Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear me...Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).展开更多
Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls ...Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.展开更多
As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several a...As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several advantages,including low immunogenicity/cytotoxicity,the ability to traverse biological barriers,and high potential for engineering.However,several challenges remain in the clinical application of EVs.Their plasma half-life is relatively short,and they tend to accumulate in parenchymal organs(e.g.,liver and spleen)within a short time.Moreover,their targeting capabilities are neither precise nor highly effective.Additionally,EVs lack controlled and sustained release properties,necessitating the design of effective delivery strategies to ensure that therapeutic concentrations are achieved and maintained at the target site for an adequate duration.This review summarizes the latest drug delivery strategies involving EVs,focusing on systemic and local applications.It introduces various engineering approaches,administration strategies,and auxiliary delivery systems.Finally,the review discusses existing challenges in EV-based drug delivery and provides insights into the trends for future development in this field.展开更多
Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigati...Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.展开更多
In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse aven...In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse avenues for growth but also led to substantial progress in certain areas while phasing out and optimizing several business models.Against this backdrop,employing effective and rational strategies to enhance corporate management standards is crucial.This is particularly important given the imperfections in current management systems,the shortage of specialized talent,and the need for digital capability improvements,all of which are vital for ensuring the long-term stability and success of enterprises.With this in mind,this paper explores corporate administration models and proposes several practical solutions to address challenges faced in business management under the digital economy,aiming to serve as a valuable resource for professionals and decision-makers alike.展开更多
BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial...BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.展开更多
The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration ...The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration Systems (LAS). LAS services involve requests and responses concerning public and private cadastral data, including credentials of parties, ownership, and spatial parcels. This study explores the integration of CTI in LAS to enhance cyber resilience, focusing on the unique vulnerabilities of LAS, such as sensitive data management and interconnection with other critical systems related to spatial data uses and changes. The approach employs a case study of a typical country-specific LAS to analyse structured vulnerabilities and their attributes to determine the degree of vulnerability of LAS through a quantitative inductive approach. The analysis results indicate significant improvements in identifying and mitigating potential threats through CTI integration, thus enhancing cyber resilience. These findings are crucial for policymakers and practitioners to develop robust cybersecurity strategies for LAS.展开更多
With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the c...With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the campus.They have been applied to teaching,scientific research,student management,and other fields,improving the quality and efficiency of management.This paper mainly studies the intelligent educational administration management system based on data mining technology.Firstly,this paper introduces the application process of data mining technology,and builds an intelligent educational administration management system based on data mining technology.Then,this paper optimizes the application of the Apriori algorithm in educational administration management through transaction compression and frequent sampling.Compared with the traditional Apriori algorithm,the optimized Apriori algorithm in this paper has a shorter execution time under the same minimum support.展开更多
Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 wer...Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 were selected as the reference group,implementing conventional medical administration.Another 39 medical incidents from October 2022 to October 2024 were chosen as the experimental group,adopting the matrix medical administration model.The practical indicators such as causes of medical disputes,dispute compensation,medical injury appraisal results,and diagnosis and treatment quality indicators were compared between the two groups.Results:In the experimental group,the primary reasons for medical disputes were patient-related,and most disputes resulted in no compensation.After medical injury appraisal,most cases were not considered medical injuries.The comparison between the two groups was statistically significant(P<0.05).The diagnosis and treatment quality indicators of the experimental group were superior to those of the reference group(P<0.05).Conclusion:The matrix medical administration model can reduce medical disputes caused by hospital factors,decrease the proportion of compensation and the incidence of medical injuries,and improve the quality of diagnosis and treatment,demonstrating high management effectiveness.展开更多
BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores ...BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.展开更多
Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary informati...Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.展开更多
The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote ...The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote economic growth and social civilization.This paper explores methods and strategies for optimizing the business environment from a public management perspective.By analyzing the significance of optimizing the business environment and addressing its current limitations,it offers practical recommendations aimed at comprehensively advancing business environment optimization and providing a solid foundation for the healthy development of enterprises.展开更多
As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This stud...As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This study explores the dynamic processes of QBO disruptions using the integrated climate model of the China Meteorological Administration(CMA)by nudging the tropical zonal winds toward observations.A comparative analysis with ERA5 reanalysis data shows that the nudged runs accurately replicate the general characteristics of the QBO,including the alternating QBO wind regimes and QBO disruption events.The evolution of the QBO winds is diagnosed using empirical orthogonal function and root-mean-square difference analyses,and the rarity of the disruption events is confirmed in the CMA model.Different aspects of the QBO disruptions and the relevant dynamics are present in the model.Firstly,the momentum budget analysis highlights the crucial roles of extratropical Rossby waves and non-orographic gravity waves in the transition from westerly to easterly winds during a disruption.Secondly,Kelvin waves and non-orographic gravity waves explain much of the transition from easterly to westerly winds near 40 hPa.Thirdly,the positive tendency from enhanced vertical advection further accelerates westerly momentum development via secondary meridional circulation.These findings underscore the importance of nudging techniques in understanding QBO dynamics,which provides valuable insights for future climate model improvements toward better forecasting QBO-related climate variability.Notably,due to model limitations,no QBO disruptions were simulated in the free-run experiments.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with ...In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with related parts. A new science branch called ＂information science＂ is defined. Importance of the political organizing of a political party is shortly explained. The necessity of the academies for public sector, private sector, and for political administration system is expressed. How to choose a person and how a person can be choose for any part of the system is defined. For both cases ＂good and/or correct＂ system criterions, determination of the criterions, and evaluation criterions are defined. New evaluation levels are defined based on the 8-basic senses in philosophical point of view to deepen the sensitivity of the evaluations. The importance of the situation notice and how to make it for each of the association are explained. The 10 main service parameters are defined to show the interactive relations between the ideology, services, person nature and others. Present and possible future problems of a country are expressed. Aims/targets are characterized with real approach for all related sides. Other systems which proposed to be connected to continuable political administration system are shortly defined and expressed. Way of system administration and administration types are shortly explained. The importance and ways of the decision making are expressed. The general ways, types of inspection are shortly explained. Official units that could be assign for the new system are defined. The importance of these units and of the persons that could be assign for these units are expressed together with the definition of the characteristics of the persons or groups that could be. The necessity of an action planning, possible supply and demand cases are defined scientifically. The importance and necessity of sense of justice is explained to make system continuable. The methods of determination of the policies/strategies are expressed.展开更多
In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past feder...In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past federations, confederations, empires, ideologies, political administration systems, thoughts and senses, doctrines, etc. are in fact each reflects a special functional processes within a general system of where the kinds of services, subjects of services, way of services, service types and persons are considered and placed as a factor in it and where these factors are arranged through different priorities, weights, and also taken under record with some rules. It is evaluated that each groups, communities, societies, countries are separate models, but at the same time each of them are factors which owns different beginning points to reach a correct country structure with five new separate groups （New Era Group, Progression of The Country Group, Unity of The Country Group, Values of The Country Group, Social Progression Group）. The continuable political administration system is defined here by considering the all possible parts and by considering the other systems eormected for a country. Possible forceful factors which can effect political system administration are given. To realize political construction, some political construction methods are defined： Political construction by putting together the values, political construction based on different value, Political construction based on the new defined values, Political construction which considers stepped transition and Ideal political construction which will carry the political points of views and other standards of judgement, points of views of persons to a same line are expressed. New ideologies are put forwarded and ideal political construction for a world country is given with details. Integration of the political groups, political ideologies to the new system is explained. Some methods of politics are mentioned. Persons related with politics are classified simply.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry...Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.展开更多
This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementati...This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementation of the“Golden Tax Phase Four.”With this backdrop,the article offers recommendations for advancing the reform of the tax collection and management system,fostering the development of intelligent taxation,and accelerating the modernization of tax collection and management in China.展开更多
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
基金supported by the National Natural Science Foundation of China(82104138)the Zhejiang Provincial Natural Science Foundation of China(LY24H310003).
文摘Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).
基金the Flourish Collective,a Cluster of Scholarly Prominence at the University of Toronto,Scarborough。
文摘Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.
基金Supported by the Natural Science Foundation of Sichuan Province,No.24NSFSC0679State Key Clinical Department of Oral&Maxillofacial Surgery.
文摘As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several advantages,including low immunogenicity/cytotoxicity,the ability to traverse biological barriers,and high potential for engineering.However,several challenges remain in the clinical application of EVs.Their plasma half-life is relatively short,and they tend to accumulate in parenchymal organs(e.g.,liver and spleen)within a short time.Moreover,their targeting capabilities are neither precise nor highly effective.Additionally,EVs lack controlled and sustained release properties,necessitating the design of effective delivery strategies to ensure that therapeutic concentrations are achieved and maintained at the target site for an adequate duration.This review summarizes the latest drug delivery strategies involving EVs,focusing on systemic and local applications.It introduces various engineering approaches,administration strategies,and auxiliary delivery systems.Finally,the review discusses existing challenges in EV-based drug delivery and provides insights into the trends for future development in this field.
基金National Research Fund of South Africa(grant number:137792).
文摘Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.
文摘In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse avenues for growth but also led to substantial progress in certain areas while phasing out and optimizing several business models.Against this backdrop,employing effective and rational strategies to enhance corporate management standards is crucial.This is particularly important given the imperfections in current management systems,the shortage of specialized talent,and the need for digital capability improvements,all of which are vital for ensuring the long-term stability and success of enterprises.With this in mind,this paper explores corporate administration models and proposes several practical solutions to address challenges faced in business management under the digital economy,aiming to serve as a valuable resource for professionals and decision-makers alike.
基金The Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, No. IF2/PSAU/2022/03/23339.
文摘BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.
文摘The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration Systems (LAS). LAS services involve requests and responses concerning public and private cadastral data, including credentials of parties, ownership, and spatial parcels. This study explores the integration of CTI in LAS to enhance cyber resilience, focusing on the unique vulnerabilities of LAS, such as sensitive data management and interconnection with other critical systems related to spatial data uses and changes. The approach employs a case study of a typical country-specific LAS to analyse structured vulnerabilities and their attributes to determine the degree of vulnerability of LAS through a quantitative inductive approach. The analysis results indicate significant improvements in identifying and mitigating potential threats through CTI integration, thus enhancing cyber resilience. These findings are crucial for policymakers and practitioners to develop robust cybersecurity strategies for LAS.
文摘With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the campus.They have been applied to teaching,scientific research,student management,and other fields,improving the quality and efficiency of management.This paper mainly studies the intelligent educational administration management system based on data mining technology.Firstly,this paper introduces the application process of data mining technology,and builds an intelligent educational administration management system based on data mining technology.Then,this paper optimizes the application of the Apriori algorithm in educational administration management through transaction compression and frequent sampling.Compared with the traditional Apriori algorithm,the optimized Apriori algorithm in this paper has a shorter execution time under the same minimum support.
文摘Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 were selected as the reference group,implementing conventional medical administration.Another 39 medical incidents from October 2022 to October 2024 were chosen as the experimental group,adopting the matrix medical administration model.The practical indicators such as causes of medical disputes,dispute compensation,medical injury appraisal results,and diagnosis and treatment quality indicators were compared between the two groups.Results:In the experimental group,the primary reasons for medical disputes were patient-related,and most disputes resulted in no compensation.After medical injury appraisal,most cases were not considered medical injuries.The comparison between the two groups was statistically significant(P<0.05).The diagnosis and treatment quality indicators of the experimental group were superior to those of the reference group(P<0.05).Conclusion:The matrix medical administration model can reduce medical disputes caused by hospital factors,decrease the proportion of compensation and the incidence of medical injuries,and improve the quality of diagnosis and treatment,demonstrating high management effectiveness.
文摘BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.
文摘The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote economic growth and social civilization.This paper explores methods and strategies for optimizing the business environment from a public management perspective.By analyzing the significance of optimizing the business environment and addressing its current limitations,it offers practical recommendations aimed at comprehensively advancing business environment optimization and providing a solid foundation for the healthy development of enterprises.
基金funded by the National Natural Science Foundation of China(Grant No.42275056).
文摘As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This study explores the dynamic processes of QBO disruptions using the integrated climate model of the China Meteorological Administration(CMA)by nudging the tropical zonal winds toward observations.A comparative analysis with ERA5 reanalysis data shows that the nudged runs accurately replicate the general characteristics of the QBO,including the alternating QBO wind regimes and QBO disruption events.The evolution of the QBO winds is diagnosed using empirical orthogonal function and root-mean-square difference analyses,and the rarity of the disruption events is confirmed in the CMA model.Different aspects of the QBO disruptions and the relevant dynamics are present in the model.Firstly,the momentum budget analysis highlights the crucial roles of extratropical Rossby waves and non-orographic gravity waves in the transition from westerly to easterly winds during a disruption.Secondly,Kelvin waves and non-orographic gravity waves explain much of the transition from easterly to westerly winds near 40 hPa.Thirdly,the positive tendency from enhanced vertical advection further accelerates westerly momentum development via secondary meridional circulation.These findings underscore the importance of nudging techniques in understanding QBO dynamics,which provides valuable insights for future climate model improvements toward better forecasting QBO-related climate variability.Notably,due to model limitations,no QBO disruptions were simulated in the free-run experiments.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
文摘In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with related parts. A new science branch called ＂information science＂ is defined. Importance of the political organizing of a political party is shortly explained. The necessity of the academies for public sector, private sector, and for political administration system is expressed. How to choose a person and how a person can be choose for any part of the system is defined. For both cases ＂good and/or correct＂ system criterions, determination of the criterions, and evaluation criterions are defined. New evaluation levels are defined based on the 8-basic senses in philosophical point of view to deepen the sensitivity of the evaluations. The importance of the situation notice and how to make it for each of the association are explained. The 10 main service parameters are defined to show the interactive relations between the ideology, services, person nature and others. Present and possible future problems of a country are expressed. Aims/targets are characterized with real approach for all related sides. Other systems which proposed to be connected to continuable political administration system are shortly defined and expressed. Way of system administration and administration types are shortly explained. The importance and ways of the decision making are expressed. The general ways, types of inspection are shortly explained. Official units that could be assign for the new system are defined. The importance of these units and of the persons that could be assign for these units are expressed together with the definition of the characteristics of the persons or groups that could be. The necessity of an action planning, possible supply and demand cases are defined scientifically. The importance and necessity of sense of justice is explained to make system continuable. The methods of determination of the policies/strategies are expressed.
文摘In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past federations, confederations, empires, ideologies, political administration systems, thoughts and senses, doctrines, etc. are in fact each reflects a special functional processes within a general system of where the kinds of services, subjects of services, way of services, service types and persons are considered and placed as a factor in it and where these factors are arranged through different priorities, weights, and also taken under record with some rules. It is evaluated that each groups, communities, societies, countries are separate models, but at the same time each of them are factors which owns different beginning points to reach a correct country structure with five new separate groups （New Era Group, Progression of The Country Group, Unity of The Country Group, Values of The Country Group, Social Progression Group）. The continuable political administration system is defined here by considering the all possible parts and by considering the other systems eormected for a country. Possible forceful factors which can effect political system administration are given. To realize political construction, some political construction methods are defined： Political construction by putting together the values, political construction based on different value, Political construction based on the new defined values, Political construction which considers stepped transition and Ideal political construction which will carry the political points of views and other standards of judgement, points of views of persons to a same line are expressed. New ideologies are put forwarded and ideal political construction for a world country is given with details. Integration of the political groups, political ideologies to the new system is explained. Some methods of politics are mentioned. Persons related with politics are classified simply.
基金financially supported by the National Natural Science Foundation(No.82304393,China)Beijing Nova Program(Nos.Z211100002121127 and 20220484219,China)+1 种基金Beijing Natural Science Foundation(No.L212059,China)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-028,China)。
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
文摘This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementation of the“Golden Tax Phase Four.”With this backdrop,the article offers recommendations for advancing the reform of the tax collection and management system,fostering the development of intelligent taxation,and accelerating the modernization of tax collection and management in China.
