Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sortin...On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.展开更多
The use of‘Electrostatic tweezers'is a promising tool for droplet manipulation,but it faces many limitations in manipulating droplets on superhydrophobic surfaces.Here,we achieve noncontact and multifunctional dr...The use of‘Electrostatic tweezers'is a promising tool for droplet manipulation,but it faces many limitations in manipulating droplets on superhydrophobic surfaces.Here,we achieve noncontact and multifunctional droplet manipulation on Nepenthes-inspired lubricated slippery surfaces via triboelectric electrostatic tweezers(TETs).The TET manipulation of droplets on a slippery surface has many advantages over electrostatic droplet manipulation on a superhydrophobic surface.The electrostatic field induces the redistribution of the charges inside the neutral droplet,which causes the triboelectric charged rod to drive the droplet to move forward under the electrostatic force.Positively or negatively charged droplets can also be driven by TET based on electrostatic attraction and repulsion.TET enables us to manipulate droplets under diverse conditions,including anti-gravity climb,suspended droplets,corrosive liquids,low-surface-tension liquids(e.g.ethanol with a surface tension of 22.3 mN·m^(-1)),different droplet volumes(from 100 nl to 0.5 ml),passing through narrow slits,sliding over damaged areas,on various solid substrates,and even droplets in an enclosed system.Various droplet-related applications,such as motion guidance,motion switching,droplet-based microreactions,surface cleaning,surface defogging,liquid sorting,and cell labeling,can be easily achieved with TETs.展开更多
As an accurate 2D/3D fabrication tool,inkjet printing technology has great potential in preparation of micro electronic devices.The morphology of droplets produced by the inkjet printer has a great impact on the accur...As an accurate 2D/3D fabrication tool,inkjet printing technology has great potential in preparation of micro electronic devices.The morphology of droplets produced by the inkjet printer has a great impact on the accuracy of deposition.In this study,the drop-on-demand(DoD)inkjet simulation model was established,and the accuracy of the simulation model was verified by corresponding experiments.The simulation result shows that the velocity of the droplet front and tail,as well as the time to disconnect from the nozzle is mainly affected by density(ρ),viscosity(μ)and surface tension(σ)of droplets.When the liquid filament is about to disconnect from the nozzle,the filament length and filament front velocity are found to have a linear correlation withσ/ρμand ln(ρ/(μσ1/2)).展开更多
The adsorption process of droplets on the liquid-liquid interface and phase separation process can regulate the spatial distribution of the fluid system,which are crucial for chemical engineering.However,the cross-lin...The adsorption process of droplets on the liquid-liquid interface and phase separation process can regulate the spatial distribution of the fluid system,which are crucial for chemical engineering.However,the cross-linking reaction,which is widely used in the field of polymers,can change the physical properties of the fluids and affect the flow behavior accordingly.A configuration of microchannels is designed to conveniently generate uniform droplets in one phase of the parallel flow.The flow behavior of the adsorption process of sodium alginate droplets on the liquid-liquid interface is investigated,and the subsequent process of phase separation is studied.In the process of droplet adsorption,the crosslinking reaction occurs synchronously,which makes the droplet viscosity and the elasticity modules of the droplet surface increase,thus affecting the dynamics of the adsorption process and the equilibrium shape of the droplet.The variation of the adsorption length with time is divided into three stages,which all conform to power law relationship.The exponents of the second and third stages deviate from the results of the Tanner's law.The flow pattern maps of droplet adsorption and phase separation are drawn,and the operating ranges of complete adsorption and complete separation are provided.This study provides a theoretical basis for further studying the flow behavior of droplets with cross-linking reaction in a microchannel.展开更多
Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants a...Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants and nozzles on droplet spectrum remain unclear.Here,we established the relationship between droplet spectrum evolution and liquid atomization by investigating the typical characteristics of droplet diameter distribution near the nozzle.Based on this,the regulation mechanisms of distinctive pesticide adjuvants on droplet spectrum were clarified,and the corresponding drift reduction performances were quantitively evaluated by wind tunnel experiments.It shows that the droplet diameter firstly shifts to the smaller due to the liquid sheet breakup and then prefers to increase caused by droplet interactions.Reducing the surface tension of sprayed liquid facilitates the uniform liquid breakup and increasing the viscosity inhibits the liquid deformation,which prolong the atomization process and effectively improve the droplet spectrum.As a result,the drift losses of flat-fan and hollow cone nozzles are reduced by about 50%after adding organosilicon and vegetable oil adjuvants.By contrast,the air induction nozzle shows a superior anti-drift ability,regardless of distinctive adjuvants.Our findings provide insights into rational adjuvant design and nozzle selection in the field application.展开更多
Droplet transport still faces numerous challenges,such as a limited transport distance,large volume loss,and liquid contamination.Inspired by the principle of‘synergistic biomimetics’,we propose a design for a platf...Droplet transport still faces numerous challenges,such as a limited transport distance,large volume loss,and liquid contamination.Inspired by the principle of‘synergistic biomimetics’,we propose a design for a platform that enables droplets to be self-propelled.The orchid leaf-like three-dimensional driving structure provides driving forces for the liquid droplets,whereas the lotus leaf-like superhydrophobic surface prevents liquid adhesion,and the bamboo-like nodes enable long-distance transport.During droplet transport,no external energy input is required,no fluid adhesion or residue is induced,and no contamination or mass loss of the fluid is caused.We explore the influence of various types and parameters of wedge structures on droplet transportation,the deceleration of droplet speed at nodal points,and the distribution of internal pressure.The results indicate that the transport platform exhibits insensitivity to pH value and temperature.It allows droplets to be transported with varying curvatures in a spatial environment,making it applicable in tasks like target collection,as well as load,fused,anti-gravity,and long-distance transport.The maximum droplet transport speed reached(58±5)mm·s^(−1),whereas the transport distance extended to(136±4)mm.The developed platform holds significant application prospects in the fields of biomedicine and chemistry,such as high-throughput screening of drugs,genomic bioanalysis,microfluidic chip technology for drug delivery,and analysis of biological samples.展开更多
The study of a droplet spreading on a circular cylinder under gravity was carried out using the pseudo-potential lattice Boltzmann high-density ratios multiphase model with a non-ideal Peng–Robinson equation of state...The study of a droplet spreading on a circular cylinder under gravity was carried out using the pseudo-potential lattice Boltzmann high-density ratios multiphase model with a non-ideal Peng–Robinson equation of state. The calculation results indicate that the motion of the droplet on the cylinder can be divided into three stages: spreading, sliding, and aggregating.The contact length and contact time of a droplet on a cylindrical surface can be affected by factors such as the wettability gradient of the cylindrical wall, the Bond number, and droplet size. Furthermore, phase diagrams showing the relationship between Bond number, cylinder wall wettability gradient, and contact time as well as maximum contact length for three different droplet sizes are given. A theoretical foundation for additional research into the heat and mass transfer process between the droplet and the cylinder can be established by comprehending the variable rules of maximum contact length and contact time.展开更多
Electron beam–directed energy deposition(EB–DED)has emerged as a promising wire-based metal additive manufacturing technique.However,the effects of EBs on pendant droplets at wire tips have not yet been determined.T...Electron beam–directed energy deposition(EB–DED)has emerged as a promising wire-based metal additive manufacturing technique.However,the effects of EBs on pendant droplets at wire tips have not yet been determined.The aim of this study is to enhance the understanding of this action by analyzing the mechanism of droplet oscillation.The pendant droplet oscillation phenomenon hinders the stable transfer of droplets to the molten pool and limits the feasibility of manufacturing complex lattice structures by EB–DED.Hence,another aim of this study is to create an oscillation suppression method.An escalating asymmetric amplitude is the main characteristic of droplet oscillation.The primary oscillationinducing force is the recoil force generated from the EB-acted local surface of the droplet.The physical mechanism of this force is the rapid increase and uneven distribution of the local surface temperature caused by the partial action of the EB.The prerequisites for droplet oscillation include vacuum conditions,high power densities,and bypass wire feeding processes.The proposed EB–dynamic surrounding melting(DSM)method can be applied to conveniently and effectively suppress oscillations,enable the accurate transfer of droplets to the molten pool,and achieve stable processes for preparing the strut elements of lattice structures.Lowering the temperature and improving the uniformity of its distribution are the mechanisms of oscillation suppression in EB–DSM.In this study,the physical basis for interpreting the mechanism by which EBs act on droplets and the technical basis for using EB–DED to prepare complex lattice structure parts are provided.展开更多
Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent ye...Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.展开更多
The controllable transfer of droplets on the surface of objects has a wide application prospect in the fields of microfluidic devices,fog collection and so on.The Leidenfrost effect can be utilized to significantly re...The controllable transfer of droplets on the surface of objects has a wide application prospect in the fields of microfluidic devices,fog collection and so on.The Leidenfrost effect can be utilized to significantly reduce motion resistance.However,the use of 3D structures limits the widespread application of self-propulsion based on Leidenfrost droplets in microelectromechanical system.To manipulate Leidenfrost droplets,it is necessary to create 2D or quasi-2D geometries.In this study,femtosecond laser is applied to fabricate a surface with periodic hydrophobicity gradient(SPHG),enabling directional self-propulsion of Leidenfrost droplets.Flow field analysis within the Leidenfrost droplets reveals that the vapor layer between the droplets and the hot surface can be modulated by the SPHG,resulting in directional propulsion of the inner gas.The viscous force between the gas and liquid then drives the droplet to move.展开更多
In continuous casting production,droplet characteristics are important parameters for evaluating the nozzle atomization quality,and have a significant impact on the secondary cooling effect and the slab quality.In ord...In continuous casting production,droplet characteristics are important parameters for evaluating the nozzle atomization quality,and have a significant impact on the secondary cooling effect and the slab quality.In order to study the behavior of atomized droplets after reaching the slab surface and to optimize the spray cooling effect,the influence of droplet diameter and droplet velocity on the migration behavior of droplets in the secondary cooling zone was analyzed by FLUENT software.Results show that the droplets in the spray zone and on the slab surface are mainly concentrated in the center,thus,the liquid volume fraction in the center is higher than that of either side.As the droplet diameter increases,the region of high liquid volume fraction on the slab surface becomes wider,and the liquid phase distribution in the slab width direction becomes uneven.Although increasing the droplet velocity at the nozzle exit has little effect on droplet diffusion in the spray zone,the distribution becomes more uneven due to more liquid reaches the slab surface per unit time.A prediction formula of the maximum water flow rate on the slab surface for specific droplet characteristics was proposed based on dimensionless analysis and validated by simulated data.A nozzle spacing of 210 mm was recommended under the working conditions in this study,which ensures effective coverage of the spray water over the slab surface and enhances the distribution uniformity of water flow rate in the transverse direction.展开更多
Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabo...Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.展开更多
In this study,numerical simulations of the pinching-off phenomena displayed by the dispersed phase in a continuous phase have been conducted using COMSOL Multiphysics(level-set method).Four flow patterns,namely“drop ...In this study,numerical simulations of the pinching-off phenomena displayed by the dispersed phase in a continuous phase have been conducted using COMSOL Multiphysics(level-set method).Four flow patterns,namely“drop flow”,“jet flow”,“squeeze flow”,and“co-flow”,have been obtained for different flow velocity ratios,channel diameter ratios,density ratios,viscosity ratios,and surface tension.The flow pattern map of two-phase flow in coaxial microchannels has been obtained accordingly,and the associated droplet generation process has been critically discussed considering the related frequency,diameter,and pinch-off length.In particular,it is shown that the larger the flow velocity ratio,the smaller the diameter of generated droplets and the shorter the pinch-off length.The pinch-off length of a droplet is influenced by the channel diameter ratio and density ratio.The changes in viscosity ratio have a negligible influence on the droplet generation pinching frequency.With an increase in surface tension,the frequency of generation and pinch-off length of droplets decrease,but for small surface tension the generation diameter of droplet increases.展开更多
Gene synthesis has provided important contributions in various fields including genomics and medicine. Current genes are 7 - 30 cents depending on the assembly and sequencing methods performed. Demand for gene synthes...Gene synthesis has provided important contributions in various fields including genomics and medicine. Current genes are 7 - 30 cents depending on the assembly and sequencing methods performed. Demand for gene synthesis has been increasing for the past few decades, yet available methods remain expensive. A solution to this problem involves microchip-derived oligonucleotides (oligos), an oligo pool with a substantial number of oligo fragments. Microchips have been proposed as a tool for gene synthesis, but this approach has been criticized for its high error rate during sequencing. This study tests a possible cost-effective method for gene synthesis utilizing fragment assembly and golden gate assembly, which can be employed for quicker manufacturing and efficient execution of genes in the near future. The droplet method was tested in two trials to determine the viability of the method through the accuracy of the oligos sequenced. A preliminary research experiment was performed to determine the efficacy of oligo lengths ranging from two to four overlapping oligos through Gibson assembly. Of the three oligo lengths tested, only two fragment oligos were correctly sequenced. Two fragment oligos were used for the second experiment, which determined the efficacy of the droplet method in reducing gene synthesis cost and speed. The first trial utilized a high-fidelity polymerase and resulted in 3% correctly sequenced oligos, so the second trial utilized a non-high-fidelity polymerase, resulting in 8% correctly sequenced oligos. After calculating, the cost of gene synthesis lowers down to 0.8 cents/base. The final calculated cost of 0.8 cents/base is significantly cheaper than other manufacturing costs of 7 - 30 cents/base. Reducing the cost of gene synthesis provides new insight into the cost-effectiveness of present technologies and protocols and has the potential to benefit the fields of bioengineering and gene therapy.展开更多
In fog, visibility is reduced. This reduction in visibility is measured by the meteorological optical range (MOR), which is important for studying human perception and various sensors in foggy conditions. The Cerema P...In fog, visibility is reduced. This reduction in visibility is measured by the meteorological optical range (MOR), which is important for studying human perception and various sensors in foggy conditions. The Cerema PAVIN Fog & Rain platform is capable of producing calibrated fog in order to better analyses it and understand its consequences. The problem is that the droplets produced by the platform are not large enough to resemble real fog. This can have a major impact on measurements since the interaction between electromagnetic waves and fog depends on the wavelength and diameter of the droplets. To remedy this, Cerema is building a new platform with new equipment capable of generating fog. This study analyses different nozzles and associated usage parameters such as the type of water used and the pressure used. The aim is to select the best nozzle with the associated parameters for producing large-diameter droplets and therefore more realistic fog.展开更多
This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numer...This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numerical simulations are exploited to investigate situations with a velocity varying from 0.004 to 1.6 m/s for the continuous phase and from 0.004 to 0.8 m/s for the dispersed phase,viscosity ratios(0.668,1,6.689,10,66.899),contact angle 80°<θ<270°and four different canal size ratios(1,1.5,2 and 4).The results show that canal size influences droplet size and the generation rate.The contact angle has an impact on the form and the quality of generated droplets.Moreover,the relationship between velocity and viscosity ratios,droplet size,and generation rate is non-monotonic.展开更多
High efficiency welding has always been one of the hot research subjects at home and overseas. Aiming at the problem of unstable droplet rotating spray transfer process in 450 A thin wire metal active gas arc(MAG) wel...High efficiency welding has always been one of the hot research subjects at home and overseas. Aiming at the problem of unstable droplet rotating spray transfer process in 450 A thin wire metal active gas arc(MAG) welding, a three-dimensional arc-droplet coupled model is established in this paper on the base of fluid dynamics to conduct numerical analysis for droplet transfer behavior with external magnetic controlled MAG welding, and used high-speed camera system to verify the simulation results. The results indicate that without external magnetic field, the droplet is transferred by the way of rotating spray, the arc is changeable and the spatter is serious. The electromagnetic force accelerates the radial liquid beam rotation under direct current(DC) magnetic field, and increases the angle between liquid beam and welding wire axis. Meanwhile, the rotation frequency of the liquid beam reaches 400 Hz, the area of arc column and heat loss increase under DC magnetic field. Based on the alternating magnetic field, the arc is the “bell shaped”, the arc stiffness raises, its temperature achieves 26 000 K, and the maximum speed of the liquid stream beam can reach 500 m/s. And the droplet transfer is more stable, the spatter significantly reduces, and welding quality is effectively improved.展开更多
BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous stud...BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.展开更多
Energetic materials pose challenges in preparation and handling due to their contradictory properties of high-energy and low-sensitivity.The emergence of co-crystal explosives is a new opportunity to change this situa...Energetic materials pose challenges in preparation and handling due to their contradictory properties of high-energy and low-sensitivity.The emergence of co-crystal explosives is a new opportunity to change this situation.If the co-crystal explosive is coated into spherical particles with uniform particle size distribution,this contradiction can be further reduced.Therefore,binder-coated hexanitrohexaazaisowurtzitane/2,4,6-trinitrotoluene(CL-20/TNT)co-crystal microspheres were prepared by droplet microfluidic technology in this work.The coating effects of different binder formulations of nitrocellulose(NC)and NC/fluorine rubber(F2604)on the co-crystal spheres were studied.The scanning electron microscopy(SEM)results showed that the use of droplet microfluidic technology with the above binders can provide co-crystal microspheres with regular spherical morphology,uniform particle size distribution and good dispersion.X-ray diffraction(XRD),fourier-transform infrared(FT-IR),differential scanning calorimetry(DSC)and thermo-gravimetric(TG)methods were employed to compare the properties of the co-crystal microspheres,raw material and pure co-crystal.The formation of CL-20/TNT co-crystal in the microspheres was confirmed,and the co-crystal microspheres exhibited better thermal stability than the raw material and pure co-crystal.In addition,the mechanical sensitivity and combustion performance of the co-crystal microspheres were further studied.The results showed that the co-crystal microspheres were more insensitive than CL-20 and pure co-crystal,and displayed excellent self-sustained combustion performance and theoretical detonation performance.This study provides a new method for the fast,simple and one-step preparation of CL-20/TNT co-crystal microspheres,with binder coating,uniform particle size distribution,and excellent performance level.展开更多
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金The authors acknowledge the financial support from the NationalNatural Science Foundation ofChina(No.52275562)the Technology Innovation Fund of Huazhong University of Science and Technology(No.2022JYCXJJ015).
文摘On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.
基金supported by the USTC Research Funds of the Double First-Class Initiative(Nos.YD2090002013,YD234000009)the National Natural Science Foundation of China(Nos.61927814,62325507,52122511,U20A20290,62005262)。
文摘The use of‘Electrostatic tweezers'is a promising tool for droplet manipulation,but it faces many limitations in manipulating droplets on superhydrophobic surfaces.Here,we achieve noncontact and multifunctional droplet manipulation on Nepenthes-inspired lubricated slippery surfaces via triboelectric electrostatic tweezers(TETs).The TET manipulation of droplets on a slippery surface has many advantages over electrostatic droplet manipulation on a superhydrophobic surface.The electrostatic field induces the redistribution of the charges inside the neutral droplet,which causes the triboelectric charged rod to drive the droplet to move forward under the electrostatic force.Positively or negatively charged droplets can also be driven by TET based on electrostatic attraction and repulsion.TET enables us to manipulate droplets under diverse conditions,including anti-gravity climb,suspended droplets,corrosive liquids,low-surface-tension liquids(e.g.ethanol with a surface tension of 22.3 mN·m^(-1)),different droplet volumes(from 100 nl to 0.5 ml),passing through narrow slits,sliding over damaged areas,on various solid substrates,and even droplets in an enclosed system.Various droplet-related applications,such as motion guidance,motion switching,droplet-based microreactions,surface cleaning,surface defogging,liquid sorting,and cell labeling,can be easily achieved with TETs.
基金supported by the Tsinghua University–Toyota Research Center Project。
文摘As an accurate 2D/3D fabrication tool,inkjet printing technology has great potential in preparation of micro electronic devices.The morphology of droplets produced by the inkjet printer has a great impact on the accuracy of deposition.In this study,the drop-on-demand(DoD)inkjet simulation model was established,and the accuracy of the simulation model was verified by corresponding experiments.The simulation result shows that the velocity of the droplet front and tail,as well as the time to disconnect from the nozzle is mainly affected by density(ρ),viscosity(μ)and surface tension(σ)of droplets.When the liquid filament is about to disconnect from the nozzle,the filament length and filament front velocity are found to have a linear correlation withσ/ρμand ln(ρ/(μσ1/2)).
基金supported by the National Natural Science Foundation of China(92034303,21978197)。
文摘The adsorption process of droplets on the liquid-liquid interface and phase separation process can regulate the spatial distribution of the fluid system,which are crucial for chemical engineering.However,the cross-linking reaction,which is widely used in the field of polymers,can change the physical properties of the fluids and affect the flow behavior accordingly.A configuration of microchannels is designed to conveniently generate uniform droplets in one phase of the parallel flow.The flow behavior of the adsorption process of sodium alginate droplets on the liquid-liquid interface is investigated,and the subsequent process of phase separation is studied.In the process of droplet adsorption,the crosslinking reaction occurs synchronously,which makes the droplet viscosity and the elasticity modules of the droplet surface increase,thus affecting the dynamics of the adsorption process and the equilibrium shape of the droplet.The variation of the adsorption length with time is divided into three stages,which all conform to power law relationship.The exponents of the second and third stages deviate from the results of the Tanner's law.The flow pattern maps of droplet adsorption and phase separation are drawn,and the operating ranges of complete adsorption and complete separation are provided.This study provides a theoretical basis for further studying the flow behavior of droplets with cross-linking reaction in a microchannel.
基金financially supported by the National Key Research and Development Program of China(2017YFD0200304)。
文摘Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants and nozzles on droplet spectrum remain unclear.Here,we established the relationship between droplet spectrum evolution and liquid atomization by investigating the typical characteristics of droplet diameter distribution near the nozzle.Based on this,the regulation mechanisms of distinctive pesticide adjuvants on droplet spectrum were clarified,and the corresponding drift reduction performances were quantitively evaluated by wind tunnel experiments.It shows that the droplet diameter firstly shifts to the smaller due to the liquid sheet breakup and then prefers to increase caused by droplet interactions.Reducing the surface tension of sprayed liquid facilitates the uniform liquid breakup and increasing the viscosity inhibits the liquid deformation,which prolong the atomization process and effectively improve the droplet spectrum.As a result,the drift losses of flat-fan and hollow cone nozzles are reduced by about 50%after adding organosilicon and vegetable oil adjuvants.By contrast,the air induction nozzle shows a superior anti-drift ability,regardless of distinctive adjuvants.Our findings provide insights into rational adjuvant design and nozzle selection in the field application.
基金supported by the National Natural Science Foundation of China(NSFC,Grant No.52275420)the National Key R&D Program of China(2022YFB3403304)the Natural Science Foundation of Hunan Province[Grant No.2022JJ30136].
文摘Droplet transport still faces numerous challenges,such as a limited transport distance,large volume loss,and liquid contamination.Inspired by the principle of‘synergistic biomimetics’,we propose a design for a platform that enables droplets to be self-propelled.The orchid leaf-like three-dimensional driving structure provides driving forces for the liquid droplets,whereas the lotus leaf-like superhydrophobic surface prevents liquid adhesion,and the bamboo-like nodes enable long-distance transport.During droplet transport,no external energy input is required,no fluid adhesion or residue is induced,and no contamination or mass loss of the fluid is caused.We explore the influence of various types and parameters of wedge structures on droplet transportation,the deceleration of droplet speed at nodal points,and the distribution of internal pressure.The results indicate that the transport platform exhibits insensitivity to pH value and temperature.It allows droplets to be transported with varying curvatures in a spatial environment,making it applicable in tasks like target collection,as well as load,fused,anti-gravity,and long-distance transport.The maximum droplet transport speed reached(58±5)mm·s^(−1),whereas the transport distance extended to(136±4)mm.The developed platform holds significant application prospects in the fields of biomedicine and chemistry,such as high-throughput screening of drugs,genomic bioanalysis,microfluidic chip technology for drug delivery,and analysis of biological samples.
文摘The study of a droplet spreading on a circular cylinder under gravity was carried out using the pseudo-potential lattice Boltzmann high-density ratios multiphase model with a non-ideal Peng–Robinson equation of state. The calculation results indicate that the motion of the droplet on the cylinder can be divided into three stages: spreading, sliding, and aggregating.The contact length and contact time of a droplet on a cylindrical surface can be affected by factors such as the wettability gradient of the cylindrical wall, the Bond number, and droplet size. Furthermore, phase diagrams showing the relationship between Bond number, cylinder wall wettability gradient, and contact time as well as maximum contact length for three different droplet sizes are given. A theoretical foundation for additional research into the heat and mass transfer process between the droplet and the cylinder can be established by comprehending the variable rules of maximum contact length and contact time.
基金supported by the National Natural Science Foundation of China(52375349)the Beijing Municipal Natural Science Foundation(3222008).
文摘Electron beam–directed energy deposition(EB–DED)has emerged as a promising wire-based metal additive manufacturing technique.However,the effects of EBs on pendant droplets at wire tips have not yet been determined.The aim of this study is to enhance the understanding of this action by analyzing the mechanism of droplet oscillation.The pendant droplet oscillation phenomenon hinders the stable transfer of droplets to the molten pool and limits the feasibility of manufacturing complex lattice structures by EB–DED.Hence,another aim of this study is to create an oscillation suppression method.An escalating asymmetric amplitude is the main characteristic of droplet oscillation.The primary oscillationinducing force is the recoil force generated from the EB-acted local surface of the droplet.The physical mechanism of this force is the rapid increase and uneven distribution of the local surface temperature caused by the partial action of the EB.The prerequisites for droplet oscillation include vacuum conditions,high power densities,and bypass wire feeding processes.The proposed EB–dynamic surrounding melting(DSM)method can be applied to conveniently and effectively suppress oscillations,enable the accurate transfer of droplets to the molten pool,and achieve stable processes for preparing the strut elements of lattice structures.Lowering the temperature and improving the uniformity of its distribution are the mechanisms of oscillation suppression in EB–DSM.In this study,the physical basis for interpreting the mechanism by which EBs act on droplets and the technical basis for using EB–DED to prepare complex lattice structure parts are provided.
基金funded by the National Natural Science Foundation of China(32102646)the Natural Science Foundation of Guangdong Province,China(2020A1515110315)+1 种基金the Start-up Research Project of Maoming Laboratory,China(2021TDQD002)the China Agriculture Research System of MOF and MARA(cars-35)。
文摘Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.
基金supported by the Beijing Municipal Natural Science Foundation(JQ20015)National Key Research and Development Program of China(No.2022YFB4601300)+3 种基金the National Science Fund for Distinguished Young Scholars(No.52325505)the National Natural Science Foundation of China(NSFC)(No.52075041)the Joint Funds of the National Natural Science Foundation of China(Grant No.U2037205)the Open Project Program of Wuhan National Laboratory for Optoelectronics(No2021WNLOKF016)。
文摘The controllable transfer of droplets on the surface of objects has a wide application prospect in the fields of microfluidic devices,fog collection and so on.The Leidenfrost effect can be utilized to significantly reduce motion resistance.However,the use of 3D structures limits the widespread application of self-propulsion based on Leidenfrost droplets in microelectromechanical system.To manipulate Leidenfrost droplets,it is necessary to create 2D or quasi-2D geometries.In this study,femtosecond laser is applied to fabricate a surface with periodic hydrophobicity gradient(SPHG),enabling directional self-propulsion of Leidenfrost droplets.Flow field analysis within the Leidenfrost droplets reveals that the vapor layer between the droplets and the hot surface can be modulated by the SPHG,resulting in directional propulsion of the inner gas.The viscous force between the gas and liquid then drives the droplet to move.
基金funded by the National Natural Science Foundation of China(Nos.51974213 and 52174324)。
文摘In continuous casting production,droplet characteristics are important parameters for evaluating the nozzle atomization quality,and have a significant impact on the secondary cooling effect and the slab quality.In order to study the behavior of atomized droplets after reaching the slab surface and to optimize the spray cooling effect,the influence of droplet diameter and droplet velocity on the migration behavior of droplets in the secondary cooling zone was analyzed by FLUENT software.Results show that the droplets in the spray zone and on the slab surface are mainly concentrated in the center,thus,the liquid volume fraction in the center is higher than that of either side.As the droplet diameter increases,the region of high liquid volume fraction on the slab surface becomes wider,and the liquid phase distribution in the slab width direction becomes uneven.Although increasing the droplet velocity at the nozzle exit has little effect on droplet diffusion in the spray zone,the distribution becomes more uneven due to more liquid reaches the slab surface per unit time.A prediction formula of the maximum water flow rate on the slab surface for specific droplet characteristics was proposed based on dimensionless analysis and validated by simulated data.A nozzle spacing of 210 mm was recommended under the working conditions in this study,which ensures effective coverage of the spray water over the slab surface and enhances the distribution uniformity of water flow rate in the transverse direction.
文摘Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.
基金funded by University Natural Science Research Project of Anhui Province,Grant Numbers (KJ2020A0826,2022AH051885,2022AH051891,2022AH030160,62303231)Intelligent Detection Research Team Funds for the Anhui Institute of Information Technology,Grant Number (AXG2023_kjc_5004).
文摘In this study,numerical simulations of the pinching-off phenomena displayed by the dispersed phase in a continuous phase have been conducted using COMSOL Multiphysics(level-set method).Four flow patterns,namely“drop flow”,“jet flow”,“squeeze flow”,and“co-flow”,have been obtained for different flow velocity ratios,channel diameter ratios,density ratios,viscosity ratios,and surface tension.The flow pattern map of two-phase flow in coaxial microchannels has been obtained accordingly,and the associated droplet generation process has been critically discussed considering the related frequency,diameter,and pinch-off length.In particular,it is shown that the larger the flow velocity ratio,the smaller the diameter of generated droplets and the shorter the pinch-off length.The pinch-off length of a droplet is influenced by the channel diameter ratio and density ratio.The changes in viscosity ratio have a negligible influence on the droplet generation pinching frequency.With an increase in surface tension,the frequency of generation and pinch-off length of droplets decrease,but for small surface tension the generation diameter of droplet increases.
文摘Gene synthesis has provided important contributions in various fields including genomics and medicine. Current genes are 7 - 30 cents depending on the assembly and sequencing methods performed. Demand for gene synthesis has been increasing for the past few decades, yet available methods remain expensive. A solution to this problem involves microchip-derived oligonucleotides (oligos), an oligo pool with a substantial number of oligo fragments. Microchips have been proposed as a tool for gene synthesis, but this approach has been criticized for its high error rate during sequencing. This study tests a possible cost-effective method for gene synthesis utilizing fragment assembly and golden gate assembly, which can be employed for quicker manufacturing and efficient execution of genes in the near future. The droplet method was tested in two trials to determine the viability of the method through the accuracy of the oligos sequenced. A preliminary research experiment was performed to determine the efficacy of oligo lengths ranging from two to four overlapping oligos through Gibson assembly. Of the three oligo lengths tested, only two fragment oligos were correctly sequenced. Two fragment oligos were used for the second experiment, which determined the efficacy of the droplet method in reducing gene synthesis cost and speed. The first trial utilized a high-fidelity polymerase and resulted in 3% correctly sequenced oligos, so the second trial utilized a non-high-fidelity polymerase, resulting in 8% correctly sequenced oligos. After calculating, the cost of gene synthesis lowers down to 0.8 cents/base. The final calculated cost of 0.8 cents/base is significantly cheaper than other manufacturing costs of 7 - 30 cents/base. Reducing the cost of gene synthesis provides new insight into the cost-effectiveness of present technologies and protocols and has the potential to benefit the fields of bioengineering and gene therapy.
文摘In fog, visibility is reduced. This reduction in visibility is measured by the meteorological optical range (MOR), which is important for studying human perception and various sensors in foggy conditions. The Cerema PAVIN Fog & Rain platform is capable of producing calibrated fog in order to better analyses it and understand its consequences. The problem is that the droplets produced by the platform are not large enough to resemble real fog. This can have a major impact on measurements since the interaction between electromagnetic waves and fog depends on the wavelength and diameter of the droplets. To remedy this, Cerema is building a new platform with new equipment capable of generating fog. This study analyses different nozzles and associated usage parameters such as the type of water used and the pressure used. The aim is to select the best nozzle with the associated parameters for producing large-diameter droplets and therefore more realistic fog.
文摘This study uses a T-junction to examine the effects of different parameters(velocity ratio,viscosity,contact angle,and channel size ratio)on the generation of microdroplets,related rate,and size.More specifically,numerical simulations are exploited to investigate situations with a velocity varying from 0.004 to 1.6 m/s for the continuous phase and from 0.004 to 0.8 m/s for the dispersed phase,viscosity ratios(0.668,1,6.689,10,66.899),contact angle 80°<θ<270°and four different canal size ratios(1,1.5,2 and 4).The results show that canal size influences droplet size and the generation rate.The contact angle has an impact on the form and the quality of generated droplets.Moreover,the relationship between velocity and viscosity ratios,droplet size,and generation rate is non-monotonic.
基金Major Scientific and Technological Project of Gansu Province(No.22ZD6GA008)the National Natural Science Foundation of China(No.51775256).
文摘High efficiency welding has always been one of the hot research subjects at home and overseas. Aiming at the problem of unstable droplet rotating spray transfer process in 450 A thin wire metal active gas arc(MAG) welding, a three-dimensional arc-droplet coupled model is established in this paper on the base of fluid dynamics to conduct numerical analysis for droplet transfer behavior with external magnetic controlled MAG welding, and used high-speed camera system to verify the simulation results. The results indicate that without external magnetic field, the droplet is transferred by the way of rotating spray, the arc is changeable and the spatter is serious. The electromagnetic force accelerates the radial liquid beam rotation under direct current(DC) magnetic field, and increases the angle between liquid beam and welding wire axis. Meanwhile, the rotation frequency of the liquid beam reaches 400 Hz, the area of arc column and heat loss increase under DC magnetic field. Based on the alternating magnetic field, the arc is the “bell shaped”, the arc stiffness raises, its temperature achieves 26 000 K, and the maximum speed of the liquid stream beam can reach 500 m/s. And the droplet transfer is more stable, the spatter significantly reduces, and welding quality is effectively improved.
基金Natural Science Foundation of Hebei Province,No.21377772DNo.H2022406034National Natural Scientific Foundation of China,No.81672700.
文摘BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.
基金National Natural Science Foundation of China(Grant No.22005275)to provide fund for conducting experiments。
文摘Energetic materials pose challenges in preparation and handling due to their contradictory properties of high-energy and low-sensitivity.The emergence of co-crystal explosives is a new opportunity to change this situation.If the co-crystal explosive is coated into spherical particles with uniform particle size distribution,this contradiction can be further reduced.Therefore,binder-coated hexanitrohexaazaisowurtzitane/2,4,6-trinitrotoluene(CL-20/TNT)co-crystal microspheres were prepared by droplet microfluidic technology in this work.The coating effects of different binder formulations of nitrocellulose(NC)and NC/fluorine rubber(F2604)on the co-crystal spheres were studied.The scanning electron microscopy(SEM)results showed that the use of droplet microfluidic technology with the above binders can provide co-crystal microspheres with regular spherical morphology,uniform particle size distribution and good dispersion.X-ray diffraction(XRD),fourier-transform infrared(FT-IR),differential scanning calorimetry(DSC)and thermo-gravimetric(TG)methods were employed to compare the properties of the co-crystal microspheres,raw material and pure co-crystal.The formation of CL-20/TNT co-crystal in the microspheres was confirmed,and the co-crystal microspheres exhibited better thermal stability than the raw material and pure co-crystal.In addition,the mechanical sensitivity and combustion performance of the co-crystal microspheres were further studied.The results showed that the co-crystal microspheres were more insensitive than CL-20 and pure co-crystal,and displayed excellent self-sustained combustion performance and theoretical detonation performance.This study provides a new method for the fast,simple and one-step preparation of CL-20/TNT co-crystal microspheres,with binder coating,uniform particle size distribution,and excellent performance level.
