The negative impact of COVID-19 pandemic has seen SME's struggling around the world. With many quickly adopting digital technologies, such as AI, in their manufacturing or services operations to achieve sustainable development. This study aims to develop a framework that informs AI-enabled sustainable development for SMEs by integrating the relevant research in the field. In this framework, we identify the opportunities that the deployment of AI technology can do to alleviate the plights of SMEs in the post-pandemic era, including the impacts on work, organizations, and performance. We further explore the challenges that SMEs face in AI transformation and recommend strategies to take on those challenges. Finally we propose an agenda for future research based on technological challenges and environmental threats. Small and medium-sized enterprises (SMEs) are the main driving force of employment and economic growth . The outThe surge of digital technology has triggered innovations in products, services, processes , and busThis study aims to develop a conceptual framework that informs AI-enabled sustainable development for SMEs by integrating the relevant research in the field. This is achieved by specifically reviewing most recent literature and attempting to answer the following research questions. First, what can the deployment of AI technology do to alleviate the plights of SMEs in the post-pandemic era? For example, where can AI be deployed? What are the benefits? What are the impacts on work, organizations, and performance? Secondly, what kind of challenges do SMEs face in AI transformation (or deployment)? How do we solve these challenges? Which stakeholders need to work together and in which direction?To address the above questions, we focus on reviewing the relevant research outputs published since 2019, when the COVID-19 pandemic started. The next section details the methodology adopted. We integrate the main theoretical viewpoints, themes of actions or strategies that SMEs should consider when developing sustainability by using AI technology. Next, we explore the challenges of AI transformation of SMEs and proposes future research directions based on the technological challenges and environmental threats.*”) and sustainable development  as keywords. The timeframe is limited to “2019–2022”, The literature type is limited to “articles, Early access or review”, and 62 articles are obtained through preliminary search. Next, we exported the detailed information of these studies  to an Excel spreadsheet.This study adopts the realist systematic approach to reviewing the relevant literature , 21. TheWe then checked whether these articles met the scope of the review and further refined the keywords by browsing the titles, abstracts, and keywords. After eliminating irrelevant and duplicate studies, we retained 10 articles. Next, according to these articles, we carried out a pre-citation and post-citation search , and expThe findings of our review are organized in a framework as presented in The COVID-19 pandemic and the lockdown and other control measures have made SMEs' operating environment the most fragile and unpredictable ever in recent history , 4. FirsNew technologies such as AI can help SMEs win competitive advantages or provide means of survival in the fields of manufacturing, e-commerce, accounting, human resources, marketing, and customer relations . ResearcSolutions based on AI can help manufacturing SMEs realize automation, which leads to process improvement and optimization . AI can AI are not only able to identify, verify and monitor customers in real time, but also determine purchasing power and interest in purchased goods, according to use traces, and then market segment products according to customers' specific needs. The pandemic control policy enables most consumers to switch to online consumption, and every customer must leave traces when using online services. Popular online sales provide AI with a large database to understand the actual needs and preferences of customers, and to advise manufacturers or retailers to target specific audiences for advertising, promotion, and sales optimization . AI can AI-based innovations such as virtual mirrors and visual search can provide services for garment or tourism organizations to improve customer interaction and narrow the gap between physical and virtual shopping experiences. The future smart kitchen and smart restaurant based on intelligent technology and highly intelligent auxiliary robots can provide a healthier kitchen lifestyle and develop a large health industry. During the COVID-19 pandemic, smart technologies have been widely used in the service industry, enabling the service organizations to carry out business activities within a safe distance, enhance customer delivery, create businesses for the organization, and provide competitive advantages during the new crown pneumonia pandemic. The customer service function of AI (such as chatbot) can help organizations answer simple requests from customers .Business risk is an important factor that hinders SMEs from achieving the goal of sustainable development. Because risk factors have the characteristics of data uncertainty and diversity, cognitive solutions based on AI can supplement the shortcomings of traditional solutions in dealing with complex data. It can solve the situation of fuzziness and uncertainty especially when the data is large or in different dimensions. Algorithms and technical solutions based on AI can help SMEs avoid business risks  and moveDue to the difficulty of demand forecasting caused by the pandemic, it is more important than ever to understand and predict consumer demand through an integrated supply chain, and AI technology may become a key component . In retaThe COVID-19 pandemic has driven SMEs to open the upstream and downstream ecology of the industry, fully meet the broad market demand of AI applications, and realize a complete industrial closed loop. For example, under the lockdown policy during the pandemic, some SMEs in the food supply chain, such as restaurants, cafés and retail organizations, could quickly carry out remote operations and allow online ordering, delivery and distribution . FurtherThe potential advantages of AI to develop multiple business models that provide customers with numerous advantages can be realized with AI-driven business models , by reduA core proposition of digital service is that digital technologies such as AI provide fundamental opportunities for services of industrial organizations, create and obtain value from new revenue streams and realize the difference from competitors by assuming greater responsibility to support customer results . For exaSMEs can take AI as the core and big data as the basis, whilst developing AI capabilities  to carry out technological R & D innovation or business model innovation, to create business activities with higher efficiency. First, to obtain and create new sources of income for SMEs, AI's value capture ability is used. It reduces errors in cost structure, potential income flow, financial feasibility, developing income models, and sorting out cash flow. Furthermore, AI can help SMEs match customer invoices with payments received .Secondly, using AI's value delivery capability, new operational processes and activities can be established to deliver the promised value. For example, AI can help small and medium-sized retail organizations use algorithms to customize products for consumers and analyze data on a large scale in digital marketing, so as to improve efficiency, achieve competition and growth .Thirdly, the value creation ability of AI can be used to help organizations make organizational decisions, obtain information and professional knowledge. For example, algorithms based on AI can find feasible solutions to problems of competitiveness and product quality and help to improve the productivity of SMEs and realize quality optimization and overall development. In the context of digital service aimed at optimizing the use and maintenance of products (product groups) in customer operations, AI services can be used by systematically evaluating AI applications and their potential value to customers and end-users . Any valThe COVID-19 pandemic has brought the digital transformation of organizations to the forefront. SMEs need to adopt new technologies to enhance, change or even destroy business models in order to remain competitive , 25. NonA considerable number of SMEs fail to successfully integrate AI capabilities into their business models due to the lack of readiness by the organization, which includes the readiness in human, financial, and material resources .To seize the opportunities enabled by AI, firms need to develop the capabilities of using AI technologies . Lack ofSuccessful AI transformation is more important to solve management problems , includiTalent shortage and skill gap are one of the primary strategic challenges of most SMEs in the AI environment , 26. At The cost of digital technology  and finaPrevious studies have shown that industrial 4.0 technologies such as autonomous robots and network physical systems are not feasible for SMEs because of the high cost . OrganizThere is little doubt that digital technology has improved quality and efficiency, according to Sjödin et al.  it is imOrganizations need a lot of data to adopt or deploy AI , which dFully functional AI requires digital connection, at the core of digitization, there are many supporting technologies enhancing the performance of products and services in a variety of ways. However, digitization may influence different stages of the co-creation process in a complex and unclear way , 57, 58.The concept of technical complexity is conceptualized through ease of use . TherefoCompatibility is the degree to which technology is assimilated and integrated within an organization's existing processes and available infrastructure . CurrentVarious environmental threats may become a dilemma for the generalization or expansion of AI services for SMEs.The successful adoption of AI technology requires the cooperation of many stakeholders. Thereby creating a digital service-oriented business model of organizations with a high-quality data ecosystem. However, bringing stakeholders together can be challenging, a shared ecosystem of digitization can affect the business model of any single organization, therefore, requires the business models of other organizations to be consistent . In an ASuccessful transformation of AI within SMEs needs the support of the government and other organizations. The government can play a key role in supporting the SMEs, by improving the existing legal and regulatory systems, raising the awareness of digital transformation, providing technical and financial support, strengthening data communication infrastructure , 45. TheThe collection of large data sets, its storage and sharing of that data derived from AI technology and raises ethical issues related to governance, quality, security, standards, privacy, and data ownership . TherefoAccording to Fletcher and Griffiths , the COVThe pandemic has affected organizations in all industries. The current research focuses on the application of AI technology in SMEs in the manufacturing industry and mainly focuses on the optimization, improvement, and upgrading processes. There is limited research in other industries and provides very little in way of new models, therefore, further research in AI technology in SMEs for other industries in the future is necessary and evaluate the preparation of SMEs for AI applications .First, organizations obtaining quality talents is a primary objective. Organizations should focus on training, recruiting, and retaining employees with AI technology . ConsideSecond, understand the principles required to use AI in the heart of the business model, such as what special resources and knowledge are needed by SMEs to formulate the transformation strategy of AI? When multiple organizations participate what are the routines that provide the basis for the large-scale implementation and use of AI in response to the pandemic? What is the accumulated knowledge and what are the interdependent actions ? How to Thirdly, we should think about how SMEs choose AI automation tasks and the degree of automation of each task . At the same time, we should consider how human intelligence can provide support in case of AI automation errors .Fourthly, investigate the financial difficulties of SMEs after COVID-19 and understand how supply chain finance uses the potential of AI technology to provide financial services to alleviate the dilemma of cash flow reduction and capital interruption , therebyFirstly, we should try and understand whether SMEs should adopt the AI strategies implemented by large organizations or formulate new AI strategies . SecondlAccording to Hansen and Bøgh , the futIn the event of continuously promoting automation, we must reflect on the concept of human beings in this cycle, the focus of AI is to enhance human ability rather than replace it. Therefore, humans may move upstream of the value chain to focus on design and integration-related activities of machines and manpower as part of the integration of AI . Future The pandemic may stimulate or accelerate the technological advancements of SMEs, including issues related to data protection and the decision-making process, which may directly affect the activities of the manufacturing sector. At this present moment, SMEs lack resources and knowledge to formulate special transformation strategies , and govFuture research can focus on the scope, strength, and type of support the government and relevant organizations can provide. For example developing an AI education strategy that can be embedded in government departments, higher education, and employers , whilst The management of data privacy is the key to the intelligent management of SMEs. It is necessary to explore the impact of security and privacy risks on the application of AI technology in SMEs. First, future research can include paying attention to how AI technology changes the working mode of SMEs, and the impact of this change on users and data privacy. Second, it can consider the specific policies that SMEs need to formulate to collect, share and analyze data , so as tWhether in Europe, the United States or China SMEs have created a number of new employment opportunities and contributed to the economy. To maintain a country's economic stability, the continuous growth of SMEs are paramount. The pandemic and its control measures have created various challenges for the sustainability of SMEs around the world, such as blocked logistics, interrupted supply chain, labor shortages, and reduction in demand. Creating uncertainty and making the most vulnerable SMEs fight for their survival and future development and thereby emphasizing the need for advancement of technology as a possible way forward. This paper integrates the latest research of AI-enabled opportunities and the challenges of AI transformation for SMEs in post-pandemic era. The various opportunities of applying AI to improve the continuous development of SMEs are identified, and the challenges of AI transformation of SMEs are discussed. Further research directions are proposed to help SMEs to better seize the opportunities enabled by AI technologies for continuous development.XL: conceptualization, formal analysis, funding acquisition, and writing—original draft. KW: conceptualization and writing—review and editing. YH: writing—review and editing. AQ: writing—review and editing and project administration. All authors contributed to the article and approved the submitted version.This research was supported by the Major Program of the National Social Science Foundation of China (Grant No. 20VHJ007), Soft Science Project of Fujian Province (Grant Nos. 2020R0066 and 2020R0067), and Xiamen Federation of Industry and Commerce (Grant No. H2021139).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Thoracic surgery carries significant risk of postoperative adverse events (AEs). Multiple international recording systems are used to define and collect AEs following thoracic surgery procedures. We hypothesized that a simple-yet-ubiquitous approach to AE documentation could be developed to allow universal data entry into separate international databases.AE definitions of the Canadian Association of Thoracic Surgeons (CATS) system and 4 international databases were matched and compared. This consisted of reviewing the definition of each AE as described by their respective database and assessing compatibility with the CATS system. We developed a single set of 4 drop-down menus to enable clear classification and facilitated data entry, using 3 single-select mandatory lists and 1 multiselect optional list classifying type and severity of these events.The CATS data elements were harmonized  with 100% (European Society of Thoracic Surgeons), 89% (Society of Thoracic Surgeons), 74% (Esophagectomy Complications Consensus Group), and 73%  of respective data elements. The addition of 17 AEs and 2 complication modifiers to the CATS system was implemented to achieve complete harmonization. Consequently, 100% of AE data elements currently included in all 4 international databases are perfectly or well-harmonized with the revised 4-choice drop down menu.We describe a framework for a ubiquitously applicable approach to AE monitoring following thoracic surgery harmonized with AE definitions of all major thoracic international associations. Use of this AE collection framework allows for comprehensive evaluation of both the incidence and severity of all AEs after thoracic surgery along with quality indicators. Four drop-down menus to classify postoperative adverse events. A ubiquitously applicable methodology using 4 drop-down menus to enable AE monitoring after thoracic surgery, harmonized with definitions of major thoracic international associations, is discussed.Multiple international recording systems are used to define and collect AEs following thoracic surgery procedures. A simple, ubiquitous approach to AE documentation was developed to allow universal data entry into separate international databases. This framework allows for comprehensive evaluation of both incidence and severity of all AEs after thoracic surgery, with potential for broad application.See Commentary on page 257.,,,,Thoracic surgery is the cornerstone of curative intent treatment for early-stage cancers of the chest, including lung and esophageal. However, it carries significant risk of postoperative adverse events (AEs), defined as any deviation from expected recovery from surgery, occurring in 30% to 60% of cases depending on the type of major thoracic surgery.,https://www.ottawatmm.org) has demonstrated feasibility, reliability, and reproducibility as a tool for systematic monitoring, reporting, and evaluation of postoperative complications following thoracic surgery.,Multiple international recording systems are used to define and collect AEs following thoracic surgery procedures. These include the Society of Thoracic Surgeons (STS),We hypothesized that a simple-yet-ubiquitous approach to AE documentation could be developed that would allow universal data entry into the separate international databases. In other words, we sought to create a single AE-documentation system that could feed data to all systems, including STS, ESTS, TM&M, ECCG, and NSQIP. In this short paper, we introduce this system and formally evaluate whether this AE documentation and classification tool would enable ubiquitous and effective translation into other validated international AE classification systems. Our intention was to use this as a method to improve deficiencies in our own system, which we ultimately hope will allow improved collaboration among international research societies.We aimed to create an AE classification system capable of harmonizing with all other database definitions. We developed a single set of 4 drop-down menus to enable clear classification and facilitated data entry . This syThe AE definitions of the CATS system and those of ESTS, STS, ECCG, and NSQIP databases were matched and compared. The matching process consisted of reviewing the definition of each AE as described by their respective database and assessing compatibility with those defined by the CATS system . Any disThe methods of AE data collection not only require clear definitions that are harmonized across international groups but also necessitate prospective recording of AE on a daily basis, ensuring the treatment team is participating in the recording of AEs. AEs may be recorded using a set of 4 drop down menus (3 single-select and 1 multiselect). In addition to daily prospective entry, weekly review is recommended to highlight all AEs and their incidence and severity, ensuring multidisciplinary discussion regarding the labeling of AEs in both incidence and severity. This prospective daily entry and weekly discussion is recommended as optimal to capture all AEs after all surgeries at any institution.The total number of AEs defined in the CATS, ESTS, STS, ECCG, and NSQIP classification systems was 65, 20, 56, 50, and 22, respectively . The CATThe recommendations for changes to the CATS classification tool were presented at the 2019 CATS National Database Meeting in April 2019. These recommendations were discussed, refined, and subsequently adopted by the CATS Database Governance Committee. Participants of the CATS national database began collecting data using these additional definitions as of July 2019.Clostridium difficile infection and bacteremia or bacteremic shock  as independent AEs. Thus, following the addition of these AEs, all AE recorded were well or perfectly harmonized with the STS, ESTS, ECCG, and NSQIP AE definitions. This capacity to create a ubiquitous data entry method in general demonstrates the broad applicability of the Clavien–Dindo classification schema adopted by TM&M and CATS. The utility of this ubiquitously applicable 4-drop down menu is that any vendor can see this information and thus feed data to ESTS, STS, CATS, NSQIP, and ECCG as they see fit. It can be adopted by any software tool and allow databases to be analyzed in a more synchronous manner.Our comparison provides insight into the degree of similarities and differences between the AE monitoring systems studied. We developed a ubiquitous AE classification system with 4 drop-down menus and matched them with the other international databases. The ESTS tracks 20 AEs and matched 100% (20/20), which can be attributed to previous collaboration between the 2 societies.Interestingly, our initial comparison of the databases showed that there were only 6 AEs  and 1 complication modifier (requiring reintubation) that are universally defined by all 5 databases. A comparison of only CATS, ESTS, STS, and ECCG increases the total of universally defined AEs to 13, with the addition of atrial arrythmia, ventricular arrythmia, delirium, recurrent nerve palsy, chylothorax, atelectasis, and acute respiratory distress syndrome . This fuIt is always a work in progress to review and maintain clearly defined AEs after thoracic surgery. One limitation in this work was the fact some AE definitions are not explicitly defined, which made determining harmonization challenging. As a small example, “deep vein thrombosis” is classified by ECCG as an AE; however, no specific criteria are provided to define this. In such cases, we considered the definition perfectly harmonized. This may have led to an overestimation in the degree of real-life harmonization if the CATS system with other databases.The primary author (G.S.) performed a review of the data elements of each classification system. The elements whose definitions either matched exactly or whose meanings were clinically indistinguishable were considered be in “Perfect” harmonization. Any definition whose wording did not match exactly was reviewed with the supervising author (A.S.) to determine its degree of harmonization. The authors recognize that this process represents a limitation in our methodology, as our outcomes are based on 2 authors' opinions as opposed to a more extensive and rigorous evaluation of opinions of other surgeons and experts in the field. However, we feel that the definitions of each classification system as a whole are straightforward and intentionally highly objective.https://www.ottawatmm.org) and provides a tool to facilitate translation of corresponding data elements between classification systems. While our project draws a specific focus to AEs following thoracic surgery, we believe our work employs a simple strategy, which can be applied broadly to monitoring AEs following many types of surgical procedures. The goal of harmonization of data collection is not synonymous with joining together multiple databases. It is rather to ensure that AEs are simply collected in the same manner, capable of participating in any or all international data-collection systems.The implementation of a ubiquitously applicable AE classification tool offers the ability to compare and share data with other international AE-monitoring systems. Broadening the volume of data available to assess surgical quality improvement has vast applications, including the study of more rare pathologies, procedures, and complications. The TM&M website reflects these changes (This paper provides a framework for discussion and advancement toward a harmonized approach for AE definition and recording following thoracic surgery . We hopeThe authors reported no conflicts of interest.Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.The


Starch is an ideal wall material for controlled release in oral delivery systems due to its non-allergic properties, availability, and cheap price. However, because of its poor mechanical behavior and high water permeability, it is necessary to modify the amphiphilic nature of starch. Surfactants are essential components to emulsify the lyophobic food ingredients. However, the interaction of starch with emulsifiers and how they affect the pasting behavior and digestion of starch are not well understood. In this paper, surfactants, such as non-ionic Tween (TW) and ionic sodium fatty acid (NaFA), with varying hydrophobic carbon chain lengths, were selected as model amphiphiles to investigate the structural, pasting, rheological properties and in vitro digestibility of regular and frozen starch samples. The results showed that, in most cases, the addition of TW reduced the viscosity of starch. However, saturated medium-chain NaFA increased the starch viscosity and rheological modulus greatly. Both surfactants inhibited starch digestion. This paper presents a comparative investigation on the effect of ionic and non-ionic surfactant on the structure and properties of corn starch, and therefore the information is useful for structural-based formulation with starch for developing colloidal delivery systems. It is also helpful for developing functional food with controllable digestion properties. Starch is one of the most abundant natural carbohydrate polymers. It is an ideal wall material for the controlled release in oral delivery systems due to its non-allergic properties, availability and low-cost . The staCorn starch was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. . Tween 20 (polyethylene glycol sorbitan monolaurate), Tween 40 , Tween 60 (polyethylene glycol sorbitan monostearate) and Tween 80 (polyethylene glycol sorbitan monooleate) , sodium n-caprylate (NaFA (C-8)), sodium capricate (NaFA (C-10)), sodium laurate (NaFA (C-12)) and sodium oleate (NaFA (C-18)) were purchased from TCI Corporation. α-Amylase from porcine pancreas was purchased from Sigma-Aldrich .w/v%) was obtained by adding corn starch into ultrapure water. The starch suspension was gelatinized in a boiling water bath for 20 min and cooled to room temperature. After it had been frozen in a refrigerator at −18 °C for 24 h, the starch was taken out and melted in a water bath at 25 °C for 3 h. The obtained starch gel was then freeze-dried before subsequent measurement.Corn starch suspension (6 w/w) starch mixture, and then surfactants were added to it. Surfactant-free corn starch was used as a control. The starch suspension was maintained at 50 °C for 1 min and heated to 95 °C (12 °C/min) for 2.5 min. The mixture was then cooled to 50 °C at 12 °C/min and held for 2 min. The pasting temperature, peak viscosity, breakdown, setback, and final viscosity was recorded throughout the process. After gelatinization, the starch paste was freeze-dried, ground into a powder with a mortar, and stored at 4 °C for structural characterization.The pasting properties of starch were measured by using a Rapid Visco Analyzer with paddle agitator . The method was referred to by Zheng et al. , with slDynamic rheological measurement was carried out by a rheometer . The gelatinized starch gel obtained in the RVA test was transferred to the test platform at 25 °C. The frequency sweep was set to a range of 0.1–10 Hz at 1% strain (within the linear viscoelastic region). The gap was set at 1 mm. The elastic modulus (G′) and viscous modulus (G″) were obtained by TA rheometer data analysis software .−1. The number of scans was 48, and the resolution was 4 cm−1. FTIR data were analyzed with OMNIC software . The starch samples used for FTIR spectroscopy were obtained by freeze-dried products from RVA. The sample (10 mg) and KBr (200 mg) were ground and pressed into sheets for the FTIR measurement . Spectra were recorded from 4000 to 400 cm−1, pH = 7.0), and the mixture was gelatinized in a boiling water bath for 20 min. The obtained starch solution (10 mg/mL) was cooled to 37 °C and used as the stock solution.The in vitro enzyme digestibility of starch was determined by 3, 5-dinitrosalicylic acid (DNS) colorimetry . Five huThe surfactant (40 mg) was mixed with starch solution (8 mL) and 12 mL phosphoric acid buffer. The obtained solution was placed in a water bath pot at 37 °C and stirred magnetically for 30 min at 300 rpm. α-Amylase was treated by centrifugation for 20 min . Next, 1 mL supernatant of α -amylase (0.19 mg/mL) was added to the above starch-surfactant mixture to start the enzymatic reaction.At a specific interval , the product was taken out and added with DNS, and then reacted in a boiling water bath for 3 min. After being rapidly cooled by ice water, the reaction mixture was diluted with ultrapure water. The content of reducing sugar content was calculated according to the absorbance at 540 nm, which was determined with a microplate reader.Each experiment was repeated three times. A statistical analysis was performed using Origin 2022b. One way Duncan analysis (SPSS-21.0) was used for the significant difference test, and the results were reported as means and standard deviations.0–d0 shows the RVA pasting curves of corn starch in the presence of TW and NaFA surfactants. The pasting parameters obtained from the RVA curves are shown in 0, after the addition of TW, the peak viscosity of corn starch decreased. As the length of the hydrophobic chain of TW20, TW40, and TW60 increased, the peak viscosity showed a slight increase. 0 shows that as the concentration of TW20 increased, the peak viscosity of starch decreased. NaFA is an ionic surfactant in which the head group undergoes strong hydration. Therefore, the interaction of its hydrophobic groups with the starch hydrophobic domain, as well as the competitive hydration of its polar group, jointly affected the gelatinization of starch. Medium-chain fatty acids, such as NaFA (C-8) and NaFA (C-10), promoted the hydration of the starch chain, which was manifested by an increase in peak viscosity (0). In 0, as the concentration of NaFA (C-8) increased, the peak viscosity of starch increased. However, within the range of several fatty acids examined, the viscosity decreased with an increase in chain length. This is different from the case of starch with TW, suggesting different hydrophobic chain-length dependence effects of ionic and nonionic surfactants. It is noteworthy that no viscosity peak was observed in starch with sodium oleate (C18). Wang [Starch pasting occurs after heating starch above the pasting temperature. Consequently, the starch granules lose their crystalline structure, absorb water, swell, and become viscous. iscosity c0. In FiAs shown in During the cooling stage (95 °C to 50 °C), a viscosity peak was observed in the TW system. It was suggested that the viscosity peak at cooling is associated with the formation of starch-surfactant complexes ,22. The Compared with regular corn starch, the frozen corn starch shows an irregular RVA curve and lower peak viscosity, trough viscosity and final viscosity a–d. Afte0–h0) shows that the addition of TW or NaFA lowered the G′ of the starch paste. As the length of the TW carbon chain or the concentration of TW20 increased, both G′ and G″ decreased gradually. This may be due to the fact that the surfactant prevented the amylose molecules in the starch particles from precipitating into the starch paste and inhibited the expansion of the starch granules [Rheological properties of unfrozen or frozen corn starch in the presence of TW and NaFA are shown in granules .In summary, in terms of rheological properties, the G′ of unfrozen starch decreased with the increase of the carbon chain length of TW and NaFA, while the G″ of starch remains unchanged in the presence of NaFA. As the length of the hydrophobic carbon chain of TW increases, G″ decreases regularly. For frozen starch, medium-chain NaFA (C-8) at lower concentrations and NaFA (C-10) increased the G′, while TW and long-chain NaFA reduced G′.−1 is ascribed to the stretch vibration of the hydroxyl group [−1 is the stretch vibration of -CH2 of the polysaccharide [−1 are attributed to C-H stretch vibrations. After the addition of surfactants, two new C-H stretching vibrations peaks appeared which comes from the asymmetrical and symmetrical components of CH2 and CH3 stretching due to the presence of hydrophobic chains of fatty acid. For systems containing TW or NaFA, peak strength at 2900 cm−1 shows chain length and concentration dependence. The strong sharp peak at 720 cm−1, which originally belonged to NaFA, disappears in the starch-NaFA mixture, possibly because NaFA entered the double helix structure of starch to form a complex.yl group . For froyl group  et al. fyl group . The peaccharide  in which−1 is the fingerprint region that characterizes the conformation changes and ordered double helix structure of the starch [−1 (I1047/1022) reflects the relative content between the ordered and amorphous structures of starch. 1047/1022 of freeze-dried corn starch paste which was mixed with TW or NaFA. For both surfactants, I1047/1022 increases as the hydrophobic chain length increases, indicating an increase in the order of medium-range structure. However, for ordinary starch containing TW, the I1047/1022 value is higher than pure starch, while the system containing NaFA has a lower I1047/1022 value than pure starch. TW with longer chain lengths made the structure of corn starch more orderly, but NaFA reduced the order of structure. TW20 and NaFA exhibited opposite concentration dependence. In the case of frozen starch, I1047/1022 is higher than that of unfrozen starch, indicating that the freezing treatment facilitated the orderly arrangement of starch granules and promoted starch retrogradation. Yang [The infrared peak range of 1065–950 cme starch . The raton. Yang  et al. a0), starch digestibility decreased as the length of the hydrophobic chain increased. The final digestibility of starch-NaFA (C-8) was 78.68%, and the final digestibility of the starch-NaFA (C-18) was 50.76%. The effects of both surfactants on starch digestion show chain-length and concentration dependence. Previous studies showed that non-waxy rice starch with long-chain saturated fatty acids had lower in vitro digestibility than those with medium-chain fatty acids added [The above results show that after the addition of TW or NaFA, the pasting properties and microstructure of both ordinary starch and frozen starch were changed. In order to investigate the enzymatic hydrolysis of starch that has been treated with freezing and surfactants, the digestibility of starch was studied. Compared with additive-free corn starch under the same conditions, the pure starch was digested by α-amylase by nearly 90% in 180 min. In the corn starch-NaFA system c0, starcds added . The decds added . The fords added . Tween 8In this study, typical ionic and non-ionic amphiphiles such as Tween (TW) and sodium fatty acid (NaFA) were selected to study their effects on pasting properties, rheological properties, structure and digestibility of regular or frozen corn starch. The results show that NaFA, an ionic surfactant, provided a stronger electrostatic effect, and therefore had a greater effect on starch viscosity than TW. NaFA with a shorter chain may be able to assist in the decrystallization of amylose, resulting in more amylose dissolving and stronger hydration, thus increasing the viscosity of starch in most cases. The effect of NaFA on viscosity was more pronounced than the effect of TW. NaFA and TW have very different effects on the rheological properties of frozen starch. The addition of TW could increase the content of medium-range ordered structure of starch whereas NaFA showed opposite behavior. However, both surfactants could inhibit the digestibility of starch. A certain chain length and concentration dependence effect were observed for both surfactants. This study has significance for understanding the mechanism of using amphiphilic food additives to modify the processing performance and digestibility of starch. Moreover, this paper presents a comparative investigation on the effect of ionic and non-ionic surfactants on the structure and properties of corn starch, and collects useful information for the development of starch-based colloidal delivery systems for control-release purposes.


Fcf) was recorded in 3-point-bending. Flexural strength (σ) in MPa, Vickers hardness (HV) in N/mm2, fracture toughness (IcK) in MPa*m1/2, Weibull Modulus (m) and characteristic Weibull strength (σw) in MPa were assessed. Statistical analysis was performed using ANOVA analysis. FS and IcK were significantly higher (p < 0.05) for Katana™ HTML (652.85 ± 143.76–887.64 ± 118.95/4.25 ± 0.43–5.01 ± 0.81) in comparison to Katana™ STML (280.17 ± 83.41–435.95 ± 73.58/3.06 ± 0.27–3.84 ± 0.47) and UTML (258.25 ± 109.98–331.26 ± 56.86/2.35 ± 0.31–2.94 ± 0.33), with no significant differences between layers and layer thicknesses. The range of indications should be carefully considered when selecting the type of monolithic zirconia for fabrication of dental restorations, as materials widely differ in mechanical properties.New monolithic multi-layered zirconia restorations are gaining popularity due to their excellent aesthetic properties. However, current knowledge of these newest multi-layer ceramics in terms of mechanical properties is scarce. Three monolithic, multi-layered zirconia materials  were selected for comparison: High Translucent Multi-layered zirconia (HTML), Super Translucent Multi-layered zirconia (STML) and Ultra Translucent Multi-layered zirconia (UTML). Fifteen specimens per group were cut from pre-sintered blocs in each of the four layers  and in different thicknesses . Critical fracture load ( Zirconia is gaining popularity as the restoration material of choice for dental prostheses and is a viable alternative to conventional metal–ceramic restorations. The main advantages of zirconia are its biocompatibility , biomechMechanical properties of ceramics are typically assessed by different material-dependent values such as flexural strength, Weibull modulus, fracture toughness and Vickers hardness . In a flMore recently, new monolithic multi-layer ceramic materials have been developed with different color and translucency gradients throughout the layers in order to improve semblance to natural tooth structure: while the incisal part of teeth is more translucent, the cervical area appears opaquer . ZirconiThus, the object of the study was to investigate whether there is a difference in mechanical properties in terms of flexural strength, Vickers hardness, Weibull modulus and fracture toughness of three different Katana™ Zirconia Multi Layered blanks: Katana Zirconia High Translucent Multi-layered (HTML), Super Translucent Multi-layered (STML) and Ultra Translucent Multi-layered (UTML). The second aim of this study was to investigate whether there is a difference between the layers within a blank. Furthermore, another advantage of these pre-layered blanks is the possibility of reducing the layer thickness due to the lack of the veneering material ,18. TherThree commercially available pre-sintered Katana™ Zirconia Multi Layered materials were selected in this comparative study: Katana™ Zirconia Multi Layered (ML), Katana™ Zirconia Super Translucent Multi Layered (STML) and Katana™ Zirconia Ultra Translucent Multi Layered (UTML). Preparation of specimens for the determination of mechanical properties was performed in accordance with the DIN standard ISO 6872:2015. Bar-shaped specimens were cut from pre-sintered ceramic blocs using a band saw  in four different layers  horizontally . SpecimeHV) was measured with a microhardness tester . Specimens were mechanically loaded with a defined force F of 49.5 N (HV) perpendicular to the surface using a Vickers diamond indenter in the shape of a pyramid with an inclination angle of 136° at the tip. A minimum of six indentations were performed per specimen. The indentation was measured by optical evaluation with a microscope with a magnification of 40 and 65 times and an integrated 18 Megapixel camera, and electronically assessed with the aid of an image-editing program . Vickers hardness HV in MPa was calculated according to the following formula:F = test force in N, and d = average of the indentation diagonal in mm. For calculation of the fracture toughness (IcK) in MPa√m by indentation fracture (IF) method according to Anstis et al. [a = ½ d  in mm, c = ½ of crack length in mm, E = Elastic modulus of Zirconia  in MPa was assessed by three point bending tests in a universal testing machine  at 1 mm/min crosshead speed. The critical fracture load (Fmax) in Newton (N) until crack formation was measured. FS was calculated as follows:L = distance between the outer support in mm, F = maximum fracture load in N, w = width of specimen in mm and b = thickness of specimen in mm.Flexural strength n = 20) were obtained and sorted in ascending order. Weibull modulus (m) and the characteristic strength in MPa (wσ) were obtained from the Weibull diagram, applying the Equation (5) with p—fracture probability, σ—flexural strength.Weibull analysis was employed for reliability evaluation of the flexural strength of the different Zirconia materials. For each material FS values . After assessment of the normal distribution using the Kolmogorov–Smirnov test the data were analyzed by one-way analysis of variance (one-way ANOVA) with post hoc Scheffé and Bonferroni for comparison of mean values. For all tests the significance level was set at σ) in MPa, Vickers hardness (HV) in MPa and fracture toughness (IcK) in MPa√m are presented in p < 0.05), in HTML ranging from 652.85 ± 143.76 to 887.64 ± 118.95, in STML from 280.17 ± 83.41 to 435.95 ± 73.58 and in UTML from 228.67 ± 39.34 to 331.26 ± 56.86. For flexural strength σ within one material there were no significant differences between layers L1, L2, L3 and L4, and between different layer thicknesses 0.4 mm, 0.8 mm and 1.2 mm (p > 0.05) within each material. However, when combining all layers in the same layer thickness within one material, a significant difference (p < 0.05) could be found between flexural strength values of samples with 0.4 mm layer thickness and with higher layer thickness of 0.8 and/or 1.2 mm layer thickness. The data were normally distributed, therefore parametric tests for statistical comparison were applied. Descriptive statistics with means and standard deviations (SD) for flexural strength .Vickers hardness p < 0.05): HTML (4.25 ± 0.43–5.01 ± 0.81), STML (3.06 ± 0.27–3.84 ± 0.47), UTML (2.35 ± 0.31–2.94 ± 0.33). Within each material there were no significant differences for fracture toughness found between different layers L1, L2, L3 and L4 and layer thicknesses 0.4 mm, 0.8 mm and 1.2 mm (p > 0.05).Fracture toughness values varied between different Katana™ materials, with lowest values in UTML and highest values in HTML . The meaResults of the Weibull moduli and characteristic strength are given in Weibull moduli in HTML ranged from 5.27  to 11.95 . Weibull moduli in STML ranged from 2.12  to 7.77 . Weibull moduli in UTML ranged from 2.84  to 14.90 . A low Weibull modulus correlates to a large variation in strength values within one group. Therefore, a higher Weibull modulus correlates to a low variation in values and a higher reliability. Within each material, Weibull moduli for 0.4 mm layer thickness were lowest, showing a low reliability for this layer thickness. Higher layer thicknesses of 0.8 and 1.2 mm led to higher Weibull moduli and thereby to better reliability of the materials’ strength. This is also visible when the Weibull modulus is calculated of all layers L1 to L4 together . Within This comparative in vitro study investigated the mechanical properties of three different multi-layer zirconia ceramics: Katana™ HTML, Katana™ UTML and Katana™ STML. Moreover, this is the first study reporting on the mechanical properties of different layers within one specific blank of Katana™.2 crystals [2O3 content and an increased amount of cubic phase . The wide range of published values on mechanical properties in the literature shows the difficulty of a direct comparison. Data are dependent on different variables such as experimental set-up, testing parameters and the test procedure . The milFracture toughness is considered as an additional and essential factor for the assessment of mechanical properties of ceramics . It is aIcK values indicate significant differences between tested materials Katana™ HTML, STML and UTML, and no significances between layers in one material. Data on Vickers hardness are consistent and in line with the scientific literature [Fracture toughness by IF method, as was undertaken in this study, is comparably simpler in preparation than other methods, such as single edge notch beam or Chevron notch beam tests. According to Anstis et al. there is only about a 30% correlation between fracture toughness values by IF and other methods . Howeverterature .Data over all layers show that specimens in Katana™ STML and UTML groups exhibited slightly lower Weibull moduli than in HTML, indicating scattering in results attributed to physical structural properties of the ceramic material, especially the size and distribution of defects. In contrast to conventional 3Y-TZP, zirconia ceramics with higher yttria content exhibit lower tetragonal phase content and therefore less transformation toughening with simultaneous crack closure mechanisms. Data are in line with another study . Within Chemical composition, microstructure and translucency properties were assessed for Katana™ STML, UTML and HTML in another laboratory study . The autMeasurement specifications for mechanical properties for dental ceramics are suggested by the ISO-6872 standard . The norFor monolithic fixed partial dentures with ≥4 units, the norm specifies a minimum of 800 MPa for flexural strength. As shown in Limitations of the present study are a lack of optical evaluation with the aid of translucency tests, microstructural analyses and material compositions in terms of yttria-content, grain size and distribution, lack of testing of aging behavior and hydrothermal degradation. These variables need further investigation. Furthermore, future research should investigate mechanical properties and fracture behavior of fully anatomical and zirconia frameworks after thermocycling, mechanical loading and aging behavior prior to clinical application.Although new multi-layered zirconia materials have optimal esthetic qualities, results implicate high differences in flexural strength and fracture toughness between conventional and more translucent zirconia materials. Biaxial strength of the investigated new highly translucent multi-layer ceramics is even comparable to lithium-disilicate ceramics ,22,31. TWithin the limitations of this in vitro study design, flexural strength and fracture toughness was significantly higher for Katana™ HTML in comparison to Katana™ STML and UTML;IcK seems relatively reliable and thus suitable as a basis for the indication;The correlation between fracture toughness and bending strength corresponds to that proposed by Filser et al.  and showThe range of indications based on these data should be carefully considered when selecting the type of monolithic zirconia material for fabrication of dental restorations, as materials widely differ in mechanical properties.


NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date.Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC.We present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of This case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy. NOTCH2NCL gene or a positive skin biopsy with characteristic pathology  is a rare neurodegenerative disease with a wide range of clinical manifestations, including dementia, movement disorder, muscle weakness, and autonomic dysfunction . Multiplathology . Whereasathology . In thisNOTCH2NLC gene was detected by repeat-primed polymerase chain reaction  was noted and the patient was subsequently diagnosed with early-stage lung cancer through the related biopsy in the operation. Analysis of cerebrospinal fluid revealed increases in protein (126.5 mg/dl) and glucose (4 mmol/l) levels with a normal cell count. No abnormalities were found in either blood or cerebrospinal fluid autoantibody tests of peripheral neuropathy, including anti-ganglioside antibodies , para-nodal antibodies , and paraneoplastic antibodies . Brain MRI showed diffuse, bilateral white matter lesions without hyperintensity in the white matter adjacent to the cortex on DWI . Howeverreaction , furtherNIID is a heterogeneous disease entity with variable clinical manifestations involving cognitive, motor, sensory and autonomic systems . SimilarThe sensory episodes in the present case were distinct from previously reported paroxysmal phenotype which usually involves diffused cortical lesions with unconsciousness, hemiplegia, aphasia, or epileptic seizures –9. RelatThis case provides a representative example of the mismatching feature between the subjective manifestation and objective examination in NIID, similar to other hereditary or neurodegenerative diseases , 11. PatThe mechanisms of paroxysmal symptoms in NIID have not been fully understood yet. According to previous studies, we proposed three possible hypotheses for the recurrent sensory attacks in our patient. First, previous studies have identified the transient vasospasm and hypoperfusion in NIID leading to stroke-like episodes , 18. HowOur patient showed a unique clinical symptom and uncommon MRI findings that made it difficult to diagnose him with NIID in the early stage. Initially, we focused on the diagnosis of peripheral neuropathy since the electrophysiological results were similar to those of Charcot–Marie–Tooth (CMT) disease . BesidesIn summary, we should consider NIID as a differential diagnosis for the undetermined etiology of sensorimotor neuropathy even lacking the characteristic brain MRI findings in the early stage. The present report demonstrates the electrophysiological characteristics of certain paroxysmal sensory deficits in NIID, which addresses the prevalence of sub-clinical peripheral nerve impairments and advances the clinical spectrum of NIID.The datasets presented in this article are not readily available because of ethical and privacy restrictions. Requests to access the datasets should be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Ethics Committee of Peking University Third Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.JF and CZ: data collection and drafting the manuscript. GH, XL, and MZ: data evaluation and manuscript revision. YSZ and DZ: pathological test. SZ, YXZ, XH, and SY: data collection. DF: funding, data collection and evaluation, supervision, manuscript revision, and final approval. All authors contributed to the article and approved the submitted version.


Proper regulation of cell death and survival is essential for cellular homeostasis. Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking cell death, modulating signal transduction, and affecting cellular proliferation. By contributing to the evasion of cell death, IAP proteins enhance the resistance of cancer cells to treatment with antitumor agents and impact tumor progression. IAP proteins can be negated by SMAC  and SMAC-mimicking IAP antagonists . IAP antUsing surface plasmon resonance (SPR), we found that IAP antagonists GDC-0917 and Debio1143 preferentially bind BIR3 domains over BIR2 domains of c-IAP1 and XIAP Fig.  10]. To. To10]. We next wanted to compare the activity of GDC-0917 and Debio1143 in vivo and evaluated the relative activity of both drugs in the MDA-MB-231 xenograft model. We chose a dose of 10 mg/kg for GDC-0917, since it was a near maximally effective dose but also a well-tolerated dose based on prior work . We testIn order to extend these observations to a second model, we dosed mice bearing subcutaneous LL/2 (LCC1) tumors with 15 mg/kg GDC-0917 or 30 mg/kg Debio1143 (the dose of Debio1143 that showed the highest tumor to plasma ratio in the MDA-MB-231 model). Analyses of both drugs over several time points revealed similar exposures for both drugs in plasma but with GDC-0917 exhibiting slightly higher T/P ratios Fig. . SimilarOverall, these findings indicate that GDC-0917 has better potency in stimulating the death of cancer cells, promoting c-IAP1 degradation, and in inhibiting tumor growth than Debio1143. Importantly, neither molecule appeared to accumulate extensively or consistently within the tumor with in vitro potency and in vivo pharmacodynamics being better predictors of in vivo antitumor activity than T/P ratio. A number of factors may contribute to the observed higher potency of GDC-0917 compared to Debio1143 . We trust that this study will help in the future evaluation of IAP antagonists in hopes of bringing these promising reagents to cancer patients who need them most.Supplemental Material


Obesity and type II diabetes are closely related to the rapid digestion of starch. Starch is the major food-energy source for most humans, and thus knowledge about the regulation of starch digestion can contribute to prevention and improved treatment of carbohydrate metabolic disorders such as diabetes. Pectins are plant polysaccharides with complex molecular structures and ubiquitous presence in food, and have diverse effects on starch digestion. Pectins can favorably regulate in vivo starch digestion and blood glucose level responses, and these effects are attributed to several reasons: increasing the viscosity of digesta, inhibiting amylase activity, and regulating some in vivo physiological responses. Pectins can influence starch digestion via multiple mechanisms simultaneously, in ways that are highly structure-dependent. Utilizing the multi-functionalities of pectin could provide more ways to design low glycemic-response food and while avoiding the unpalatable high viscosity in food by which is commonly caused by many other dietary fibers.  Pectic polysaccharides, or pectins, form a family of polysaccharides in the cell walls of higher plants . The majpA) residues. Carboxyl groups in HG are largely methyl-esterified when originally synthesized by the Golgi apparatus, and are then gradually de-esterified in vivo by pectinesterase during the growth of the plant. Based on the degree of esterification (DE), pectins can be divided into low methoxyl (LM) pectins (DE < 50%) and high methoxyl (HM) pectins (DE > 50%). The backbone of RG-I is the repeating disaccharide unit, [→4)- α -D-GalpA-(1→2)- α -L-Rhap-, β-D-galactopyranosyl  or acidic β-D-glucuronosyl (GlcpA) residues [p. Both rhamnogalacturonan-II and xylogalacturonans can be classified as substituted galacturonans [Pectins have galacturonic acid  as their main component, and as many as 16 other monosaccharides as co-monomers . A schemins DE < 0% and hi2+) via coordination bonds [Pectins from different sources, locations and growth conditions of plants and processing methods can differ in monosaccharide composition, molecular size/weight , degree of methyl esterification (DE) and degree of acetylation (DA), thus making the molecular structure of pectins very complex. Although sharing the same name, pectic polysaccharides with diverse compositions or structures can differ significantly in physicochemical and physiological properties as well as functions. For example, LM-pectins form a gel in the presence of divalent ions  ubiquity in food and wide applications in food industry, (2) reliable safety, (3) abundant health benefits, and (4) versatile molecular structures with the potential for tailor-made properties. With these advantages, people have studied pectin’s effects on starch in vitro digestion and in vivo utilization for decades, and from human subjects to a range of animals. However, there is no recent review summarizing pectin’s effects on starch digestion  tract, absorption of glucose and the resulting postprandial blood glucose level), making the findings in this field difficult to integrate. Additionally, many previous studies ignored the importance of pectin’s structure-property relationships, leading to ambiguous or misleading conclusions. To help solve these problems, in this review we discuss how pectin affects the in vivo utilization of starchy food. Generally, pectins regulate the digestion of starch by any or all of (1) inducing physicochemical changes in digesta, (2) inhibiting enzyme activities of amylases, (3) interacting with starch substrates, (4) being structural components in cell walls and (5) causing a series of physiological responses. The review concludes with discussion of the characteristics of pectins as modulators of starch digestion, some concluding remarks and suggestions on future perspectives. The results obtained from in vivo investigations provide additional information as to how pectin ingestion affects physiological responses of humans and other animals. Pectin’s in vivo effects are complicated by the inherent variability in animal experiments , for exaIt is well accepted that a high fasting blood-glucose level (fBGL) is seen as a good indicator of diabetes, and the postprandial blood glucose level (pBGL) change is seen as a good measure of the metabolic processes that underlie type 2 diabetes . TherefoIn the 1970s, Jenkins and co-workers  conducteThe positive effect of pectins as a food additive was further confirmed with healthy human volunteers . The resIt was also found by Jenkins and co-workers  that pecThe positive correlation between the food (chyme) viscosity induced by pectin and other DFs, and the average decrease in the maximum rise as well as the area under curve (AUC) in blood glucose concentration was confirmed in a subsequent work . This sup < 0.005) and returned to normal 3 weeks after discontinuing pectin supplementation [Holt et al. (1979) further confirmed pectin could delay the gastric emptying (GE). The authors found (1) when taking pectin and glucose together, the BGLs of volunteers were significantly reduced, and (2) the ingestion of pectin induced fewer gastric contents being emptied in 30 min and significantly longer gastric emptying half-times . The lonentation . Bacteroidetes to Firmicutes in normal weight subjects compared to overweight subjects.Jones and co-workers  studied Although in many cases the addition of pectin to food showed regulating effects on BGL, its effects were not always favorable. Many factors, such as dosage and composition of other staple foods, could influence or mask the effects of pectins. This is because pectin is usually used only as a food additive, and, to avoid unpalatability, its content in food should not be dominant; therefore, when the starch is highly susceptible to amylase or the pectin concentration is rather low, there would be no significant impact from added pectin on starch digestibility. Nevertheless, pectin in a food may still affect the in vivo physiological responses to that food, without influencing the BGL. Two studies ,35 have Some other experiments focusing on the long-term ingestion of pectin by healthy  and unheUsing animals as subjects gives researchers more technical choices and flexibility than using human subjects, thus yielding more mechanistic and interesting results. Sánchez and co-workers added HM-pectin and β-glucan to the feed of obese rats and found that diets with both fibers reduced body weight, total cholesterol and triglycerides in Zucker fatty rats, while the pectin-enriched diet significantly decreased the fBGL and plasma insulin concentrations, showing pectin’s potential use in prevention against some of cardiovascular risk factors related to metabolic syndrome .A comparative study on several DFs linked pectin’s effects on in vitro starch digestion to its influence in rat’s in vivo pBGL . Pectin 2+ supplements under in vivo conditions formed a gel bolus. Both forms of pectin flattened the pBGL curve favorably; pectin itself reduced the BGL in the first 30 min of the postprandial period, while pectin-Ca2+ inhibited the glycemic response over a longer period. The presence of both forms of pectin significantly increased the viscosity of gastric digesta, but with different patterns. This shows that the physicochemical status of pectin supplements in the GI tract largely relates to its influence on digestion process. These researchers suggested that LM-pectin cross-linked with Ca2+ presented better effects on reducing starch digestion. However, these findings are not general, as results may be different from case to case, based on the variables in Khramova et al.  elucidatIn most of the studies discussed above, only one type of pectin was used. To compare the glucose absorption inhibition of pectins with pectins’ DE values, Kim  tested bTogether with commercially available pectins, pectic polysaccharides extracted from natural sources, especially those that are common in food or herbal medicines, also exhibited decreasing BLG and anti-diabetic effects in rats ,50. A seFicus pumila L. and found FPLP significantly reduced the fBGL and serum insulin of db/db mice in a dose-dependent manner after four weeks’ administration. FPLP is a typical HG-type LM-pectin with branched-chain hexenuronic acids. The authors suggested that the anti-hyperglycemic effect of FPLF comes from its improvement in hepatic glycogen metabolism in db/db mice, because FPLF (1) activates the IRS-1/PI3K/Akt/GSK3β/GS insulin signaling pathway and AMPK/GSK3β/GS signaling pathway and (2) regulates glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expressions involved in hepatic glycogenesis and glycogenolysis. Recent researches in pectic polysaccharides extracted from natural food and medicinal plants also concentrated on looking for novel biochemical mechanisms for pectin’s hypoglycemic effects. Wu et al.  extracteGomphidiaceae rutilus. They found that the total polysaccharide (denoted AGRP) and its neutral fraction (AGRP-N) reduced the BGL of ob/ob mice after four weeks’ oral administration, while the acidic fraction (AGRP-A) did not have this effect. The hypoglycemic effect of AGRP and AGRP-N may arise from enhancing lipolysis and autophagy to inhibit lipid accumulation in the liver, resulting in increased insulin sensitivity. Yang and co-workers  extractePanax ginseng C. A. Meyer (ginseng) is a common traditional herbal medicine and food supplement with many health benefits [benefits . Extractbenefits  or severbenefits  all exhibenefits .Several studies have explored the relationship between consumption of whole foods with high pectin content  and the blood glucose response in human and rats ,32,48. UAs summarized in the previous section, pectin can affect in vivo digestion and absorption of starches, which are widely considered as beneficial for health. From the studies mentioned above, pectins with various origins and molecular structures have been tested in a large number of experiments, and have exhibited different effects on starch digestion and BGL regulation. The mechanisms underlying pectin’s effects are discussed in this section and are illustrated in When dissolved in solution, hydrophilic chains of pectin molecules will hydrate and entangle with each other to form complex networks , which mNumerous in vivo investigations ,28,39,53Starch is digested sequentially in humans by salivary and pancreatic α-amylase, and by brush-border enzymes, specifically mucosal maltase–glucoamylase and sucrase–isomaltase. The end-product, glucose, is transported via enterocytes into the bloodstream. Inhibiting the activity of amylases has long been used as an effective approach to control postprandial blood glucose level and in vivo starch digestion ,57. ThusMany researchers have studied the interaction between pectins and amylases; some of the results are as follows. Firstly, pectin can affect amylase activity under both in vitro ,59 and iEffects on amylase activity by the addition of pectin could be due to several reasons. Firstly, this could reflect the changed physicochemical properties of digesta, for instance, increasing the viscosity of chyme ,58, chanSecondly, some pectins or pectic polysaccharides are able to inhibit amylase activity by intermolecular interaction. Ref.  reporteda,pectin < pH < pI,protein, which satisfies the optimal electrostatic interaction condition. Another HM-pectin fraction, CP, significantly accelerated initial in vitro digestion rates of corn starch under the same conditions, which may be caused by (1) the pectin gel network expelling α-amylase into the soluble phase, thus causing a higher amylase activity in that phase [Other interaction conditions may also exist. For example, Bai et al. found pectins with lower DE values had better α-amylase inhibitory effects in a pH 6.0 sodium acetate buffer . They foat phase  or the hFinally, pectins in the diet can affect amylase activity by changing the physiological morphology of the GI tract. The pectin in the diet could be hydrated and form a viscous network after ingestion, and thus put a sticky layer on the surface of the GI tract during its transportation, affecting the activity of amylases around mucosa. Forman and co-workers found that pectin in the diet increased the total enzyme activity of mucosal-scraping amylase in the small intestine of rats, with a significant increase in the volume of small intestinal contents and the weight of the mucosal scraping . ThomsenWhen dispersed in water, pectin powder will undergo wetting, swelling, hydration, dissolution (often under heating or cooking conditions) and gelation when the chemical environment is favorable . During Plant cell walls play a significant role in the bioavailability and bioaccessibility of macromolecules: for example, the starch entrapped in cell walls . In a whPectin as a major cell-wall material significantly affects the morphology of plant cell walls, adhesion between cells and the texture of tissue ,79; as aDE values of pectins have also been shown to be closely related to the digestibility of starch . Thus, dDietary fibers in food can induce a series of in vivo physiological responses related to starch digestion and glycaemia increase ,81,82. PGE is closely related to postprandial blood glucose level, because the stomach controls the provision of food load to the intestines, where food is digested and absorbed. The rate of GE and blood glucose level interact with each other so as to provide energy homeostasis . Pectin Ingested food could stimulate the GI tract to release hormones from enteroendocrine cells because of mechanical (such as inducing stomach distension) and chemical properties  . GastroiThe sustained ingestion of pectin can lead to histological and morphological changes in the GI tract. This results in increases in the weight or length of the pancreas , small iThe importance of gut microbiota in digestion has been extensively studied ,92,93. PFrom the above mentioned studies about pectins as nutritional additives in food targeted to regulate starch digestion, we can find that the addition of pectin to digesta can normally regulate the in vivo BGL of subjects from different species and health conditions. Pectins share some similarities to other DF nutritional additives: for example (1) causing an increase in viscosity is one of the major reasons to their changes and (2) the effects are normally concentration-dependent. Nevertheless, pectins also exhibit unique characteristics: some functional properties are determined by their complex and specific molecular structures. Many publications have clearly confirmed that pectin substrates with various structural parameters  exhibit different extents of retardation of starch digestion. In addition, it was also observed that starch-containing digesta with pectin could have ideal digestibility ,40 and aThe structure-based multi-functionality of pectins in affecting starch digestion showed great potentials in future applications. Pectic fractions with different molecular structure, although generically classified as pectins, could result in very different properties under the same conditions. One disadvantage in many previous studies has been the lack of structural characterization of the pectin samples used, meaning that the results obtained from these studies cannot be used to understand which property or molecular domain of pectin functions were determinant. Although pectin’s effects on starch digestion and regulation on BGL have often been studied, the absence of extensive structure-property relationships leaves much to be done. Comparisons on functions from structurally different pectins are needed. To achieve that goal, firstly, structural information of the selected pectin sample should be obtained. Some basic parameters, like DE, monosaccharide composition and molecular sizes are essential, while more detailed data including acetylation degree, sugar linkage composition and side-chain composition would be beneficial. The experimental methods for investigating pectin’s effects on starch digestion could be standardized. For in vitro experiments, impracticable conditions  should be replaced by methods  its ubiquity in plant foods, (2) its versatile functions as an artificial food additive, (3) safety and reliability, and (4) various health benefits. Pectins have considerable complexity in molecular structure. Many researchers have studied the effects of pectin on starch digestion and the changes in in vivo blood glucose level brought by pectin in food, and most of these researches demonstrated that the presence of pectin could retard the digestion process or flatten the BGL. There are three major reasons for pectin’s decreasing effect on digestibility and BGL, as follows. (1) Pectin would normally increase the viscosity of digesta or food chyme, thus inducing a series of physicochemical and physiological changes; (2) pectin could interact with amylases and inhibit their activity; and (3) the ingestion and fermentation of pectin in intestines also regulate digestion-related in vivo physiological responses. In vivo, an increased viscosity of chyme or food bolus could prolong the transit time of food in the GI tract, which would delay gastric emptying ,34,35,36


Background: In kidney transplantation, the relative contribution of various donor, procedure and recipient-related factors on clinical outcomes is unknown. Previous paired studies have largely focused on examining factors predicting early outcomes, where the effect of donor factors is thought to be most important. Here, we sought to examine the relationship between early and long-term outcomes in a UK-wide paired kidney analysis. Methods: UK Transplant Registry data covering 24,090 kidney transplants performed between 2001–2018, where both kidneys from each donor were transplanted, were analysed. Case-control studies were constructed using matched pairs of kidneys from the same donor discordant for outcome, to delineate the impact of transplant and recipient factors on longer-term outcomes. Results: Multivariable conditional logistic regression identified HLA mismatch as an important predictor of prolonged delayed graft function (DGF), in the context of a paired study controlling for the influence of donor factors, even when adjusting for early acute rejection. Prolonged DGF, but not human leucocyte antigen (HLA) mismatch, strongly predicted 12-month graft function, and impaired 12-month graft function was associated with an increased risk of graft failure. Conclusions: This study indicates prolonged DGF is associated with adverse long-term outcomes and suggests that alloimmunity may contribute to prolonged DGF by a mechanism distinct from typical early acute rejection. Early post-transplant events are important determinants of graft survival and function . IschaemOutcome data concerning transplantation of pairs of kidneys donated by a common deceased donor to different recipients enables assessment of the relative contribution of donor and non-donor factors. Paired kidney analysis has therefore been used to examine specific predictors that are discordant between recipients ,8, outcoDGF is well known to occur at different frequencies, and carry different significance, in donation after brain death (DBD) and donation after circulatory death (DCD) donor kidneys ,15. It iThe study used data supplied by the NHSBT Transplant Registry. All analyses were performed using a fully anonymised extract with no identifiable information available to the research team; therefore, institutional review board approval was not required. The registry includes data on all donors and transplant recipients in the UK. The initial study population consisted of all UK deceased-donor renal transplants performed between 1 January 2001 and 1 January 2018 where both donor kidneys were transplanted. All transplantation centres in the United Kingdom were represented and therefore geographical variations were minimized. For the primary analysis (prolonged DGF), exclusions were made where records had missing DGF data, primary non-function (PNF) or graft survival was less than 30 days, or where recipients were pre-dialysis at the point of transplantation. The dataset was then reduced to consider only those transplants where both kidneys from each donor met these inclusion criteria. Finally, a DGF-discordant dataset was created by extracting those cases where outcomes were discordant within pairs—in this case, where one donor kidney from each pair went on having prolonged DGF, defined as greater than or equal to 14 days, and the other donor kidney had DGF of less than 14 days or no DGF.2, and poor graft function as less than 45 mL/min/1.73 m2. Exclusions were made for missing 12-month eGFR data, or graft survival under 1 year. Again, transplants were only included if both donor kidneys met these inclusion criteria. A 12-month function-discordant dataset was then generated, where, within each transplant pair, one transplant had resulted in a recipient 12-month eGFR of greater than 45 mL/min/1.72 m2, and the other in a recipient 12-month eGFR of less than 45 mL/min/1.73 m2.An equivalent dataset was constructed for analysis of 12-month eGFR by defining good graft function as an eGFR of greater than or equal to 45 mL/min/1.73 mDGF was defined as the need for dialysis within seven days of transplantation. Duration was defined as the number of days between transplantation and the last dialysis treatment where recipients subsequently attained dialysis independence. Prolonged DGF was defined as that lasting ≥ 14 days. Rejection was defined as a treated, clinically diagnosed rejection episode. Recipients were defined as being highly sensitised if they had a calculated reaction frequency > 85%. eGFR was recalculated from raw data recorded in the registry using the CKD-EPI formula . HLA mist-tests. Where data was missing, variables were inspected for the pattern of missingness, and the assumption that data was missing at random was tested. Missing data was dealt with by means of multiple imputation by chained equations, using the MICE package for R with m = 10; this procedure was applied after initial inclusion criteria were applied for each study, but before any records with intact outcome variables were excluded based on a missing contralateral kidney, or due to outcome concordance within a pair. This approach maximises the amount of information available for use during imputation. Following an initial imputation round, model convergence was inspected, and the predictor subset and imputation methods refined as necessary as described elsewhere [R version 4.0.2 was used for the statistical analysis. The raw variables were cleaned. Univariate analyses were performed where appropriate, comparing categorical variables using chi-square tests, and continuous variables with lsewhere . The mulThe pattern of missing data for clinically important predictors was examined see . In genep < 0.001; DCD: 49.6 vs. 40.3, p < 0.001). Prolonged DGF was also associated with impaired long-term graft survival in both the DBD and DCD cohorts (p = 0.02); however, when donor and recipient age were included, there was no residual independent effect of donor type . Prolonged DGF remained an important predictor . We therefore concluded that prolonged DGF carried sufficiently similar implications in the DBD and DCD cohorts for them to be combined in our paired analysis, which, by design, controls for donor type.We performed an exploratory analysis of the DBD and DCD cohorts separately, to test the hypothesis that, when considering prolonged DGF defined using a cut-off of 14 days as the outcome of interest, it is reasonable to combine these cohorts, in line with the findings of Philips et al. . For uni cohorts . In a muThere were 24,090 kidney transplants performed in the United Kingdom between 1 January 2001 and 1 January 2018 where both donor kidneys were transplanted. Demographic information for the entire cohort is presented in The donor demographics for this study population are shown in The results of a multiply imputed multivariate analysis considering this paired discordant cohort are shown in A dichotomous outcome is necessary for paired analysis of this sort, so DGF cannot be treated as a three-level categorical variable (primary function vs. short-duration DGF vs. long-duration DGF). This paired analysis mandates choice of a cut-off value, and the comparator group (short or no DGF) is necessarily heterogenous. We therefore repeated the analysis considering DGF duration as a binary variable ‘longer’ or ‘shorter’ within each pair, thereby avoiding a threshold effect . Primary2 for those who did not . We therefore elected to dichotomise 12-month graft function at the KDIGO CKD 3a/3b cut-off of 45 mL/min/1.73 m2 for the purposes of generating a case-control cohort determined on good or poor graft function. Good 12-month function was defined as an eGFR of greater than or equal to 45 mL/min/1.73 m2, poor function as less than 45 mL/min/1.73 m2.The mean 12-month eGFR in those patients in analysis 1 who experienced prolonged DGF was 41.2 mL/min/1.73 m, compared to 46.2 mL/min/1.73 mA total of 5276 transplants were identified for inclusion in this case-control study after excluding those with missing 12-month eGFR data, those with graft survival of less than one year, those missing a paired donor kidney, and those with concordant 12-month graft function .Those recipients with good 12-month graft function were more likely to be male, with a lower BMI, to have received tacrolimus and prednisolone at transplant, and to have received a right donor kidney. They were less likely to be recipients of a retransplant, to be highly sensitised, or to have experienced prolonged DGF. The donors included in this study cohort were an average age of 51.7, were slightly more likely to be male (51.9%), and 31.3% were DCD donors. These population characteristics and between-group differences are shown in p < 0.0001); The results of a multivariable paired conditional logistic regression analysis examining predictors of 12-month functional category are shown in This study aimed to estimate the impact of transplant and recipient factors on graft function and outcomes, using paired kidneys from a large national registry, in the modern era when acceptance of older and higher risk donor kidneys in deceased donor transplantation is increasing. Where the outcome of interest is binary, observation of outcome-discordant donor kidney pairs allows construction of a natural experiment which controls for donor factors. This is important for control of unmeasured donor factors but also for dealing with missing data; our analysis shows that the pattern of missingness with respect to donor variables is not random, and, in fact, missingness is associated with observation of adverse outcomes of interest. Use of a study design that abrogates the impact of missing donor factors, as well as controls for those which are unmeasured, appears therefore to be highly desirable.Prolonged DGF has previously been shown to be an important predictor of longer-term outcomes, even in the DCD cohort . This isThe effect of prolonged delayed graft function on 12-month graft function was restated in our paired analysis. Further, in this paired case-control cohort without donor-derived effects, 12-month function was highly significant for prediction of long-term graft survival. Our interpretation is that prolonged DGF is a good surrogate for cumulative peri-transplant graft injury which is in part due to an adaptive recipient immune effect distinct from typical rejection. The effect of early graft injury sufficient to cause DGF of more than two weeks is detectable and important when considering 12-month graft function, which, when impaired, predicts early transplant failure.p < 0.001), which may reflect a tendency to transplant right kidneys into technically easier recipients where possible; this may translate to better 12-month function.Recipient and transplant variates other than HLA mismatch which predicted prolonged DGF are generally associated with a pro-inflammatory recipient state , consistent with previous reports . The infThere are a number of limitations of this study. Firstly, we were unable to include the effect of induction immunosuppression or anastomotic time due to a high proportion of missing data and inconsistent coding in the registry. Secondly, some variables (particularly recipient BMI) required significant imputation due to missing data. Despite these limitations, our data shows the residual importance of transplant and recipient variables on prediction of meaningful long-term outcomes in kidney transplantation, and that HLA matching and alloreaction may be an important mediator of outcomes, much earlier than previously recognised, by a mechanism distinct from typical acute rejection.