Toxic advanced glycation end-products (TAGE), formed by glyceraldehyde (GA) as an intermediate in the non-enzymatic reaction with intracellular proteins, are highly cytotoxic and have been implicated in the pathogenesis of various diseases. However, the mechanisms underlying the degradation and removal of TAGE remain largely unknown. In the present study, we identified the checkpoint kinase-1 (CHK1) mutant, d270KD, which was rapidly degraded intracellularly by GA, and showed that its degradation was mainly mediated by the ubiquitin-proteasome pathway. The high-molecular-weight complexes formed by the GA stimulation of d270KD were abundant in the RIPA-insoluble fraction, which also contained high levels of TAGE. The knockdown of p62/SQSTM1 reduced the amount of high-molecular-weight complexes in the RIPA-insoluble fraction, indicating its involvement in the formation of TAGE aggregates. The present results suggest that the ubiquitin-proteasome pathway and p62 play a role in the degradation and aggregation of intracellular TAGE formed by GA. This study provides new insights into the mechanisms underlying TAGE metabolism and may lead to the development of novel therapeutic strategies for diseases associated with TAGE accumulation.

Chronic high glucose (HG) exposure increases methylglyoxal (MG)-derived AGEs and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic‐degenerative diseases. Under physiologic condition the harmful effects of MG are contrasted by glyoxalase system that is involved in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. The study aimed at investigating the role of polyphenols extracted from an apple high in polyphenols (Calville White Winter), on glyco-oxidative stress induced by chronic HG-exposure. Intestinal Caco-2 cells were treated in physiological glucose condition (25mM) as a control and in HG condition (50mM) with or without apple extract for one week. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significantly increase in ROS, lipid peroxidation, AGEs and Glyoxalase I (GlxI) activity with a significant decrease in total antioxidant intracellular defense. Treatment with polyphenols under HG condition restores to the control levels GlxI activity, decreases Glyoxalase II (GlxII) in relation to the control and induces a drop of glyco-oxidative damage. This paper seeks to highlight the roles of polyphenols in glyco-oxidative stress.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study conducted from January 2017 to June 2018. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify aortic abdominal calcification AAC. Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher number of diabetic related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications.

Towns emerged as dynamic economic and political centers during the Middle Ages, giving rise to the emergence of new social classes. As a result of these functions, a new relationship began to be forged with the rural world, which supplied towns with foodstuffs that satisfied new social demands. Archaeobotanical analysis (carpology) allows us to understand the flow of cash crops by tracing seeds and fruits produced in the countryside that were consumed in and redistributed from the towns. The study of waterlogged contexts from medieval archaeological sites in the Kingdom of Galicia (Santiago de Compostela, Padrón, and Pontevedra) has provided a set of species that played a crucial role in the economy of the urban dwellers and that possibly were related to differential access or food preferences. Evidence for fruits (grapes, chestnuts, figs, apples, and cherries, among others), garden crops (melon), and cereals (foxtail millet, rye, naked wheat, and oat) has been documented. Broomcorn millet is particularly abundant, demonstrating that it was important for subsistence. Some of the species found (medlar and turnip/grelo) are novel in the archaeobotanical literature of the medieval period in the Iberian Peninsula.

Plant proteins being considered to become the most important protein source of the future, they must be able to replace the animal-derived proteins currently in use as technofunctional food ingredients. This poses challenges because plant proteins are oftentimes storage proteins with a high molecular weight and low water solubility. One promising approach to overcome these limitations is the glycation of plant proteins. The covalent bonding between the proteins and different carbohydrates created via the initial stage of the Maillard reaction can improve the technofunctional characteristics of these proteins without the involvement of potentially toxic chemicals. However, compared to studies with animal-derived proteins, glycation studies on plant proteins are currently still underrepresented in literature. This review provides an overview of the existing studies on the glycation of the major groups of plant proteins with different carbohydrates using different preparation methods. Emphasis is put on the reaction conditions used for glycation as well as the modifications to physicochemical properties and technofunctionality. Different applications of these glycated plant proteins in emulsions, foams, films, and encapsulation systems are introduced. Another focus lies on the reaction chemistry of the Maillard reaction and ways to harness it for controlled glycation and to limit the formation of undesired advanced glycation products. Finally, challenges related to the controlled glycation of plant proteins to improve their properties are discussed.

Soil organic carbon (SOC) mineralization is closely related to carbon source or sink of terrestrial ecosystem. Understanding soil organic carbon (SOC) mineralization under plum plantation is essential for improving our understanding of SOC responses to land-use change in karst rocky desertification ecosystem. In this study, 2-y, 5-y and 20-y plum plantations and adjacent woodland were sampled and a 90-day incubation experiment was conducted to investigate the effect of plum plantation with different years on SOC mineralization in subtropical China. Results showed that: (1) there was no significant difference in SOC content between different planting years, but there were significant differences in accumulative SOC mineralization (C_t) and potential SOC mineralization (C₀); (2) the dynamics of the SOC mineralization was a good fit to a first-order kinetic model. Both C₀ and C_t in calcareous soil of this study was several to ten folds lower than that in other soils, indicating that SOC in karst region has higher stability. (3) Correlation analysis revealed that both C_t and C₀ was significantly correlated with soil calcium (Ca) and C/N, indicating the important role of Ca and C/N in SOC mineralization in karst rocky desertification area.

At the entrance of some churches in Tuscany (Italy), the reproduction of an apparently undecipherable inscription can be found. At least from the 18^th century, this epigraphic puzzle has originated a debate on its interpretation. This study proposes a hypothesis based on the Latin alphabet used in texts contemporary to the churches where the inscription is reproduced and a possible interpretation of the message consistent with the official religious doctrine. The proposed deciphering is extended to the full text, including some signs that were previously considered as geometric forms or a specific elaboration of letters not attested in other contemporary documents.

This paper compares the Medieval (ca. 400–1500 CE) dynamics of forests from low-mountain (Montcortès; ca. 1000 m a.s.l.) and high-mountain (Sant Maurici; 1900 m a.s.l.) areas of the Iberian Pyrenees, both of which experienced similar climatic forcing but different anthropogenic pressures. The main aim is to identify forest changes over time and associate them with the corresponding climatic and anthropogenic drivers (or synergies among them) to test how different forests at different elevations respond to external forcings. This could be useful to evaluate the hypothesis of general Pyrenean deforestation during the Middle Ages leading to present-day landscapes and to improve the background for forest conservation. The study uses palynological analysis of lake sediments, historical documents and paleoecological reconstructions based on pollen-independent proxies. The two sites studied showed different forest trajectories. The Montcortès area was subjected to intense human pressure during regional deforestation up to a maximum of ca. 1000 CE. Further forest recovery took place until the end of the Middle Ages due to a change in forest management, including the abandonment of slash-and-burn practices. Climatic shifts indirectly influenced forest trends by regulating human migrations and the resulting shifts in the type and intensity of forest exploitation. The highland Sant Maurici forests exhibited a remarkably long-standing constancy and an exceptional resilience to climatic shifts, which were unable to affect forest extension and composition, and to local human pressure, from which they rapidly recovered. The Montcortès and Sant Maurici records did not follow the rule of an irreversible forest clearing during the Middle Ages leading to present-day landscapes. The present Montcortès landscape was shaped after a Medieval forest recovery, a new Modern-Age deforestation and a further forest recovery during the last centuries. The Sant Maurici forests remained apparently untouched since the Bronze Age and were never cleared during the Middle Ages. The relevance of these findings for forest conservation is briefly addressed, and the need for the development of more high-resolution studies on Pyrenean forest dynamics is highlighted.

Various environmental challenges, related to oil palm commodity has became a major environmental challenge to oil palm production. The aim and objective of this study is to analyze the actual water footprint of oil palm based on root water uptake under varying crop age and soil type. The research was conducted in Pundu Village, Central Kalimantan. The methodology adopted in carrying out this study consists of various stages which includes observing soil moisture, rainfall, and water table, ETo, root water uptake and oil palm water footprint. The highest rate of water consumption was the 13 years oil palm on spodosol soil type with an average daily rate of 3.73 mm/day. The lowest evapotranspiration was represented by the 7th year oil palm on spodosol with an average rate of 3.07 mm/day. The total water footprint value obtained was between 0.56 – 1.14 m3/kg for a variety of plants with various age and soil types. It can be deduced that the water footprint value of oil palm vary for different crop age and soil types on temporal scale. The study also presented that the source of green water from the first root zone of oil palm deliver the highest contribution for oil palm root water uptake.

The Universe is treated as an unbound thermodynamic system in which two forces of Nature compete: Attractive gravity loss and repulsive entropic gain. Entropic gain, although not presently considered a force of Nature, is otherwise well known and can be expressed with the gas laws. The Universe at the time of last scattering was all gas. Its instant gain is expressed as gas pressure. When the Gibbs equation is properly applied to this unbound gas, the resulting atomic Hubble parameter is found to be exclusively dependent on baryon density, giving a constant and perpetual two-to-one gain/loss ratio. Instant loss to gravity cannot offset gas pressure in this “thermal equation”. By contrast, the Friedmann equation, a ΛCDM foundation, treats baryon mass as accreted, having little if any entropic gain. These two equations are actually equivalent. Expanding accreted matter at its comoving critical density is herein shown to behave exactly like a freely expanding gas. However, neither equation includes all of today’s Universal kinetic energy, and cannot by themselves fully account for observed stellar movement. The present paper proposes the plausible existence of highly energetic or “suprathermal” free electrons which comprise about half of the intergalactic medium’s kinetic total. It is this suprathermal energy which Λ expresses. The fluid equation, another ΛCDM foundation, eliminates entropic gain from the Gibbs equation. Additionally, rest mass’s Einstein energy E=Mc² is treated as a thermal variable. These two assumptions, isoentropy and energy conflation, led astronomers to populate Λ as they followed the prior art.

Cancer is a condition in which the body's cells proliferate unchecked. Skin cancer is one of the deadliest diseases that impacts the skin on many levels. There are several different types of the disease, including melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanocytic nevus. Due to its increased prevalence, skin cancer, in particular melanoma, is be-coming a serious health problem. Early identification of skin lesions is crucial for successful treatment. Due to their resemblance, many skin lesions are misclassified, which is a severe issue. Researchers seek computer-aided diagnostic tools for early malignant tumor detection. First, a new model based on the combination of "you only look once" (YOLOv5) and "ResNet50" is proposed for melanoma detection with its degree using humans against a machine with 10,000 training images (HAM10000). Second, feature maps integrate gradient change, which allows rapid inference, boosts precision, and reduces the number of hyperparameters in the model, making it smaller. Finally, to get the desired outcomes, the current YOLOv5 model is changed by adding new classes for dermatoscopic images of typical lesions with pigmented skin. The pro-posed approach improves melanoma detection with a real-time speed of 0.4 ms non-maximum suppression (NMS) per image. The performance metrics average is 99.0%, 98.6%, 98.8%, 99.5, 98.3%, and 98.7% for precision, recall, dice similarity coefficient (DSC), accuracy, mean average precision (MAP) from 0.0 to 0.5, and MAP from 0.5 to 0.95, respectively. Compared to cur-rent melanoma detection approaches, the provided approach is more efficient using deep fea-tures.

The craft guilds have been at the core of important historiographical debates on the economic, social and political history of medieval cities for twenty years. The aim of this article is to examine the seamen’s guilds in the town ports of Northern Peninsula in the late Middle Ages. This study analyzes fundamental aspects of the social assistance, labour organization and social identity of the town ports, located on the maritime border of the Kingdom of Castile. In contrast to the more classical view of the craft guilds as protectionist institutions, which only served the interests of a privileged group of masters, this analysis highlights the contribution of the seamen craft guilds to the organization of labor at sea, the training of sea workers, the ability to negotiate with merchants and avoid labor exploitation, the provision of social assistance to the most vulnerable population, and the ability to lead the social protest for the guilders’ representation in the urban government. In summary, it is concluded that the seafarers’ guilds were constituted as networks of mutual help between individuals in the labor, welfare and political spheres of the population of the town ports of Northern Iberia in the late Middle Ages.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications, formed by reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied in respect of glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in dramatic suppression of primary seed metabolism, although secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.