Currently, urbanization driven by global capital flows entails a main trend in many large cites in China, while global capital investment in small inland cities especially in western China is extremely scarce, where their globalization characters the powerful nationalization power and market activation. Dunhuang, a small inland city in western China, has transformed successfully from an agricultural county to an international tourist city, a platform for worldwide cultural communication, and a node city in the Belt and Road region because of its unique and brilliant resources: Mogao Grottoes and Dunhuangology. Therefore, this paper develops a conceptual framework of the multiple cooperative mechanisms and globalization path (MCMGP) of Dunhuang, elaborating the process of industrial transformation, urban globalization, and multiple cooperative mechanisms between government and market actors based on interviewing records and statistics. Findings show that the MCMGP features government-led intervention, resource orientation, and centralization that embodies the driver of state-owned enterprises (SOEs). Also, the MCM in Dunhuang’s globalization contains the mechanism of enrolment, mobilization and action, governance and global marketing, distributed in the two phases. Equally important, in response to the Belt and Road Initiative (BRI) and Silk Road (Dunhuang) International Cultural Expo (SRDICE) from the state, the city government has significantly reinvested and refined cultural tourism via governance mechanisms, carving out a key node city in the Silk Road and elevating an international tourist city. Environmentally, Dunhuang’s tourism internationalization enhances the process of the development of a sustainable shared mobility industry. Furthermore, its tourism development and social–ecology system maintain the synergistic relationships which international tourism promotes such as urban ecosystem and public welfare and in turn, social–ecological enhancement serve Dunhuang’s international tourism well. Practical implications of how Dunhuang’s experience may have lessons for others are discussed in China’s peculiar socialist market economy discourse. Since the 1970s, global capital flows, foreign direct investment of transnational corporations (TNCs), and the changes and shifts of global production networks have largely accelerated urban globalization development ,3. In geSince the 1980s, in-depth urban globalization has been inseparable from the broad support of governments. On the one hand, different types of multinational institutions with complex and diverse global political geographies have been triggered ,22,23,24After revisiting previous research ,11,12,17Dunhuang, a small inland city in western China has a UGP which could vividly shed light on the above argument. After over 40-years of urban globalization, Dunhuang has transformed from a traditional agricultural county to an international tourist city, a platform for world cultural exchanges, by which it successfully integrates into the globalization process. On the one hand, the unique resource that is Mogao Grottoes is a worldwide Buddhist art storehouse and Dunhuangology is a world cultural heritage tourist destination. On the other hand, it is actively in line with the national BRI and acted as the permanent venue of SRDICE, bridging countries involved in the BRI for cultural cooperation and communication. The local authorities have seized these opportunities and marketed Dunhuang as an international hub city on the BRI, which has profoundly triggered Dunhuang’s modernization and globalization. As a government-led organization path with a cultural engine and unique resource endowment, Dunhuang’s UGP could provide novel insight not only in China but also other countries. Specially, Dunhuang’s local experience could fertilize other cities in two ways: first, it heuristically notes how to internationalize local unique tourism resources, and secondly, shapes the city as an international tourism destination. Eventually, the city’s physical built environment, social-ecological system, public well-being, sustainable environmental awareness and action, service facilities and landscape, and greenery designs appear globalizing turn. More essentially, Dunhuang’s experience is the epitome of fully utilizing nationalization power and market mechanism. Therefore, we would mainly argue: In the context of marginal location and insufficient FDI, how could an initially enclosed market and economy break such path lock-ins and integrate into globalization in a small inland city in China? What kinds of cooperation mechanisms between government and market-related actors should be established? As well as to what extent tourism and social-ecology systems mutually impact and synergistically develop? Concisely, the study further validates and enriches the issue that the locals escalate urban transformation, social-ecology improvement, and globalization change via distinctive resources, and focuses more on the hybrid triggers of “government + SOE + market” under China’s special socialist market economic institution. Below, employing Dunhuang as an empirical study, we will attempt to build a conceptual framework of inland cities’ UGP in China. Then we seize it to expound the process and characteristics of Dunhuang’s globalization, as well as MCM under government intervention. Lastly, we concisely summarize the conclusion and discussions.Since the reform and opening-up policy in 1978, China’s transitional institutions and development levels have formed a zonal gradient strategy from the eastern coast to the northwest inland . A signiThere are three representative UGPs of western inland cities. (1) The specialty product trade and industrial internationalization. Natural resource-based cities in western China possess affluent mineral resources, rare metals and special agricultural and sideline products, developing, selling and expanding distinctive and resource-based products and gradually joining the global market via product international trade , such asWith the worldwide prevalence of neoliberalism since the mid-1980s, urban growth and globalization are increasingly dependent on various international capital forces and stakeholders . EspeciaThe essence of such unique UGP in western cities is manifested in the powerful intervention of government willpower or other public powers. Firstly, owing to the extreme shortage of foreign capitals and investment, the development of inland cities relies on the central governmental policy preference and innate resource endowment. Previously, in the support of “the Third-Front Movement” policy and “the development of the western region in China”, industrial systems of resource-based primary product processing industry and heavy industry have been formed . More imDunhuang, located on the largest oasis of the Dang and Shule Rivers and surrounded by the Gobi Desert, is a county-level city in the northwest Gansu Province, China. Its city prefecture covers seven towns and two villages, peculiarly, Shazhou town is the seat of the city government and is the political, economic and cultural center of Dunhuang . Before Notwithstanding Dunhuang does not possess a developed industrial foundation, it attracts a worldwide preoccupation due to its unique cultural and natural assets. In the sphere of human and historical landscapes, there are 265 cultural heritage sites in Dunhuang, three of which are World Cultural Heritage sites, the Mogao Grottoes, the Yumen Pass, and the site of the Xuanquanzhi Posthouse. Specifically, Mogao Grottoes is the largest- and richest-surviving Buddhist art holy site with mysteriously “Oriental” charm, bearing the most continuous historical Buddhism preservation worldwide. Besides, Yumen Pass and Yangguan Pass are strategic passes on the Silk Road from Dunhuang to the north and south of the ancient Western Regions, respectively. The site of the Xuanquanzhi Posthouse is the seat of the administrative institutions, postal system of Dunhuang during the Han Dynasty (94 BC) in China, where massive unearthed vestiges and remains are priceless materials for archaeologists to study the history of the Han Dynasty. The ancient Dunhuang city, also called a movie and television city, is designed and built by the Japanese imitating the ancient Shazhou City of the Song Dynasty in China, where the Sino-Japanese jointly shot the grand historical film “Dunhuang” in 1987. As for natural landscapes, Mingsha Mountain Crescent Spring is a rare desert spectacle in the world, it is commonsense that deserts and clear springs rarely coexist, thus, such a unique landform combination of mountains and springs has enhanced the irreplaceability of Dunhuang’s tourism resources. Moreover, Yardan National Geopark is the largest aeolian landform group in Asia, which is also called Demon Castle due to its breathtaking desert wind-eroded landscape. It is the setting for many film and television works and an important venue for off-road and auto rallies . In shorThe research data mainly include two parts: (1) the field survey data and in-depth interview data in Dunhuang. We conducted semi-structured interviews with respondents through an interview questionnaire, recorded in the form of audio, and on-site conservation notes, and finally we organized the recorded notes as the first-hand material. Specifically, respondents encompass officials and staffs of the city government and its related sectors , Dunhuang Tourism Board, Dunhuang Academy China, SRDICE Bureau, SRDICE’s International Conference and Exhibition Center, Management Committee of Scenic Spots, Dunhuang Cultural Tourism Group , international tourism agency, and local residents. (2) Statistical data and planning documents of Dunhuang as second-hand data, include Dunhuang Statistical Yearbook (2010~2019), Dunhuang National Economic and Social Development Statistical Bulletin, Dunhuang Academy China Yearbook (2005~2017), Dunhuang 13th Five-Year Plan, historical and cultural city protection planning documents.Primary data were acquired from 19-day incessant field trips in Dunhuang from 28 September 2020 to 15 October 2020, coupled with follow-up telephone interviews. The content encompassed interview outlines on Dunhuang’s globalizing mechanism and survey questionnaires on residents’ perception of Dunhuang’s globalization. Concretely, the interview outline contains the typical period of Dunhuang’s foreign exchanges, storylines, landmark events, distinctive performances, paths, mechanisms of Dunhuang’s globalization in different periods, and the motivation and experience of tourists visiting Dunhuang. The questionnaires on residents’ globalizing perception of Dunhuang employ 6 dimensions and 21 indicators: globalized cultural identity, city image, cultural exchange, transportation and communication, urban landscape and physical environment, and tourism uniqueness. In term of the structure of respondents, we were acquainted with the main participants in Dunhuang tourism construction and urban globalization, and then eventually determined our six respondent subjects, related government departments, Dunhuang Academy China, CTG (SOE), international travel agencies, local residents, and international tourists. During the process of investigation, two students formed group during the formal survey, one was responsible for the interview with the respondents, the other was responsible for audio recordings and taking notes of key information on site, then the recordings and notes were sorted into electronic texts according to a corresponding questionnaire number. Consequently, 52 written interviews, each taking half an hour to 1 h, and 346 valid questionnaires were obtained. Moreover, the author applied anonymous coding disposal later to protect the privacy of respondents. “####Y*” as coding form appears in the paper, the four #s represent month and day of the interview, Y is the code for respondents’ identity, * indicates respondents’ order number. Respondents’ identity is coded as below: A shows local residents, B represents staff of government and tourism-related departments, C specifies staff of Dunhuang Academy China, D expresses the commercial service operators, E is for tourists, and F indicates tourism developers. For example, “0931A1” means the first local resident interviewed on 31st, September.To date, Dunhuang’s industrial structure has emerged with significant transformation since Dunhuang developed tourism. As shown in Inbound tourists played a leading role to reinvigorate the tourism industry in Dunhuang. First, inbound tourists of Dunhuang are mainly from foreign countries such as Chinese Hong Kong, Macau, and Taiwan a. BrieflThe urban globalization of Dunhuang originates from tourism opening to the world and international communications of Dunhuang culture. Having witnessed its tourism development over the past 40 years, Dunhuang has developed and formed a sophisticated tourism market, which has been depicted clearly by four phases in its process of tourism development and urban globalization .Stage I: The booming phase of inbound tourists and tourism industry growth (1979~2000). Since China founded in 1949, Dunhuang was a traditional agricultural county. Later, Dunhuang was designated as one of the first tourism opening cities to the world. By the state. In fact, as early as the 1900s, the discovery of the Library Cave of Mogao Grottoes arose as a severe hit worldwide, after that, plenty of cultural relics, Dunhuang Manuscripts, and Documents of Mogao Grottoes were scattered to many western countries around the world, and the consequent preoccupation with Dunhuang surged due to Mogao Grottoes. Therefore, before the Dunhuang tourism opening to the world, Mogao Grottoes and Dunhuangology had been vastly expanded beyond their shores. Since inbound tourists were able to enter Dunhuang in 1979, Dunhuang has been flooded with spontaneous large-scale worldwide tourists who are eager to witness the rare Buddhist art treasure trove, and overriding arrivals emanated from Japan. As a scholar of Dunhuang Academy China  said: “what attracts most the surge of inbound tourists is Mogao Grottoes, due to its own unique brilliant historical continuity alongside over 1600 years of elaboration history, the massiveness of this culture is at the top in the world. Especially, Japanese have a special affection and attachment for Mogao Grottoes. Dunhuang is consider as their cultural homeland, and coming to Dunhuang is essential for their root-seeking tourism.” A tourist (1002E3) said: “grand statues, elegant apsaras, amazing murals, exquisitely arranged caisson ceilings of Mogao Grottoes, holy world of Buddhism, secular life, the hardships of ancient silk businessmen and the luxury of the Western Regions palaces a thousand years ago were all vividly visible in Mogao Grottoes, which shocked me a lot.” In addition, the UK’s BBC, Japan’s NHK TV, and China’s CCTV jointly filmed the documentary “Silk Road”, Dunhuang was one of the vital nodes, and the documentary contributed to a global sensation. The UNESCO listed Mogao Grottoes on the World Cultural Heritage List in 1987. The film “Dunhuang” co-produced by China and Japan premiered in 1988. These international events have greatly established and enhanced a global presence of Dunhuang.Localized reforms of institutions, industries, and related services are conducted the step-by-step urban globalization For example, to serve foreign guests well, the city government established the Foreign Affairs Office in 1979, with its branched China International Travel Agency, and Dunhuang Hotel, the three departments are jointly in charge of the reception and hospitality of foreign guests. An office director of Dunhuang Tourism Board (0928B2) said: “the tourism industry in Dunhuang was referred more as a diplomatic affair at that time, foreign tourists dominated the whole tourists, so the Dunhuang Tourism Board also evolved from the past Foreign Affairs Office.” As a local resident (1005A2) said: “with Dunhuang’s tourism opening to the world in 1980s, ever-increasing foreigners came here because of Mogao Grottoes and its Library Cave. We were lingering curious about foreigners. It was not until the mid 1980s that we often met foreigners, and we became gradually accustomed to them”.Stage II: The policy-driven development of tourism destination (2001~2008). Dunhuang experienced a peak period of foreign tourists in the 1980s~1990s. But Dunhuang’s infrastructure failed to meet tourists’ surge in demands at that time. Also, Suoyang City, Yumenguan Pass, and the Site of the Xuanquan Posthouse in Dunhuang were successfully nominated for the World Heritage Sites in 2006, plus Mogao Grottoes and the Ruins of Great Wall. Now there are five World Cultural Heritage Sites in Dunhuang to date. Subsequently, the city government proceeded with forming the “Tourism Nurturing the City” strategy. Under the strategy of tourism-based urban development, the city government gradually envisioned a blueprint strategy of “Tourism Nurturing City”, and then it laid stress on Dunhuang’s tourism, which became the invigorate pillar industry.Since 2001, the government has released various types of tourism development plans as a buffer to sustain Dunhuang’s tourism, vigorously building tourism-supporting facilities, strengthening tourism management, and encouraging local residents to participate in the tourism market. (1) Transportation system: The government upgrades and updates the transportation systems, accommodation systems, and the related tourism industry management. The government has expanded the capacity of Dunhuang Airport three times, Dunhuang International Airport was formally opened with international airlines in 2007; the Dunhuang Railway and other roads from the urban area to various tourist attractions were large-built and opened to traffic. (2) Accommodation: in addition to attracting foreign investment to build star hotels in Dunhuang, the city government encouraged local residents to build pubs or inns. (3) Tourism industry management: the city government established the Dunhuang Tourism Management Committee that was in charge of the management, supervision and evaluation of Dunhuang’s tourism market. (4) The makeover of cityscape and environment: the mayor S made abundant reformations during his tenure, such as the renovation of the cityscape and environment, the makeover of the Danghe River Landscape Line, the exploitation of tourism projects, and etc. A government official  said: “Dunhuang’s urban environment was deadly poor previously. Mayor S considered that such environment was incompatible with an tourist city image. Dunhuang was deemed a world-famous tourist resort, and antiseptic city environment and civilized behavior of the populace should be developed as a mirror of its tourism reputation. So he carried out voluntary cleaning exercise of urban garbage, the sewage treatment and Danghe river landscape construction, and appealed to the public improving tourism service awareness”. Another local resident (1006A5) said: “There existed a key time node in 2005~2006, cityscape and environment appeared dramatic amelioration. Dunhuang was not always a tourism city that only relies on Mogao Grottoes to attract tourists since then. Mayor S said that our livelihood were directly linked to Dunhuang tourism, only when we did well in urban sanitation and landscape can Dunhuang attract ever-increasing tourist arrivals. Hence, everyone was enthusiasm and took care of the cityscape as a habit”.Stage III: Centralized organization and operation of the tourism market (2009~2015). The city government attempted to reorganize and optimize Dunhuang’s tourism market, the core of which is centralized governance of city-owned tourism resources. Detailed action was launched as follow: (1) The city government has devised various development and protection plans, in addition to master plans of the Silk Road Economic Belt, aiming to strengthen the conservation of world cultural heritages and the construction of urban landscape. (2) The germination stage of international tourism festivals in Dunhuang City government has six-times hosted the Dunhuang Apsaras International Cultural Tourism Festivals since 2000. In 2013, the United Nations World Tourism Organization hosted the Silk Road International Tourism Festival and International Conference in Dunhuang; the city government held the Dunhuang International Music Festival, International Cultural Relics Expo, and International Urban Sculpture Exhibition in 2014~2015. (3) The construction stage of Dunhuang’s Smart Tourism. Dunhuang was listed as a smart city pilot by the State Council in 2013, which largely prompted the construction of smart tourist attractions and the digital protection mode in Dunhuang. (4) The stage of centralized operation and governance of city-owned tourism resources. The city government successively established operational companies for each tourist attraction with smart management systems since 2014. Recently, the government established a SOE, Dunhuang Cultural Tourism Group (CTG), a core carrier about centralized operation of city government. A deputy director  said: “The city government integrated other tourism resources except Mogao Grottoes, and seized the SOE mode to collectively govern Dunhuang tourism. In practice, the mode has markedly altered previous Dunhuang tourism market dominated by folk spontaneous behaviors, since then the tourism market has been stepping into a standardized and sophisticated stage. Moreover, the reason why the government set up CTG to start centralized pilot is that the government aim to establish a market-oriented tourism system”.Stage IV: International mega-event marketing and government-driven cultural exchange (2016~present). In 2013, Chairman Xi Jinping of PRC laid out “BRI”, aiming to promote international cooperation by joint actions between China and the “Belt-and-Road” regions. In response to this national strategy, the city government began to carve out a specialized niche as an international tourist city and a hub of on the Silk Road by the world-renowned Mogao Grottoes and Dunhuangology. With the approval of the state, SRDICE has been held in Dunhuang annually since 2016, and Dunhuang became the permanent conference site. In 2016, six foreign state leaders and former state leaders attended the Open Ceremony of SRDICE, and 95 delegations from 85 countries, five international organizations or NGOs, 66 foreign institutions, 434 foreign guests and 1700 Chinese guests participated. Finally, the official “Dunhuang Declaration”, a programmatic file with high-level intergovernmental cultural dialogue, was jointly issued. In this period, the government-led preparatory work markedly boosted the globalization of Dunhuang: (1) The city government expanded Dunhuang Airport and multiple international air routes were added. (2) The renovation and upgrading of Dunhuang international or star-rated hotels were accelerated, and more developers were attracted to invest high-end hotels. There are 243 newly built hotels in Dunhuang, which is much higher than the total number of the previous stages. (3) More significant international exhibition venues and related facilities of SRDICE were conducted. Specifically, the city government built the Silk Road International Convention and Exhibition Center after the regional government released the planning scheme in 2013.Benefits in the urban social-ecology system induced by tourism are assessed as illustrated in The related actors of the city government of Dunhuang are the Dunhuang Academy China, tourists, local populace, international travel agencies, and tourism developers (CTG). The details of related actors are: (1) The city government: Previously, Dunhuang was predominantly equipped with an agricultural economy but the harvest has become stagnant. In response to the state’s appeal of tourism opening to the world, the city government establishes the Dunhuang’s transformation route with tourism as its leading industry. Specifically, in order to bolster struggling urban economies and melt Dunhuang into a globalization process, the city government utilizes Mogao Grottoes and other tourism resources to expand its international tourism market, formulates tourism strategies and plans, renovates urban environment, builds infrastructure, and implements national policies. (2) The Dunhuang Academy China: In reaction to state government’s conservation strategy for Mogao Grottoes, The Dunhuang Academy China was established and takes responsibility of protecting, studying, promoting, and managing the World Cultural Heritage Mogao Grottoes, with its affiliated West Thousand Buddha Grottoes and Yulin Grottoes. The techniques of repairing the ravages, permanent preservation and cultural transmission are the primary preoccupations. (3) International travel agencies: limited by its limited urban size, local travel agencies are clustered, and rather isolated conditions of transportation and communication for themselves and foreign tourists. (4) The CTG: its main task is to pool city-owned resources for centralized management and operation, and advance smart tourism and cultural tourism projects. (5) Local residents: There exists recurrent droughts, sandstorms, and water shortage in the wake of substantially low agricultural land utilization. Peculiarly, local cottons threatened by long-staple cotton in Xinjiang province of China have encountered unsalable dilemma since 1990s, which largely affected residents’ livelihood due to a flagging agriculture sector. Fortunately, they have recognized that they could improve their income and expand employment opportunities by the participation in the promising tourism industry. (6) Tourists: as for global scholars and academic groups with strong interests in Dunhuangology, Buddhist culture, grotto art, architecture, music, etc., there are few destinations that have been constantly elaborated for 1600 years like Mogao Grottoes.The globalizing process of Dunhuang indicates that its urban transformation and globalization can be divided into two phases, “Construction and Operation”. (1) The World cultural heritage destination construction (1979~2008): Dunhuang has been converted into a typical World Heritage Site, and a worldwide tourist city with escalating infrastructure. (2) The centralized operation and global city marketing (2009~present): drawing on BRI and the international platform of SRDICE, the city government spreads Dunhuang culture worldwide and carves out an international cultural tourist city. More details are as follows .Four types of enrolment can be summarized in the formation of MCM. (1) Administrative enrollment: The incentives for the world cultural heritage destination construction of Dunhuang were initiated by the central government, which enrolled the local government of Dunhuang to implement all aspects of tourism deployment. Additionally, Dunhuang Academy China preserves and nurtures cultural heritages of Mogao Grottoes since it was founded in 1944. Ever since Chairman Deng Xiaoping visited Dunhuang Academy China and Mogao Grottoes in 1981 and the successive national leaders all came here for inspections. Chairman Deng Xiaoping said: “The conservation of Mogao Grottoes is a pressing matter, Dunhuang’s cultural relics are world-famous and the priceless treasure, which must be protected by all means”. Chairman Xi Jinping said: “We must well preserve our national quintessence and make Mogao Grottoes an excellent model for heritage conservation (cited by the People’s Daily Overseas Edition)”. Under the instructions of the successive national leaders and their conservation policy, Dunhuang’s heritage conservation has been translated into tangible results through unremitting efforts of the Dunhuang Academy staff led by successive deans Chang Shuhong, Duan Wenjie and Fan Jinshi. (2) Environmental enrollment: since 1982, in order to build a world cultural heritage destination equipped with pleasing tourism infrastructure and physical environment, city government has enrolled every town government to add “soft touch” and “refinement” to urban landscape. (3) Image marketing: to enhance Dunhuang’s international presence, the city government enrolled related actors to actively participate in the tourism industry and to market Dunhuang tourism by online and actual means. (4) Unique resource enrollment. Dunhuang’s well-endowed world cultural heritages and miraculous natural landscapes have attracted the BBC, NHK, and CCTV to film documentaries, movies, and TV series. Massive domestic and abroad scholars and teams interested in Dunhuangology have studied and written scholarly monographs, papers, novels and poems.Three types of mobilization mechanisms were conducted. (1) Incentives and financial supports: The city government issued relevant policies to encourage other actors to supply tourism services. First, the city government encouraged residents in urban areas and near scenic spots to build hotels, inns, or pubs . Aside f(3) International communication. Firstly, the city government takes communication of Dunhuang tourism seriously, through a combination of physical media, promotion meetings in various cities and international sister cities, and virtual media such as marketing films, global social media , and press coverage in addition to government websites, which have greatly enhanced and expanded the city marketing power. Most notably, Dunhuang Academy China was still the dominant actor transmitting Dunhuang culture to the world. Detailed approaches are summarized: (a) International cooperation projects : Dunhuang Academy China conducts joint studies in Japan, as well as conservation postgraduate exchange projects and technical collaborations with University of Illinois, University of Oxford, University of London, University of Nottingham, Osaka University. As for cave digitization, Japanese government funded the construction of the Dunhuang Caves Conservation and Research Exhibition Centre in 1994; Dunhuang Academy formally began digital study of Mogao Grottoes s in 1998 in collaboration with the Mellon Foundation of the USA, followed by the International Dunhuang Project (IDP) with the British Library about international standard digitization work of Dunhuang scriptures and cultural relics. (b) International exhibitions: Since the mid-1940s, Dunhuang Academy China on its own or jointly with international institutions has been exhibiting globally in 37 cities worldwide, involving murals, cultural relics, scripts, and cultural products. (c) International academic exchange and hospitality: It mainly includes overseas visits and international conferences participated by researchers of Dunhuang Academy, international conferences and forums and foreign scholars’ lectures at Dunhuang Academy, and the hospitality of foreign official guests, national delegations, international organizations, academic teams, and scholars. (d) Digital Dunhuang and International website marketing: For decades, Dunhuang Academy collaborated with many domestic and abroad research institutions to preserve the precious materials of Dunhuang Caves using computer digital technology. Moreover, Dunhuang Academy set up its own global website and digital Dunhuang website, making a significant contribution to the promotion of Dunhuang culture.In this phrase appears the changeable intentions of key actors and governance mechanisms . After eThe establishment of Dunhuang CTG is the milestone of governance mechanism reform. Since 2013, the city government integrated ICT infrastructure, urban management, transportation planning, and other tourism assets into the Dunhuang smart tourism system based on Smart Tourism Co., Ltd. as a pilot item. A staff of the human resources Department of CTG said (0931F2): “Recently, tourists almost search a public WiFi signal called “zhihuilvyou” during their travels in Dunhuang thanks to government’s vigorous efforts to project smart cities construction, which greatly advances the online experience of tourists”. On this premise, the city government established a new SOE and CTG, and started a market-oriented operation mode of tourism resources. Firstly, the mode has brought reforms to Dunhuang’s international travel agencies. Erstwhile enterprises like Dunhuang CITS have gradually faded, whereas emerging “Internet +” international travel agencies represented by Chenguang Smart Tourism have vastly appeared in Dunhuang. Secondly, CTG has a stringent and meticulous supervision on the entire tourism market, i.e., it distributes camel numbers to the camel keepers in Yueyaquan village and Mingshan village, and establishes electronic archives of camels according to the number; it renovates and rebuilds retail and stall outlets of the Shazhou Night Market, and then gives shopkeepers respective numbers for smart regulation; it projects plenty of scenic spot activities, such as a car rally in Yandan, sand skiing festival, desert camping, Gobi hiking, motorcycle surfing, etc.Cultural tourism governance is introduced in wake of SRDICE. Currently, the site of SRDICE is permanently settled in Dunhuang, which could offer a superior international communication springboard. In fact, it is emblematic of new departure for Dunhuang’s cultural tourism where distinctive cityscape and emerging industries vastly emerge. (a) Refashioning urban landscape: The city government always explores how to commercialize Dunhuang culture and repackage cultural landscapes by tapping new cultural visual elements and narratives into urban spaces. A staff of the Development and Reform Commission in the city government (1009B5) said: “since first SRDICE, the city government attempts to infuse a sense of historicity in the cityscape and built environment drawing upon Dunhuang culture. In a similar vein, urban landscape like floor tiles, street lights, information plaques and signages, guardrails, seats, are embedded in cultural elements of Mogao Grottoes including flying apsaras, rebound pipa, caisson ceiling, nine-color deer, lotusbricks, and the city brims over with cultural ambience”. (b) Emerging cultural industries. First, Dunhuang’s cultural and innovation industry begun to flourish since SRDICE. The CTG holds Dunhuang international design week and collects design schemes incorporating Dunhuang elements from global designers during SRDICE, then it purchases the IP rights and puts them into further production. Afterwards, the artefacts will have been sold at the physical and online stores. Also, the Center of Silk Arts Fan Yanyan are set in Dunhuang museum. The brands are collected by lots of international senior politicians and celebrities, which bridges culture communication worldwide . Second,In the construction phase of the world cultural heritage destination, the city government and Dunhuang Academy China were key actors. The government acted as a guide for the local tourism market and provided various types of offerings for other actors. Dunhuang Academy China carried out the restoration, conservation research, and cultural promotion of Dunhuang Grottoes. Then, in the second phase, the city government repositioned itself and then formed Dunhuang CTG, where city government has completed centralized governance by resource reorganization, culture enhancement and infrastructure support. Afterwards, with the emergence of BRI and SRDICE, the city government officially started globally marketing and repackaging local culture. A staff of the SRDICE Bureau  stated, “Dunhuang’s tourism has started since the 1980s, nonetheless, its tourism always remains at the level of spontaneous non-governmental communications initially. It has only been since the SRDICE that single model was altered. Specifically, the concept of human Dunhuang and world Dunhuang is formally laid out in the form of global intergovernmental dialogues. Later, an official, multi-participant international cultural communication has been formed, which further magnifies global influence of Dunhuang”.Generally, the national government is responsible for macro-control strategic deployment, regional government forms a connecting link between centrals and locals, acting as a coordinator/mediator; local government is the direct operator and executor of tourism activation. (1) The will of national government focuses on three aspects locating the main direction of Dunhuang’s development. Most notably, it prioritized the conservation of Mogao Grottoes, the inheritance and international promotion of Dunhuangology fostering China’s Dunhuangology research into international frontier. Later, it allowed that Mogao Grottoes was accessible to foreign tourists and designed Dunhuang’s trajectory of the international tourism change since China’s reform policy in 1978. Finally, grounded on BRI, it launched the scheme of holding SRDICE annually with Dunhuang acting as the permanent venue, bridging the Belt and Road region. (2) The regional government is more responsive in configuration to the central government’s policy. Initially, it positioned Dunhuang Tourism as the core of the whole regional tourism and provided policy initiatives and software and hardware facilities. Then, it formulated Dunhuang’s all-for-one tourism development plan and historical and cultural city conservation plan. More noteworthily, it is the host unit of SRDICE and initiates SRDICE Bureau in charge of coordinating and operating the international event. (3) In addition to responsive actions to its superior government, local government also carried out extra autonomous activation. To start with, it supplemented alot of tourism-related departments, and cooperated or assisted with various works of the Dunhuang Academy China. Moreover, it energetically advanced the cityscape, physical environment, the residents’ tourism hospitality and etiquette, and etc. More importantly, the local government pooled city-owned resources except the Mogao Grottoes, and initiated CTG, whose duty includes projected global smart tourism, city marketing and social media promotion.Compared with other SOEs in the traditional China’s discourse, like resource-based SOEs  and SOEs of pillar industry for national economy development , CTG has more market vitality and flexibility. Likewise, CTG is still transformed from the initial government department, but more innovative business modes and IT technology are applied. In particular, CTG grew out of Dunhuang Smart Tourism Company whose core business consisted in Internet, cloud computing, IoT, big data, and Dunhuang tourism promotion on social media and tourism-related apps . Thus, the local government centralizes and activates state-owned resources based on a more innovative and vigorous Internet company, and adopts a novel operating model of SOE that combines online and offline, belonging to a relatively successful local experience of national tourism operation that also inspires some traditional tourist cities or SOEs.The main conclusions of the work can be reached: (1) essentially, the UGP of inland cities is characterized by the drivers of more government-led centralization and intervention, innate trigger of resources, and centralization by SOEs. (2) Dunhuang’s UGP evolves from four stages, the development clue is that Dunhuang’s world cultural heritage tourism is initially driven by global visits and international hospitality. Subsequently, the international tourism boom promotes notable urban transformation and social-ecology renewal. Ultimately its cultural stock repackaging feedback afresh urban tourism and marketing. (3) As an environmental reflection during globalization, it is pointed out that tourism is not an isolated activity but it interacts with local social-ecology systems, forming synergistically supportive relations with environmental health and public well-being. Meanwhile, ameliorated social-ecology systems could well serve and foster international tourism. (4) The MCMGP of Dunhuang entails enrollment mechanism, mobilization and action mechanism, governance mechanism, and global city marketing mechanism. These mechanisms distribute in two phases: world cultural heritage destination construction and centralized operation and global marketing. In the former phase, the global presence of Mogao Grottoes and Dunhuang culture attracts numerous inbound tourists. City government and Dunhuang Academy China, as key actors, mobilize related actors bonding common interest via various enrollment methods, and put Dunhuang’s tourism “hardware” in place drawing upon action mechanisms. And (5) in the latter phase, the city government organized governance mechanisms, and established the CTG to project smart tourism and conduct centralized operation by pooling city-owned resources. In response to BRI and SRDICD, city government vigorously nurtured cultural tourism via marketing mechanism, and Dunhuang is marketed as a node city on Silk Road and an international tourism city seizing the marketing tagline “Human Dunhuang, World Dunhuang”. The city government acted as a key actor, which is a typical governance process from decentralization to centralization. Furthermore, Dunhuang tourism has also shifted from non-governmental folk or academic communications to an intergovernmental dialogue form.Most notably, Dunhuang’s indigenous practice actually exists such as relatedness and enlightenment compared to other practices in the world. (1) International tourism is supportive to urban sustainable development transformation associated with enhancement of residents’ sustainable livelihoods . Nunkoo There still exist some limitations of this work. (1) The interacted relations and changes of international tourism and social-ecological sustainability has not been explored in detail in this study, from quantitative measurement to qualitative elaboration. (2) The research lacks in-depth analysis to explore the social equity issues triggered by the development of urban globalization, summarily comprising social justice, social, and social welfare. (3) The eloquent conceptualization and theorization of Dunhuang’s open innovation business model is not well summarized within discourse of China’s socialist political-economic specificity. For the future, additional studies will be needed to address the above gaps. (1) Environmentally, the author plans to supplement the well-rounded consideration on sustainable development. Of vital concern is the interacting relationships, trigger process, evolutionary dynamics amongst international tourism, and social and environmental sustainability through an empirical insight into how sustainable livelihood and ecology feedback positively and negatively to urban globalized transformation via international tourism. (2) Socially, some extensions to social responsibility and diversity triggered by tourism warrant further observation, with a tight focus on the structural change and differentiation of social classes, enhanced participation of people in all walks of life, and then emergence of social diversity. During the process, we should highlight the role of enterprises by which to undertake social responsibility and improve social welfare not confining to the role of government. (3) Creatively, as for a shared innovative business mode, we should strengthen comparative analysis of Dunhuang’s smart tourism and similar practices implemented in the world. Notably, the study necessitates refining the novelty of Dunhuang’s smart tourism model, highlighting the innovation and contribution of Dunhuang’s smart tourism to the shared business model. Moreover, it is worth examining residents’ behavioral mobility and travel based on the quantification of big data sharing.


Increasingly medical students pursue medical education abroad. Graduates from International Medical Programs (IMPs) practice globally, yet how to prepare students for an unknown international environment is complex. Following IMP graduates throughout their early careers, this study offers insights into gaps in current undergraduate education.In this international, longitudinal, mixed-methods study, 188 graduates from seven IMPs completed baseline surveys on career choice and job preparedness. Forty-two participants completed follow-up until three years after graduation. Nine graduates participated in semi-structured interviews on individual experiences and the evolution of their perspectives. The multiphase, sequential design allowed data collected at baseline to inform further data collection instruments.Two typical student profiles emerged. The first depicts a student who, despite the challenges of studying abroad, pursues a medical degree ‘anyhow’, with a common aim of practicing in their home country. The other deliberately selects an IMP while envisaging an international career. Two years after graduation, the majority (> 70%) of our participants were practicing in a country other than their country of training. They reported challenges around licensing, the job application process and health system familiarization. Participants’ experiences point towards potential curriculum adaptations to facilitate cross-border transitions, including career guidance, networking and entrance exam preparation.IMP graduates lack support in practical aspects of career orientation and international exposure. Most IMPs essentially prepare their graduates for a career elsewhere. Gaps and challenges that IMP graduates experience in this cross-border career transition entail a responsibility for preparation and guidance that is currently lacking in IMP curricula.The online version of this article (10.1007/s40037-022-00721-z) contains supplementary material, which is available to authorized users. In the past decade, increasing numbers of students have pursued medical education outside their home country . EuropeaIMPs are a response to increasing global standardization of medical school accreditation , 7 and rThis transition, whether to a graduate’s home country or onwards to a third country, is not without challenges. Scholarly work on International Medical Graduates , highlights the adaptation difficulties these graduates face when entering a new healthcare context, especially around language, intercultural communication and health system familiarization –11. The Against this background, the challenges of curriculum design for IMPs become apparent. It is questionable whether a merely translated local curriculum best meets the specific needs of the diverse student group in IMPs . Yet, idThe IMP context thus offers a unique opportunity to fill the gap between earlier research in the post-graduate IMG context and undergraduate curriculum internationalization. Studying the experiences of IMP graduates can give valuable insights in career preparedness and highlight gaps in their current undergraduate education. Previous research has shown that following these experiences longitudinally through their early career gives the most reliable information on career choice and curriculum evaluation , 19. BetThis longitudinal mixed-method study aimed to explore the alignment of IMPs to early career requirements as experienced by recent IMP graduates. The research questions were: (1) What are the career choices  made by IMP graduates and what are the motivations behind these choices? (2) What  job requirements do they encounter? (3) How do they evaluate the IMP curriculum’s success in preparing them for the job market?We conducted a longitudinal mixed-methods study, employing surveys and semi-structured interviews at four data collection moments spanning 2017–2020. The study takes a pragmatic approach to provide a more complete understanding of the research problem from multiple perspectives  test” . Studying medicine was hard work, and doing so in an unfamiliar country in his second language made it even more challenging. After six years of perseverance he graduated and achieved his goal of becoming a doctor.Anthony moved back to his home country, hoping to find a junior doctor position. Getting his license was not as easy as expected, though. His foreign qualifications were not easily transferred and he had to take additional exams. Job applications were tough, as future employers were unconvinced of the quality of this unfamiliar international education. He felt his “chances of getting into super competitive residencies afterwards [were] considerably lower”  because of having studied in the IMP.At last, he found a job in a hospital near his hometown. The first year came with many new challenges, as is true for any young doctor—however, Anthony felt disadvantaged because he had less clinical experience than his peers who had studied medicine in X and felt unfamiliar with the healthcare system.[The IMP] was a lot of theory, so I really got the theory part but yeah (…) We do meet patients but it’s not like, it’s not the same as when you work by yourself as a doctor. (…) I mean I can only compare myself to the doctors I have met now when I work and I feel like the doctors that are educated [locally], they have more practical skills. He does not regret his choice though, and with the years his confidence has grown. Two years after graduation, he feels a part of the X healthcare system and having studied abroad feels like an adventure long ago, nice yet tough, that ultimately helped him achieve his dream.Isabel always dreamed of becoming a doctor. She grew up in country W, with a strong interest in travelling. She could picture herself practicing abroad. When learning about “International Medical Programs” she was immediately interested. This sounded like the ideal combination of medical education with studying in a foreign language and the additional benefit of meeting people from all over the world.Isabel explored different IMP options in both her home country and abroad, and chose one in country Z, because she “want[ed] to have a whole new experience and develop [her]self in a new environment” .Studying medicine was hard work, and the student diversity indeed offered many options for intercultural learning. She graduated with many options in her mind. A career in a lower income country? Moving back to W? Or maybe staying in Z—as she had learned to appreciate the country, the language and the people.I always thought I would end up somewhere in South America (…) and then Tanzania happened so Africa kind of got me. And I’m now planning on visiting some more places. Could be anywhere actually. Isabel felt the IMP was a strong asset on her CV. However, logistic challenges eventually limited her options. It was difficult to determine exactly what was needed to get a medical license in other countries, and it was costly and time consuming to prepare all exams and paperwork. Eventually, she moved back to W for specialty training, with all the additional experiences in her pocket. The first months were challenging, for sure, catching up with the local healthcare system and brushing up on her mother tongue.I was super worried in the beginning that (…) I would be lost and everything. But in the end, it didn’t [turn out that way], like the first weeks of course were hard, but they were super nice and helped me to learn. A few years into her specialty program, Isabel speaks fondly of her IMP experience and, sometimes, still dreams about future practice abroad.Analysing the participants’ experienced job requirements and their evaluation of the IMP curriculum’s success in preparing them for the job market, we identified two sets of curriculum suggestions for IMPs: specific international knowledge and skills, and guidance around international career preparation.“On a scale from 1–10, how well do you think your IMP has prepared you for your career?”  Language barriers prevented me from gaining enough knowledge about how to communicate with the patient and be comfortable with my role as a doctor. I feel completely unprepared and I think will end up spending the first months of my career in fear. The most frequently discussed issues were clinical exposure and language. In some institutions, graduates felt they had little clinical experience overall, and many elaborated on the quality of clinical education during rotations heavily depending on patient interaction. Graduates agreed it was crucial to learn the local language in the pre-clinical years, as was common in some but not all of the IMPs in this study.We were particularly interested in international and intercultural competencies graduates needed in their early careers. However, these questions did not prompt elaborate responses in the survey nor interviews. Contrary to our expectations, a small minority  of respondents, like both Isabel and Anthony, crossed borders directly after graduation to either their home country or a new destination. Two years later, this number had increased to 73% and essentially only those native to the study country remained  that could be very fruitful” . Isabel also suggested inviting international speakers from a broad range of countries and specialties to offer inspiration and insight in international careers.Anthony always knew that he would move back to his home country. He thought the IMP could have better supported his preparation for remigration, for example, by allowing curricular time to prepare for his licensing exam. Ideally, the teaching staff would have been available to assist in this process.I have seen [IMPs] that help their students by building up their CVs with international courses (…) or even motivate and help their students to do the USMLE exams. In general, these colleges also prepare their students for what’s after their graduation internationally. Anthony also wished he’d had the opportunity to do placements in his home country. This would not only have helped him in career orientation, but also in networking to increase his success rate in job applications.The schools should probably ramp-up their effort and their support for people getting electives and to encourage it because if people are going to end up in [countries], they need to train there and have a chance to acclimate themselves before they even apply. In summary, graduates did not report a lack of specific academic content, but their experiences mainly point towards curriculum adaptation on support levels and international transition guidance.Following IMP graduates from seven different universities into their early international careers, we identified two typical student profiles and a need for better international transition guidance.The identification of these two profiles in part aligns with our earlier work around IMPs. In three different institutions, we studied curricula and interviewed teachers about their curriculum design experiences . We founSome challenges that our participants experienced during the transition into their early career match those of any new doctor shortly after graduation. For example, the experienced lack of clinical skills and sudden high responsibility are commonly reported , 27. FurOur study also contributes to our understanding of curriculum internationalization. Defined as “incorporating intercultural, international and global dimensions into higher education curricula”, this process aims to better prepare university graduates for a globalized, interconnected world . PreviouThis study is, to our knowledge, unique in the diversity of both institutions and participants, its mixed-methods approach and three-year longitudinal follow-up. The study limitations are inherent to this design: organizing recruitment through different local procedures was challenging with a relatively low response rate as a result. Also, as with many longitudinal studies, the loss to follow-up, especially between the first and second data collection point, was substantial. A self-selection bias, leading to a sample of participants, particularly among the interview candidates, who share a more positive perspective on IMPs, is plausible. We therefore purposely monitored the more critical and deviant voices throughout the follow-up and analysis. The authors are all from one of the participating institutions and therefore may have missed certain nuances of the other institutional contexts.IMP graduates generally regard their curriculum content effective in terms of career preparation. However, they miss support in practical aspects of international career orientation and preparation. Most IMPs essentially prepare their graduates for a career elsewhere. This entails a responsibility for cross-border transition guidance that is currently lacking.Besides posing challenges to curriculum design, globalization offers a range of opportunities that medical schools with and without IMPs insufficiently embrace. Sharing international graduates’ stories, for example, through strong alumni networks, is only one approach. There is a world to win.Annex A—Baseline QuestionnaireAnnex B—Follow-up QuestionnaireAnnex C—Interview guide T1Annex D—Interview guide T2&3


Pharmaceutical excipients are compounds or substances other than API which are added to a dosage form, these excipients basically act as carriers, binders, bulk forming agents, colorants, and flavouring agents, and few excipients are even used to enhance the activity of active pharmaceutical ingredient (API) and various more properties. However, despite of these properties, there are problems with the synthetic excipients such as the possibility of causing toxicity, inflammation, autoimmune responses, lack of intrinsic bioactivity and biocompatibility, expensive procedures for synthesis, and water solubility. However, starch as an excipient can overcome all these problems in one go. It is inexpensive, there is no toxicity or immune response, and it is biocompatible in nature. It is very less used as an excipient because of its high digestibility and swelling index, high glycemic index, paste clarity, film-forming property, crystalline properties, etc. All these properties of starch can be altered by a few modification processes such as physical modification, genetic modification, and chemical modification, which can be used to reduce its digestibility and glycemic index of starch, improve its film-forming properties, and increase its paste clarity. Changes in some of the molecular bonds which improve its properties such as binding, crystalline structure, and retrogradation make starch perfect to be used as a pharmaceutical excipient. This research work provides the structural modifications of native starch which can be applicable in advanced drug delivery. The major contributions of the paper are advances in the modification of native starch molecules such as physically, chemically, enzymatically, and genetically traditional crop modification to yield a novel molecule with significant potential for use in the pharmaceutical industry for targeted drug delivery systems. Starch has been utilised in everyday life for centuries. Egyptians generally used cooked flour of various cereal pastes which was diluted with vinegar to prepare cement papyrus strips, although the early Chinese public covered the papers with starch which had less viscosity when gelatinized to avoid ink permeation. Carbohydrate chemists began synthesising several starch compounds in the 1930s, considerably expanding starch's utility. Starches are essential carbohydrates which are included in our nutritional intake and come from a variety of environmental sources which can be listed as such as rice, wheat, potato, maize and wheat, potato, rice, maize, and tropical plants. They have a wide variety of qualities that help to obtain the preferred quality of food products. Due to the limitations of raw starch obtained directly from natural sources, during processing, some of its characteristics being resistance to high temperature, viscosity, and thermal disintegration, the food industries have a preference for starches with superior behavioural qualities [Starches are carbohydrates composed of primarily of two components called amylopectin and amylose. This biodegradable and nontoxic biopolymer is abundant in nature and creates consistent pastes and gels when heated in the presence of adequate water. As a result, starch is widely considered as an industrial ingredient in large quantities in a wide range of industries including chemicals, petrochemicals, pharmaceuticals, bioethanol, food, feed, paper, cloth, laundry finishing, construction resources, and other decomposable products .Free fatty acids and lipids present in the form of phospholipids in starch  and tendIn the past decades, to enhance patient amenability, biocompatibility, and effectiveness, more importance has been given to the effects of excipients on formulation and to the decrease in the use of synthetic/chemical grade excipients in pharmaceutical formulations .Excipients have been proven in studies to change the rate at which the drugs are released from the formulations, hence changing the system's efficiency and the active pharmaceutical ingredients absorption. As a result, there is a growing trend in the direction of use of naturally obtained excipients, sometimes known as “herbal excipients” . The extInappropriately, starches have limited functionality in their natural state, which can make them difficult to use. The temperature of gelatinization, digestibility, rheological properties, crystalline quality, different amounts of water absorbed at different temperatures, pasting capability, and strength of the gel are only a few of the properties that each starch source has. Due to the paucity of economical sources, modified starches have been frequently prepared and used to improve quality and overcome various limitations of native starches, henceforth broadening their use in industry. Modification methods can alter a variety of features including gelatinization, swelling, solubility, pasting and retrogradation quality, digestibility, and rheological properties, among others . As a reChemical alteration procedures are most commonly carried out in industry because they are efficient in cost and simple to use. The three accessible -OH functional groups    of the mThe weak associated interactions of starch can indicate its disintegrating ability , which iAs a result, this paper examines the different processes to alter the various properties of the native starch. From the plant sources, native starch with minimal treatment was obtained . Starch In the food industries, physical changes are applied since they do not require any chemical entity for reaction processes. Several new technologies have emerged in the physical modification of starch. Deep freezing, osmotic pressure treatment, and dry heating are few of the latest physical alterations that have been researched in the recent decade . It doesMiller and Huber  studied The changes in the molecular structure of starch samples have been studied through FT-IR, and X-ray diffraction results are shown in Figures Pukkahuta et al. studied through SEM results  that theHydrolysing enzymes have been widely used in enzymatic modifications . The disHydrolytic enzymes, also known as hydrolases, break different groups of biomolecules such as esters, glycosides, and peptides. They break down lipids, nucleic acids, proteins, carbohydrate, and fat molecules into their simplest units . The proAs per Li et al., native rice starch grains are polyhedral, angular, and irregular, and the surfaces are smooth with no cracks as displayed in αGT [Jiang et al. have found the alteration in the rheological properties of normal starch and enzymatically modified starch as shown in αGT .The alteration in genetic material of the plant or biotechnological alteration of plant DNA is referred to as genetic modifications. The enzymes responsible for the production of starch are targeted by transgenic technology; thus, it is considered a genetic alteration technique which can also be done through traditional plant breeding techniques or biotechnology . Plant bPlants generate a range of proteins, including mammalian antibodies, blood substitutes, vaccines, and some other therapeutic substances using gene editing, which has led to a renaissance of interest in getting novel pharmaceutical molecules from botanical extracts . ForeignThe traditional methods of modification of the plant such as selective breeding and cross-breeding are one of the processes in which plant breeding is used to selectively develop a particular phenotypic trait by selecting which male and females will reproduce and have offspring together.It is basically a method in which authorized experts copy a particular gene with a look for a trait from one plant and put it into the other plant in which the desired characteristics are incorporated, and it builds the scientific advantages through DNA technology.Genome edition is a novel approach that allows some researchers to generate new crop types in a more precise and targeted manner. The use of a genome editing tool makes modifications easy and efficient that were previously possible through traditional breeding .It is done by attaching a functional group in to the molecular structure of starch in its natural state resulting in specific physicochemical properties for the starch molecule. These alterations influence the retro gradation, pasting ability, proximal composition, and gelatinization of unmodified starch granules . At variThe starch is recyclable and the existence of particular functional groups and the macroscopic structure of starch are all factors that influence its sensitivity towards modification. Furthermore, regarding chemical modifications subjected to the position of -OH group and alpha-1, 4-glycosidic bonds versus alpha-1,4-glycosidic bonds and alpha-1,6-glycosidic bonds in starch have different properties. Primary alcohols have a hydroxyl group at carbon C6, whereas secondary alcohols have a hydroxyl group at carbons C2 and C3. Unmodified starch is a triol compound which can be converted to hemiacetal whenever the glucose ring component –CHOH–CHOH– replaces the carbon atoms at C2 and C3 positions. The existence of three -OH groups in glucose renders it amenable to replacement processes allowing for a wide range of starch alterations. The reactivity of starch is also affected by its grain size. The susceptibility to modification increases with the size of the grains. This is due to the fact that external influences have comparatively easier contact with larger grains. Modification is the procedure of altering normal properties through physical, chemical, or enzymatic processes .The most commonly used alteration technique to obtain specific changes in molecular structure is the oxidation of starch. In this process, the primary and secondary –OH groups present in the glucose molecule led to the development of aldehyde or carboxyl groups. The efficiency of the oxidation reaction is determined by the nature of the oxidant, the biological origin of the starch, and the procedural parameters. Furthermore, the oxidation method can affect the intermolecular bonds and/or fractional depolymerisation of polymer chains present in the starch molecule . TypicalIn recent years, oxidised starch has been widely used in the food sector to create adherent surfaces and coatings . BecauseAs reported by Lima et al. 2O2 is increased, and it is significant if the molecular weight is reduced. It occurs due to breakage of glycosidic bonds during the reaction and consequently, due to modification. However, the oxidation reaction is not at all easy to identify due to bands' overlapping and suppression. Therefore, a 2nd derivative process is carried out on the spectra to develop the sensitivity for the possible changes in chemical structures which are changed during process. In −1 [According to Barbosa et al., there are structural changes in potato starch as presented in s. In −1 .It is a procedure in which three easily accessible -OH groups of starch molecules are converted to alkyl or aryl derivatives. This alteration process usually affects various properties, and one of the most important is its retro gradation ability resulting in reduced in-between amylase connections with the outside chain of amylopectin . This ca−1. This new absorption band is linked to the extending vibration of C=O bond of the carboxylic acid group. With the increase in the degree of substitution of citric acid, the peak at 1740 cm−1 becomes stronger. These results confirm the esterification reaction carried out between canna, starch molecules, and citric acid [Wu et al. reported that citrate-modified raw starch of canna is different from the citrate modified starch, because a new peak is observed by them in the modified starches at 1740 cmric acid .Lee and Chang reported that the shapes of maca starch granules as shown in However, these physical and chemical alterations may limit starch's utility in some formulations while enhancing its functional quality in others. Functionalizing delivery systems with these physicochemical features create new possibilities for enhancing the overall efficacy of starch related systems. The most common starch modification methods are chemical modification methods, which basically include esterification and oxidation and few other modification techniques. These are the modification methods which can alter various properties of starch like digestibility, chemical bonds, molecular structure, amylose, and amylopectin chain, and these can be altered according to the necessity of the properties which are required. In essence, physical modification shows that it significantly alters the physical properties of starch such as the morphology of granules or viscosity of the starch paste. Altering these properties can be beneficial for a targeted drug delivery systems. Genetic and enzymatic are other techniques which are also capable of altering the various properties of starch enzymatic modification and are also used to alter the nutritional content or gelatinization properties or granule morphology. Although enzymatic modifications which alter the properties in a similar fashion as chemical modifications but carrying out an enzymatic reaction is not feasible and cannot be performed without professionals, chemical modifications are preferred over enzymatic modifications. The genetic modification alters with the plant genetic material and the properties of starch automatically get modified in its native form itself. Furthermore, this modified starch can be used in the formulation of novel drug delivery systems or in the preparation of various products according to the needs. If the chemical modifications were enhanced, novel drugs were isolated in the future having potential for use in the medical industry for a targeted drug delivery system.


Biopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18–39 years (young), 40–55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.Patients transplanted between 1995 and 2005 (Rejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).Rejection is a major cause of graft loss but recipient’s age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved. Graft survival of the transplanted kidney is documented in detail for the first years after transplantation in many publications. The causes for graft loss are predominantly acute T cell-mediated rejection (TCMR), primary non-function in case of deceased donor donation, surgical complications, and increased risk of death because of cardiovascular events or infection. Data of long-term graft survival are usually derived from large registries and, in general, provide an analysis of graft loss because of death with functioning graft or graft loss censored for death. However, there is a growing interest in the causes of kidney graft loss in the (very) long term but the number of publications is still limited. A major paradigm shift has occurred by leaving the ill-defined concept of chronic allograft nephropathy , 2 and rIn addition, death with functioning graft is a major cause of graft loss and is a competitive risk factor for all other causes of graft failure, particularly in the elderly. This issue is recognized but poorly addressed, although a recent publication drew attention for this cause of graft loss . AnotherIn this study, a cohort of kidney transplant recipients with prospective collection of relevant data and a high level of kidney biopsies-proven diagnoses was analyzed to describe the changes in cause of graft loss in different age groups over a very long time after transplantation, taking death with a functioning graft into account.This study included all 737 kidney transplantations performed between January 1995 and December 2005 at the Erasmus Medical Center in the Netherlands. The last follow-up date before data analysis was 1 March 2021. Recipients were seen at least once a year at our out-patient clinic for follow-up and data were registered in a national database (see below) which was locally supplemented with additional clinical parameters. If the regular visits were discontinued recipients were considered lost to follow-up from their last visit. All transplantations were performed with a negative complement-dependent cytotoxicity cross-match with both current and historic sera and ABO blood group-compatible. The standard immune suppressive medication protocol with a calcineurin inhibitor was either tacrolimus  or ciclosporin (aiming for predose concentrations of 150–200 μg/L tapered to 100–150 μg/L at 6 months), combined with mycophenolate mofetil  and glucocorticoids. All patients received 50 mg prednisolone b.i.d. intravenously on days 0–3. Thereafter, 20 mg oral prednisolone was started and subsequently tapered to 5 mg at month 3.For analysis, the baseline and clinical follow-up transplantation data were retrieved from the Netherlands Organ Transplant Registry (NOTR), which was over 99% complete for our center at time of this study. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul as outlined in the “Declaration of Istanbul on Organ Trafficking and Transplant Tourism” and in accordance with the declaration of Helsinki. The use of clinical data and assessment of donor-specific antibodies in stored serum samples was approved by the Research Ethics Committee for Biobanks and the Medical Ethics Committee of the University Medical Center Utrecht.per protocol biopsies were performed. All kidney biopsies were evaluated by experienced renal pathologists and commented on in detail. The original descriptions of the glomerular and tubular-interstitial compartment were used to reclassify the biopsies with rejection according to the Banff 2018 reference guide (n = 10) and for statistical analysis these cases were combined with the humoral rejections. The presence of anti-HLA donor specific antibodies (DSA) were retrospectively measured at the pretransplant phase by Luminex single beads assay, as part of the PROCARE study  and interstitial fibrosis with tubulus atrophy (IFTA) which category contains all biopsies without a classifying diagnosis other than the presence of IFTA as a sign of chronic renal damage. Underlying kidney disease of the recipients is shown in For data analysis the outcome of the kidney biopsy was further categorized recurrence original kidney disease , diagnosis of In 38 recipients, a kidney biopsy was not performed although no obvious clinical diagnosis for their progressive deterioration of graft function was present. Reviewing the charts revealed that in less than 10% this was because of refusal of the recipient, a high risk for complication or end-stage renal disease at presentation. In most cases the treating physician considered a diagnosis of “chronic allograft nephropathy” and concluded that kidney biopsy would not alter treatment policy.for cause kidney biopsy was used to categorize the type of graft failure. The other outcome categories were a clinical diagnosis of cause for graft failure  and “unknown.” The latter category contained all cases of graft failure in which no biopsy was performed and a clinical diagnosis for allograft failure could not be made.If graft failure occurred the diagnosis of the Delayed graft function (DGF) was defined as the need for continuing dialysis after transplantation and duration of DGF was counted in days from transplantation to the last dialysis.Within the first year after transplantation, the category “perioperative complications” was applied.The cause of death of the recipients was documented and shown in U-test for continuous variables. All p-values were 2-tailed.Three age groups were made based on age at the time of transplantation: 18–39 years (young), 40–55 years (middle age), and > 55 years old (elderly) which roughly matched to tertiles of recipients age distribution and were considered clinically relevant age categories. Differences in patient, donor, and transplant characteristics were assessed by the Fisher’s exact test for categorical variables and Mann-Whitney p-value of < 0.1 were considered for further analysis by stepwise forward regression to calculate hazard ratios and corresponding confidence intervals. PH assumption of variables were tested by visual inspection of log-minus log graphs and further tested by assessment of time-dependency using the Cox regression with time-dependent covariate module in SPSS. All variables met the demands of PH unless stated otherwise. Interaction terms that met statistical significance (p < 0.05) were included in the multivariate model. Normal probability plots were made and presence of significant correlations was assessed. Absence of collinearity in the model covariates was formally assessed by calculating the variance inflation factor. Statistical analysis was performed with software IBM SPSS statistics 21.Death censored graft loss and incidence of different causes of graft loss were assessed by Kaplan-Meier analysis with log-rank statistics for difference between strata. As all recipients had, by definition, a follow-up of 15 years, the causes of graft failure were specifically given for that point in time . Univarip = 0.01) but not recipient survival.The clinical and transplant characteristics of recipients stratified according to their age category are given in At 15 years after transplantation the frequency of death with a function graft ranges from 5.3% in the young group to 43% in the elderly group . Within p-value 0.08 compared to the young age group), and relatively more malignancies in the young age group  were noted .In all age categories, the major cause of graft loss other than death was rejection-related see . Figure The cumulative risk for AMBR increased steadily until about 15 years after transplantation after which only very few new cases were observed . The prep = 0.2). The much higher risk for graft loss because of death in the elderly group obviously greatly reduced the impact of ABMR on graft survival. For instance, in the period 15–26 years after transplantation the relative and absolute number of cases with ABMR-related graft failure in the elderly group was significantly lower  as compared to the younger group .The percentage of biopsy-proven ABMR cases leading to graft loss at the end of follow-up was high (74.4%) and tended to be higher in the young recipient group . At maximal follow-up, 27 out of 369 recipients (7.3%) with no TCMR episode  and 18 out of 93 recipients (19.3%) with a previous TCMR had IFTA-related graft loss (p = 0.001).A previous rejection may lead to IFTA and subsequent graft loss at longer follow-up . To testn = 2), auto-immune vasculitis (n = 3), diabetic nephropathy (n = 3), membranoproliferative glomerulonephritis (n = 3), thrombotic microangiopathy (n = 1), and focal segmental glomerulosclerose (n = 3). As expected based on the higher frequency of glomerulonephritis and glomerulopathy  and middle age groups  with only 1 case in the elderly group (0.5%) which is illustrated by Graft failure because of recurrent disease was relatively rare with 15 identified cases  with great diversity in biopsy diagnosis; IgA nephropathy ; BKV nephropathy (n = 2), JC-virus nephropathy (n = 1), tubulo-interstitial nephritis (n = 1), cholesterol emboli (n = 1), diabetic nephropathy (n = 2), and anti-GBM disease in a recipient with Alport disease (n = 1).This analysis of a very long-term follow-up study of kidney transplant recipients up to 26 years is first in its kind to show that causes of graft failure are a function of post-transplantation time and recipient’s age. The data obtained in this study indicate that TCMR is in particular contributing to graft loss in the young patients but the impact becomes negligible after 5 years post-transplantation and about 2 years earlier in the elderly recipients. The incidence of AMBR in for cause biopsies is remarkably constant in the period of 1–15 years after transplantation and not age-dependent.After 15 years, there are very few new cases of ABMR and similar to TCMR, the ABMR-free survival curve flattens. A previous TCMR increases the incidence of ABMR shortly after transplantation but in the long run there is no influence of TCMR on the cumulative incidence of ABMR. Taken together the data suggest that a particular load of antigenic mismatches is required to develop ABMR, in accordance with recent studies on the association between the number of predicted indirect recognizable donor-derived HLA epitopes (PIRCHE) which can be presented by recipients HLA class II and long-term graft survival , 22. Thea priori chance of losing the kidney graft because of ABMR in these vulnerable recipients is relatively small. In contrast, young patients have a substantial risk for graft loss because of either TCMR in the first couple of years and ABMR, thereafter. These recipients will have the greatest benefit of a well HLA-matched kidney allograft.For clinical decision making, it is important to realize that death with functioning graft is a major competitive risk for long term causes of graft loss, in particular ABMR. Elderly recipients with a high burden of comorbidities will have a limited life span after transplantation although they may still benefit from kidney transplantation over continuing dialysis , 25. TheRecurrence of original kidney disease, newly diagnosed kidney disease, and clinically diagnosed causes of graft failure beyond 1 year post-transplantation are relatively infrequent causes of allograft failure.for-cause kidney biopsies. However, we realize that such a prolonged observation period as in this study introduces many confounders which are difficult to account for. For instance, immune suppressive drug regimens have changed over time and within patients. In addition, it is unclear to what extent the result of our center can be generalized, in particular, with respect to the incidence of death with function graft. In our center we tend to have a relative liberal transplantation policy with respect to the eligibility of patients with a high co -morbidity score (The strength of our study is the unique long and close follow-up of the recipients with relative few lost to follow-up and a high score of ty score , 26. Howty score . MoreoveIn accordance with other studies, delayed graft function in the recipients receiving a deceased donor kidney negatively impacts the graft survival  and undeAlthough we recognize that graft loss may have many contributing factors as recently demonstrated , this usIn summary, this study shows the impact of rejection on graft failure as a function of time-after-transplantation and age with death as a very strong competitive risk factor in the elderly recipients. For the younger recipients, ABMR in the long term is a dominant cause of graft failure, specifically in the group with pre-transplantation DSA. A plateau in the cumulative incidence of ABMR in the group without pretransplant DSA suggest that particular or total number of epitope mismatches are important determinants for the absolute risk for ABMR-related graft loss over a prolonged time of follow up.The original contributions presented in this study are included in the article/The studies involving human participants were reviewed and approved by the Research Ethics Committee for Biobanks and the Medical Ethics Committee of the University Medical Center Utrecht. The patients/participants provided their written informed consent to participate in this study.MB participated in research design, writing of the manuscript, and data analysis. DR participated in research design and writing of the manuscript and provided analytical tool. MA and JK participated in data analysis and writing of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.