Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mec...Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole body.In this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of nanocrystals.Cellular uptake studies were conducted with KB cells and characterized by confocal microscopy,fow cytometry,and quantitative analyses.The results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved molecules.The cellular uptake was found to be concentration-and timedependent.In addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and nanocrystals.Kinetic modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on frst-order ordinary differential equations(ODEs).By ftting the kinetic model against experimental measurements,it was found that the initial nanocrystal concentration had a great infuence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE nanocrystals.As the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the effux of THPE molecules from cells.展开更多
Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with...Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.展开更多
Water-borne pathogenic bacteria are always the top priority to be removed through disinfection process in water treatment due to their threat to human health. It was necessary to develop novel disinfection methods sin...Water-borne pathogenic bacteria are always the top priority to be removed through disinfection process in water treatment due to their threat to human health. It was necessary to develop novel disinfection methods since the conventional chlorine disinfection was inefficient in inactivating chlorine-resistant bacteria, inducing the viable but non-culturable(VBNC) bacteria and forming disinfection by-products(DBPs). In this study, the inactivation of four model strains including Gram-negative(G), Gram-positive(G) and environmental samples by atmospheric-pressure air-liquid discharge plasma(ALDP) was assessed systematically. The results showed that ALDP was superior in inactivating all of the samples compared with chlorination. During 10 min ALDP treatment, the Gbacteria were completely inactivated, and the Gone was inactivated by more than 4.61 logs. The inactivation of bacteria from a campus lake and a wastewater treatment plant effluent exceeded 99.82% and 97.78%, respectively. For G-bacteria, ALDP resulted in a much lower(10~2~10~3 times) levels of VBNC cells than chlorination. ALDP could effectively remove the chlorine-resistant bacteria. More than 96.41% of the intracellular DNA and 99.99% of the extracellular DNA were removed, whereas it was only 56.35% and 12.82% for chlorination. ALDP had a stronger ability to destroy cell structure than chlorination, presumably due to the existence of ROS( ·OH, ~1Oand O). GC-MS analysis showed that ALDP produced less DBPs than chlorination. These findings provided new insights for the application of discharge plasma in water disinfection, which could be complemental or alternative to the conventional disinfection methods.展开更多
The discharge patterns of neurons in auditory centers encode information about sounds.However,few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular record...The discharge patterns of neurons in auditory centers encode information about sounds.However,few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular recording techniques.Here,we investigated the discharge patterns of inferior collicular（IC）neurons using intracellular recordings to further elucidate the mechanisms underlying the shaping of discharge patterns.Under in vivo intracellular recording conditions,recordings were obtained from 66 IC neurons in 18 healthy adult mice（Mus musculus,Km）under free field-stimulation.Fiftyeight of these neurons fired bursts of action potentials（APs）to auditory stimuli and the remaining eight just generated local responses such as excitatory（n=4）or inhibitory（n=4）postsynaptic potentials.Based on the APs and subthreshold responses,the discharge patterns were classified into seven types：phasic（24/58,41.4%）,phasic burst（8/58,13.8%）,pauser（4/58,6.9%）,phasic-pauser（1/58,1.7%）,chopper（2/58,3.4%）,primary-like tonic（14/58,24.1%）and sound-induced inhibitory（5/58,8.6%）.We concluded that（1）IC neurons exhibit at least seven distinct discharge patterns;（2）inhibition participates in shaping the discharge pattern of most IC neurons and plays a role in sculpting the pattern,except for the primary-like tonic pattern which was not shapedby inhibition;and（3）local neural circuits are the likely structural basis that shapes the discharge patterns of IC neurons and can be formed either in the IC or in lower-level auditory structures.展开更多
基金the financial support by the China Scholarship Council(No.201806995008,China)Key Projects of Chinese Medicine Research of Chongqing Municipal Health Bureau(ZY201701004,China)the Chao Endowment and Purdue Research Foundation for support(USA)。
文摘Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole body.In this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of nanocrystals.Cellular uptake studies were conducted with KB cells and characterized by confocal microscopy,fow cytometry,and quantitative analyses.The results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved molecules.The cellular uptake was found to be concentration-and timedependent.In addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and nanocrystals.Kinetic modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on frst-order ordinary differential equations(ODEs).By ftting the kinetic model against experimental measurements,it was found that the initial nanocrystal concentration had a great infuence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE nanocrystals.As the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the effux of THPE molecules from cells.
基金This work was supported by the National Natural Science Foundation of China(No.81930102 to Bo Yang)the National Natural Science Foundation of China(No.81773754 to Ling Ding).
文摘Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.
基金supported by the Natural Science Foundation of China (Nos. 41861144023 and U2005206)the Natural and Science Guiding Project of Fujian Province (No. 2019H0036)the Xiamen Municipal Bureau of Science and Technology (No. YDZX20203502000003)。
文摘Water-borne pathogenic bacteria are always the top priority to be removed through disinfection process in water treatment due to their threat to human health. It was necessary to develop novel disinfection methods since the conventional chlorine disinfection was inefficient in inactivating chlorine-resistant bacteria, inducing the viable but non-culturable(VBNC) bacteria and forming disinfection by-products(DBPs). In this study, the inactivation of four model strains including Gram-negative(G), Gram-positive(G) and environmental samples by atmospheric-pressure air-liquid discharge plasma(ALDP) was assessed systematically. The results showed that ALDP was superior in inactivating all of the samples compared with chlorination. During 10 min ALDP treatment, the Gbacteria were completely inactivated, and the Gone was inactivated by more than 4.61 logs. The inactivation of bacteria from a campus lake and a wastewater treatment plant effluent exceeded 99.82% and 97.78%, respectively. For G-bacteria, ALDP resulted in a much lower(10~2~10~3 times) levels of VBNC cells than chlorination. ALDP could effectively remove the chlorine-resistant bacteria. More than 96.41% of the intracellular DNA and 99.99% of the extracellular DNA were removed, whereas it was only 56.35% and 12.82% for chlorination. ALDP had a stronger ability to destroy cell structure than chlorination, presumably due to the existence of ROS( ·OH, ~1Oand O). GC-MS analysis showed that ALDP produced less DBPs than chlorination. These findings provided new insights for the application of discharge plasma in water disinfection, which could be complemental or alternative to the conventional disinfection methods.
基金supported by grants from the National Natural Science Foundation of China (31070971,31000959)
文摘The discharge patterns of neurons in auditory centers encode information about sounds.However,few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular recording techniques.Here,we investigated the discharge patterns of inferior collicular（IC）neurons using intracellular recordings to further elucidate the mechanisms underlying the shaping of discharge patterns.Under in vivo intracellular recording conditions,recordings were obtained from 66 IC neurons in 18 healthy adult mice（Mus musculus,Km）under free field-stimulation.Fiftyeight of these neurons fired bursts of action potentials（APs）to auditory stimuli and the remaining eight just generated local responses such as excitatory（n=4）or inhibitory（n=4）postsynaptic potentials.Based on the APs and subthreshold responses,the discharge patterns were classified into seven types：phasic（24/58,41.4%）,phasic burst（8/58,13.8%）,pauser（4/58,6.9%）,phasic-pauser（1/58,1.7%）,chopper（2/58,3.4%）,primary-like tonic（14/58,24.1%）and sound-induced inhibitory（5/58,8.6%）.We concluded that（1）IC neurons exhibit at least seven distinct discharge patterns;（2）inhibition participates in shaping the discharge pattern of most IC neurons and plays a role in sculpting the pattern,except for the primary-like tonic pattern which was not shapedby inhibition;and（3）local neural circuits are the likely structural basis that shapes the discharge patterns of IC neurons and can be formed either in the IC or in lower-level auditory structures.
