Atmospheric pressure cold plasma, with advantages such as high particle activity, no thermal damage, high efficiency and direct and friendly contact with human tissues, is considered to have great potential in biomedi...Atmospheric pressure cold plasma, with advantages such as high particle activity, no thermal damage, high efficiency and direct and friendly contact with human tissues, is considered to have great potential in biomedical applications. Therefore, 'plasma medicine' as a new interdiscipline has been developed in the past two decades. This review first briefly describes the development of typical plasma sources suitable for biomedical applications, and those with different discharge forms are simply compared, evaluated and summarized. Subsequently, measurement of the crucial gaseous reactive particles(e.g. OH and O) and their spatio-temporal distributions are introduced. Meanwhile, the generation and variation rules and the related critical macroscopic parameters of the plasma-induced aqueous reactive species are summarized. Finally, related studies in the last ten years on the mechanisms of the plasma-driven microbial inactivation and plasma-induced apoptosis of cancer cells are introduced. Moreover, some scientific problems that need to be urgently solved in the field of plasma medicine are also discussed. This review will provide useful guidance for future related research.展开更多
A typical quinolones antibiotic ciprofloxacin(CIP) in aqueous solution was degraded by a gas–liquid discharge non-thermal plasma system. The discharge plasma power and the emission intensity of the excited reactive s...A typical quinolones antibiotic ciprofloxacin(CIP) in aqueous solution was degraded by a gas–liquid discharge non-thermal plasma system. The discharge plasma power and the emission intensity of the excited reactive species(RS) generated in the gas phase were detected by the oscilloscope and the optical emission spectroscopy. The effects of various parameters on CIP degradation, i.e. input powers, initial concentrations addition of radical scavengers and p H values were investigated. With the increase of discharge power, the degradation efficiency increased but the energy efficiency significantly reduced. The degradation efficiency also reduced under high concentration of initial CIP conditions due to the competitive reactions between the plasma-induced RS with the degradation intermediates of CIP. Different radical scavengers(isopropanol and CCl_4) on ·OH and H· were added into the reaction system and the oxidation effects of ·OH radicals have been proved with high degradation capacity on CIP.Moreover, the long-term degradation effect on CIP in the plasma-treated aqueous solution proved that the long-lived RS(H_2O_2 and O_3, etc) might play key roles on the stay effect through multiple aqueous reactions leading to production of ·OH. The degradation intermediates were determined by the method of electrospray ionization(+)-mass spectroscopy, and the possible degradation mechanism were presented.展开更多
We investigate characteristics of multi-arc torches with three pairs of electrodes(three cathodes and three anodes)and their performance on the spheroidization of SiO2 powder.The effect of electrode arrangement,includ...We investigate characteristics of multi-arc torches with three pairs of electrodes(three cathodes and three anodes)and their performance on the spheroidization of SiO2 powder.The effect of electrode arrangement,including adjacent pattern(AD pattern,adjacent electrodes powered by one power supply)and opposite pattern(OP pattern,opposite electrodes powered by one power supply),on the dynamics of arc plasma is investigated based on synchronous acquisition of electrical and optical signals.The results show that both the voltage and spatial distribution of each arc of multiple arcs are more stable compared with those of a single arc.The fluctuation of an arc in multiple arcs mainly comes from the small-scale arc-to-arc restrikes among multiple arcs.Moreover,these arc-to-arc restrikes occur more frequently among multiple arc columns in OP pattern than in AD pattern.Moreover,the high-temperature area of the central region of arc chamber in OP pattern is larger than that in AP pattern.For the spheroidization of SiO2 in this multi-arc generator,the spheronization degrees of plasma treated silica in OP pattern are at least 20%higher than those in AD pattern.展开更多
Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized t...Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized to degrade aqueous SMX,and the effects of various operating parameters(working gas,discharge power,etc)on SMX degradation performance were studied.The experimental results showed that the DBD plasma jet can obtain a relatively high degradation efficiency for SMX when the discharge power is high with an oxygen atmosphere,the initial concentration of SMX is low,and the aqueous solution is under acidic conditions.The reactive species produced in the liquid phase were detected,and OH radicals and O3were found to play a significant role in the degradation of SMX.Moreover,the process of SMX degradation could be better fitted by the quasi-first-order reaction kinetic equation.The analysis of the SMX degradation process indicated that SMX was gradually decomposed and 4-amino benzene sulfonic acid,benzene sulfonamide,4-nitro SMX,and phenylsulfinyl acid were detected,and thus three possible degradation pathways were finally proposed.The mineralization degree of SMX reached 90.04%after plasma treatment for 20 min,and the toxicity of the solution fluctuated with the discharge time but eventually decreased.展开更多
Atmospheric pressure helium/water dielectric barrier discharge(DBD) plasma is used to investigate the generation of reactive species in a gas–liquid interface and in a liquid. The emission intensity of the reactive s...Atmospheric pressure helium/water dielectric barrier discharge(DBD) plasma is used to investigate the generation of reactive species in a gas–liquid interface and in a liquid. The emission intensity of the reactive species is measured by optical emission spectroscopy(OES)with different discharge powers at the gas–liquid interface. Spectrophotometry is used to analyze the reactive species induced by the plasma in the liquid. The concentration of OH radicals reaches 2.2 μm after 3 min of discharge treatment. In addition, the concentration of primary longlived reactive species such as H_2O_2, NO_3^- and O_3 are measured based on plasma treatment time.After 5 min of discharge treatment, the concentration of H_2O_2, NO_3^-, and O_3 increased from 0 mg?·?L^(-1) to 96 mg?·?L^(-1), 19.5 mg?·?L^(-1), and 3.5 mg?·?L^(-1), respectively. The water treated by plasma still contained a considerable concentration of reactive species after 6 h of storage. The results will contribute to optimizing the DBD plasma system for biological decontamination.展开更多
To obtain large-volume non-thermal arc plasma(NTAP), a multiple NTAP generator with three pairs of electrodes has been developed. The arc plasma characteristics, including dynamic process, spatial distribution, and ro...To obtain large-volume non-thermal arc plasma(NTAP), a multiple NTAP generator with three pairs of electrodes has been developed. The arc plasma characteristics, including dynamic process, spatial distribution, and rotation velocity in the discharge zone, were investigated by high speed photograph and image processing methods. The results showed that the dynamic behaviors and spatial distribution of the arc plasma were strongly related to the electrode configuration.A swirl flow of multi-arc plasma was formed by adjusting the electrode configuration, and a steady luminance area was clearly observed in the center of the discharge zone. Moreover, the size of the luminance area increased by decreasing the gas flow rate. The electrical connection in series could be formed between/among these arc columns with their respective driving power supplies in the multi-arc dynamic evolution process. An approximately periodical process of acceleration and deceleration of the arc rotation velocity was observed in the multi-arc generator with swirl flow configuration. In general, the mean velocity of arc rotation was higher in the multi-arc generator with swirl flow configuration when a pair of electrodes driven by a power supply were opposite to each other rather than adjacent.展开更多
The enhanced volume of thermal plasma is produced by a multi-arc thermal plasma generator with three pairs of discharge electrodes driven by three directed current power suppliers.Combined with a high-speed camera and...The enhanced volume of thermal plasma is produced by a multi-arc thermal plasma generator with three pairs of discharge electrodes driven by three directed current power suppliers.Combined with a high-speed camera and an oscilloscope,which acquire optical and electric signals synchronously,the dynamic behavior of different kinds of multi-arc discharge adjusted by the electrode arrangement is investigated.Also,the spatial distributions and instability of the arc discharge are analyzed in four electrode configurations using the gray value statistical method.It is found that the cathodic arcs mainly show a contracting state,while the anodic arcs have a trend of transition from shrinkage to a diffusion-like state with the increase of the discharge current.As a result of the adjustment of the electrode configuration,a high temperature region formed in the center of the discharge region in configurations of adjacent electrodes with opposite flow distribution and opposite electrodes with swirl flow distribution due to severe fluctuation of arcs.The discharge voltage rises with increased discharge current in this novel multi-arc plasma generator.It is also found that anode ablation mainly occurs on the conical surface at the copper electrode tip,while cathode erosion mainly occurs on the surface of the inserted tungsten and the nearby copper.展开更多
The transition process in ring-to-volume discharge in H mode in inductively coupled plasma torches at atmospheric pressure is investigated by analyzing the time resolved image taken by a high speed camera. The effects...The transition process in ring-to-volume discharge in H mode in inductively coupled plasma torches at atmospheric pressure is investigated by analyzing the time resolved image taken by a high speed camera. The effects of input power, plasma working gas flow rate, and its composition on the transition dynamics are also discussed.The results show that the discharge plasma has experienced ring discharge, and the development stage diffused from the boundary to the center in the confinement tube, and steady volume discharge after entering the H mode. Increasing input power, sheath gas flow rate and hydrogen contents in plasma working gas are all able to lessen the time consumed in the transition process in ring-to-volume discharge.展开更多
The oscillator strengths of the valence-shell excitations of C_(2)H_(2) are extremely important for testing theoretical models and studying interstellar gases.In this study,the high-resolution inelastic x-ray scatteri...The oscillator strengths of the valence-shell excitations of C_(2)H_(2) are extremely important for testing theoretical models and studying interstellar gases.In this study,the high-resolution inelastic x-ray scattering(IXS)method is adopted to determine the generalized oscillator strengths(GOSs)of the valence-shell excitations of C_(2)H_(2) at a photon energy of10 ke V.The GOSs are extrapolated to their zero limit to obtain the corresponding optical oscillator strengths(OOSs).Through taking a completely different experimental method of the IXS,the present results offer the high energy limit for electron collision to satisfy the first Born approximation(FBA)and cross-check the previous experimental and theoretical results independently.The comparisons indicate that an electron collision energy of 1500 e V is not enough for C_(2)H_(2) to satisfy the FBA for the large squared momentum transfer,and the line saturation effect limits the accuracy of the OOSs measured by the photoabsorption method.展开更多
microRNAs (miRNAs)are endogenous small non-coding RNAs that bind to mRNAs and target them for cleavage and/or translational repression,leading to gene silencing.We previously developed short tandem target mimic (STTM)...microRNAs (miRNAs)are endogenous small non-coding RNAs that bind to mRNAs and target them for cleavage and/or translational repression,leading to gene silencing.We previously developed short tandem target mimic (STTM)technology to deactivate endogenous miRNAs in Arabidopsis.Here,we created hundreds of STTMs that target both conserved and species-specific miRNAs in Arabidopsis,tomato,rice,and maize,providing a resource for the functional interrogation of miRNAs.We not only revealed the functions of several miRNAs in plant development,but also demonstrated that tissue-specific inactivation of a few miRNAs in rice leads to an increase in grain size without adversely affecting overall plant growth and development.RNA-seq and small RNAseq analyses of STTM156/157 and STTM165/166 transgenic plants revealed the roles of these miRNAs in plant hormone biosynthesis and activation,secondary metabolism,and ion-channel activity-associated electrophysiology,demonstrating that STTM technology is an effective approach for studying miRNA functions.To facilitate the study and application of STTM transgenic plants and to provide a useful platform for storing and sharing of information about miRNA-regulated gene networks,we have established an online Genome Browser (https://blossom.ffr.mtu.edu/designindex2.php) to display the transcriptomic and miRNAomic changes in STTMinduced miRNA knockdown plants.展开更多
Insulin-producing pancreaticβcell death is the fundamental cause of type 1 diabetes(T1D)and a contributing factor to type 2 diabetes(T2D).Moreover,metabolic disorder is another hallmark of T2D.Mammalian sterile 20-li...Insulin-producing pancreaticβcell death is the fundamental cause of type 1 diabetes(T1D)and a contributing factor to type 2 diabetes(T2D).Moreover,metabolic disorder is another hallmark of T2D.Mammalian sterile 20-like kinase 1(MST1)contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreaticβcell dysfunction.AMP-activated protein kinase(AMPK)is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic diseases.Thus,pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes therapy.Here,we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39,which exhibits anti-apoptosis efficacy and improves the survival of pancreaticβcells under diabetogenic conditions,as well as primary pancreatic islets in an ex vivo disease model.Mechanistically,IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro,combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic mice.Taken together,IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.展开更多
The two most common inherited forms of colorectal cancer(CRC)are familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.They are caused by germline mutations in the APC and mismatch repair genes,...The two most common inherited forms of colorectal cancer(CRC)are familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.They are caused by germline mutations in the APC and mismatch repair genes,respectively.1 The simultaneous inheritance of both an APC gene mutation and a mismatch repair gene mutation is very rare.In this study,we reported a coinheritance of mutations in the APC and MLH1 genes in a 20-year-old patient with CRC and multiple polyposes.We described for the first time the somatic mutational profile of a colorectal tumor harboring concurrent germline mutations in the APC and MLH1 genes.展开更多
Since the dinical approval of imatinib,the discovery of protein kinase downregulators entered a prosperous age.However,challenges still exist in the discovery of kinase downregulator drugs,such as the high failure rat...Since the dinical approval of imatinib,the discovery of protein kinase downregulators entered a prosperous age.However,challenges still exist in the discovery of kinase downregulator drugs,such as the high failure rate during development,side effects,and drug-resistance problems.With the progress made through multidisciplinary efforts,an increasing number of new approaches have bee n applied to solve the above problems duri ng the discovery process of kin ase down regulators.In terms of in vitro and in vivo drug evaluation,progress was also made in cellular and animal model platforms for better and more clinically relevant drug assessme nt.Here,we review the adva nces in drug desig n strategies,drug property evaluatio n tech no logies,and efficacy evaluatio n models and tech no logies.Finally,we discuss the challenges and perspectives in the development of kin ase down regulator drugs.展开更多
Dear Editor,Bruton’s tyrosine kinase(BTK)plays a crucial role in the B-cell receptor(BCR)signaling which is essential for B-cell proliferation,differentiation,and cell migration.Aberrant BCR activation has been ident...Dear Editor,Bruton’s tyrosine kinase(BTK)plays a crucial role in the B-cell receptor(BCR)signaling which is essential for B-cell proliferation,differentiation,and cell migration.Aberrant BCR activation has been identified as a major pathogenic factor in several B-cell non-Hodgkin lymphoma(B-NHL)subtypes,including diffuse large Bcell lymphoma(DLBCL),mantle cell lymphoma(MCL),follicular lymphoma(FL),and chronic lymphocytic leukemia(CLL).1 Therefore,BTK has been recognized as a validated therapeutic target for B-cell malignancies.Ibrutinib,the first approved BTK inhibitor that binds irreversibly to cysteine residue 481,has shown potent clinical activity in the majority of CD20 positive B-cell malignancies.2 However,due to the inhibition of off-target kinases such as EGFR,ITK,and TXK,which have a cysteine residue at the identical position of Cys481 of BTK,Ibrutinib also results in some adverse events,such as the antagonizing Rituximab-dependent NK-cell-mediated antibody-dependent cell-mediated cytotoxicity(ADCC)due to its irreversible binding to ITK,which is required for FcR-stimulated NK cell function.3 Although several secondary generation inhibitors have shown improved selectivity,4,5 more pharmacologically diverse novel inhibitors are still highly demanded in the clinic.展开更多
Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival.Targeting CDK9 has shown potent anti-tumor activity in clinical trials amon...Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival.Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers.However,the study and knowledge on drug resistance to CDK9 inhibitors are very limited.In this study,we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152.Through genomic sequencing,we identified in the kinase domain of CDK9 a mutation L156F,which is also a coding SNP in the CDK9 gene.By knocking in L156F into cancer cells using CRISPR/Cas9,we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors,not only ATP competitive inhibitor but also PROTAC degrader.Mechanistically,CDK9 L156F disrupts the binding with inhibitors due to steric hindrance,further,the mutation affects the thermal stability and catalytic activity of CDK9 protein.To overcome the drug resistance mediated by the CDK9-L156F mutation,we discovered a compound,IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant.Together,we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.展开更多
Enhancer of zeste homolog 2(EZH2),an enzymatic subunit of PRC2 complex,plays an important role in tumor development and progression through its catalytic and noncatalytic activities.Overexpression or gain-of-function ...Enhancer of zeste homolog 2(EZH2),an enzymatic subunit of PRC2 complex,plays an important role in tumor development and progression through its catalytic and noncatalytic activities.Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer(TNBC)and diffuse large B-cell lymphoma(DLBCL).As a result,it has gained interest as a potential therapeutic target.The currently available EZH2 inhibitors,such as EPZ6438 and GSK126,are of benefit for clinical using or reached clinical trials.However,certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins.Thus,it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition.Here,through a rational design and chemical screening,we discovered a new irreversible EZH2 inhibitor,IHMT-337,which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway.Moreover,we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4,a novel PRC2 complex-and enzymatic activity-independent function of EZH2.More significantly,our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo.Taken together,our findings demonstrate that in addition to enzymatic inhibition,destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.展开更多
Herein,we report a homemade new Nd:YAG crystal rod that contains a gradient dopant of 0.39–0.80 at.%Nd3+ from end to end,achieving superior performance of a 2 kHz Nd:YAG pulse laser at 1064 nm. The optical-tooptical ...Herein,we report a homemade new Nd:YAG crystal rod that contains a gradient dopant of 0.39–0.80 at.%Nd3+ from end to end,achieving superior performance of a 2 kHz Nd:YAG pulse laser at 1064 nm. The optical-tooptical conversion efficiency reached 53.8%,and the maximum output power of the laser was 24.2 W,enhanced by 35.9% compared with a uniform crystal rod with the same total concentration of Nd3+. Significantly,our experiments revealed that the gradient concentration crystal produced a relatively even pumping distribution along the rod axis,greatly reducing the temperature gradient as well as having a smaller thermal effect. The pump and thermal distribution smoothing obviously improved the features of laser oscillation and output.展开更多
Acute myeloid leukemia (AML) is an aggressive hematologicmalignancy characterized by the abnormal differentiation andrapid proliferation of hematopoietic cells. The causes of this typeof blood cancer are multiple, wit...Acute myeloid leukemia (AML) is an aggressive hematologicmalignancy characterized by the abnormal differentiation andrapid proliferation of hematopoietic cells. The causes of this typeof blood cancer are multiple, with approximately 30% of AMLpatients characterized by expression of the internal tandemduplication (ITD) of the Fms-like tyrosine kinase 3 (FLT3) gene.1Despite the availability of effective FLT3 inhibitors, alone orcombined with conventional chemotherapy, for the treatment ofFLT3-ITD AML, there is a risk of leukemia relapse due to drugresistance. Reasons for drug resistance include the evolution ofthe secondary mutations of FLT3 in response to drug treatmentand compensatory activation of survival signaling pathways.2Therefore, the discovery of new drug targets and noveltherapeutic strategies for FLT3-ITD-positive AML is imperativefor overcoming resistance to FLT3 inhibitors.展开更多
Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by ...Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by risks because it seriously harms normal cells while killing cancer cells.The side effects can lower cancer patients’quality of life and are very unpredictable due to individual differences(Bentzen,2006).展开更多
基金financially supported by National Natural Science Foundation of China (Grant Nos. 51777206, 51807046 and 51877208)the Natural Science Foundation of Anhui Province (Grant Nos. 1908085MA29 and 1808085MA13)。
文摘Atmospheric pressure cold plasma, with advantages such as high particle activity, no thermal damage, high efficiency and direct and friendly contact with human tissues, is considered to have great potential in biomedical applications. Therefore, 'plasma medicine' as a new interdiscipline has been developed in the past two decades. This review first briefly describes the development of typical plasma sources suitable for biomedical applications, and those with different discharge forms are simply compared, evaluated and summarized. Subsequently, measurement of the crucial gaseous reactive particles(e.g. OH and O) and their spatio-temporal distributions are introduced. Meanwhile, the generation and variation rules and the related critical macroscopic parameters of the plasma-induced aqueous reactive species are summarized. Finally, related studies in the last ten years on the mechanisms of the plasma-driven microbial inactivation and plasma-induced apoptosis of cancer cells are introduced. Moreover, some scientific problems that need to be urgently solved in the field of plasma medicine are also discussed. This review will provide useful guidance for future related research.
基金financially supported by National Natural Science Foundation of China (Nos. 51777206 and 51541807)Natural Science Foundation of Anhui Province (Nos. 1708085MB47 and 1708085MA13)+2 种基金Foundation of Anhui Province Key Laboratory of Medical Physics and Technology (No. LMPT2017Y7BP0U1581)Doctoral Fund of Ministry of Education of China (No. 2017M612058)Specialized Research Fund for the Doctoral Program of Hefei University of Technology (Nos. JZ2016HGBZ0768, JZ2016HGBZ0769, and JZ2017HGBZ0944)
文摘A typical quinolones antibiotic ciprofloxacin(CIP) in aqueous solution was degraded by a gas–liquid discharge non-thermal plasma system. The discharge plasma power and the emission intensity of the excited reactive species(RS) generated in the gas phase were detected by the oscilloscope and the optical emission spectroscopy. The effects of various parameters on CIP degradation, i.e. input powers, initial concentrations addition of radical scavengers and p H values were investigated. With the increase of discharge power, the degradation efficiency increased but the energy efficiency significantly reduced. The degradation efficiency also reduced under high concentration of initial CIP conditions due to the competitive reactions between the plasma-induced RS with the degradation intermediates of CIP. Different radical scavengers(isopropanol and CCl_4) on ·OH and H· were added into the reaction system and the oxidation effects of ·OH radicals have been proved with high degradation capacity on CIP.Moreover, the long-term degradation effect on CIP in the plasma-treated aqueous solution proved that the long-lived RS(H_2O_2 and O_3, etc) might play key roles on the stay effect through multiple aqueous reactions leading to production of ·OH. The degradation intermediates were determined by the method of electrospray ionization(+)-mass spectroscopy, and the possible degradation mechanism were presented.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11875295 and 11535003)the National Key R&D Program of China(Grant No.2019YFC0119000)+1 种基金Provincial Science and Technology Major Project of Anhui Province,China(Grant No.17030801035)Key Program of 13th Five-Year Plan,CASHIPS,China(Grant No.KP-2017-25).
文摘We investigate characteristics of multi-arc torches with three pairs of electrodes(three cathodes and three anodes)and their performance on the spheroidization of SiO2 powder.The effect of electrode arrangement,including adjacent pattern(AD pattern,adjacent electrodes powered by one power supply)and opposite pattern(OP pattern,opposite electrodes powered by one power supply),on the dynamics of arc plasma is investigated based on synchronous acquisition of electrical and optical signals.The results show that both the voltage and spatial distribution of each arc of multiple arcs are more stable compared with those of a single arc.The fluctuation of an arc in multiple arcs mainly comes from the small-scale arc-to-arc restrikes among multiple arcs.Moreover,these arc-to-arc restrikes occur more frequently among multiple arc columns in OP pattern than in AD pattern.Moreover,the high-temperature area of the central region of arc chamber in OP pattern is larger than that in AP pattern.For the spheroidization of SiO2 in this multi-arc generator,the spheronization degrees of plasma treated silica in OP pattern are at least 20%higher than those in AD pattern.
基金supported jointly by National Natural Science Foundation of China(Nos.U20A20372,51807046,51777206)the Natural Science Foundation of Anhui Province(Nos.2108085MD136,1908085MA29)。
文摘Sulfamethoxazole(SMX)is an antibiotic and widely present in aquatic environments,so it presents a serious threat to human health and sustainable development.A dielectric barrier discharge(DBD)plasma jet was utilized to degrade aqueous SMX,and the effects of various operating parameters(working gas,discharge power,etc)on SMX degradation performance were studied.The experimental results showed that the DBD plasma jet can obtain a relatively high degradation efficiency for SMX when the discharge power is high with an oxygen atmosphere,the initial concentration of SMX is low,and the aqueous solution is under acidic conditions.The reactive species produced in the liquid phase were detected,and OH radicals and O3were found to play a significant role in the degradation of SMX.Moreover,the process of SMX degradation could be better fitted by the quasi-first-order reaction kinetic equation.The analysis of the SMX degradation process indicated that SMX was gradually decomposed and 4-amino benzene sulfonic acid,benzene sulfonamide,4-nitro SMX,and phenylsulfinyl acid were detected,and thus three possible degradation pathways were finally proposed.The mineralization degree of SMX reached 90.04%after plasma treatment for 20 min,and the toxicity of the solution fluctuated with the discharge time but eventually decreased.
基金jointly supported by the Science Foundation of the Institute of Plasma Physics, the Chinese Academy of Sciences (No. DSJJ-14-YY02)National Natural Science Foundation of China (Grant Nos. 11475174 and 51777206)
文摘Atmospheric pressure helium/water dielectric barrier discharge(DBD) plasma is used to investigate the generation of reactive species in a gas–liquid interface and in a liquid. The emission intensity of the reactive species is measured by optical emission spectroscopy(OES)with different discharge powers at the gas–liquid interface. Spectrophotometry is used to analyze the reactive species induced by the plasma in the liquid. The concentration of OH radicals reaches 2.2 μm after 3 min of discharge treatment. In addition, the concentration of primary longlived reactive species such as H_2O_2, NO_3^- and O_3 are measured based on plasma treatment time.After 5 min of discharge treatment, the concentration of H_2O_2, NO_3^-, and O_3 increased from 0 mg?·?L^(-1) to 96 mg?·?L^(-1), 19.5 mg?·?L^(-1), and 3.5 mg?·?L^(-1), respectively. The water treated by plasma still contained a considerable concentration of reactive species after 6 h of storage. The results will contribute to optimizing the DBD plasma system for biological decontamination.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11875295 and 11535003)Provincial Science and Technology Major Project of Anhui Province,China(Grant No.17030801035)Key Program of 13th Five-year Plan,CASHIPS,China(Grant No.KP-2017-25)
文摘To obtain large-volume non-thermal arc plasma(NTAP), a multiple NTAP generator with three pairs of electrodes has been developed. The arc plasma characteristics, including dynamic process, spatial distribution, and rotation velocity in the discharge zone, were investigated by high speed photograph and image processing methods. The results showed that the dynamic behaviors and spatial distribution of the arc plasma were strongly related to the electrode configuration.A swirl flow of multi-arc plasma was formed by adjusting the electrode configuration, and a steady luminance area was clearly observed in the center of the discharge zone. Moreover, the size of the luminance area increased by decreasing the gas flow rate. The electrical connection in series could be formed between/among these arc columns with their respective driving power supplies in the multi-arc dynamic evolution process. An approximately periodical process of acceleration and deceleration of the arc rotation velocity was observed in the multi-arc generator with swirl flow configuration. In general, the mean velocity of arc rotation was higher in the multi-arc generator with swirl flow configuration when a pair of electrodes driven by a power supply were opposite to each other rather than adjacent.
基金supported by National Natural Science Foundation of China(No.11875295)the National Key R&D Program of China(No.2019YFC0119000)。
文摘The enhanced volume of thermal plasma is produced by a multi-arc thermal plasma generator with three pairs of discharge electrodes driven by three directed current power suppliers.Combined with a high-speed camera and an oscilloscope,which acquire optical and electric signals synchronously,the dynamic behavior of different kinds of multi-arc discharge adjusted by the electrode arrangement is investigated.Also,the spatial distributions and instability of the arc discharge are analyzed in four electrode configurations using the gray value statistical method.It is found that the cathodic arcs mainly show a contracting state,while the anodic arcs have a trend of transition from shrinkage to a diffusion-like state with the increase of the discharge current.As a result of the adjustment of the electrode configuration,a high temperature region formed in the center of the discharge region in configurations of adjacent electrodes with opposite flow distribution and opposite electrodes with swirl flow distribution due to severe fluctuation of arcs.The discharge voltage rises with increased discharge current in this novel multi-arc plasma generator.It is also found that anode ablation mainly occurs on the conical surface at the copper electrode tip,while cathode erosion mainly occurs on the surface of the inserted tungsten and the nearby copper.
基金Supported by the National Natural Science Foundation of China under Grant Nos 21377133,11535003 and 11505223the Provincial Science and Technology Major Project of Anhui Province under Grant No 17030801035the Science and Technology Service Network Initiative of Chinese Academy of Sciences
文摘The transition process in ring-to-volume discharge in H mode in inductively coupled plasma torches at atmospheric pressure is investigated by analyzing the time resolved image taken by a high speed camera. The effects of input power, plasma working gas flow rate, and its composition on the transition dynamics are also discussed.The results show that the discharge plasma has experienced ring discharge, and the development stage diffused from the boundary to the center in the confinement tube, and steady volume discharge after entering the H mode. Increasing input power, sheath gas flow rate and hydrogen contents in plasma working gas are all able to lessen the time consumed in the transition process in ring-to-volume discharge.
基金Project supported by the Strategic Priority Research Program of the Chinese Academy of Science(Grant No.XDB34000000)the National Natural Science Foundation of China(Grant Nos.U1932207 and 12104437)+3 种基金the National Key Research and Development Program of China(Grant No.2017YFA0402300)The support from the Heavy Ion Research Facility in Lanzhou(HIRFL)the BL12XU of SPring-8 with the approval of Japan Synchrotron Radiation Research Institute(Proposal No.2019A4275)“National”Synchrotron Radiation Research Center,Taiwan,China(Proposal No.2019-2-089-1)。
文摘The oscillator strengths of the valence-shell excitations of C_(2)H_(2) are extremely important for testing theoretical models and studying interstellar gases.In this study,the high-resolution inelastic x-ray scattering(IXS)method is adopted to determine the generalized oscillator strengths(GOSs)of the valence-shell excitations of C_(2)H_(2) at a photon energy of10 ke V.The GOSs are extrapolated to their zero limit to obtain the corresponding optical oscillator strengths(OOSs).Through taking a completely different experimental method of the IXS,the present results offer the high energy limit for electron collision to satisfy the first Born approximation(FBA)and cross-check the previous experimental and theoretical results independently.The comparisons indicate that an electron collision energy of 1500 e V is not enough for C_(2)H_(2) to satisfy the FBA for the large squared momentum transfer,and the line saturation effect limits the accuracy of the OOSs measured by the photoabsorption method.
基金the National Science Foundation,USA (IOS-1048216 and IOS-1340001)the National Natural Science Foundation of China (31571679,31501292,31871554)+1 种基金the Major Science and Technology Project of Henan Province (141100110600)the Support Plan of Science and Technology Innovation Team in Universities of Henan Province (171RTSTHN015),and the Key Scientific Research Project in Universities of Henan Province (16A210009).G.T.is also supported by the Guangdong Innovation Research Team Fund (2014ZT058078)and the 111 Project (D16014)to Henan University.S.T.was supported by a post-doctoral fellowship from Henan Agricultural University.F.M.was a visiting scholar supported by the China Scholarship Council (CSC).T.P.,Z.Z.,L.S.,and L.T.were visiting PhD students supported by scholarships from Henan Agricultural University.
文摘microRNAs (miRNAs)are endogenous small non-coding RNAs that bind to mRNAs and target them for cleavage and/or translational repression,leading to gene silencing.We previously developed short tandem target mimic (STTM)technology to deactivate endogenous miRNAs in Arabidopsis.Here,we created hundreds of STTMs that target both conserved and species-specific miRNAs in Arabidopsis,tomato,rice,and maize,providing a resource for the functional interrogation of miRNAs.We not only revealed the functions of several miRNAs in plant development,but also demonstrated that tissue-specific inactivation of a few miRNAs in rice leads to an increase in grain size without adversely affecting overall plant growth and development.RNA-seq and small RNAseq analyses of STTM156/157 and STTM165/166 transgenic plants revealed the roles of these miRNAs in plant hormone biosynthesis and activation,secondary metabolism,and ion-channel activity-associated electrophysiology,demonstrating that STTM technology is an effective approach for studying miRNA functions.To facilitate the study and application of STTM transgenic plants and to provide a useful platform for storing and sharing of information about miRNA-regulated gene networks,we have established an online Genome Browser (https://blossom.ffr.mtu.edu/designindex2.php) to display the transcriptomic and miRNAomic changes in STTMinduced miRNA knockdown plants.
基金supported by the National Natural Science Foundation of China (Grant No.32171479)the Natural Science Foundation of Anhui Province (Grant No,2108085QH377,1908085QH345)+2 种基金the Frontier Science Key Research Program of CAS (Grant QYZDB-SSW-SLH037)the Collaborative Innovation Program of Hefei Science Center,CAS (Grant No.2021HSC-CIP014)the CASHIPS Director’s Fund (Grant Nos.YZJJZX202011,YZJJ2021QN38).
文摘Insulin-producing pancreaticβcell death is the fundamental cause of type 1 diabetes(T1D)and a contributing factor to type 2 diabetes(T2D).Moreover,metabolic disorder is another hallmark of T2D.Mammalian sterile 20-like kinase 1(MST1)contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreaticβcell dysfunction.AMP-activated protein kinase(AMPK)is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic diseases.Thus,pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes therapy.Here,we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39,which exhibits anti-apoptosis efficacy and improves the survival of pancreaticβcells under diabetogenic conditions,as well as primary pancreatic islets in an ex vivo disease model.Mechanistically,IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro,combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic mice.Taken together,IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.
基金supported by the Key Research and Development Program of Anhui Province,China(No.2022e07020048)the Clinical Research Incubation Program of The Second Hospital of Anhui Medical University,China(No.2020LCZD07)+2 种基金the National Natural Science Foundation of China(No.81872438)the Program of Research and Development of Key Common Technologies and Engineering of Major Scientific and Technological Achievements in Hefei,China(No.2021YL007)the Collaborative Innovation Program of Hefei Science Center CAS(China)(No.2022HSC-CIP015).
文摘The two most common inherited forms of colorectal cancer(CRC)are familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.They are caused by germline mutations in the APC and mismatch repair genes,respectively.1 The simultaneous inheritance of both an APC gene mutation and a mismatch repair gene mutation is very rare.In this study,we reported a coinheritance of mutations in the APC and MLH1 genes in a 20-year-old patient with CRC and multiple polyposes.We described for the first time the somatic mutational profile of a colorectal tumor harboring concurrent germline mutations in the APC and MLH1 genes.
基金This work was supported by the National Natural Science Foundation of China(Grant No.81903650)the Natural Science Foundation of Anhui Province(Grant Nos.1808085MH274 and 2008085MH274)+3 种基金the China Postdoctoral Science Foundation(Grant Nos.2020M671916 and 2019M652057)the Postdoctoral Science Foundation of Anhui Province(Grant Nos.2019B326 and 2019B300)the Frontier Science Key Research Program of CAS(Grant No.QYZDB-SSW-SLH037)the CASHIPS Directors Found(Grant Nos.BJPY2019A03 and YZJJZX202011).
文摘Since the dinical approval of imatinib,the discovery of protein kinase downregulators entered a prosperous age.However,challenges still exist in the discovery of kinase downregulator drugs,such as the high failure rate during development,side effects,and drug-resistance problems.With the progress made through multidisciplinary efforts,an increasing number of new approaches have bee n applied to solve the above problems duri ng the discovery process of kin ase down regulators.In terms of in vitro and in vivo drug evaluation,progress was also made in cellular and animal model platforms for better and more clinically relevant drug assessme nt.Here,we review the adva nces in drug desig n strategies,drug property evaluatio n tech no logies,and efficacy evaluatio n models and tech no logies.Finally,we discuss the challenges and perspectives in the development of kin ase down regulator drugs.
基金supported by the National Natural Science Foundation of China(Grant Nos.81773777,81872748,and 81803366)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(Grant No.2018ZX09711002)+4 种基金the Natural Science Foundation of Anhui Province(Grant No.1808085MH268)the China Postdoctoral Science Foundation(Grants Nos.2018T110634 and 2018M630720)the Frontier Science Key Research Program of CAS(Grant No.QYZDB-SSW-SLH037)the Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology(Grant No.2019HSCCIP011)the CASHIPS Director’s Fund(Grant No.BJPY2019A03)the Key Program of 13th five-year plan of CASHIPS(Grant No.KP-2017-26).
文摘Dear Editor,Bruton’s tyrosine kinase(BTK)plays a crucial role in the B-cell receptor(BCR)signaling which is essential for B-cell proliferation,differentiation,and cell migration.Aberrant BCR activation has been identified as a major pathogenic factor in several B-cell non-Hodgkin lymphoma(B-NHL)subtypes,including diffuse large Bcell lymphoma(DLBCL),mantle cell lymphoma(MCL),follicular lymphoma(FL),and chronic lymphocytic leukemia(CLL).1 Therefore,BTK has been recognized as a validated therapeutic target for B-cell malignancies.Ibrutinib,the first approved BTK inhibitor that binds irreversibly to cysteine residue 481,has shown potent clinical activity in the majority of CD20 positive B-cell malignancies.2 However,due to the inhibition of off-target kinases such as EGFR,ITK,and TXK,which have a cysteine residue at the identical position of Cys481 of BTK,Ibrutinib also results in some adverse events,such as the antagonizing Rituximab-dependent NK-cell-mediated antibody-dependent cell-mediated cytotoxicity(ADCC)due to its irreversible binding to ITK,which is required for FcR-stimulated NK cell function.3 Although several secondary generation inhibitors have shown improved selectivity,4,5 more pharmacologically diverse novel inhibitors are still highly demanded in the clinic.
基金supported by the National Natural Science Foundation of China(Grant Nos.81903650,32171479,82103976)the Natural Science Foundation of Anhui Province(Grant Nos.2008085MH274,2108085QH377,China)+2 种基金the Collaborative Innovation Program of Hefei Science Center,CAS(Grant No.2021HSC-CIP014,China)the CASHIPS Director’s Found(Grant Nos.YZJJZX202011,YZJJ2021QN38,China)supported by the High Magnetic Field Laboratory of Anhui Province。
文摘Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival.Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers.However,the study and knowledge on drug resistance to CDK9 inhibitors are very limited.In this study,we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152.Through genomic sequencing,we identified in the kinase domain of CDK9 a mutation L156F,which is also a coding SNP in the CDK9 gene.By knocking in L156F into cancer cells using CRISPR/Cas9,we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors,not only ATP competitive inhibitor but also PROTAC degrader.Mechanistically,CDK9 L156F disrupts the binding with inhibitors due to steric hindrance,further,the mutation affects the thermal stability and catalytic activity of CDK9 protein.To overcome the drug resistance mediated by the CDK9-L156F mutation,we discovered a compound,IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant.Together,we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.82104198,32171479,82104239)the Natural Science Foundation of Anhui Province(Grant Nos.2008085MH274,2108085QH377)+4 种基金the China Postdoctoral Science Foundation(Grant No.2020M671916)the Frontier Science Key Research Program of CAS(Grant No.QYZDB-SSW-SLH037)the Collaborative Innovation Program of Hefei Science Center,CAS(Grant No.2021HSC-CIP014)the CASHIPS Director’s Found(Grant Nos.BJPY2019A03,YZJJZX202011,YZJJ2021QN38)We are also grateful for the support of the Youth Innovation Promotion Association of CAS support(No.2019437)for H.W.A portion of this work was supported by the High Magnetic Field Laboratory of Anhui Province.
文摘Enhancer of zeste homolog 2(EZH2),an enzymatic subunit of PRC2 complex,plays an important role in tumor development and progression through its catalytic and noncatalytic activities.Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer(TNBC)and diffuse large B-cell lymphoma(DLBCL).As a result,it has gained interest as a potential therapeutic target.The currently available EZH2 inhibitors,such as EPZ6438 and GSK126,are of benefit for clinical using or reached clinical trials.However,certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins.Thus,it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition.Here,through a rational design and chemical screening,we discovered a new irreversible EZH2 inhibitor,IHMT-337,which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway.Moreover,we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4,a novel PRC2 complex-and enzymatic activity-independent function of EZH2.More significantly,our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo.Taken together,our findings demonstrate that in addition to enzymatic inhibition,destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.
基金National Key Research and Development Program of China (2018YFB0407204,2016YFB0701001)。
文摘Herein,we report a homemade new Nd:YAG crystal rod that contains a gradient dopant of 0.39–0.80 at.%Nd3+ from end to end,achieving superior performance of a 2 kHz Nd:YAG pulse laser at 1064 nm. The optical-tooptical conversion efficiency reached 53.8%,and the maximum output power of the laser was 24.2 W,enhanced by 35.9% compared with a uniform crystal rod with the same total concentration of Nd3+. Significantly,our experiments revealed that the gradient concentration crystal produced a relatively even pumping distribution along the rod axis,greatly reducing the temperature gradient as well as having a smaller thermal effect. The pump and thermal distribution smoothing obviously improved the features of laser oscillation and output.
基金We thank Dr Sara J.Buhrlage and Dr James D.Griffin at Dana-Farber Cancer Institutc—Harvard Medical School for theirgenerous and valuable scientific support.Our work wassupported and funded by the National Natural ScienceFoundation of China(82104198)Claudia Adams Barr Award,MPN Rescarch Foundation,and Gabrielle's Angel Foundation.Authorship Contributions:JY wrote the manuscript and EWprovided valuable scientific feedback.
文摘Acute myeloid leukemia (AML) is an aggressive hematologicmalignancy characterized by the abnormal differentiation andrapid proliferation of hematopoietic cells. The causes of this typeof blood cancer are multiple, with approximately 30% of AMLpatients characterized by expression of the internal tandemduplication (ITD) of the Fms-like tyrosine kinase 3 (FLT3) gene.1Despite the availability of effective FLT3 inhibitors, alone orcombined with conventional chemotherapy, for the treatment ofFLT3-ITD AML, there is a risk of leukemia relapse due to drugresistance. Reasons for drug resistance include the evolution ofthe secondary mutations of FLT3 in response to drug treatmentand compensatory activation of survival signaling pathways.2Therefore, the discovery of new drug targets and noveltherapeutic strategies for FLT3-ITD-positive AML is imperativefor overcoming resistance to FLT3 inhibitors.
基金supported by the National Natural Science Foundation of China(Nos.21876176,21777163,21705152,and 22076190)the Youth Innovation Promotion Association,Chinese Academy of Sciences(No.2019432)+3 种基金the Presidential Foundation of Hefei Institute of Physical Sciences of Chinese Academy of Sciences(No.YZJJZX202009)the Functional Development Program of Instrument and Equipment in Chinese Academy of Sciences(No.Y9BS0C1291)the Anhui Provincial Key R&D Program(No.202104d07020003)the Joint Fund of the Second Affiliated Hospital of Anhui Medical University and the Center of Medical Physics and Technology of Hefei Institute of Physical Sciences of the Chinese Academy of Sciences(No.LHJJ2020006)。
文摘Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment(Hachadorian et al.,2020).However,it is accompanied by risks because it seriously harms normal cells while killing cancer cells.The side effects can lower cancer patients’quality of life and are very unpredictable due to individual differences(Bentzen,2006).
基金supported by the National Key R&D Program of China(2021YFA1600202)the National Natural Science Foundation of China(U2032162,81972191,U1932158,and 81871085)+7 种基金Hefei Institutes of Physical Science Director’s Fund(BJPY2021B06)the Collaborative Innovation Program of Hefei Science Center of CAS(2022HSCCIP013)Anhui Provincial Natural Science Foundation(2208085J10)Hefei Municipal Natural Science Foundation(2021009)the Natural Science Foundation of Shandong Province(ZR2019LZL018)the High Magnetic Field Laboratory of Anhui Province(AHHM-FX-2021-04)the Project of China Postdoctoral Science Foundation(2019M652403)the Project of Postdoctoral Innovation of Shandong Province(202002048)。
