Self-suspended proppants,which enable clear-water fracturing,represent a promising new class of materials for reservoir stimulation.Given the economic limitations associated with their exclusive use,this study investi...Self-suspended proppants,which enable clear-water fracturing,represent a promising new class of materials for reservoir stimulation.Given the economic limitations associated with their exclusive use,this study investigates proppant transport behavior in hybrid systems combining self-suspended proppants with conventional 40/70 mesh quartz sand at various mixing ratios.A dedicated experimental apparatus was developed to replicate field-relevant complex fracture networks,consisting of a main fracture and two branching fractures with different deflection angles.Using this system,sand bank formation and proppant distribution were examined for both conventional quartz sand fracturing and fracturing augmented with self-suspended proppants.The effects of slurry discharge volume,proppant mixing ratio,sand ratio,and injection location of the self-suspended proppant on transport and placement behavior were systematically analyzed.According to the results,the incorporation of self-suspended proppants markedly enhances the proppant-carrying capacity of the slurry and substantially modifies sand bank morphology.Increasing the discharge volume raises the inlet slope angle and promotes greater proppant penetration into branch fractures.The proportion of self-suspended proppant governs slurry viscoelasticity and,consequently,proppant settling behavior.As the fraction of self-suspended proppant decreases,the equilibrium height of the sand bank increases,while the proppant mass fraction within branch fractures exhibits a non-monotonic response,initially decreasing and then increasing.Variations in sand ratio alter both overall proppant concentration and the self-suspended proppant-to-water ratio,thereby modulating slurry rheology and influencing proppant placement.In addition,changes in injection location affect near-wellbore vortex structures,leading to distinct sand bank morphologies.展开更多
In contemporary society,rapid and accurate optical cable fault detection is of paramount importance for ensuring the stability and reliability of optical networks.The emergence of novel faults in optical networks has ...In contemporary society,rapid and accurate optical cable fault detection is of paramount importance for ensuring the stability and reliability of optical networks.The emergence of novel faults in optical networks has introduced new challenges,significantly compromising their normal operation.Machine learning has emerged as a highly promising approach.Consequently,it is imperative to develop an automated and reliable algorithm that utilizes telemetry data acquired from Optical Time-Domain Reflectometers(OTDR)to enable real-time fault detection and diagnosis in optical fibers.In this paper,we introduce a multi-scale Convolutional Neural Network–Bidirectional Long Short-Term Memory(CNN-BiLSTM)deep learning model for accurate optical fiber fault detection.The proposed multi-scale CNN-BiLSTM comprises three variants:the Independent Multi-scale CNN-BiLSTM(IMC-BiLSTM),the Combined Multi-scale CNN-BiLSTM(CMC-BiLSTM),and the Shared Multi-scale CNN-BiLSTM(SMC-BiLSTM).These models employ convolutional kernels of varying sizes to extract spatial features from time-series data,while leveraging BiLSTM to enhance the capture of global event characteristics.Experiments were conducted using the publicly available OTDR_data dataset,and comparisons with existing methods demonstrate the effectiveness of our approach.The results show that(i)IMC-BiLSTM,CMC-BiLSTM,and SMC-BiLSTM achieve F1-scores of 97.37%,97.25%,and 97.1%,(ii)respectively,with accuracy of 97.36%,97.23%,and 97.12%.These performances surpass those of traditional techniques.展开更多
Background:Given the suboptimal quality of end‐of‐life care among patients with cancer in China,promoting living wills is critical in this population.Living wills ensure that individuals can receive the medical care...Background:Given the suboptimal quality of end‐of‐life care among patients with cancer in China,promoting living wills is critical in this population.Living wills ensure that individuals can receive the medical care they desire during the terminal phase of an illness,maintain their dignity,and ultimately achieve a good death.However,current awareness and attitudes about living wills among Chinese patients with cancer remain unclear.We administered a questionnaire survey on living wills to patients with malignant tumors to assess their most important needs and increase understanding about living wills.Methods:In this cross‐sectional study using convenience sampling,inpatients with malignant tumors in Wuhan completed our questionnaire between July 2020 and June 2021.We collected patients'sociodemographic characteristics and details regarding their knowledge and attitudes about living wills.Results:Among 213 patients with malignant tumors,114(53.52%)had heard of living wills;125(58.69%)expressed their willingness to sign the“Five Wishes”living will document after learning about it through the questionnaire.Patients with malignant tumors had a high level of desire for the following living will items:the lives of family and friends return to normal as soon as possible after their death,maintaining personal hygiene and dignity,and remaining pain‐free.The knowledge level of patients with malignant tumors was related to their educational level(p<0.05)and self‐care ability(p<0.05).Conclusions:Patients with malignant tumors have a high need for comfort,cleanliness,and pain relief in the terminal stages.Patients with a higher level of education and those with poorer self‐care ability had greater knowledge and acceptance of living wills.Promotion can first be targeted toward more highly educated patients and can then be gradually expanded to other groups.展开更多
Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination str...Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance.Biguanides,with excellent anti-tumor effects,have recently attracted much attention for this potential.The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.Methods:A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI.Proteomics,co-immunoprecipitation mass spectrometry,RNA sequencing,and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy.NSCLC tumor tissues,especially OSI-resistant tissues,obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.Results:SMK-010,a highly potent biguanide compound,effectively overcame OSI resistance in vitro and in vivo.Mechanistical studies showed that BMI1/FGFR1 pathway activation is responsible for OSI resistance.Specifically,silencing BMI1 promoted NEDD4-mediated FGFR1 ubiquitination and proteasomal degradation,whereas SMK-010 treatment induced FGFR1 lysosomal degradation.This reduction in FGFR1 levels impaired homologous recombination,increased DNA damage,and surmounted OSI resistance.Analysis of clinical samples revealed overexpression of BMI1 and FGFR1 in NSCLC tissues and represented potential biomarkers for OSI resistance.Conclusions:These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide,SMK-010,in combination with OSI.展开更多
A 12-metal Zn(Ⅱ)-Nd(Ⅲ) cluster 1(sizes:1.8 nm×2.0 nm×2.0 nm) was synthesized from a long-chain type Schiff base ligand.It displays ratiometric fluorescence response to neopterin(Neo) with high selectivity ...A 12-metal Zn(Ⅱ)-Nd(Ⅲ) cluster 1(sizes:1.8 nm×2.0 nm×2.0 nm) was synthesized from a long-chain type Schiff base ligand.It displays ratiometric fluorescence response to neopterin(Neo) with high selectivity and sensitivity,which can be expressed by the equation I_(545)_(nm)/I_(1060)_(nm)=A·[Neo]^(2)+B·[Neo]+C.1 is used to quantitatively test Neo concentrations in fetal calf serum(FCS) and urine,and the recovery ranges are 98.57%-103.82% and 99.25%-103.50%,respectively,while the relative standard deviations(RSDs) are 7.89%-9.46% and 1.85%-4.16%,respectively.The limits of detection of 1 to Neo in FCS and urine are 0.034 and 0.021 μmol/L,respectively.展开更多
The aqueous preparation of Na_(3)(VOPO_(4))_(2)F cathode material with low cost and good structural stability has attracted extensive attention for advancing sodium-ion batteries(SIBs).However,the inclusive heterogene...The aqueous preparation of Na_(3)(VOPO_(4))_(2)F cathode material with low cost and good structural stability has attracted extensive attention for advancing sodium-ion batteries(SIBs).However,the inclusive heterogeneous cations incorporated into the material lattice,dominated by coordination chemistry,are always overlooked.Herein,the embroiled NH_(4)^(+)/H_(3)O^(+)cations in the Na_(3)(VOPO_(4))_(2)F lattice have been first disclosed during aqueous co-precipitation.It involves the electrostatic interactions between hydrogen protons(NH_(4)^(+)/H_(3)O^(+))and electronegative oxygen atoms(V=O and V–O–P groups),which induces the terrible Na^(+)-storage performance,as demonstrated by multiple characterizations.Followingly,the very-facile operation,i.e.heat treatment,has been raised to remove NH_(4)^(+)/H_(3)O^(+)cations and then achieved high-performance Na_(3)(VOPO_(4))_(2)F.Therefore,the Na_(3)(VOPO_(4))_(2)F||Na cell contributes to the significantly improved discharge capacity(129.7 mAh g^(−1))and voltage plateau from 3.63 to 3.87 V(vs.Na/Na^(+))at 0.2 C.The ultrahigh capacity retentions of 93.7%and 76.7%after 1000 and 3500 cycles at 1 and 20 C rates under 25°C are harvested,respectively,as well as high/low-temperature performances and rate capability.Eventually,the as-assembled Na_(3)(VOPO_(4))_(2)F||hard carbon full-cell delivers excellent long-term cycling stability over 1000 cycles with 97.5%retention at 3 C.These emphasize the high-efficacy synthesis of Na_(3)(VOPO_(4))_(2)F and provide insights into the aqueous co-precipitation for the development of materials used in SIBs.展开更多
Lithium batteries (LBs) have become increasingly important energy storage systems in our daily life. However, their practical applications are still severely plagued by the safety issues from liquid electrolyte, espec...Lithium batteries (LBs) have become increasingly important energy storage systems in our daily life. However, their practical applications are still severely plagued by the safety issues from liquid electrolyte, especially when the batteries are exposed to mechanical, thermal, or electrical abuse conditions. Gel polymer electrolytes (GPEs) are being considered as an effective solution to replace currently available organic liquid electrolyte for building safer LBs. This review provides recent advancements in GPEs applied for high-performance LBs. On the one hand, from the environmental and economic point of view, the skeletons of GPEs changed from traditional polymer to renewable and degradable polymer. On the other hand, in addition to being as a component with good electrochemical and physical characterizations, the GPEs also need to provide some functions for addressing the concerns of lithium (Li) dendrites, unstable cathode electrolyte interface, dissolution and migration of transition metal ions,"shuttle effect" of polysulfides, and so on. Finally, to synchronously meet the challenges from the advanced cathode and Li metal anode, the bio-based GPEs with multi-functionality are proposed to develop high-energy/powerdensity batteries in the future.展开更多
A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capa...A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capacitance fabricated via one-step carbonization/activation of dense bacterial cellulose(BC)precursor followed by nitrogen/sulfur dual doping is reported.The microporous carbon possesses highly concentrated micropores(~2 nm)and a considerable amount of sub-micropores(<1 nm).The unique porous structure provides high specific surface area(1554 m^2 g^-1)and packing density(1.18 g cm^-3).The synergistic effects from the particular porous structure and optimal doping effectively enhance ion storage and ion/electron transport.As a result,the remarkable specific capacitances,including ultrahigh gravimetric and volumetric capacitances(430 F g^-1 and 507 F cm^-3 at 0.5 A g^-1),and excellent cycling and rate stability even at a high current density of 10 A g^-1(327 F g^-1 and 385 F cm^-3)are realized.Via compositing the porous carbon and BC skeleton,a robust all-solid-state cellulose-based supercapacitor presents super high areal energy density(~0.77 mWh cm^-2),volumetric energy density(~17.8 W L^-1),and excellent cyclic stability.展开更多
Metabolites can directly reflect and modulate cell responses and phenotypical changes by influencing energy balances,intercellular signals,and many other cellular functions throughout the lifespan of cells.Taking into...Metabolites can directly reflect and modulate cell responses and phenotypical changes by influencing energy balances,intercellular signals,and many other cellular functions throughout the lifespan of cells.Taking into account the heterogeneity of cells,single-cell metabolite analysis offers an insight into the functional process within one cell.Microfluidics as a powerful tool has attracted significant interest in the single-cell metabolite analysis field.The microfluidic platform is possible to observe,classify,and stimulate individual cells.It can also transport single-cell to subsequent analysis steps in a fast and controllable way to determine and analyze the composition and content of metabolites.The reviews of topics in microfluidics for single-cell metabolite analysis have been published in the past few years.However,most of them focused on metabolite analysis with mass spectrometry.Here,we covered the advances of microfluidic devices for single-cell metabolite analysis,with a focus on single-cell isolation and manipulation.What is more,we summarized the detection methods and applications of single-cell metabolites.展开更多
Energetic electron measurements and spacecraft charging are of great significance for theoretical research in space physics and space weather applications.In this paper,the energetic electron detection package(EEDP)de...Energetic electron measurements and spacecraft charging are of great significance for theoretical research in space physics and space weather applications.In this paper,the energetic electron detection package(EEDP)deployed on three Chinese navigation satellites in medium Earth orbit(MEO)is reviewed.The instrument was developed by the space science payload team led by Peking University.The EEDP includes a pinhole medium-energy electron spectrometer(MES),a high-energy electron detector(HED)based onΔE-E telescope technology,and a deep dielectric charging monitor(DDCM).The MES measures the energy spectra of 50−600 keV electrons from nine directions with a 180°×30°field of view(FOV).The HED measures the energy spectrum of 0.5−3.0 MeV electrons from one direction with a 30°cone-angle FOV.The ground test and calibration results indicate that these three sensors exhibit excellent performance.Preliminary observations show that the electron spectra measured by the MES and HED are in good agreement with the results from the magnetic electron-ion spectrometer(MagEIS)of the Van Allen Probes spacecraft,with an average relative deviation of 27.3%for the energy spectra.The charging currents and voltages measured by the DDCM during storms are consistent with the highenergy electron observations of the HED,demonstrating the effectiveness of the DDCM.The observations of the EEDP on board the three MEO satellites can provide important support for theoretical research on the radiation belts and the applications related to space weather.展开更多
Ca3Co409/polyaniline bulk composites have been successfully fabricated by ball-milling and hot-pressing method. Our results indicate that the Seebeck coefficient can be increased nearly by 400% with adding 15 wt% 0a3C...Ca3Co409/polyaniline bulk composites have been successfully fabricated by ball-milling and hot-pressing method. Our results indicate that the Seebeck coefficient can be increased nearly by 400% with adding 15 wt% 0a3Co409 to the polyaniline. The thermal conductivity changes slightly with increasing filler content. The highest figure of merit, ZT can reach 5× 10-4 at 329 K for these bulk composites, which is almost 50 times larger than that of pure polyaniline, suggesting that the polymer-thermoelectric oxide composites are promising candidates for light-weight, low-cost and non-toxic thermoelectric applications.展开更多
Four mono-and bi-nuclear lanthanide complexes [LnL1(No3)(H2O)DMF](Ln=Nd(1) and Yb(2)) and[Ln2(L2)2(OAc)2](Ln=Nd(3) and Yb(4)) were synthesized by using two new Schiff base ligands with long(CH2)2 NH(CH2)2 backbone.The...Four mono-and bi-nuclear lanthanide complexes [LnL1(No3)(H2O)DMF](Ln=Nd(1) and Yb(2)) and[Ln2(L2)2(OAc)2](Ln=Nd(3) and Yb(4)) were synthesized by using two new Schiff base ligands with long(CH2)2 NH(CH2)2 backbone.The lengths of the Schiff base ligands are about 1.8 nm.The bi-nuclear lanthanide complexes 3 and 4 have nanoscale structures with sizes of approximately 0.7 nm×1.1 nm×1.6 nm.For 3,the molar ratio of Nd:Br:O obtained by the energy dispersive X-ray spectroscopy analysis is in agreement with the crystal structure.The chromogenic Schiff base ligands in1-4 can efficiently transfer energy to lanthanide ions,thus,these complexes exhibit the typical NIR luminescence of lanthanide ions.Interestingly,3 and 4 have higher NIR emission quantum yields(Φem)than 1 and 2,respectively.展开更多
One 6-metal Zn-Nd complex[Zn_(2)Nd_(4)L_(2)(OAc)_(10)(OH)_(2)(CH_(3)OH)_(2)](1)with Schiff base ligand bis(3-methoxysalicylidene)ethylene-1,2-phenylenediamine(H_(2)L)was constructed,and it has nanoscale rectangular st...One 6-metal Zn-Nd complex[Zn_(2)Nd_(4)L_(2)(OAc)_(10)(OH)_(2)(CH_(3)OH)_(2)](1)with Schiff base ligand bis(3-methoxysalicylidene)ethylene-1,2-phenylenediamine(H_(2)L)was constructed,and it has nanoscale rectangular structure(8×11×28 A).Excited by ligand-centered absorption bands,1 shows NIRemission of Nd^(3+)ion.Interestingly,1 exhibits lanthanide luminescent response towards metal ions,especially to alkali metal ions(Li^(+),Na^(+) and K^(+))at ppm level.展开更多
The progress of zinc(Zn)metal batteries(ZMBs)is greatly limited by poor cycling stability because of the mutual restrictions of dendrite growth,corrosion reactions,and passivation.In this work,an ultralong lifespan(~7...The progress of zinc(Zn)metal batteries(ZMBs)is greatly limited by poor cycling stability because of the mutual restrictions of dendrite growth,corrosion reactions,and passivation.In this work,an ultralong lifespan(~7800 h),dendrite-free Zn metal anode is enabled via fabricating a functional hydrogel electrolyte out of polyacrylamide/graphene oxide(GO)/agarose(PGA)with a multifully cross-linked network.The synergetic integration of GO nanosheets and double-network structure endows the PGA hydrogel electrolyte with high ionic conductivity and excellent mechanical performance.More importantly,the abundant hydrophilic groups and stable three-dimensional cross-linked network of PGA electrolyte effectively constrain Zn^(2+)diffusion laterally along the Zn surface,which simultaneously prohibits waterinduced corrosion and thus significantly enhances Zn anode reversibility.Both theoretical simulations and experiments reveal that the PGA electrolyte is capable of optimizing de-solvation kinetics and harmonizing Zn^(2+)flux at the electrolyte-electrode interface,ensuring uniform Zn^(2+)deposition.Consequently,an ultra-long lifespan of 7800 h is achieved in the symmetric cell with the PGA electrolyte.Even at a high Zn utilization of 42.7%,it still delivers stable cycling over 1100 h.This work provides a practical and beneficial approach to dramatically extending the lifespan of the Zn anode and thus achieving high-performance ZMBs.展开更多
Co-base refractory alloy coating was prepared on carbon steel substrate by cold spray technology; microstructure and nano-mechenieal property were examined by scanning electron microscope （SEM） and nano indenter ind...Co-base refractory alloy coating was prepared on carbon steel substrate by cold spray technology; microstructure and nano-mechenieal property were examined by scanning electron microscope （SEM） and nano indenter individually. The results showed that about 250 μm Co-base refractory alloy coating could be deposited o11 steel substrate by cold spray technique, interface between coating and substrate was combined well, and the refractory alloy particle had a significant plastic deformation during deposition process; mixing Ni powders into Co-base refractory alloy powders could increase the density and decrease the nano-hardness of coating, the nano-hardness and elastic modulus of refractory alloy coating was higher than 6 GPa and 160 GPa, respectively.展开更多
基金the China National Petroleum Corporation’s Forward-Looking Fundamental Technology Breakthrough Project(2021DJ2305).
文摘Self-suspended proppants,which enable clear-water fracturing,represent a promising new class of materials for reservoir stimulation.Given the economic limitations associated with their exclusive use,this study investigates proppant transport behavior in hybrid systems combining self-suspended proppants with conventional 40/70 mesh quartz sand at various mixing ratios.A dedicated experimental apparatus was developed to replicate field-relevant complex fracture networks,consisting of a main fracture and two branching fractures with different deflection angles.Using this system,sand bank formation and proppant distribution were examined for both conventional quartz sand fracturing and fracturing augmented with self-suspended proppants.The effects of slurry discharge volume,proppant mixing ratio,sand ratio,and injection location of the self-suspended proppant on transport and placement behavior were systematically analyzed.According to the results,the incorporation of self-suspended proppants markedly enhances the proppant-carrying capacity of the slurry and substantially modifies sand bank morphology.Increasing the discharge volume raises the inlet slope angle and promotes greater proppant penetration into branch fractures.The proportion of self-suspended proppant governs slurry viscoelasticity and,consequently,proppant settling behavior.As the fraction of self-suspended proppant decreases,the equilibrium height of the sand bank increases,while the proppant mass fraction within branch fractures exhibits a non-monotonic response,initially decreasing and then increasing.Variations in sand ratio alter both overall proppant concentration and the self-suspended proppant-to-water ratio,thereby modulating slurry rheology and influencing proppant placement.In addition,changes in injection location affect near-wellbore vortex structures,leading to distinct sand bank morphologies.
基金supported in part by the Guangxi Science and Technology Department Key Research and Development Project(Grant No.23026149)in part by the Guangxi Key Research and Development Plan Project(Grant No.AB24010073).
文摘In contemporary society,rapid and accurate optical cable fault detection is of paramount importance for ensuring the stability and reliability of optical networks.The emergence of novel faults in optical networks has introduced new challenges,significantly compromising their normal operation.Machine learning has emerged as a highly promising approach.Consequently,it is imperative to develop an automated and reliable algorithm that utilizes telemetry data acquired from Optical Time-Domain Reflectometers(OTDR)to enable real-time fault detection and diagnosis in optical fibers.In this paper,we introduce a multi-scale Convolutional Neural Network–Bidirectional Long Short-Term Memory(CNN-BiLSTM)deep learning model for accurate optical fiber fault detection.The proposed multi-scale CNN-BiLSTM comprises three variants:the Independent Multi-scale CNN-BiLSTM(IMC-BiLSTM),the Combined Multi-scale CNN-BiLSTM(CMC-BiLSTM),and the Shared Multi-scale CNN-BiLSTM(SMC-BiLSTM).These models employ convolutional kernels of varying sizes to extract spatial features from time-series data,while leveraging BiLSTM to enhance the capture of global event characteristics.Experiments were conducted using the publicly available OTDR_data dataset,and comparisons with existing methods demonstrate the effectiveness of our approach.The results show that(i)IMC-BiLSTM,CMC-BiLSTM,and SMC-BiLSTM achieve F1-scores of 97.37%,97.25%,and 97.1%,(ii)respectively,with accuracy of 97.36%,97.23%,and 97.12%.These performances surpass those of traditional techniques.
文摘Background:Given the suboptimal quality of end‐of‐life care among patients with cancer in China,promoting living wills is critical in this population.Living wills ensure that individuals can receive the medical care they desire during the terminal phase of an illness,maintain their dignity,and ultimately achieve a good death.However,current awareness and attitudes about living wills among Chinese patients with cancer remain unclear.We administered a questionnaire survey on living wills to patients with malignant tumors to assess their most important needs and increase understanding about living wills.Methods:In this cross‐sectional study using convenience sampling,inpatients with malignant tumors in Wuhan completed our questionnaire between July 2020 and June 2021.We collected patients'sociodemographic characteristics and details regarding their knowledge and attitudes about living wills.Results:Among 213 patients with malignant tumors,114(53.52%)had heard of living wills;125(58.69%)expressed their willingness to sign the“Five Wishes”living will document after learning about it through the questionnaire.Patients with malignant tumors had a high level of desire for the following living will items:the lives of family and friends return to normal as soon as possible after their death,maintaining personal hygiene and dignity,and remaining pain‐free.The knowledge level of patients with malignant tumors was related to their educational level(p<0.05)and self‐care ability(p<0.05).Conclusions:Patients with malignant tumors have a high need for comfort,cleanliness,and pain relief in the terminal stages.Patients with a higher level of education and those with poorer self‐care ability had greater knowledge and acceptance of living wills.Promotion can first be targeted toward more highly educated patients and can then be gradually expanded to other groups.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172653 and 82472728)the Key Project of Developmental Biology and Breeding from Hunan Province(Grant No.2022XKQ0205)+1 种基金the Research Team for Reproduction Health and Translational Medicine of Hunan Normal University(Grant No.2023JC101)the Natural Science Foundation of Hunan Province(Grant No.2025JJ80150).
文摘Objective:Osimertinib(OSI)therapy,a cornerstone in treating non-small cell lung cancer(NSCLC),has been severely limited by rapidly developing acquired resistance.Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance.Biguanides,with excellent anti-tumor effects,have recently attracted much attention for this potential.The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.Methods:A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI.Proteomics,co-immunoprecipitation mass spectrometry,RNA sequencing,and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy.NSCLC tumor tissues,especially OSI-resistant tissues,obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.Results:SMK-010,a highly potent biguanide compound,effectively overcame OSI resistance in vitro and in vivo.Mechanistical studies showed that BMI1/FGFR1 pathway activation is responsible for OSI resistance.Specifically,silencing BMI1 promoted NEDD4-mediated FGFR1 ubiquitination and proteasomal degradation,whereas SMK-010 treatment induced FGFR1 lysosomal degradation.This reduction in FGFR1 levels impaired homologous recombination,increased DNA damage,and surmounted OSI resistance.Analysis of clinical samples revealed overexpression of BMI1 and FGFR1 in NSCLC tissues and represented potential biomarkers for OSI resistance.Conclusions:These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide,SMK-010,in combination with OSI.
基金Project supported by the National Natural Science Foundation of China (21771141)。
文摘A 12-metal Zn(Ⅱ)-Nd(Ⅲ) cluster 1(sizes:1.8 nm×2.0 nm×2.0 nm) was synthesized from a long-chain type Schiff base ligand.It displays ratiometric fluorescence response to neopterin(Neo) with high selectivity and sensitivity,which can be expressed by the equation I_(545)_(nm)/I_(1060)_(nm)=A·[Neo]^(2)+B·[Neo]+C.1 is used to quantitatively test Neo concentrations in fetal calf serum(FCS) and urine,and the recovery ranges are 98.57%-103.82% and 99.25%-103.50%,respectively,while the relative standard deviations(RSDs) are 7.89%-9.46% and 1.85%-4.16%,respectively.The limits of detection of 1 to Neo in FCS and urine are 0.034 and 0.021 μmol/L,respectively.
基金the Natural Science Foundation of China(52162030,52272234,52172233)the Major Science and Technology Projects of Yunnan Province(202202AG050003)+7 种基金the Yunnan Thousand Talents Program for Young Talents(KKS2202052001,KKRD202252091)the Yunnan Fundamental Research Projects(202401AT070368,202401AU070163)the Scientific Research Foundation of Kunming University of Science and Technology(20220122)the Analysis and Test Foundation of Kunming University of Science and Technology(2023T20220122)the Yunnan Engineering Research Center Innovation Ability Construction and Enhancement Projects(2023-XMDJ00617107)the National Key Research and Development Program of China(2020YFA0715000)the International Science and Technology Cooperation Program of Hubei Province(2024EHA039)the Independent Innovation Project of Hubei Longzhong Laboratory(2022ZZ-20).
文摘The aqueous preparation of Na_(3)(VOPO_(4))_(2)F cathode material with low cost and good structural stability has attracted extensive attention for advancing sodium-ion batteries(SIBs).However,the inclusive heterogeneous cations incorporated into the material lattice,dominated by coordination chemistry,are always overlooked.Herein,the embroiled NH_(4)^(+)/H_(3)O^(+)cations in the Na_(3)(VOPO_(4))_(2)F lattice have been first disclosed during aqueous co-precipitation.It involves the electrostatic interactions between hydrogen protons(NH_(4)^(+)/H_(3)O^(+))and electronegative oxygen atoms(V=O and V–O–P groups),which induces the terrible Na^(+)-storage performance,as demonstrated by multiple characterizations.Followingly,the very-facile operation,i.e.heat treatment,has been raised to remove NH_(4)^(+)/H_(3)O^(+)cations and then achieved high-performance Na_(3)(VOPO_(4))_(2)F.Therefore,the Na_(3)(VOPO_(4))_(2)F||Na cell contributes to the significantly improved discharge capacity(129.7 mAh g^(−1))and voltage plateau from 3.63 to 3.87 V(vs.Na/Na^(+))at 0.2 C.The ultrahigh capacity retentions of 93.7%and 76.7%after 1000 and 3500 cycles at 1 and 20 C rates under 25°C are harvested,respectively,as well as high/low-temperature performances and rate capability.Eventually,the as-assembled Na_(3)(VOPO_(4))_(2)F||hard carbon full-cell delivers excellent long-term cycling stability over 1000 cycles with 97.5%retention at 3 C.These emphasize the high-efficacy synthesis of Na_(3)(VOPO_(4))_(2)F and provide insights into the aqueous co-precipitation for the development of materials used in SIBs.
基金financial support from the National Natural Science Foundation of China (No. 51873011 and U1664251)the Fundamental Research Fund for the Central Universities (No. JC1504)
文摘Lithium batteries (LBs) have become increasingly important energy storage systems in our daily life. However, their practical applications are still severely plagued by the safety issues from liquid electrolyte, especially when the batteries are exposed to mechanical, thermal, or electrical abuse conditions. Gel polymer electrolytes (GPEs) are being considered as an effective solution to replace currently available organic liquid electrolyte for building safer LBs. This review provides recent advancements in GPEs applied for high-performance LBs. On the one hand, from the environmental and economic point of view, the skeletons of GPEs changed from traditional polymer to renewable and degradable polymer. On the other hand, in addition to being as a component with good electrochemical and physical characterizations, the GPEs also need to provide some functions for addressing the concerns of lithium (Li) dendrites, unstable cathode electrolyte interface, dissolution and migration of transition metal ions,"shuttle effect" of polysulfides, and so on. Finally, to synchronously meet the challenges from the advanced cathode and Li metal anode, the bio-based GPEs with multi-functionality are proposed to develop high-energy/powerdensity batteries in the future.
文摘A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capacitance fabricated via one-step carbonization/activation of dense bacterial cellulose(BC)precursor followed by nitrogen/sulfur dual doping is reported.The microporous carbon possesses highly concentrated micropores(~2 nm)and a considerable amount of sub-micropores(<1 nm).The unique porous structure provides high specific surface area(1554 m^2 g^-1)and packing density(1.18 g cm^-3).The synergistic effects from the particular porous structure and optimal doping effectively enhance ion storage and ion/electron transport.As a result,the remarkable specific capacitances,including ultrahigh gravimetric and volumetric capacitances(430 F g^-1 and 507 F cm^-3 at 0.5 A g^-1),and excellent cycling and rate stability even at a high current density of 10 A g^-1(327 F g^-1 and 385 F cm^-3)are realized.Via compositing the porous carbon and BC skeleton,a robust all-solid-state cellulose-based supercapacitor presents super high areal energy density(~0.77 mWh cm^-2),volumetric energy density(~17.8 W L^-1),and excellent cyclic stability.
基金1226 Engineering Health Major Project(Nos.BWS17J028 and AWS16J018)。
文摘Metabolites can directly reflect and modulate cell responses and phenotypical changes by influencing energy balances,intercellular signals,and many other cellular functions throughout the lifespan of cells.Taking into account the heterogeneity of cells,single-cell metabolite analysis offers an insight into the functional process within one cell.Microfluidics as a powerful tool has attracted significant interest in the single-cell metabolite analysis field.The microfluidic platform is possible to observe,classify,and stimulate individual cells.It can also transport single-cell to subsequent analysis steps in a fast and controllable way to determine and analyze the composition and content of metabolites.The reviews of topics in microfluidics for single-cell metabolite analysis have been published in the past few years.However,most of them focused on metabolite analysis with mass spectrometry.Here,we covered the advances of microfluidic devices for single-cell metabolite analysis,with a focus on single-cell isolation and manipulation.What is more,we summarized the detection methods and applications of single-cell metabolites.
基金supported by the National Natural Science Foundation of China(No.41374167,41421003,41474140)China's National Basic Research and Development Program(No.2012CB825603).
文摘Energetic electron measurements and spacecraft charging are of great significance for theoretical research in space physics and space weather applications.In this paper,the energetic electron detection package(EEDP)deployed on three Chinese navigation satellites in medium Earth orbit(MEO)is reviewed.The instrument was developed by the space science payload team led by Peking University.The EEDP includes a pinhole medium-energy electron spectrometer(MES),a high-energy electron detector(HED)based onΔE-E telescope technology,and a deep dielectric charging monitor(DDCM).The MES measures the energy spectra of 50−600 keV electrons from nine directions with a 180°×30°field of view(FOV).The HED measures the energy spectrum of 0.5−3.0 MeV electrons from one direction with a 30°cone-angle FOV.The ground test and calibration results indicate that these three sensors exhibit excellent performance.Preliminary observations show that the electron spectra measured by the MES and HED are in good agreement with the results from the magnetic electron-ion spectrometer(MagEIS)of the Van Allen Probes spacecraft,with an average relative deviation of 27.3%for the energy spectra.The charging currents and voltages measured by the DDCM during storms are consistent with the highenergy electron observations of the HED,demonstrating the effectiveness of the DDCM.The observations of the EEDP on board the three MEO satellites can provide important support for theoretical research on the radiation belts and the applications related to space weather.
基金supported by the National Basic Research Program of China("973 Program",No.2013CB632506)the National Natural Science Foundation of China(No.51025205)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20120002110006)
文摘Ca3Co409/polyaniline bulk composites have been successfully fabricated by ball-milling and hot-pressing method. Our results indicate that the Seebeck coefficient can be increased nearly by 400% with adding 15 wt% 0a3Co409 to the polyaniline. The thermal conductivity changes slightly with increasing filler content. The highest figure of merit, ZT can reach 5× 10-4 at 329 K for these bulk composites, which is almost 50 times larger than that of pure polyaniline, suggesting that the polymer-thermoelectric oxide composites are promising candidates for light-weight, low-cost and non-toxic thermoelectric applications.
基金supported by the National Natural Science Foundation of China(21771141).
文摘Four mono-and bi-nuclear lanthanide complexes [LnL1(No3)(H2O)DMF](Ln=Nd(1) and Yb(2)) and[Ln2(L2)2(OAc)2](Ln=Nd(3) and Yb(4)) were synthesized by using two new Schiff base ligands with long(CH2)2 NH(CH2)2 backbone.The lengths of the Schiff base ligands are about 1.8 nm.The bi-nuclear lanthanide complexes 3 and 4 have nanoscale structures with sizes of approximately 0.7 nm×1.1 nm×1.6 nm.For 3,the molar ratio of Nd:Br:O obtained by the energy dispersive X-ray spectroscopy analysis is in agreement with the crystal structure.The chromogenic Schiff base ligands in1-4 can efficiently transfer energy to lanthanide ions,thus,these complexes exhibit the typical NIR luminescence of lanthanide ions.Interestingly,3 and 4 have higher NIR emission quantum yields(Φem)than 1 and 2,respectively.
基金supported by the National Natural Science Foundation of China(No.21771141)。
文摘One 6-metal Zn-Nd complex[Zn_(2)Nd_(4)L_(2)(OAc)_(10)(OH)_(2)(CH_(3)OH)_(2)](1)with Schiff base ligand bis(3-methoxysalicylidene)ethylene-1,2-phenylenediamine(H_(2)L)was constructed,and it has nanoscale rectangular structure(8×11×28 A).Excited by ligand-centered absorption bands,1 shows NIRemission of Nd^(3+)ion.Interestingly,1 exhibits lanthanide luminescent response towards metal ions,especially to alkali metal ions(Li^(+),Na^(+) and K^(+))at ppm level.
基金supported by the National Key R&D Program of China(No.2020YFC1910200)the National Natural Science Foundation of China(Nos.51873011 and U1664251).
文摘The progress of zinc(Zn)metal batteries(ZMBs)is greatly limited by poor cycling stability because of the mutual restrictions of dendrite growth,corrosion reactions,and passivation.In this work,an ultralong lifespan(~7800 h),dendrite-free Zn metal anode is enabled via fabricating a functional hydrogel electrolyte out of polyacrylamide/graphene oxide(GO)/agarose(PGA)with a multifully cross-linked network.The synergetic integration of GO nanosheets and double-network structure endows the PGA hydrogel electrolyte with high ionic conductivity and excellent mechanical performance.More importantly,the abundant hydrophilic groups and stable three-dimensional cross-linked network of PGA electrolyte effectively constrain Zn^(2+)diffusion laterally along the Zn surface,which simultaneously prohibits waterinduced corrosion and thus significantly enhances Zn anode reversibility.Both theoretical simulations and experiments reveal that the PGA electrolyte is capable of optimizing de-solvation kinetics and harmonizing Zn^(2+)flux at the electrolyte-electrode interface,ensuring uniform Zn^(2+)deposition.Consequently,an ultra-long lifespan of 7800 h is achieved in the symmetric cell with the PGA electrolyte.Even at a high Zn utilization of 42.7%,it still delivers stable cycling over 1100 h.This work provides a practical and beneficial approach to dramatically extending the lifespan of the Zn anode and thus achieving high-performance ZMBs.
文摘Co-base refractory alloy coating was prepared on carbon steel substrate by cold spray technology; microstructure and nano-mechenieal property were examined by scanning electron microscope （SEM） and nano indenter individually. The results showed that about 250 μm Co-base refractory alloy coating could be deposited o11 steel substrate by cold spray technique, interface between coating and substrate was combined well, and the refractory alloy particle had a significant plastic deformation during deposition process; mixing Ni powders into Co-base refractory alloy powders could increase the density and decrease the nano-hardness of coating, the nano-hardness and elastic modulus of refractory alloy coating was higher than 6 GPa and 160 GPa, respectively.
