Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteins and peptides from vegetable food sources as therapeutic adjuvants for the type 2 diabetes mellitus

Abstract Proteins and peptides are fundamental components of the cereals, pseudocereals, and legumes, giving them numerous health-beneficial properties. Previous studies have demonstrated that these molecules exerted effects on current therapeutic targets related to type 2 diabetes mellitus, such as incretin hormones (responsible for appetite suppression), dipeptidyl peptidase IV (an enzyme involved in the inactivation and degradation of the incretin hormones), and glucose transporters (molecules that transport glucose in or out of cells). Therefore, this review presents the current biological activity of protein derivatives and peptides isolated from cereals, pseudocereals, and legumes on these therapeutic markers, highlighting their potential as a possible pharmacological treatment for type 2 diabetes mellitus.
Microtip focused electrohydrodynamic jet printing with nanoscale resolution.

Electrohydrodynamic jet (E-Jet) printing is a promising manufacturing technique for micro-/nano-patterned structures with high resolution, high efficiency and high material compatibility. However, further improvement of the necking ratio of the E-Jet is still limited by the focusing principle. Moreover, ink viscosity is limited to values well below 90 mPa s owing to the high probability of nozzle blockage. Here, we propose a microtip focused electrohydrodynamic jet (MFEJ) printing to overcome these limitations. This technique uses a solid microtip with a radius of curvature (ROC) of several micrometers rather than a hollow nozzle, which is very simple and highly efficient to prepare and can effectively avoid nozzle clogging problems even with high-viscosity printing ink. High-resolution patterns in diverse geometries were printed using different inks with a wide range of viscosities (8.4-3500 mPa s). Nanodroplets with an average diameter of 73 nm were achieved. Moreover, nanofibers with a diameter of 30 nm were obtained using a 4 μm ROC microtip and the necking ratio was as high as 266 : 1. To the best of our knowledge, this is the smallest droplet or fiber diameter directly obtained via E-Jet printing to date without further physical or chemical processing. This MFEJ printing technique can improve printing resolution at the nanoscale, significantly enlarge the material applicability and effectively avoid nozzle clogging for the fabrication of nanodevices.
Exploring Potential Bioactive Peptides in Fermented Bactrian Camel’s Milk and Mare’s Milk Made by Mongolian Nomads

To date, bioactive proteins and peptides from minor livestock milks and their fermented products have been scarcely reported. In Mongolia, nomads are commonly rearing five livestock animal species (i.e., cow, camel, goat, horse, and sheep) for milking and other purposes. In this study, we analyzed the peptide composition in fermented milks of Bactrian camels (Camelus bactrianus) and horses, produced by Mongolian nomads for self-consumption. Peptides from skimmed fermented milks were separated by ultrafiltration and reverse-phase high-performance liquid chromatography. Then, their amino acid sequences were determined by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. Consequently, eleven peptides were identified in the fermented camel’s milk including four from β-casein (β-CN), three from αs1-CN, and two from both κ-CN and lactophorin. On the other hand, twenty-four peptides were identified in the fermented mare’s milk including nineteen from β-CN, three from αs1-CN, and one from both κ-CN and αs2-CN. According to previous reports on the bioactivities of milk-derived peptides, antibacterial and antihypertensive activities were promising in both the fermented camel’s milk and mare’s milk. In addition, potential antioxidant activity was conjectured in the fermented camel’s milk. Further investigations are currently needed to clarify the potential role of immunomodulatory peptides in the two fermented milks.
SYSTEMIC BUT NOT LOCAL REHYDRATION RESTORES DEHYDRATION-INDUCED CHANGES IN PULMONARY FUNCTION IN HEALTHY ADULTS.

Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were: i) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and ii) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice, and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole-body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration, and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7±0.7% and 2.5±0.4% body mass loss, respectively; p<0.001) and elevated plasma osmolality (p<0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152±143 mL, p<0.01) and concomitant increases in residual volume (216±177 mL, p<0.01) and functional residual capacity (130±144 mL, p<0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption, but not nebulization. Our results suggest that, in healthy adults: i) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and ii) systemic, but not local, rehydration reverses these potentially deleterious alterations.
Associations among circulating sphingolipids, β-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China

Background Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms. Methods and findings The current study included 826 men and 1,148 women who were aged 50–70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14–1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%–42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05–1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication. Conclusions In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
Plant TDP1 (Tyrosyl-DNA Phosphodiesterase 1): A Phylogenetic Perspective and Gene Expression Data Mining

The TDP1 (tyrosyl-DNA phosphodiesterase 1) enzyme removes the non-specific covalent intermediates between topoisomerase I and DNA, thus playing a crucial role in preventing DNA damage. While mammals possess only one TDP1 gene, in plants two genes (TDP1α and TDP1β) are present constituting a small gene subfamily. These display a different domain structure and appear to perform non-overlapping functions in the maintenance of genome integrity. Namely, the HIRAN domain identified in TDP1β is involved in the interaction with DNA during the recognition of stalled replication forks. The availability of transcriptomic databases in a growing variety of experimental systems provides new opportunities to fill the current gaps of knowledge concerning the evolutionary origin and the specialized roles of TDP1 genes in plants. Whereas a phylogenetic approach has been used to track the evolution of plant TDP1 protein, transcriptomic data from a selection of representative lycophyte, eudicots, and monocots have been implemented to explore the transcriptomic dynamics in different tissues and a variety of biotic and abiotic stress conditions. While the phylogenetic analysis indicates that TDP1α is of non-plant origin and TDP1β is plant-specific originating in ancient vascular plants, the gene expression data mining comparative analysis pinpoints for tissue- and stress-specific responses.
Dimensional Change Card Sorting of American Children: Marginalization-Related Diminished Returns of Age.

Background While age is associated with an increase in cognitive flexibility and executive functioning as a result of normal development during childhood, less is known about the effect of racial variation in children's age-related cognitive development. The Marginalization-related Diminished Returns (MDRs) phenomenon suggests that, under racism, social stratification, segregation, and discrimination, individual-level economic and non-economic resources and assets show weaker effects on children's development for marginalized, racialized, and minoritized families. Aim We conducted this study to compare racial groups of children for age-related changes in their card sorting abilities. Methods This cross-sectional study included 10,414 9-10-year-old American children. Data came from the Adolescent Brain Cognitive Development (ABCD) study. The independent variable was age, a continuous variable measured in months. The dependent variable was dimensional change card sort (DCCS) score, which reflected cognitive flexibility, and was measured by the NIH Dimensional Change Card Sort. Ethnicity, sex, parental education, and marital status were the covariates. Results Older age was associated with higher DCCS score, reflecting a higher card-sorting ability and cognitive flexibility. However, age showed a weaker association with DCCS for Black than for White children. This was documented by a significantly negative interaction between race and age on children's DCCS scores. Conclusion Age shows a weaker correlation with the cognitive flexibility of Black than of White children. A similar pattern can be seen when comparing low-income with high-income children. Conceptualizing race as a social factor that alters normal childhood development is a finding that is in line with MDRs. Marginalization due to social stratification and racism interfere with the normal age-related cognitive development of American children.
Development and validation of a new microplate assay that utilises optical density to quantify the antibacterial activity of honeys including Jarrah, Marri and Manuka

The phenol equivalence assay is the current industry-adopted test used to quantify the antibacterial activity of honeys in Australia and New Zealand. Activity is measured based on the diffusion of honey through agar and resulting zone of growth inhibition. Due to differences in the aqueous solubilities of antibacterial compounds found in honeys, this method may not be optimal for quantifying activity. Therefore, a new method was developed based on the existing broth microdilution assay that is widely used for determining minimum inhibitory concentrations (MICs). It utilises the four organisms Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, and an optical density endpoint to quantify bacterial growth. Decreases in bacterial growth in the presence of honey, relative to the positive growth control, are then used to derive a single value to represent the overall antibacterial activity of each honey. Antibacterial activity was quantified for a total of 77 honeys using the new method, the phenol equivalence assay and the standard broth microdilution assay. This included 69 honeys with undisclosed floral sources and the comparators Manuka, Jarrah (Eucalyptus marginata), Marri (Corymbia calophylla), artificial and multifloral honey. For the 69 honey samples, phenol equivalence values ranged from 0–48.5 with a mean of 34 (% w/v phenol). Mean MICs, determined as the average of the MICs obtained for each of the four organisms for each honey ranged from 7–24% (w/v honey). Using the new assay, values for the 69 honeys ranged from 368 to 669 activity units, with a mean of 596. These new antibacterial activity values correlated closely with mean MICs (R2 = 0.949) whereas the relationship with phenol equivalence values was weaker (R2 = 0.649). Limit of detection, limit of quantitation, measuring interval, limit of reporting, sensitivity, selectivity, repeatability, reproducibility, and ruggedness were also investigated and showed that the new assay was both robust and reproducible.
Translation is required for miRNA‐dependent decay of endogenous transcripts

Post‐transcriptional repression of gene expression by miRNAs occurs through transcript destabilization or translation inhibition. mRNA decay is known to account for most miRNA‐dependent repression. However, because transcript decay occurs co‐translationally, whether target translation is a requirement for miRNA‐dependent transcript destabilization remains unknown. To decouple these two molecular processes, we used cytosolic long noncoding RNAs (lncRNAs) as models for endogenous transcripts that are not translated. We show that, despite interacting with the miRNA‐loaded RNA‐induced silencing complex, the steady‐state abundance and decay rates of these transcripts are minimally affected by miRNA loss. To further validate the apparent requirement of translation for miRNA‐dependent decay, we fused two lncRNA candidates to the 3’‐end of a protein‐coding gene reporter and found this results in their miRNA‐dependent destabilization. Further analysis revealed that the few natural lncRNAs whose levels are regulated by miRNAs in mESCs tend to associate with translating ribosomes, and possibly represent misannotated micropeptides, further substantiating the necessity of target translation for miRNA‐dependent transcript decay. In summary, our analyses suggest that translation is required for miRNA‐dependent transcript destabilization, and demonstrate that the levels of coding and noncoding transcripts are differently affected by miRNAs.
Effects of Aging Process on the Damping Performance of ZK60 Magnesium Alloys Prepared by Large Strain Rolling

In this study, the effects of an aging treatment (T5) and a solution + aging treatment (T6) on the microstructure and damping properties of a ZK60 magnesium alloy prepared by large strain rolling (LSR) were studied by an optical microscope (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic thermomechanical analysis (DMA). The results showed that both the T5 and T6 processes had a great impact on the microstructure and damping properties of the ZK60 magnesium alloy. With the increase in aging time, the grain size was basically unchanged, and the amount of the second phase increased, resulting in a gradual decrease in the damping performance. However, compared with the damping performance of the un-aged ZK60 magnesium alloy, the damping performance of the 4 h-aged ZK60 magnesium alloy was enhanced. At the same aging time, the increase in the aging temperature promoted the precipitation of the second phase, thereby reducing the damping performance of the ZK60 magnesium alloy. It was found that the T6-treated ZK60 magnesium alloy had a larger grain size, which led to a better damping performance; in addition, the T6-treated ZK60 magnesium alloy exhibited a damping plateau, which was determined by the distribution and amount of the second phase.
miR-576-5p promotes epithelial-to-mesenchymal transition in colorectal cancer by targeting the Wnt5a-mediated Wnt/β-catenin signaling pathway

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer-associated mortality. MicroRNA (miR)-576-5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR-576-5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR-576-5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR-576-5p and Wnt5a. Reverse transcription-quantitative PCR and western blotting were used to analyze the expression levels of miR-576-5p, E-cadherin, N-cadherin, vimentin, Snail1, Wnt5a, β-catenin, c-myc, cyclin D1 and p/t-c-Jun. Using bioinformatics analysis, high expression of miR-576-5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR-576-5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial-to-mesenchymal transition (EMT). In addition, miR-576-5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/β-catenin signaling. The results from rescue experiments further demonstrated that the effect of miR-576-5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV-939, which is an inhibitor of the Wnt/β-catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR-576-5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a-mediated Wnt/β-catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.
Predicting Tumor Killing and T-Cell Activation by T-Cell Bispecific Antibodies as a Function of Target Expression: Combining In Vitro Experiments with Systems Modeling

Targeted T-cell redirection is a promising field in cancer immunotherapy. T-cell bispecific antibodies (TCB) are novel antibody constructs capable of binding simultaneously to T cells and tumor cells, allowing cross-linking and the formation of immunologic synapses. This in turn results in T-cell activation, expansion, and tumor killing. TCB activity depends on system-related properties such as tumor target antigen expression as well as antibody properties such as binding affinities to target and T cells. Here, we developed a systems model integrating in vitro data to elucidate further the mechanism of action and to quantify the cytotoxic effects as the relationship between targeted antigen expression and corresponding TCB activity. In the proposed model, we capture relevant processes, linking immune synapse formation to T-cell activation, expansion, and tumor killing for TCBs in vitro to differentiate the effect between tumor cells expressing high or low levels of the tumor antigen. We used cibisatamab, a TCB binding to carcinoembryonic antigen (CEA), to target different tumor cell lines with high and low CEA expression in vitro. We developed a model to capture and predict our observations, as a learn-and-confirm cycle. Although full tumor killing and substantial T-cell activation was observed in high expressing tumor cells, the model correctly predicted partial tumor killing and minimal T-cell activation in low expressing tumor cells when exposed to cibisatamab. Furthermore, the model successfully predicted cytotoxicity across a wide range of tumor cell lines, spanning from very low to high CEA expression.
Family's Subjective Economic Status and Children's Matrix Reasoning: Blacks' Diminished Returns.

Background Due to a pattern known as Marginalization-related Diminished Returns (MDRs), historically oppressed non-Hispanic Black Americans show weaker effects of economic status on health and development, when compared to socially privileged non-Hispanic White Americans. Such MDRs are also documented for the effects of economic status on the school performance of non-Hispanic Black children. However, the existing knowledge is minimal on similar diminished returns on children's intelligence. Aim To compare racial and ethnic groups for the effect of subjective economic status on children's cognitive performance, we compared non-Hispanic White and non-Hispanic Black children for the effects of subjective economic status on children's matrix reasoning. Methods This cross-sectional study included 7898 children from the Adolescent Brain Cognitive Development (ABCD) study. The predictor variable was subjective economic status, which was treated as a continuous measure. The primary outcome was children's matrix reasoning, a domain of cognitive performance, measured by the Wechsler Intelligence Scales for Children-IV (WISC-V) matrix reasoning total score. Results Overall, high subjective economic status was associated with higher matrix reasoning score. Race showed a statistically significant interaction with subjective economic status on children's matrix reasoning score. This interaction suggested that high subjective economic status has a smaller boosting effect on increasing matrix reasoning score for non-Hispanic Black children relative to non-Hispanic White children. Conclusion The degree by which subjective economic status correlates with matrix reasoning score, an important domain of cognitive performance, depends on race and racialization. Non-Hispanic Black children may show weaker gains in matrix reasoning from their subjective economic status than their non-Hispanic White counterparts. To minimize the racial gap in cognitive performance, we need to address diminished returns that occur as a result of the racialization of racial and ethnic minority children. Not only should we equalize economic status, but also increase the marginal returns of economic status for racial minorities, particularly non-Hispanic Black families. Such efforts require public policies that go beyond access and also consider how we can empower non-Hispanic Black communities and families so they can more effectively leverage and utilize their economic resources to secure measurable and tangible outcomes. Structural and societal barriers such as residential and school segregation may hinder non-Hispanic Black children from receiving the full effects of their family-level economic status on a variety of outcomes, including their cognitive performance.