Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases,such as cardiovascular diseases(CVD),neurodegenerative diseases and cancers,particularly the CVD in which the accumulation...Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases,such as cardiovascular diseases(CVD),neurodegenerative diseases and cancers,particularly the CVD in which the accumulation of lipids(mainly the cholesteryl esters)within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually.More and more studies have shown that lowering cholesterol level,especially low-density lipoprotein cholesterol level,protects cardiovascular system and prevents cardiovascular events effectively.Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis,uptake,efflux,transport,storage,utilization,and/or excretion.All the processes should be precisely controlled by the multiple regulatory pathways.Based on the regulation of cholesterol homeostasis,many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion.Herein,we summarize the historical review and research events,the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis,and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances.More importantly,we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases,obesity,diabetes,nonalcoholic fatty liver disease,cancer,neurodegenerative diseases,osteoporosis and virus infection.展开更多
It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain im...It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain imaging scans across the world,the Lifespan Brain Chart Consortium(LBCC)recently published brain charts for the human lifespan in Nature[1].展开更多
With the improvement of electricity markets,the gradual aggravation of energy shortage and the environment pollution,it is urgent to formulate a new model to precisely satisfy the system demand for energy and reserve....With the improvement of electricity markets,the gradual aggravation of energy shortage and the environment pollution,it is urgent to formulate a new model to precisely satisfy the system demand for energy and reserve.Currently,power system opti-mization dispatching is always formulated as a discrete-time scheduling model.In this paper,we first demonstrate through an example that the upper and lower bounds of spinning reserve offered by a unit,given in the discrete-time model framework as constraints,is unreachable.This causes the problem that the reserve delivery obtained by the discrete-time scheduling model cannot be carried out precisely.From the detailed analysis of the ramp rate constraints,it is proved that the reachable upper and lower bounds of spinning reserve in every period can be expressed as functions of two variables,i.e.,generation level of unit at the start and end of this period.Thus,a new method is provided to calculate the upper and lower bounds of spinning reserve which are reachable in average.Furthermore,a new model based on this proposed method for joint scheduling of generation and reserve is presented,which considers the ability to realize the scheduled energy and reserve delivery.It converts the opti-mization based accurate scheduling for generation and reserve of power system from a continuous-time optimal control prob-lem to a nonlinear programming problem.Therefore,the proposed model can avoid the difficulties in solving a continu-ous-time optimal control problem.Based on the sequential quadratic programming method,numerical experiments for sched-uling electric power production systems are performed to evaluate the model and the results show that the new model is highly effective.展开更多
Emerging as a catalyst for international trade,digital trade has introduced numerous novel forms and models with its dynamic growth and development.Nevertheless,in the realm of digital trade management,authenticating ...Emerging as a catalyst for international trade,digital trade has introduced numerous novel forms and models with its dynamic growth and development.Nevertheless,in the realm of digital trade management,authenticating transactions and precisely determining their value pose significant challenges.This raises issues to the current foreign exchange regulatory framework.展开更多
In their recently published paper in Opto-Electronic Ad-vances,Pietro Ferraro and his colleagues report on a new high-throughput tomographic phase instrument that precisely quantifies intracellular lipid droplets(LDs)...In their recently published paper in Opto-Electronic Ad-vances,Pietro Ferraro and his colleagues report on a new high-throughput tomographic phase instrument that precisely quantifies intracellular lipid droplets(LDs)1.LDs are lipid storage organelles found in most cell types and play an active role in critical biological pro-cesses,including energy metabolism,membrane homeo-stasis.展开更多
Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evi...Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.展开更多
New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given ra...New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given rate. However, almost all command and control（C＆C） mechanisms only provide publishing one com- mand to the whole once, so-called one-to-all C＆C model, and are not productive to support CXPST-alike attacks. In this paper, we present one-to-any C＆C model on coordination among the unco- operative controlled nodes. As an instance of one-to-any C＆C model, directional command publishing （DCP） mechanism lever- aging on Kademlia is provided with a range-mapping key creating algorithm for commands to compute the publishing range and a statistically stochastic node querying scheme to obtain the com- mands immediately. With theoretical analysis and simulation, it is indicated that one-to-any C＆C model fits for precisely coordi- nated operation on uncooperative controlled nodes with least complexity, better accuracy and efficiency. Furthermore, DCP mechanism can support one-to-all command publishing at the same time. As an example of future C＆C model, studying on one-to-any C＆C model may help to promote the development of more efficient countermeasures.展开更多
Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The pr...Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.展开更多
Introduction In the past decade,three-dimensional(3D)bioprinting,which precisely deposits bioink composed of the biological materials and the living cells into delicate structures with the living cells encapsulated,ha...Introduction In the past decade,three-dimensional(3D)bioprinting,which precisely deposits bioink composed of the biological materials and the living cells into delicate structures with the living cells encapsulated,has made numerous important advances in tissue engineering and regenerative medicine[1,2].Depending on the printing mechanism,3D bioprinting technologies are generally categorized into four types:inkjet-based bioprinting,microextrusion-based bioprinting,laser-assisted bioprinting,and stereolithography-based bioprinting[3].展开更多
The use of optogenetic and chemogenetic approaches to control cellular activities with high temporal,spatial and cell-type specific resolution has profoundly transformed the field of neuroscience.In addition to enabli...The use of optogenetic and chemogenetic approaches to control cellular activities with high temporal,spatial and cell-type specific resolution has profoundly transformed the field of neuroscience.In addition to enabling the manipulation of neuronal excitability,there is a great need for targeting intracellular signalling proteins and secondary messengers precisely。展开更多
To realize scale quantum processors,the surface-electrode ion trap is an effective scaling approach,including singlelayer,double-layer,and quasi-double-layer traps.To calculate critical trap parameters such as the tra...To realize scale quantum processors,the surface-electrode ion trap is an effective scaling approach,including singlelayer,double-layer,and quasi-double-layer traps.To calculate critical trap parameters such as the trap center and trap depth,the finite element method（FEM） simulation was widely used,however,it is always time consuming.Moreover,the FEM simulation is also incapable of exhibiting the direct relationship between the geometry dimension and these parameters.To eliminate the problems above,House and Madsen et al.have respectively provided analytic models for single-layer traps and double-layer traps.In this paper,we propose a semi-analytical model for quasi-double-layer traps.This model can be applied to calculate the important parameters above of the ion trap in the trap design process.With this model,we can quickly and precisely find the optimum geometry design for trap electrodes in various cases.展开更多
The author proves that any quadratic system in the plane can be changed into the quadratic system （E<sub>1</sub>） or （E<sub>2</sub>） by means of linear transformations, and then gives a nec...The author proves that any quadratic system in the plane can be changed into the quadratic system （E<sub>1</sub>） or （E<sub>2</sub>） by means of linear transformations, and then gives a necessary and sufficient condition for the systems （E<sub>1</sub>） and （E<sub>2</sub>） to be bounded for t≥0 and to have precisely one monotone unboundol orbit for t≥0 respectively.展开更多
Chamdo,situated within the Hengduan Mountains,is known as Tibet's easternmost pearl.It is also renowned for three dances—the Chamdo Gordro (circle dance),Markham String,and Tenchen Rapa—which people refer to as ...Chamdo,situated within the Hengduan Mountains,is known as Tibet's easternmost pearl.It is also renowned for three dances—the Chamdo Gordro (circle dance),Markham String,and Tenchen Rapa—which people refer to as the three specialties of local artistic culture as well as (perhaps more precisely) the three shining treasures of Chinese culture.展开更多
Since the early afternoon,Hou Yong(pseudonym)has been watching the sky for the return of one of his 50 racing pigeons as it finds its way home from nearly 700 kilometers away in a pigeon race on April 29.The previous ...Since the early afternoon,Hou Yong(pseudonym)has been watching the sky for the return of one of his 50 racing pigeons as it finds its way home from nearly 700 kilometers away in a pigeon race on April 29.The previous morning,the 60-year-old Beijing resident had brought the 2-year-old bird to the Guang'an Gymnasium as his sole entry to the Beijing Xicheng District Racing Pigeon Association(BXDRPA).There,the bird and 1,181 of its fellow racers were loaded into nine-layered metalcages on a truck and transported to a parking lot in Zhoukou,Henan province,where they were released atprecisely 6:08 a.m.the following day to fly back to their respective homes in Beijing.展开更多
基金The work was funded by the National Natural Science Foundation of China(NSFC)Grants 81973316 to J.H,82173807 to Y.D.Tianjin Municipal Science and Technology Commission of China Grant 20JCZDJC00710the Fundamental Research Funds for the Central Universities(Nankai University)63211045 to J.H.
文摘Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases,such as cardiovascular diseases(CVD),neurodegenerative diseases and cancers,particularly the CVD in which the accumulation of lipids(mainly the cholesteryl esters)within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually.More and more studies have shown that lowering cholesterol level,especially low-density lipoprotein cholesterol level,protects cardiovascular system and prevents cardiovascular events effectively.Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis,uptake,efflux,transport,storage,utilization,and/or excretion.All the processes should be precisely controlled by the multiple regulatory pathways.Based on the regulation of cholesterol homeostasis,many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion.Herein,we summarize the historical review and research events,the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis,and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances.More importantly,we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases,obesity,diabetes,nonalcoholic fatty liver disease,cancer,neurodegenerative diseases,osteoporosis and virus infection.
基金supported by the STI 2030–the major project of the Brain Science and Brain-Inspired Intelligence Technology(2021ZD0200500)。
文摘It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain imaging scans across the world,the Lifespan Brain Chart Consortium(LBCC)recently published brain charts for the human lifespan in Nature[1].
基金supported by the National Natural Science Foundation of China(Grant Nos.60921003,60736027,61174161,60974101)the Spe-cialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20090121110022)+3 种基金the Fundamental Research Funds for the Central Universities of Xiamen University(Grant Nos.2011121047,201112G018,CXB2011035)the Key Research Project of Fujian Province of China(Grant No.2009H0044)Xiamen University National 211 3rd Period Project of China)(Grant No.0630-E72000)the Natural Sci-ence Foundation of Fujian Province,China(Grant No.2011J05154)
文摘With the improvement of electricity markets,the gradual aggravation of energy shortage and the environment pollution,it is urgent to formulate a new model to precisely satisfy the system demand for energy and reserve.Currently,power system opti-mization dispatching is always formulated as a discrete-time scheduling model.In this paper,we first demonstrate through an example that the upper and lower bounds of spinning reserve offered by a unit,given in the discrete-time model framework as constraints,is unreachable.This causes the problem that the reserve delivery obtained by the discrete-time scheduling model cannot be carried out precisely.From the detailed analysis of the ramp rate constraints,it is proved that the reachable upper and lower bounds of spinning reserve in every period can be expressed as functions of two variables,i.e.,generation level of unit at the start and end of this period.Thus,a new method is provided to calculate the upper and lower bounds of spinning reserve which are reachable in average.Furthermore,a new model based on this proposed method for joint scheduling of generation and reserve is presented,which considers the ability to realize the scheduled energy and reserve delivery.It converts the opti-mization based accurate scheduling for generation and reserve of power system from a continuous-time optimal control prob-lem to a nonlinear programming problem.Therefore,the proposed model can avoid the difficulties in solving a continu-ous-time optimal control problem.Based on the sequential quadratic programming method,numerical experiments for sched-uling electric power production systems are performed to evaluate the model and the results show that the new model is highly effective.
文摘Emerging as a catalyst for international trade,digital trade has introduced numerous novel forms and models with its dynamic growth and development.Nevertheless,in the realm of digital trade management,authenticating transactions and precisely determining their value pose significant challenges.This raises issues to the current foreign exchange regulatory framework.
文摘In their recently published paper in Opto-Electronic Ad-vances,Pietro Ferraro and his colleagues report on a new high-throughput tomographic phase instrument that precisely quantifies intracellular lipid droplets(LDs)1.LDs are lipid storage organelles found in most cell types and play an active role in critical biological pro-cesses,including energy metabolism,membrane homeo-stasis.
基金financially supported by the Liaoning Revitalization Talents Program (No. XLYC1907129)the Excellent Youth Science Foundation of Liaoning Province (No. 2020-YQ-06)the China Postdoctoral Science Foundation (No. 2020M670794)。
文摘Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
基金Supported by the National Natural Science Foundation of China(61402526,61502528)
文摘New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given rate. However, almost all command and control（C＆C） mechanisms only provide publishing one com- mand to the whole once, so-called one-to-all C＆C model, and are not productive to support CXPST-alike attacks. In this paper, we present one-to-any C＆C model on coordination among the unco- operative controlled nodes. As an instance of one-to-any C＆C model, directional command publishing （DCP） mechanism lever- aging on Kademlia is provided with a range-mapping key creating algorithm for commands to compute the publishing range and a statistically stochastic node querying scheme to obtain the com- mands immediately. With theoretical analysis and simulation, it is indicated that one-to-any C＆C model fits for precisely coordi- nated operation on uncooperative controlled nodes with least complexity, better accuracy and efficiency. Furthermore, DCP mechanism can support one-to-all command publishing at the same time. As an example of future C＆C model, studying on one-to-any C＆C model may help to promote the development of more efficient countermeasures.
文摘Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.
文摘Introduction In the past decade,three-dimensional(3D)bioprinting,which precisely deposits bioink composed of the biological materials and the living cells into delicate structures with the living cells encapsulated,has made numerous important advances in tissue engineering and regenerative medicine[1,2].Depending on the printing mechanism,3D bioprinting technologies are generally categorized into four types:inkjet-based bioprinting,microextrusion-based bioprinting,laser-assisted bioprinting,and stereolithography-based bioprinting[3].
文摘The use of optogenetic and chemogenetic approaches to control cellular activities with high temporal,spatial and cell-type specific resolution has profoundly transformed the field of neuroscience.In addition to enabling the manipulation of neuronal excitability,there is a great need for targeting intracellular signalling proteins and secondary messengers precisely。
文摘To realize scale quantum processors,the surface-electrode ion trap is an effective scaling approach,including singlelayer,double-layer,and quasi-double-layer traps.To calculate critical trap parameters such as the trap center and trap depth,the finite element method（FEM） simulation was widely used,however,it is always time consuming.Moreover,the FEM simulation is also incapable of exhibiting the direct relationship between the geometry dimension and these parameters.To eliminate the problems above,House and Madsen et al.have respectively provided analytic models for single-layer traps and double-layer traps.In this paper,we propose a semi-analytical model for quasi-double-layer traps.This model can be applied to calculate the important parameters above of the ion trap in the trap design process.With this model,we can quickly and precisely find the optimum geometry design for trap electrodes in various cases.
文摘The author proves that any quadratic system in the plane can be changed into the quadratic system （E<sub>1</sub>） or （E<sub>2</sub>） by means of linear transformations, and then gives a necessary and sufficient condition for the systems （E<sub>1</sub>） and （E<sub>2</sub>） to be bounded for t≥0 and to have precisely one monotone unboundol orbit for t≥0 respectively.
文摘Chamdo,situated within the Hengduan Mountains,is known as Tibet's easternmost pearl.It is also renowned for three dances—the Chamdo Gordro (circle dance),Markham String,and Tenchen Rapa—which people refer to as the three specialties of local artistic culture as well as (perhaps more precisely) the three shining treasures of Chinese culture.
文摘Since the early afternoon,Hou Yong(pseudonym)has been watching the sky for the return of one of his 50 racing pigeons as it finds its way home from nearly 700 kilometers away in a pigeon race on April 29.The previous morning,the 60-year-old Beijing resident had brought the 2-year-old bird to the Guang'an Gymnasium as his sole entry to the Beijing Xicheng District Racing Pigeon Association(BXDRPA).There,the bird and 1,181 of its fellow racers were loaded into nine-layered metalcages on a truck and transported to a parking lot in Zhoukou,Henan province,where they were released atprecisely 6:08 a.m.the following day to fly back to their respective homes in Beijing.
