The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine...Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.展开更多
Electricity-driven water splitting to produce hydrogen is one of the most efficient ways to alleviate energy crisis and environmental pollution problems,in which the anodic oxygen evolution reaction(OER)is the key hal...Electricity-driven water splitting to produce hydrogen is one of the most efficient ways to alleviate energy crisis and environmental pollution problems,in which the anodic oxygen evolution reaction(OER)is the key half-reaction of performance-limiting in water splitting.Given the complicated reaction process and surface reconstruction of the involved catalysts under actual working conditions,unraveling the real active sites,probing multiple reaction intermediates and clarifying catalytic pathways through in-situ characterization techniques and theoretical calculations are essential.In this review,we summarize the recent advancements in understanding the catalytic process,unlocking the water oxidation active phase and elucidating catalytic mechanism of water oxidation by various in-situ characterization techniques.Firstly,we introduce conventionally proposed traditional catalytic mechanisms and novel evolutionary mechanisms of OER,and highlight the significance of optimal catalytic pathways and intrinsic stability.Next,we provide a comprehensive overview of the fundamental working principles,different detection modes,applicable scenarios,and limitations associated with the in-situ characterization techniques.Further,we exemplified the in-situ studies and discussed phase transition detection,visualization of speciation evolution,electronic structure tracking,observation of reaction active intermediates,and monitoring of catalytic products,as well as establishing catalytic structure-activity relationships and catalytic mechanism.Finally,the key challenges and future perspectives for demystifying the water oxidation process are briefly proposed.展开更多
Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS a...Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS and GS is still a difficult challenge to overcome.In this study,113 indica rice varieties(V)and their 565 testcross hybrids(TC)were used as the materials to investigate the genetic basis of 12 quality traits and nine agronomic traits.The original traits and general combining ability of the parents,as well as the original traits and midparent heterosis of TC,were subjected to genome-wide association analysis.In total,381 primary significantly associated loci(SAL)and 1,759 secondary SALs that had epistatic interactions with these primary SALs were detected.Among these loci,322 candidate genes located within or nearby the SALs were screened,204 of which were cloned genes.A total of 39 MAS molecular modules that are beneficial for trait improvement were identified by pyramiding the superior haplotypes of candidate genes and desirable epistatic alleles of the secondary SALs.All the SALs were used to construct genetic networks,in which 91 pleiotropic loci were investigated.Additionally,we estimated the accuracy of genomic prediction in the parent V and TC by incorporating either no SALs,primary SALs,secondary SALs or epistatic effect SALs as covariates.Although the prediction accuracies of the four models were generally not significantly different in the TC dataset,the incorporation of primary SALs,secondary SALs,and epistatic effect SALs significantly improved the prediction accuracies of 5(26%),3(16%),and 11(58%)traits in the V dataset,respectively.These results suggested that SALs and epistatic effect SALs identified based on an additive genotype can provide considerable predictive power for the parental lines.They also provide insights into the genetic basis of complex traits and valuable information for molecular breeding in rice.展开更多
BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and dea...BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.展开更多
Due to the complexity of leadership and its variability across situations,it is suggested that research on leadership should focus on attempts to understand leadership in specific situations or roles,and develop local...Due to the complexity of leadership and its variability across situations,it is suggested that research on leadership should focus on attempts to understand leadership in specific situations or roles,and develop local knowledge about leadership in each situation or role.This paper validates the possibility and importance of building indigenous leadership theories from historical perspective.We demonstrated how to carry out research on indigenous Chinese leadership from a historical perspective by comparative case studies using historical data.Based on the principles of typicalness,representativeness,and comparativeness,we selected six counterparts of political elites in ancient China as comparative cases,which includes Guan Zhong&Shang Yang(organizational reformer),Liu Bang&Xiang Yu(entrepreneur),Li Shimin&Qin Shihuang(intergenerational transition successor),Zhuge Liang&Zeng Guofan(professional manager),Lu Su&Zhang Juzheng(mess-to-order maker),and Zuo Zongtang&Wang Anshi(national dream driver).The paper aims to develop indigenous leadership theory specific to Chinese mental states and culture.展开更多
The application of environment-behavior studies plays an important role in studying the renewal of shantytowns.One of the most humane ways of renewal is designing and constructing the necessary urban spatial environme...The application of environment-behavior studies plays an important role in studying the renewal of shantytowns.One of the most humane ways of renewal is designing and constructing the necessary urban spatial environment from the perspective of human daily behavior.Most of the shantytown renovation projects currently carried out in China are mainly focused on demolition and reconstruction,which not only incurs high costs but also damages the original social structure and economic model.During the process of shantytown renewal,it should improve the urban landscape,living environment,and life quality of residents,and ensure the daily life of shantytown residents without increasing their economic burden,and preserve the traces of urban development.In order to achieve this goal,it should explore the renewal strategies of shantytowns from the perspective of environment-behavior studies through behavior maps,on-site research,and literature review.Updating and design from a human perspective often achieve faster and better development;the renewal of shantytowns should be a bottom-up approach and start from a grassroots perspective,completing the renovation design through the composition of the population and behavioral patterns.展开更多
In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which...In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which we have known less about the genetic parameters and underlying candidate genes in relation to the body size traits.In this study,we obtained the genome-wide single nucleotide polymorphisms(SNPs)using the Illumina Bovine BeadChip in 275 Shuxuan cattle.These SNPs were first used for estimating genetic parameters for the withers height(WH)and diagonal body length(BL).Using the bivariate animal model,the estimates(±standard error)of heritabilities were 0.71±0.22 and 0.49±0.29 for BL,and their genetic correlation was 0.64±0.37.Second,the genome-wide association study(GWAS)was performed.However,these did not result into genome-wide significant SNPs for both WH and BL traits.According to a less stringent suggestive significance,some positional candidate genes were found,and some of them(such as FAM110B,TAS1R2,PAX3,and FHIT)were previously reported in literature to be associated with body size traits in cattle.In conclusion,we estimated the genetic parameters in Shuxuan cattle using genomic information for the first time,which are required for implementing the genomic selection programs in the future.展开更多
Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key ...Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.展开更多
A history of the Islamic studies in China,not only includes studies on world Islam,it also includes research on Islam and Muslims in China.Before the Reform and Opening Up,China did not achieve much in this field,sinc...A history of the Islamic studies in China,not only includes studies on world Islam,it also includes research on Islam and Muslims in China.Before the Reform and Opening Up,China did not achieve much in this field,since then,the research field of Islam and Muslim in China has been expanding and the results have been published,forming a new trend.In this field,scholars such as Jin Yijiu,Li Xinghua,Qin Huibin,Zhou Guoli,Sha Qiuzhen,Zhou Xiefan,Wu Yungui,and Yang Huaizhong have made the most outstanding achievements.Especially in the collation of reference books and historical materials,in the past 20 years,The Encyclopedia of the history of Islam,The Chinese Encyclopedia of Islam have emerged,and the Chinese and World Encyclopedia of Islamic Law and other important historical books have been published.This paper focuses on the field of historical research and divided into academic research history at home and abroad,which is discussed from several fields such as general history,special history,national history,and regional history.展开更多
This paper attempts to explore interdisciplinary integration from four aspects:the necessity of interdisciplinary integration between legal studies and auditing,the difficulties and challenges encountered in this inte...This paper attempts to explore interdisciplinary integration from four aspects:the necessity of interdisciplinary integration between legal studies and auditing,the difficulties and challenges encountered in this integration,the ideas for teaching reform in the context of interdisciplinary integration,and the expected outcomes.The aim is to achieve an organic integration of legal studies and auditing through systematic teaching reforms,thereby providing students with comprehensive and integrated knowledge and skills training,ensuring the quality of talent cultivation,and adapting to the needs of social development.展开更多
Objective:To conduct a scoping review of longitudinal studies related to disease perception in cancer patients and to provide a reference for the improvement of disease perception in cancer patients.Methods:Using the ...Objective:To conduct a scoping review of longitudinal studies related to disease perception in cancer patients and to provide a reference for the improvement of disease perception in cancer patients.Methods:Using the scoping method,PubMed,Web of Science,The Cochrane Library,Medline,CNKI,Wanfang Database,VIP Chinese Scientific and Technical Journals Database,and China Biomedical Literature Database were searched up to July 2023 for analysis and discussion of the included literature.Results:A total of 19 articles were included,distributed across 9 countries including China,the Netherlands,and the United Kingdom,with 8 articles published in China.The study subjects included patients with breast cancer,colorectal cancer,laryngeal cancer,lung cancer,esophageal cancer,and bladder cancer.The content covered dynamic changes in disease perception,the impact of disease perception,and the influencing factors of disease perception.Conclusion:The number of longitudinal studies on disease perception in cancer patients is gradually increasing and becoming more diverse.However,issues such as a small total number of studies,single research methods,and short observation periods persist.In the future,it is necessary to conduct in-depth longitudinal research on disease perception in cancer patients,expand the scope of research fields,and provide more comprehensive theories to guide clinical treatment and nursing practices,ultimately improving the treatment outcomes and quality of life for cancer patients.展开更多
Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)e...Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)exhibit strong chemopreventive capabilities.The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication.In this study,the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs.In traditional Indian medicine,this plant extract is recognized as a significant anti-diabetic agent.The flavonoids tetrahydroxylflavone,7-hydroxyflavanone,and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity.These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs.At a concentration of 13μg/mL,the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line.The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment.Additionally,the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting(FACS)method,indicating that SeNPs could efficiently differentiate cancer cells from normal cells.Notably,it showed a significant improvement in diethylnitrosamine(DEN)-induced Swiss Wistar rat groups.This scientific investigation highlights the high anti-cancer potential of SeNPs,positioning them as a promising therapeutic agent for liver cancer treatment.展开更多
Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economica...Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.展开更多
Tea is one of the most popular non-alcoholic beverages in the world,and free amino acids,especially theanine,make a major contribution to the umami taste of tea.However,the genetic basis of the variation in amino acid...Tea is one of the most popular non-alcoholic beverages in the world,and free amino acids,especially theanine,make a major contribution to the umami taste of tea.However,the genetic basis of the variation in amino acid content in tea plants remains largely unknown.Here,we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing.Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids.A total of 69 quantitative trait loci(–log10(P-value)>5)were identified.Functional annotation revealed that branched-chain amino acid aminotransferase,glutamine synthetase,nitrate transporter,and glutamate decarboxylase might be important for amino acid metabolism.Two significant loci,glutamine synthetase(Glu1,P=3.71×10^(−4);Arg1,P=4.61×10^(−5))and branched-chain amino acid aminotransferase(Val1,P=4.67×10^(−5);I_Leu1,P=3.56×10^(−6)),were identified,respectively.Based on the genotyping result,two alleles of CsGS(CsGS-L and CsGS-H)and CsBCAT(CsBCAT-L and CsBCAT-H)were selected to perform function verification.Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants,and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine,isoleucine and leucine.Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine.Furthermore,CsGS-L and CsGS-H differentially regulated the accumulation of glutamine,and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids.In summary,the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.展开更多
This review paper provides an overview of the micropillar compression technique as applied to magnesium(Mg) and its alloys. It explores the influence of various factors, such as pillar size, shape, temperature, and st...This review paper provides an overview of the micropillar compression technique as applied to magnesium(Mg) and its alloys. It explores the influence of various factors, such as pillar size, shape, temperature, and strain rate on the mechanical properties of Mg.Additionally, the impact of alloying elements, aging, and precipitates in Mg alloys has been extensively examined, revealing their significant influence on mechanical performance. The study highlights the strength and strain hardening improvements in Mg with decreasing pillar size in micropillar compression. Furthermore, the role of precipitates as strengthening agents, affecting deformation mechanisms and overall mechanical response, is explored. These valuable insights are crucial for designing Mg-based materials with enhanced mechanical properties for advanced engineering applications.展开更多
Recorded stories of the clinical encounter stretch back to ancient times.Throughout their history,these narratives have been called by different names,reflecting changes in format,function,and audience.This paper exam...Recorded stories of the clinical encounter stretch back to ancient times.Throughout their history,these narratives have been called by different names,reflecting changes in format,function,and audience.This paper examines and explains the differences in two related forms of clinical writing as practiced by East Asian Medicine clinicians in the United States today-the case study and the case report.Each has its strengths and weaknesses;each is suited to different roles.The case study is ideal for education and the practice of narrative medicine,whereas the case report has played a vital role in propelling East Asian Medicine into the arena of modern scientific research.展开更多
Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows th...Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows that the plant is often substituted for Artemisia annua L.(A.annua)by herbalists in Western Uganda due to similarities in their morphology.Misidentification of medicinal plants and mislabelling of herbal products have been incriminated in toxicity and adverse health outcomes in traditional medicine practise.Because safety continues to be a major issue with the use of herbal remedies,it becomes imperative therefore that medicinal plants should be correctly identified.Methods:This study focused on investigating the macroscopic,microscopic,physicochemical characteristics and phytochemical composition of A.vulgaris leaves compared to A.annua to ease its correct identification.Results:The results showed that there are some colour differences between the leaves of the two species,with a close arrangement of microscopic features but different leaf constants.The leaves of the two Artemisia species had similar tastes,but their shapes and colours(greenish-yellow for A.annua and dark green for A.vulgaris)can be used by the local community to distinguish between them.The artemisinin content was higher in A.vulgaris leaves(1.72%)than in A.annua(1.43%),but the reverse was observed for the total flavonoid content.Conclusion:This observation could justify the change in the use of A.vulgaris by the indigenous community in western Uganda.Further studies should consider the pharmacognostic comparison of A.annua with other species in the genus Artemisia and the use of molecular techniques such as DNA barcoding.展开更多
It has been applied for many diseases such as plague fever, cold cough, sore throat and so on. In order to better study Huhegaridi-9, this paper started from the production process of Mongolian Patent Medicine Huhegar...It has been applied for many diseases such as plague fever, cold cough, sore throat and so on. In order to better study Huhegaridi-9, this paper started from the production process of Mongolian Patent Medicine Huhegaridi-9. It analyzed and discussed the clinical application, chemical components and pharmacological research of Huhegaridi-9. It is expected to provide a reference for relevant researchers and workers.展开更多
Increasing calls for zero-carbon cities invite transformative solutions for people and places within our cities around the world. Key to the transformation is cities and regions shifting in mobility away from fossil-f...Increasing calls for zero-carbon cities invite transformative solutions for people and places within our cities around the world. Key to the transformation is cities and regions shifting in mobility away from fossil-fuel based car-oriented solutions. The paper investigates a range of case studies where “tram-based boulevards” have been planned or implemented to provide such opportunities. The case studies share a common broader policy objective: to transform the car-oriented or car-saturated areas to an intensified urban template based on a critical presence of dedicated mid-tier transit infrastructure and active transport. “Trams”, or mid-tier, mid-capacity transit when combined with Transit oriented development (TOD) along whole corridors can provide transformative pathways towards zero-carbon outcomes as well as multiple, strong urban benefits. However, many successful or instructive examples of this practice from non-English speaking countries, particularly in Europe, are underdocumented in the international literature. The paper addresses this gap by investigating opportunities and challenges evident in a range of European case studies. These are explored for insight towards policy learning particularly in New World cities seeking to transform into a zero-carbon and more transit-oriented template: How can decision-makers avoid repeating the identified pitfalls, and instead focus on emulating the successful approaches and outcomes? We conclude the need for recognition of the inherent synergies between transport and land use settings in any endeavour, and their translation into policy priorities in both fields of planning. We also conclude the importance of decision makers proactively identifying and critically appraising specific opportunities for change, concerning funding, technology, public opinion, stakeholder alliances or market dynamics, and capitalising on them at suitable moments in time.展开更多
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.
基金supported by the Natural Science Foundation of Liaoning Province,China(Grant No.:2023-MS-172).
文摘Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.
基金support from National Natural Science Foundation of China(Grant Nos.22125903,22209174)the National Key R&D Program of China(Grants 2022YFA1504100)+2 种基金Dalian Innovation Support Plan for High Level Talents(2019RT09)Dalian National Laboratory For Clean Energy(DNL),CAS,DNL Cooperation Fund,CAS(DNL202016,DNL202019)DICP(DICP I2020032).
文摘Electricity-driven water splitting to produce hydrogen is one of the most efficient ways to alleviate energy crisis and environmental pollution problems,in which the anodic oxygen evolution reaction(OER)is the key half-reaction of performance-limiting in water splitting.Given the complicated reaction process and surface reconstruction of the involved catalysts under actual working conditions,unraveling the real active sites,probing multiple reaction intermediates and clarifying catalytic pathways through in-situ characterization techniques and theoretical calculations are essential.In this review,we summarize the recent advancements in understanding the catalytic process,unlocking the water oxidation active phase and elucidating catalytic mechanism of water oxidation by various in-situ characterization techniques.Firstly,we introduce conventionally proposed traditional catalytic mechanisms and novel evolutionary mechanisms of OER,and highlight the significance of optimal catalytic pathways and intrinsic stability.Next,we provide a comprehensive overview of the fundamental working principles,different detection modes,applicable scenarios,and limitations associated with the in-situ characterization techniques.Further,we exemplified the in-situ studies and discussed phase transition detection,visualization of speciation evolution,electronic structure tracking,observation of reaction active intermediates,and monitoring of catalytic products,as well as establishing catalytic structure-activity relationships and catalytic mechanism.Finally,the key challenges and future perspectives for demystifying the water oxidation process are briefly proposed.
基金partially supported by the Science and Technology Innovation Program of Hunan Province,China(2023NK2001)the Hubei Key Laboratory of Food Crop Germplasm and Genetic Improvement,China(2022LZJJ08)+2 种基金the Special Funds for Construction of Innovative Provinces in Hunan Province,China(2021NK1011)the Natural Science Foundation of Hunan Province,China(2020JJ4039)the Key Research and Development Program of Hubei Province,China(2021BBA223)。
文摘Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS and GS is still a difficult challenge to overcome.In this study,113 indica rice varieties(V)and their 565 testcross hybrids(TC)were used as the materials to investigate the genetic basis of 12 quality traits and nine agronomic traits.The original traits and general combining ability of the parents,as well as the original traits and midparent heterosis of TC,were subjected to genome-wide association analysis.In total,381 primary significantly associated loci(SAL)and 1,759 secondary SALs that had epistatic interactions with these primary SALs were detected.Among these loci,322 candidate genes located within or nearby the SALs were screened,204 of which were cloned genes.A total of 39 MAS molecular modules that are beneficial for trait improvement were identified by pyramiding the superior haplotypes of candidate genes and desirable epistatic alleles of the secondary SALs.All the SALs were used to construct genetic networks,in which 91 pleiotropic loci were investigated.Additionally,we estimated the accuracy of genomic prediction in the parent V and TC by incorporating either no SALs,primary SALs,secondary SALs or epistatic effect SALs as covariates.Although the prediction accuracies of the four models were generally not significantly different in the TC dataset,the incorporation of primary SALs,secondary SALs,and epistatic effect SALs significantly improved the prediction accuracies of 5(26%),3(16%),and 11(58%)traits in the V dataset,respectively.These results suggested that SALs and epistatic effect SALs identified based on an additive genotype can provide considerable predictive power for the parental lines.They also provide insights into the genetic basis of complex traits and valuable information for molecular breeding in rice.
文摘BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.
文摘Due to the complexity of leadership and its variability across situations,it is suggested that research on leadership should focus on attempts to understand leadership in specific situations or roles,and develop local knowledge about leadership in each situation or role.This paper validates the possibility and importance of building indigenous leadership theories from historical perspective.We demonstrated how to carry out research on indigenous Chinese leadership from a historical perspective by comparative case studies using historical data.Based on the principles of typicalness,representativeness,and comparativeness,we selected six counterparts of political elites in ancient China as comparative cases,which includes Guan Zhong&Shang Yang(organizational reformer),Liu Bang&Xiang Yu(entrepreneur),Li Shimin&Qin Shihuang(intergenerational transition successor),Zhuge Liang&Zeng Guofan(professional manager),Lu Su&Zhang Juzheng(mess-to-order maker),and Zuo Zongtang&Wang Anshi(national dream driver).The paper aims to develop indigenous leadership theory specific to Chinese mental states and culture.
文摘The application of environment-behavior studies plays an important role in studying the renewal of shantytowns.One of the most humane ways of renewal is designing and constructing the necessary urban spatial environment from the perspective of human daily behavior.Most of the shantytown renovation projects currently carried out in China are mainly focused on demolition and reconstruction,which not only incurs high costs but also damages the original social structure and economic model.During the process of shantytown renewal,it should improve the urban landscape,living environment,and life quality of residents,and ensure the daily life of shantytown residents without increasing their economic burden,and preserve the traces of urban development.In order to achieve this goal,it should explore the renewal strategies of shantytowns from the perspective of environment-behavior studies through behavior maps,on-site research,and literature review.Updating and design from a human perspective often achieve faster and better development;the renewal of shantytowns should be a bottom-up approach and start from a grassroots perspective,completing the renovation design through the composition of the population and behavioral patterns.
基金Supported by the Sichuan Province Key Research and Development Project(2022YFYZ0006)the Sichuan Province Science and Technology Planning Project(2021YFYZ0001).
文摘In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which we have known less about the genetic parameters and underlying candidate genes in relation to the body size traits.In this study,we obtained the genome-wide single nucleotide polymorphisms(SNPs)using the Illumina Bovine BeadChip in 275 Shuxuan cattle.These SNPs were first used for estimating genetic parameters for the withers height(WH)and diagonal body length(BL).Using the bivariate animal model,the estimates(±standard error)of heritabilities were 0.71±0.22 and 0.49±0.29 for BL,and their genetic correlation was 0.64±0.37.Second,the genome-wide association study(GWAS)was performed.However,these did not result into genome-wide significant SNPs for both WH and BL traits.According to a less stringent suggestive significance,some positional candidate genes were found,and some of them(such as FAM110B,TAS1R2,PAX3,and FHIT)were previously reported in literature to be associated with body size traits in cattle.In conclusion,we estimated the genetic parameters in Shuxuan cattle using genomic information for the first time,which are required for implementing the genomic selection programs in the future.
基金financially supported by the National Natural Science Foundation of China(32201868 and 32001575)。
文摘Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.
文摘A history of the Islamic studies in China,not only includes studies on world Islam,it also includes research on Islam and Muslims in China.Before the Reform and Opening Up,China did not achieve much in this field,since then,the research field of Islam and Muslim in China has been expanding and the results have been published,forming a new trend.In this field,scholars such as Jin Yijiu,Li Xinghua,Qin Huibin,Zhou Guoli,Sha Qiuzhen,Zhou Xiefan,Wu Yungui,and Yang Huaizhong have made the most outstanding achievements.Especially in the collation of reference books and historical materials,in the past 20 years,The Encyclopedia of the history of Islam,The Chinese Encyclopedia of Islam have emerged,and the Chinese and World Encyclopedia of Islamic Law and other important historical books have been published.This paper focuses on the field of historical research and divided into academic research history at home and abroad,which is discussed from several fields such as general history,special history,national history,and regional history.
文摘This paper attempts to explore interdisciplinary integration from four aspects:the necessity of interdisciplinary integration between legal studies and auditing,the difficulties and challenges encountered in this integration,the ideas for teaching reform in the context of interdisciplinary integration,and the expected outcomes.The aim is to achieve an organic integration of legal studies and auditing through systematic teaching reforms,thereby providing students with comprehensive and integrated knowledge and skills training,ensuring the quality of talent cultivation,and adapting to the needs of social development.
文摘Objective:To conduct a scoping review of longitudinal studies related to disease perception in cancer patients and to provide a reference for the improvement of disease perception in cancer patients.Methods:Using the scoping method,PubMed,Web of Science,The Cochrane Library,Medline,CNKI,Wanfang Database,VIP Chinese Scientific and Technical Journals Database,and China Biomedical Literature Database were searched up to July 2023 for analysis and discussion of the included literature.Results:A total of 19 articles were included,distributed across 9 countries including China,the Netherlands,and the United Kingdom,with 8 articles published in China.The study subjects included patients with breast cancer,colorectal cancer,laryngeal cancer,lung cancer,esophageal cancer,and bladder cancer.The content covered dynamic changes in disease perception,the impact of disease perception,and the influencing factors of disease perception.Conclusion:The number of longitudinal studies on disease perception in cancer patients is gradually increasing and becoming more diverse.However,issues such as a small total number of studies,single research methods,and short observation periods persist.In the future,it is necessary to conduct in-depth longitudinal research on disease perception in cancer patients,expand the scope of research fields,and provide more comprehensive theories to guide clinical treatment and nursing practices,ultimately improving the treatment outcomes and quality of life for cancer patients.
文摘Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)exhibit strong chemopreventive capabilities.The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication.In this study,the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs.In traditional Indian medicine,this plant extract is recognized as a significant anti-diabetic agent.The flavonoids tetrahydroxylflavone,7-hydroxyflavanone,and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity.These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs.At a concentration of 13μg/mL,the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line.The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment.Additionally,the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting(FACS)method,indicating that SeNPs could efficiently differentiate cancer cells from normal cells.Notably,it showed a significant improvement in diethylnitrosamine(DEN)-induced Swiss Wistar rat groups.This scientific investigation highlights the high anti-cancer potential of SeNPs,positioning them as a promising therapeutic agent for liver cancer treatment.
基金Narodowe Centrum Nauki,Grant/Award Number:SONATA 2021/43/D/NZ3/01798 and SONATA BIS 2020/38/E/NZ3/00090。
文摘Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.
基金supported by the Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation, China (2017RC002)。
文摘Tea is one of the most popular non-alcoholic beverages in the world,and free amino acids,especially theanine,make a major contribution to the umami taste of tea.However,the genetic basis of the variation in amino acid content in tea plants remains largely unknown.Here,we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing.Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids.A total of 69 quantitative trait loci(–log10(P-value)>5)were identified.Functional annotation revealed that branched-chain amino acid aminotransferase,glutamine synthetase,nitrate transporter,and glutamate decarboxylase might be important for amino acid metabolism.Two significant loci,glutamine synthetase(Glu1,P=3.71×10^(−4);Arg1,P=4.61×10^(−5))and branched-chain amino acid aminotransferase(Val1,P=4.67×10^(−5);I_Leu1,P=3.56×10^(−6)),were identified,respectively.Based on the genotyping result,two alleles of CsGS(CsGS-L and CsGS-H)and CsBCAT(CsBCAT-L and CsBCAT-H)were selected to perform function verification.Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants,and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine,isoleucine and leucine.Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine.Furthermore,CsGS-L and CsGS-H differentially regulated the accumulation of glutamine,and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids.In summary,the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.
文摘This review paper provides an overview of the micropillar compression technique as applied to magnesium(Mg) and its alloys. It explores the influence of various factors, such as pillar size, shape, temperature, and strain rate on the mechanical properties of Mg.Additionally, the impact of alloying elements, aging, and precipitates in Mg alloys has been extensively examined, revealing their significant influence on mechanical performance. The study highlights the strength and strain hardening improvements in Mg with decreasing pillar size in micropillar compression. Furthermore, the role of precipitates as strengthening agents, affecting deformation mechanisms and overall mechanical response, is explored. These valuable insights are crucial for designing Mg-based materials with enhanced mechanical properties for advanced engineering applications.
文摘Recorded stories of the clinical encounter stretch back to ancient times.Throughout their history,these narratives have been called by different names,reflecting changes in format,function,and audience.This paper examines and explains the differences in two related forms of clinical writing as practiced by East Asian Medicine clinicians in the United States today-the case study and the case report.Each has its strengths and weaknesses;each is suited to different roles.The case study is ideal for education and the practice of narrative medicine,whereas the case report has played a vital role in propelling East Asian Medicine into the arena of modern scientific research.
基金This study was financially supported by the Pharm-Biotechnology and Traditional Medicine Centre(PHARMBIOTRAC).We would like to thank and acknowledge Pharm-Biotechnology and Traditional Medicine Centre hosted at Mbarara University of Science and Technology for funding the study,Mrs.Venerandah Biryabarema Bushenyi and Africa Volunteer Association-Kamwenge for providing us with the study plants.The authors also thank Mr.Gershom Muganga who was a research assistant during the study.
文摘Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows that the plant is often substituted for Artemisia annua L.(A.annua)by herbalists in Western Uganda due to similarities in their morphology.Misidentification of medicinal plants and mislabelling of herbal products have been incriminated in toxicity and adverse health outcomes in traditional medicine practise.Because safety continues to be a major issue with the use of herbal remedies,it becomes imperative therefore that medicinal plants should be correctly identified.Methods:This study focused on investigating the macroscopic,microscopic,physicochemical characteristics and phytochemical composition of A.vulgaris leaves compared to A.annua to ease its correct identification.Results:The results showed that there are some colour differences between the leaves of the two species,with a close arrangement of microscopic features but different leaf constants.The leaves of the two Artemisia species had similar tastes,but their shapes and colours(greenish-yellow for A.annua and dark green for A.vulgaris)can be used by the local community to distinguish between them.The artemisinin content was higher in A.vulgaris leaves(1.72%)than in A.annua(1.43%),but the reverse was observed for the total flavonoid content.Conclusion:This observation could justify the change in the use of A.vulgaris by the indigenous community in western Uganda.Further studies should consider the pharmacognostic comparison of A.annua with other species in the genus Artemisia and the use of molecular techniques such as DNA barcoding.
文摘It has been applied for many diseases such as plague fever, cold cough, sore throat and so on. In order to better study Huhegaridi-9, this paper started from the production process of Mongolian Patent Medicine Huhegaridi-9. It analyzed and discussed the clinical application, chemical components and pharmacological research of Huhegaridi-9. It is expected to provide a reference for relevant researchers and workers.
文摘Increasing calls for zero-carbon cities invite transformative solutions for people and places within our cities around the world. Key to the transformation is cities and regions shifting in mobility away from fossil-fuel based car-oriented solutions. The paper investigates a range of case studies where “tram-based boulevards” have been planned or implemented to provide such opportunities. The case studies share a common broader policy objective: to transform the car-oriented or car-saturated areas to an intensified urban template based on a critical presence of dedicated mid-tier transit infrastructure and active transport. “Trams”, or mid-tier, mid-capacity transit when combined with Transit oriented development (TOD) along whole corridors can provide transformative pathways towards zero-carbon outcomes as well as multiple, strong urban benefits. However, many successful or instructive examples of this practice from non-English speaking countries, particularly in Europe, are underdocumented in the international literature. The paper addresses this gap by investigating opportunities and challenges evident in a range of European case studies. These are explored for insight towards policy learning particularly in New World cities seeking to transform into a zero-carbon and more transit-oriented template: How can decision-makers avoid repeating the identified pitfalls, and instead focus on emulating the successful approaches and outcomes? We conclude the need for recognition of the inherent synergies between transport and land use settings in any endeavour, and their translation into policy priorities in both fields of planning. We also conclude the importance of decision makers proactively identifying and critically appraising specific opportunities for change, concerning funding, technology, public opinion, stakeholder alliances or market dynamics, and capitalising on them at suitable moments in time.
