Lactobacillus plantarum, Koji and yeast as the main fermenting agents. The cooking, textural and digestive properties of the noodles were studied, followed by the morphological, crystalline and thermal properties of the starch. The results show that, compared to unfermented noodles, the optimal cooking time of Koji pre-fermented noodles (KJHN) decreased from 460 s to 253 s, and they possessed a higher percentage of weakly bound water and degree of gelatinization at the same cooking time. After cooking, KJHN had a softer texture and higher starch digestibility. In addition, the physicochemical properties of the KJHN and Lactobacillus plantarum pre-fermented noodles (LPHN) showed a decrease in pH and amylose content, and an increase in reducing sugars content. The starch extracted from KJHN and LPHN had significant superficial erosion and pore characteristics, and the gelatinization enthalpy, relative crystallinity and short-range order were all increased. These changes in the starch properties and the quality characteristics of noodles resulting from Koji fermentation might provide a reference for the development of easy-to-cook and easy-to-digest noodles.Crumbly dough fermentation was applied to produce dried hollow noodles, with  As one of the staple foods, noodles have a long history in China. Among them, the hand-made dried hollow noodles are naturally fermented and have a porous cross-section, originating from Shaanxi province in China. Hollow noodles are easy to cook and digest, have a soft and elastic texture and are especially popular for the elderly, pregnant women and infants. The production of hand-made hollow noodles consists of more than a dozen processes, including repeated kneading, dividing, relaxing, hanging, pulling and, finally, naturally drying. Since the whole process is done by hand, it is time-consuming and labor-intensive. In order to simplify the production process while retaining the quick cooking characteristics and soft texture characteristics, machine-made dried hollow noodles were introduced.Lactobacillus plantarum to ferment the noodles, which increased the pore structure of the noodles and shortened the cooking time. The porous structure formed by the fermentation not only gave the noodles a shorter cooking time, but also effectively reduced the hardness of the noodles after cooking. At the same time, the production process of machine-made hollow noodles greatly simplified the manufacturing process and saved the manpower workload. Fermentation is a complex and slow process; microbial metabolism may alter or degrade the starch after a long fermentation time, which affects its water absorption and swelling properties during cooking, which in turn affects the cooking time of the noodles and ultimately results in different textural properties. Li et al. [Lactobacillus and yeast resulted in the rice noodle having a crisper and softer texture, which was explained by the fact that the microbial fermentation disturbed the crystalline order of the rice starch, breaking up the starch and allowing it to swell more easily during processing. Zhu et al. [Lactobacillus to ferment rice flour; organic acids and enzymes were produced in the system, which might hydrolyze starch to some extent, thus shortening the rehydration time of rice noodles. In addition, a large amount of amylose leached, thus forming a strong network structure, which led to the increase in the hardness and chewiness of the rice noodles.The common production method is to dissolve yeast in water and mix it with flour to form a crumbly dough, and then the final product is obtained through the operations of relaxing, sheeting, cutting, noodle fermenting and machine air-drying. All procedures can be done independently by mechanical equipment, with little or no human involvement. Xiong et al.  concludei et al.  concludeu et al.  used mixAt present, the production process of machine-made dried hollow noodles has not been well established and is still in the stage of exploration and innovation. The existing literature has mainly investigated the use of yeast for noodle fermentation, while pre-fermentation of the crumbly dough and Koji fermentation have not been reported for the production of machine-made hollow noodles. Therefore, in this study, different fermentation methods were used to make noodles in order to find a suitable method for the production of hollow noodles with a shorter cooking time, softer texture and higher in vitro digestibility, thus satisfying the current pursuit of a fast pace of life and providing recommendations for the development of diets for specific groups of people such as the elderly, children and pregnant women.The main objectives in this study were as follows: (1) to study the effect of the fermentation formulation on the cooking properties, textural and chemical properties of hollow noodles; (2) to study the water absorption properties and gelatinization properties during cooking, and in vitro digestive properties after cooking; (3) to study the morphological properties, thermal properties and crystallization properties of the starch isolated from dried noodles using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Raman spectroscopy.Lactobacillus plantarum powder was purchased from Zhenjiang Tianyi Biotechnology Co., Ltd. . All chemicals were analytical grade.The wheat flour was provided from COFCO Corporation  ; glucose oxidase kit ; pepsin , pancreatic enzymes , alpha-amylase  were purchased from Sigma; amyloglucosidase  was purchased from JK Chemical; commercial yeast and Koji were purchased from Angel Yeast Co. Ltd. ; commercial Unfermented noodles (control): 400 g of flour and 128 g of water were mixed using a needle dough mixer  and then equilibrated at 30 °C and 75% humidity for 30 min. After that, the crumbly dough was pressed to 0.8 mm from 2 mm, 1.6 mm and 1.2 mm by a noodle machine , then cut into 2.3 mm width, dried in a noodle drying machine to 13 ± 0.5% moisture  and, finally, packed into plastic bags for later analysis. Unfermented noodles were used as the control for this experiment.Hollow noodles 1 (HN1): 4 g yeast was dissolved in 128 g water and then mixed with 400 g flour. After relaxing, sheeting and cutting, the noodles were fermented at 30 °C and 75% humidity for 90 min, then dried and packaged. Yeast was used in this recipe for noodle fermentation.Hollow noodles 2 (HN2): 2 g yeast was dissolved in 64 g water, then mixed with 200 g flour to form a crumbly dough, fermented at 30 °C and 75% humidity for 24 h, and then mixed with 200 g flour containing 2 g yeast and 64 g water. After relaxing, sheeting and cutting, the noodles were fermented at 30 °C and 75% humidity for 90 min, then dried and packaged. In this recipe, yeast was used for crumbly dough pre-fermentation and noodle fermentation.Lactobacillus plantarum-fermented hollow noodles (LPHN): 9 g Lactobacillus plantarum powder was dissolved in 64 g water, then mixed with 200 g flour to form a crumbly dough, fermented at 30 °C and 75% humidity for 24 h, and then mixed with 200 g flour containing 2 g yeast and 64 g water. After relaxing, sheeting and cutting, the noodles were fermented at 30 °C and 75% humidity for 90 min, then dried and packaged. In this recipe, Lactobacillus plantarum was used for crumbly dough pre-fermentation.Koji fermented hollow noodles (KJHN): 3 g koji powder was dissolved in 64 g water, then mixed with 200 g flour to form a crumbly dough, fermented at 30 °C and 75% humidity for 24 h, and then mixed with 200 g flour containing 2 g yeast and 64 g water. After relaxing, sheeting and cutting, the noodles were fermented at 30 °C and 75% humidity for 90 min, then dried and packaged. In this recipe, Koji was used for crumbly dough pre-fermentation.The cooking characteristics of the noodles mainly include optimal cooking time, water absorption and cooking loss, which were determined according to the method by Chillo et al.  with appOptimal cooking time: 25 g of noodles were placed in 500 mL of boiling water. One noodle was taken out every 15 s and placed in two transparent glass plates and squeezed. The time when the white core in the middle of the noodle just disappeared was the optimal cooking time.The water absorption of dried noodles cooked for 3, 5 and 7 min was calculated by the following formula:The cooking water at the optimal cooking time was collected and the volume fixed to 500 mL with deionized water. Then, 100 mL was taken out in a constant weight beaker, heated on an infrared oven and then placed in a 105 °C oven for constant weight, and the cooking loss was calculated using the following formula:The texture properties were determined by the method of Han et al.  with somTPA  mainly included hardness, springiness and chewiness of the noodles after cooking by a TA-XT2i Texture Analyzer . The noodles were cooked for the optimum cooking time, then three noodles were placed on the platform using a P36/R probe to simulate the chewing test with the following test parameters: pre-test velocity, 2.0 mm/s; test velocity, 1.0 mm/s; post-test velocity, 2.0 mm/s; strain, 75%; trigger force, 5.0 g.Tensile properties analysis was determined by measuring the tensile force and distance of the cooked noodles. Noodles were cooked for the optimal cooking time and tensile measurements were carried out using the A/SPR probe until the noodles broke with the following test parameters: pre-test velocity, 1.0 mm/s; test velocity, 2.0 mm/s; post-test velocity, 2.0 mm/s; distance, 150 mm. trigger force, 5.0 g.Both TPA and tensile analysis were measured 10 times in parallel.The pH of the noodles was determined by using a pH meter . This was done by taking 10 g of noodles and adding 90 mL of deionized water, magnetic stirring for 30 min and then measuring.Reducing sugar was determined according to the method of Su et al. . ApproxiThe amylose content of the starch was determined by the Megazyme amylose/amylopectin assay procedure  using a selective precipitation reaction of concomitant cuttlefish globulin A (Con A) with amylopectin starch .The water distribution characteristics were determined by the method of Yang et al.  with appThe determination of the degree of gelatinization was based on the method of Liu et al.  with appIn vitro digestion of cooked noodles was measured according to Minekus et al. , with apOral digestion (2 min): 1 mL of α-amylase (pH = 4.7), 25 μL of calcium chloride (0.3 M), 4 mL of sodium acetate buffer solution (ABS)  were added to a centrifuge in order to make the final α-amylase enzyme activity of 75 U/mL.Gastric digestion : 1.3 mL HCl (1 M), 1.6 mL pepsin (pH = 2), 5 μL calcium chloride (0.3 M), 7.1 mL ABS  were added sequentially, making the final pepsin enzyme activity of 2000 U/mL.Intestinal digestion : 1.4 mL NaOH (1 M), 5 mL pancreatic enzyme, 40 μL calcium chloride (0.3 M), 13.6 mL ABS  were added sequentially to make the final pancreatic protease enzyme activity of 100 U/mL.g for 10 min. 0.1 mL of the supernatant (0.1 mL of deionized water for control) was mixed with 0.5 mL amyloglucosidase , and the reaction was shaken for 60 min at 37 °C. Then, the glucose content was determined using the glucose oxidase kit.Inactivation and determination: 0.1 mL of the reaction solution removed at 0, 20, 60, 120, 180 and 240 min was mixed with 0.3 mL of 100% ethanol, vortexed for 30 s to inactivate the enzyme and centrifuged at 10,000× The starch was extracted according to the method of Noda et al. , with apThe sample was soaked for 60 min in a beaker with deionized water and then washed by hand, centrifuged at 5000 rpm for 10 min and the supernatant and yellow precipitate were discarded. This operation was repeated three times until no yellow precipitate was visible. The white precipitate was then dispersed in 40 mL of water and sieved through a 75 μm sieve. The filtrate was collected, centrifuged, and the lower precipitate was starch. The precipitate was washed with 70% ethanol, centrifuged and repeated twice. Finally, the sample was dehydrated in 100% ethanol and dried in an oven at 40 °C for 24 h.The microstructures of starch were observed using a scanning electron microscope  with an accelerating voltage of 3.0 kV. The samples were sprinkled in appropriate amounts on conductive adhesive and then sprayed gold.The thermal properties of starch were determined by reference to the method of Ding et al. . DSC 3  of the band at 480 cm−1, which was used to analyze the short-range molecular order of starch, was calculated using Origin 2021 software .Raman spectroscopy was performed using LCM-Raman  with a 532 nm green diode laser source. The starch samples were laid flat on tinfoil-covered slides and the spectra were collected in the range of 3200–100 cmAll experiments were performed at least three times, and results were expressed as mean ± standard deviation. Significance analysis was performed using the one-way analysis of variance (ANOVA) of SPSS  software, and plotting was performed using Origin 2021 (OriginLab).Lactobacillus plantarum-fermented hollow noodles (LPHN) and Koji-fermented hollow noodles (KJHN), which also underwent the pre-fermentation of the crumbly dough and noodle fermentation, reduced the optimal cooking time to 267 s and 253 s. The possible reason is that the addition of Lactobacillus plantarum and Koji had a greater effect on the properties of the starch during the long pre-fermentation time of the crumbly dough compared with HN2, thus conferring a shorter cooking time to the hollow noodles. The KJHN had the shortest cooking time, which might be more in line with people’s demand for noodles that can be cooked in a short time.Cooking time and cooking loss are important quality indicators of dried noodles, which affect the degree of acceptance by consumers. The cooking properties of dried hollow noodles prepared by different fermentation methods are shown in Lactobacillus plantarum and Koji during the crumbly dough fermentation possessed relatively high cooking losses at a shorter cooking time, probably due to some hydrolysis of the starch by microorganisms or their metabolites during the long fermentation time of the crumbly dough, which affected the structural properties of the starch and resulted in the leaching of amylose during cooking [Lactobacillus plantarum pre-fermentation might also cause hydrolysis of gluten [From the results in  cooking . In addif gluten , thus maLactobacillus plantarum-fermented hollow noodles (LPHN) and Koji-fermented hollow noodles (KJHN) also exhibited lower firmness and chewiness, the reason for which might be attributed to the metabolic gas production by yeast using sugars and the hydrolysis of starch or protein by metabolites, which in turn affected the textural properties of the noodles by the affecting water absorption capacity of the noodle matrix during cooking. Similar results were obtained by Baik et al. [The texture properties included the TPA  and tensile test of the cooked noodles, which are commonly used to characterize the eating quality of noodles. From the results in k et al. , where nLactobacillus plantarum and Koji pre-fermentation groups (LPHN and KJHN) exhibited the lower breaking force, probably due to a series of microbial metabolic behaviors during fermentation that not only produced a porous structure but also might have affected the starch or protein properties, thus affecting the tensile properties of the noodles after cooking. Xu et al. [As could be seen from u et al.  concludeLactobacillus plantarum, reduced the pH to 4.02; and KJHN, which replaced yeast with Koji, reduced the pH to 5.67. The reason for the decrease in pH values of un-pre-fermented HN1 and yeast pre-fermented HN2 might be that acidic substances such as succinic acid were produced during fermentation [Lactobacillus plantarum pre-fermented LPHN might be due to Lactobacillus plantarum-produced acids such as lactic acid and acetic acid during fermentation [According to the results of entation , and theentation . The decentation . Moreovep < 0.5), while the LPHN (Lactobacillus plantarum pre-fermentation) and KJHN (Koji pre-fermentation) showed a significant increase in reducing sugars (p < 0.5). Where HN2 had a lower reducing sugar content than HN1, the possible reason is that the rate of reducing sugar production was lower than the rate of reducing sugar utilization during the long fermentation time. In contrast, LPHN had a higher amount of reducing sugars, probably due to some acidolysis of starch by microorganisms during the fermentation process, as it also had a lower pH [In the fermentation process, microorganisms use reducing sugar for respiration and, on the other hand, they decompose substrates to produce reducing sugar. Therefore, by detecting the content of reducing sugar, the degree of fermentation can be predicted. From the lower pH . Moreovelower pH , and, thlower pH , where Rp < 0.05). HN1 and HN2 were both yeast-fermented, in which HN2 underwent a long crumbly dough pre-fermentation. Yeast mainly metabolizes sucrose and raffinose by intracellular transposase [Lactobacillus plantarum pre-fermentation group (LPHN) and Koji pre-fermentation group (KJHN) exhibited a lower amylose content, probably due to the production of acids/enzymes capable of hydrolyzing starch during the fermentation process, which always starts from the amorphous region rich in amylose. Similar results were reported by Reyes et al. [From the data in nsposase ; althougs et al. , where ms et al.  showed tLactobacillus plantarum group (LPHN) consistently possessed a higher water uptake rate during cooking, and based on its lower pH (4), it might be speculated that the acidic hydrolysis made it easier for starch or protein to hydrate with water molecules. When cooked for 5 min, the water uptake rate and optimal cooking time varied between noodles. Compared to the unfermented control, the LPHN group possessed the highest water uptake rate, followed by HN2, KJHN and HN1. In order to understand the distribution characteristics of water during the cooking process, the noodles cooked 5 min were tested by LF-NMR experiments and the results are shown in 21  and A23  values and higher A22  values [22 played an important role in the cooking process of dried noodles and might contribute to the water absorption, starch gelatinization and stretching behavior of the gluten. Zhang et al. [The cooking process of dried noodles is a process of starch gelatinization and cross-linking polymerization of gluten, and water plays an important role in this process. From ) values ; therefog et al.  also repLactobacillus plantarum and Koji pre-fermentation groups (LPHN and KJHN), acids and enzymes might have subjected the starch to hydrolysis, thus making it easier for water molecules to enter the amorphous growth ring structure of the starch and disrupt the starch crystallization zone, which in turn exhibited easier gelatinization [In general, the degree of gelatinization of noodles could be used to determine the gelatinization state of the starch and the cooking state of the noodles. From nization .The starch digestibility of the noodles is shown in The morphological properties of the starch isolated from noodles are shown in p < 0.05). Combining the results of SEM and the reduced amylose content, it can be inferred that, in the fermentation process of KJHN and LPHN, acids or enzymes hydrolyzed starch, especially in the amorphous area, which manifested itself as a more crystalline area when weighing the same weight of sample during DSC testing, thus requiring more thermal energy to disrupt the double-helix structure and crystalline area. A similar result was obtained by Al-Ansi et al. [The results of thermal parameters of starch gelatinization are shown in i et al. , where tp < 0.05). The possible reason is that, during fermentation, Lactobacillus plantarum (LPHN) and Rhizopus (KJHN) produced acids and enzymes, which hydrolyzed the amorphous region rich in amylose [From the results of  amylose , thus af amylose ,34, wher amylose , during  amylose . HN2, wh amylose , and the amylose  on starc−1 originates from the sensitivity of the glucopyranose ring structure to changes in the short-range molecular order of the double helix in starch. In particular, the area and intensity of the full width at half maximum (FWHM) and 480 cm−1 spectral bands were negatively correlated with the crystallinity of the starch. Many studies have shown that the FWHM of the 480 cm−1 spectral band is a good indicator of the short-range order degree in crystalline starches, and the narrower the FWHM, the higher the degree of the short-range order [The characteristic spectral band at 480 cmge order . From thge order , where mLactobacillus plantarum, Koji and yeast as the main fermenting agents. Among these fermentation methods, hollow noodles fermented with Koji had a shorter cooking time, lower pH, lower amylose content and higher amount of reducing sugars. The Koji-fermented noodles after cooking were softer and had higher in vitro starch digestibility. In further studies of starch-related properties, the surface of the starch possessed corrosive and porous properties (from the SEM results) and the enthalpy of gelatinization, relative crystallinity and short-range orderliness of starch increased. This series of changes also allowed water to enter the interior of the noodles and starch more easily during cooking, resulting in noodles with higher percentages of weakly bound water and degree of gelatinization, as well as a shorter cooking time. The advantages of a short cooking time, soft and elastic texture, and easy digestibility after cooking of Koji-fermented hollow noodles might provide a reference for the development of diets suitable for infants, the elderly and pregnant women.This experiment applied the crumbly dough fermentation to produce dried hollow noodles with


The development of a new type of international relations is the advancement and improvement of diplomatic thinking among contemporary nations. It also serves as a crucial yardstick for assessing the future global pattern and the direction of order changes. Proper interaction between major powers can foster the growth of new international relations and has a significant impact on advancing global cooperation and the promotion of human peace. The goal of this essay is to examine how friendly interactions between major powers have affected the development of new international relations. A deep learning network model is presented for this purpose. The deep learning model was used to identify the emotions of the survey results, analyze each person's emotional tendencies, and summarize and compare the data. Relevant questionnaire surveys were conducted using the online questionnaire survey method on individuals in various countries. The survey results in this paper demonstrate that 96.5 percent of Chinese, 89.3 percent of Russians, and 81.6 percent of Americans support friendly relations between major nations. Only a very small percentage of the investigators supported hostile relations, with their support being 1.06 percent, 3.11 percent, and 2.94 percent, respectively. Therefore, creating a win-win partnership between major powers is exactly what the people of all nations are calling for. In contrast to the past, it is no longer hostile and violent. People anticipate that more great powers will coexist peacefully. The course of world history demonstrates that the relationships between major powers have an impact on not only how the international community develops but also how the world is currently organized. Major nations are at the centre of the global stage as the world experiences a major change that is unprecedented. It is imperative to actively promote the creation of a global community of shared destiny as well as the idea and process of forging new international relations in light of the crucial question of how global relations will develop. In addition to being a crucial step in creating a world community with a shared future, the development of new international relations represents a significant advancement of the field. In the process of actively fostering the development of new international relations, it is important to highlight the regular international exchanges between major powers, which are based on reciprocal coordination and friendly interaction between nations, rather than competitive hostility. Additionally, maintaining international peace and stability depends heavily on the orderly expansion of trade between nations. Studying the friendly relations between great powers and creating a suitable new type of international relations are therefore crucial in the current international environment.International relations have always been a hot topic, and many scholars have made a series of related researches on it. Willardson and Johnson conducted research on arms transfer, organized and analyzed its related literature, and discussed the general adaptability between arms transfer and international relations theory. Starting from seven theories such as realism, liberalism, and constructivism, seven hypotheses were verified, and the results showed that the support for the realism hypothesis was limited . Shih exDeep learning is emerging machine learning technology, which is introduced into machine learning to make machines go further to artificial intelligence . In receIn this paper, a deep learning model is introduced in the analysis of the benign interaction of major power relations and the construction of new international relations. The opinions and views of the people of various countries on the relationship between major countries were collected through an online questionnaire. Through the built deep learning model ,10 for eThe concept of “win-win cooperation” is essential to developing a new type of international relations. In contrast to the old “zero-sum” game mentality, where you lose and I win, and you lose and I gain, “cooperation” and “win-win” refer to a relationship of mutual benefit. The path to achieving “win-win” is through the new form of international relations. “Win-win” and “cooperation” go hand in hand and are mutually beneficial.Win-win outcomes are desired, and cooperation is the way to achieve them. A great power's growth is necessary to preserve international harmony and advance global economic growth, and a great power's growth and strength are favourable to international harmony and stability. The world experienced financial turmoil in 2008, and the economy as a whole experienced a Waterloo. The United States, Europe, and Japan, the three major western economies, all experienced a recession at the same time. It is well known that China, an emerging economy, has been crucial to the recovery of the world economy.In the modern era, “win-win cooperation” is a crucial component of international relations theory. The main goal of international exchanges among the major powers is to establish win-win cooperation, which is consistent with the trend of economic globalization and democratization of international relations. It has a beneficial and extensive impact on the development and evolution of future international relations, opening up a new avenue for resolving intercountry conflict. The key concept in today's international relations is “win-win cooperation,” which is also the path to peace and prosperity.(1) Historical Perspective. From a historical perspective, international relations are constantly changing and require the right guidance. After a large-scale war in Europe in the first half of the 17th century, the basic norms of modern international relations appeared. The Peace of Westphalia established at that time was a norm for international relations based on sovereign equality. Since then, many international treaties have been signed internationally, including the Vienna System, the Washington System, the Yalta System, the League of Nations, and the United Nations that has continued to this day. The United Nations Charter laid the foundation for modern international relations, but the confrontation between the two major military alliances led by the United States and the Soviet Union played an important role in international relations after World War II, leading to the Cold War that lasted for fifty years [ty years .After the Cold War, the Soviet Union in Europe died along with the Warsaw Pact, while NATO continued to develop and expand its legitimacy. In Asia, the United States still maintains a system of military alliances and strives to use it as the “cornerstone” of the East Asian region, strengthening and expanding its means. In order to prove its existence, the United States and its allies have resorted to any means to find or create “strategic opponents,” which has brought great harm to the stable development and peace of the Asia-Pacific region. Recently, issues such as the Ukraine crisis and the “rebalancing” of the US in the Asia-Pacific region have been filled with Cold War mentality. A military alliance built on the basis of an enemy is very different from its closedness, uniqueness, and peaceful development. Recently, issues such as the Ukraine crisis and the “rebalancing” of the US in the Asia-Pacific have been filled with Cold War mentality. A military alliance built on the basis of an enemy is very different from its closedness, uniqueness and peaceful development.70 years later, the beautiful blueprint depicted in the UN Charter has not yet been completed , and loc(2) International Perspective. In an international perspective, the world expects major powers to play a more important role. Every major country is one of the largest economies in the world, and their words and deeds are under the spotlight. The interests of major powers have been closely integrated with global interests. Whether it is to promote economic development, to resolve various crises and contradictions, or to establish a fair and reasonable new world order, the participation of major powers is required [required . This shThe development of a new kind of international relations benefits from the peaceful interaction between major powers. These nations with strong global influence and overall strength are the major factors currently influencing the global pattern. In the modern world, China, the United States, Russia, and Europe all play significant roles. The mutual cooperation between major powers must be taken into consideration when constructing a new type of international relations. Instead of ruthless competition, this new kind of relationship is based on coordination and cooperation between major powers as well as positive mutual influence.The meaning of positive interaction is as follows.The trilateral relationship between China, the United States, and Russia has once again emerged as one of the major factors affecting global development in the world's most intense geopolitical competition today. For the time being, the United States views China and Russia as strategic rivals. China and the United States now engage in a much more intense strategic rivalry. Russia is playing a more competitive game with the US, Europe, and China, and the level of strategic cooperation between the two countries has significantly increased. The relationship between the United States and Russia will be challenging to improve in a short period of time due to the political opposition of the United States and the significant conflicts of geopolitical and strategic interests of the two countries, even though both the Presidents of the United States and Russia hope that it can . While tAs permanent members of the UN Security Council, China, the US, and Russia are all represented. International affairs would find it challenging to find a solution without their combined efforts. The trilateral relationship between China, the United States, and Russia should be pushed to a goal that is conducive to the realization of a community with a shared future for humanity by countries using their growing influence and international strategizing abilities.Russia and China are both global superpowers, and the two nations are situated close to one another. The two countries' interests share a lot of similarities. For instance, the smooth development of relations between China and Russia is a model for the relationship between major countries today in terms of military cooperation in acting and diplomatic trade. China and Russia steadfastly support and defend one another's development and core interests. There is now a comprehensive strategic cooperative partnership between China and Russia. The two sides adhere to the pragmatic cooperation of “nonalignment, nonconfrontation, and nontargeting of third parties” as the foundation of their strategic partnership, which is built on the basis of their respective development needs. Given that the world is presently experiencing its most turbulent period in a century, with frequent occurrences of uncertainty, “black swans,” and “grey rhinos,” Sino-Russian relations are the aspect of current international relations which is the most stable.The direction in which the relationship between China and the United States is moving merits attention. If China and the United States can work well together, they will undoubtedly play a key role in maintaining global stability and advancing global peace and development. China and the United States can and should seek a new strategy that differs from the conflict and confrontation between major powers in the past in the context of today's globalization. Economic growth, counterterrorism, preventing the spread of weapons, fighting transnational crimes, and stopping the spread of the epidemic are all issues that China and the US have in common. In light of the new circumstances, China and the US should forgo the “zero-sum game” that has traditionally existed between traditional major powers, actively pursue consensus, and encourage Sino-US relations to be based on coordination, cooperation, and stability.The global system is changing in light of the new historical circumstances. As a result, global governance is facing a number of fresh issues and difficulties . ExpandiAlthough the concept of deep learning  is very Compared with the cultivation of advanced thinking, deep learning is to improve its ability to solve various complex and changeable problems by itself. Its specific performance is as follows: the ability to respond to thinking problems, the ability to judge complex things, the ability to further accurately understand problems, and so forth. The connotations of cognitive goals are shown in (1) Algorithm Principle. RBM is a unique structure of Markov random field [h and a visible layer v. The difference from the common Boltzmann machine is that the weight connection in RBM only appears between layers, and the units within the layer are not connected, as shown in om field . It consv and y.The basis of the RBM model is statistical mechanics. Based on the energy probability model, when the parameter is a fixed value, RBM is the distribution of energy functions related to layer units S value normalizes the convergence factor, and its double accumulation formula is as follows:Formula  is an esFor the RBM model of the double-layer structure, it can be expressed by a Bernoulli energy formula. The energy formula expression of the RBM model isn and m represent the unit datasets of visible layer and hidden layer, respectively; qij is the weight of the connecting edge between the visible layer and the hidden layer.In the above formula, vj follows a certain distribution probability, according to the RBM model, the independent active state parameters of the visible unit vj and the hidden layer unit are obtained, and then the visible layer and the hidden layer can use Formula (When  Formula  to expreβ(y) is the Sigmoid threshold function whose expression isFrom the above formula, This expression is only valid for the two-layer structure consisting of visible layer and hidden layer. When the model structure is larger than two layers, the expression will be invalid. For the multilayer structure model with more than two layers, the Gaussian Bernoulli formula is generally used, and its formula expression isvj is continuous actual value; Qijhi indicates obeying the mean.The expression for the conditional probability distribution of continuous actual numerical RBM is(2) Deep Model. Through Formulas (Formulas ∼4), the, the(2) Formulas ∼8) are  are (2) (1) Principle of AE Algorithm. From a structural point of view, autoencoding is to encode the initial data of the visual layer. That is, a space set contains feature map data extracted from very complex input layer data, and these feature map data will be aggregated into hidden layers and output. The process of decoding is that the data space accepts the reflected feature map data [map data  and reesR indicates that the model minimizes the reconstruction error; U is weight decay term; ε is output representation with respect to {Q, b} construction parameters; ε′ indicates that the output representation obtained after encoding is about {Q′, b′} construction parameters; n is sample data; x is original input dimension; y is reconstruction dimension.In the above formula, (2) Deep Structure Based on AE Algorithm. Compared with RBM, the AE algorithm has a simpler structure and has a better effect on deep stacking to form a deep network structure. The training steps of the model are as follows: first, input the initial data into it, and encode the input data with the encoder. Then the decoder performs decoding and adjusts the relevant parameters of the encoder and the decoder to minimize the error of the reconstructed data, thereby obtaining the first layer of coding. Then, take the obtained first layer encoding as input data, and repeat the encoding process. It can be completed when all hidden layer data training is completed. When the top hidden layer is output, add a supervision layer. Finally, according to the added supervision layer standard, the hidden layer data is slightly adjusted, and the multilayer automatic encoding overlap can form the deep structure of the AE algorithm. Multilayer automatic coding is shown in This paper conducts a questionnaire survey on people from different countries among the three major world powers, China, Russia, and the United States. The content of the questionnaire survey is an opinion on what kind of relationship should be maintained between the major powers in the world at present. The survey results of the youth, middle-aged, and old age groups are summarized, respectively. The survey results are shown in the following table.From The mentioned data is substituted into the multilevel deep structure training model as the initial data for training, so that the model can learn and improve continuously, and then the model is used to perform language recognition on the questionnaire responses of various countries. The recognition accuracy is shown in The average recognition accuracy of the depth recognition model based on the AE algorithm reaches 90%, while the average recognition accuracy of the depth recognition model based on the RBM algorithm is only 88%. The recognition accuracy of the deep recognition model based on the AE algorithm is relatively higher. Therefore, this paper selects the AE algorithm for further experimental investigation.The deep recognition model based on the AE algorithm is applied to the network survey through the network to investigate the views of the people of various countries on the unreasonable relationship between China and the United States and between China and Russia and the relationship between Russia and the United States and use the deep learning model for identification. The results are shown in From the data in From The degree to which Americans and Russians support the various aspects of the bilateral relations is depicted in China, the United States, and Russia now have a different relationship than the Cold War's original three participants—China, the US, and the USSR. Russia and the United States will not be affected by China and Russia's close relationship. Russia-US relations are deteriorating for internal reasons. The improvement in Sino-US relations is unrelated to the decline in US-Russian relations. Russia and the United States are focused on political and military influence, China and Russia are focused on all-around cooperation, and Sino-US relations are centred on economy, trade, and global governance. However, there are also some interactions between China, the US, and Russia on a global scale. To encourage the development of constructive interactions in the trilateral relationship between China, the United States, and Russia and to advance the trilateral relationship between China, the United States, and Russia to a goal that is conducive to realizing a community with a shared future for mankind, each major country should utilize its growing influence and international strategizing capabilities.This paper conducts a network survey based on a deep learning model in order to study how to construct a new type of major power relationship. The content of the survey is the views of people of various countries on the relationship between major countries, and the collected survey results are identified and analyzed by deep learning models to analyze their semantic sentiment trends and organize the data. The experimental data shows that although there are still conflicts and frictions between major powers, most people maintain a friendly attitude towards the relationship between major powers and support the friendly coexistence between major powers and win-win cooperation. Therefore, the construction of a new type of international relations should advocate a new concept of win-win, multiwin, and establish a new concept of new interests and destiny and implement a new approach of sharing responsibilities and emphasizing both righteousness and interests. Of course, there are still some flaws in the experimental investigation of this paper. Only the opinions of the people of China, the United States, and Russia are collected, and the opinions of people in other countries are not collected. There is a lack of universality and this needs to be improved and developed in future research.


IbpPGM, containing 22 exons and 21 introns, was cloned from the sweet potato line Xu 781. This gene was highly expressed in the storage roots and leaves, and its expression was induced by exogenous sucrose treatments. The mature IbpPGM protein was successfully expressed in Escherichia coli when a 73-aa chloroplastic transit peptide detected in the N-terminus was excised. The subcellular localization confirmed that IbpPGM was localized to the chloroplasts. The low-starch sweet potato cultivar Lizixiang IbpPGM-overexpression lines showed significantly increased starch, glucose, and fructose levels but a decreased sucrose level. Additionally, the expression levels of the starch synthetic pathway genes in the storage roots were up-regulated to different extents. Thus, IbpPGM significantly increased the starch content of the sweet potato storage roots, which makes it a candidate gene for the genetic engineering of the sweet potato.Sweet potato (Ipomoea batatas), an important root crop, has storage roots rich in starch that are edible and serve as a raw material in bioenergy production. Increasing the storage-root starch contents is a key sweet potato breeding goal. Phosphoglucomutase (PGM) is the catalytic enzyme for the interconversion of glucose-6-phosphate and glucose-1-phosphate, precursors in the plant starch synthetic pathway. Plant PGMs have plastidial and cytosolic isoforms, based on their subcellular localization. Here,  Starch is the main storage form of carbohydrates in plants. During the day, leaves synthesize transitory starch in the chloroplasts through photosynthesis. It is then degraded into sucrose at night and transported to non-photosynthetic organs as an energy source ,2. ADP-gArabidopsis, tobacco and maize [The interconversion between glucose-1-phosphate (G1P), the precursor of ADPG, and glucose-6-phosphate (G6P) is catalyzed by PGM. Two types of PGM exist in plants, cytosolic and plastidial, and they play synergistic roles in the distribution of photosynthetic carbohydrates . In plannd maize ,13,14.PGM have been characterized in different plant species. In the leaves of the pPGM-deficient Arabidopsis and tobacco mutants, the starch levels are barely detectable, but the soluble sugar levels increase [rug3 locus encoding pPGM in the pea results in the decreased starch contents in the leaves and seeds, which demonstrates that G6P is the source of phosphohexose in pea amyloplasts [pPGM or cPGM genes in the potato reduces the photosynthetic rate in the leaves and the starch content in the tubers [pPGM mutants of Arabidopsis also show a photosynthetic inhibition, whereas there is no change in the photosynthetic rate of the transgenic tobacco overexpressing AtpPGM or AtcPGM [The functions of increase ,13,15. Aloplasts ,16. The e tubers ,18. The r AtcPGM ,12. Althr AtcPGM ,20. Therr AtcPGM .pPGM or cPGM expression results in a decreased tuber starch content, but no significant difference was found in the tuber starch content between the transgenic and wild-type (WT) potato when both genes are inhibited, simultaneously. This indicates that starch-synthesis precursors  are transported to the heterotrophic organs to replace G6P [There is increasing evidence of alternative starch synthetic pathways in plants, such as ADPG, acting as a starch synthesis substrate, being directly catalyzed by the sucrose synthase in the cytoplasm and transported to the chloroplasts ,3,22,23.lace G6P ,24,25. TPGM gene remains unclear. In this study, a plastidial PGM gene, IbpPGM, was cloned from the sweet potato, and its expression profiles were analyzed. The overexpression of IbpPGM in the sweet potato significantly altered the storage-root carbohydrate content, and the underlying mechanism is discussed.Sweet potato (Ipomoea batatas) is an important crop with starch-enriched storage roots that act as both a staple food source and a bio-energy raw material. The functions of the key genes in the starch synthesis have been reported in sweet potato ,31,32,33Nicotiana benthamiana) plants, vectors  and Agrobacterium tumefaciens EHA105 competent cells were kindly provided by the Key Laboratory of Sweet Potato Biology and Biotechnology, Ministry of Agriculture of China. Xu 781 was used for the IbpPGM isolation, and Lizixiang was used for the gene’s functional characterization.The sweet potato line Xu 781, cultivar Lizixiang, tobacco  was conducted to obtain the full-length cDNA. The genomic IbpPGM sequence was amplified with primers GF/R using genomic DNA extracted from the leaves of Xu 781 as the template. The online tools ORFfinder , ExPASy , TargetP-2.0  and Gene Structure Display Server  were used to analyze the open reading frame (ORF), the protein molecular weight, signal peptide, phylogenic tree and gene structure, respectively. A multiple sequence alignment between IbpPGM and other PGM proteins was conducted using DNAMAN software. The sequences of the primers used in this study are listed in The total RNA was extracted from the leaves of Xu 781, using a RNAprep Pure Plant Kit  and then transcribed it into first-strand cDNA using a PrimeScript II 1st Strand cDNA Synthesis Kit . A pair of degenerate primers (DF/R) was designed on the basis of the most homologous region identified in a multiple alignment of IbpPGM transcript levels using the gene-specific primers qPGM-F/R. The control, IbActin, was amplified using the primers Actin-F/R.The total RNA was isolated from five different tissues  of Xu 781 plants grown in the field for approximately 100 days, and the first-strand cDNA was synthesized using PrimeScriptTM RT Reagent Kit with gDNA Eraser  . The qRT-PCR was conducted on a 7500 Real-Time PCR System  to determine the IbpPGM to exogenous sucrose. Briefly, the leaf-petioles (10 cm) of the Xu 781 plants were cultured in water in darkness for 1 d as a starvation treatment. Then, they were supplied with water or 175 mmol L−1 sucrose in darkness at 28 °C. The qRT-PCR was conducted to determine the transcript levels of IbpPGM in the cuttings harvested at different time points  after treatment. Three cuttings were used as biological replicates per time point for each treatment.The Xu 781 plants that were grown in the field for approximately one month, were used to investigate the response of IbpPGM encodes a mature protein, the gene was expressed in E. coli. The full-length ORF and the signal peptide-cleaved ORF (ΔORF) of IbpPGM were amplified with primers pET-F/R and pET-ΔF/R, respectively. The sequence-verified fragments were ligated independently into the expression vector pET-28a. Then, the recombinant vectors pET-28a-IbpPGM and pET-28a-ΔIbpPGM, as well as the pET-28a native vector, were introduced independently into the competent E. coli strain Transetta (DE3) cells . Fresh Luria-Bertani medium was inoculated independently with the positive clones, and they were cultured at 28 °C until the OD600 values reached 0.8. The soluble cytoplasmic proteins were prepared from the isopropyl β-D-thiogalactopyranoside-induced Transetta (DE3) cells. Then, the expressed IbpPGM protein was subjected to an SDS-PAGE analysis.To determine whether IbpPGM was amplified using primers 83-F/R and inserted into the pMDC83 vector between PacI and AscI cleavage sites. The recombinant vector pMDC83-IbpPGM and the native vector were introduced independently into the A. tumefaciens strain EHA105, and the positive strains were injected independently into the N. benthamiana leaf epidermal cells for the transient expression. Following the co-cultivation at 28 °C for approximately 36 h, the agroinfiltrated tobacco leaves were visualized using a laser scanning confocal microscope.The ORF of IbpPGM, which had been amplified using primers OPGM-F/R, was inserted into pBI121 between BamHI and SacI to replace the glucuronidase (gusA) gene. Subsequently, the expression cassette 35S-IbpPGM-NOS was excised from the pBI121-IbpPGM vector using HindIII and PstI and then ligated between the same cleavage sites in pCAMBIA3301, to generate the recombinant overexpression vector pC3301-121-IbpPGM. This plasmid was transfected into the A. tumefaciens strain EHA105. The plant transformation and regeneration were performed, as described by Wang et al. [IbpPGM expression levels were selected for further phenotypic analyses.To construct the overexpression vector, the sequence-verified ORF of g et al.  using emg et al. . The put−1 and the temperature of the column was maintained at 35 °C. The sugars were identified, based on the retention time of the standards, and the sample concentrations were calculated from the external standard curve. The quantifications were carried out with three replicates for each plant line.The starch contents in the storage roots of the transgenic and WT plants were analyzed in accordance with the method of Smith and Zeeman , and higIpomoea batatas genes were AGP-sTL1 and 2 , AGP-TLI (encoding the large subunit of IbAGPase), granule-bound starch synthase I (GBSSI), soluble starch synthase I (SSI), SSII, SSIII, SSIV, starch branching enzymes I and II (SBEI and SBEII), isoamylase1 (ISA1), and pullulanase (PUL). The primers used to amplify these genes are listed in The transcript levels of 12 key genes in the starch biosynthetic pathways of the transgenic and WT storage roots were investigated using qRT-PCR. The 12 The RACE method was used to clone IbpPGM from the Xu 781 sweet potato line. The cloned 2182-bp full-length IbpPGM cDNA contained a 1917-bp ORF that generated a 638-aa protein with a molecular weight of 69.3 kDa. The genomic sequence of IbpPGM was 5583 bp and contained 22 exons and 21 introns. TargertP 2.0 and ChloroP 1.1 predicted that the N-terminus of the IbpPGM protein contains a 73-aa chloroplast transit peptide. The molecular weight of IbpPGM without the transit peptide was 61.7 kDa. A multiple-sequence alignment of the PGM protein showed that IbpPGM shared a conserved domain similar with those from several other plants and from Saccharomyces cerevisiae . AdditioIbpPGM was expressed in all five tested tissues of Xu 781 plants, with the highest expression occurring in the storage root, followed, successively, by the leaves, the fibrous roots, the stems, and the petioles , to eliminate the effect of the chloroplast transit peptide on the prokaryotic expression. These two vectors were then expressed independently in E. coli  with its counterparts from other species, such as Brassica napus and A. thaliana, whereas cPGMs shared a similar gene structure of 18 exons and 17 introns. This demonstrated that the functional differentiation of the PGM genes into plastidial and cytosolic forms was accompanied by gene structural changes. Additionally, the deletion of the chloroplast transit peptides from the cPGM proteins, compared with the pPGM proteins, also indicated that the gene function is closely related to the gene structure.In the plant starch synthetic pathway, PGM is responsible for the synthesis of the upstream precursor G1P. Functional studies of PGM have mainly focused on how the starch contents in the plants changed when this gene is mutated or subject to RNA interference ,12,15,24IbpPGM was high in storage roots and leaves, which was consistent with its characterized role in starch synthesis. IbpPGM exists in amyloplasts in storage roots, whereas in leaves, it is mainly found in chloroplasts. Sucrose is an important signaling molecule in starch synthesis, and it induces the expression of starch synthesis-related genes through the abscisic acid pathway. When the sucrose contents in leaves (or in-vitro sucrose feeding) exceeds the need for respiration, starch synthesis is induced [IbGBSSI, IbAGP-sTL1, and IbSSI are all significantly induced by exogenous sucrose treatments [IbpPGM expression was induced at a low level. When the continuous sucrose feeding exceeded the respiratory demand, the IbpPGM expression began to increase rapidly, reaching 28 times the 0 h level by the end of the treatment. However, the continuous feeding of water after the starvation pre-treatment did not induce the IbpPGM expression. In agronomic practices, spraying sucrose-based polymers on leaves may improve the yield and quality of some fruits, which may result from induced alterations in the carbohydrate metabolism in leaves and then fruits. Thus, determining whether a leaf spray of sugar-based growth regulators to increase the yield and quality of the sweet potato, would be of interest in the future.The expression level of  induced ,38. In seatments ,33,39. IIbpPGM encodes a mature protein, two recombinant vectors for the prokaryotic expression were constructed. One carried the complete coding sequence of IbpPGM, and the other carried the same sequence minus the chloroplast transit peptide (ΔIbpPGM). The former could not be expressed in E. coli, whereas the latter expressed a mature protein. Thus, the transit peptide of IbpPGM may form a complex secondary structure at the mRNA level that affects the initial translation in a prokaryotic system. The fluorescence of the GFP protein fused with the complete coding sequence of IbpPGM mainly targeted the chloroplasts, which indicated that the transit peptide was successfully translated in the eukaryotic system and directed the IbpPGM protein to the chloroplasts.To determine whether IbpPGM, it was overexpressed in the sweet potato low-starch cultivar Lizixiang, by infecting the embryogenic suspension cells, and 10 positive transgenic lines were obtained. The three lines having the highest IbpPGM expression levels exhibited significant 4.5%, 5.5%, and 12.0% increases in the storage-root starch content, compared with the WT line. Owing to the overexpression of IbpPGM, the precursor G1P accumulated, which up-regulated the downstream genes involved in amylose and amylopectin synthesis, leading to further increases in the starch contents (IbpPGM consumed more G6P for the G1P synthesis, which accelerated the degradation of sucrose in the cytoplasm, leading to further increases in the glucose and fructose contents.To characterize the function of contents . In heteIbpPGM gene was cloned from the Xu 781 sweet potato line. IbpPGM was mainly expressed in the storage roots and leaves. Its expression was strongly induced by the exogenous sucrose treatments. The IbpPGM protein was subcellularly localized to the chloroplasts and was successfully expressed in E. coli when its 73-aa chloroplastic transit peptide was excised. The overexpression of IbpPGM significantly increased the starch contents of the transgenic sweet potato storage root and altered its soluble sugar levels. Meanwhile, the expression levels of starch biosynthetic genes in transgenic sweet potato storage roots showed increased expression levels to different extents. These results indicated that IbpPGM has the great potential as an important candidate gene for increasing the starch content of the sweet potato through genetic engineering.In the present study, the


Yellow fever (YF) vaccination is often mandatory for travelers to YF-endemic areas. The areas with risk of YF partially overlap with those of dengue, for which there is currently no recommended vaccine available for dengue-naïve individuals. This phase 3 study assessed the immunogenicity and safety of concomitant and sequential administration of YF (YF-17D) and tetravalent dengue (TAK-003) vaccines in healthy adults aged 18–60 years living in areas of the US non-endemic for either virus.Participants were randomized 1:1:1 to receive the following vaccinations at Months 0, 3, and 6, respectively: YF-17D+placebo, TAK-003, and TAK-003 (Group 1); TAK-003+placebo, TAK-003, and YF-17D (Group 2); or YF-17D+TAK-003, TAK-003, and placebo (Group 3). The primary objective was to demonstrate non-inferiority  of YF seroprotection rate one month following concomitant administration of YF-17D and TAK-003 (Group 3) compared with YF-17D plus placebo (Group 1). The secondary objectives included demonstration of non-inferiority of YF and dengue geometric mean titers (GMTs) (UB95%CI for GMT ratio <2.0), and safety.900 adults were randomized. YF seroprotection rates one month post-YF-17D (Month 1) were 99.5% and 99.1% in Group 1 and 3, respectively, and non-inferiority was demonstrated (UB95%CI = 2.69% i.e. <5%). Non-inferiority was also demonstrated for GMTs against YF one month post-YF-17D, and against DENV-2, -3, and -4 (UB95%CI <2), but not DENV-1 (UB95%CI: 2.22), one month post-second TAK-003 vaccination. Adverse event rates following TAK-003 were consistent with previous results, and no important safety risks were identified.In this study, YF-17D vaccine and TAK-003 were immunogenic and well tolerated when sequentially or concomitantly administered. The non-inferiority of immune responses to YF-17D and TAK-003 was demonstrated for concomitant administration of the 2 vaccines compared to separate vaccination, except against DENV-1 but with GMTs similar to those observed in other TAK-003 trials.NCT03342898.ClinicalTrials.gov identified:  Dengue and yellow fever are diseases endemic to tropical regions, often occurring in the same areas. There are highly effective vaccines against yellow fever, but there remains an unmet need for a dengue vaccine which can be used in people regardless of previous dengue infection. As multiple vaccines are often given together, particularly in travel medicine, we investigated the immunogenicity and safety of co-administration and sequential administration of a yellow fever vaccine and a tetravalent dengue vaccine (TAK-003) in adults living in areas of the US non-endemic for either disease. Most participants did not have pre-existing antibodies to either disease. We found that there was no reduction in immune response to the yellow fever vaccine when given at the same time as the dengue vaccine. There was also no reduction in response to dengue serotypes 2, 3, and 4, but this could not be established for the response to serotype 1. When sequentially administered, temporary increases were observed in yellow fever seroprotection rates after receipt of TAK-003, and in dengue seropositivity rates after receipt of the yellow fever vaccine, but these differences among groups were no longer seen by the end of the study. Both vaccines were well tolerated with acceptable safety profiles. Aedes aegypti mosquitoes, with four virus serotypes  broadly co-circulating in endemic regions [A. aegypti has been increasing with global temperature changes, risk of DENV transmission remains predominantly in tropical regions of South-East Asia, Central and South America, the Caribbean, and Sub-Saharan Africa [Dengue, a disease caused by the dengue flavivirus (DENV), is endemic in 129 countries worldwide, and was named by the World Health Organization (WHO) as one of the top ten threats to human health in 2019 [Aedes and Haemogogus mosquitoes [Yellow fever (YF) virus, the archetypal flavivirus, is closely related to DENV and is predominantly transmitted by squitoes . YF is esquitoes . YF virusquitoes , 7. Vaccsquitoes . The higsquitoes . YF neutsquitoes . In addisquitoes .While a highly effective vaccine against YF has been available for decades, there remains an unmet need for an effective vaccine against dengue which is suitable for use in individuals without prior exposure to the virus. TAK-003 is a tetravalent dengue vaccine candidate based on a DENV-2 backbone, which was originally designed and constructed by scientists at the Division of Vector-Borne Diseases of the US Centers for Disease Control and Prevention (CDC) . The DENThe overlapping geographical distributions of YF and dengue mean that travelers to endemic areas could be offered both vaccines. Concomitant administration increases the likelihood that recipients will receive all the necessary vaccines . HoweverThe aim of this study was to assess the immunogenicity and safety of TAK-003 and YF-17D administered either concomitantly or sequentially in healthy adults aged 18–60 years living in areas non-endemic for either disease.The study was performed in accordance with the International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Harmonized Tripartite Guideline and Good Clinical Practice (ICH E6(R2)-GCP) ethical principles that have their origin in the Declaration of Helsinki, and applicable regulatory requirements. The protocol, amendments, informed consent forms, and translations were approved by Schulman central institutional review board  prior to commencement of the study. Written informed consent was obtained from all participants prior to enrollment. The study protocol and the statistical analysis plan are available online at ClinicalTrials.gov where the study was registered (NCT03342898).2; pregnancy or breastfeeding; participation in another clinical trial within 30 days; receipt of vaccines prior to enrollment ; previous vaccination against any flavivirus or tick-borne encephalitis; current or previous flavivirus infection and ≥1 year living in a dengue-endemic area.Healthy adults aged 18–60 years were eligible for enrollment in the study. Exclusion criteria included fever (≥38°C) within three days of vaccination; known hypersensitivity or allergy to the vaccine or components; contraindications to YF-17D vaccine receipt; any serious chronic or progressive disease; altered immune function; body mass index ≥ 35kg/mFig 1. Group 1 received YF-17D plus placebo at Month 0, TAK-003 at Month 3, and TAK-003 at Month 6. Group 2 received TAK-003 plus placebo at Month 0, TAK-003 at Month 3, and YF-17D at Month 6. Group 3 received TAK-003 and YF-17D at Month 0, TAK-003 at Month 3, and placebo at Month 6. This study design allowed for YF-17D and TAK-003 control groups up until the second injection at Month 3. Participants were followed for approximately six months following the third vaccination, leading to a total study duration of 12 months. All study participants, the site personnel responsible for the evaluation of the study endpoint, and relevant sponsor staff were kept blinded to the random assignment until completion of the study and database lock. Due to differences in the appearance of the study vaccines, vaccines were prepared and administered by qualified unblinded personnel who did not participate in any of the study assessments.This phase 3, observer-blind, placebo-controlled randomized study was conducted at 11 sites across the US between February 2018 and May 2019. Participants were randomized 1:1:1 at enrollment using sequence of random numbers centrally-generated in blocks of 6 participants. The vaccine scheme for each of the groups is shown in 50). Seroprotection against YF was defined as reciprocal anti-YF neutralizing antibody titers ≥10 [50) [Blood samples were collected pre-vaccination at baseline (Month 0) and post-vaccination on Months 1, 3, 4, 6, and 7. Blood samples obtained at Months 3 and 6 were collected prior to the scheduled Month 3 and 6 vaccinations. Assessment of GMTs of YF neutralizing antibodies was performed using a validated plaque reduction neutralization test  at baseline and Months 1, 6, and 7, with GMTs corresponding to the dilution which resulted in a 50% plaque reduction (PRNTters ≥10 . DENV ne≥10 [50) . Partici10 plaque-forming units of TDV-1, TDV-2, TDV-3, and TDV-4, respectively. YF-17D (Stamaril) was also lyophilized and reconstituted with NaCl prior to injection. A single dose contained ≥4.74 log10 pfu YF-17D virus. While the licensed YF-17D vaccine in the US is YF-VAX , Stamaril  was used in this study, in agreement with the FDA, as there was a shortage of YF-VAX at the time of the study. Normal saline for injection (0.9% NaCl) was used as placebo. Concomitant vaccines were administered into opposite arms.TAK-003 was provided as a lyophilized formulation which was reconstituted with NaCl solution prior to administration. A single 0.5 mL dose of TAK-003 contained approximately 5.1, 4.5, 5.4, and 5.9 logThe primary study objective was non-inferiority (NI) of the YF seroprotection rate one month after concomitant administration of YF-17D with TAK-003 (Group 3) vs YF-17D with placebo (Group 1).Secondary objectives included assessments of NI of GMTs of neutralizing antibodies against individual DENV serotypes one month after the second dose of TAK-003 (Month 4) concomitantly administered with YF-17D vs TAK-003 with placebo (Group 3 vs Group 2) and NI of GMTs of neutralizing antibodies against YF, one month following concomitant administration of YF-17D with TAK-003 compared to YF-17D with placebo .Additional secondary immunogenicity objectives were seropositivity rates for individual DENV serotypes, one month post-second dose of TAK-003; GMTs of neutralizing antibodies and the seropositivity rates for all four DENV serotypes, one month post-first dose of TAK-003; GMTs of YF neutralizing antibodies and seroprotection rate in Group 2 one month post-YF-17D; GMTs of neutralizing antibodies and seropositivity rates for all four DENV serotypes one month post-second dose of TAK-003 in Group 1. Safety profiles of each vaccine were also assessed.® 6.01.The sample size of 300 participants per group (assuming approximately 15% drop-out) was sufficient to achieve approximately 90% overall power for demonstrating NI for the primary and secondary objectives. Sample size calculations assumed a one-sided significance level of 0.025 and were performed using nQuery AdvisorDENV and YF GMTs and seroprotection/seropositivity rates are presented as means with corresponding 95% CIs. Titers below 10 were given an arbitrary value 5. For the primary immunogenicity endpoint, NI was concluded if the upper bound of the 95% CI of the difference in YF seroprotection rates (Group 1 minus Group 3) at Month 1 was <5%. The Newcombe score method was used to compute the 95% CI of the rate difference . For theData are presented for the per-protocol sets (PPS). The YF PPS, i.e. all randomized participants who received planned Day 1 study vaccination(s) and for whom a valid pre-dose (baseline) and at least one post-dose measurement (Day 30) were available for YF immunogenicity assessments, and who had no major protocol violations, excluding those who were seroprotected for YF virus and/or who were seropositive for any DENV serotype at baseline, was used for assessment of the primary endpoint. The PPS, i.e. all randomized participants who received all planned study vaccinations, who provided a valid baseline measurement and at least one post-vaccination measurement for immunogenicity assessments, and had no major protocol violations, excluding those who were seroprotected for YF virus and/or who were seropositive for any DENV serotype at baseline, was used for assessment of all other immunogenicity endpoints. Safety was analyzed descriptively for the safety set, i.e. all participants who were randomized and received at least one dose of any study vaccines. All statistical analysis was performed using SAS version 9.4.Fig 2). Discontinuation rates were similar in each group, with majority of participants who did not complete the vaccination regimen and/or the study follow-up being lost to follow-up. Baseline characteristics were similar across the three treatment groups; the mean age was 41 years, 57% were female, and 66% were white (Table 1).All 900 randomized participants received at least 1 vaccination. Of them, 723 (80.3%) received the 3 vaccinations, and 739 (82.1%) completed the study follow-up (Table 2). YF GMTs and seroprotection rates after YF-17D vaccination were high in all groups (Table 3). One month after the first vaccination (Month 1), seroprotection rates were 99.5% (95% CI: 97.4–100.0%) and 99.1 (96.9–99.9%) in Groups 1 (YF-17D plus placebo) and 3 (YF-17D plus TAK-003), respectively. Similarly, the seroprotection rate in Group 2 one month after the YF-17D vaccination (Month 7) was 98.4% (95.4–99.7%). In Group 2, seroprotection rates rose to 9.8% by Month 1 and 12.0% by Month 6, despite not having received the YF-17D vaccine yet.The primary study objective of NI of YF seroprotection rate at Month 1 for Groups 1 vs 3 was met . GMTs were of similar magnitude at Month 1 in Groups 1 and 3 (4246 versus 4322), although GMTs were lower in Group 3 than Group 1 by Months 6 and 7 (Table 3). YF GMT in Group 2  was 3078 one month after YF-17D vaccination.The secondary endpoint of NI of YF GMTs between Groups 1 and 3 at Month 1 was also met, as the upper bound of the 95% CI for the GMT ratio was <2 (Table 2). However, NI was not concluded against DENV-1, where higher GMTs were observed in Group 2 than Group 3. GMTs against all four DENV serotypes increased post-vaccination with TAK-003 in all three groups. Lower GMTs were observed in Group 3 (concomitant administration of YF-17D and TAK-003) than in Group 2  against all serotypes, particularly between TAK-003 doses (S1 Table). GMTs against DENV-3 and DENV-4 following the first and second dose of TAK-003 were of higher magnitude in Group 1 than those observed at either time point in the other two groups. In Group 2, GMTs against DENV-1, -3, and -4 were of higher magnitude post-YF-17D than just after the first or second dose of TAK-003. When sequentially administered, GMTs against DENV-1, -2, -3, and -4 one month after the second dose of TAK-003 were 268, 2248, 302, and 347 in Group 1 (Month 7); and 297, 2616, 131, and 121 in Group 2 (Month 4). GMTs in the concomitant administration group (Group 3) were 183, 1948, 105, and 98 (Month 4) (S1 Table).The secondary objective of NI of DENV neutralizing antibodies was concluded against DENV-2, -3, and -4, as the upper bound of the 95% CI for the GMT ratio between Groups 2 and 3 at Month 4 was <2 (S2 Table). Tetravalent seropositivity rates by one month after the second dose of TAK-003 were 99.4% (96.8–100.0%) and 97.0% (93.5–98.9%), in the sequential administration Groups 1 and 2, and 97.7% (94.3–99.4%) in the concomitant administration Group 3. In Group 1, seropositivity rates increased to 4.3–15.8% across serotypes one month after receipt of the YF-17D vaccine but prior to receipt of TAK-003 (Month 1).Seropositivity rates were high in all groups post-vaccination (Table 4). The majority of these AEs were mild to moderate and did not persist beyond the diary period. The most frequently reported local AE across groups was injection-site pain, with rates varying depending on the vaccine received  . Rates of solicited systemic AEs were similar across groups , and mostly mild to moderate (Table 4). The most frequent solicited systemic AE was headache. Rates of solicited AEs tended to decrease with subsequent vaccinations . Unsolicited AEs were reported by 20.3%, 25.3%, and 21.4% of participants in Groups 1, 2, and 3, respectively. The most commonly occurring AEs were injection site conditions and upper respiratory tract infections (Table 5), with rash reported after TAK-003 by four participants, and after YF-17D by one participant; all these events were considered mild to moderate.Solicited local AEs were reported by 45.9%, 56.4%, and 60.3% of participants in Groups 1, 2, and 3, respectively .S9 Table). None of the SAEs were considered related to the study vaccinations.Across groups, twelve participants experienced AEs leading to withdrawal, including two deaths , which were considered unrelated to the study vaccinations. SAEs were reported by 4.3%, 3.3%, and 2.3% of participants in Groups 1, 2, and 3, respectively  in the group that received both vaccines (Group 3) compared with the group that received only TAK-003 (Group 2) at this time point. The clinical relevance of this observation is unknown as there is no correlate of protection established for dengue. However, the immune response against DENV-1 was similar to that observed in the clinical development program, specifically the pivotal efficacy trial in subjects who were DENV seronegative prior to vaccination . The serAs both vaccines assessed in this study were live attenuated vaccines against flaviviruses, there was the potential for immunological interferences and development of cross-reactive antibodies, leading to altered immunogenicity of one or both of the vaccines. Cross-reactivity of flavivirus antibodies has been observed following sequential natural infections , 37, 38,In our study, while NI of the response to the YF-17D vaccine, and to TAK-003 for DENV-2, -3, and -4 was demonstrated, DENV GMTs were numerically lower against all four serotypes 30 days after concomitant administration of the first dose of TAK-003 with YF-17D, compared with administration of TAK-003 alone. However, after the second dose of TAK-003, GMTs were mostly of similar magnitude in Groups 2 and 3, indicating that the effect was transient. The clinical implications of these observed interferences is unknown. Additionally, higher DENV GMTs following sequential vaccination (Groups 1 and 2), when compared with those following concomitant vaccination (Group 3), suggest a potential immune-enhancing effect of YF-17D (when administered prior to or after TAK-003) on TAK-003 antibody responses. Additionally, YF GMTs at Months 6 and 7 were higher in Group 1 than in Group 3 but were lower in Group 2 at Month 7 than in Groups 1 and 3 at Month 1, signaling that these immune interferences are complex, and may be influenced by the time and sequence of vaccination. As YF seroprotection rates remained near 100% at all time points post-sequential vaccination, this likely has no clinical impact for YF-17D vaccination. For TAK-003 vaccination, the clinical significance of this potential enhancing effect following sequential vaccination is currently unknown in absence of any immune correlates of protection for dengue.The short duration of follow up for immunogenicity endpoints (one month following receipt of the last vaccination) was a limitation for this particular study. While antibody persistence and long-term safety has been reported from a four-year study in children and adolescents living in endemic areas of Latin America and Asia , the immOne of the strengths of this study was that the design allowed analysis of concomitant and sequential administration of TAK-003 and YF-17D in a large group of participants who were seronegative for both diseases. As there is already a wealth of data available for both vaccines administered separately, we also chose not to include single vaccine groups to maximize the number of participants receiving the two vaccines concomitantly or sequentially. Performing the study in a non-endemic area for either virus allowed us to assess vaccine interactions without any additional impact of flavivirus exposure, either previously or during the study, as well as adding to the safety database of TAK-003 in seronegative vaccine recipients. Both vaccines in the study were well tolerated, and the safety profile of TAK-003 was similar to that observed in previous studies across baseline seronegative and seropositive participants –23. MostIn summary, no reduction in immune response to YF-17D vaccine, nor in immune responses to TAK-003 for DENV-2, -3, and -4, was observed when the 2 vaccines are co-administered. Marginally lower DENV-1 GMTs were observed. The clinical relevance of this is unknown but these titers remain similar to those observed in other trials, in particular in the pivotal efficacy trial that demonstrated the efficacy of TAK-003 against dengue cases (including those caused by DENV-1) in subjects who were DENV seronegative prior vaccination.S1 CONSORT checklist(DOC)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S5 Table(PDF)Click here for additional data file.S6 Table(PDF)Click here for additional data file.S7 Table(PDF)Click here for additional data file.S8 Table(PDF)Click here for additional data file.S9 Table(PDF)Click here for additional data file.


Overall, modified starches derived from KJ CMU-107 could potentially be developed into new pharmaceutical excipients.Starch extracted from KJ CMU-107 rice, with amylose content of 13.4%, was modified to yield pre-gelatinized starch (PGS), carboxymethyl starch (CMS), crosslinked carboxymethyl starch (CLCMS), crosslinked starch (CLS), and hydroxypropyl starch (HPS). Their physicochemical properties were assessed in comparison with the native starch (NS), and their functional properties were then evaluated for potential use as pharmaceutical excipients. Scanning electron microscopic (SEM) images and X-ray diffraction (XRD) patterns showed that granules of all but one of the modified starches retained the native character and crystalline arrangement. The exception, PGS, exhibited extensive granular rupture, which correlated with the loss of crystallinity suggested by the amorphous halo in XRD. Energy-dispersive X-ray (EDX) data confirmed the modification by the presence of related elements. Carboxymethylation increased solubility in unheated water, while crosslinking improved swelling. All modified starches displayed improved oil absorption capacity by 17–64%, while CMS and CLCMS also exhibited significant moisture sorption at above 75% RH PGS and HPS exhibited lower gelatinization temperature (Tg) and enthalpic change (ΔH), while CLS showed higher Tg and ΔH. CMS, CLCMS, and CLS showed adequate powder flow and compactibility, qualifying as potential tablet excipients. The 5%  Starches have long been utilized as pharmaceutical excipients, especially in the solid dosage form. Due to its availability, inertness, and low cost, native starch powder has been used as a diluent as well as a disintegrant in tablets. Starch paste has also been applied as a binder to facilitate the manufacturing of pharmaceutical tablets ,2. CommeOryza sativa L.) is one of the major starch-producing food crops. With the 2020 worldwide market value of rice starch reported at over 201.6 million USD, and the demand trending upward for applications in food, pharmaceutical, cosmetics, and other industries [Rice . Monochloroacetic acid  was purchased from Merck . Sodium trimetaphosphate  and propylene oxide  were supplied by Aldrich . All other chemicals employed in the preparation and analysis of modified starches were of AR grade or equivalent.The preparation of the flour from the rice grains was carried out by the conventional wet-milling method. For starch extraction, 700 mL of sodium hydroxide  was mixed with a 250 g portion of rice flour and mechanically stirred for 5 h at room temperature. The suspension was subsequently filtered through a 75 μm wire mesh, and the slurry was allowed to settle for 12 h. The clear supernatant was discarded, and the sediment was washed three times with distilled water. The pH of the mixture was adjusted to 7.0 with 1 M hydrochloric acid (HCl), allowed to settle, and the supernatant was removed. The extracted starch was washed several more times with water (600 mL each) and was finally collected via vacuum filtration. Following an air-dry and a subsequent oven-dry at 40 °C for 12 h, the native starch powder was ground to pass through sieve no. 60  before use.Five modified rice starches, namely, pre-gelatinized starch (PGS), carboxymethyl starch (CMS), crosslinked carboxymethyl starch (CLCMS), crosslinked starch (CLS), and hydroxypropyl starch (HPS), were prepared according to the scheme shown in For CMS and CLCMS, the degree of substitution (DS) of carboxymethyl groups was determined as described previously . The degThe amylose content (AC) of native starch was determined according to the method described by Gibson et al. , using aSEM studies to visualize the granule surface, shape, and size were conducted using a JEOL instrument model JSM-5410LV  equipped with a tungsten filament K-type. The acceleration voltage was 15 kV under the low vacuum mode (0.7–0.8 torr). The sample was mounted on a copper stub covered with carbon tape and sputter-coated with gold. The magnification was set at 2000×. The analysis of chemical composition was performed using an energy-dispersive X-ray (EDX) spectrometer .X-ray diffraction (XRD) analysis of starch and modified starch samples was carried out using a Siemens D-500 X-ray diffractometer. Diffractograms were recorded in the Bragg Angle (2θ) range of 5° to 40°. The scan rate was 2.5°/min, and the step size was 0.02°.g for 15 min. The clear supernatant was transferred to a preweighed crucible and dried at 120 °C to a constant weight, which was used to calculate the solubility percentage. The weight of the water-absorbing sediment was used to determine the swelling power. The process was repeated 5 times for each sample.Starch samples (0.1 g) were accurately weighed into a pre-weighed centrifuge tube. Then, 10 mL water was added, the mixture was vortexed for 1 min, and then heated at a controlled temperature of 70 °C with regular stirring. After 10 min, the tube was cooled and centrifuged at 3000× q) was calculated as follows:tm is the total weight of the teabag and the swelling content; tbm is the weight of the empty, dry teabag; wm is the weight of the water absorbed by the empty teabag; and sm is the weight of the dry sample.The teabag method described by Heß et al.  was usedThe moisture content of the starch sample was determined using an Ohaus MB25 moisture content balance  equipped with a halogen radiator. Approximately 2 g of the sample was spread on the pan and the accurate weight was recorded. The sample was heated at 105 °C until a constant weight was obtained. The moisture content was then calculated as the difference between the two weights divided by the original weight of the sample.The moisture sorption of starch samples was assessed for 7 days at various relative humidity (RH) levels. One gram of each sample, previously dried for 4 h at 80 °C, was accurately weighed into a pre-weighed, 2.5 cm diameter cup. The cups were then stored in desiccator housing beakers of saturated salt solutions, which provided 51, 62, 75, 83, and 92% RH at 30 °C for 7 days. The weight differences on day 0 and day 7 were determined and used in the calculation of moisture sorption of samples in terms of the percentage of weight gained.g for 20 min. The unabsorbed oil at the top of the tube was discarded, and the weight of the oil-absorbing sample was determined. The OAC value was calculated and reported as gram of oil absorbed per gram of starch sample.OAC analysis employed a method described by Bhosale and Singhal , with soo), peak temperature (Tp), and conclusion temperature (Tc) were recorded. The temperature range  of each sample was calculated. The enthalpy (ΔH) of gelatinization transition was expressed as J/g of dry starch.Thermal properties were evaluated using a DSC-7 differential scanning calorimeter . The analysis was carried out at a temperature between 30 °C and 120 °C, at a rate of 10 °C/min. Each sample pan contained 3 mg of starch and 15 μL of water. An empty pan was used as a reference. The onset temperature (TThe bulk and tapped densities of starch samples were determined according to the standard USP method . Carr’s The powder flow was assessed using the fixed funnel method and the angle of repose (AR) calculation. In brief, the sample (100 g) was poured through a 15 cm diameter glass funnel held at a height of 15 cm onto a piece of paper on a level bench top. As the sample formed a conical pile, its height (h) and radius (r) were determined. The inverse tangent of the h/r ratio yielded the angle of repose.The starch sample (250 mg) was filled into a 4.6 mm flat-face punch and die set, which was then compressed using a hydraulic press  at compression forces of 0.5, 1.0, 1.5, and 2.0 tons. The hardness of the resulting tablet was measured in triplicate using a hardness tester . A pressure-hardness profile (PHP) was plotted between the compression force applied and the hardness of the tablets.Starch samples (5 g) were dispersed in 100 mL deionized water while stirring at 150 rpm using a magnetic stirrer . For NS, PGS, CLS, and HPS, heat was applied to facilitate gelatinization, while CMS and CLCMS were dissolved in unheated water. Each solution was degassed, and 30 mL was poured on a Teflon plate and then dried in a hot-air oven at 50 °C for 16 h. The film-forming ability of each starch sample was inspected visually. Intact films were stored in a humidity chamber  for mechanical tests. Tensile strength (MPa) and elongation at break percentage (%) of the intact films were determined, in triplicates, using a TA-XT Plus Texture Analyzer  according to the ASTM standard method  with slight modifications. Intact films were cut into rectangular strips (2 × 6 cm) and stored at 25 °C and 58% RH for 48 h before testing. The initial grip separation and crosshead speed were set to 50 mm and 0.5 mm/s, respectively.p < 0.05).All tests were carried out in triplicate, unless indicated otherwise, and the data are presented as average values. Statistical analysis was conducted using a one-way analysis of variance (ANOVA) in SPSS (version 19.0). Tukey’s honestly significant difference (HSD) multiple range test was used to determine significance at a 95% confidence level (The amylose content (AC) of native KJ CMU-107 rice starch was determined to be 13.4%, which was classified into the group of low-amylose rice starch (10–19% AC). This value, which was determined by the lectin concanavalin A procedure, was slightly lower than the 14% AC previously reported for this rice strain . Pre-gelGranules of native KJ CMU-107 rice starch (NS) were mainly polygonal with diameter sizes ranging from 2 to 6 μm. Some granules appeared agglomerated, forming large, irregular shape mass with a slightly rough, indented surface. This was likely due to damage to the starch during the extraction process A. SEM ofThe energy-dispersive X-ray (EDX) data and spectra of the native and modified rice starches are presented in Native KJ CMU-107 rice starch exhibited a typical A-type XRD pattern, with major diffraction peaks at Bragg angles (2θ) of 15.1, 17.9, and 23.0 . PGS shoThe swelling power and the solubility of each starch, assessed at 70 °C, are displayed in Free swelling capacity (FSC) of native and modified starches, determined at 37 °C after 15 min, yielded results in the order of CLCMS > CMS > CLS > PGS > NS ~ HP . This pag/g) was physically modified into pre-gelatinized starch (OAC = 1.97 g/g). A higher particle surface area due to the physical disruption of PGS granules was likely the main contributor to this result. Modification of starch by carboxymethylation or crosslinking reactions significantly increased the OAC, while a combination of both reactions further increased the value to 2.76 g/g. The OAC value was also increased in the case of hydroxypropylated starch  up to 75% . The exco), peak temperature (Tp), conclusion temperature (Tc), and the order–disorder transition enthalpy (ΔH) of KJ CMU-107 rice starch and modified starches are presented in g) of KJ CMU-107 native starch occurred at 72.1 ± 1.1 °C, with the enthalpy change (ΔH) was calculated at 8.5 ± 0.5 J/g. Both values were on the lower side compared to those reported for rice starch in other studies [The onset temperature (T studies ,42. This studies . Starch  studies . PGS was studies . CMS and studies ,36,40. I studies  and enha studies . HPS gelAll modified starches exhibited lower tapped and bulk densities compared to those of native starch . Carr’s The pressure–hardness profile PHP,  represenw/v solution on Teflon plates. CMS film, in particular, exhibited a smooth surface with adequate flexibility. In contrast, NS, PGS, and CLS films were brittle and easily broken (CMS, CLCMS, and HPS formed intact films upon casting the 5% y broken .The TS and Eb were determined on the three intact films. For CMS, CLCMS, and HPS, TS values were 20.1 ± 1.4, 24.3 ± 1.9, and 16.1 ± 2.1 MPa, and Eb values were 3.76%, 2.87%, and 1.22%, respectively. All three intact films shared a common feature in that the hydroxyl groups were substituted with the larger moieties, which were able to disrupt the inter- and intra-molecular hydrogen bonding in the starch polymer . This inPhysical and chemical modifications constitute effective means to optimize the physicochemical and functional properties of starch. From altering fundamental properties such as solubility, swellability, moisture sorption, and water and oil absorption to improving mechanical properties such as flowability, compactibility, film-forming ability, and film strength, modified rice starches offer opportunities for broad applications in the food, pharmaceutical, and cosmetic industries.


We welcome them and look forward to seeing their impact on the Journal. You will also see some changes in the team of Associate Editors. After 4 years of service Hidekazu Suzuki and Deidre McNamara will leave us. They are wonderful colleagues and made great contributions to the Journal.Daniel Keszthelyi and Yasuko Maeda. Daniel is a Gastroenterologist from Maastricht, The Netherlands, has experience in the field of Neurogastroenterology and Motility, and regularly contributes to the Journal.This special issue of the UEG Journal marks the end of an era for the Editorial board. As of 2023, we are parting with the current team of trainee editors. Just over 2 years ago, we selected, with the help of the UEG Young Talent Group, 10 great European talents. They have made all the difference for us. This team, amongst others consisting of Chloe Melchior, Diogo Libânio, Alberto Zanetto, Dragos Ciocan, and Alexandre Nuzzo, assisted us in the review process and have honed their skills in making razor‐sharp assessments when judging scientific work. They provided us with a different perspective and helped us to select those manuscripts that will eventually make a difference in your clinical practice. The activities of the trainee editors have rapidly expanded over the last 2 years. We expanded our presence on Social Media and amplified the message from the published material. For those who follow us on Twitter, you are not alone! Indeed, on Twitter, we have created a network with >8000 professionals who receive regular updates on the UEG Journal and our editorial work. If you decide to publish with us, we offer you a host of communication tools to get the message out. In the last issue we published on the benefits of search engine optimization, and Marcus Hollenbach and Willem‐Pieter Brouwer helped us to adapt title and abstract so that the paper is easily findable amongst the competitors. With the help of Livia Archibugi, we create a visual abstract of each published article that is used on social media. The start of 2023 will also be published on the Journal's website. Iago Rodriguez Lago and Katarzyna Pawlak spearhead the podcast initiative, and since its inception, they have interviewed 13 authors who co‐authored UEG Journal articles. The trainee editors have been very prolific and have contributed significantly to the UEG Journal over the last 2 years.Clinical image to the UEG Journal as a new article type, providing you with exceptional pictures that capture a GI disease or clinical manifestation. More precisely, we hope to see the unusual visual presentations of a common disease, unexpected association between two relatively uncommon symptoms, or abrupt events in the course of managing a patient. Finally, UEG Journal is churning out guidelines thanks to the fine collaboration with the Quality of Care Task Force. Only in the last 2 years, the eight guidelines have been published covering functional and immunity disorders like achalasia, functional dyspepsia, gastroparesis, and microscopic colitis, but also diagnosis standards including carbon 13, hydrogen, and methane breath tests performance.UEG Journal continues further work under the Wiley® flag. This active, nearly 3‐year collaboration resulted in many improvements, including a smoother publishing process, increasing reach in the scientific market, introducing new marketing strategies, and upgrading the UEG Journal's website. We believe that all this, together with rigorously selected articles, contributed to an increase in Impact Factor that almost doubled (2017—3.543 to 2021—6.866)! Also, the UEG Journal visibility was boosted. Particular emphasis was put on engineering a way to share the journal's content in the most accessible form. Following trends, we wanted to send out a clear message: here you find top‐notch science, a can't‐miss. For this reason, the idea of UEG Journal brand‐specific visual abstracts was developed, and until now, almost 100 have already been published for selected articles. We are convinced that illustrations tell stories. That is why we introduced The future is bright for the UEG Journal thanks to its readers, contributors, editors, reviewers, and the UEG community!


This article  has beenPLOS ONE Editors issue this Expression of Concern.PLOS will be investigating these concerns in accordance with COPE guidance and journal policies. Meanwhile, the The journal has been informed that corresponding author CD is deceased.