Allergic airway disease (AAD) is a collective term for respiratory disorders that can be exacerbated upon exposure to airborne allergens. The contribution of fungal allergens to AAD has become well established over recent years. We conducted a comprehensive review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to better understand the mechanisms involved in the allergic response to fungi in airway epithelia, identify knowledge gaps and make recommendations for future research. The search resulted in 61 studies for final analysis. Despite heterogeneity in the models and methods used, we identified major pathways involved in fungal allergy. These included the activation of protease-activated receptor 2, the EGFR pathway, adenosine triphosphate and purinergic receptor-dependent release of IL33, and oxidative stress, which drove mucin expression and goblet cell metaplasia, Th2 cytokine production, reduced barrier integrity, eosinophil recruitment, and airway hyperresponsiveness. However, there were several knowledge gaps and therefore we recommend future research should focus on the use of more physiologically relevant methods to directly compare key allergenic fungal species, clarify specific mechanisms of fungal allergy, and assess the fungal allergy in disease models. This will inform disease management and future interventions, ultimately reducing the burden of disease.

With the continual increase in global cheese consumption, rennet, the traditional milk coagulant, is unable to meet the growing demand in cheese production. Although several proteases from other sources have been used for cheese-making, they suffer various shortcomings. The ocean is home to a huge and diverse range of life forms, which represent a vast potential source of proteases. Marine proteases have been isolated from a number of marine species, including sponge, jellyfish, seaweed and marine animals, and some have been shown to be suitable as milk-clotting enzymes for cheese making. This review summarizes the latest studies on rennet substitutes from marine resources and their role in cheese-making. The emphasis of the review is on the isolation and purification of the marine proteases, the biochemical characteristics of these enzymes, especially their caseinolytic and milk-clotting properties, as well as their cleavage sites on casein. Some of the marine proteases have been applied as milk-clotting agent in cheese-making, with the resultant production of cheese with comparable characteristics, including sensory characteristics, to calf rennet cheese. The review concludes by highlighting the challenges and opportunities for future research in the field.

While proteins have been widely used to encapsulate, protect, and regulate the release of bioactive food compounds, little is known about the influence of co-consumed proteins on the absorption of lipophilic constituents following digestion, such as vitamins (A, D, E, K), carotenoids, and curcumin. Their bioavailability is often low and very variable, depending on the food matrix and host factors. Some proteins can act as emulsifiers during digestion. Their liberated peptides have amphiphilic properties that can facilitate the absorption of microconstituents, by improving their transition from lipid droplets into mixed micelles. Contrarily, the less well digested proteins could negatively impinge on enzymatic accessibility to the lipid droplets, slowing down their processing into mixed micelles and entrapping apolar food compounds. Interactions with mixed micelles and proteins are also plausible, as shown earlier for drugs. This review focuses on the ability of proteins to act as effective emulsifiers of lipophilic vitamins, carotenoids, and curcumin during digestion. The functional properties of proteins, their chemical interactions with enzymes and food constituents during gastro-intestinal digestion, potentials and limitations for their use as emulsifiers are emphasized and data from human, animal, and in vitro trials are summarized.

Proteases and protease inhibitors (P/PIs) are involved in many biological processes in human skin, yet often only specific families or related groups of P/PIs are investigated. Proteomics approaches, such as mass spectrometry, can define proteome signatures (including P/PIs) in tissues; however, they struggle to detect low-abundance proteins. To overcome these issues, we aimed to produce a comprehensive proteome of all P/PIs present in normal and diseased human skin, in vivo, by carrying out a modified systematic review using a list of P/PIs from MEROPS and combining this with key search terms in Web of Science. Resulting articles were manually reviewed against inclusion/exclusion criteria and a dataset constructed. This study identified 111 proteases and 77 protease inhibitors in human skin, comprising the serine, metallo-, cysteine and aspartic acid catalytic families of proteases. P/PIs showing no evidence of catalytic activity or protease inhibition, were designated non-peptidase homologs (NPH), and no reported protease inhibitory activity (NRPIA), respectively. MMP9 and TIMP1 were the most frequently published P/PIs and were reported in normal skin and most skin disease groups. Normal skin and diseased skin showed significant overlap with respect to P/PI profile; however, MMP23 was identified in several skin disease groups, but was absent in normal skin. The catalytic profile of P/PIs in wounds, scars and solar elastosis was distinct from normal skin, suggesting that a different group of P/PIs is responsible for disease progression. In conclusion, this study uses a novel approach to provide a comprehensive inventory of P/PIs in normal and diseased human skin reported in our database. The database may be used to determine either which P/PIs are present in specific diseases or which diseases individual P/PIs may influence.

The purpose of this systematic review was to identify the available literature of production, purification, and characterization of proteases by endophytic fungi. There are few complete studies that entirely exhibit the production, characterization, and purification of proteases from endophytic fungi. This study followed the PRISMA, and the search was conducted on five databases: PubMed, PMC, Science Direct, Scopus Articles, and Web of Science up until 18 May 2021, with no time or language restrictions. The methodology of the selected studies was evaluated using GRADE. Protease production, optimization, purification, and characterization were the main evaluated outcomes. Of the 5540 initially gathered studies, 15 met the inclusion criteria after a two-step selection process. Only two studies optimized the protease production using statistical design and two reported enzyme purification and characterization. The genus Penicillium and Aspergillus were the most cited among the eleven different genera of endophytic fungi evaluated in the selected articles. Six studies proved the ability of some endophytic fungi to produce fibrinolytic proteases, demonstrating that endophytic fungi can be exploited for the further production of agents used in thrombolytic therapy. However, further characterization and physicochemical studies are required to evaluate the real potential of endophytic fungi as sources of industrial enzymes.

Supplementing exogenous enzymes in pig diets is an alternative solution to increase dietary energy and fiber digestibility to improve pig production performance at a low production cost and to reduce environmental impact with lower N and P excretions. The production stage, diet composition, enzyme source, amount and number of enzymes added, are factors to consider before using them. A database composed by 227 individual diets, resulting from 43 studies with 48 experimental records were divided in different production stages, with 19 records for weaning, 17 records for growing and 12 records for finishing. A descriptive statistical analysis of the chemical composition of the diets and enzyme doses was carried out. The data with normal distribution were analyzed calculating the mean, the minimum and maximum length, the standard deviation and the coefficient of variation. It was found that combined enzymes are the most widely reported enzyme combination in the supplementation of pigs at all stages of production. Phytases and Mannanases are commonly used at weaning and growing stages. Xylanases and Proteases have been reported to be used in all production stages. However, the highest yielding enzymes at weaning, growing and finishing stages were Phytases and Mannanases. Dietary supplementation of exogenous enzymes improves production characteristics at all stages of production. However, an improvement in growth performance and nutrient digestibility is not always observed. Future studies should focus on the interaction between production stages, composition of the diet, origin of the enzyme and the amount and number of enzymes added.

Alzheimer\'s disease (AD) is the most common cause of dementia affecting millions of people. Neuronal death in AD is initiated by oligomeric amyloid-β (Aβ) peptides. The amyloid channel hypothesis readily explains the primary molecular damage but does not address major observations associated with AD such as autophagy failure and decreased metabolism. The amyloid degradation toxicity hypothesis provides the interpretation as a sequence of molecular events. Aβ enters a cell by endocytosis, and the endocytic vesicle is merged with a lysosome. Lysosomal peptidases degrade the peptide. Fragments form membrane channels in lysosomal membranes that have a significant negative charge due to the presence of acidic phospholipids. Amyloid channels can transfer various ions (including protons) and even relatively large compounds, which explains lysosomal permeabilization. The neutralization of lysosomal content inactivates degradation enzymes, results in an accumulation of undigested amyloid, and stalls autophagy. Inadequate quality control of mitochondria is associated with an increased production of reactive oxygen species and decreased energy production. Also, the passage of lysosomal proteases through rare extremely large channels results in cell death. Proposed hypothesis identifies biochemical pathways involved in the initiation and progression of cellular damage induced by beta-amyloid and provides new potential pharmacological targets to treat Alzheimer\'s disease.

It is generally assumed that breakdown of plant material in the rumen is a process mediated by gut microorganisms. This view arose because of the identification of a pre-gastric fermentation in the rumen, brought about by a large and diverse microbial population. The extensive use of dried and ground feed particles in forage evaluation might have helped to promote this assumption. However, although the assumption might be correct in animals feeding on conserved forage (hay and silage) where the cells of ingested forage are dead, it is possible that with grazed (living) forage, the role played by plant enzymes in the rumen has been overlooked. In a grazing situation, plant cells that remain intact on entering the rumen are not inert, but will respond to the perceived stresses of the rumen environment for as long as they are metabolically viable. Metabolic adjustments could include anaerobic and heat-shock responses that could promote premature senescence, leading to remobilization of cell components, especially proteins. Moreover, contact of plant cells with colonizing microorganisms in the rumen might promote a type of hypersensitive response, in much the same way as it does outside the rumen. After fresh plant material enters the rumen and prior to extensive plant cell-wall degradation, there is often a phase of rapid proteolysis providing N in excess of that required to maintain the rumen microbial population. The inefficient use of this ingested N results in generation of ammonia and urea in exhaled breath and urine, which promotes welfare and environmental pollution concerns. Therefore an important research goal in livestock agriculture is to find ways of decreasing this initial rate of proteolysis in the rumen. This will benefit the farmer financially (through decreased use of feed supplements), but will also benefit the environment, as N pollution can adversely affect pasture diversity and ecology. This review considers the possible responses of plant metabolism to the rumen environment, and how such considerations could alter current thinking in ruminant agriculture. Contents Summary 37 I. INTRODUCTION 37 II. DIGESTION OF PLANTS IN THE RUMEN: OLD AND NEW CONCEPTS 39 III. RUMEN-INDUCED PLANT METABOLISM: CELL DEGRADATION AND DEATH 41 IV. FUTURE PROSPECTS 50 Acknowledgements 51 References 51.

Coronavirus disease (COVID-19) pandemic is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 13, 2021, more than 118.9 million cases were infected with COVID-19 worldwide. SARS-CoV-2 is a positive-sense single-stranded RNA beta-CoV. Most COVID-19 infected individuals recover within 1-3 weeks. Nevertheless, approximately 5% of patients develop acute respiratory distress syndrome and other systemic complications, leading to death. Structural genetic analyses of SARS-CoV-2 have shown genomic resemblances but a low evolutionary correlation to SARS-CoV-1 responsible for the 2002-2004 outbreak. The S glycoprotein is critical for cell adhesion and the entrance of the virus into the host. The process of cell entry uses the cellular receptor named angiotensin-converting enzyme 2. Recent evidence proposed that the CD147 as a SARS-CoV-2\'s potential receptor. The viral genome is mainly held by two non-structural proteins (NSPs), ORF1a and ORF1ab, along with structural proteins. Although NSPs are conserved among the βCoVs, mutations in NSP2 and NSP3 may play critical roles in transmitting the virus and cell tropism. To date, no specific/targeted anti-viral treatments exist. Notably, more than 50 COVID-19 candidate vaccines in clinical trials, and a few being administered. Preventive precautions are the primary strategy to limit the viral load transmission and spread, emphasizing the urgent need for developing significant drug targets and vaccines against COVID-19. This review provides a cumulative overview of the genomic structure, transmission, phylogeny of SARS-CoV-2 from Indian clusters, treatment options, updated discoveries, and future standpoints for COVID-19.
BACKGROUND: The online version contains supplementary material available at 10.1007/s13205-021-02749-0.

Proteases are widely found in organisms participating in the decomposition of proteins to maintain the organisms\' normal life activities. Protease inhibitors regulate the activities of target proteases by binding to their active sites, thereby affecting protein metabolism. The key amino acid mutations in proteases and protease inhibitors can affect their physiological functions, stability, catalytic activity, and inhibition specificity. More active, stable, specific, environmentally friendly and cheap proteases and protease inhibitors might be obtained by excavating various natural mutants of proteases and protease inhibitors, analyzing their key active sites by using protein engineering methods. Here, we review the studies on proteases\' key active sites and protease inhibitors to deepen the understanding of the active mechanism of proteases and their inhibitors.
蛋白酶广泛存在于生物体中，参与分解蛋白质，维持生物体正常的生命活动。蛋白酶抑制剂通过与蛋白酶活性位点结合调控靶蛋白酶活性，从而影响蛋白质代谢。蛋白酶及其抑制剂关键氨基酸的突变，可以影响其生理功能、稳定性、催化活性、抑制特异性等。通过挖掘自然界蛋白酶及其抑制剂的各种突变体，分析它们的关键活性位点，并运用蛋白质工程手段改造和设计活性更强、稳定性更高、特异性更好、环境更友好、成本更低的蛋白酶及其抑制剂，已成为当前的热点研究之一。文中对近年来蛋白酶及其抑制剂关键活性位点研究进行了简要综述，以期深化人们对蛋白酶及其抑制剂活性作用机制的认识，并为蛋白酶及其抑制剂的生物学活性改造研究提供理论参考。.