Environmental pollution has become a hot topic of concern for the government, academia and the public. The evaluation of environmental health should not only relate to environmental quality and exposure channels but also the level of economic development, social environmental protection responsibility and public awareness. We put forward the concept of the “healthy environment” and introduced 27 environmental indicators to evaluate and classify the healthy environment of 31 provinces and cities in China. Seven common factors were extracted and divided into economic, medical, ecological and humanistic environment factors. Based on the four environmental factors, we classify the healthy environment into five categories—economic leading healthy environment, robust healthy environment, developmental healthy environment, economic and medical disadvantageous healthy environment and completely disadvantageous healthy environment. The population health differences among the five healthy environment categories show that economic environment plays a major role in population health. Public health in regions with sound economic environment is significantly better than that in other areas. Our classification result of healthy environment can provide scientific support for optimizing environmental countermeasures and realizing environmental protection. The mosdiseases ,4. Improdiseases .3 concentrations in 34 atmospheric environmental monitoring stations in Beijing from 2014 to 2020 and evaluated the health effects of air pollution prevention; results show that there were 790 excess deaths related to PM 2.5 and 2180 excess deaths related to O3 in 2019. In addition, more studies tend to discuss social environments, such as the community environment [This relationship between the environment and human health has been prominent amongst the concerns of international organizations including the World Health Organization (WHO), the World Bank, the United Nations, the Organization for Economic Co-operation and Development and the European Union (EU) . Currentironment ,11, resiironment , neighboironment . Liu, etThe second category is how indoor environments impact on residents’ health. The influences of indoor environment quality on occupant health have long been one of the main focuses in built environment and public health research. Previous studies have identified various indicators for indoor environmental quality, including indoor air quality, thermal comfort, ventilation, visual condition, and acoustic condition . ScholarThe rapid deterioration of the ecological environment and the increasingly fierce social competition aggravate people’s internal and external pressures and increase the prevalence of occupational diseases and mental diseases. This phenomenon has also become a hot and important topic for government, academia and the public. Health policy analysts cannot overlook the importance of the environment to human health. The European Union funded the Integrating Environment and Health Research project (HERA) to set priorities for the future European research agenda in the environment, climate and health nexus . In ordeAiming at the health problems brought by the environment, many studies have established indicators to comprehensively evaluate environmental health risks and assess the level of regional environmental health risks. Wu, et al.  construcWe can find from the previous studies the following. First, scholars mainly discuss the impact of a certain type of environment, such as natural environment or indoor and outdoor environment on residents’ health, and few of them measure them from multiple aspects. Second, the existing indicators to measure residents’ health are more focused on the death rate or prevalence rate of certain diseases, lacking integrity and representation of the population. Third, the assessment concentrates on the level of regional environmental health risk, with assessment results of high or low risk, and fail to clarify the environmental risk characteristics through further segmentation. Generally, the environment includes a variety of environmental categories such as natural environment, cultural environment and economic environment, but the “healthy environment” is rarely put forward. What is a “healthy environment”? We define “healthy environment” as a healthy, safe and comfortable social environment that can secure for the public a good physical and mental state by meeting the public’s physiological, psychological and social demands. Therefore, the evaluation of a “healthy environment” should not only be linked to ecological factors but also be integrated into the overall evaluation system along with the social and economic environment, the medical environment and other aspects of human life. The study of the healthy environment index system provides theoretical guidance and a qualitative and quantitative basis for us to measure and judge healthy environments.Based on various indicators such as the economic and social environment, we evaluated and classified the healthy environment of 31 provinces and cities in China, discussed the characteristics of different kinds of healthy environment, and discussed their relationship with public health. The main possible innovation in our work lies in the concept of the “healthy environment” and its classification. Through four types of environmental factor, we evaluated and classified regional healthy environments. We believe that this triage is really important because public health can behave differently in different types of health settings. For example, Mitchell  concludeIndicators are measurements selected to represent a larger phenomenon of interest to the researcher , in our The medical environment mainly reflects medical infrastructure and public health awareness, including the proportion of maternity insurance, the number of practicing (assistant) physicians per 1000 persons, the number of health institutions and so on. The economic environment not only takes basic economic indicators into account, but also includes consumption, expenditure and disposable income per capita to reflect residents’ income and consumption levels. The ecological environment includes measures of the energy intensity and emission intensity of polluting gases, which represent the environmental factors that may affect regional air quality and population health. In addition, urban environmental protection investment represents governments’ emphasis on environment, and the water resources and green park area per capita are used to represent the regional environmental quality. The humanistic environment covers educational attainment level, internet penetration rate and so on. Finally, 27 indicators were selected to build the whole healthy environment system . The datFactor analysis can be crudely described as an extension of the correlational method. When several variables are found to be rather highly correlated, it may be inferred that they are connected in some way, perhaps by a common underlying variable which is not immediately present in the measurements, but which nevertheless would account for them to a major extent . TherefoThe above model is called the factor model. Matrix  or 10:1 . In addiThe principal component method is often used to extract common factors. This method assumes that the variable is a linear combination of various common factors, to make the variance of the variable be explained by the principal component as much as possible, and ensure that the interpretation ratio of each common factor decreases successively. In the total variance interpretation table, common factors are extracted according to the default criterion of eigenvalues greater than 1. In addition, it should be emphasized that each common factor in factor analysis should have practical significance. To make the coefficient in the factor load matrix more significant, the initial load matrix can be rotated to redistribute the relationship between the common factor and the original variable, so that the absolute value of the correlation coefficient is differentiated to the two ends of the interval , and obtain more explicit results and make the interpretation of each common factor more meaningful. The commonly used factor rotation method is maximum variance orthogonal rotation (varimax), which maximizes the variance difference of common factors as far as possible to facilitate the interpretation of factors.Firstly, we determine the cluster number and divide the categories into 5 categories according to different environmental factors.According to the specified clustering center, or the center of the structure of the data itself, we set the initial clustering center.Next we calculate the distance between each case and the initial clustering center, classify them into each category according to the principle of minimum distance, and calculate the new clustering center of each category. Euclidean distance is commonly used to measure the distance between sample According to the new clustering center, we recalculate the distance between each case and the new clustering center, and reclassify and update the category clustering center.Step (4) is repeated until the moving distance of all clustering centers is less than 2% of the minimum moving distance of the initial clustering center, or the maximum number of iterations specified is reached.We use a non-hierarchical clustering method to divide the categories into 5 categories. The purpose of non-hierarchical clustering is to quickly divide cases into K categories. Generally, the specific number of categories needs to be determined before classification, and the entire analysis process is carried out iteratively. The K-means clustering steps are as follows:p < 0.01),and the KMO test statistical value is 0.828  and the mortality rates of Class A and Class B notifiable infectious diseases  rather than typical environment-related diseases such as lung cancer and bronchitis, to study the impact of healthy environment types on public health. The Games–Howell multiple comparison results are shown in The five categories of healthy environment are economic leading healthy environment, robust healthy environment, developmental healthy environment, economic and medical disadvantageous healthy environment and completely disadvantageous healthy environment. There is a significant imbalance in regional economic development; only a few regions have a large economic advantage. All regions perform well in ecological environment, but the medical and humanistic environment needs to be improved.The economic leading healthy environments include Beijing, Shanghai and Tianjin. These regions have significant advantages in the economic environment and complete disadvantages in the medical environment, and also have certain disadvantages in ecological and humanistic environments. Health indicators in these regions perform better than in other regions. It should be noted that due to the limitation of indicators, we only introduce basic medical facilities as the medical environment, and fail to take indicators that reflect local rich medical resources, such as medical equipment and doctors’ qualifications into account. We still insist that the results of our work are reasonable, since rich medical resources attract more patients, which means higher medical pressure and will squeeze on the medical care of local residents.Robust healthy environments include Guangdong, Zhejiang, Jiangsu and so on, which have relative economic advantages and no obvious disadvantages in medical, ecological and humanistic environments. The maternal mortality rate in robust healthy environments was slightly higher than that in the economic leading environments and there was no significant difference in the mortality rate of Class A and Class B notifiable infectious diseases. Developmental healthy environments are mainly concentrated in Henan, Anhui and so on, with an economic disadvantage, and dominant in medical, ecological and humanistic environments. The maternal mortality rate was significantly higher than that in the economic leading healthy environments and robust healthy environments, and there was little difference in the mortality rate of Category A and Category B notifiable infectious diseases. The completely disadvantageous healthy environment is mainly in Xinjiang, where the health condition is poor and the mortality rate of diseases is significantly higher than that of other regions. Due to the small sample size, we will not elaborate it to avoid errors.Based on the population health differences among the five healthy environment categories, we believe that the economic environment plays a major role in population health. Public health in areas with a good economic environment is significantly better than that in other areas. A better medical environment and ecological environment can also bring positive effects on population health. To further improve healthy environment levels in China, on the one hand, we should focus on enhancing the economic environment and reducing the gap between regional economies. On the other hand, it is necessary to improve the ecological and humanistic environment to enhance the social environment, so as to improve public health levels.Additionally, as can be seen in The health environment evaluation itself should integrate theories of geography, ecology, climatology, social economics and other fields to guide the evaluation process. We put forward the concept of the “healthy environment” and divide 27 environmental indicators into economic environment, medical environment, ecological environment and humanistic environment to evaluate and classify the healthy environments of 31 provinces and cities in China. Based on the rotated principal component analysis matrix, seven common factors were divided into economic environment factors, medical environment factors, ecological environment factors and humanistic environment factors, to entitle factors to a practical meaning, and obtain scores of four environmental factors in each region. We classify the healthy environment into five categories based on the four environmental factor scores. Finally, the maternal mortality rate and the mortality rate of Class A and Class B notifiable infectious diseases are taken as population health indicators to discuss the population health differences under five healthy environments. In the context that current research is generally focused on the level of environmental health risk, it is meaningful to classify the healthy environment and figure out its characteristics. The overall health environment score in five healthy environments decreased successively, and public health also decreased gradually. Different healthy environment categories show different characteristics. Based on different environmental characteristics, we believe that the economic environment plays a major role in population health.A good interactive relationship can be established between environment and health, and the understanding of this relationship will help decision-makers to have an insight into the possible consequences of policy implementation. The evaluation method of the healthy environment can provide scientific support for optimizing environmental countermeasures and realizing environmental protection and sustainable development of the economy and society. There are some deficiencies in selecting environment and health indicators. On the one hand, due to the availability of data, we can only take provinces and cities as the evaluation unit. On the other hand, the lack of detailed ecological environmental data such as air quality in the evaluation index may affect the accuracy of the evaluation results. Although there are some imperfections, it can still provide a new idea for the study of environmental health by constructing an indicator system and classifying the healthy environment.


Patent thickets create external resource constraints that reduce the market value of enterprises. In the process of technological innovation, it is no longer possible to obtain competitive advantage by relying on individual resource endowment alone. Patent cooperation is considered an important institutional element in social network relations, through which enterprises can integrate external innovation resources to counteract their shortcomings and obtain competitive advantages. In this study, 419 electronic equipment manufacturing enterprises in China between 2009 and 2019 are used as the research objects, and panel data include the financial data of enterprises, the number of patent citations, and the number of patents jointly applied for by enterprises. Based on the patent fragmentation index, social network analysis is used to construct a patent cooperation network. Using UCINET and Gephi tools, the structure of corporate patent thicket networks and their evolutionary characteristics can be obtained. A panel regression model is used to empirically test the social network effect and the effect of patent thickets on the market value of firms in the context of patent cooperation. The findings show that patent thickets can discount the market value of enterprises. However, if a firm is at the center of patent cooperation, it can obtain more innovation resources. If it is at the intermediary of cooperation, it can absorb external knowledge and technology and occupy a richer structural hole, which can positively regulate the negative effect of the patent thicket. In addition, the negative effects of patent thickets are weaker for firms with more than five years of patent maintenance compared to those with less. Our study has important implications for improving the efficiency of patent cooperation and helping governments and firms to effectively cope with patent thickets. For exaExisting studies have verified patent thicket density in specific technology areas based on the “fragmentation index” constructed from the Herfindahl index and the number of citation triangles of patentees ,12. SemaTherefore, this study aims to fill the aforementioned research gap. Specifically, we seek to understand the impact of the “informal system” established by patent collaboration on the escape from innovation resource constraints , that isSecond, by constructing a patent cooperation network and combining it with the impact of patent thickets on enterprise market value, we strengthen our understanding of the latter  under social network context factors. This innovative development should overcome resource constraints formed by the patent thicket. It is imperative to adopt effective governance mechanisms to mitigate the crowding-out effect of the patent thicket. Enterprises are constrained by patent thickets, and increasingly realize that they can no longer gain competitive advantages solely through their own resource endowments in the process of technological innovation. Furthermore, the social network relationship through patent cooperation can not only integrate external innovation resources to compensate for enterprises' shortcomings ,33, but The remainder of the paper is structured as follows. Section 22.1Patent protection with firm market value is a trade-off between the super marginal concept of monopoly distortion and increasing the number of available ideas through innovation . ExcessiApart from studies on the relationship between patent thickets and firm market value, there has been research into the mechanism by which patent thickets affect firm market value in terms of patent-related costs ,40. FirmH1Patent thickets have a negative effect on firm market value.Next, we suggest that the effect of patent thickets on firm market value is different if firms have different patent maintenance durations. This refers to the actual time from the date of patent application, or the granting of a patent, to the date of invalidation, termination, revocation, or expiration of the patent . Patent At present, the mechanism of the impact of patent thickets on the market value of a firm is unclear and the existing research needs to be expanded. The market value of a firm reflects the present value of the firm's future cash flows as a result of investors' participation in the firm's evaluation . The ret2.2A patent cooperation network refers to the social network relationship formed by two or more applicants who jointly apply for patents . When paExisting literature has yet to examine the role of patent cooperation networks in the relationship between patent thickets and firm market value. Open innovation theory suggests that organizations gradually shift from independent to collaborative innovation . Some stNetwork density is the ratio of the number of edges present in the network to the upper limit of the number of edges that can be accommodated and can be used to characterize the density of interconnected edges between nodes in a network . In highH2Network density has a positive moderating effect on the relationship between patent thickets and firm market value.Network locales, considered key indicators in the social network analysis method, describe the structural characteristics of the network ,68. In aEach firm is endowed with unique technological resources and capabilities. A firm's technological innovation behavior is embedded into the patent cooperation network, enabling it to acquire other complementary knowledge and technologies. By sharing these patents, the firm can reduce the cost of patent acquisition , thus elH3Network centrality has a positive moderating effect on the relationship between patent thickets and firm market value.Patent cooperation establishes a network relationship that integrates technology, institution, and economics. The firm's position in the network determines whether it has better access to resources and information. Firms located in the center of the local network and occupying a rich variety of structural holes are found to have significant advantages in information acquisition , which iAccordingly, we believe that the more companies occupy the structural holes in the patent cooperation network, the more they can break the “resource curse,” that is, the patent thicket causing fragmentation of patent rights, thus alleviating its negative effect on their market value. In the process of coping with the patent thicket, firms should integrate and absorb internal and external patents to form their own comprehensive technology chain. Firms that occupy more structural holes in the cooperative network tend to play the role of intermediaries for organizations connected to them, improving the efficiency of knowledge spillovers and the ability to access information ,71. OrgaThe greater the variety of structural holes in the patent cooperation network, the more firms can promote knowledge sharing and technology. The formation of common technologies cultivated can facilitate better integration and reorganization of the cooperative partners' respective fragmented patented technologies, which is conducive to overcoming the negative effect of the patent thicket on firm market value. Through patent cooperation, inter-organizational communication is strengthened . In a paH4Structural holes have a positive moderating effect on the relationship between patent thickets and firm market value.Research suggests that firms in these intermediary positions can link two areas of dense relationships, thus bringing new information to these linked parties and allowing resources to flow through this new linkage . Social Innovation is a continuous, cumulative investment process  that neeH5Betweenness has a positive moderating effect on the relationship between patent thickets and firm market value.In the patent cooperation network, firms close to the central belt can not only obtain a larger competitive edge, but also gain and utilize external complementary resources by identifying these from inter-firm relationships and the network . The intH6Closeness has a positive moderating effect on the relationship between patent thickets and firm market value.The conceptual framework of this study is presented in We posit that firms can obtain social capital through network relationships formed by patent cooperation. By embedding themselves into the network in an appropriate and suitable fashion, firms can focus their limited time and energy on identifying high-quality resources and avoid blindly searching for patents in external technology markets, eschewing over-dependence on external patent behaviors. High-density network linkages can help firms obtain valuable resources to easily form a win-win model of collaboration, which in turn facilitates a faster rise in firm market value . If firm33.1Our study sample was drawn from the China Stock Market & Accounting Research (CSMAR) database for the 10-year period 2009–2019. We first selected our samples from a limited range by targeting the electronic equipment manufacturing sector, under the secondary technical classification of the China Securities Regulatory Commission in 2012. We excluded companies penalized for unusual financial status, and those that had continuously made losses, eliminating companies that were delisted from the Shanghai Stock Exchange STAR Market, Main Board, ChiNext market, or SME board. We also excluded all companies from the financial and insurance sectors. Companies with incomplete/missing data were excluded during processing. The final sample came to 419 companies. In our panel data regression, we considered the inventions and patents of the sample firms, and the technical information included therein, attributes, technical fields, citations of the patents by other patent owners and the protection scope of the patent rights. We used a Python program to extract the patentees who jointly applied for patents from the sample firm's information, who were then matched as pairs, and the intersection of the two patentees was the number of jointly applied-for patents. We used the Derwent database for firms' patents data. We used the 419 selected companies to search for the desired corporate patents in the Derwent database using the name of the patentee as the search term and our selected time period, 2009–2019. We performed manual data cleaning on the raw data, merging patents of the same patentee and excluding homologous patents to ensure the accuracy of the company patent data. The core explanatory variables of this study are centered on patent thickets, and we investigated patent thickets by focusing on individual enterprises. Based on prior studies, we constructed a fragmentation index to study patent thickets at the individual firm level ; the Humanities and Social Sciences Foundation, Ministry of Education of the People's Republic of China [18YJC630113]; the Humanities and Social Sciences Project of Hubei Provincial Education Department [19Q082].Professor kai luo was supported by https://dataverse.harvard.edu/loginpage.xhtml?redirectPage=%2Fdataset.xhtml%3FownerId%3D1.Data associated with this study has been deposited at The authors declare no conflict of interest.


Lactobacillales play a prominent role. Here, we give an overview on protective cultures in food products. We summarize the mode of actions of antibacterial mechanisms. We display the strategies for the isolation and characterization of protective cultures in order to have them market-ready. A survey of the growing market reveals promising perspectives. Finally, a comprehensive chapter discusses the current legislation issues concerning protective cultures, leading to the conclusion that the application of protective cultures is superior to the usage of defined bacteriocins regarding simplicity, economic costs, and thus usage in less-developed countries. We believe that further discovery of bacteria to be implemented in food preservation will significantly contribute to customer’s food safety and food security, badly needed to feed world’s growing population but also for food waste reduction in order to save substantial amounts of greenhouse gas emissions.An ultimate goal in food production is to guarantee food safety and security. Fermented food products benefit from the intrinsic capabilities of the applied starter cultures as they produce organic acids and bactericidal compounds such as hydrogen peroxide that hamper most food pathogens. In addition, highly potent small peptides, bacteriocins, are being expelled to exert antibiotic effects. Based on ongoing scientific efforts, there is a growing market of food products to which protective cultures are added exclusively for food safety and for prolonged shelf life. In this regard, most genera from the order  Food safety and food security are of primary importance to fight the hunger of a reported 828 million people in 2021, so to deliver the required amounts of nutritive and highly valuable food products for everybody ,4. In adLactobacillales can be included in food products as protective cultures to fight pathogenic and food spoiling bacteria without interfering with food taste and texture paved the way for the field of bio-protection [Chemical preservation is one option, which has its limitations. Food preserved with sugar, salt, or organic acids changes texture and taste or, as in the case of sorbic acid, are not acceptable by the customer, because all-natural products that contain as few food additives as possible are en vogue ,8. Physiotection . Hence, In this review, we address the application of LAB as food protective cultures. We describe the characteristic features of protective microorganisms regarding the underlying mechanisms. We outline the strategies for strain identification and validation relating to application in diverse food products and provide a survey on the market. For the first time, we extensively attribute the legal restrictions for the use of protective cultures to provide a guideline to the interested user.The concept of bio-protection of food by the implementation of protective cultures is widely accepted, is substantiated in numerous studies, and is implemented into a wide range of products on the market ,14,15. AThe addition of live bacteria to food products as protective cultures was based on the observation that bacteria have developed a number of strategies to outplace competing species. An initial observation was that a bacterial species can overgrow in co-culture experiments other species simply by the higher cell amount of the inoculum, depriving nutrients and minerals. The so-called Jameson-Effect proved to be valid in many cases ,18,19,20Streptomycetes that secret bio-active secondary metabolites as a survival strategy against other microorganisms, a process that is triggered by carbon regulation [Lactobacillales exert as well a multitude of measures against other microorganisms  in vivo detection of antibacterial activity against indicator strains or (ii) by genome sequencing followed by bioinformatic searches for the presence of bacteriocin-encoding genes. For detection in vivo, the point inoculation assay B, the spIn order to meet the required criteria for food safety, it is necessary to show the absence of antibiotic resistant genes and genes encoding virulence factors ,84,85. IWhile the examination of the safety criteria is ongoing, experiments could be conducted in parallel to implement the new isolated protection strain into the chosen food product. The microbiological profile should be followed to determine the shelf-life. Absence or prevention against potential food pathogens, texture analysis, and proof of unchanged organoleptic properties will complete characterization. Subsequently, the upscaling process must follow in order to commercially sell the food product in sufficient quantities.The industrial production of protective cultures in a bioreactor follows those for LAB used as food starter cultures. The protective cultures are cultivated from a stock culture using small-volume batches of about 2 mL to 100 mL or a fed-batch process to grow the bacteria until a desired biomass concentration is reached. The biomass serves to inoculate 200 L to 50,000 L bioreactors in a batch or fed-batch process . At thisA compromise between protective culture as maximum biomass and pure bacteriocin production are fermentates. Fermentates are the bacterial cells propagated in the reactor plus medium into which bacteriocins are secreted. Under optimally adapted physical and chemical conditions in vitro, LAB are able to secrete bacteriocins into significantly higher amounts than in vivo in a food matrix . HoweverEscherichia coli and Corynebacterium glutamicum has been demonstrated [An alternative approach for bacteriocin production is the molecular biology approach in which bacteriocin-encoding genes or operons are cloned into strains that are widely used in biotechnology. Since the gene sequences of numerous bacteriocins are readily available ,106, thenstrated ,110,111.The use of microbial protective cultures is not generally regulated as an ingredient, additive, or processing aid in the regulatory framework of the European Union (EU) with its 27 member states and the European Economic Area (EEA) and does not necessarily require approval and safety assessment. The duty of care and the sole responsibility for the specific use lies for the time being solely by the user. Further regulation is carried out outside the legal requirements of the Basic Food Regulation (EC) No. 178/2002  on the bIn addition, food- or feed-associated microorganisms must always undergo a safety assessment and be approved by the European Food Safety Authority (EFSA)  in the EThe effect is based on displacement cause by microorganisms that have a higher colonization rate. They can outcompete nutrients through more efficient transport systems of carbon sources or by an accelerated metabolism. They also may exert superior adaptation to aerobic or anaerobic, or other growth conditions. In such cases, the activity is attributed to a non-specific protective culture ,122,123.Specific protective cultures are distinguished from non-specific ones by their technological purpose and their action by means of bacteriocins, proteins, or protein-like compounds, such as nisin, with antagonistic activity against defined foodborne pathogens . This diThe prohibition does not refer to the microorganisms themselves but to the substances produced by them. This is further differentiated in the Enzyme Regulation (EC) No. 1332/2008 ; the exeIf an application for market authorization and with it a safety assessment on the part of EFSA is required, there are two approaches depending on the organism used. In principle, the application procedure for food additives is carried out in accordance with Regulation (EC) No 1331/2008 . The tecThe two approaches for safety assessment differ in terms of their depth of testing. If the EFSA already has a qualified presumption of safety (QPS) status for the microorganism used, an accelerated generic safety assessment will be performed. This procedure was introduced by the EFSA in 2007 to simplify the marketing authorization process and save resources. For a microorganism to have QPS status, the taxonomic unit of the organism used must be at species level for bacteria, fungi, and microalgae/protists and at the family level for viruses, and it must be on the QPS list  maintainIf a microorganism is used that does not have QPS status, there may be two reasons: First, the organism has never been evaluated because no dossier was ever submitted for authorization and therefore the QPS evaluation process was not initiated by EFSA. Second, the micro-organism in question was not granted QPS status following a QPS evaluation by the BIOHAZ Panel . The QPSIn contrast to the partially undefined European legal framework for microbial cultures, the Federal Food, Drug, and Cosmetic Act  has provIn the US, according to the Federal Food, Drug, and Cosmetic Act , a food In addition, the GRAS status is not determined by the FDA, as is the case with food additives, but by qualified experts. The first distributor or manufacturer is free to decide how the expert panel is convened and staffed. An evaluation can also be carried out by the FDA if desired. The Guidance for Industry  assists In Mexico, the use of microbial protective cultures in food products is regulated by the Federal Commission for Protection against Sanitary Risks (COFEPRIS) under the Ministry of Health. The use of these cultures is permitted only when they are considered safe for human consumption and do not alter the nutritional value of the food product. The manufacturer of the protective culture must provide evidence that the culture is safe and effective for use in the specific food product. This requires GRAS status on the part of the FDA or its homologation. Further, a sample of the microbiological culture used must be deposited in the strain collection for microorganisms of the National Institute of Forestry, Agriculture and Livestock Research (INIFAP) .The use of microbial protective cultures in Brazil is regulated by the National Health Surveillance Agency (ANVISA). ANVISA requires that manufacturers of protective cultures provide evidence that the culture is safe and effective for use in food products. Since the revision of Resolution RDC 27/2010: Categories of food and packaging that require pre-market approval by Anvisa by Resolution—RDC No. 240, of 26 July 2018 the registration and approval of microbial cultures as technical adjuvants is no longer required .In Peru, the General Directorate of Environmental Health (DIGESA) of the Ministry of Health is responsible for regulating the food industry. Currently, there is no regulatory framework for the use of microbial protection cultures in food.The regulatory framework for microbial-protective cultures in China is primarily governed by the Food Safety Law, which sets the basic principles for food safety, and the Regulations for the Administration of Food Additives, which provides specific requirements for the use of food additives, including microbial protective cultures. The regulatory authorities in China are the National Health Commission and the Department of Food Safety Standards, Monitoring and Evaluation, which since 2010 has had a separate regulation for food cultures, including protective cultures. From this date, all new strains placed on the market must be on the official list. The list was last updated on 18 August 2022 .Some other countries have also established positive lists for food and protective crops. Examples include Thailand and Malaysia. In Thailand, industrially used cultures are considered food additives. The regulatory framework requires the submission of strain level documentation for registration with the Food and Drug Administration . TraditiThe economic importance of protective cultures for food processing should be appreciated. The global market volume in 2022 was already 1.3 billion USD  in the fHowever, the market for protective cultures is quite fragmented and is not dominated by large international companies. In addition to finished products, start-ups and medium-sized companies in particular develop customer- and product-specific cultures ,155. ProThe implementation of protective cultures of lactic acid bacteria in diverse perishable food products contributes substantially to food protection, food safety and food security. The here thoroughly discussed regulatory frameworks show that the use of foods harboring protective cultures is superior to the application of specifically defined agents, such as a pure bacteriocins. This accounts even more regarding the production costs. The current state of knowledge through studies providing proof of principle for all categories of risky foods shows that a wealth of protective cultures is available. Furthermore, nature still has an untapped unlimited reservoir for more protective bacterial species that remain to uncover. Bio-protection could thus contribute to nourish the hundreds of millions of starving people and to reduce significantly greenhouse gas emissions by food waste reduction. The biggest challenge to making this true is probably to speed up the transfer of scientific knowledge towards food production companies.


The COVID-19 pandemic posed challenges to communicating accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reassure the public by communicating early on about the development and approval of COVID-19 vaccines. The EMA surveyed patients/consumers, healthcare professional organizations, and individual stakeholders, both at the EU level and in an Italian regional context. The objectives of the study were to see if the EMA’s core information materials were informative and well-understood and which communication channels were preferred by the public. The main findings showed that individual patients/consumers generally prefer to obtain information about COVID-19 vaccines from the internet or mass media, while organizations and individual healthcare professionals prefer to obtain information from national and international health authorities. Both at EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some improvements were recommended to the visual, text, and dissemination formats, including publishing more information on safety and using a more public-friendly language. Also, it was recommended to maintain the EMA’s approach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. In conclusion, user-testing of proactive communication materials aimed to prebunk misinformation during a public health crisis helps to ensure that users understand the development and safety of novel vaccine technologies. This information can then be used as a basis for further evidence-based communication activities by regulators and public health bodies in an emergency context. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current COVID-19 global pandemic, proclaimed a public health emergency of global concern by the World Health Organization (WHO) between March 2020 and May 2023  was preferred by individual patients and consumers  and HCPOs . The second safety statement  was preferred by the individual HCPs . PCOs preferred either statement (4 out of 8).The survey also user-tested two key messages that the EMA can use to explain COVID-19 vaccine safety when considering the benefits . Both stAt the regional level, the first safety statement was preferred by HCPOs . The second safety statement was preferred by individual patients and consumers  and individual HCPs . On the basis of this feedback, and given that PCOs had no preference for either statement, the EMA has decided to use the first safety statement proposal, given that HCPOs preferred it, and healthcare professionals are normally the first point of contact for questions on vaccines and they deal with vaccination-hesitant individuals. The survey further explored open feedback from stakeholders on ideas for other types of formats, translations into EU languages, and whether any key information was missing.To identify other possible formats that could be used to share COVID-19 vaccine information, the survey included a question to see if the participants would be interested in having the Tier 1 information “COVID-19 vaccines: basic facts” in another shareable format besides the webpage . Around Although most of the participants (>70%) stated that they did not have an issue understanding the documents in English , 4% of EThe survey also asked participants to identify areas where more information was needed, as part of an open question. A recurrent missing item identified by stakeholders was more information on COVID-19 vaccine safety . The materials subject to user-testing from Tier 1 and Tier 2 were non-product-specific and were published before individual vaccines were approved and rolled out in vaccination campaigns; thus, there was no safety information available from real-world data at the time. The EMA has since published regular public safety updates on the approved vaccines on the corporate website, after mass vaccination campaigns had taken place and clinical data had become available . Public The quantitative data showed an overall satisfaction of the participants with both EMA documents (Tier 1 and Tier 2) explaining COVID-19 vaccines. The quantitative and qualitative results from the survey were used to draw recommendations for regulators to improve information materials according to areas of improvement or missing information identified by participants. In Some text and headings were updated to improve understandability in response to the substantially incorrect answers to one comprehension question about “COVID-19 vaccines: fey facts” and to the participants’ calls to use as much lay language as possible. Due to the fact that these materials were created in the context of a public health emergency, it was not possible to conduct a user-testing study before publishing these materials. However, by introducing retrospective improvements, the EMA has been able to address the public’s information needs and formatting preferences captured in this study. This research aimed to user-test the EMA’s core information materials on COVID-19 vaccines. More specifically, it tested whether the language was clear, whether enough information was provided, and whether it increased stakeholders’ understanding of how COVID-19 vaccines were developed and approved in a short period without compromising safety, efficacy, and quality standards. We have also user-tested some key graphics and messages used by EMA to communicate on these vaccines to the public.These materials were proactively prepared before the approval of the first vaccines and were subsequently repurposed by the EMA through different channels and communication tools during the COVID-19 pandemic. As such, the EMA webpages containing the information subject to this study have been regularly visited since their publication, with visit peaks coinciding with the start of the COVID-19 vaccination campaigns in Europe, announcements of COVID-19 vaccine approvals, start of rolling reviews, and evaluation of safety signals (unpublished data).Subjecting the EMA’s core content to user-testing is relevant not only for selecting messages and figures for webpages but also because this content is repurposed by regulators in response to queries from patients and HCPs, media interviews, and explaining vaccine development and regulatory oversight during public stakeholder meetings held by the EMA. These messages and graphics were included in public webpages before the first COVID-19 vaccine was approved in the EU to anticipate mis- and disinformation, as well as to address legitimate stakeholders’ questions and concerns circulating on  media with regard to the fast-tracked development, evaluation, and approval of COVID-19 vaccines . As described by Blastland et al., obtaining a better understanding of the target audience and their concerns is required to be able to prebunk misinformation .When trying to establish how applicable our results can be to the general EU population, or to different stakeholder groups, it is important to examine who responded to the survey. The EU-level participants were predominantly members of patient or healthcare professional organizations, followed by individual patients, consumers, and HCPs. The EMA routinely uses stakeholders registered in its stakeholders’ database for consulting with PCOs or HCPOs different initiatives and regulatory issues and for disseminating information to organizations. The response rates obtained are aligned with responses generally obtained by the EMA with these types of surveys. In particular, the response rates for HCPOs (around 37%) and PCOs (around 22%) were higher than what has been found in other EMA communication research initiatives . This proportion differed in the regional context, where most respondents were individual HCPs, followed by HCPOs and individual patients and consumers. This suggests a broad profile of participants; representatives from organizations tend to be more familiar with regulatory processes and language, while individual patients or HCPs tend to be less familiar with them. We can then assume a certain balance in our results.In general, during the first phases of the European vaccination campaign against COVID-19, individual HCPs and HCPOs played a key role in promoting correct information and counselling on the COVID-19 vaccines available ,28. MoreThe choice to compare the EU with the regional Italian context data was relevant in order to conduct an in-depth evaluation of the readability and reproducibility of the user-testing material in the local context, where there could be participants with a limited knowledge of English, the working language of the EMA . From thIn order to guarantee an appropriate data comparison, the authors tried to administer the survey to similar patterns of respondents at EU and regional levels. Effectively, a similar distribution of representatives and individual HCPs and/or of consumer and patient organizations was observed. Moreover, in both cases, 23 participants out of 30 completed Tier 1 and 2 of the survey. The possibility of translating Tier 1 and 2 content into local EU languages could be considered for documents that are made available for the general public in order to promote a wide dissemination of information, also among people with limited English knowledge or low health literacy levels. The current user-testing of materials was carried out on a population of HCPs  and representatives of PCOs that may have a better knowledge of the English language and a better capacity to understand scientific language and regulatory processes . Based on the participants who responded to this survey, individual patients and consumers mainly consulted internet search engines, newspapers, and their family doctor as a source of COVID-19 vaccine information. It therefore seems crucial that regulators use these same channels that are easily accessible to the general population in order to effectively counteract the circulation of misinformation. As for doctors themselves, it is also necessary for them to receive complete and clear information from authoritative and unbiased sources since they represent a point of reference for the population, as also shown by the results of the ADVANCE project . The role of HCPs in countering mis- and disinformation among their patients has also been emphasized by the Employment, Social Policy, Health, and Consumer Affairs (EPSCO) Council on the 9 December 2022, in which ministers responsible for policy on employment, social affairs, health, and consumers from EU member states and relevant European commissioners participate ,34. ThisSome of the participants’ feedback in the survey shows that, compared to individuals, representatives of PCOs and HCPOs are more willing to vaccinate (unpublished data). This observation can probably be attributed to an increased trust in the regulatory system of these representatives. Trust in scientific and medical institutions is one of the strongest motivators for vaccine acceptance and being part of such institutions increases vaccination numbers precisely because of a lower exposure to misinformation ,37.During a public health emergency characterized by considerable scientific uncertainty and political leaders acting as frontline crisis managers, it often becomes a challenge to ensure that evidence-based recommendations take precedence over political interests . The recAs mentioned before and as described by Cavaleri et al. , it is fMoreover, the COVID-19 pandemic provided the EMA with the opportunity to improve its transparency. An example of such a measure is the introduction of shorter publishing timeframes for assessment reports and assessed clinical data . In addiWhile the regional survey revealed that information in English was not a barrier to understanding the information, the above-mentioned reasons prompt consideration of the possibility of translating more EMA documents into local EU languages to promote the wide dissemination of information to the public and to reach people with low health literacy and limited knowledge of English. The EMA already publishes translations of key documents and information of great relevance and impact in all official EU languages. This includes information on medicines that the EMA evaluates, such as overviews of authorized human medicines, medicines for which authorization has been refused, withdrawn applications, product information for authorized medicines, and referrals of medicines. Furthermore, general information on the activities and work of the Agency is translated. In addition, citizens can send inquiries to the EMA and receive a response in the same language . AnotherThis study needs to be interpreted in light of several limitations that may limit the generalizability of the results. First, a possible lack of representativeness due to the limited number of participants needs to be taken into account. In this regard, considering the EMA’s experience running stakeholder surveys among PCOs and HCPOs, 60 respondents in total to the EU and regional surveys can provide meaningful feedback. A second limitation could be that respondents from EU organizations have a better knowledge of the regulatory system and its outcomes, and this could represent a source of bias in the understanding of the information. On the contrary, there were more individual HCPs/patients that organizations recruited in local hospitals at the Italian regional level. Thirdly, since the surveys were mainly conducted through online recruitment and participants were volunteers, selection bias should be considered as a possible limitation. Fourth, even though an analysis of the regional Italian context revealed similarities in the understanding of key messages, it is unknown how representative this is of other EU regions. Another limitation of this study is that EU stakeholders responding to this survey were sent the Tier 1 and 2 documents in PDF format and it is not possible to establish how long they spent reading the documents.Our research shows the importance of user-testing information materials during a public health crisis to guide regulators and HCPs in creating future evidence-based communication materials on vaccines. The similarities between the results at both EU and local levels reinforce the findings of this study. The proactive provision of information by authorities on COVID-19 vaccines during the public health crisis is considered important to counteract hesitancy and prebunk misinformation. The key messages and concepts tested were generally well understood, but areas of improvement were identified, including simplifying language and displaying key concepts/messages more prominently. Individual patients tend to search the internet and media more, while representatives of PCOs and HCPOs rely more on government sources and scientific publications. This indicates the importance of science communication through different channels , and that complementing efforts with visuals helps to convey information. Moreover, user-testing graphics revealed that the public’s preferences may differ from those of regulatory authorities. Ultimately, tailoring information materials to the needs of the public may improve trust and raise awareness of the science underpinning vaccines developed in a public health crisis.


The transportation control infrastructure serves as the foundation for regional traffic signal control. However, in practice, this infrastructure is often imperfect and complex, characterized by factors such as heterogeneity and uncertainty, which pose significant challenges to existing methods and systems. Therefore, this paper proposes a novel approach to coordinated traffic signal control that emphasizes flexibility. To achieve this flexibility, we combine the flexible model of complex networks with robust fuzzy control methods. This approach enables us to overcome the complexity of the transportation control infrastructure and ensure efficient management of traffic signals. Additionally, to ensure long-term operational ease, we develop a regional traffic signal control system using steam computing technology, which provides high scalability and compatibility. Finally, computational experiments are performed to validate adaptability and performance of our proposed approach. Furthermore, some areas may have a high density of devices, while others may have sparse coverage. These heterogeneous situations are very common during urbanization and necessitate high compatibility for RTSC systems;Engineering complexity (dynamic): The operation of the transportation control infrastructure is heavily influenced by environmental factors such as adverse weather, power outages, and traffic accidents. Any hardware or communication failures can affect RTSC operations. Furthermore, some junctions may operate in higher priority modes  and be out of coordinated control at times. These uncertain situations are unavoidable during long-term operation and require RTSC systems with high flexibility.Application complexity The regional traffic signal control (RTSC) ,2,3 heavThe two types of complexity mentioned are significant challenges that must be addressed when deploying RTSC in practice. Otherwise, the RTSC system may struggle to operate effectively and may even be abandoned after a period of use. The urban transportation system is an open and complex giant system . As the A novel flexible regional traffic signal coordinated control method is proposed, focusing on adaptability to the complexity of the actual transportation control infrastructure;An easy-to-maintain RTSC system is created using the steam computing technology, with a focus on the scalability and compatibility of RTSC systems required for actual traffic management;A triple-random principle is proposed to design the testing experiments on simulation software. Both the performance and the adaptability of the proposed approach are validated.Therefore, this paper proposes a novel regional traffic signal coordinated control approach and system that can not only optimize the traffic signal but also adapt to the complicated transportation control infrastructure. The contributions of this paper are listed below:The remainder of this paper is organized as follows. As early as 1963, the first RTSC system came into use in Toronto, Canada. Since then, numerous methods and systems of RTSC have been proposed and adopted in practice. Currently, TRANSYT, SCOOT, and SCATS are the three most widely used systems. TRANSYT was an offline regional fixed-time coordinated control system developed by the British Institute of Transport and Roads in 1968 . The latThe above three systems were developed in the last century and have undergone 30+ years of iterative improvement both in theory research and system development. In this period, plenty of researchers have been devoted to this area, and numerous network-based and intelligent RTSC methods have been proposed . ResearcIn the first category, fuzzy logic , rough sThough many RTSC methods have been explored, most of them are still far away from practical applications. The main reasons for this are twofold: first, the complexity of the actual transportation control infrastructure has not been adequately addressed; second, the high scalability and compatibility required by RTSC systems in actual long-term operation have not been met. Taking these requirements into account will bring many constraints to the RTSC research. For example, research can no longer assume that it can obtain the traffic conditions of all junctions and roads, and all junctions cannot be assumed to accept unified coordinated control at any time. Almost all methods without sufficient flexibility do not work anymore, and this situation prompted us to carry out the work in this paper.The network of junctions is modelled as a directed graph of nodes For driving habits, safety, and fairness, the composition of the phase scheme for a junction is usually fixed, and the sequence in the scheme cannot be adjusted frequently. The phase scheme of Among traffic flow parameters, traffic volume is the most easily measured, and its detection error is relatively small. In our model, induction loops are placed at each entrance and exit of a junction to count the arrival and departure of vehicles in a section during each phase. As illustrated in t, assume that the junction mth lane at the start section of mth lane at the start section of mth lane at the end section of mth lane at the end section of The vehicle arrival rate, departure rate, and saturation of each section can be derived from traffic volume data easily. At time All data are collected and calculated independently based on phases, and there is no uniform sensing cycle for all junctions. In particular, detectors should also be installed on lanes that keep being released (such as right-turn lanes) so that the corresponding exit can estimate more accurately how many arriving vehicles are released in phases.To coordinate phases within an area reasonably, it is critical to model their relationship first. Our approach is simple and intuitive—that is, we connect the signal phases of adjacent junctions into a network according to their influence on the same road. The following takes the road At time For a road, its upstream arrival rate and downstream departure rate, which are affected by phases of upstream and downstream junction, will determine the number of vehicles stranded. Mismatched arrival and departure rates can easily cause road congestion. Therefore, the connection strength between the phases of Repeat the above process for all roads, resulting in a network called the phase coordination network (PCN). The PCN is reconstructed periodically and does not have strong coupling constraints, such as uniform cycle and phase offset among connected phases.In the PCN, each directed link is associated with a corresponding actual road and its traffic sensing data, while each node is associated with a certain phase and its green time. Hence, the PCN actually provides a loosely coupled platform for RTSC by integrating all required input and output. Based on this platform, a two-stage RTSC method is proposed.The load strategy is used to optimize the green time of phases. Firstly, we define the upstream and downstream loads of each link and node. Without loss of generality, the following takes the link mth lane at the start section of The upstream load of On this basis, the local upstream load of q-order upstream neighbor nodes of q steps, and they are noted as q-order downstream neighbor nodes of Then, the local load situation is extended to the neighbor network. q-order neighbor network. The q-order upstream load of q-order downstream load of According to the shortest path, the local load of nodes can be generalized to the q-order downstream load of q-order upstream load is similar.The above calculation process depends on the topology of the PCN. Algorithm 1 gives a breadth-first search method to compute the Algorithm 1. Compute the q-order downstream load of  ENQUEUE, S (short), Z (middle), L (long), and VL (very long). Their membership functions, taking the phase VL. In addition, the number of vehicles in the detection section of each lane is also divided into five fuzzy language values: VF (very few), F(few), Z(middle), M(many), and VM (very many). A membership function similar to that shown in VM.Firstly, the length of green time of a phase is divided into five fuzzy language values: At the beginning of a phase, the number of vehicles currently released on the lanes and those waiting to be released can be obtained by the detectors of end sections, denoted as Our method differs from the existing research on applying fuzzy control to traffic signal control, which often decides whether to extend the green light or not in a short time before the end of phases. In our method, the green time is decided directly at the beginning of phases, so it does not affect the use of countdown displays in practice, which must know the exact green time in advance . Moreover, benefiting from the optimized green time, the fuzzy rule table can adopt a simple greedy strategy, i.e., when Algorithm 2. Traffic signal coordination control of the junction while Truefor k According to Algorithm 1, calculate the  Similar to Algorithm 1, calculate the  Calculate the optimized green light time  Get the  Input  The traffic signal controller sequentially outputs green, yellow, and red lights for the corresponding time period.; Update vehicle arrival rate, departure rate, and saturation for each lane during  updating of PCN.Integrating the aforementioned two methods, taking the junction In research, we have always kept the principles of simplicity and practicality in mind. In the PCN model, the traffic volume data used are a type of traffic flow parameter that is easy to collect and that has high accuracy. In addition to induction loops, many vehicle detectors, such as video detectors, ultrasonic detectors, radar detectors, etc., can detect traffic volume. When constructing the PCN, for roads that cannot be sensed, all detection data can simply be set to zero. Similarly, for junctions that cannot be included in the RTSC, it can be assumed that only an empty phase is contained.In the RTSC method based on the PCN, we further keep the signal control at each junction loosely coupled for flexibility. This approach ensures that the entire method is highly adaptable to the engineering and application complexity that may arise in actual transportation infrastructure.The designed RTSC method also follows the simplicity and practicality principles. Specifically, we employ load strategies for global phase optimization and fuzzy rules for local phase execution. These straightforward methods are highly consistent with the experience of transportation managers and are expected to yield promising optimization results. In The transportation control infrastructure of a city is constantly evolving due to various reasons, such as the installation of new detectors or controllers on new roads or junctions or the removal or upgrading of existing ones. To ensure smooth functioning of the RTSC system, it must adapt accordingly to these changes in infrastructure. Therefore, the maintainability of the RTSC system is also very critical in actual long-term operation.The flexible stream-computing framework, called Storm , is intrTrafficDataSpout node is responsible for receiving and processing all traffic detection data at the corresponding junction. It then passes the FuzzyControlBolt node, which decides the green time of the current phase according to the fuzzy rules and the optimized green time. Finally, the green time for execution is passed to the DeviceCommondBolt node, which is responsible for translating the results into instructions for the corresponding controller and issuing them through the network. In addition to this, the PCN module is responsible for storing historical traffic detection data and periodically updating the phase coordination network to optimize the green time of phases. This ensures that the system can adapt to changes in traffic flow and adjust the signal control timing accordingly. Overall, this architecture provides a flexible and efficient approach to managing traffic flow in a transportation control infrastructure.The signal control of each junction corresponds to a topology composed of three types of nodes. Firstly, the TrafficDataSpout and DeviceCommandBolt nodes. The steam computing architecture allows for dynamic addition or removal of junctions, making it easy to expand or modify the network. Additionally, each node has a backup mechanism that can automatically restart in case of failure, providing high fault tolerance for the entire system. These features make the RTSC system highly adaptable and reliable, ensuring smooth operation in various transportation control environments.The RTSC system can be customized to accommodate different equipment manufacturers by customizing the nodes, such as the To analyze the time complexity of the proposed RTSC method, we consider an extreme case in which all traffic detectors collect and upload data directly to the system without any processing and in which all traffic signal controllers only request and receive green time information from the RTSC system without making any local decisions. In this case, the RTSC system has the largest computational load.TrafficDataSpout receives traffic detection data, it calculates the volume and saturation of vehicles in each start and end section. The time complexity is q-order upstream and downstream nodes of each node and The workflow of the RTSC system is event-driven and distributed in clusters. When the Based on the analysis, it can be concluded that the entire RTSC method has a low time complexity of no more than For legal and safety reasons, it is almost impossible to long-term test an RTSC system in practice, so it is common to use traffic simulation software. TransWorld, a microscopic traffic simulation software based on artificial transportation system theory . This so2, which is a relatively dense road network. There are four channelized lanes at the entrances of each junction. The lengths of each start and end section are set to 60 m and 120 m, respectively, and the maximum number of vehicles in each section is converted according to an average of 6 m per vehicle. Uniformly, the minimum and maximum green times for all phases are set to 15 s and 45 s, respectively, and their yellow and red times are both set to 3 s. The sliding time window in PCN is set to 3 periods, i.e., As illustrated in Randomly generate vehicles crossing boundary nodes. Vehicles are randomly generated at each boundary node according to the Poisson distribution, and other boundary nodes are randomly selected as destinations. The entire area is set to generate an average of Randomly select phase schemes for junctions. There are two typical four-phase configurations for a four-way junction, i.e., release in opposite directions at the same time and release each direction in turn. Depending on whether the right turn is signal-controlled or not, a total of five configurations can be derived, as shown in Randomly select some junctions or roads, assuming that there are special circumstances of engineering or application complexity. The associated junctions will be excluded from the RTSC, and their signal control could be degraded to traditional traffic signal full-actuated control, since the same traffic detectors as full-actuated control are used. The minimum and maximum green times of each phase remain unchanged, and the unit extension of green time is set to 3 s.In addition, computational experiments are configured following the triple random principle:To verify the adaptability, 10 groups of experiments (denoted as Exp1–10) are designed with random traffic flow distributions and phase configurations. Each group experiment is further divided into 6 subgroups, randomly assuming that there are 0%, 3%, 6%, 9%, 12%, and 25% junctions that are excluded from the RTSC, denoted as H00, H03, H06, H09, H12, and H25, respectively. To reduce random errors, each experiment is repeated 10 times, resulting in a total of 600 (10 × 6 × 10) experiments. At the end of every 10 experiments, the average travel distance, speed, and stop time of all passing vehicles are calculated and drawn in In terms of average travel speed and stop time, with the increase in complexity , the average travel speed decreases gradually and the average stopping time increases gradually. However, all of them are better than H25. TransWorld simulates situations in which people are forced to change lanes due to long queues or are unable to change lanes due to congestion, which can result in differences in the average travel distances of vehicles within the same subgroup of experiments. In 10 groups of experiments, the average travel distances of H00–H12 are all less than that of H25, indicating that the proposed RTSC method can alleviate regional traffic congestion in time and reduce times to change paths for traffic congestion.Ignoring traffic flow distribution and phase configuration, a statistical comparison can be made based solely on the degree of complexity. As shown in The average degree of a network is a useful metric that measures the number of edges compared to the number of vertices. This can provide insight into the connectivity density between nodes within the network. In As the complexity of the transportation control infrastructure increases, the average degree of the PCN gradually decreases. However, each phase node in H12 is still connected to about nine phase nodes on average and has the basis for signal coordination. In conclusion, the proposed RTSC method exhibits strong adaptability and can effectively optimize traffic signal control for varying degrees of complexity in transportation control infrastructure.In addition to adaptability, the performance of the RTSC in improving traffic efficiency through coordinated control is also very critical. In the previous test, we only adopted the load-balancing strategy (Another 10 groups of experiments (denoted as Exp11–20) are designed with random traffic flow distributions and phase configurations, and each group experiment is further divided into four subgroups. The four subgroups respectively run four types of strategies. Similarly, each experiment is repeated 10 times to reduce random errors, and a total of 400  is sufficient to verify whether the proposed method has adequate flexibility to ensure universal applicability.We do not simulate the process of complexity that occurs in the transportation control infrastructure but exclude the associated junctions from the RTSC directly. This unified processing method is simple, but it also loses some useful traffic information. For example, when a junction enters the manual control mode, its associated detectors still normally collect traffic flow parameters.Given that the generated traffic flow distribution is uniform and random throughout the simulation period, the junctions that are excluded from the RTSC are confirmed at the beginning of the simulation rather than appearing randomly during the simulation. This can avoid assuming the start time and duration of the exception. Otherwise, it will lead to a combination explosion (since the time is continuous), and it is not helpful to obtain a statistically significant conclusion.The paper proposes a flexible RTSC method based on the innovative phase coordination network for achieving effective traffic signal coordinated control even with complicated transportation control infrastructure. The proposed model and method are both built around phases, beginning with modelling the relationship between phases based on data, then using load strategies to optimize the green time of phases, and finally applying fuzzy rules to optimize the execution of phases. Data, heuristic strategies, and rules drive the entire process. Furthermore, using stream-computing technology, an easy-to-maintain RTSC system is developed.From method to system, practicality has always been the top priority. At present, the application of complex network theory in our method is still relatively preliminary. Though it is consistent with intuition and practical experience, it still lacks rigorous theoretical derivation and proof, which is one of the next steps to be carried out based on the theory of complex network dynamics. On the other hand, the academic community does not yet have a unified testing platform to compare different RTSC methods fairly. This is a very meaningful research direction that needs to be filled, and we are very interested in doing some work in this area based on the existing TransWorld in the future.A Regional Traffic Signal Coordination Control Method and System for Complex Traffic Control Environments, China: ZL 202110097004.6, 22 August 2022.