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
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
Using the coherent state representation we derive some new operator identities and study some mathematical relations in comblnatorics. The technique of integral within an ordered product （IWOP） of operators plays an...Using the coherent state representation we derive some new operator identities and study some mathematical relations in comblnatorics. The technique of integral within an ordered product （IWOP） of operators plays an essential role in realizing our goal.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
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
The n-way combination testing is a specification-based testing criterion, which requires that for a system consisted of a few parameters, every combination of valid values of arbitrary n(n >_2) parameters be covere...The n-way combination testing is a specification-based testing criterion, which requires that for a system consisted of a few parameters, every combination of valid values of arbitrary n(n >_2) parameters be covered by at least one test. This letter proposed two different test generation algorithms based on combinatorial design for the n-way coverage criterion. The automatic test generators are implemented and some valuable empirical results are obtained.展开更多
There are several types of brain tumors but glioblastoma(GBM)is one of the highly malignant tumors.A primary concern with GBM is that the treatment is inadequate.Even after giving many multi-stacked combinations of th...There are several types of brain tumors but glioblastoma(GBM)is one of the highly malignant tumors.A primary concern with GBM is that the treatment is inadequate.Even after giving many multi-stacked combinations of therapies to patients,inclusive of chemotherapy,radiation,and surgery,the median survival rate remains poor.Due to its heterogeneous nature,the use of selective therapy for specific targeting of tumor cells is of particular importance.Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available,the prognosis of the disease is very poor.Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials.In this review,we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM.The prospects for alternative glioblastoma therapy are also discussed.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
The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient uti...The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.展开更多
Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally adv...Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally advanced or unresectable disease.This review outlines recent technological developments in EUS-RFA,including innovations in energy delivery systems,probe design,and real-time thermal monitoring,which have improved the precision and safety of the procedure.Clinical studies combining EUS-RFA with chemotherapy have demonstrated encouraging outcomes,with improvements in overall survival,progression-free survival,tumor necrosis,and symptom control compared to chemotherapy alone.Additionally,RFA-induced tumor antigen release and modulation of the tumor microenvironment suggest a potential synergistic role with immunotherapy.Despite its promise,the widespread adoption of EUS-RFA is limited by a lack of large-scale randomized controlled trials and standardized treatment protocols.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients wit...Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients with early-stage HCC develop recurrence by the time of follow-up.Immunotherapeutic intervention has emerged as a novel,effective treatment to delay the progression of aggressive tumors and suppress tumor recurrence and metastasis.However,few clinical immunotherapy trials have been conducted in HCC patients,and there is an unmet need for novel therapeutic strategies.The combination of conventional treatments with specific immunotherapeutic approaches may dramatically improve the efficacy of HCC treatment and the clinical outcome of HCC patients.In this review,we briefly summarize immunotherapy strategies and discuss new advances in combined immunotherapeutic approaches for the treatment of patients with liver cancer.展开更多
Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great ...Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge.In this work,a single model drug,paclitaxel(PTX),is used to realize combination therapy and solve the problems mentioned above.Either PTX or its triphenylphosphine derivative(TPTX)is encapsulated in galactose-modified liposomes(GLips)to obtain GLips-P or GLips-TP,which are simply mixed in different ratios to finely control the proportion of PTX and TPTX.These mixed liposomes,GLips-P/TP,feature a cascade target delivery of PTX,from tissue to cell,and then to organelle.PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm,while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway.Notably,GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models.This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment,but also offers a novel platform to design combinatory therapy systems using a single drug.展开更多
Immune therapy has become the fourth approach after surgery,chemotherapy,and radiotherapy in cancer treatment.Many immune checkpoints were identified in the last decade since ipilimumab,which is the first immune check...Immune therapy has become the fourth approach after surgery,chemotherapy,and radiotherapy in cancer treatment.Many immune checkpoints were identified in the last decade since ipilimumab,which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4,had been approved by the US Food and Drug Administration(FDA)for the treatment of unresectable or metastatic melanoma in 2011.The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA.However,fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers.Approximately 80%of patients do not respond appropriately because of primary or acquired therapeutic resistance.Along with the characterization of more immune checkpoints,the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response.In this work,the author focuses on the combination therapy of multiple immune checkpoints(does not include targeted therapy of oncogenes or chemotherapy),introduces the current progression of multiple immune checkpoints and their related inhibitors,and discusses the advantages of combination therapy,as well as the risk of immune-related adverse events.展开更多
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.
基金The project supported by National Natural Science Foundation of China under Grant No. 10475056
文摘Using the coherent state representation we derive some new operator identities and study some mathematical relations in comblnatorics. The technique of integral within an ordered product （IWOP） of operators plays an essential role in realizing our goal.
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.
文摘The n-way combination testing is a specification-based testing criterion, which requires that for a system consisted of a few parameters, every combination of valid values of arbitrary n(n >_2) parameters be covered by at least one test. This letter proposed two different test generation algorithms based on combinatorial design for the n-way coverage criterion. The automatic test generators are implemented and some valuable empirical results are obtained.
文摘There are several types of brain tumors but glioblastoma(GBM)is one of the highly malignant tumors.A primary concern with GBM is that the treatment is inadequate.Even after giving many multi-stacked combinations of therapies to patients,inclusive of chemotherapy,radiation,and surgery,the median survival rate remains poor.Due to its heterogeneous nature,the use of selective therapy for specific targeting of tumor cells is of particular importance.Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available,the prognosis of the disease is very poor.Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials.In this review,we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM.The prospects for alternative glioblastoma therapy are also discussed.
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financially supported by the Excellent Youth Scholars Program of State Key Laboratory of Complex Nonferrous Metal Resource Clean Utilization,Kunming University of Science and Technology,China(No.YXQN-2024003)the Central Government-Guided Local Science and Technology Development Fund Project,China(No.202407AB110022)。
文摘The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
文摘Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally advanced or unresectable disease.This review outlines recent technological developments in EUS-RFA,including innovations in energy delivery systems,probe design,and real-time thermal monitoring,which have improved the precision and safety of the procedure.Clinical studies combining EUS-RFA with chemotherapy have demonstrated encouraging outcomes,with improvements in overall survival,progression-free survival,tumor necrosis,and symptom control compared to chemotherapy alone.Additionally,RFA-induced tumor antigen release and modulation of the tumor microenvironment suggest a potential synergistic role with immunotherapy.Despite its promise,the widespread adoption of EUS-RFA is limited by a lack of large-scale randomized controlled trials and standardized treatment protocols.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
文摘Hepatocellular carcinoma(HCC) is the most frequent primary liver cancer,leading to 74.6 thousand deaths annually.The prognosis of HCC over the last few decades has remained unsatisfactory,and over half of patients with early-stage HCC develop recurrence by the time of follow-up.Immunotherapeutic intervention has emerged as a novel,effective treatment to delay the progression of aggressive tumors and suppress tumor recurrence and metastasis.However,few clinical immunotherapy trials have been conducted in HCC patients,and there is an unmet need for novel therapeutic strategies.The combination of conventional treatments with specific immunotherapeutic approaches may dramatically improve the efficacy of HCC treatment and the clinical outcome of HCC patients.In this review,we briefly summarize immunotherapy strategies and discuss new advances in combined immunotherapeutic approaches for the treatment of patients with liver cancer.
基金supported by grants from the National Natural Science Foundation of China(31870946,31470916 and 51672010)the Funding of Double First-rate discipline construction(CPU2018GF07,China)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance(DQCP2015MS01,China).
文摘Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment.However,the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge.In this work,a single model drug,paclitaxel(PTX),is used to realize combination therapy and solve the problems mentioned above.Either PTX or its triphenylphosphine derivative(TPTX)is encapsulated in galactose-modified liposomes(GLips)to obtain GLips-P or GLips-TP,which are simply mixed in different ratios to finely control the proportion of PTX and TPTX.These mixed liposomes,GLips-P/TP,feature a cascade target delivery of PTX,from tissue to cell,and then to organelle.PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm,while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway.Notably,GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models.This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment,but also offers a novel platform to design combinatory therapy systems using a single drug.
基金This project was partially supported by the National Natural Science Foundation of China(Nos.82072602 and 81772505)Yingyan Yu,the Shanghai Science and Technology Committee(Nos.20DZ2201900 and 18411953100)+1 种基金Yingyan Yu,the Chinese National Key Program(Nos.MOST-2017YFC0908300 and 2016YFC1303200)Yingyan Yu,and the Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine(No.TM202001)to Yingyan Yu.
文摘Immune therapy has become the fourth approach after surgery,chemotherapy,and radiotherapy in cancer treatment.Many immune checkpoints were identified in the last decade since ipilimumab,which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4,had been approved by the US Food and Drug Administration(FDA)for the treatment of unresectable or metastatic melanoma in 2011.The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA.However,fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers.Approximately 80%of patients do not respond appropriately because of primary or acquired therapeutic resistance.Along with the characterization of more immune checkpoints,the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response.In this work,the author focuses on the combination therapy of multiple immune checkpoints(does not include targeted therapy of oncogenes or chemotherapy),introduces the current progression of multiple immune checkpoints and their related inhibitors,and discusses the advantages of combination therapy,as well as the risk of immune-related adverse events.
