Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Alginate-Microencapsulated Hydrogels on the Survival of Lactobacillus rhamnosus under Simulated Gastrointestinal Conditions

Thanks to the beneficial properties of probiotic bacteria, there exists an immense demand for their consumption in probiotic foods worldwide. Nevertheless, it is difficult to retain a high number of viable cells in probiotic food products during their storage and gastrointestinal transit. Microencapsulation of probiotic bacteria is an effective way of enhancing probiotic viability by limiting cell exposure to extreme conditions via the gastrointestinal tract before releasing them into the colon. This research aims to develop a new coating material system of microencapsulation to protect probiotic cells from adverse environmental conditions and improve their recovery rates. Hence, Lactobacillus rhamnosus was encapsulated with emulsion/internal gelation techniques in a calcium chloride solution. Alginate–probiotic microbeads were coated with xanthan gum, gum acacia, sodium caseinate, chitosan, starch, and carrageenan to produce various types of microcapsules. The alginate+xanthan microcapsules exhibited the highest encapsulation efficiency (95.13 ± 0.44%); they were simulated in gastric and intestinal juices at pH 3 during 1, 2, and 3 h incubations at 37 °C. The research findings showed a remarkable improvement in the survival rate of microencapsulated probiotics under simulated gastric conditions of up to 83.6 ± 0.89%. The morphology, size, and shape of the microcapsules were analyzed using a scanning electron microscope. For the protection of probiotic bacteria under simulated intestinal conditions; alginate microbeads coated with xanthan gum played an important role, and exhibited a survival rate of 87.3 ± 0.79%, which was around 38% higher than that of the free cells (49.4 ± 06%). Our research findings indicated that alginate+xanthan gum microcapsules have a significant potential to deliver large numbers of probiotic cells to the intestines, where cells can be released and colonized for the consumer’s benefit.
Exogenous Enzymes Influenced Eimeria-Induced Changes in Cecal Fermentation Profile and Gene Expression of Nutrient Transporters in Broiler Chickens

Simple Summary Eimeria-induced coccidiosis, a common disease in the poultry industry, causes substantial economic loss globally. The developed resistance to synthetic anticoccidial drugs and increasing public and legislative pressures to decrease antibiotic utilization drive research exploring non-antibiotic alternatives to control coccidiosis. Two experiments were conducted to investigate the potential mechanisms by which enzymes may mitigate the negative effects of Eimeria on growth performance, nutrient-transporter gene expression, and cecal fermentation patterns. The results demonstrated that Eimeria changed the expression of tight junctions and nutrient transporters genes, promoted cecal protein fermentation, and inhibited cecal saccharolytic fermentation. Exogenous xylanase and protease supplementation alleviated negative effects of Eimeria effects on the above responses, and thus demonstrated benefits of enzyme supplementation beyond improvement in nutrient utilization. Abstract Two 21-day experiments were conducted to investigate the effects of exogenous enzymes on growth performance, tight junctions, and nutrient transporters, jejunal oligosaccharides and cecal short-chain fatty acids (SCFA) of broiler chickens challenged with mixed Eimeria. Two different basal diets: high fiber-adequate protein (HFAP; Expt. 1) or low fiber-low protein (LFLP; Expt. 2) were used in the two experiments. In each experiment, birds were allocated to four treatments in a 2 × 2 factorial arrangement (with or without protease and xylanase combination; with or without Eimeria challenge). In Expt. 1, with HFAP diets, Eimeria upregulated (p < 0.05) the expression of claudin-1, but downregulated (p < 0.05) glucose transporters GLUT2/GLUT5. On the contrary, enzymes downregulated (p < 0.05) claudin-1 and alleviated the Eimeria-depressed GLUT2/GLUT5 expression. In both experiments, Eimeria decreased (p < 0.05) cecal saccharolytic SCFA and increased (p < 0.05) cecal branched-chain fatty acids. The challenge × enzyme interaction (p < 0.05) showed that enzymes reversed the Eimeria effects on fermentation pattern shift. In conclusion, Eimeria altered tight junctions and nutrient transporters expression promoted cecal proteolytic fermentation and inhibited saccharolytic fermentation. Exogenous enzymes showed the potential of alleviating the Eimeria-induced intestinal gene expression changes and reversing the unfavorable cecal fermentation pattern.
Non-Contact Oxygen Saturation Measurement Using YCgCr Color Space with an RGB Camera

Oxygen saturation (SPO2) is an important indicator of health, and is usually measured by placing a pulse oximeter in contact with a finger or earlobe. However, this method has a problem in that the skin and the sensor must be in contact, and an additional light source is required. To solve these problems, we propose a non-contact oxygen saturation measurement technique that uses a single RGB camera in an ambient light environment. Utilizing the fact that oxygenated and deoxygenated hemoglobin have opposite absorption coefficients at green and red wavelengths, the color space of photoplethysmographic (PPG) signals recorded from the faces of study participants were converted to the YCgCr color space. Substituting the peaks and valleys extracted from the converted Cg and Cr PPG signals into the Beer–Lambert law yields the SPO2 via a linear equation. When the non-contact SPO2 measurement value was evaluated based on the reference SPO2 measured with a pulse oximeter, the mean absolute error was 0.537, the root mean square error was 0.692, the Pearson correlation coefficient was 0.86, the cosine similarity was 0.99, and the intraclass correlation coefficient was 0.922. These results confirm the feasibility of non-contact SPO2 measurements.
Molecular Basis of Artemisinin Derivatives Inhibition of Myeloid Differentiation Protein 2 by Combined in Silico and Experimental Study

Artemisinin (also known as Qinghaosu), an active component of the Qinghao extract, is widely used as antimalarial drug. Previous studies reveal that artemisinin and its derivatives also have effective anti-inflammatory and immunomodulatory properties, but the direct molecular target remains unknown. Recently, several reports mentioned that myeloid differentiation factor 2 (MD-2, also known as lymphocyte antigen 96) may be the endogenous target of artemisinin in the inhibition of lipopolysaccharide signaling. However, the exact interaction between artemisinin and MD-2 is still not fully understood. Here, experimental and computational methods were employed to elucidate the relationship between the artemisinin and its inhibition mechanism. Experimental results showed that artemether exhibit higher anti-inflammatory activity performance than artemisinin and artesunate. Molecular docking results showed that artemisinin, artesunate, and artemether had similar binding poses, and all complexes remained stable throughout the whole molecular dynamics simulations, whereas the binding of artemisinin and its derivatives to MD-2 decreased the TLR4(Toll-Like Receptor 4)/MD-2 stability. Moreover, artemether exhibited lower binding energy as compared to artemisinin and artesunate, which is in good agreement with the experimental results. Leu61, Leu78, and Ile117 are indeed key residues that contribute to the binding free energy. Binding free energy analysis further confirmed that hydrophobic interactions were critical to maintain the binding mode of artemisinin and its derivatives with MD-2.
Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia

Renal hypouricemia is a rare genetic disorder. Hypouricemia can present as renal stones or exercise-induced acute renal failure, but most cases are asymptomatic. Our previous study showed that two recessive variants of SLC22A12 (p.Trp258*, pArg90His) were identified in 90% of the hypouricemia patients from two independent cohorts: the Korean genome and epidemiology study (KoGES) and the Korean Cancer Prevention Study (KCPS-II). In this work, we investigate the genetic causes of hypouricemia in the rest of the 10% of unsolved cases. We found a novel non-synonymous mutation of SLC2A9 (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in SLCA9b (p.Met155Val in SLC2A9a) hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using Xenopus oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the SLC2A9 protein expression level. Our results will shed light on a better understanding of SLC2A9-mediated uric acid transport and the development of a uric acid-lowering agent.
Development and Optimization of Djulis Sourdough Bread Fermented by Lactic Acid Bacteria for Antioxidant Capacity

This study developed a nutritionally valuable product with bioactive activity that improves the quality of bread. Djulis (Chenopodium formosanum), a native plant of Taiwan, was fermented using 23 different lactic acid bacteria strains. Lactobacillus casei BCRC10697 was identified as the ideal strain for fermentation, as it lowered the pH value of samples to 4.6 and demonstrated proteolysis ability 1.88 times higher than controls after 24 h of fermentation. Response surface methodology was adopted to optimize the djulis fermentation conditions for trolox equivalent antioxidant capacity (TEAC). The optimal conditions were a temperature of 33.5 °C, fructose content of 7.7%, and dough yield of 332.8, which yielded a TEAC at 6.82 mmol/kg. A 63% increase in TEAC and 20% increase in DPPH were observed when compared with unfermented djulis. Subsequently, the fermented djulis was used in different proportions as a substitute for wheat flour to make bread. The total phenolic and flavonoid compounds were 4.23 mg GAE/g and 3.46 mg QE/g, marking respective increases of 18% and 40% when the djulis was added. Texture analysis revealed that adding djulis increased the hardness and chewiness of sourdough breads. It also extended their shelf life by approximately 2 days. Thus, adding djulis to sourdough can enhance the functionality of breads and may provide a potential basis for developing djulis-based functional food.
Genome-Wide Identification and Analyses of Drought/Salt-Responsive Cytochrome P450 Genes in Medicago truncatula

Cytochrome P450 monooxygenases (P450s) catalyze a great number of biochemical reactions and play vital roles in plant growth, development and secondary metabolism. As yet, the genome-scale investigation on P450s is still lacking in the model legume Medicago truncatula. In particular, whether and how many MtP450s are involved in drought and salt stresses for Medicago growth, development and yield remain unclear. In this study, a total of 346 MtP450 genes were identified and classified into 10 clans containing 48 families. Among them, sixty-one MtP450 genes pairs are tandem duplication events and 10 MtP450 genes are segmental duplication events. MtP450 genes within one family exhibit high conservation and specificity in intron–exon structure. Meanwhile, many Mt450 genes displayed tissue-specific expression pattern in various tissues. Specifically, the expression pattern of 204 Mt450 genes under drought/NaCl treatments were analyzed by using the weighted correlation network analysis (WGCNA). Among them, eight genes (CYP72A59v1, CYP74B4, CYP71AU56, CYP81E9, CYP71A31, CYP704G6, CYP76Y14, and CYP78A126), and six genes (CYP83D3, CYP76F70, CYP72A66, CYP76E1, CYP74C12, and CYP94A52) were found to be hub genes under drought/NaCl treatments, respectively. The expression levels of these selected hub genes could be induced, respectively, by drought/NaCl treatments, as validated by qPCR analyses, and most of these genes are involved in the secondary metabolism and fatty acid pathways. The genome-wide identification and co-expression analyses of M. truncatula P450 superfamily genes established a gene atlas for a deep and systematic investigation of P450 genes in M. truncatula, and the selected drought-/salt-responsive genes could be utilized for further functional characterization and molecular breeding for resistance in legume crops.
Ent-abietane diterpenoids and their probable biogenetic precursors from the roots of Euphorbia fischeriana

Five new ent-abietane diterpenoids (1–5), along with nine known analogues (6–14), were isolated from the roots of Euphorbia fischeriana. Their structures and absolute configurations were determined by the analysis of extensive spectroscopic data (UV, IR, HRESIMS, NMR) and the comparison of the experimental and calculated electronic circular dichroism (ECD). Among the isolates, it's notable that the ent-abietane diterpenoids bearing an additional five-membered lactone ring might be derived from the proposed precursors of fischeriabietane B (2) and C (3), and their plausible biosynthetic relationship was detailed discussed. All the isolates were evaluated for cytotoxicity against three human cancer cell lines (Panc-28, Bel-7402, and HT-29), 2 and 3 exhibited moderate cytotoxicity.
Identification of Substances Produced by Cercospora brachiata in Absence of Light and Evaluation of Antibacterial Activity

Cercospora brachiata is a phytopathogenic fungus. To know more about the metabolites produced by this fungus, the objective of this work was to identify, isolate and characterize substances present in extracts of the growth broth and mycelium, using gas chromatography with mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR). It was also objective to evaluate the antibacterial activity of the extracts. Among the compounds identified, fatty acids, esters, and steroids can be highlighted. The main compounds identified are 9-hexadecenoic, hexadecenoic, oleic, octadecanoic, lauric, myristic, palmitic, doceno-13-enoic, stearic, linoleic, and nonadecanoic acids present in almost all extracts. For the antibacterial activity, the broth microdilution method was used. The ethyl acetate extract of the mycelium presented inhibitory concentrations (MICs) against the bacterium Actinomyces naeslundii (100 μg mL−1) and Streptococcus sanguinis (200 μg mL−1). Finally, two steroids were isolated and identified in the hexane extract of mycelium: ergosta-6,22-dien-3β,5α,8α-triol and brassicasterol.
Combined Profiling of Transcriptome and DNA Methylome Reveal Genes Involved in Accumulation of Soluble Sugars and Organic Acid in Apple Fruits

Organic acids and soluble sugars are the major determinants of fruit organoleptic quality. Additionally, DNA methylation has crucial regulatory effects on various processes. However, the epigenetic modifications in the regulation of organic acid and soluble sugar accumulation in apple fruits remain uncharacterized. In this study, DNA methylation and the transcriptome were compared between ‘Honeycrisp’ and ‘Qinguan’ mature fruits, which differ significantly regarding soluble sugar and organic acid contents. In both ‘Honeycrisp’ and ‘Qinguan’ mature fruits, the CG context had the highest level of DNA methylation, and then CHG and CHH contexts. The number and distribution of differentially methylated regions (DMRs) varied among genic regions and transposable elements. The DNA methylation levels in all three contexts in the DMRs were significantly higher in ‘Honeycrisp’ mature fruits than in ‘Qinguan’ mature fruits. A combined methylation and transcriptome analysis revealed a negative correlation between methylation levels and gene expression in DMRs in promoters and gene bodies in the CG and CHG contexts and in gene bodies in the CHH context. Two candidate genes (MdTSTa and MdMa11), which encode tonoplast-localized proteins, potentially associated with fruit soluble sugar contents and acidity were identified based on expression and DNA methylation levels. Overexpression of MdTSTa in tomato increased the fruit soluble sugar content. Moreover, transient expression of MdMa11 in tobacco leaves significantly decreased the pH value. Our results reflect the diversity in epigenetic modifications influencing gene expression and will facilitate further elucidating the complex mechanism underlying fruit soluble sugar and organic acid accumulation.
Real Sample Consistency Regularization for GANs

Mode collapse has always been a fundamental problem in generative adversarial networks. The recently proposed Zero Gradient Penalty (0GP) regularization can alleviate the mode collapse, but it will exacerbate a discriminator’s misjudgment problem, that is the discriminator judges that some generated samples are more real than real samples. In actual training, the discriminator will direct the generated samples to point to samples with higher discriminator outputs. The serious misjudgment problem of the discriminator will cause the generator to generate unnatural images and reduce the quality of the generation. This paper proposes Real Sample Consistency (RSC) regularization. In the training process, we randomly divided the samples into two parts and minimized the loss of the discriminator’s outputs corresponding to these two parts, forcing the discriminator to output the same value for all real samples. We analyzed the effectiveness of our method. The experimental results showed that our method can alleviate the discriminator’s misjudgment and perform better with a more stable training process than 0GP regularization. Our real sample consistency regularization improved the FID score for the conditional generation of Fake-As-Real GAN (FARGAN) from 14.28 to 9.8 on CIFAR-10. Our RSC regularization improved the FID score from 23.42 to 17.14 on CIFAR-100 and from 53.79 to 46.92 on ImageNet2012. Our RSC regularization improved the average distance between the generated and real samples from 0.028 to 0.025 on synthetic data. The loss of the generator and discriminator in standard GAN with our regularization was close to the theoretical loss and kept stable during the training process.
Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

The Coronavirus disease 2019 (COVID-19) pandemic has represented an unprecedented challenge for humankind from health, economic, and social viewpoints. In February 2020, Italy was the first western country to be deeply hit by the pandemic and suffered the highest case/fatality rate among western countries. Brand new anti-COVID-19 vaccines have been developed and made available in <1-year from the viral sequence publication. Patients with compromised immune systems, such as autoimmune-autoinflammatory disorders (AIAIDs), primary (PIDs) and secondary (SIDs) immunodeficiencies, have received careful attention for a long time regarding their capacity to safely respond to traditional vaccines. The Italian Immunological Societies, therefore, have promptly faced the issues of safety, immunogenicity, and efficacy/effectiveness of the innovative COVID-19 vaccines, as well as priority to vaccine access, in patients with AIADs, PIDs, and SIDs, by organizing an ad-hoc Task Force. Patients with AIADs, PIDs, and SIDs: (1) Do not present contraindications to COVID-19 vaccines if a mRNA vaccine is used and administered in a stabilized disease phase without active infection. (2) Should usually not discontinue immunosuppressive therapy, which may be modulated depending on the patient’s clinical condition. (3) When eligible, should have a priority access to vaccination. In fact, immunizing these patients may have relevant social/health consequences, since these patients, if infected, may develop chronic infection, which prolongs viral spread and facilitates the emergence of viral variants.
Molecular Insights in Atrial Fibrillation Pathogenesis and Therapeutics: A Narrative Review

The prevalence of atrial fibrillation (AF) is bound to increase globally in the following years, affecting the quality of life of millions of people, increasing mortality and morbidity, and beleaguering health care systems. Increasingly effective therapeutic options against AF are the constantly evolving electroanatomic substrate mapping systems of the left atrium (LA) and ablation catheter technologies. Yet, a prerequisite for better long-term success rates is the understanding of AF pathogenesis and maintenance. LA electrical and anatomical remodeling remains in the epicenter of current research for novel diagnostic and treatment modalities. On a molecular level, electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. These overlapping cellular and molecular alterations hinder us from distinguishing the cause from the effect in AF pathogenesis. Yet, a plethora of therapeutic modalities target these molecular perturbations and hold promise in combating the AF burden. Namely, atrial selective ion channel inhibitors, AF gene therapy, anti-fibrotic agents, AF drug repurposing, immunomodulators, and indirect cardiac neuromodulation are discussed here.
Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants

Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which can be used in combination with approved antimicrobial drugs. In this work, a library of nineteen marine natural products, isolated from marine-derived fungi of the genera Neosartorya and Aspergillus, was evaluated for their potential as bacterial efflux pump inhibitors as well as the antimicrobial-related mechanisms, such as inhibition of biofilm formation and quorum-sensing. Docking studies were performed to predict their efflux pump action. These compounds were also tested for their cytotoxicity in mouse fibroblast cell line NIH/3T3. The results obtained suggest that the marine-derived fungal metabolites are a promising source of compounds with potential to revert antimicrobial resistance and serve as an inspiration for the synthesis of new antimicrobial drugs.