Miracle-dz/UniFAR-FTUs huggingface dataset:
miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy

Simple Summary Cancer onset and progression are promoted by high deregulation of the immune system. Recently, major advances in molecular and clinical cancer immunology have been achieved, offering new agents for the treatment of common tumors, often with astonishing benefits in terms of prolonged survival and even cure. Unfortunately, most tumors are still resistant to current immune therapy approaches, and basic knowledge of the resistance mechanisms is eagerly awaited. We focused our attention on noncoding RNAs, a class of RNA that regulates many biological processes by targeting selectively crucial molecular pathways and that, recently, had their role in cancer cell immune escape and modulation of the tumor microenvironment identified, suggesting their function as promising immunotherapeutic targets. In this scenario, we point out that noncoding RNAs are progressively emerging as immunoregulators, and we depict the current information on the complex network involving the immune system and noncoding RNAs and the promising therapeutic options under investigation. Novel opportunities are emerging from noncoding-RNAs for the treatment of immune-refractory tumors. Abstract Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recently, the key roles of miRNA and lncRNAs as regulators of the immune-response in cancer have progressively emerged, since they may act (i) by shaping the intrinsic tumor cell and microenvironment (TME) properties; (ii) by regulating angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and drug resistance; and (iii) by acting as potential biomarkers for prognostic assessment and prediction of response to immunotherapy. In this review, we provide an overview on the role of ncRNAs in modulating the immune response and the TME. We discuss the potential use of ncRNAs as potential biomarkers or as targets for development or clinical translation of new therapeutics. Finally, we discuss the potential combinatory approaches based on ncRNA targeting agents and tumor immune-checkpoint inhibitor antibodies or CAR-T for the experimental treatment of human cancer.
Biomedical Applications of Bacteria-Derived Polymers

Plastics have found widespread use in the fields of cosmetic, engineering, and medical sciences due to their wide-ranging mechanical and physical properties, as well as suitability in biomedical applications. However, in the light of the environmental cost of further upscaling current methods of synthesizing many plastics, work has recently focused on the manufacture of these polymers using biological methods (often bacterial fermentation), which brings with them the advantages of both low temperature synthesis and a reduced reliance on potentially toxic and non-eco-friendly compounds. This can be seen as a boon in the biomaterials industry, where there is a need for highly bespoke, biocompatible, processable polymers with unique biological properties, for the regeneration and replacement of a large number of tissue types, following disease. However, barriers still remain to the mass-production of some of these polymers, necessitating new research. This review attempts a critical analysis of the contemporary literature concerning the use of a number of bacteria-derived polymers in the context of biomedical applications, including the biosynthetic pathways and organisms involved, as well as the challenges surrounding their mass production. This review will also consider the unique properties of these bacteria-derived polymers, contributing to bioactivity, including antibacterial properties, oxygen permittivity, and properties pertaining to cell adhesion, proliferation, and differentiation. Finally, the review will select notable examples in literature to indicate future directions, should the aforementioned barriers be addressed, as well as improvements to current bacterial fermentation methods that could help to address these barriers.
Optimized Atomic Partial Charges and Radii Defined by Radical Voronoi Tessellation of Bulk Phase Simulations

We present a novel method for the computation of well-defined optimized atomic partial charges and radii from the total electron density. Our method is based on a two-step radical Voronoi tessellation of the (possibly periodic) system and subsequent integration of the total electron density within each Voronoi cell. First, the total electron density is partitioned into the contributions of each molecule, and subsequently the electron density within each molecule is assigned to the individual atoms using a second set of atomic radii for the radical Voronoi tessellation. The radii are optimized on-the-fly to minimize the fluctuation (variance) of molecular and atomic charges. Therefore, our method is completely free of empirical parameters. As a by-product, two sets of optimized atomic radii are produced in each run, which take into account many specific properties of the system investigated. The application of an on-the-fly interpolation scheme reduces discretization noise in the Voronoi integration. The approach is particularly well suited for the calculation of partial charges in periodic bulk phase systems. We apply the method to five exemplary liquid phase simulations and show how the optimized charges can help to understand the interactions in the systems. Well-known effects such as reduced ion charges below unity in ionic liquid systems are correctly predicted without any tuning, empiricism, or rescaling. We show that the basis set dependence of our method is very small. Only the total electron density is evaluated, and thus, the approach can be combined with any electronic structure method that provides volumetric total electron densities—it is not limited to Hartree–Fock or density functional theory (DFT). We have implemented the method into our open-source software tool TRAVIS.
Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications

The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta‐related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p‐FoxO3a) in placental tissue from healthy pregnant women and pre‐eclampsia patients were first compared. Then, HTR‐8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit‐8, wound‐healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT‐PCR and ChIP‐qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p‐FoxO3a was increased in pre‐eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule‐1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.
Heavy metal pollution in soil and plants at bone char site

This study determined the heavy metal concentration in soil and plants at a bone char site in Umuahia, Nigeria. Soil and plant samples collected in a randomized complete block design (RCBD) were analyzed for zinc (Zn), lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As). The concentration of metals in soil and plants in the vicinity of the bone char site are as follows: Zn (172 mg kg−1) and Ni (0.62 mg kg−1) in soil were highest at site P3, Pb (2.37 mg kg−1) and As (0.08 mg kg−1) at site P1, and Cd (18.30 mg kg−1) at site P2. In plants, the concentrations of Zn (41.17 mg kg−1) and Cd (3 mg kg−1) were highest in Albizia ferruginea, Ni in Dialium guineense (0.09 mg kg−1), while Pb was in D. guineense (0.08 mg kg−1) and Spathodea companulata (0.06 mg kg−1). The levels of Zn, Cd, Pb, Ni, and As in soil ranged from 11.2 to 172, 2.68 to 18.2, 0.026 to 2.37, 0.33 to 0.62, and 0.02 to 0.08 mg kg−1, respectively. In plants, the concentration of Zn, Cd, Pb, and Ni ranged from 2.01 to 41.17, 0.12 to 3, 0.02 to 0.08, and 0.03 to 0.09 mg kg−1, respectively. There were significant correlations between Zn and Cd, and Pb and As in soil. The high concentration of Cd in soil might affect soil productivity.
Comparison of Different Cermet Coatings Sprayed on Magnesium Alloy by HVOF

In the present study, two different cermet coatings, WC–CrC–Ni and Cr3C2–NiCr, manufactured by the high-velocity oxy-fuel (HVOF) method were studied. They are labeled as follows: WC–CrC–Ni coating—WC and Cr3C2–NiCr coating—CrC. These coatings were deposited onto a magnesium alloy (AZ31) substrate. The goal of the study was to compare these two types of cermet coating, which were investigated in terms of microstructure features and selected mechanical properties, such as hardness, instrumented indentation, fracture toughness, and wear resistance. The results reveal that the WC content influenced the hardness and Young’s modulus. The most noticeable effect of WC addition was observed for the wear resistance. WC coatings had a wear intensity value that was almost two times lower, equal to 6.5·10−6 mm3/N·m, whereas for CrC ones it was equal to 12.6·10−6 mm3/N·m. On the other hand, the WC coating exhibited a lower value of fracture toughness.
Albendazole Exhibits Anti-Neoplastic Actions against Gastric Cancer Cells by Affecting STAT3 and STAT5 Activation by Pleiotropic Mechanism(s)

Albendazole (ABZ) has been reported to display anti-tumoral actions against various maliganncies, but possible impact of ABZ on gastric cancer has not been deciphered. As aberrant phosphorylation of STAT3 and STAT5 proteins can regulate the growth and progression of gastric cancer, we postulated that ABZ may interrupt the activation of these oncogenic transcription factors. We found that ABZ exposure abrogated STAT3/5 activation, inhibited phosphorylation of Janus-activated kinases 1/2 and Src and enhanced the levels of SHP-1 protein. Silencing of SHP-1 gene by small interfering RNA (siRNA) reversed the ABZ-promoted attenuation of STAT3 as well as STAT5 activation and cellular apoptosis. In addition, these effects were noted to be driven by an augmented levels of reactive oxygen species caused by drug-induced GSH/GSSG imbalance. Thus, the data indicates that ABZ can modulate the activation of STAT3 and STAT5 by pleiotropic mechanisms in gastric cancer cells.
A Non-Destructive, Tuneable Method to Isolate Live Cells for High-Speed AFM Analysis

Suitable immobilisation of microorganisms and single cells is key for high-resolution topographical imaging and study of mechanical properties with atomic force microscopy (AFM) under physiologically relevant conditions. Sample preparation techniques must be able to withstand the forces exerted by the Z range-limited cantilever tip, and not negatively affect the sample surface for data acquisition. Here, we describe an inherently flexible methodology, utilising the high-resolution three-dimensional based printing technique of multiphoton polymerisation to rapidly generate bespoke arrays for cellular AFM analysis. As an example, we present data collected from live Emiliania huxleyi cells, unicellular microalgae, imaged by contact mode High-Speed Atomic Force Microscopy (HS-AFM), including one cell that was imaged continuously for over 90 min.
Telecommuting, Off-Time Work, and Intrusive Leadership in Workers’ Well-Being

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the COVID-19 pandemic. There is still limited evidence on the effects it has on workers’ health. In this survey we invited 905 workers of companies that made a limited use of telecommuting to fill out a questionnaire to evaluate intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (Bergen Work Addiction Scale (BWAS)), effort/reward imbalance (ERI), happiness, and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occupational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety, and depression. These results indicate the need to guarantee the right to disconnect to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.
TMK4 receptor kinase negatively modulates ABA signaling by phosphorylating ABI2 and enhancing its activity.

In plants, clade A type 2C protein phosphatases (PP2CAs) have emerged as major players in abscisic acid (ABA)-regulated stress responses by inhibiting protein kinase activity. However, how different internal and external environmental signals modulate the activity of PP2CAs are not well known. The Transmembrane Kinase (TMK) protein 4 (TMK4), one member of a previously identified receptor kinase subfamily on the plasma membrane that play vital roles in plant cell growth, directly interacts with PP2CAs member (ABA-Insensitive 2, ABI2). tmk4 mutant is hypersensitive to ABA in both ABA-inhibited seed germination and primary root growth, indicating that TMK4 is a negative regulator in ABA signaling pathway. Further analyses indicate that TMK4 phosphorylates ABI2 at three conserved Ser residues, thus enhancing the activity of ABI2. The phosphorylation-mimic ABI2S139DS140DS266D can complement but non-phosphorylated form ABI2S139AS140AS266A cannot complement ABA hypersensitive phenotype of the loss-of- function mutant abi1-2abi2-2. This study provides a previously unidentified mechanism for positively regulating ABI2 by a plasma membrane protein kinase. This article is protected by copyright. All rights reserved.
Optimized Tapered Fiber Decorated by Ag Nanoparticles for Raman Measurement with High Sensitivity

A tapered fiber decorated by Ag nanoparticles is prepared as a surface-enhanced Raman scattering (SERS) substrate. There are two key parameters during the preparation process, the fiber cone angle and the density of decorated AgNPs on the fiber tip surface. Their theoretical analysis on the forming mechanism and the optimization process is studied in detail. The tapered fibers with angles from 0.5 to 30° are successfully prepared, with a chemical method in a small tube using a bending interface. AgNPs with different densities are decorated on the surface of the tapered fibers with an electrostatic adsorption method. The optimized tapered fiber SERS probe with an angle of 12° and AgNPs density of 26.67% provides the detection of Rhodamine 6G (R6G) with 10−10 mol/L.
Computational Analysis of the Interactions between the S100B Extracellular Chaperone and Its Amyloid β Peptide Client

S100B is an astrocytic extracellular Ca2+-binding protein implicated in Alzheimer’s disease, whose role as a holdase-type chaperone delaying Aβ42 aggregation and toxicity was recently uncovered. Here, we employ computational biology approaches to dissect the structural details and dynamics of the interaction between S100B and Aβ42. Driven by previous structural data, we used the Aβ25–35 segment, which recapitulates key aspects of S100B activity, as a starting guide for the analysis. We used Haddock to establish a preferred binding mode, which was studied with the full length Aβ using long (1 μs) molecular dynamics (MD) simulations to investigate the structural dynamics and obtain representative interaction complexes. From the analysis, Aβ-Lys28 emerged as a key candidate for stabilizing interactions with the S100B binding cleft, in particular involving a triad composed of Met79, Thr82 and Glu86. Binding constant calculations concluded that coulombic interactions, presumably implicating the Lys28(Aβ)/Glu86(S100B) pair, are very relevant for the holdase-type chaperone activity. To confirm this experimentally, we examined the inhibitory effect of S100B over Aβ aggregation at high ionic strength. In agreement with the computational predictions, we observed that electrostatic perturbation of the Aβ-S100B interaction decreases anti-aggregation activity. Altogether, these findings unveil features relevant in the definition of selectivity of the S100B chaperone, with implications in Alzheimer’s disease.
Metabolic and Productive Response and Grazing Behavior of Lactating Dairy Cows Supplemented with High Moisture Maize or Cracked Wheat Grazing at Two Herbage Allowances in Spring

Simple Summary Energy supplements such as high moisture maize or cracked wheat increase total dry matter intake (DMI) and dairy cow performance compared to pasture-only diets. However, the effectiveness of such a feeding strategy depends upon the level of herbage allowance (HA). In this study, increasing HA from 20 to 30 kg DM/cow had no effect on milk production but increased the concentration of urea in milk and plasma regardless of the type of energy supplement offered to grazing dairy cows. These results demonstrate that in high-quality pasture, low HA is appropriate to improve milk production performance per cow and per hectare. Abstract The aim was to determine the effect of the herbage allowance (HA) and supplement type (ST) on dry matter intake (DMI), milk production and composition, grazing behavior, rumen function, and blood metabolites of grazing dairy cows in the spring season. Experiment I: 64 Holstein Friesian dairy cows were distributed in a factorial design that tested two levels of daily HA (20 and 30 kg of dry matter (DM) per cow) and two ST (high moisture maize (HMM) and cracked wheat (CW)) distributed in two daily rations (3.5 kg DM/cow/day). Experiment II: four mid-lactation rumen cannulated cows, supplemented with either HMM or CW and managed with the two HAs, were distributed in a Latin square design of 4 × 4, for four 14-d periods to assess ruminal fermentation parameters. HA had no effect on milk production (averaging 23.6 kg/day) or milk fat and protein production (823 g/day and 800 g/day, respectively). Cows supplemented with CW had greater protein concentration (+1.2 g/kg). Herbage DMI averaged 14.17 kg DM/cow.day and total DMI averaged 17.67 kg DM/cow.day and did not differ between treatments. Grazing behavior activities (grazing, rumination, and idling times) and body condition score (BCS) were not affected by HA or ST. Milk and plasma urea concentration increased under the high HA (+0.68 mmol/L and +0.90 mmol/L, respectively). Cows supplemented with HMM had lower milk and plasma urea concentrations (0.72 mmol/L and 0.76 mmol/L less, respectively) and tended (p = 0.054) to have higher plasma β-hydroxybutyrate. Ruminal parameters did not differ between treatments.
Towards a Sustainable Reproduction Management of Dairy Sheep: Glycerol-Based Formulations as Alternative to eCG in Milked Ewes Mated at the End of Anoestrus Period

Simple Summary Reproductive management of sheep for autumnal lambing often require induction and synchronization of oestrus and ovulation, either for natural mating or artificial insemination, by the use of pharmacological treatments. Such treatments are mostly based on the administration of progesterone followed by a single intramuscular dose of equine chorionic gonadotrophin (eCG) at progesterone withdrawal. However, repeated eCG treatments in consecutive mating seasons can result in the outbreak of resistance with a rise of anti-eCG antibodies. Furthermore, the future use and availability of eCG appears to be strongly challenged by the highly active animal-rights movement because the hormone is obtained from pregnant mares. The present study demonstrated that the administration of glycerol-based formulations to milked ewes is a valid alternative to eCG treatment in reproductive management protocols based on the induction of ovulation with progesterone-releasing devices at the end of anoestrus period. The glucogenic treatment administration to late lactation dairy ewes at the end of the anoestrus period improved their metabolism without harming animal production or animal welfare, thus promoting a sustainable reproductive management of dairy sheep. Abstract This study investigated whether the administration of equine chorionic gonadotrophin (eCG) in a protocol to induce and synchronize ovulations before mating could be replaced by the administration of glycerol-based formulations in milked ewes at the end of their seasonal anoestrus. Forty-eight late-lactation dairy ewes of the Sarda breed were synchronized using sponges impregnated with progestogen and then joined with fertile rams (day (D) 0, ram introduction). From D−4 to D−1, the ewes received by gavage either 100 mL of a glucogenic mixture (70% glycerol, 20% propylene glycol and 10% water; GLU group; n = 24) or 100 mL of water (GON group; n = 24) twice daily. Moreover, on the day of sponge withdrawal (D−1), GON ewes received 200 IU of eCG. There were no differences in reproductive performances between groups. GLU ewes showed higher glycemia (p < 0.001), insulinemia (p < 0.05), plasma glycerol (p < 0.001), triglycerides (p < 0.001) and lower cholesterol (p < 0.001), non-esterified fatty acids (NEFA; p < 0.05) and urea (p < 0.001). Plasma osmolality was higher in GLU but only 4 h after dosing (p < 0.001). Milk yield and milk composition were not affected by the treatments with exception of milk glycerol (p < 0.001) and milk urea (p < 0.001), which were higher and lower in GLU than GON ewes, respectively. In conclusion, the administration of the glucogenic mixture to late lactation dairy ewes at the end of anoestrus period resulted in reproductive responses as good as the ones obtained by the eCG treatment, suggesting that the objective of a sustainable reproductive management of dairy sheep can be successfully pursued.