breeding of bacteria could cause the cutting fluid to fail,increase manufacturing costs,and even endanger the health of workers.Traditional bactericides could improve the biological stability of cutting fluids,but they are toxic to the environment and do not conform to the development trend of low-carbon manufacturing.Low-carbon manufacturing is inevitable and the direction of sustainable manufacturing.The use of nanomaterials,transition metal complexes,and physical sterilization methods on the bacterial cell membrane and genetic material could effectively solve this problem.In this article,the mechanism of action of additives and microbial metabolites was first analyzed.Then,the denaturation mechanism of traditional bactericides on the target protein and the effect of sterilization efficiency were summarized.Further,the mechanism of nanomaterials disrupting cell membrane potential was discussed.The effects of lipophilicity and the atomic number of transition metal complexes on cell membrane penetration were also summarized,and the effects of ultraviolet rays and ozone on the destruction of bacterial genetic material were reviewed.In other words,the bactericidal performance,hazard,degradability,and economics of various sterilization methods were comprehensively evaluated,and the potential development direction of improving the biological stability of cutting fluid was proposed.
文摘The unsteady flow of an incompressible fractional Maxwell fluid between two infinite coaxial cylinders is studied by means of integral transforms. The motion of the fluid is due to the inner cylinder that applies a time dependent tor- sional shear to the fluid. The exact solutions for velocity and shear stress are presented in series form in terms of some generalized functions. They can easily be particularized to give similar solutions for Maxwell and Newtonian fluids. Fi- nally, the influence of pertinent parameters on the fluid motion, as well as a comparison between models, is highlighted by graphical illustrations.
文摘The 3-D seismic dataset is a key tool to analyze and understand the mechanism of structural and stratigraphic hydrocarbon(HC)trapping in the subsurface.Conventionally used subsurface seismic characterization methods for fractures are based on the theory of effective anisotropy medium.The aim of this work is to improve the structural images with dense sampling of 3-D survey to evaluate structural and stratigraphic models for reservoir development to predict reservoir quality.The present study of the Gullfaks Field,located in the Norwegian North Sea Gullfaks sector,identifies the shallowest structural elements.The steepness of westward structural dip decreases eastward during the Upper Jurassic to Lower Cretaceous deposition.Reservoir sands consist of the Middle Jurassic deltaic deposits and Lower Jurassic fluvial channel and delta plain deposits.Sediment supply steadily prevails on sea-level rise and the succession displays a regressive trend indicated by a good continuous stacking pattern.The key factor for the development of reservoirs in the Gullfaks Field is fault transmissibility with spatially distributed pressure.The majority of mapped faults with sand-to-sand contacts are non-sealing,which provide restriction for the HC flow between the fault blocks.The traps for HC accumulation occur between the post-rift and syn-rift strata,i.e.antiform set by extensional system,unconformity trap at the top of syndeposition,and structural trap due to normal faults.Overall reservoir quality in the studied area is generally excellent with average 35%porosity and permeability in the Darcy range.Our findings are useful to better understand the development of siliciclastic reservoirs in similar geological settings worldwide.
文摘Geostatistical data plays a vibrant role for surface-based reservoir modeling through outcrop analogues,which is used to understand three-dimensional(3D)variability of petrophysical properties.The main purpose of this study is to improvise the surface-based 3D geo-modeling to demonstrate petrophysical characteristics and heterogeneities of Sandakan reservoirs,NW Borneo.We used point cloud data from Light Detection and Ranging(Li DAR)to build high-resolution virtual outcrop modeling(VOM)onto which we mapped 6 different lithofacies.Porosity and permeability of core plugs were measured to determine the average variance of petrophysical properties for each lithofacies.By utilizing the integration of VOMs analogues and petrophysical properties in Petrel^(TM),we demonstrated the distribution and associations of all lithofacies in pseudo wells that have inherent thin beds heterogeneities in 3D geocellular model.The results concluded that the heterogeneity of thin beds in lithofacies is dependent on porosity and permeability with input dataset.According to the final model,cross-bedding sandstone(CBS),hummocky cross-stratified sandstone(HCSS)and trough cross-bedding sandstone(TCBS)show good reservoir quality due to high porosity ranging from:25.6%to 20.4%and,19.3%-14.5%,and permeability ranging from:74.03 mD to 66.84 mD and,64.86 mD to 21.01 mD.In contrast,massive to weak laminae sandstone(MWLS)and bioturbated sandstone(BS)show fair to poor reservoir quality,caused baffling of surrounding mud sediments in the reservoir lithofacies.Results also revealed that Li DAR based VOM with petrophysical properties can significantly reduce the risk and minimize the cost of reservoir modeling in petroleum industry.
基金Supported by the Kohat University of Science and Technology,Kohat,PakistanInstitute of Biomedical and Genetic Engineering,Islamabad,Pakistan
文摘AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation.· METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome(USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat(STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene.· RESULTS: By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them,c.1304AC was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype.This, c.1304 A C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435(p.D435A) of its protein product.Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic.·CONCLUSION:Theidentificationofc.1304ACpathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is thefirst example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.
基金funded by Yayasan Universiti Teknologi PETRONAS(Y.U.T.P.),Cost Center 015LC0-278.
文摘An emerging definition of the fractal-fractional operator has been used in this study for the modeling of Casson fluid flow.The magnetohydrodynamics flow of Casson fluid has cogent in a channel where the motion of the upper plate generates the flow while the lower plate is at a static position.The proposed model is non-dimensionalized using the Pi-Buckingham theorem to reduce the complexity in solving the model and computation time.The non-dimensional fractal-fractional model with the power-law kernel has been solved through the Laplace transform technique.The Mathcad software has been used for illustration of the influence of various parameters,i.e.,Hartman number,fractal,fractional,and Casson fluid parameters on the velocity of fluid flow.Through graphs and tables,the results have been implemented and it is shown that the boundary conditions are fully satisfied.The results reveal that the flow velocity is decreasing with the increasing values of the Hartman number and is increasing with the increasing values of the Casson fluid parameter.The findings of the fractal-fractional model have elucidated that the memory effect of the flow model has higher quality than the simple fractional and classical models.Furthermore,to show the validity of the obtained closed-form solutions,special cases have been obtained which are in agreement with the already published solutions.
文摘This paper establishes the velocity field and the adequate shear stress corresponding to the motion of an Oldroyd-B fluid between two infinite coaxial circular cylinders by means of finite Hankel transforms. The flow of the fluid is produced by the inner cylinder which applies a time-dependent longitudinal shear stress to the fluid. The exact analytical solutions, presented in series form in terms of Bessel functions, satisfy all imposed initial and boundary conditions. The general solutions can be easily specialized to give similar solutions for Maxwell, second grade and Newtonian fluids performing the same motion. Finally, some characteristics of the motion as well as the influence of the material parameters on the behavior of the fluid motion are graphically illustrated.
基金the following organizations:the National Natural Science Foundation of China(Nos.51975305,51905289)the Major Research Project of Shandong Province(Nos.2019GGX104040 and2019GSF108236)+2 种基金the Shandong Provincial Natural Science Foundation of China(Nos.ZR2019PEE008)Major Science and Technology Innovation Engineering Projects of Shandong Province(No.2019JZZY020111)Applied Basic Research Youth Project of Qingdao Science and Technology Plan(No.19-6-2-63-cg)。
文摘Corundum abrasives with good chemical stability can be fabricated into various free abrasives and bonded abrasive tools that are widely used in the precision machining of various parts.However,these abrasives cannot satisfy the machining requirements of difficult-to-machine materials with high hardness,high strength,and strong wearing resistance.Although superhard abrasives can machine the above-mentioned materials,their dressing and manufacturing costs are high.By contrast,ceramic corundum abrasives fabricated by sol–gel method is a costeffective product between conventional and superhard abrasives.Ceramic corundum abrasives exhibit self-sharpening and high toughness.In this review,the optimization methods of ceramic corundum abrasive properties are introduced from three aspects:precursor synthesis,particle shaping,and sintering.Firstly,the functional mechanism of seeds and additives on the microstructural and mechanical properties of abrasives is analyzed.Specifically,seeds can reduce the phase transition temperature and improve fracture toughness.The grain size and uniformly dense structure can be controlled by applying an appropriate amount of multicomponent additives.Then,the urgent need of engineering application and machinability of special shape ceramic corundum abrasives is reviewed,and three methods of abrasive shaping are summarized.The micromold replication technique is highly advanced and can be used to prepare functional abrasives.Additionally,the influence of a new sintering method,namely,two-step sintering technique,on the microstructural and mechanical performance of ceramic corundum abrasives is summarized.Finally,the challenge and developmental trend of the optimization of ceramic corundum abrasives are prospected.
基金This paper was financially supported by the National Natural Science Foundation of China(Grant Nos.51975305 and 51905289)the Key Project of Shandong Province,China(Grant No.ZR2020KE027)+2 种基金the Major Research Project of Shandong Province,China(Grant Nos.2019GGX104040 and 2019GSF108236)the Natural Science Foundation of Shandong Province,China(Grant No.ZR2020ME158)the Applied Basic Research Youth Project of Qingdao Science and Technology Plan,China(Grant No.19-6-2-63-cg).
文摘Cutting fluid plays a cooling-lubrication role in the cutting of metal materials.However,the substantial usage of cutting fluid in traditional flood machining seriously pollutes the environment and threatens the health of workers.Environmental machining technologies,such as dry cutting,minimum quantity lubrication(MQL),and cryogenic cooling technology,have been used as substitute for flood machining.However,the insufficient cooling capacity of MQL with normal-temperature compressed gas and the lack of lubricating performance of cryogenic cooling technology limit their industrial application.The technical bottleneck of mechanical-thermal damage of difficult-to-cut materials in aerospace and other fields can be solved by combining cryogenic medium and MQL.The latest progress of cryogenic minimum quantity lubrication(CMQL)technology is reviewed in this paper,and the key scientific issues in the research achievements of CMQL are clarified.First,the application forms and process characteristics of CMQL devices in turning,milling,and grinding are systematically summarized from traditional settings to innovative design.Second,the cooling-lubrication mechanism of CMQL and its influence mechanism on material hardness,cutting force,tool wear,and workpiece surface quality in cutting are extensively revealed.The effects of CMQL are systematically analyzed based on its mechanism and application form.Results show that the application effect of CMQL is better than that of cryogenic technology or MQL alone.Finally,the prospect,which provides basis and support for engineering application and development of CMQL technology,is introduced considering the limitations of CMQL.
文摘To eliminate the negative effect of traditional metal-working fluids and achieve sustainable manufacturing,the usage of nano-enhanced biolubricant(NEBL)is widely researched in minimum quantify lubrication(MQL)machining.It's improved tool wear and surface integrity have been preliminarily verified by experimental studies.The previous review papers also concluded the major influencing factors of processability including nano-enhancer and lubricant types,NEBL concentration,micro droplet size,and so on.Nevertheless,the complex action of NEBL,from preparation,atomization,infiltration to heat transfer and anti-friction,is indistinct which limits preparation of process specifications and popularity in factories.Especially in the complex machining process,in-depth understanding is difficult and meaningful.To fll this gap,this paper concentrates on the comprehensive quantitative assessment of processability based on tribological,thermal,and machined surface quality aspects for NEBL application in turning,milling,and grinding.Then it attempts to answer mechanisms systematically considering multi-factor influence of molecular structure,physicochemical properties,concentration,and dispersion.Firstly,this paper reveals advanced lubrication and heat transfer mechanisms of NEBL by quantitative comparison with biolubricant-based MQL machining.Secondly,the distinctive filmformation,atomization,and infiltration mechanisms of NEBL,as distinguished from metal-working fluid,are clarified combining with its unique molecular structure and physical properties.Furtherly,the process optimization strategy is concluded based on the synergistic relationship analysis among process variables,physicochemical properties,machining mechanisms,and performance of NEBL.Finally,the future development directions are put forward aiming at current performance limitations of NEBL,which requires improvement on preparation and jet methods respects.This paper will help scientists deeply understand effective mechanism,formulate process specifications,and find future development trend of this technology.
基金co-supported by the National Natural Science Foundation of China(No.51405226)Postgraduate Research&Practice Innovation Program of Jiangsu Province of China(No.KYCX19_0165)。
文摘Owing to reliability and high strength-to-weight ratio,large thin-walled components are widely used in the aviation and aerospace industry.Due to the complex features and sequence involved in the machining process of large thin-walled components,machining deformation of component is easy to exceed the specification.In order to address the problem,it is important to retain the appropriate finishing allowance.To find the overall machining deformation,finishing allowance-induced deformation(web finishing allowance,sidewall finishing allowance)and initial residual stress-induced deformation were considered as major factors.Meanwhile,machined surface residual stress-induced deformation,clamping stress-induced deformation,thermal deformation,gravity-induced deformation and inertial force-induced deformation were neglected in the optimization model.Six-peak Gaussian function was introduced to fit the initial residual stress.Based upon the obtained function of initial residual stress,a deformation prediction model between initial residual stress and finishing allowance was established to attain the finishing allowanceinduced deformation.In addition,linear programming optimization model based on the simplex algorithm was developed to optimize the overall machining deformation.Results have concluded that the overall machining deformation reached the minimum value when sidewall finishing allowance and web finishing allowance varied between 1 and 2 mm.Additionally,web finishing allowance-induced deformation and sidewall finishing allowance-induced deformation were1.05 mm and 0.7 mm.Furthermore,the machining deformation decreased to 0.3–0.38 mm with the application of optimized finishing allowance allocation strategy,which made 39–56%reduction of the overall machining deformation compared to that in conventional method.
基金supported by the National Natural Science Foundation of China(Nos.51975305 and 51905289)the Major Research Project of Shandong Province(No.2019GGX104040)+2 种基金the Major Science and Technology Innovation Engineering Projects of Shandong Province(No.2019JZZY020111)the Natural Science Foundation of Shandong Province(Nos.ZR2020KE027 and ZR2020ME158)the Applied Basic Research Youth Project of Qingdao science and technology plan(No.19-6-2-63-cg)。
文摘It is an inevitable trend of sustainable manufacturing to replace flood and dry machining with minimum quantity lubrication(MQL)technology.Nevertheless,for aeronautical difficult-tomachine materials,MQL couldn’t meet the high demand of cooling and lubrication due to high heat generation during machining.Nano-biolubricants,especially non-toxic carbon group nano-enhancers(CGNs)are used,can solve this technical bottleneck.However,the machining mechanisms under lubrication of CGNs are unclear at complex interface between tool and workpiece,which characterized by high temperature,pressure,and speed,limited its application in factories and necessitates in-depth understanding.To fill this gap,this study concentrates on the comprehensive quantitative assessment of tribological characteristics based on force,tool wear,chip,and surface integrity in titanium alloy and nickel alloy machining and attempts to answer mechanisms systematically.First,to establish evaluation standard,the cutting mechanisms and performance improvement behavior covering antifriction,antiwear,tool failure,material removal,and surface formation of MQL were revealed.Second,the unique film formation and lubrication behaviors of CGNs in MQL turning,milling,and grinding are concluded.The influence law of molecular structure and micromorphology of CGNs was also answered and optimized options were recommended by considering diverse boundary conditions.Finally,in view of CGNs limitations in MQL,the future development direction is proposed,which needs to be improved in thermal stability of lubricant,activity of CGNs,controllable atomization and transportation methods,and intelligent formation of processing technology solutions.