To address fixed-time consensus problems of a class of leader-follower second-order nonlinear multi-agent systems with uncertain external disturbances,the event-triggered fixed-time consensus protocol is proposed.Firs...To address fixed-time consensus problems of a class of leader-follower second-order nonlinear multi-agent systems with uncertain external disturbances,the event-triggered fixed-time consensus protocol is proposed.First,the virtual velocity is designed based on the backstepping control method to achieve the system consensus and the bound on convergence time only depending on the system parameters.Second,an event-triggered mechanism is presented to solve the problem of frequent communication between agents,and triggered condition based on state information is given for each follower.It is available to save communication resources,and the Zeno behaviors are excluded.Then,the delay and switching topologies of the system are also discussed.Next,the system stabilization is analyzed by Lyapunov stability theory.Finally,simulation results demonstrate the validity of the presented method.展开更多
The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional ...The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional regenerative medicine and tissue engineering strategies have created specialized tissues using progenitor cells and various biological stimuli.To date,there are many US Food and Drug Administration(FDA)-approved regenerative medicine therapies,such as those for wound healing and orthopedic injuries.Nonetheless,these therapies face challenges,including off-target effects,a lack of precision,and failure to target the disease or injury at its origin.In search of novel,precise,and efficient alternatives,the regenerative medicine landscape is shifting towards genome engineering technologies,particularly gene editing.Clustered regularly interspaced short palindromic repeats(CRISPR)-based gene editing systems enable precise knock-ins,knockouts,transcriptional activation and repression,as well as specific base conversions.This advancement has allowed researchers to treat genetic and degenerative diseases,control cell fate for highly regulated tissue repair,and enhance tissue functions.In this review,we explore the progress and future prospects of CRISPR technologies in regenerative medicine,focusing on how gene editing has led to advanced therapeutic applications and served as a versatile research tool for understanding tissue development and disease progression.展开更多
Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisio...Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisions that align with citizens'perceptions.However,research on ecosystem services in Romania has been limited,with a notable gap in the assessment of CES provided by urban green spaces.This study is the first to focus on Băneasa Forest,the only urban forest in Bucharest,which serves as a vital recreational area for thousands of residents and visitors.For the first time in Romania,this research uses a web-based Participatory GIS survey to collect spatially referenced data.The survey,which combines questionnaires and mapping exercises,allows us to produce high-resolution CES maps based on 816 responses.The results reveal that the forest's natural characteristics are perceived as the primary contributors to CES.These findings are valuable for urban planners,as they highlight the needs and expectations of forest visitors,promote conservation efforts,and foster collaboration to prevent conflicts.Alongside factors frequently discussed in the literature,such as age and accessibility,the percentage of green space in residents'neighborhoods emerges as a significant factor influencing CES preferences.This insight presents a novel contribution to the literature,being of particular importance for urban planners and policymakers,as it underscores the need to consider not just the green space within parks and forests,but also the broader context of surrounding neighborhoods when planning for CES.Understanding that the availability of nearby green space influences residents'CES preferences can guide more effective strategies to enhance access to CES in urban areas,both in Bucharest and elsewhere.This is especially relevant in the face of climate change and other emerging challenges,which are likely to increase the demand for CES in the future.展开更多
Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment ...Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.展开更多
Dear Editor,This letter studies the bipartite consensus tracking problem for heterogeneous multi-agent systems with actuator faults and a leader's unknown time-varying control input. To handle such a problem, the ...Dear Editor,This letter studies the bipartite consensus tracking problem for heterogeneous multi-agent systems with actuator faults and a leader's unknown time-varying control input. To handle such a problem, the continuous fault-tolerant control protocol via observer design is developed. In addition, it is strictly proved that the multi-agent system driven by the designed controllers can still achieve bipartite consensus tracking after faults occur.展开更多
The article "Data-driven soft sensors in blast furnace ironmaking:a survey,"written by Yueyang LUO,Xinmin ZHANG,Manabu KANO,Long DENG,Chunjie YANG,and Zhihuan SONG,was originally published electronically on ...The article "Data-driven soft sensors in blast furnace ironmaking:a survey,"written by Yueyang LUO,Xinmin ZHANG,Manabu KANO,Long DENG,Chunjie YANG,and Zhihuan SONG,was originally published electronically on the publisher's Internet portal on Mar.27,2023 without open access.展开更多
A grey-box modelling framework was developed for the estimation of cut point temperature of a crude distillation unit(CDU)under uncertainty in crude composition and process conditions.First principle(FP)model of CDU w...A grey-box modelling framework was developed for the estimation of cut point temperature of a crude distillation unit(CDU)under uncertainty in crude composition and process conditions.First principle(FP)model of CDU was developed for Pakistani crudes from Zamzama and Kunnar fields.A hybrid methodology based on the integration of Taguchi method and genetic algorithm(GA)was employed to estimate the optimal cut point temperature for various sets of process variables.Optimised datasets were utilised to develop an artificial neural networks(ANN)model for the prediction of optimum values of cut points.The ANN model was then used to replace the hybrid framework of the Taguchi method and the GA.The integration of the ANN and FP model makes it a grey-box(GB)model.For the case of Zamama crude,the GB model helped in the decrease of up to 38.93%in energy required per kilo barrel of diesel and an 8.2%increase in diesel production compared to the stand-alone FP model under uncertainty.Similarly,for Kunnar crude,up to 18.87%decrease in energy required per kilo barrel of diesel and a 33.96%increase in diesel production was observed in comparison to the stand-alone FP model.展开更多
Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogeni...Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance.Angiogenesis,driven primarily by VEGF/VEGFR signaling,is critical for tumor sustenance but is often insufficient under hypoxic conditions,prompting melanoma cells to adapt by forming vascular-like structures(i.e.,vasculogenic mimicry).These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis.Molecular drivers,including VE-cadherin,EphA2,and hypoxia-inducible factors,have been identified as key regulators of these processes.Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry.The review highlights the need for therapeutic strategies targeting both mechanisms,emphasizing the importance of combination treatments to overcome resistance.Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes.展开更多
The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differ...The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differences between SHS and cobalt-60 isotope(^(60)Co)radiation treatment.The number of total plate count(TPC)and mold colonies(MC)remained within the limits of the standards after SHS treatment at 140℃for 2 min.Neither TPC nor MC were detected after^(60)Co irradiation.Peroxidase(POD)and polyphenol oxidase(PPO)activities significantly decreased with increasing temperature and duration of SHS,while^(60)Co radiation completely inactivated PPO.Compared to^(60)Co radiation,SHS treatment inhibited the deterioration of rape bee pollen by avoiding hydroperoxide production and lipid oxidation due to lack of oxygen.These results suggested SHS under 140℃for 2 min was the most suitable to inactivate the microorganisms and enzymes in rape bee pollen with minimal lipid oxidation.展开更多
In this study,a Grey-box(GB)model was developed to predict the optimum mass flow rates of inlet streams of a Shell and Tube Heat Exchanger(STHE)under varying process conditions.Aspen Exchanger Design and Rating(Aspen-...In this study,a Grey-box(GB)model was developed to predict the optimum mass flow rates of inlet streams of a Shell and Tube Heat Exchanger(STHE)under varying process conditions.Aspen Exchanger Design and Rating(Aspen-EDR)was initially used to construct a first principle model(FP)of the STHE using industrial data.The Genetic Algorithm(GA)was incorporated into the FP model to attain the minimum exit temperature for the hot kerosene process stream under varying process conditions.A dataset comprised of optimum process conditions was generated through FP-GA integration and was utilised to develop an Artificial Neural Networks(ANN)model.Subsequently,the ANN model was merged with the FP model by substituting the GA,to form a GB model.The developed GB model,that is,ANN and FP integration,achieved higher effectiveness and lower outlet temperature than those derived through the standalone FP model.Performance of the GB framework was also comparable to the FP-GA approach but it significantly reduced the computation time required for estimating the optimum process conditions.The proposed GB-based method improved the STHE's ability to extract energy from the process stream and strengthened its resilience to cope with diverse process conditions.展开更多
Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depe...Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depending on the characteristics of tumor cells,as well as the immune status.The main purpose of this study was to experimentally prove the feasibility of combining the Karanahan technology and in situ vaccination withαOX40 antibodies into a single therapeutic platform to achieve a potent additive antitumor therapeutic effect.Methods:BALB/c mice grafted with B-cellular lymphoma A20 were treated using the Karanahan technology consisting of intraperitoneal cyclophosphamide administrations and intratumoral DNA injections according to an individually determined therapeutic regimen,together with in situ vaccination withαOX40.A pathomorphological analysis of the organs of experimental animals that died during the initial attempt to combine the two technologies was carried out.An analysis of blood cell populations was performed to determine the safe time for antibody administration:the number of immune cells capable of activating systemic inflammation(CD11b+Ly-6C+,CD11b+Ly-6G+,CD3–NKp46+CD11b+),the presence of Fc receptor and OX40 on the surface of these cells,and the number of neutrophils activated to NETosis were analyzed.Based on the analysis results,the antitumor efficacy of various modes of combining the Karanahan technology and in situ vaccination was studied.Results:WhenαOX40 was administered 5 h after each treatment using the Karanahan technology,mass death of mice caused by systemic inflammation and multiple organ failure was observed.The state of blood cells after the treatment using the Karanahan technology at the time points corresponding to antibody injections was analyzed to elucidate the reasons for this effect.It was found that at some time points,there occurs activation of the immune system and a powerful release(up to 16%)of monocytes and granulocytes carrying Fc receptor and OX40 on their surface into blood;when interacting withαOX40,they can activate the lytic potential of these cells.Activation of neutrophils to NETosis was also observed.Based on these findings,a study was carried out in different time regimes to combine the Karanahan technology andαOX40 injections.WhenαOX40 was injected into the points of minimal release of myeloid cells into the blood,increased survival rate and the greatest antitumor efficacy were observed:37%of animals survived without relapses on day 100 after experiment initiation.Conclusions:The results obtained indicate that it is possible to combine the Karanahan technology and in situ vaccination withαOX40,with obligatory constant monitoring of the number of myeloid cells in peripheral blood to determine the safe time for antibody injection.展开更多
BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and h...BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.展开更多
In this paper, we propose an adaptive fuzzy dynamic surface control(DSC) scheme for single-link flexible-joint robotic systems with input saturation. A smooth function is utilized with the mean-value theorem to deal w...In this paper, we propose an adaptive fuzzy dynamic surface control(DSC) scheme for single-link flexible-joint robotic systems with input saturation. A smooth function is utilized with the mean-value theorem to deal with the difficulties associated with input saturation. An adaptive DSC design with an auxiliary first-order filter is used to solve the "explosion of complexity"problem. It is proved that all the signals in the closed-loop system are semi-globally uniformly ultimately bounded, and the tracking error eventually converges to a small neighborhood around zero. The main advantage of the proposed method is that only one adaptation parameter needs to be updated,which reduces the computational burden significantly. Simulation results demonstrate the feasibility of the proposed scheme and the comparison results show that the improved DSC method can reduce the computational burden by almost two thirds in comparison with the standard DSC method.展开更多
The method of stabilizing switched systems based on the optimal control is applied,with all modes unstable,for a typical example of the multi-agent system.First,the optimal control method for stabilizing switched syst...The method of stabilizing switched systems based on the optimal control is applied,with all modes unstable,for a typical example of the multi-agent system.First,the optimal control method for stabilizing switched systems is introduced.For this purpose,a switching table rule procedure is constructed.This procedure is inspired by the optimal control that identifies the optimal trajectory for the switched systems.In the next step,the stability of a multi-agent system is studied,considering different unstable connection topologies.Finally,the optimal control method is successfully applied to an aircraft team,as an example of the multi-agent systems.Simulation results evaluate and confirm the successful application of this method in the aircraft team example.展开更多
Robust adaptive control of nonholonomic systems in chained form with linearly parameterized and strongly nonlinear disturbance and drift terms is dicussed.The novelty of the proposed method is a combined use of the st...Robust adaptive control of nonholonomic systems in chained form with linearly parameterized and strongly nonlinear disturbance and drift terms is dicussed.The novelty of the proposed method is a combined use of the state-scaling and the back-stepping procedure.展开更多
Psychometric scales,commonly used to gauge sexual function,can sometimes be influenced by response biases.In our researchfrom June 2020 to April 2021,we examined the accuracy of self-reported sexual function scales.We...Psychometric scales,commonly used to gauge sexual function,can sometimes be influenced by response biases.In our researchfrom June 2020 to April 2021,we examined the accuracy of self-reported sexual function scales.We invited patients from theDepartment of Infertility and Sexual Medicine at the Third Affiliated Hospital of Sun Yat-sen University(Guangzhou,China),whohave male sexual dysfunction,to participate by filling out a self-reported version of a specific questionnaire.In addition,they wentthrough a clinician-assisted version of this questionnaire,encompassing tools such as the Premature Ejaculation Diagnostic Tool(PEDT),the 6-item International Index of Erectile Function(IIEF-6),the Erection Hardness Scale(EHS),and the MasturbationErection Index(MEI).Using the clinician-assisted version as a reference,we categorized patients and applied various statisticalmethods,such as the Chi-square test,intraclass correlation coefficient(ICC),logistic regression,and the Bland–Altman plot,to gauge reliability.In our study with 322 participants,we found that while there were no notable discrepancies in error ratesbased on our categorization,certain scales showed significant differences in terms of overestimation and underestimation,withthe exception of the PEDT.The positive diagnosis rate consistency between the self-reported and clinician-assisted versions wasobserved.High ICC values between the two versions across the scales were indicative of remarkable reliability.Our findings showthat the self-reported versions of tools such as EHS,IIEF-6,MEI,and PEDT are credible and hold clinical reliability.However,employing a dual-diagnosis approach might be more prudent to circumvent potential misdiagnoses.展开更多
Orthogonal Frequency Division Multiplexing (OFDM) is a multi-carrier scheme used in modern broadband wireless communication systems to transmit data over a number of orthogonal subcarriers. When transmitted signals ar...Orthogonal Frequency Division Multiplexing (OFDM) is a multi-carrier scheme used in modern broadband wireless communication systems to transmit data over a number of orthogonal subcarriers. When transmitted signals arrive at the receiver by more than one path of different length, the received signals are staggered in time;this is multipath propagation. To mitigate the effect of dispersed channel distortion caused by random channel delay spread, Cyclic Prefix (CP) is introduced to eliminate Inter-Symbol Interference (ISI). In the literature, researchers have focused on carrying out investigations (or studies) mainly on the two existing CP insertions, namely: normal and extended CPs. Both CPs have limitations with respect to handling channel delay spreads. In the current work, a new CP, herein referred to as “ultra extended” CP is proposed to address delay spreads beyond the limits of the normal and extended CPs. The efficacy of the proposed ultra extended CP is tested via simulation under different scenarios. It is shown by the results obtained that the proposed CP can efficiently handle delay spreads beyond the limits of the existing normal and extended CP, and can indeed be implemented in the design of future telecommunication systems to accommodate higher channel delay spreads and it ensures wider cell coverage.展开更多
Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle g...Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.展开更多
In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible ...In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.展开更多
基金National Natural Science Foundation of China(No.62073296)Natural Science Foundation of Zhejiang Province,China(No.LZ23F030010)Key Laboratory of Intelligent Manufacturing Quality Big Data Tracing and Analysis of Zhejiang Province,China Jiliang University(No.ZNZZSZ-CJLU2022-03)Rights and permissions。
文摘To address fixed-time consensus problems of a class of leader-follower second-order nonlinear multi-agent systems with uncertain external disturbances,the event-triggered fixed-time consensus protocol is proposed.First,the virtual velocity is designed based on the backstepping control method to achieve the system consensus and the bound on convergence time only depending on the system parameters.Second,an event-triggered mechanism is presented to solve the problem of frequent communication between agents,and triggered condition based on state information is given for each follower.It is available to save communication resources,and the Zeno behaviors are excluded.Then,the delay and switching topologies of the system are also discussed.Next,the system stabilization is analyzed by Lyapunov stability theory.Finally,simulation results demonstrate the validity of the presented method.
基金supported by the National Institutes of Health(UH3NS115598).
文摘The potential of regenerative medicine in the clinical space is vast,given its ability to repair and replace damaged tissues,restore lost functions due to age or disease,and transform personalized therapy.Traditional regenerative medicine and tissue engineering strategies have created specialized tissues using progenitor cells and various biological stimuli.To date,there are many US Food and Drug Administration(FDA)-approved regenerative medicine therapies,such as those for wound healing and orthopedic injuries.Nonetheless,these therapies face challenges,including off-target effects,a lack of precision,and failure to target the disease or injury at its origin.In search of novel,precise,and efficient alternatives,the regenerative medicine landscape is shifting towards genome engineering technologies,particularly gene editing.Clustered regularly interspaced short palindromic repeats(CRISPR)-based gene editing systems enable precise knock-ins,knockouts,transcriptional activation and repression,as well as specific base conversions.This advancement has allowed researchers to treat genetic and degenerative diseases,control cell fate for highly regulated tissue repair,and enhance tissue functions.In this review,we explore the progress and future prospects of CRISPR technologies in regenerative medicine,focusing on how gene editing has led to advanced therapeutic applications and served as a versatile research tool for understanding tissue development and disease progression.
基金supported by the University of Bucharest through the“People and trees”CIVIS project.
文摘Cultural ecosystem services(CES)provided by urban green infrastructure are essential for enhancing social well-being and resilience.Identifying and mapping CES at a local scale is crucial for informed land-use decisions that align with citizens'perceptions.However,research on ecosystem services in Romania has been limited,with a notable gap in the assessment of CES provided by urban green spaces.This study is the first to focus on Băneasa Forest,the only urban forest in Bucharest,which serves as a vital recreational area for thousands of residents and visitors.For the first time in Romania,this research uses a web-based Participatory GIS survey to collect spatially referenced data.The survey,which combines questionnaires and mapping exercises,allows us to produce high-resolution CES maps based on 816 responses.The results reveal that the forest's natural characteristics are perceived as the primary contributors to CES.These findings are valuable for urban planners,as they highlight the needs and expectations of forest visitors,promote conservation efforts,and foster collaboration to prevent conflicts.Alongside factors frequently discussed in the literature,such as age and accessibility,the percentage of green space in residents'neighborhoods emerges as a significant factor influencing CES preferences.This insight presents a novel contribution to the literature,being of particular importance for urban planners and policymakers,as it underscores the need to consider not just the green space within parks and forests,but also the broader context of surrounding neighborhoods when planning for CES.Understanding that the availability of nearby green space influences residents'CES preferences can guide more effective strategies to enhance access to CES in urban areas,both in Bucharest and elsewhere.This is especially relevant in the face of climate change and other emerging challenges,which are likely to increase the demand for CES in the future.
基金supported by #NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-(DN.155311.10.2022)supported by Sapienza Grant 2021(RM12117A60BDF685).
文摘Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.
基金supported by the National Natural Science Foundation of China(62325304,U22B2046,62073079,62376029)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the China Postdoctoral Science Foundation(2023M730255,2024T171123)
文摘Dear Editor,This letter studies the bipartite consensus tracking problem for heterogeneous multi-agent systems with actuator faults and a leader's unknown time-varying control input. To handle such a problem, the continuous fault-tolerant control protocol via observer design is developed. In addition, it is strictly proved that the multi-agent system driven by the designed controllers can still achieve bipartite consensus tracking after faults occur.
文摘The article "Data-driven soft sensors in blast furnace ironmaking:a survey,"written by Yueyang LUO,Xinmin ZHANG,Manabu KANO,Long DENG,Chunjie YANG,and Zhihuan SONG,was originally published electronically on the publisher's Internet portal on Mar.27,2023 without open access.
基金Higher Education Commission,Pakistan,under the National Research Program for Universities Project,Grant/Award Number:NBU-FPEJ-2024-1243-02。
文摘A grey-box modelling framework was developed for the estimation of cut point temperature of a crude distillation unit(CDU)under uncertainty in crude composition and process conditions.First principle(FP)model of CDU was developed for Pakistani crudes from Zamzama and Kunnar fields.A hybrid methodology based on the integration of Taguchi method and genetic algorithm(GA)was employed to estimate the optimal cut point temperature for various sets of process variables.Optimised datasets were utilised to develop an artificial neural networks(ANN)model for the prediction of optimum values of cut points.The ANN model was then used to replace the hybrid framework of the Taguchi method and the GA.The integration of the ANN and FP model makes it a grey-box(GB)model.For the case of Zamama crude,the GB model helped in the decrease of up to 38.93%in energy required per kilo barrel of diesel and an 8.2%increase in diesel production compared to the stand-alone FP model under uncertainty.Similarly,for Kunnar crude,up to 18.87%decrease in energy required per kilo barrel of diesel and a 33.96%increase in diesel production was observed in comparison to the stand-alone FP model.
基金supported by the European Union-Next Generation EU-PNRR M6C2-Investment 2.1 Enhancement and Strengthening of Biomedical Research in the NHS-Project:PNRR-MCNT2-2023-12377670(Grant No.CUP F93C24000250007).
文摘Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance.Angiogenesis,driven primarily by VEGF/VEGFR signaling,is critical for tumor sustenance but is often insufficient under hypoxic conditions,prompting melanoma cells to adapt by forming vascular-like structures(i.e.,vasculogenic mimicry).These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis.Molecular drivers,including VE-cadherin,EphA2,and hypoxia-inducible factors,have been identified as key regulators of these processes.Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry.The review highlights the need for therapeutic strategies targeting both mechanisms,emphasizing the importance of combination treatments to overcome resistance.Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes.
基金supported by National Natural Science Foundations of China(32472396,31871861 and 31501548)The Apicultural Industry Technology System(NCYTI-43-KXJ17)The Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2015-IAR)。
文摘The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differences between SHS and cobalt-60 isotope(^(60)Co)radiation treatment.The number of total plate count(TPC)and mold colonies(MC)remained within the limits of the standards after SHS treatment at 140℃for 2 min.Neither TPC nor MC were detected after^(60)Co irradiation.Peroxidase(POD)and polyphenol oxidase(PPO)activities significantly decreased with increasing temperature and duration of SHS,while^(60)Co radiation completely inactivated PPO.Compared to^(60)Co radiation,SHS treatment inhibited the deterioration of rape bee pollen by avoiding hydroperoxide production and lipid oxidation due to lack of oxygen.These results suggested SHS under 140℃for 2 min was the most suitable to inactivate the microorganisms and enzymes in rape bee pollen with minimal lipid oxidation.
基金National Research Program for Universities,Grant/Award Number:10215/FederalNorthern Border University,Arar,KSA,Grant/Award Number:NBU-FPEJ-2024-1243-01。
文摘In this study,a Grey-box(GB)model was developed to predict the optimum mass flow rates of inlet streams of a Shell and Tube Heat Exchanger(STHE)under varying process conditions.Aspen Exchanger Design and Rating(Aspen-EDR)was initially used to construct a first principle model(FP)of the STHE using industrial data.The Genetic Algorithm(GA)was incorporated into the FP model to attain the minimum exit temperature for the hot kerosene process stream under varying process conditions.A dataset comprised of optimum process conditions was generated through FP-GA integration and was utilised to develop an Artificial Neural Networks(ANN)model.Subsequently,the ANN model was merged with the FP model by substituting the GA,to form a GB model.The developed GB model,that is,ANN and FP integration,achieved higher effectiveness and lower outlet temperature than those derived through the standalone FP model.Performance of the GB framework was also comparable to the FP-GA approach but it significantly reduced the computation time required for estimating the optimum process conditions.The proposed GB-based method improved the STHE's ability to extract energy from the process stream and strengthened its resilience to cope with diverse process conditions.
基金supported by Inga N.Zaitseva“Karanahan”LLC and the Ministry of Science and Higher Education of the Russian Federation via the Institute of Cytology and Genetics(State Budget Project No.FWNR-2022-0016).
文摘Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depending on the characteristics of tumor cells,as well as the immune status.The main purpose of this study was to experimentally prove the feasibility of combining the Karanahan technology and in situ vaccination withαOX40 antibodies into a single therapeutic platform to achieve a potent additive antitumor therapeutic effect.Methods:BALB/c mice grafted with B-cellular lymphoma A20 were treated using the Karanahan technology consisting of intraperitoneal cyclophosphamide administrations and intratumoral DNA injections according to an individually determined therapeutic regimen,together with in situ vaccination withαOX40.A pathomorphological analysis of the organs of experimental animals that died during the initial attempt to combine the two technologies was carried out.An analysis of blood cell populations was performed to determine the safe time for antibody administration:the number of immune cells capable of activating systemic inflammation(CD11b+Ly-6C+,CD11b+Ly-6G+,CD3–NKp46+CD11b+),the presence of Fc receptor and OX40 on the surface of these cells,and the number of neutrophils activated to NETosis were analyzed.Based on the analysis results,the antitumor efficacy of various modes of combining the Karanahan technology and in situ vaccination was studied.Results:WhenαOX40 was administered 5 h after each treatment using the Karanahan technology,mass death of mice caused by systemic inflammation and multiple organ failure was observed.The state of blood cells after the treatment using the Karanahan technology at the time points corresponding to antibody injections was analyzed to elucidate the reasons for this effect.It was found that at some time points,there occurs activation of the immune system and a powerful release(up to 16%)of monocytes and granulocytes carrying Fc receptor and OX40 on their surface into blood;when interacting withαOX40,they can activate the lytic potential of these cells.Activation of neutrophils to NETosis was also observed.Based on these findings,a study was carried out in different time regimes to combine the Karanahan technology andαOX40 injections.WhenαOX40 was injected into the points of minimal release of myeloid cells into the blood,increased survival rate and the greatest antitumor efficacy were observed:37%of animals survived without relapses on day 100 after experiment initiation.Conclusions:The results obtained indicate that it is possible to combine the Karanahan technology and in situ vaccination withαOX40,with obligatory constant monitoring of the number of myeloid cells in peripheral blood to determine the safe time for antibody injection.
文摘BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.
基金supported in part by the National Natural Science Foundation of China (61773051,61773072,61761166011)the Fundamental Research Fund for the Central Universities (2016RC021,2017JBZ003)
文摘In this paper, we propose an adaptive fuzzy dynamic surface control(DSC) scheme for single-link flexible-joint robotic systems with input saturation. A smooth function is utilized with the mean-value theorem to deal with the difficulties associated with input saturation. An adaptive DSC design with an auxiliary first-order filter is used to solve the "explosion of complexity"problem. It is proved that all the signals in the closed-loop system are semi-globally uniformly ultimately bounded, and the tracking error eventually converges to a small neighborhood around zero. The main advantage of the proposed method is that only one adaptation parameter needs to be updated,which reduces the computational burden significantly. Simulation results demonstrate the feasibility of the proposed scheme and the comparison results show that the improved DSC method can reduce the computational burden by almost two thirds in comparison with the standard DSC method.
基金Supported by National Natural Science Foundation of China （60504024）, Zhejiang Provincial Natural Science Foundation of China （Y106010）, and the Specialized Research Fund for the Doctoral Program of Higher Education of China （20060335022）
文摘The method of stabilizing switched systems based on the optimal control is applied,with all modes unstable,for a typical example of the multi-agent system.First,the optimal control method for stabilizing switched systems is introduced.For this purpose,a switching table rule procedure is constructed.This procedure is inspired by the optimal control that identifies the optimal trajectory for the switched systems.In the next step,the stability of a multi-agent system is studied,considering different unstable connection topologies.Finally,the optimal control method is successfully applied to an aircraft team,as an example of the multi-agent systems.Simulation results evaluate and confirm the successful application of this method in the aircraft team example.
文摘Robust adaptive control of nonholonomic systems in chained form with linearly parameterized and strongly nonlinear disturbance and drift terms is dicussed.The novelty of the proposed method is a combined use of the state-scaling and the back-stepping procedure.
基金supported for this study by the Italian Ministryof University PRIN(Grant No.2017S9KTNE_002)supported by theScientific Research Project of the Traditional Chinese Medicine Bureau of Guangdong Province(No.20221086).
文摘Psychometric scales,commonly used to gauge sexual function,can sometimes be influenced by response biases.In our researchfrom June 2020 to April 2021,we examined the accuracy of self-reported sexual function scales.We invited patients from theDepartment of Infertility and Sexual Medicine at the Third Affiliated Hospital of Sun Yat-sen University(Guangzhou,China),whohave male sexual dysfunction,to participate by filling out a self-reported version of a specific questionnaire.In addition,they wentthrough a clinician-assisted version of this questionnaire,encompassing tools such as the Premature Ejaculation Diagnostic Tool(PEDT),the 6-item International Index of Erectile Function(IIEF-6),the Erection Hardness Scale(EHS),and the MasturbationErection Index(MEI).Using the clinician-assisted version as a reference,we categorized patients and applied various statisticalmethods,such as the Chi-square test,intraclass correlation coefficient(ICC),logistic regression,and the Bland–Altman plot,to gauge reliability.In our study with 322 participants,we found that while there were no notable discrepancies in error ratesbased on our categorization,certain scales showed significant differences in terms of overestimation and underestimation,withthe exception of the PEDT.The positive diagnosis rate consistency between the self-reported and clinician-assisted versions wasobserved.High ICC values between the two versions across the scales were indicative of remarkable reliability.Our findings showthat the self-reported versions of tools such as EHS,IIEF-6,MEI,and PEDT are credible and hold clinical reliability.However,employing a dual-diagnosis approach might be more prudent to circumvent potential misdiagnoses.
文摘Orthogonal Frequency Division Multiplexing (OFDM) is a multi-carrier scheme used in modern broadband wireless communication systems to transmit data over a number of orthogonal subcarriers. When transmitted signals arrive at the receiver by more than one path of different length, the received signals are staggered in time;this is multipath propagation. To mitigate the effect of dispersed channel distortion caused by random channel delay spread, Cyclic Prefix (CP) is introduced to eliminate Inter-Symbol Interference (ISI). In the literature, researchers have focused on carrying out investigations (or studies) mainly on the two existing CP insertions, namely: normal and extended CPs. Both CPs have limitations with respect to handling channel delay spreads. In the current work, a new CP, herein referred to as “ultra extended” CP is proposed to address delay spreads beyond the limits of the normal and extended CPs. The efficacy of the proposed ultra extended CP is tested via simulation under different scenarios. It is shown by the results obtained that the proposed CP can efficiently handle delay spreads beyond the limits of the existing normal and extended CP, and can indeed be implemented in the design of future telecommunication systems to accommodate higher channel delay spreads and it ensures wider cell coverage.
基金supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III(CD21/00138).PLV,DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139)TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Tomas Pinos,Grant No.PI22/00201).
文摘Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.
文摘In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.
