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Pancreatic diseases include intractable ones including acute and chronic pancreatitis, and pancreatic cancer. In recent years, great advances have been made in the field of pancreatology, including the pathogenesis, diagnostic modalities, and development of novel therapeutic interventions. It has been established that pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis in chronic pancreatitis as well as in pancreatic cancer known as desmoplastic reaction. Although it might be still controversial, accumulating evidence has shown that interaction between pancreatic stellate cells-cancer cells contribute to the progression of pancreatic cancer through the increased proliferation and migration, and production of cytokines and extracellular matrix components. In addition, pancreatic stellate cells lead to the resistance to chemotherapy and radiation therapy. Pancreatic stellate cells attract the researchers as a novel therapeutic target of pancreatic cancer. Genetic studies have shown that mutations in the trypsin-related genes such as cationic trypsinogen (PRSS1) gene and the serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with pancreatitis. In general, each of these factors appears to limit trypsin activation or enhance inactivation, and is believed to increase intrapancreatic trypsin activity and predispose to pancreatitis when the gene is mutated. These results have supported a concept that pancreatic protease/anti-protease plays pivotal roles in the pathogenesis of pancreatitis. In addition, genetic studies focusing on phenotypic variances would provide us with important information how genetic variants would affect the phenotypic variances. Autophagy is an intracellular bulk degradation system in which cytoplasmic components are directed to the lysosome/vacuole by a membrane-mediated process. Recent studies have highlighted a role of autophagy in acute pancreatitis. Using a conditional knockout mouse that lacks the autophagy-related (Atg) gene Atg5 in the pancreatic acinar cells, autophagy exerts a detrimental effect in pancreatic acinar cells by activation of trypsinogen to trypsin. A theory in which autophagy accelerates trypsinogen activation by lysosomal hydrolases under acidic conditions, thus triggering acute pancreatitis in its early stage. The epithelial-mesenchymal transition is a developmental process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal phenotype. The phenotype associated with epithelial-mesenchymal transition includes enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of extracellular matrix components. In addition to its role in development, tissue regeneration, and fibrosis, epithelial-mesenchymal transition is now considered as a critical process in cancer progression. Induction of epithelial-mesenchymal transition in cancer cells results in the acquisition of invasive and metastatic properties. Epithelial-mesenchymal transition could be an important mechanism in the progression of pancreatic cancer and its poor prognosis. Autoimmune pancreatitis is a unique form of pancreatitis in which autoimmune mechanisms are suspected to be involved in the pathogenesis. There is accumulating study to deal with this new disease concept. In addition to these topics, we have selected several topics in pancreatology, focusing on recent studies increasingly deepening our knowledge in both basic and clinical researches.

Trypsin --- Epithelial-Mesenchymal Transition --- Fibrosis --- Pancreatitis --- autoimmune pancreatitis --- Pancreatic Cancer --- Pancreatic Stellate Cells --- Cystic Fibrosis Transmembrane Conductance Regulator

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The introduction and widespread implementation of newborn bloodspot screening (NBS) for cystic fibrosis (CF) has offered earlier diagnosis and better outcomes for children with CF in many countries of the world. It represents a paradigm shift in the diagnostic pathway for these families. In contrast to a clinical diagnosis, infants are now referred for diagnostic testing after a positive NBS result. The introduction of NBS has enabled the provision of early appropriate treatment to prevent the manifestations of the disease. In the near future, early diagnosis will facilitate the prompt use of new CFTR modulator therapies that correct the basic underlying molecular defect. NBS for CF has been a global success but continues to raise questions with many varied approaches and the development of new technologies, in particular the ability to undertake extensive gene examination. Which is the best protocol to achieve high sensitivity and specificity, and how to evaluate and manage infants with inconclusive diagnosis are all subjects of ongoing discussion. It is also open to question: what is the best approach to informing and counselling the parents about a positive or inconclusive NBS result? These questions are not easy to answer and require a balanced solution that reflects the local health care system and may appropriately result in different answers around the globe. The articles in this book try to answer these questions and give an overview of the current state of knowledge in NBS for CF.

newborn screening --- immunoreactive trypsin(ogen) --- dried blood spot --- radioimmunoassay --- DNA --- cystic fibrosis --- incidence --- malnutrition --- cost --- health policy --- CF transmembrane conductance regulator-related metabolic syndrome --- CF screen positive --- inconclusive diagnosis --- DNA analysis --- next generation sequencing --- extended genetic analysis --- presumptive diagnosis --- sweat test --- parental information --- newborn bloodspot screening --- psychological impact --- biochemical screening --- pancreatitis associated protein --- immunoreactive trypsinogen --- cystic fibrosis screen positive --- inconclusive diagnosis (CFSPID) --- bioethics --- newborn screen --- target disorder --- missed case --- sensitivity --- CFSPID --- immunoreactive trypsin --- meconium ileus --- diagnosis --- therapy --- prognosis --- n/a

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In the two last decades, proteases have constituted one of the primary and important targets in drug discovery. The U.S. FDA has approved more than 12 protease therapies in the last 10 years, and a number of next-generation or completely new proteases are under clinical development. Protease inhibition strategies are one of the fastest expanding areas in the field of of drugs that show considerable promise. This Special Issue will focus on the recent advances in the discovery and development of protease inhibitors, covering the synthesis of protease inhibitors, the design of new chemical entities acting as inhibitors of special/particular types of proteases, and their mode of actions (Frolova et al. 2020; Slapak et al. 2020; Künnapuu et al. 2021). In addition, the new applications of these interesting compounds/biomolecules and their limitations have been discussed and described (Wang et al. 2020; Bartošová-Sojková et al. 2021).

MMP --- MMP2 --- MMP9 --- MMP7 --- MMP14 --- matrix metalloproteases --- PDAC --- pancreatic cancer --- Bowman–Birk inhibitor --- ranacyclin --- trypsin inhibitor --- structure–activity relationship --- synergistic effect --- Gentamicin --- matrix metalloproteinase --- extracellular matrix --- nuclei --- cancer --- apoptosis --- immune response --- cysteine protease inhibitor --- stefin --- signal peptide --- parasite --- phylogenetic analysis --- diversification --- protein structure --- vascular endothelial growth factors (VEGFs) --- VEGF-A --- PlGF --- VEGF-B --- VEGF-C --- VEGF-D --- angiogenesis --- lymphangiogenesis --- CCBE1 --- proteases --- ADAMTS3 --- plasmin --- cathepsin D --- KLK3 --- prostate-specific antigen (PSA) --- thrombin --- wound healing --- metastasis --- proteolytic activation --- vascular biology --- lymphedema

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Cereal-based products such as pasta and baked goods represent staple foods for human nutrition. Due to their worldwide diffusion, these products can be carriers of nutrients and bioactive compounds; therefore, they lend themselves very well to the fortification process. Furthermore, among new formulations of cereal-based food, gluten-free products have become popular even among people without celiac disease who have chosen a gluten-free lifestyle. The improvement of well-being, sustainable lifestyles, and waste control are also aims of the United Nations for the Agenda 2030, which has motivated food scientists and industrial producers to research new and healthier formulations for pasta and baked goods preparations. In this context, researchers are also encouraged to use agro-industrial by-products of high added value for food fortification. The Special Issue “Improving the Sensory, Nutritional and Technological Profile of Conventional and Gluten-Free Pasta and Bakery Products” collected ten original articles focused on new types of gluten-free pasta or baked product formulations as well as agro-industrial by-product utilization. The final aim was the preparation of valuable products from a nutritional, technological, and sensory viewpoint.

agro-industrial by-product --- fortified pasta --- dietary fiber --- phenolic compounds --- starch digestibility --- prebiotics --- trypsin inhibitors --- inositol phosphates --- phenols --- legumes --- functional foods --- gluten-free --- durum wheat --- precision harvest --- pasta quality --- pasta short chain --- pasta --- glycaemic index --- high amylose --- resistant starch --- gluten-free bread --- hydration --- hydroxypropyl methylcellulose --- xanthan gum --- psyllium --- sucrose replacement --- cake --- dietary fibre --- clean label --- texture profile --- sensory quality --- obesity --- celiac disease --- bread fortification --- grape pomace --- agro-industrial by-products --- antioxidant activity --- sensory analysis --- dumpling --- gnocchi --- gluten free pasta --- fiber content --- cooking behavior --- color --- texture --- liking predictors --- consumer acceptability --- gluten analysis --- ELISA --- sandwich method --- R5 antibody --- G12 antibody --- n/a

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Bacillus thuringiensis (Bt)-based products are the most successful microbial insecticides to date. This entomopathogenic bacterium produces different kinds of proteins whose specific toxicity has been shown against a wide range of insect orders, nematodes, mites, protozoa, and human cancer cells. Some of these proteins are accumulated in parasporal crystals during the sporulation phase (Cry and Cyt proteins), whereas other proteins are secreted in the vegetative phase of growth (Vip and Sip toxins). Currently, insecticidal proteins belonging to different groups (Cry and Vip3 proteins) are widely used to control insect pests and vectors both in formulated sprays and in transgenic crops (the so-called Bt crops). Despite the extensive use of these proteins in insect pest control, especially Cry and Vip3, their mode of action is not completely understood. The aim of this Special Issue was to gather information that could summarize (in the form of review papers) or expand (research papers) the knowledge of the structure and function of Bt proteins, as well as shed light on their mode of action, especially regarding the insect receptors. This subject has generated great interest, and this interest has been materialized into the 18 papers of important scientific value in the field (5 reviews and 13 research papers) that have been compiled in this issue.

Bacillus thuringiensis --- Plutella xylostella --- Cry1Ac resistance --- trypsin-like midgut protease --- protoxin activation --- Spodoptera spp., Helicoverpa armigera --- Mamestra brassicae --- Anticarsia gemmatalis --- Ostrinia furnacalis --- Cry2Ab toxin --- Bombyx mori --- ATP-binding cassette subfamily a member 2 (ABCA2) --- genome editing --- transcription activator-like effector-nucleases (TALENs) --- HEK293T cell --- functional receptor --- Vip3Aa --- lysosome --- mitochondria --- apoptosis --- Sf9 cells --- Cry1Ab --- oligomer formation --- Sf21 cell line --- Ostrinia nubilalis --- Lobesia botrana --- Leptinotarsa decemlineata --- bioassay --- Cyt2Aa2 toxin --- protein-lipid binding --- erythrocyte membrane --- AFM --- QCM-D --- Asian corn borer --- ABCC2 --- CRISPR/Cas9 --- Cry1Fa --- resistance --- chitin-binding protein --- adhesion --- peritrophic matrix --- Vip3A --- Spodoptera litura --- site-directed mutagenesis --- Cry --- Cyt --- parasporins --- S-layer proteins --- Vip --- Sip --- membrane receptors --- insecticidal activity --- anticancer activity --- Aedes aegypti --- minor proteins --- synergy --- mosquito control --- Bti --- Spodoptera frugiperda --- cadherin --- mode of action of Cry toxin --- insecticidal proteins --- insect resistance --- tobacco budworm --- Bacillus thuringiensis proteins --- coleopteran pests --- structure --- mode of action --- 3D-structure --- biological control --- antimicrobial peptide --- gut microbiota --- vegetative insecticidal proteins --- pyramids --- 3D-Cry toxins --- in vitro evolution --- rational design --- toxin enhancement --- n/a