Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering the Dynamics of Signaling Cascades and Virulence Factors of B. cinerea during Tomato Cell Wall Degradation

The ascomycete Botrytis cinerea is one of the most relevant plant pathogenic fungi, affecting fruits, flowers, and greenhouse-grown crops. The infection strategy used by the fungus comprises a magnificent set of tools to penetrate and overcome plant defenses. In this context, the plant-pathogen communication through membrane receptors and signal transduction cascades is essential to trigger specific routes and the final success of the infection. In previous reports, proteomics approaches to B. cinerea signal transduction cascades changes in response to different carbon source and plant-based elicitors have been performed. Analyzing the secretome, membranome, phosphoproteome, and the phosphomembranome. Moreover, phenotypic changes in fungal biology was analyzed, specifically toxin production. To obtain the whole picture of the process and reveal the network from a system biology approach, this proteomic information has been merged with the phenotypic characterization, to be analyzed using several bioinformatics algorithms (GO, STRING, MCODE) in order to unravel key points in the signal transduction regulation crucial to overcome plant defenses, as well as new virulence/pathogenicity factors that could be used as therapeutic targets in the control of the gray mold rot disease. A total of 1721 and 663 exclusive or overexpressed proteins were identified under glucose (GLU) and deproteinized tomato cell walls (TCW), summarizing all of the protein identifications under phenotypic characterized stages. Under GO analysis, there are more biological process and molecular functions described in GLU, highlighting the increase in signaling related categories. These results agree with the high number of total identified proteins in GLU, probably indicating a more varied and active metabolism of the fungus. When analyzing only GO annotations related with signal transduction, it was revealed that there were proteins related to TOR signaling, the phosphorelay signal transduction system, and inositol lipid-mediated signaling, only under GLU conditions. On the contrary, calcium-mediated signaling GO annotation is only present between the proteins identified under TCW conditions. To establish a potential relationship between expressed proteins, cluster analyses showed 41 and 14 clusters under GLU and TCW conditions, confirming an increase in biological activity in GLU, where we identified a larger number of clusters related to transcription, translation, and cell division, between others. From these analyses, clusters related to signal transduction and clusters related to mycotoxin production were found, which correlated with the phenotypic characterization. The identification of the proteins encompassed in each condition and signal transduction cascade would provide the research community with new information about the B. cinerea infection process and potential candidates of pathogenicity/virulence factors, overcoming plant defenses, and new therapeutic targets.
Identifying Plectin Isoform Functions through Animal Models

Plectin, a high-molecular-weight cytoskeletal linker protein, binds with high affinity to intermediate filaments of all types and connects them to junctional complexes, organelles, and inner membrane systems. In addition, it interacts with actomyosin structures and microtubules. As a multifunctional protein, plectin has been implicated in several multisystemic diseases, the most common of which is epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). A great part of our knowledge about plectin’s functional diversity has been gained through the analysis of a unique collection of transgenic mice that includes a full (null) knockout (KO), several tissue-restricted and isoform-specific KOs, three double KOs, and two knock-in lines. The key molecular features and pathological phenotypes of these mice will be discussed in this review. In summary, the analysis of the different genetic models indicated that a functional plectin is required for the proper function of striated and simple epithelia, cardiac and skeletal muscle, the neuromuscular junction, and the vascular endothelium, recapitulating the symptoms of humans carrying plectin mutations. The plectin-null line showed severe skin and muscle phenotypes reflecting the importance of plectin for hemidesmosome and sarcomere integrity; whereas the ablation of individual isoforms caused a specific phenotype in myofibers, basal keratinocytes, or neurons. Tissue-restricted ablation of plectin rendered the targeted cells less resilient to mechanical stress. Studies based on animal models other than the mouse, such as zebrafish and C. elegans, will be discussed as well.
The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies

Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression.
Energy: Protein Ratio in Ruminants: Insights from the Intragastric Infusion Technique

Simple Summary One key question that has confounded nutritional scientists for years is how the ruminant responds metabolically with respect to energy and nitrogen utilisation when no exogenous energy is consumed. Fasting metabolism studies using the intragastric infusion technique (IIT) showed this to be a glucose-deficient state characterised by elevated nitrogen excretion and heat production. However, modern feeding systems continue to adopt fasting as the basis for measuring utilisation efficiency of nutritionally balanced diets, giving rise to the false concept of greater feed utilisation below than above energy maintenance. Another IIT finding was that given the animal’s genetic capacity for protein accretion and provided a rumen undegradable protein is fed, ruminants do not catabolise amino acids as an energy source but instead retain these to attain substantial gains in tissue protein deposition, fuelled by endogenous energy reserves. This suggests that endogenous fat reserves could be used to retain body protein when feed supplies are scarce or of poor nutritive value and questions the need to use high-energy diets in the finishing pre-slaughter period. Moreover, body protein and body fat deposition were also shown to be negatively correlated, contradicting current feeding systems which assume that nitrogen retention is always negative in an underfeeding situation. Abstract Studies on energy:protein ratio in ruminants are constrained by rumen fermentation since it governs nutrient metabolism and the ratio of energy:protein yielding nutrients available for absorption. By circumventing rumen fermentation, the total intragastric infusion technique (IIT) allowed objective quantification of maintenance energy and protein requirements, volatile fatty acid utilisation efficiency, efficiency of energy utilisation for maintenance (Km) and growth (Kf) and the origin of N retention responses to independent variation of energy and protein intake. This review outlines the key IIT findings and whether they are reflected in current feeding systems with implications for different production systems worldwide. Maintenance energy requirements are similar to those derived from comparative slaughter but maintenance N requirements are significantly lower. No differences in utilisation efficiency exist between acetic, propionic and butyric acids. At low energy intakes, endogenous energy reserves are utilised to retain amino acids and fuel substantial tissue protein gains. The use of fasting metabolism to measure the utilisation of nutritionally balanced diets is questioned since it is a glucose-deficient state. Inter-species differences in glucose metabolism appear to exist, suggesting that glucose requirements may be higher in cattle than sheep. The difficulty in predicting nutrient requirements, particularly protein, with any one technique is highlighted.
Development of Optimal Digesting Conditions for Microplastic Analysis in Dried Seaweed Gracilaria fisheri

Currently, research on the accumulation of microplastics (MPs) in the marine food web is being highlighted. An accurate and reliable digestion method to extract and isolate MPs from complex food matrices has seldom been validated. This study aimed to compare the efficacy of MP isolation among enzymatic-, oxidative-, and the combination of two digestion methods on red seaweed, Gracilaria fisheri. The dried seaweed sample was digested using three different methods under various conditions using enzymes (cellulase and protease), 30% H2O2, and a combination of enzymes and 30% H2O2. The method possessing the best digestion efficiency and polymer recovery rate of MPs was selected, and its effect on spiked plastic polymer integrity was analyzed by Raman spectroscopy. As a result, the enzymatic method rendered moderate digestion efficiency (59.3–63.7%) and high polymer recovery rate (94.7–98.9%). The oxidative method using 30% H2O2 showed high digestion efficiency (93.0–96.3%) and high polymer recovery rate (>98%). The combination method was the most effective method in terms of digestion efficiency, polymer recovery rate, and expenditure of digestion time. The method also showed no chemical changes in the spiked plastic polymers (PE, PP, PS, PVC, and PET) after the digestion process. All the spiked plastic polymers were identifiable using Raman spectroscopy.
Functionality and Applicability of Starch-Based Films: An Eco-Friendly Approach

The accumulation of high amounts of petro-based plastics is a growing environmental devastation issue, leading to the urgent need to innovate eco-safe packaging materials at an equivalent cost to save the environment. Among different substitutes, starch-based types and their blends with biopolymers are considered an innovative and smart material alternative for petrol-based polymers because of their abundance, low cost, biodegradability, high biocompatibility, and better-quality film-forming and improved mechanical characteristics. Furthermore, starch is a valuable, sustainable food packaging material. The rising and growing importance of designing starch-based films from various sources for sustainable food packaging purposes is ongoing research. Research on “starch food packaging” is still at the beginning, based on the few studies published in the last decade in Web of Science. Additionally, the functionality of starch-based biodegradable substances is technically a challenge. It can be improved by starch modification, blending starch with other biopolymers or additives, and using novel preparation techniques. Starch-based films have been applied to packaging various foods, such as fruits and vegetables, bakery goods, and meat, indicating good prospects for commercial utilization. The current review will give a critical snapshot of starch-based films’ properties and potential applicability in the sustainable smart (active and intelligent) new packaging concepts and discuss new challenges and opportunities for starch bio composites.
Extraction of Microcrystalline Cellulose from Washingtonia Fibre and Its Characterization

Washingtonia is a desert plant with great sustainability and renewability in nature and is abundantly cultivated across global urban regions. Its fibre biomass comprises cellulose as the major structural part, and this is why it can be potentially utilized as an alternative biomaterial for manufacturing microcrystalline cellulose (MCC) products that can be widely applied in industrial fields. In the present study, NaOH-treated Washingtonia fibre (WAKL), NaClO2-treated Washingtonia fibre (WBLH), and Washingtonia microcrystalline cellulose (WMCC) were extracted through combined treatments of alkalization, bleaching, and acidic hydrolysis, respectively. The obtained chemically treated fibre samples were subjected to characterization to investigate their morphology, physico-chemistry, and thermal stability. In a morphological examination, the large bunch WAKL fibre reduced into small size WMCC fibrils, evidencing that the lignin and hemicellulose components were greatly eliminated through chemical dissolution. The elemental composition revealed that almost all impurities of anions and cations had been removed, particularly for the WMCC sample, showing its high purity of cellulose content. Additionally, the WMCC sample could attain at 25% yield, giving it the advantage for feasible economic production. Furthermore, the physicochemical analysis, Fourier Transform Infrared-ray (FTIR), indicated the presence of a crystalline cellulose region within the WMCC structure, which had promoted it with high crystallinity of 72.6% as examined by X-ray diffraction (XRD). As for thermal analysis, WMCC showed greater thermal stability comparing to WAKL and WBLC samples at high temperature. Therefore, Washingtonia fibre can be a reliable biosubstituent to replace other plant material for MCC production in the future.
Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Simple Summary Acquired resistance to chemotherapy by cancer cells is the predominant factor in chemotherapy failure, which ultimately leads to disease progression and death. Recent studies have presented compelling evidence of the various mechanisms and pathways through which cancer cells have developed resistance to drugs. This review summarises the mechanisms pertaining to 5-FU resistance and discusses ongoing efforts to prevent chemotherapy resistance in cancer cells and to re-sensitise them to cancer drugs. Abstract 5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.
Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.
Nano-Curcumin Prevents Cardiac Injury, Oxidative Stress and Inflammation, and Modulates TLR4/NF-κB and MAPK Signaling in Copper Sulfate-Intoxicated Rats

Copper (Cu) is essential for a plethora of biological processes; however, its high redox reactivity renders it potentially toxic. This study investigated the protective effect of curcumin (CUR) and nano-CUR (N-CUR) against Cu cardiotoxicity, emphasizing the role of oxidative stress, TLR4/NF-κB and mitogen-activated protein kinase (MAPK) signaling and cell death in rats. Rats received 100 mg/kg copper sulfate (CuSO4), a pesticide used for repelling pests, and were concurrently treated with CUR or N-CUR for 7 days. Cu caused cardiac injury manifested by elevated serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), as well as histopathological alterations. Cardiac malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 were increased, and reduced glutathione (GSH), superoxide dismutase (SOD) and catalase were decreased in Cu-treated rats. CUR and N-CUR prevented cardiac tissue injury, decreased serum cTnI, CK-MB, and LDH, and cardiac MDA, NF-κB p65, TNF-α, and IL-6, and enhanced cellular antioxidants. CUR and N-CUR downregulated TLR4 and AP-1, and decreased the phosphorylation levels of p38 MAPK, JNK, and ERK1/2. In addition, CUR and N-CUR increased cardiac Bcl-2 and BAG-1, decreased Bax and caspase-3, and prevented DNA fragmentation. In conclusion, N-CUR prevents Cu cardiotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis, and modulating TLR4/NF-κB and MAPK signaling. The cardioprotective effect of N-CUR was more potent than the native form.
A Framework for Weather-Driven Dengue Virus Transmission Dynamics in Different Brazilian Regions

This study investigated a model to assess the role of climate fluctuations on dengue (DENV) dynamics from 2010 to 2019 in four Brazilian municipalities. The proposed transmission model was based on a preexisting SEI-SIR model, but also incorporates the vector vertical transmission and the vector’s egg compartment, thus allowing rainfall to be introduced to modulate egg-hatching. Temperature and rainfall satellite data throughout the decade were used as climatic model inputs. A sensitivity analysis was performed to understand the role of each parameter. The model-simulated scenario was compared to the observed dengue incidence and the findings indicate that the model was able to capture the observed seasonal dengue incidence pattern with good accuracy until 2016, although higher deviations were observed from 2016 to 2019. The results further demonstrate that vertical transmission fluctuations can affect attack transmission rates and patterns, suggesting the need to investigate the contribution of vertical transmission to dengue transmission dynamics in future assessments. The improved understanding of the relationship between different environment variables and dengue transmission achieved by the proposed model can contribute to public health policies regarding mosquito-borne diseases.
Cerium-Promoted Ginsenosides Accumulation by Regulating Endogenous Methyl Jasmonate Biosynthesis in Hairy Roots of Panax ginseng

Among rare earth elements, cerium has the unique ability of regulating the growth of plant cells and the biosynthesis of metabolites at different stages of plant development. The signal pathways of Ce3+-mediated ginsenosides biosynthesis in ginseng hairy roots were investigated. At a low concentration, Ce3+ improved the elongation and biomass of hairy roots. The Ce3+-induced accumulation of ginsenosides showed a high correlation with the reactive oxygen species (ROS), as well as the biosynthesis of endogenous methyl jasmonate (MeJA) and ginsenoside key enzyme genes (PgSS, PgSE and PgDDS). At a Ce3+ concentration of 20 mg L−1, the total ginsenoside content was 1.7-fold, and the total ginsenosides yield was 2.7-fold that of the control. Malondialdehyde (MDA) content and the ROS production rate were significantly higher than those of the control. The activity of superoxide dismutase (SOD) was significantly activated within the Ce3+ concentration range of 10 to 30 mg L−1. The activity of catalase (CAT) and peroxidase (POD) strengthened with the increasing concentration of Ce3+ in the range of 20–40 mg L−1. The Ce3+ exposure induced transient production of superoxide anion (O2•−) and hydrogen peroxide (H2O2). Together with the increase in the intracellular MeJA level and enzyme activity for lipoxygenase (LOX), there was an increase in the gene expression level of MeJA biosynthesis including PgLOX, PgAOS and PgJMT. Our results also revealed that Ce3+ did not directly influence PgSS, PgSE and PgDDS activity. We speculated that Ce3+-induced ROS production could enhance the accumulation of ginsenosides in ginseng hairy roots via the direct stimulation of enzyme genes for MeJA biosynthesis. This study demonstrates a potential approach for understanding and improving ginsenoside biosynthesis that is regulated by Ce3+-mediated signal transduction.