Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based ...glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.
Hypoxia, the most commonly observed characteristic in cancers, is implicated in the establishment of an immunosuppressive niche. Recent studies have indicated that extracellular vesicle (EV)-mediated ...cancer-stroma interactions are considered to play a critical role in the regulation of various cellular biological functions, with phenotypic consequences in recipient cells. However, the mechanisms underlying the relationship between EVs and hypoxia during cancer progression remain largely unknown. In this study, we found that EVs derived from hypoxic lung cancers increased M2-type polarization by miR-103a transfer. Decreased PTEN levels caused by hypoxic cancer-cell-derived EV miR-103a increased activation of AKT and STAT3 as well as expression of several immunosuppressive and pro-angiogeneic factors. In contrast, inhibition of miR-103a by an miRNA inhibitor effectively decreased hypoxic cancer-mediated M2-type polarization, improving the cytokine prolife of tumor infiltration macrophages. Macrophages received cancer-cell-derived EV miR-103a feedback to further enhance cancer progression and tumor angiogenesis. Finally, circulating EV miR-103a levels were higher in patients with lung cancer and closely associated with the M2 polarization. In conclusion, our results delineate a novel mechanism by which lung cancer cells induce immunosuppressive and pro-tumoral macrophages through EVs and inspire further research into the clinical application of EV inhibition or PTEN restoration for immunotherapy.
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Extracellular vesicle (EV) miR-103 can be transferred from hypoxic cancer cells to macrophages, resulting in the enhancement of M2 polarization by the downregulation of miR-103a’s direct target PTEN. EV miR-103a increases the stimulatory effects of macrophages on cancer progression and angiogenesis.
The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents ...such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.
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•FRIL is a plant lectin with potent anti-influenza and anti-SARS-CoV-2 activity•FRIL preferentially binds to complex-type N-glycans on viral glycoproteins•FRIL inhibits influenza virus entry by sequestering virions in late endosomes•Intranasal administration of FRIL protects against lethal H1N1 challenge in mice
Liu et al. demonstrate that FRIL, a plant lectin isolated from the hyacinth bean, has potent antiviral activity against SARS-CoV-2 and diverse influenza virus strains. FRIL is effective in vivo against H1N1. FRIL’s antiviral activity is mediated by binding to complex-type N-glycans on viral glycoproteins, interfering with viral entry.
The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) ...with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.
Carbohydrates have been shown to play important roles in biological processes. The pace of development in carbohydrate research is, however, relatively slow due to the problems associated with the ...complexity of carbohydrate structures and the lack of general synthetic methods and tools available for the study of this class of biomolecules. Recent advances in synthesis have demonstrated that many of these problems can be circumvented. In this Review, we describe the methods developed to tackle the problems of carbohydrate‐mediated biological processes, with particular focus on the issue related to the development of the automated synthesis of oligosaccharides. Further applications of carbohydrate microarrays and vaccines to human diseases are also highlighted.
Sweet dreams: Carbohydrates play important roles in biological processes. The pace of carbohydrate research is, however, relatively slow due, amongst other things, to the lack of general synthetic methods. Current developments in the automated synthesis of oligosaccharides can help overcome many of these problems and to pave the way for biomedical applications.
The increased consumers' interest in high quality foods with fresh-like sensory and additive free attributes led to the development of non-thermal food processing technologies as alterative to ...conventionally heat treatments. This review describes the current application status and market trends of high-pressure processing (HPP) technology in food industry. As the most successfully commercialized non-thermal processing technology, HPP eliminates food pathogens at room temperature and extends the shelf life of foods circulated through the cold chain. These processes maintain the organoleptic properties and nutritional value of the foods, which is not possible using traditional thermal pasteurization. The U.S. Food and Drug Administration has officially approved HPP as a non-thermal pasteurization technology that can replace traditional pasteurization in the food industry. Clearly defined regulations and specifications will facilitate the development of the application market to improve product quality and consumer trust. The widespread application of HPP technology has boosted the development and market demand for HPP equipment. HPP has been widely used in the production of packaged vegetables, fruits, meat, seafood, and dairy products. By the end of 2015, more than 300 units of HPP equipment were operating globally. Despite the high price and high barriers to investment, the specialized original equipment manufacturer service sector has been gradually increasing, and the annual output value of global HPP market has approached $10 billion. HPP technology also can be combined with existing food trends, as organic food, health food or clean label to boost the development in the food market.
•The widespread application of HPP has boosted the development and market demand for equipment.•By the end of 2015, more than 300 units of HPP equipment were operating globally.•The annual output value of global HPP market has approached $10 billion.•HPP also can be combined with organic food, health food or clean label to boost the development in the food market.
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy ...preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).
Accurately forecasting the demand for tourism can help governments formulate industrial policies and guide the business sector in investment planning. Combining forecasts can improve the accuracy of ...forecasting the demand for tourism, but limited work has been devoted to developing such combinations. This article addresses two significant issues in this context. First, the linear combination is the commonly used method of combining tourism forecasts. However, additive techniques unreasonably ignore interactions among the inputs. Second, the available data often do not adhere to specific statistical assumptions. Grey prediction has thus drawn attention because it does not require that the data follow any statistical distribution. This study proposes a nonadditive combination method by using the fuzzy integral to integrate single-model forecasts obtained from individual grey prediction models. Using China and Taiwan tourism demand as empirical cases, the results show that the proposed method outperforms the other combined methods considered here.
Cardiopulmonary resuscitation (CPR) education for the public may improve bystander intention to perform CPR on cardiac arrest patients. Studies have shown that different CPR education intervention ...methods can improve learning performance, with key indicators including attitude toward to CPR, intention to perform CPR, and degree of CPR knowledge and skills. The present study compared the traditional face-to-face method to hybrid and virtual reality (VR) methods to observe difference in learning performance and length of performance retention. This study adopted randomized controlled trial to compare CPR learning performance between traditional face-to-face, hybrid, and VR methods. Participants from each intervention group completed a pretest and 2 posttests. The measurement tools included an attitude and intention questionnaire, knowledge examination, and skill examination with a RESUSCI ANNE QCPR ® manikin. The performance among all participants in pretest showed no significant difference between the intervention groups, indicating no difference in their background attitude, knowledge, and skill level. Significant differences were observed in the average degree of intention to perform CPR between the hybrid and traditional groups in 1st and 2nd posttest. Compared to the pretest results, the posttests revealed significantly higher attitude toward CPR, intention to perform CPR, knowledge examination results, accuracy of overall chest compression, accuracy of CPR procedure, accuracy of AED usage, accuracy of chest compression rate, and accuracy of chest compression depth. The average time to reattending CPR learning and practice session was 11-12 weeks reported by participants. The hybrid and VR methods to CPR education resulted in the same level of improvement in learning performance as traditional face-to-face teaching. The suggested frequency for renewing CPR knowledge and skills is 12 weeks which may be considered in new strategies aimed at promoting CPR education and exposure to the public.
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