Rapid online analysis of liquid slag is essential for optimizing the quality and energy efficiency of steel production. To investigate the key factors that affect the online measurement of refined slag using laser-ind...Rapid online analysis of liquid slag is essential for optimizing the quality and energy efficiency of steel production. To investigate the key factors that affect the online measurement of refined slag using laser-induced breakdown spectroscopy(LIBS), this study examined the effects of slag composition and temperature on the intensity and stability of the LIBS spectra. The experimental temperature was controlled at three levels: 1350℃, 1400℃, and 1450℃. The results showed that slag composition and temperature significantly affected the intensity and stability of the LIBS spectra. Increasing the Fe content and temperature in the slag reduces its viscosity, resulting in an enhanced intensity and stability of the LIBS spectra. Additionally, 42 refined slag samples were quantitatively analyzed for Fe, Si, Ca, Mg, Al, and Mn at 1350℃, 1400℃, and 1450℃.The normalized full spectrum combined with partial least squares(PLS) quantification modeling was used, using the Ca Ⅱ 317.91 nm spectral line as an internal standard. The results show that using the internal standard normalization method can significantly reduce the influence of spectral fluctuations. Meanwhile, a temperature of 1450℃ has been found to yield superior results compared to both 1350℃ and 1400℃, and it is advantageous to conduct a quantitative analysis of the slag when it is in a “water-like” state with low viscosity.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
Lithium-sulfur(Li-S)batteries are one of the most promising modern-day energy supply systems because of their high theoretical energy density and low cost.However,the development of high-energy density Li-S batteries ...Lithium-sulfur(Li-S)batteries are one of the most promising modern-day energy supply systems because of their high theoretical energy density and low cost.However,the development of high-energy density Li-S batteries with high loading of flammable sulfur faces the challenges of electrochemical performance degradation owing to the shuttle effect and safety issues related to fire or explosion accidents.In this work,we report a three-dimensional(3D)conductive nitrogen-doped carbon foam supported electrostatic self-assembled MXene-ammonium polyphosphate(NCF-MXene-APP)layer as a heat-resistant,thermally-insulated,flame-retardant,and freestanding host for Li-S batteries with a facile and costeffective synthesis method.Consequently,through the use of NCF-MXene-APP hosts that strongly anchor polysulfides,the Li-S batteries demonstrate outstanding electrochemical properties,including a high initial discharge capacity of 1191.6 mA h g^(-1),excellent rate capacity of 755.0 mA h g^(-1)at 1 C,and long-term cycling stability with an extremely low-capacity decay rate of 0.12%per cycle at 2 C.More importantly,these batteries can continue to operate reliably under high temperature or flame attack conditions.Thus,this study provides valuable insights into the design of safe high-performance Li-S batteries.展开更多
Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental compositi...Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an object.The back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments.The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n.This study reveals its potential future applications.展开更多
Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regu...Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.展开更多
We present a Brillouin–Raman random fiber laser(BRRFL)with full-open linear cavity structure to generate broadband Brillouin frequency comb(BFC)with double Brillouin-frequency-shift spacing.The incorporation of a reg...We present a Brillouin–Raman random fiber laser(BRRFL)with full-open linear cavity structure to generate broadband Brillouin frequency comb(BFC)with double Brillouin-frequency-shift spacing.The incorporation of a regeneration portion consisting of an erbium-doped fiber and a single-mode fiber enables the generation of broadband BFC.The dynamics of broadband BFC generation changing with the pump power(EDF and Raman)and Brillouin pump(BP)wavelength are investigated in detail,respectively.Under suitable conditions,the bidirectional BRRFL proposed can produce a flatamplitude BFC with 40.7-nm bandwidth ranging from 1531 nm to 1571.7 nm,and built-in 242-order Brillouin Stokes lines(BSLs)with double Brillouin-frequency-shift spacing.Moreover,the linewidth of single BSL is experimentally measured to be about 2.5 kHz.The broadband bidirectional narrow-linewidth BRRFL has great potential applications in optical communication,optical sensing,spectral measurement,and so on.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive underst...BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete.AIM To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients.METHODS Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic analyses.Subse-quent validations were conducted through spatial transcriptomics and immuno-histochemistry.The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data types.RESULTS CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness.MUC5AC-high cells were found to promote CCA progression through WNT signaling.MUC5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral treatments.MUC13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor immunity.MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils.Utilizing the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple cohorts.CCA samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer prognosis.CONCLUSION Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.展开更多
Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits pro...Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
The hydrocarbon generation effectiveness of lacustrine limestone has been gradually proven. The Da'anzhai Member limestone is the most important Jurassic oil-producing layer in the central Sichuan Basin, and the c...The hydrocarbon generation effectiveness of lacustrine limestone has been gradually proven. The Da'anzhai Member limestone is the most important Jurassic oil-producing layer in the central Sichuan Basin, and the characteristics of limestone organic matter are often overlooked. 175 typical samples of different lithologies from 19 wells were systematically analyzed to determine hydrocarbon generation, controlling factors and formation models by analyses of organic matter, minerals, elements, isotopes and petrography. (1) Lacustrine paleoenvironments can be beneficial for the enrichment of organic matter in limestone. A favorable environment would be a quiet, low-energy zone in a warm and humid climate with an appropriate supply of terrestrial inputs. (2) Lacustrine limestone has a higher organic matter conversion rate, and a lower hydrocarbon generation threshold than argillaceous source rocks, and can be effective source rock. (3) The mud-bearing shell limestone from the forebeach to the lake slope is thick, with a relatively high abundance of organic matter, and its hydrocarbon generation is effective. This study can clarify the effectiveness and enrichment of the limestone organic matters in the study area, and contribute to an understanding of hydrocarbon generation for full-rock system in a lacustrine mixed sedimentary environment.展开更多
Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
High thickness uniformity and large-scale films of α-Ga_(2)O_(3) are crucial factors for the development of power devices.In this work, a high-quality 2-inch α-Ga_(2)O_(3) epitaxial film on c-plane sapphire substrat...High thickness uniformity and large-scale films of α-Ga_(2)O_(3) are crucial factors for the development of power devices.In this work, a high-quality 2-inch α-Ga_(2)O_(3) epitaxial film on c-plane sapphire substrates was prepared by the mist-CVD method.The growth rate and phase control mechanisms were systematically investigated. The growth rate of the α-Ga_(2)O_(3) films was limited by the evaporation of the microdroplets containing gallium acetylacetonate. By adjusting the substrate position(z) from 80 to 50 mm, the growth rate was increased from 307 nm/h to 1.45 μm/h when the growth temperature was fixed at 520 °C.When the growth temperature exceeded 560 °C, ε-Ga_(2)O_(3) was observed to form at the edges of 2-inch sapphire substrate.Phase control was achieved by adjusting the growth temperature. When the growth temperature was 540 °C and the substrate position was 50 mm, the full-width at half maximum(FWHM) of the rocking curves for the(0006) and(10-14) planes were 0.023° and 1.17°. The screw and edge dislocations were 2.3 × 10~6 and 3.9 × 10~(10)cm~(-2), respectively. Furthermore, the bandgaps and optical transmittance of α-Ga_(2)O_(3) films grown under different conditions were characterized utilizing UV-visible and near-IR scanning spectra.展开更多
基金financially supported by the National Key R&D Program Projects of China (No.2021YFB3202402)National Natural Science Foundation of China (No.62173321)。
文摘Rapid online analysis of liquid slag is essential for optimizing the quality and energy efficiency of steel production. To investigate the key factors that affect the online measurement of refined slag using laser-induced breakdown spectroscopy(LIBS), this study examined the effects of slag composition and temperature on the intensity and stability of the LIBS spectra. The experimental temperature was controlled at three levels: 1350℃, 1400℃, and 1450℃. The results showed that slag composition and temperature significantly affected the intensity and stability of the LIBS spectra. Increasing the Fe content and temperature in the slag reduces its viscosity, resulting in an enhanced intensity and stability of the LIBS spectra. Additionally, 42 refined slag samples were quantitatively analyzed for Fe, Si, Ca, Mg, Al, and Mn at 1350℃, 1400℃, and 1450℃.The normalized full spectrum combined with partial least squares(PLS) quantification modeling was used, using the Ca Ⅱ 317.91 nm spectral line as an internal standard. The results show that using the internal standard normalization method can significantly reduce the influence of spectral fluctuations. Meanwhile, a temperature of 1450℃ has been found to yield superior results compared to both 1350℃ and 1400℃, and it is advantageous to conduct a quantitative analysis of the slag when it is in a “water-like” state with low viscosity.
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.
基金supported by the National Research Foundation of Korea(NRF-2021R1A2C1008272)supported by the Institute of Information&communications Technology Planning&Evaluation(IITP)grant funded by the Korean government(MSIT)(No.2021-0-00259,Development of a Fast Wireless Charging System for Portable Terminals with improved heat dissipation and shielding performance)supported by the Applied Basic Research Program of Changzhou City(CJ20220030).
文摘Lithium-sulfur(Li-S)batteries are one of the most promising modern-day energy supply systems because of their high theoretical energy density and low cost.However,the development of high-energy density Li-S batteries with high loading of flammable sulfur faces the challenges of electrochemical performance degradation owing to the shuttle effect and safety issues related to fire or explosion accidents.In this work,we report a three-dimensional(3D)conductive nitrogen-doped carbon foam supported electrostatic self-assembled MXene-ammonium polyphosphate(NCF-MXene-APP)layer as a heat-resistant,thermally-insulated,flame-retardant,and freestanding host for Li-S batteries with a facile and costeffective synthesis method.Consequently,through the use of NCF-MXene-APP hosts that strongly anchor polysulfides,the Li-S batteries demonstrate outstanding electrochemical properties,including a high initial discharge capacity of 1191.6 mA h g^(-1),excellent rate capacity of 755.0 mA h g^(-1)at 1 C,and long-term cycling stability with an extremely low-capacity decay rate of 0.12%per cycle at 2 C.More importantly,these batteries can continue to operate reliably under high temperature or flame attack conditions.Thus,this study provides valuable insights into the design of safe high-performance Li-S batteries.
基金This work was supported by the National Natural Science Foundation of China(No.12035017)Youth Innovation Promotion Association CAS(No.2023014)Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515010360 and 2022B1515120032).
文摘Nondestructive and noninvasive neutron assays are essential applications of neutron techniques.Neutron resonance transmission analysis(NRTA)is a powerful nondestructive method for investigating the elemental composition of an object.The back-streaming neutron line(Back-n)is a newly built time-of-flight facility at the China Spallation Neutron Source(CSNS)that provides neutrons in the eV to 300 MeV range.A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments.The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n.This study reveals its potential future applications.
基金supported by the Project from the Ministry of Agriculture of China for Transgenic Research(2014ZX0800927B)the National Natural Science Foundation of China(31871667).
文摘Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 62175116 and 91950105)the 1311 Talent Plan of Nanjing University of Posts and Telecommunications, Chinathe Postgraduate Research & Practice Innovation Program, Jiangsu Province, China (Grant No. SJCX21_0276)
文摘We present a Brillouin–Raman random fiber laser(BRRFL)with full-open linear cavity structure to generate broadband Brillouin frequency comb(BFC)with double Brillouin-frequency-shift spacing.The incorporation of a regeneration portion consisting of an erbium-doped fiber and a single-mode fiber enables the generation of broadband BFC.The dynamics of broadband BFC generation changing with the pump power(EDF and Raman)and Brillouin pump(BP)wavelength are investigated in detail,respectively.Under suitable conditions,the bidirectional BRRFL proposed can produce a flatamplitude BFC with 40.7-nm bandwidth ranging from 1531 nm to 1571.7 nm,and built-in 242-order Brillouin Stokes lines(BSLs)with double Brillouin-frequency-shift spacing.Moreover,the linewidth of single BSL is experimentally measured to be about 2.5 kHz.The broadband bidirectional narrow-linewidth BRRFL has great potential applications in optical communication,optical sensing,spectral measurement,and so on.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete.AIM To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients.METHODS Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic analyses.Subse-quent validations were conducted through spatial transcriptomics and immuno-histochemistry.The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data types.RESULTS CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness.MUC5AC-high cells were found to promote CCA progression through WNT signaling.MUC5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral treatments.MUC13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor immunity.MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils.Utilizing the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple cohorts.CCA samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer prognosis.CONCLUSION Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.
文摘Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.
基金supported by the National Natural Science Foundation of China(Grants 41902131 and 41821002 and 4169130014).
文摘The hydrocarbon generation effectiveness of lacustrine limestone has been gradually proven. The Da'anzhai Member limestone is the most important Jurassic oil-producing layer in the central Sichuan Basin, and the characteristics of limestone organic matter are often overlooked. 175 typical samples of different lithologies from 19 wells were systematically analyzed to determine hydrocarbon generation, controlling factors and formation models by analyses of organic matter, minerals, elements, isotopes and petrography. (1) Lacustrine paleoenvironments can be beneficial for the enrichment of organic matter in limestone. A favorable environment would be a quiet, low-energy zone in a warm and humid climate with an appropriate supply of terrestrial inputs. (2) Lacustrine limestone has a higher organic matter conversion rate, and a lower hydrocarbon generation threshold than argillaceous source rocks, and can be effective source rock. (3) The mud-bearing shell limestone from the forebeach to the lake slope is thick, with a relatively high abundance of organic matter, and its hydrocarbon generation is effective. This study can clarify the effectiveness and enrichment of the limestone organic matters in the study area, and contribute to an understanding of hydrocarbon generation for full-rock system in a lacustrine mixed sedimentary environment.
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
基金National Natural Science Foundation of China (Grant Nos. 52002219, 51932004 and 61975098)Key-Area Research and Development Program of Guangdong Province (Grant No. 2020B010174002)+2 种基金Shenzhen Fundamental Research Program (Grant No. JCYJ20210324132014038)Natural Science Foundation of Shandong (Grant No. ZR202105230005)the 111 Project 2.0 (Grant No. BP2018013)。
文摘High thickness uniformity and large-scale films of α-Ga_(2)O_(3) are crucial factors for the development of power devices.In this work, a high-quality 2-inch α-Ga_(2)O_(3) epitaxial film on c-plane sapphire substrates was prepared by the mist-CVD method.The growth rate and phase control mechanisms were systematically investigated. The growth rate of the α-Ga_(2)O_(3) films was limited by the evaporation of the microdroplets containing gallium acetylacetonate. By adjusting the substrate position(z) from 80 to 50 mm, the growth rate was increased from 307 nm/h to 1.45 μm/h when the growth temperature was fixed at 520 °C.When the growth temperature exceeded 560 °C, ε-Ga_(2)O_(3) was observed to form at the edges of 2-inch sapphire substrate.Phase control was achieved by adjusting the growth temperature. When the growth temperature was 540 °C and the substrate position was 50 mm, the full-width at half maximum(FWHM) of the rocking curves for the(0006) and(10-14) planes were 0.023° and 1.17°. The screw and edge dislocations were 2.3 × 10~6 and 3.9 × 10~(10)cm~(-2), respectively. Furthermore, the bandgaps and optical transmittance of α-Ga_(2)O_(3) films grown under different conditions were characterized utilizing UV-visible and near-IR scanning spectra.
