Aim: 2-bromopropane (2-BP) is known as an environmentalendocrine disrupter. Recently its reproductive and hematopoitic tox-icity has aroused the attention of the toxicologists. The presentstudy was designed to study i...Aim: 2-bromopropane (2-BP) is known as an environmentalendocrine disrupter. Recently its reproductive and hematopoitic tox-icity has aroused the attention of the toxicologists. The presentstudy was designed to study its testicular toxicity in male rats.Methods; Forty male SD rats were divided into four groups of10 rats each. 2-BP was administered intraperitoneally at doses of1800 mg, 600 mg or 200 mg per kg body weight per day for 5days. The control rats were given a similar volume of the vehicle.The animals were sacrificed two days after the last dose. Results: With increasing doses, the seminiferous tubular damage wasgradually increased and the percentage of spermatogonia in the totalgerm cells gradually decreased ( P < 0. 05). The seminiferoustubular area of rats taking 1800 mg/kg was also reduced significant-ly . The body weight, testicular weight and relative testicular weightof rats taking the highest dose level were all significantly decreasedas compared with the controls. (Reprod Contracep 2001; 21; 157-60)展开更多
2-Bromopropane (2-BP) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five ye...2-Bromopropane (2-BP) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five years.In the present study, we aimed to determine experimentally the testicular toxicity of 2-BP in male rats. Materials & Methods Forty SD male rats were divided into four groups of 10 rats each. The rats were intra-abdominally administered 2-BP once per day for 5 days continuously at the doses of 1800 mg/kg, 600 mg/kg, 200 mg/kg and normal saline, respectively. The rats were dissected one week after the first administration. Results The body weight, absolute testes weight and relative testes weight of the rats in 1 800 mg/kg dose group decreased significantly with comparison to those of the con- trol group,while the weight of accessory gonads showed no significant change. With the increase of dosage, the seminiferous tubules damage rate aggravated while the ratio of spermatogonia in total germ cells fell with P<0. 05. The seminiferous tubule area of rats in 1800 mg/kg group also reduced significantly. Under light microscopic examination, the spermatogonia of administered rats showed degeneration and chro- matin condensation. The nucleus of spermatocytes appeared hyperchromatic and py- knotic.Obvious testicular damage could be found in rats of high dose group, including large amount of spermatogonia necrosis or loss and reduced spermatocyte number. The electron microscopic findings were similar to those of the light microscopy, except that typical morphological change was found in the middle dose group: the structure of spermatogonia was destroyed, mitochondrion and endoplasmic reticulum scattered outside, nucleus disintegrated; some of the spermatocytes' membrane became nuclear, chromatin condensed and cogulation necrosis appeared; the nuclear membrane of round spermatids also showed slight damage. Conclusion The results indicated that testis was the target organ of 2-BP's reproduc- tive toxicity. The testicular toxicity of 2-BP started from damaging spermatogonia and its damage on spermatogonia was most obvious among all germ cells.展开更多
The nutrient digestion,absorption and biological activity of bee pollen may be limited due to the complex pollen wall.Here,the effect of superfine grinding technology on the release of nutrients from bee pollen were i...The nutrient digestion,absorption and biological activity of bee pollen may be limited due to the complex pollen wall.Here,the effect of superfine grinding technology on the release of nutrients from bee pollen were investigated,and their antioxidant activities and in vitro digestion were explored in this study.Results showed that the content of nutrients in bee pollen increased after wall disruption.Among them,fat content increased by 22.55%-8.31%,protein content increased by 0.54%-4.91%,starch content increased by 36.31%-48.64%,soluble sugar content increased by 20.57%-29.67%,total phenolic acid content increased by 11.73%-86.98%and total flavonoids content increased by 14.29%-24.79%.At the same time,the antioxidant activity increased by 14.84%-46.00%.Furthermore,the active components such as phenolic compounds in the wall-disruption bee pollen were more readily to be released during the in vitro digestion,and easier to be absorbed because of their higher bioaccessibility.Antioxidant activities during in vitro digestion were also improved in walldisruption bee pollen.These findings provide evidence that bee pollen wall disruption was suggested,thus,it is more conducive to exerting the value of bee pollen in functional foods.展开更多
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvatio...Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.展开更多
Purpose:The transformative impact of disruptive technologies on the restructuring of the times has attracted widespread global attention.This study aims to analyze the characteristics and shortcomings of China’s arti...Purpose:The transformative impact of disruptive technologies on the restructuring of the times has attracted widespread global attention.This study aims to analyze the characteristics and shortcomings of China’s artificial intelligence(AI)disruptive technology policy,and to put forward suggestions for optimizing China’s AI disruptive technology policy.Design/methodology/approach:Develop a three-dimensional analytical framework for“policy tools-policy actors-policy themes”and apply policy tools,social network analysis,and LDA topic model to conduct a comprehensive analysis of the utilization of policy tools,cooperative relationships among policy actors,and the trends in policy theme settings within China’s innovative AI technology policy.Findings:We find that the collaborative relationship among the policy actors of AI disruptive technology in China is insufficiently close.Marginal subjects exhibit low participation in the cooperation network and overly rely on central subjects,forming a“center-periphery”network structure.Policy tool usage is predominantly focused on supply and environmental types,with a severe inadequacy in demand-side policy tool utilization.Policy themes are diverse,encompassing topics such as“Intelligent Services”“Talent Cultivation”“Information Security”and“Technological Innovation”,which will remain focal points.Under the themes of“Intelligent Services”and“Intelligent Governance”,policy tool usage is relatively balanced,with close collaboration among policy entities.However,the theme of“AI Theoretical System”lacks a comprehensive understanding of tool usage and necessitates enhanced cooperation with other policy entities.Research limitations:The data sources and experimental scope are subject to certain limitations,potentially introducing biases and imperfections into the research results,necessitating further validation and refinement.Practical implications:The study introduces a three-dimensional analysis framework for disruptive technology policy texts,which is significant for formulating and enhancing disruptive technology policies.Originality/value:This study utilizes text mining and content analysis techniques to quantitatively analyze disruptive technology policy texts.It systematically evaluates China’s AI policies quantitatively,focusing on policy tools,policy actors,policy themes.The study uncovers the characteristics and deficiencies of current AI policies,offering recommendations for formulating and enhancing disruptive technology policies.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with ...Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.展开更多
A neural network model with a classical annotation method has been used on the EXL-50tokamak to predict impending disruption.However,the results revealed issues of overfitting and overconfidence in predictions caused ...A neural network model with a classical annotation method has been used on the EXL-50tokamak to predict impending disruption.However,the results revealed issues of overfitting and overconfidence in predictions caused by inaccurate labeling.To mitigate these issues,an improved training framework has been proposed.In this approach,soft labels from previous training serve as teachers to supervise the further learning process;this has lead to a significant improvement in predictive model performance.Notably,this enhancement is primarily attributed to the coupling effect of the soft labels and correction mechanism.This improved training framework introduces an instance-specific label smoothing method,which reflects a more nuanced model assessment on the likelihood of a disruption.It presents a possible solution to effectively address the challenges associated with accurate labeling across different machines.展开更多
BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mech...BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mechanisms of CALD1 in epithe-lial-mesenchymal transition(EMT)in GC are unknown.AIM To investigate the role and mechanism of CALD1 in GC progression,invasion,and migration.METHODS In this study,the relationship between CALD1 and GC,as well as the possible network regulatory mechanisms of CALD1,was investigated by bioinformatics and validated by experiments.CALD1-siRNA was synthesized and used to trans-fect GC cells.Cell activity was measured using the CCK-8 method,cell migration and invasive ability were measured using wound healing assay and Transwell assay,and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot.A GC cell xenograft model RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues,and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC.The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression,and a prognostic model was constructed and evaluated.The experimental results were consistent with the results of the bioinformatics analysis.The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1,with the strongest expression found in AGS and MKN45 cells.Cell activity was significantly reduced after CALD1-siRNA trans-fection of AGS and MKN45 cells.The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection,and the related mRNA and protein expression was altered.According to bioinfor-matics findings in GC samples,the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway,and was closely related to the PI3K-Akt signaling pathway.Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K,p-AKT,and p-mTOR,members of the PI3K-Akt pathway,while decreasing the expression of PTEN;PI3K-Akt inhibitor treatment decreased the expression of PI3K,p-AKT,and p-mTOR in cells overexpressing CALD1(still higher than that in the normal group),but increased the expression of PTEN(still lower than that in the normal group).CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor.Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor.The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1,whereas the effect of overex-pression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor.Animal experiments showed that tumour growth was slow after inhibition of CALD1,and the expression of some PI3K-Akt and EMT pathway proteins was altered.CONCLUSION Increased expression of CALD1 is a key factor in the progression,invasion,and metastasis of GC,which may be associated with regulating the PI3K-Akt pathway to promote EMT.展开更多
This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian...This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle,energy metabolism,immune function,and cell proliferation.The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles,while peripheral tissue clocks are influenced by cues such as feeding times.Circadian disruption,linked to modern lifestyle factors like night shift work,correlates with adverse health outcomes,including metabolic syndrome,cardiovascular diseases,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations between circadian disruption and endocrine tumors,spanning breast,ovarian,testicular,prostate,thyroid,pituitary,and adrenal gland cancers,are highlighted.Shift work is associated with increased breast cancer risk,with PER genes influencing tumor progression and drug resistance.CLOCK gene expression correlates with cisplatin resistance in ovarian cancer,while factors like aging and intermittent fasting affect prostate cancer.Our review underscored the intricate interplay between circadian rhythms and cancer,involving the regulation of the cell cycle,DNA repair,metabolism,immune function,and the tumor microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions could lead to novel therapeutic approaches.Evidence supports circadian rhythm-focused therapies,particularly chronotherapy,for treating endocrine tumors.Our review called for further research to uncover detailed connections between circadian clocks and cancer,providing essential insights for targeted treatments.We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.展开更多
This study aimed to understand disruptive thinking and how its ideas can change the food industry. This was achieved by identifying, studying, and understanding the impacts, current trends, and different disruptive id...This study aimed to understand disruptive thinking and how its ideas can change the food industry. This was achieved by identifying, studying, and understanding the impacts, current trends, and different disruptive ideas and innovations emerging in the food industry. The study was conducted through interpretive research philosophy by carrying out secondary data collection processes, where both qualitative and quantitative information was presented. Deductive approaches were also selected to apply existing theories and models, which were used to construct research hypotheses and present detailed findings. The study finds that, with disruptive thinking, enhancements in the product life cycle, new flavors, and improvements in food packaging have been possible. The supply chain, which is always considered a complex part of the food industry, has been streamlined, offering greater transparency and real-time tracking and improving quality control across distribution systems.展开更多
Objective: This study aims to evaluate the feasibility and effectiveness of neurofeedback therapy based on brain-computer interface (BCI) games in enhancing cognitive functions and reducing disruptive behaviors in pat...Objective: This study aims to evaluate the feasibility and effectiveness of neurofeedback therapy based on brain-computer interface (BCI) games in enhancing cognitive functions and reducing disruptive behaviors in patients with Alzheimer’s disease (AD). Methods: Forty-six AD patients aged 49 - 76 years were recruited for the study. Neurofeedback regulation was conducted using a BCI game designed to modulate EEG rhythms. Cognitive function was assessed using MMSE, MoCA, and ADAS-cog scales before and after a 10-day training period. EEG measurements were taken to evaluate changes in brain activity complexity. Statistical analyses were performed using SPSS25.0 software to compare pre- and post-training scores. Results: Post-intervention results showed significant improvement in the cognitive function of AD patients. The total scores of MMSE, MoCA, and ADAS-cog scales increased significantly (P < 0.01). Notable improvements were observed in memory, language, and attention domains. EEG complexity in the left frontal area also showed a significant increase (P < 0.05). Additionally, the disruptive behaviors of patients were significantly reduced, improving their overall quality of life. Conclusions: Neurofeedback therapy based on BCI games is a promising intervention for enhancing cognitive functions and reducing disruptive behaviors in AD patients. This innovative approach demonstrates significant potential for clinical application, providing a non-invasive method to improve patient outcomes. Further studies with larger sample sizes and long-term follow-ups are recommended to validate these findings and explore the specific effects of NFB training on different cognitive impairment levels.展开更多
Objectives:This study aims to assess sleep disorders among secondary school adolescents and explore the relationship between sociodemographic factors(age,gender,household income,and sleep duration)and the occurrence o...Objectives:This study aims to assess sleep disorders among secondary school adolescents and explore the relationship between sociodemographic factors(age,gender,household income,and sleep duration)and the occurrence of these disorders.Methods:A quantitative,descriptive,cross-sectional study,was conducted from November 20th,2022,to May 25th,2023,involving 200 secondary school students selected through convenience sampling.Data collection utilized a structured questionnaire divided into sociodemographic and sleep disorder sections.Validity was ensured by a panel of ten experts,and reliability was confirmed using Cronbach’s Alpha(0.77).Statistical analysis employed SPSS version 26.Results:Findings revealed that a majority of participants(70.5%)had low-level sleep disorders,followed by moderate disorders represented(29%).Significant associations were found between sleep disorders and gender(P=0.000),economic status for family(P=0.020),and nightly sleep duration(P=0.016).However,no significant relationship was observed between sleep disorders and family structure or age(P>0.05).Conclusions:The study highlights that most secondary school students experience mild sleep disorders,followed by moderate disorders.Notably,gender,income,and sleep duration showed significant correlations with sleep disorders.展开更多
In the realm of Artificial Intelligence (AI), there exists a complex landscape where promises of efficiency and innovation clash with unforeseen disruptions across Information Technology (IT) and broader societal real...In the realm of Artificial Intelligence (AI), there exists a complex landscape where promises of efficiency and innovation clash with unforeseen disruptions across Information Technology (IT) and broader societal realms. This paper sets out on a journey to explore the intricate paradoxes inherent in AI, focusing on the unintended consequences that ripple through IT and beyond. Through a thorough examination of literature and analysis of related works, this study aims to shed light on the complexities surrounding the AI paradox. It delves into how this paradox appears in various domains, such as algorithmic biases, job displacement, ethical dilemmas, and privacy concerns. By mapping out these unintended disruptions, this research seeks to offer a nuanced understanding of the challenges brought forth by AI-driven transformations. Ultimately, its goal is to pave the way for the responsible development and deployment of AI, fostering a harmonious integration of technological progress with societal values and priorities.展开更多
The recent rapid development of China’s foreign trade has led to the significant increase in waterway transportation and automated container ports. Automated terminals can significantly improve the loading and unload...The recent rapid development of China’s foreign trade has led to the significant increase in waterway transportation and automated container ports. Automated terminals can significantly improve the loading and unloading efficiency of container terminals. These terminals can also increase the port’s transportation volume while ensuring the quality of cargo loading and unloading, which has become an inevitable trend in the future development of ports. However, the continuous growth of the port’s transportation volume has increased the horizontal transportation pressure on the automated terminal, and the problems of route conflicts and road locks faced by automated guided vehicles (AGV) have become increasingly prominent. Accordingly, this work takes Xiamen Yuanhai automated container terminal as an example. This work focuses on analyzing the interference problem of path conflict in its horizontal transportation AGV scheduling. Results show that path conflict, the most prominent interference factor, will cause AGV scheduling to be unable to execute the original plan. Consequently, the disruption management was used to establish a disturbance recovery model, and the Dijkstra algorithm for combining with time windows is adopted to plan a conflict-free path. Based on the comparison with the rescheduling method, the research obtains that the deviation of the transportation path and the deviation degree of the transportation path under the disruption management method are much lower than those of the rescheduling method. The transportation path deviation degree of the disruption management method is only 5.56%. Meanwhile, the deviation degree of the transportation path under the rescheduling method is 44.44%.展开更多
To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupte...To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupted events.Three states of tractors including towing loaded trailers,towing empty trailers,and idle driving are taken into account.Based on the disruption management theory,a scheduling model is constructed to minimize the total deviation cost including transportation time,transportation path,and number of used vehicles under the three states of tractors.A heuristics based on the contract net and simulated annealing algorithm is designed to solve the proposed model.Through comparative analysis of examples with different numbers of newly added transportation tasks and different types of road networks,the performance of the contract net algorithm in terms of deviations in idle driving paths,empty trailer paths,loaded trailer paths,time,number of used vehicles,and total deviation cost are analyzed.The results demonstrate the effectiveness of the model and algorithm,highlighting the superiority of the disruption management model and the contract net annealing algorithm.The study provides a reference for handling unexpected events in the tractor and trailer transportation industry.展开更多
Objective:To review the research status and progress of minimally disruptive medicine(MDM)with a view and to provide a theoretical basis for reducing the treatment burden of patients with multimorbidity.Methods:"...Objective:To review the research status and progress of minimally disruptive medicine(MDM)with a view and to provide a theoretical basis for reducing the treatment burden of patients with multimorbidity.Methods:"Minimal Destructive Medicine"was used as searching term in HowNet Database and Wanfang Database,and"Minimally Disruptive Medicine"was used as searching term in PubMed database.The literature was reviewed for a review of the concepts of minimally destructive medicine(MDM),four basic principles,care models,and tools and strategies for clinical implementation.Results:MDM was developed for the coexistence burden of chronic diseases.It had formed a detailed and detailed application of basic principles and care models.The tools and strategies developed by MDM have been applied in clinical practice with good Results.Conclusion:MDM has a positive effect on reducing the burden of treatment for the multimorbidity and it is worthy of further research and promotion.展开更多
In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term ...In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term consequences that businesses encounter. This study integrates findings from various research, including quantitative reports, drawing upon real-world incidents faced by both small and large enterprises. This investigation emphasizes the profound intangible costs, such as trade name devaluation and potential damage to brand reputation, which can persist long after the breach. By collating insights from industry experts and a myriad of research, the study provides a comprehensive perspective on the profound, multi-dimensional impacts of cybersecurity incidents. The overarching aim is to underscore the often-underestimated scope and depth of these breaches, emphasizing the entire timeline post-incident and the urgent need for fortified preventative and reactive measures in the digital domain.展开更多
Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease ...Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression.Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier.For example,astrocytic cove rage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions.Astrocyte activation is often observed in Alzheimer’s disease patients,with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta.Structural alte rations in Alzheimer’s disease astrocytes including swollen endfeet,somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arte rioles levels.In addition,Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration.In this review,we summarize the findings of existing literature on the relevance of astrocyte alte ration in response to amyloid pathology in the context of blood-brain barrier dysfunction.First,we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance.Then,we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models.We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte.Finally,we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes,providing potential molecular mechanisms underlying blood-brain barrier modulation.We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease.展开更多
In EAST long-pulsed discharge(hundreds of seconds),electric magnetic diagnosis(EMD)is very important,since EMD not only monitors tokamak security status but also provides accurate measurement accuracy for reconstructi...In EAST long-pulsed discharge(hundreds of seconds),electric magnetic diagnosis(EMD)is very important,since EMD not only monitors tokamak security status but also provides accurate measurement accuracy for reconstruction of the plasma boundary.To avoid current measurement drift,a fiber optic current sensor,based on the Faraday effect,is developed and used for poloidal and plasma current feedback control for the first time,relative current measurement accuracy is within 0.5%.To ensure plasma boundary control accuracy,a detailed set of magnetic measurement calibration methods is developed before the plasma discharge.The maximum relative error is less than 1%,the corresponding control accuracy is within 1 cm.To minimize integrator drift error,a long-pulse integrator test is essential,the corresponding drift error needs to be subtracted in plasma control system.Besides,the saddle coil and Mirnov coil not only help to detect MHD issues,but are also utilized for plasma disruption prediction during the long-pulse discharge.展开更多
文摘Aim: 2-bromopropane (2-BP) is known as an environmentalendocrine disrupter. Recently its reproductive and hematopoitic tox-icity has aroused the attention of the toxicologists. The presentstudy was designed to study its testicular toxicity in male rats.Methods; Forty male SD rats were divided into four groups of10 rats each. 2-BP was administered intraperitoneally at doses of1800 mg, 600 mg or 200 mg per kg body weight per day for 5days. The control rats were given a similar volume of the vehicle.The animals were sacrificed two days after the last dose. Results: With increasing doses, the seminiferous tubular damage wasgradually increased and the percentage of spermatogonia in the totalgerm cells gradually decreased ( P < 0. 05). The seminiferoustubular area of rats taking 1800 mg/kg was also reduced significant-ly . The body weight, testicular weight and relative testicular weightof rats taking the highest dose level were all significantly decreasedas compared with the controls. (Reprod Contracep 2001; 21; 157-60)
基金This study is under the support of Shanghai Science and Technology Committee
文摘2-Bromopropane (2-BP) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five years.In the present study, we aimed to determine experimentally the testicular toxicity of 2-BP in male rats. Materials & Methods Forty SD male rats were divided into four groups of 10 rats each. The rats were intra-abdominally administered 2-BP once per day for 5 days continuously at the doses of 1800 mg/kg, 600 mg/kg, 200 mg/kg and normal saline, respectively. The rats were dissected one week after the first administration. Results The body weight, absolute testes weight and relative testes weight of the rats in 1 800 mg/kg dose group decreased significantly with comparison to those of the con- trol group,while the weight of accessory gonads showed no significant change. With the increase of dosage, the seminiferous tubules damage rate aggravated while the ratio of spermatogonia in total germ cells fell with P<0. 05. The seminiferous tubule area of rats in 1800 mg/kg group also reduced significantly. Under light microscopic examination, the spermatogonia of administered rats showed degeneration and chro- matin condensation. The nucleus of spermatocytes appeared hyperchromatic and py- knotic.Obvious testicular damage could be found in rats of high dose group, including large amount of spermatogonia necrosis or loss and reduced spermatocyte number. The electron microscopic findings were similar to those of the light microscopy, except that typical morphological change was found in the middle dose group: the structure of spermatogonia was destroyed, mitochondrion and endoplasmic reticulum scattered outside, nucleus disintegrated; some of the spermatocytes' membrane became nuclear, chromatin condensed and cogulation necrosis appeared; the nuclear membrane of round spermatids also showed slight damage. Conclusion The results indicated that testis was the target organ of 2-BP's reproduc- tive toxicity. The testicular toxicity of 2-BP started from damaging spermatogonia and its damage on spermatogonia was most obvious among all germ cells.
基金the Program of State Key Laboratory of Food Science and Technology,Nanchang University (SKLF-ZZB-202119)。
文摘The nutrient digestion,absorption and biological activity of bee pollen may be limited due to the complex pollen wall.Here,the effect of superfine grinding technology on the release of nutrients from bee pollen were investigated,and their antioxidant activities and in vitro digestion were explored in this study.Results showed that the content of nutrients in bee pollen increased after wall disruption.Among them,fat content increased by 22.55%-8.31%,protein content increased by 0.54%-4.91%,starch content increased by 36.31%-48.64%,soluble sugar content increased by 20.57%-29.67%,total phenolic acid content increased by 11.73%-86.98%and total flavonoids content increased by 14.29%-24.79%.At the same time,the antioxidant activity increased by 14.84%-46.00%.Furthermore,the active components such as phenolic compounds in the wall-disruption bee pollen were more readily to be released during the in vitro digestion,and easier to be absorbed because of their higher bioaccessibility.Antioxidant activities during in vitro digestion were also improved in walldisruption bee pollen.These findings provide evidence that bee pollen wall disruption was suggested,thus,it is more conducive to exerting the value of bee pollen in functional foods.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
基金supported by the National Social Science Foundation of China(Grant No.22BTQ089).
文摘Purpose:The transformative impact of disruptive technologies on the restructuring of the times has attracted widespread global attention.This study aims to analyze the characteristics and shortcomings of China’s artificial intelligence(AI)disruptive technology policy,and to put forward suggestions for optimizing China’s AI disruptive technology policy.Design/methodology/approach:Develop a three-dimensional analytical framework for“policy tools-policy actors-policy themes”and apply policy tools,social network analysis,and LDA topic model to conduct a comprehensive analysis of the utilization of policy tools,cooperative relationships among policy actors,and the trends in policy theme settings within China’s innovative AI technology policy.Findings:We find that the collaborative relationship among the policy actors of AI disruptive technology in China is insufficiently close.Marginal subjects exhibit low participation in the cooperation network and overly rely on central subjects,forming a“center-periphery”network structure.Policy tool usage is predominantly focused on supply and environmental types,with a severe inadequacy in demand-side policy tool utilization.Policy themes are diverse,encompassing topics such as“Intelligent Services”“Talent Cultivation”“Information Security”and“Technological Innovation”,which will remain focal points.Under the themes of“Intelligent Services”and“Intelligent Governance”,policy tool usage is relatively balanced,with close collaboration among policy entities.However,the theme of“AI Theoretical System”lacks a comprehensive understanding of tool usage and necessitates enhanced cooperation with other policy entities.Research limitations:The data sources and experimental scope are subject to certain limitations,potentially introducing biases and imperfections into the research results,necessitating further validation and refinement.Practical implications:The study introduces a three-dimensional analysis framework for disruptive technology policy texts,which is significant for formulating and enhancing disruptive technology policies.Originality/value:This study utilizes text mining and content analysis techniques to quantitatively analyze disruptive technology policy texts.It systematically evaluates China’s AI policies quantitatively,focusing on policy tools,policy actors,policy themes.The study uncovers the characteristics and deficiencies of current AI policies,offering recommendations for formulating and enhancing disruptive technology policies.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81773566 and 21602092)Innovation Project of Medicine and Health Science and Technology of Chinese Academy of Medical Sciences(2019-I2M-5-074)+1 种基金the Funds for Fundamental Research Creative Groups of Gansu Province(No.20JR5RA310)the Fundamental Research Funds for the Central Universities(No.lzujbky-2021-38).
文摘Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.
基金supported by National Natural Science Foundation of China(Nos.12175277 and 11975271)the National Key R&D Program of China(No.2022YFE 03050003)。
文摘A neural network model with a classical annotation method has been used on the EXL-50tokamak to predict impending disruption.However,the results revealed issues of overfitting and overconfidence in predictions caused by inaccurate labeling.To mitigate these issues,an improved training framework has been proposed.In this approach,soft labels from previous training serve as teachers to supervise the further learning process;this has lead to a significant improvement in predictive model performance.Notably,this enhancement is primarily attributed to the coupling effect of the soft labels and correction mechanism.This improved training framework introduces an instance-specific label smoothing method,which reflects a more nuanced model assessment on the likelihood of a disruption.It presents a possible solution to effectively address the challenges associated with accurate labeling across different machines.
基金The Hebei Provincial Major Science and Technology Special Project,No.23297701ZBeijing-Tianjin-Hebei Basic Research Cooperation Special Project,No.22JCZXJC00140Hebei Provincial Government-Funded Clinical Talent Project,No.ZF2023047.
文摘BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mechanisms of CALD1 in epithe-lial-mesenchymal transition(EMT)in GC are unknown.AIM To investigate the role and mechanism of CALD1 in GC progression,invasion,and migration.METHODS In this study,the relationship between CALD1 and GC,as well as the possible network regulatory mechanisms of CALD1,was investigated by bioinformatics and validated by experiments.CALD1-siRNA was synthesized and used to trans-fect GC cells.Cell activity was measured using the CCK-8 method,cell migration and invasive ability were measured using wound healing assay and Transwell assay,and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot.A GC cell xenograft model RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues,and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC.The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression,and a prognostic model was constructed and evaluated.The experimental results were consistent with the results of the bioinformatics analysis.The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1,with the strongest expression found in AGS and MKN45 cells.Cell activity was significantly reduced after CALD1-siRNA trans-fection of AGS and MKN45 cells.The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection,and the related mRNA and protein expression was altered.According to bioinfor-matics findings in GC samples,the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway,and was closely related to the PI3K-Akt signaling pathway.Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K,p-AKT,and p-mTOR,members of the PI3K-Akt pathway,while decreasing the expression of PTEN;PI3K-Akt inhibitor treatment decreased the expression of PI3K,p-AKT,and p-mTOR in cells overexpressing CALD1(still higher than that in the normal group),but increased the expression of PTEN(still lower than that in the normal group).CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor.Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor.The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1,whereas the effect of overex-pression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor.Animal experiments showed that tumour growth was slow after inhibition of CALD1,and the expression of some PI3K-Akt and EMT pathway proteins was altered.CONCLUSION Increased expression of CALD1 is a key factor in the progression,invasion,and metastasis of GC,which may be associated with regulating the PI3K-Akt pathway to promote EMT.
文摘This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle,energy metabolism,immune function,and cell proliferation.The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles,while peripheral tissue clocks are influenced by cues such as feeding times.Circadian disruption,linked to modern lifestyle factors like night shift work,correlates with adverse health outcomes,including metabolic syndrome,cardiovascular diseases,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations between circadian disruption and endocrine tumors,spanning breast,ovarian,testicular,prostate,thyroid,pituitary,and adrenal gland cancers,are highlighted.Shift work is associated with increased breast cancer risk,with PER genes influencing tumor progression and drug resistance.CLOCK gene expression correlates with cisplatin resistance in ovarian cancer,while factors like aging and intermittent fasting affect prostate cancer.Our review underscored the intricate interplay between circadian rhythms and cancer,involving the regulation of the cell cycle,DNA repair,metabolism,immune function,and the tumor microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions could lead to novel therapeutic approaches.Evidence supports circadian rhythm-focused therapies,particularly chronotherapy,for treating endocrine tumors.Our review called for further research to uncover detailed connections between circadian clocks and cancer,providing essential insights for targeted treatments.We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.
文摘This study aimed to understand disruptive thinking and how its ideas can change the food industry. This was achieved by identifying, studying, and understanding the impacts, current trends, and different disruptive ideas and innovations emerging in the food industry. The study was conducted through interpretive research philosophy by carrying out secondary data collection processes, where both qualitative and quantitative information was presented. Deductive approaches were also selected to apply existing theories and models, which were used to construct research hypotheses and present detailed findings. The study finds that, with disruptive thinking, enhancements in the product life cycle, new flavors, and improvements in food packaging have been possible. The supply chain, which is always considered a complex part of the food industry, has been streamlined, offering greater transparency and real-time tracking and improving quality control across distribution systems.
文摘Objective: This study aims to evaluate the feasibility and effectiveness of neurofeedback therapy based on brain-computer interface (BCI) games in enhancing cognitive functions and reducing disruptive behaviors in patients with Alzheimer’s disease (AD). Methods: Forty-six AD patients aged 49 - 76 years were recruited for the study. Neurofeedback regulation was conducted using a BCI game designed to modulate EEG rhythms. Cognitive function was assessed using MMSE, MoCA, and ADAS-cog scales before and after a 10-day training period. EEG measurements were taken to evaluate changes in brain activity complexity. Statistical analyses were performed using SPSS25.0 software to compare pre- and post-training scores. Results: Post-intervention results showed significant improvement in the cognitive function of AD patients. The total scores of MMSE, MoCA, and ADAS-cog scales increased significantly (P < 0.01). Notable improvements were observed in memory, language, and attention domains. EEG complexity in the left frontal area also showed a significant increase (P < 0.05). Additionally, the disruptive behaviors of patients were significantly reduced, improving their overall quality of life. Conclusions: Neurofeedback therapy based on BCI games is a promising intervention for enhancing cognitive functions and reducing disruptive behaviors in AD patients. This innovative approach demonstrates significant potential for clinical application, providing a non-invasive method to improve patient outcomes. Further studies with larger sample sizes and long-term follow-ups are recommended to validate these findings and explore the specific effects of NFB training on different cognitive impairment levels.
文摘Objectives:This study aims to assess sleep disorders among secondary school adolescents and explore the relationship between sociodemographic factors(age,gender,household income,and sleep duration)and the occurrence of these disorders.Methods:A quantitative,descriptive,cross-sectional study,was conducted from November 20th,2022,to May 25th,2023,involving 200 secondary school students selected through convenience sampling.Data collection utilized a structured questionnaire divided into sociodemographic and sleep disorder sections.Validity was ensured by a panel of ten experts,and reliability was confirmed using Cronbach’s Alpha(0.77).Statistical analysis employed SPSS version 26.Results:Findings revealed that a majority of participants(70.5%)had low-level sleep disorders,followed by moderate disorders represented(29%).Significant associations were found between sleep disorders and gender(P=0.000),economic status for family(P=0.020),and nightly sleep duration(P=0.016).However,no significant relationship was observed between sleep disorders and family structure or age(P>0.05).Conclusions:The study highlights that most secondary school students experience mild sleep disorders,followed by moderate disorders.Notably,gender,income,and sleep duration showed significant correlations with sleep disorders.
文摘In the realm of Artificial Intelligence (AI), there exists a complex landscape where promises of efficiency and innovation clash with unforeseen disruptions across Information Technology (IT) and broader societal realms. This paper sets out on a journey to explore the intricate paradoxes inherent in AI, focusing on the unintended consequences that ripple through IT and beyond. Through a thorough examination of literature and analysis of related works, this study aims to shed light on the complexities surrounding the AI paradox. It delves into how this paradox appears in various domains, such as algorithmic biases, job displacement, ethical dilemmas, and privacy concerns. By mapping out these unintended disruptions, this research seeks to offer a nuanced understanding of the challenges brought forth by AI-driven transformations. Ultimately, its goal is to pave the way for the responsible development and deployment of AI, fostering a harmonious integration of technological progress with societal values and priorities.
文摘The recent rapid development of China’s foreign trade has led to the significant increase in waterway transportation and automated container ports. Automated terminals can significantly improve the loading and unloading efficiency of container terminals. These terminals can also increase the port’s transportation volume while ensuring the quality of cargo loading and unloading, which has become an inevitable trend in the future development of ports. However, the continuous growth of the port’s transportation volume has increased the horizontal transportation pressure on the automated terminal, and the problems of route conflicts and road locks faced by automated guided vehicles (AGV) have become increasingly prominent. Accordingly, this work takes Xiamen Yuanhai automated container terminal as an example. This work focuses on analyzing the interference problem of path conflict in its horizontal transportation AGV scheduling. Results show that path conflict, the most prominent interference factor, will cause AGV scheduling to be unable to execute the original plan. Consequently, the disruption management was used to establish a disturbance recovery model, and the Dijkstra algorithm for combining with time windows is adopted to plan a conflict-free path. Based on the comparison with the rescheduling method, the research obtains that the deviation of the transportation path and the deviation degree of the transportation path under the disruption management method are much lower than those of the rescheduling method. The transportation path deviation degree of the disruption management method is only 5.56%. Meanwhile, the deviation degree of the transportation path under the rescheduling method is 44.44%.
基金support provided by the National Natural Science Foundation of China(Grant No.52362055)the Science and Technology Plan Project of Guangxi Zhuang Autonomous Region(Grant No.2021AC19334)Guangxi Science and Technology Major Program(Grant No.AA23062053).
文摘To provide a much more resilient transport scheme for tractor and trailer transportation systems,this paper explores the generation method of tractor and trailer transport schemes considering the influence of disrupted events.Three states of tractors including towing loaded trailers,towing empty trailers,and idle driving are taken into account.Based on the disruption management theory,a scheduling model is constructed to minimize the total deviation cost including transportation time,transportation path,and number of used vehicles under the three states of tractors.A heuristics based on the contract net and simulated annealing algorithm is designed to solve the proposed model.Through comparative analysis of examples with different numbers of newly added transportation tasks and different types of road networks,the performance of the contract net algorithm in terms of deviations in idle driving paths,empty trailer paths,loaded trailer paths,time,number of used vehicles,and total deviation cost are analyzed.The results demonstrate the effectiveness of the model and algorithm,highlighting the superiority of the disruption management model and the contract net annealing algorithm.The study provides a reference for handling unexpected events in the tractor and trailer transportation industry.
文摘Objective:To review the research status and progress of minimally disruptive medicine(MDM)with a view and to provide a theoretical basis for reducing the treatment burden of patients with multimorbidity.Methods:"Minimal Destructive Medicine"was used as searching term in HowNet Database and Wanfang Database,and"Minimally Disruptive Medicine"was used as searching term in PubMed database.The literature was reviewed for a review of the concepts of minimally destructive medicine(MDM),four basic principles,care models,and tools and strategies for clinical implementation.Results:MDM was developed for the coexistence burden of chronic diseases.It had formed a detailed and detailed application of basic principles and care models.The tools and strategies developed by MDM have been applied in clinical practice with good Results.Conclusion:MDM has a positive effect on reducing the burden of treatment for the multimorbidity and it is worthy of further research and promotion.
文摘In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term consequences that businesses encounter. This study integrates findings from various research, including quantitative reports, drawing upon real-world incidents faced by both small and large enterprises. This investigation emphasizes the profound intangible costs, such as trade name devaluation and potential damage to brand reputation, which can persist long after the breach. By collating insights from industry experts and a myriad of research, the study provides a comprehensive perspective on the profound, multi-dimensional impacts of cybersecurity incidents. The overarching aim is to underscore the often-underestimated scope and depth of these breaches, emphasizing the entire timeline post-incident and the urgent need for fortified preventative and reactive measures in the digital domain.
基金supported by the Science and Technology Development Fund (Macao SAR)(120015/2019/ASC,0023/2020/AFJ,0035/2020/AGJ)the University of Macao Research Grant (MYRG2022-00248-ICMS)(all to MPMH)。
文摘Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression.Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier.For example,astrocytic cove rage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions.Astrocyte activation is often observed in Alzheimer’s disease patients,with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta.Structural alte rations in Alzheimer’s disease astrocytes including swollen endfeet,somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arte rioles levels.In addition,Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration.In this review,we summarize the findings of existing literature on the relevance of astrocyte alte ration in response to amyloid pathology in the context of blood-brain barrier dysfunction.First,we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance.Then,we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models.We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte.Finally,we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes,providing potential molecular mechanisms underlying blood-brain barrier modulation.We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease.
基金supported by the National Magnetic Confinement Fusion Program of China(Nos.2018YFE0302100 and 2022YFE03010002)National Natural Science Foundation of China(Nos.12205195)。
文摘In EAST long-pulsed discharge(hundreds of seconds),electric magnetic diagnosis(EMD)is very important,since EMD not only monitors tokamak security status but also provides accurate measurement accuracy for reconstruction of the plasma boundary.To avoid current measurement drift,a fiber optic current sensor,based on the Faraday effect,is developed and used for poloidal and plasma current feedback control for the first time,relative current measurement accuracy is within 0.5%.To ensure plasma boundary control accuracy,a detailed set of magnetic measurement calibration methods is developed before the plasma discharge.The maximum relative error is less than 1%,the corresponding control accuracy is within 1 cm.To minimize integrator drift error,a long-pulse integrator test is essential,the corresponding drift error needs to be subtracted in plasma control system.Besides,the saddle coil and Mirnov coil not only help to detect MHD issues,but are also utilized for plasma disruption prediction during the long-pulse discharge.