Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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.

Effect of wall-disruption on nutrient composition and in vitro digestion of camellia and lotus bee pollens

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.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

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.

A quantitative study of disruptive technology policy texts:An example of China’s artificial intelligence policy

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.

The Future of Environmental Engineering Technology:A Disruptive Innovation Perspective

Scientific and technological revolutions and industrial transformations have accelerated the rate of innovation in environmental engineering technologies.However,few researchers have evaluated the current status and future trends of technologies.This paper summarizes the current research status in eight major subfields of environmental engineering—water treatment,air pollution control,soil/solid waste management,environmental biotechnology,environmental engineering equipment,emerging contaminants,synergistic reduction of pollution and carbon emissions,and environmental risk and intelligent management—based on bibliometric analysis and future trends in greenization,low carbonization,and intelligentization.Disruptive technologies are further identified based on discontinuous transformation,and ten such technologies are proposed,covering general and specific fields,technical links,and value sources.Additionally,the background and key innovations in disruptive technologies are elucidated in detail.This study not only provides a scientific basis for strategic decision-making,planning,and implementation in the environmental engineering field but also offers methodological guidance for the research and determination of breakthrough technologies in other areas.

Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy

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.

Understanding the Resilience of Urban Rail Transit:Concepts,Reviews,and Trends

As the scale of urban rail transit(URT)networks expands,the study of URT resilience is essential for safe and efficient operations.This paper presents a comprehensive review of URT resilience and highlights potential trends and directions for future research.First,URT resilience is defined by three primary abilities:absorption,resistance,and recovery,and four properties:robustness,vulnerability,rapidity,and redundancy.Then,the metrics and assessment approaches for URT resilience were summarized.The metrics are divided into three categories:topology-based,characteristic-based,and performance-based,and the assessment methods are divided into four categories:topological,simulation,optimization,and datadriven.Comparisons of various metrics and assessment approaches revealed that the current research trend in URT resilience is increasingly favoring the integration of traditional methods,such as conventional complex network analysis and operations optimization theory,with new techniques like big data and intelligent computing technology,to accurately assess URT resilience.Finally,five potential trends and directions for future research were identified:analyzing resilience based on multisource data,optimizing train diagram in multiple scenarios,accurate response to passenger demand through new technologies,coupling and optimizing passenger and traffic flows,and optimal line design.

Improved training framework in a neural network model for disruption prediction and its application on EXL-50

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.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

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.

Circadian rhythm disruption and endocrine-related tumors

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.

The Effects of Disruptive Thinking on the Food Industry*

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.

Feasibility Study of Neurofeedback Therapy for Alzheimer’s Disease

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.

Disruption of sleep patterns among secondary school adolescents

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.

The AI Paradox: Mapping the Unintended Disruptions in IT and Beyond

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.

AGV Scheduling Optimization of Automated Port Based on Disruption Management

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%.

Scheduling on tractor and trailer transportation considering the influence of disrupted events based on the contract net and simulated annealing algorithm

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.

Research Progress of Minimally Destructive Medicine Applied to Multimorbidity

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.

Cyberattack Ramifications, The Hidden Cost of a Security Breach

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.

Effects of Blood Cell Membrane Disruption by Ultrasonic Technology on the Quality of Duck Blood Tofu

[Objective] The aim was to improve the quality of the duck blood tofu by ultrasonic technology. [Method] Ultrasonic technology was used to break the blood cell membrane. The optimal ultrasonic condition was determined by single factor de- sign, and the differences in sensory quality and nutritional value between the duck blood tofu treated with and without ultrasonication were studied. [Result] The optimal ultrasonic power was 400 W and the optimal ultrasonic time was 6 min. Under these conditions, the content of duck blood haemoglobin increased by 43.46%, the content of iron increased by 10.85%, and the breakage rate was 100%. The a＊ value of the duck blood tofu increased significantly under ultrasonic treatment. Both internal micro-structure and texture parameters proved that the ultrasonic contributed to the formation of gel structure. After treatment by artificial gastric juice and artifi- cial intestinal juice, the total amino acids in the digestive juice were 9.25% higher than that of the duck blood tofu without ultrasonic treatment. [Conclusion] The duck blood tofu under ultrasonic treatment would be beneficial to human body absorption, and the nutrition value would be higher as well.

Supply chain coordination mechanisms under asymmetric information with retailer cost disruptions

A two-level supply chain model involving one supplier and one retailer with linear demand is developed, and supply chain coordination mechanisms under asymmetric information （the retailer＇ s cost structure is asymmetric information） are proposed by employing game theory in two scenarios： coordination mechanisms under asymmetric information in a regular scenario （without disruption）; and coordination mechanisms under asymmetric information in an irregular scenario （ with retailer cost disruptions）. It is optimal for the supply chain to maintain the original production plan and to guarantee a steadily running system if variations of retailer costs are sufficiently low and do not exceed an upper bound. This shows that the original production plan has certain robustness under disruptions. Decisions must be re-made if a retailer＇ s cost change is greater and exceeds an upper bound. Impacts of retailer cost disruptions on the order quantity, the retail price, the wholesale price and each party＇ s as well as the system＇ s expected profits are investigated through numerical analyses.