Based on bipolar dynamic logic (BDL) and bipolar quantum linear algebra (BQLA) this work introduces bipolar quantum logic gates and quantum cellular combinatorics with a logical interpretation to quantum entanglement....Based on bipolar dynamic logic (BDL) and bipolar quantum linear algebra (BQLA) this work introduces bipolar quantum logic gates and quantum cellular combinatorics with a logical interpretation to quantum entanglement. It is shown that: 1) BDL leads to logically definable causality and generic particle-antiparticle bipolar quantum entanglement;2) BQLA makes composite atom-atom bipolar quantum entanglement reachable. Certain logical equivalence is identified between the new interpretation and established ones. A logical reversibility theorem is presented for ubiquitous quantum computing. Physical reversibility is briefly discussed. It is shown that a bipolar matrix can be either a modular generalization of a quantum logic gate matrix or a cellular connectivity matrix. Based on this observation, a scalable graph theory of quantum cellular combinatorics is proposed. It is contended that this work constitutes an equilibrium-based logical extension to Bohr’s particle-wave complementarity principle, Bohm’s wave function and Bell’s theorem. In the meantime, it is suggested that the result may also serve as a resolution, rather than a falsification, to the EPR paradox and, therefore, a equilibrium-based logical unification of local realism and quantum non-locality.展开更多
Partition-and-Recur (PAR) method is a simple and useful formal method. It can be used to design and testify algo-rithmic programs. In this paper, we propose that PAR method is an effective formal method on solving com...Partition-and-Recur (PAR) method is a simple and useful formal method. It can be used to design and testify algo-rithmic programs. In this paper, we propose that PAR method is an effective formal method on solving combinatorics problems. Furthermore, we formally derive combinatorics problems by PAR method, which cannot only simplify the process of algorithmic program's designing, but also improve its automatization, standardization and correctness. We develop algorithms for two typical combinatorics problems, the number of string scheme and the number of error per-mutation scheme. Lastly, we obtain accurate C++ programs which are transformed by automatic transforming system of PAR platform.展开更多
Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain m...Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain multiple related targets and an appropriate combination can maximize benefits while minimizing adverse reactions.As such,it is especially important to derive mathematical models for their quantitative calculation.In this paper,we introduce mathematical rules for the synergistic,additive,and antagonistic effects of multi-drug combinations developed in our laboratory.We have established a“onebelt,one-line”model and provide examples of the quantitative calculation of the synergistic,additive,and antagonistic effects of a combination of multiple components.We also explain how to scientifically and precisely determine the intensity of these synergies,additions and antagonisms,as well as their corresponding dose ranges,thereby laying a solid theoretical foundation for market listing combinatorial drugs and foods for special medical purposes.展开更多
Modeling of solute transport is a key issue in the area of soil physics and hydrogeology. The most common approach (the convection-dispersion equation) considers an average convection flow rate and Fickian-like disper...Modeling of solute transport is a key issue in the area of soil physics and hydrogeology. The most common approach (the convection-dispersion equation) considers an average convection flow rate and Fickian-like dispersion. Here,we propose a solute transport model in porous media of continuously expanding scale, according to the combinatorics principle. The model supposed actual porous media as a combinative body of many basic segments. First, we studied the solute transport process in each basic segment body, and then deduced the distribution of pore velocity in each basic segment body by difference approximation, finally assembled the solute transport process of each basic segment body into one of the combinative body. The simulation result coincided with the solute transport process observed in test. The model provides useful insight into the solute transport process of the non-Fickian dispersion in continuously expanding scale.展开更多
In recent times,approaches to flood prevention and mitigation have changed a lot.These changes are to shift the focus from flood control to flood risk management,in which the assessment of vulnerability to floods caus...In recent times,approaches to flood prevention and mitigation have changed a lot.These changes are to shift the focus from flood control to flood risk management,in which the assessment of vulnerability to floods caused by each sector and field corresponding to each flood magnitude is typical.Current flood vulnerability assessment studies are basically holistic based on factors affected by floods or in aspects:economy,society and ecological environment,and aspects that are mentioned in all areas of social life.The content of the flood vulnerability assessment method usually considers 3 components:E(Exposure),S(Susceptibility),A(Adaptability-Recovery).Each component will contain many different variables belonging to different objects and different natural-economic-social characteristics in each area.Therefore,for each research area,the evaluation method needs to establish an appropriate set of indicators.A set of indicators used to assess flood vulnerability must:be scientific;be practical;simplify the investigation,collection and synthesis of data.This study has established a set of combinatorial indicators including 27 indicators for the T-BRB(Thach Han-Ben Hai River Basin)on the basis of analysis and synthesis from case studies.展开更多
Security weaknesses in web applications deployed in cloud architectures can seriously affect its data confidentiality and integrity.The construction of the procedure utilized in the static analysis tools of source cod...Security weaknesses in web applications deployed in cloud architectures can seriously affect its data confidentiality and integrity.The construction of the procedure utilized in the static analysis tools of source code security differs and therefore each tool finds a different number of each weakness type for which it is designed.To utilize the possible synergies different static analysis tools may process,this work uses a new method to combine several source codes aiming to investigate how to increase the performance of security weakness detection while reducing the number of false positives.Specifically,five static analysis tools will be combined with the designed method to study their behavior using an updated benchmark for OWASP Top Ten Security Weaknesses(OWASP TTSW).The method selects specific metrics to rank the tools for different criticality levels of web applications considering different weights in the ratios.The findings show that simply including more tools in a combination is not synonymous with better results;it depends on the specific tools included in the combination due to their different designs and techniques.展开更多
Tylosin is a 16-membered macrolide antibiotic widely used in veterinary medicine to control infections caused by Gram-positive pathogens and mycoplasmas.To improve the fermentation titer of tylosin in the hyperproduci...Tylosin is a 16-membered macrolide antibiotic widely used in veterinary medicine to control infections caused by Gram-positive pathogens and mycoplasmas.To improve the fermentation titer of tylosin in the hyperproducing Streptomyces xinghaiensis strain TL01,we sequenced its whole genome and identified the biosynthetic gene cluster therein.Overexpression of the tylosin efflux gene tlrC,the cluster-situated S-adenosyl methionine(SAM)synthetase gene metK_(cs),the SAM biosynthetic genes adoK_(cs)-metFcs,or the pathway-specific activator gene tylR enhanced tylosin production by 18%,12%,11%,and 11%in the respective engineered strains TLPH08-2,TLPH09,TLPH10,and TLPH12.Co-overexpression of metK_(cs)and adoK_(cs)-metFcs as two transcripts increased tylosin production by 22%in the resultant strain TLPH11 compared to that in TL01.Furthermore,combinational overexpression of tlrC,metK_(cs),adoK_(cs)-metFcs,and tylR as four transcripts increased tylosin production by 23%(10.93g/L)in the resultant strain TLPH17 compared to that in TL01.However,a negligible additive effect was displayed upon combinational overexpression in TLPH17 as suggested by the limited increment of fermentation titer compared to that in TLPH08-2.Transcription analyses indicated that the expression of tlrC and three SAM biosynthetic genes in TLPH17 was considerably lower than that of TLPH08-2 and TLPH11.Based on this observation,the five genes were rearranged into one or two operons to coordinate their overexpression,yielding two engineered strains TLPH23 and TLPH24,and leading to further enhancement of tylosin production over TLPH17.In particular,the production of TLPH23 reached 11.35 g/L.These findings indicated that the combinatorial strategy is a promising approach for enhancing tylosin production in high-yielding industrial strains.展开更多
The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
This paper is contributed to the combinatorial properties of the MSS sequences, which are the periodic kneading words of quadratic maps defined on a interval. An explicit expression of adjacency relations on MSS seque...This paper is contributed to the combinatorial properties of the MSS sequences, which are the periodic kneading words of quadratic maps defined on a interval. An explicit expression of adjacency relations on MSS sequences of given lengths is established.展开更多
This paper is contributed to the combinatorial properties of the periodic kneading words of antisymmetric cubic maps defined on a interval. The least words of given lengths, the adjacency relations on the words of giv...This paper is contributed to the combinatorial properties of the periodic kneading words of antisymmetric cubic maps defined on a interval. The least words of given lengths, the adjacency relations on the words of given lengths and the parity-alternative property in some sets of such words are established.展开更多
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome ...Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.展开更多
Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of ...Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of soil and water conservation practices.Numerous studies used the sediment fingerprint techniques to investigate the contribution of different sources in suspended and bed sediment yield of the watersheds.However,the contribution of various land use/land covers in suspended and bed sediment yield for the great Caspian Sea basin is in an aura of ambiguity and the present study was conducted to gather information about an important part of this area in northern Iran,where rangelands are located upstream of Hyrcanian forests and dense agricultural lands are located downstream.The surface soil of different land use/land covers including forest,rangeland,agriculture and streambank lands were sampled in 30 points.Suspended and bed sediments were sampled in the watershed outlet in two high and low water periods.Geochemical characteristics of soil and sediment samples containing 59 elements were measured using ICP-OES GBC Integra.The reliable and suitable tracers from 59 elements were then selected using Range test,Kruskal-Wallis and Discriminant Function Analysis,respectively,in FingerPro package of R software.The results showed that for suspended sediment,streambank and rangeland had the highest contributions of 86.2%and 47.5%,respectively,in two high and low water periods.For bed sediment,in two high and low water periods,rangeland and streambank had the highest contributions of 73.8%and 84.4%,respectively.Land use change and especially human activities such as agriculture,road construction and development of residential areas along the main river riparian zone has led to a significant increase in suspended and bed sediments.展开更多
An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation devi...An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation device and gated MCP imager,and a spatial resolution of 100μm by using an electronic imaging system comprising combined magnetic lenses.The spatial resolution characteristics of the camera were studied both theoretically and experimentally.The results showed that the camera with combined magnetic lenses reduced the field curvature and acquired a larger working area.A working area with a diameter of 53 mm was created by applying four magnetic lenses to the camera.Furthermore,the camera was used to detect the X-rays produced by the laser-targeting device.The diagnostic results indicated that the width of the X-ray pulse was approximately 18 ps.展开更多
Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in undergroun...Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.展开更多
A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the mol...A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.展开更多
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvatio...Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.展开更多
The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitud...The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
文摘Based on bipolar dynamic logic (BDL) and bipolar quantum linear algebra (BQLA) this work introduces bipolar quantum logic gates and quantum cellular combinatorics with a logical interpretation to quantum entanglement. It is shown that: 1) BDL leads to logically definable causality and generic particle-antiparticle bipolar quantum entanglement;2) BQLA makes composite atom-atom bipolar quantum entanglement reachable. Certain logical equivalence is identified between the new interpretation and established ones. A logical reversibility theorem is presented for ubiquitous quantum computing. Physical reversibility is briefly discussed. It is shown that a bipolar matrix can be either a modular generalization of a quantum logic gate matrix or a cellular connectivity matrix. Based on this observation, a scalable graph theory of quantum cellular combinatorics is proposed. It is contended that this work constitutes an equilibrium-based logical extension to Bohr’s particle-wave complementarity principle, Bohm’s wave function and Bell’s theorem. In the meantime, it is suggested that the result may also serve as a resolution, rather than a falsification, to the EPR paradox and, therefore, a equilibrium-based logical unification of local realism and quantum non-locality.
文摘Partition-and-Recur (PAR) method is a simple and useful formal method. It can be used to design and testify algo-rithmic programs. In this paper, we propose that PAR method is an effective formal method on solving combinatorics problems. Furthermore, we formally derive combinatorics problems by PAR method, which cannot only simplify the process of algorithmic program's designing, but also improve its automatization, standardization and correctness. We develop algorithms for two typical combinatorics problems, the number of string scheme and the number of error per-mutation scheme. Lastly, we obtain accurate C++ programs which are transformed by automatic transforming system of PAR platform.
文摘Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain multiple related targets and an appropriate combination can maximize benefits while minimizing adverse reactions.As such,it is especially important to derive mathematical models for their quantitative calculation.In this paper,we introduce mathematical rules for the synergistic,additive,and antagonistic effects of multi-drug combinations developed in our laboratory.We have established a“onebelt,one-line”model and provide examples of the quantitative calculation of the synergistic,additive,and antagonistic effects of a combination of multiple components.We also explain how to scientifically and precisely determine the intensity of these synergies,additions and antagonisms,as well as their corresponding dose ranges,thereby laying a solid theoretical foundation for market listing combinatorial drugs and foods for special medical purposes.
文摘Modeling of solute transport is a key issue in the area of soil physics and hydrogeology. The most common approach (the convection-dispersion equation) considers an average convection flow rate and Fickian-like dispersion. Here,we propose a solute transport model in porous media of continuously expanding scale, according to the combinatorics principle. The model supposed actual porous media as a combinative body of many basic segments. First, we studied the solute transport process in each basic segment body, and then deduced the distribution of pore velocity in each basic segment body by difference approximation, finally assembled the solute transport process of each basic segment body into one of the combinative body. The simulation result coincided with the solute transport process observed in test. The model provides useful insight into the solute transport process of the non-Fickian dispersion in continuously expanding scale.
文摘In recent times,approaches to flood prevention and mitigation have changed a lot.These changes are to shift the focus from flood control to flood risk management,in which the assessment of vulnerability to floods caused by each sector and field corresponding to each flood magnitude is typical.Current flood vulnerability assessment studies are basically holistic based on factors affected by floods or in aspects:economy,society and ecological environment,and aspects that are mentioned in all areas of social life.The content of the flood vulnerability assessment method usually considers 3 components:E(Exposure),S(Susceptibility),A(Adaptability-Recovery).Each component will contain many different variables belonging to different objects and different natural-economic-social characteristics in each area.Therefore,for each research area,the evaluation method needs to establish an appropriate set of indicators.A set of indicators used to assess flood vulnerability must:be scientific;be practical;simplify the investigation,collection and synthesis of data.This study has established a set of combinatorial indicators including 27 indicators for the T-BRB(Thach Han-Ben Hai River Basin)on the basis of analysis and synthesis from case studies.
文摘Security weaknesses in web applications deployed in cloud architectures can seriously affect its data confidentiality and integrity.The construction of the procedure utilized in the static analysis tools of source code security differs and therefore each tool finds a different number of each weakness type for which it is designed.To utilize the possible synergies different static analysis tools may process,this work uses a new method to combine several source codes aiming to investigate how to increase the performance of security weakness detection while reducing the number of false positives.Specifically,five static analysis tools will be combined with the designed method to study their behavior using an updated benchmark for OWASP Top Ten Security Weaknesses(OWASP TTSW).The method selects specific metrics to rank the tools for different criticality levels of web applications considering different weights in the ratios.The findings show that simply including more tools in a combination is not synonymous with better results;it depends on the specific tools included in the combination due to their different designs and techniques.
基金the National Key Research and Development Program of China(grant no.2022YFC210540303)the“Major Project”of Haihe Laboratory of Synthetic Biology(22HHSWSS00001).
文摘Tylosin is a 16-membered macrolide antibiotic widely used in veterinary medicine to control infections caused by Gram-positive pathogens and mycoplasmas.To improve the fermentation titer of tylosin in the hyperproducing Streptomyces xinghaiensis strain TL01,we sequenced its whole genome and identified the biosynthetic gene cluster therein.Overexpression of the tylosin efflux gene tlrC,the cluster-situated S-adenosyl methionine(SAM)synthetase gene metK_(cs),the SAM biosynthetic genes adoK_(cs)-metFcs,or the pathway-specific activator gene tylR enhanced tylosin production by 18%,12%,11%,and 11%in the respective engineered strains TLPH08-2,TLPH09,TLPH10,and TLPH12.Co-overexpression of metK_(cs)and adoK_(cs)-metFcs as two transcripts increased tylosin production by 22%in the resultant strain TLPH11 compared to that in TL01.Furthermore,combinational overexpression of tlrC,metK_(cs),adoK_(cs)-metFcs,and tylR as four transcripts increased tylosin production by 23%(10.93g/L)in the resultant strain TLPH17 compared to that in TL01.However,a negligible additive effect was displayed upon combinational overexpression in TLPH17 as suggested by the limited increment of fermentation titer compared to that in TLPH08-2.Transcription analyses indicated that the expression of tlrC and three SAM biosynthetic genes in TLPH17 was considerably lower than that of TLPH08-2 and TLPH11.Based on this observation,the five genes were rearranged into one or two operons to coordinate their overexpression,yielding two engineered strains TLPH23 and TLPH24,and leading to further enhancement of tylosin production over TLPH17.In particular,the production of TLPH23 reached 11.35 g/L.These findings indicated that the combinatorial strategy is a promising approach for enhancing tylosin production in high-yielding industrial strains.
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
基金the National Natural Science Foundation of China (Grant No.10731040)
文摘This paper is contributed to the combinatorial properties of the MSS sequences, which are the periodic kneading words of quadratic maps defined on a interval. An explicit expression of adjacency relations on MSS sequences of given lengths is established.
基金the National Natural Science Foundation of China (Grant No.10731040)
文摘This paper is contributed to the combinatorial properties of the periodic kneading words of antisymmetric cubic maps defined on a interval. The least words of given lengths, the adjacency relations on the words of given lengths and the parity-alternative property in some sets of such words are established.
基金supported by the Natural Science Foundation of China(Grant Nos.:22225702 and 32322048)the National Key R&D Program of China(Grant No.:2020YFE0202200)+8 种基金the Shanghai Academic/Technology Research Leader Program,China(Grant No.:22XD1420900)Guangdong High-level New R&D Institute,China(Grant No.:2019B090904008)Guangdong High-level Innovative Research Institute,China(Grant No.:2021B0909050003)the Shanghai Rising-Star Program,China(Grant No.:22QA1411100)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.:2021276)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology,China(Grant No.:2022QNRC001)the open fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,China(Grant No.:KF-202201)We also thank the support of the Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20212700)Sanofi scholarship program.
文摘Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
基金the doctoral dissertation of Nabiyeh Karimi with the financial support of Sari University of Agricultural Sciences and Natural Resources, Iran
文摘Complete and comprehensive information about sediment dynamic and identification of hotspots of sediment production and transport are necessary for understanding the erosion processes and increasing the efficiency of soil and water conservation practices.Numerous studies used the sediment fingerprint techniques to investigate the contribution of different sources in suspended and bed sediment yield of the watersheds.However,the contribution of various land use/land covers in suspended and bed sediment yield for the great Caspian Sea basin is in an aura of ambiguity and the present study was conducted to gather information about an important part of this area in northern Iran,where rangelands are located upstream of Hyrcanian forests and dense agricultural lands are located downstream.The surface soil of different land use/land covers including forest,rangeland,agriculture and streambank lands were sampled in 30 points.Suspended and bed sediments were sampled in the watershed outlet in two high and low water periods.Geochemical characteristics of soil and sediment samples containing 59 elements were measured using ICP-OES GBC Integra.The reliable and suitable tracers from 59 elements were then selected using Range test,Kruskal-Wallis and Discriminant Function Analysis,respectively,in FingerPro package of R software.The results showed that for suspended sediment,streambank and rangeland had the highest contributions of 86.2%and 47.5%,respectively,in two high and low water periods.For bed sediment,in two high and low water periods,rangeland and streambank had the highest contributions of 73.8%and 84.4%,respectively.Land use change and especially human activities such as agriculture,road construction and development of residential areas along the main river riparian zone has led to a significant increase in suspended and bed sediments.
基金National Natural Science Foundation of China(NSFC)(No.11775147)Guangdong Basic and Applied Basic Research Foundation(Nos.2019A1515110130 and 2024A1515011832)+1 种基金Shenzhen Key Laboratory of Photonics and Biophotonics(ZDSYS20210623092006020)Shenzhen Science and Technology Program(Nos.JCYJ20210324095007020,JCYJ20200109105201936 and JCYJ20230808105019039).
文摘An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were reported.The camera achieved a temporal resolution of 10 ps by using a pulse-dilation device and gated MCP imager,and a spatial resolution of 100μm by using an electronic imaging system comprising combined magnetic lenses.The spatial resolution characteristics of the camera were studied both theoretically and experimentally.The results showed that the camera with combined magnetic lenses reduced the field curvature and acquired a larger working area.A working area with a diameter of 53 mm was created by applying four magnetic lenses to the camera.Furthermore,the camera was used to detect the X-rays produced by the laser-targeting device.The diagnostic results indicated that the width of the X-ray pulse was approximately 18 ps.
基金supported by National Key R&D Program of China(No.2022YFC3004705)the National Natural Science Foundation of China(Nos.52074280,52227901 and 52204249)National Natural Science Foundation of China Youth Fund(No.52104230).
文摘Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.
基金This work was supported by the Chinese TMSR Strategic Pioneer Science and Technology Project(No.XDA02010300).
文摘A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
基金Project supported by Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No.2020029)。
文摘The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.