Miracle-dz/UniFAR-FTUs huggingface dataset:
Megakaryocyte Diversity in Ontogeny, Functions and Cell-Cell Interactions

Hematopoietic stem cells (HSCs) rely on local interactions in the bone marrow (BM) microenvironment with stromal cells and other hematopoietic cells that facilitate their survival and proliferation, and also regulate their functions. HSCs and multipotent progenitor cells differentiate into lineage-specific progenitors that generate all blood and immune cells. Megakaryocytes (Mks) are hematopoietic cells responsible for producing blood platelets, which are essential for normal hemostasis and blood coagulation. Although the most prominent function of Mks is platelet production (thrombopoiesis), other increasingly recognized functions include HSC maintenance and host immune response. However, whether and how these diverse programs are executed by different Mk subpopulations remains poorly understood. This Perspective summarizes our current understanding of diversity in ontogeny, functions and cell-cell interactions. Cumulative evidence suggests that BM microenvironment dysfunction, partly caused by mutated Mks, can induce or alter the progression of a variety of hematologic malignancies, including myeloproliferative neoplasms (MPNs) and other disorders associated with tissue scarring (fibrosis). Therefore, as an example of the heterogeneous functions of Mks in malignant hematopoiesis, we will discuss the role of Mks in the onset and progression of BM fibrosis. In this regard, abnormal interactions between of Mks and other immune cells might directly contribute to fibrotic diseases. Overall, further understanding of megakaryopoiesis and how Mks interact with HSCs and immune cells has potential clinical implications for stem cell transplantation and other therapies for hematologic malignancies, as well as for treatments to stimulate platelet production and prevent thrombocytopenia.
Designing New Material Based on Functionalized Multi-Walled Carbon Nanotubes and Cu(OH)2–Cu2O/Polypyrrole Catalyst for Ethanol Oxidation in Alkaline Medium

In this work, copper(II) hydroxide (Cu(OH)2) and copper oxide (Cu2O) nanostructures are deposited on functionalized multi-walled carbon nanotubes/polypyrrole to report an efficient electrocatalyst for ethanol oxidation in alkaline medium. In the first step, the deposition of functionalized multi-walled nanotubes of carbon (F-MWCNTs) on the electrode surface was carried out using drop casting mode followed by the electrodeposition of polypyrrole (PPy) and copper nanoparticles (Cu-Nps) using galvanostatic mode. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were performed in order to study the morphology and the structure of the elaborated catalysts. Electrochemical characterization conducted by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) revealed that the introduction of functionalized multi-walled carbon nanotubes enhances the electric properties of the nanocomposites and offers a large active surface area. The prepared electrocatalyst was then tested in a solution of 0.1 M NaOH containing 0.2 M of ethanol showing high performance (7 mA cm−2 at 0.85 V vs Ag/AgCl) and good stability (over 1800 s) toward ethanol oxidation.
An Efficient Method for the Isolation and Cultivation of Hypothalamic Neural Stem/Progenitor Cells From Mouse Embryos

The hypothalamus is the key region that regulates the neuroendocrine system as well as instinct behaviors, and hypothalamic dysfunction causes refractory clinical problems. Recent studies have indicated that neural stem/progenitor cell (NSPC) in the hypothalamus play a crucial role in hypothalamic function. However, specific hypothalamic NSPC culture methods have not been established, especially not detailed or efficient surgical procedures. The present study presented a convenient, detailed and efficient method for the isolation and cultivation of hypothalamic NSPCs from embryonic day 12.5 mice. The procedure includes embryo acquisition, brain microdissection to quickly obtain hypothalamic tissue and hypothalamic NSPC culture. Hypothalamic NSPCs can be quickly harvested and grow well in both neurosphere and adherent cultures through this method. Additionally, we confirmed the cell origin and evaluated the proliferation and differentiation properties of cultured cells. In conclusion, we present a convenient and practical method for the isolation and cultivation of hypothalamic NSPCs that can be used in extensive hypothalamic studies.
A Study of Word Complexity Under Conditions of Non-experimental, Natural Overt Speech Production Using ECoG

The linguistic complexity of words has largely been studied on the behavioral level and in experimental settings. Only little is known about the neural processes underlying it in uninstructed, spontaneous conversations. We built up a multimodal neurolinguistic corpus composed of synchronized audio, video, and electrocorticographic (ECoG) recordings from the fronto-temporo-parietal cortex to address this phenomenon based on uninstructed, spontaneous speech production. We performed extensive linguistic annotations of the language material and calculated word complexity using several numeric parameters. We orthogonalized the parameters with the help of a linear regression model. Then, we correlated the spectral components of neural activity with the individual linguistic parameters and with the residuals of the linear regression model, and compared the results. The proportional relation between the number of consonants and vowels, which was the most informative parameter with regard to the neural representation of word complexity, showed effects in two areas: the frontal one was at the junction of the premotor cortex, the prefrontal cortex, and Brodmann area 44. The postcentral one lay directly above the lateral sulcus and comprised the ventral central sulcus, the parietal operculum and the adjacent inferior parietal cortex. Beyond the physiological findings summarized here, our methods may be useful for those interested in ways of studying neural effects related to natural language production and in surmounting the intrinsic problem of collinearity between multiple features of spontaneously spoken material.
Focus on the Predictive Value of Subclassification of Extratumoral Structural Abnormalities for Malignant Nonspiculate and Noncalcified Masses on Digital Mammography

Purpose: To determine the independent risk factors associated with malignant nonspiculate and noncalcified masses (NSNCMs) and evaluate the predictive values of extratumoral structural abnormalities on digital mammography. Methods: A total of 435 patients were included between January and May 2018. Tumor signs included shape, density, and margin, which were evaluated. Extratumoral signs were classified into extratumoral structural abnormalities (parenchymal and trabecular) and halo; subclassification included contraction, distortion, pushing and atrophy sign of parenchyma, parallel, vertical, and reticular trabecula sign, and narrow and wide halo. Univariate and multivariate analysis was performed. The positive predictive value (PPV) of the independent predictor was calculated, and diagnostic performance was evaluated using the receiver operating characteristic curve. Results: Of all cases, 243 (55.8%) were benign and 192 (44.2%) were malignant. Extratumoral contraction sign of parenchyma was the strongest independent predictor of malignancy (odds ratio [OR] 36.2, p < 0.001; PPV = 96.6%), followed by parenchymal distortion sign (OR 10.2, p < 0.001; PPV = 92%), parallel trabecula sign (OR 7.2, p < 0.001; PPV = 85.6%), and indistinct margin of tumor (OR 4.3, p < 0.001; PPV =70.9%), and also parenchymal atrophy sign, wide halo, vertical trabecula, age ≥ 47.5 years, irregular shape, and size ≥ 22.5 mm of tumor (OR range, 1.3-4.0; PPV range, 56.6-83.6%). The diagnostic performance of most of the extratumoral signs was between that of indistinct margin and irregular shape of tumor. Conclusion: The subclassification of extratumoral structural abnormalities has important predictive value for mammographic malignant NSNCM, which should be given more attention.
Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond

Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. The results showed that the major bioactive components in IDT were include 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. Rats fed with IDT (0.27–0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. For instance, Ruminococcaceae_UCG-005 was significantly correlated with body weight, TG, HDL-C, Nfr2, FABP3, SCD1, Cyp4a1, and Kcnn2. Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia.
Supply Chain Management of Mango (Mangifera indica L.) Fruit: A Review With a Focus on Product Quality During Postharvest

Mango (Mangifera indica L.) is a widely consumed fruit in tropical/subtropical regions around the world due to its excellent flavor and taste, and valuable source of nutrients and phytochemical compounds. As a climacteric fruit, mango is easily perishable after harvesting due to the ripening process, environmental conditions, and improper postharvest handling, leading to significant quality losses as well as economic loss throughout a supply chain. Postharvest losses are attributed to harvesting at an improper maturity stage, poor postharvest pretreatment, improper packing and packaging, inappropriate storage temperature and distribution conditions. These caused mechanical damage, sap burn, spongy tissue, weight loss, fruit softening, decay, chilling injury, and postharvest diseases. Currently, each step in the supply chain has been applied many postharvest technologies to reduce the quality losses of mango fruits as well as improving their marketability with the highest retention of quality. This review documented available possible causes for the quality losses and observed the physicochemical changes of mango fruit when applying postharvest technologies at each critical step in the mango supply chain from harvesting, pre-treatment, packaging, storage, to distribution. The summarized information is expected to provide comprehensive quality changes of mango fruits and point out the proper technology at each step of the supply chain.
Trypanosoma cruzi Mitochondrial Peroxiredoxin Promotes Infectivity in Macrophages and Attenuates Nifurtimox Toxicity

Trypanosoma cruzi is the causative agent of Chagas disease which is currently treated by nifurtimox (NFX) and benznidazole (BZ). Nevertheless, the mechanism of action of NFX is not completely established. Herein, we show the protective effects of T. cruzi mitochondrial peroxiredoxin (MPX) in macrophage infections and in response to NFX toxicity. After a 3-day treatment of epimastigotes with NFX, MPX content increased (2.5-fold) with respect to control, and interestingly, an MPX-overexpressing strain was more resistant to the drug. The generation of mitochondrial reactive species and the redox status of the low molecular weight thiols of the parasite were not affected by NFX treatment indicating the absence of oxidative stress in this condition. Since MPX was shown to be protective and overexpressed in drug-challenged parasites, non-classical peroxiredoxin activity was studied. We found that recombinant MPX exhibits holdase activity independently of its redox state and that its overexpression was also observed in temperature-challenged parasites. Moreover, increased holdase activity (2-fold) together with an augmented protease activity (proteasome-related) and an enhancement in ubiquitinylated proteins was found in NFX-treated parasites. These results suggest a protective role of MPX holdase activity toward NFX toxicity. Trypanosoma cruzi has a complex life cycle, part of which involves the invasion of mammalian cells, where parasite replication inside the host occurs. In the early stages of the infection, macrophages recognize and engulf T. cruzi with the generation of reactive oxygen and nitrogen species toward the internalized parasite. Parasites overexpressing MPX produced higher macrophage infection yield compared with wild-type parasites. The relevance of peroxidase vs. holdase activity of MPX during macrophage infections was assessed using conoidin A (CA), a covalent, cell-permeable inhibitor of peroxiredoxin peroxidase activity. Covalent adducts of MPX were detected in CA-treated parasites, which proves its action in vivo. The pretreatment of parasites with CA led to a reduced infection index in macrophages revealing that the peroxidase activity of peroxiredoxin is crucial during this infection process. Our results confirm the importance of peroxidase activity during macrophage infection and provide insights for the relevance of MPX holdase activity in NFX resistance.
Human-Induced CD49a+ NK Cells Promote Fetal Growth

CD49a+ natural killer (NK) cells play a critical role in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface during the early stages of pregnancy. However, given their residency in human tissue, thorough studies and clinical applications are difficult to perform. It is still unclear as to how functional human CD49a+ NK cells can be induced to benefit pregnancy outcomes. In this study, we established three no-feeder cell induction systems to induce human CD49a+ NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs, and peripheral blood NK cells in vitro. These induced NK cells (iNKs) from three cell induction systems display high levels of CD49a, CD9, CD39, CD151 expression, low levels of CD16 expression, and no obvious cytotoxic capability. They are phenotypically and functionally similar to decidual NK cells. Furthermore, these iNKs display a high expression of growth-promoting factors and proangiogenic factors and can promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo. This research demonstrates the ability of human-induced CD49a+ NK cells to promote fetal growth via three cell induction systems, which could eventually be used to treat patients experiencing adverse pregnancy outcomes.
Synthesis, Characterization, and Application of Ag-Biochar Composite for Sono-Adsorption of Phenol

The silver-embedded wheat straw biochar (Ag–WBC) composite was tailored effectively via the green synthetic route and was used as a nano-adsorbent for the removal of phenol by using adsorption and sono-adsorption processes. Ligustrum lucidum leaf extract was employed as a reducer to prepare silver nanoparticles, and biochar was synthesized from wheat straw via pyrolysis at 450–500°C. The synthesized biochar and Ag–WBC were characterized by using UV–Vis, SEM, EDX, and FTIR. The study confirms the ability of plant leaf extract of L. lucidum to synthesize AgNPs and Ag–WBC composites for the first time. UV–vis spectroscopic analysis confirms the formation of AgNPs and Ag–WBC composites (400–440 nm). SEM results showed that the size of the Ag–WBC composite is in the range of 80–100 nm. The elemental profile of the synthesized Ag–WBC composite shows a higher count at 3 kev due to silver. FTIR analysis revealed the presence of various functional groups involved in reducing Ag metal ions into Ag nanoparticles onto the surface of the composite. Batch experiments executed adsorption and sono-adsorption studies on WBC and Ag–WBC composites, and the results revealed that under optimum conditions, that is, pH= 3, adsorbate concentration= 10 mg L−1, adsorbents dosage= 0.05 g, time= 90 min, and US power = 80 W, the phenol removal efficiencies onto Ag–WBC composite were 78% using sono-adsorption compared to the non-sonicated adsorption. Langmuir and Freundlich isotherm models for fitting the experimental equilibrium data were studied, and the Langmuir model was chosen as an efficient model for the sono-adsorption process. The feasibility of the sono-adsorption process was also evaluated by calculating kinetics.
LLT1-CD161 Interaction in Cancer: Promises and Challenges

The success of immune checkpoint therapy in cancer has changed our way of thinking, promoting the design of future cancer treatments that places the immune system at the center stage. The knowledge gained on immune regulation and tolerance helped the identification of promising new clinical immune targets. Among them, the lectin-like transcript 1 (LLT1) is the ligand of CD161 (NKR-P1A) receptor expressed on natural killer cells and T cells. LLT1/CD161 interaction modulates immune responses but the exact nature of the signals delivered is still partially resolved. Investigation on the role of LLT1/CD161 interaction has been hampered by the lack of functional homologues in animal models. Also, some studies have been misled by the use of non-specific reagents. Recent studies and meta-analyses of single cell data are bringing new insights into the function of LLT1 and CD161 in human pathology and notably in cancer. The advances made on the characterization of the tumor microenvironment prompt us to integrate LLT1/CD161 interaction into the equation. This review recapitulates the key findings on the expression profile of LLT1 and CD161, their regulation, the role of their interaction in cancer development, and the relevance of targeting LLT1/CD161 interaction.
Elevated Detection of Dual Antibody B Cells Identifies Lupus Patients With B Cell-Reactive VH4-34 Autoantibodies

About 5% of B cells in healthy mice and humans are allelically or isotypically included and hence co-express two different antibodies. In mice, dual antibody B cells (B2R) expand with systemic autoimmunity, co-express autoreactive and non-autoreactive antibodies, and participate in immune responses, but this phenomenon is strain dependent. This study was developed with two goals: 1) to establish the contribution of TLR and IFN receptor signaling to the development of germinal center B cells that express two antibodies in MRL/lpr mice; and 2) to determine whether B2R B cells are increased and particularly activated in a subset of adult patients diagnosed with systemic lupus erythematosus (SLE). Results from the MRL/lpr studies indicate that the enhanced differentiation of dual-κ B cells into germinal center B cells is due to a heightened response to TLR7 and TLR9 signaling, further fueled by an increased response to type II IFN. To understand the clinical and translational implications of our observations in mouse B2R B cells, cohorts of SLE patients and healthy controls were recruited and evaluated for expression of dual BCRs. Results from flow cytometry and microscopy revealed supraphysiological frequencies of κ+λ+ B2R cells in one fourth of the SLE patients. Abnormal numbers of κ+λ+ B cells correlated with higher frequencies of activated naïve B cells and age-associated B cells, and a lower proportion of “B cells that are naïve IgD+” (BND). However, results from single cell V(D)J sequencing demonstrated that these high κ+λ+ SLE patients harbored normal frequencies of κ+λ+ and other B2R B cells. and we further show that their B cells were instead decorated by κ and λ VH4-34 autoantibodies. Thus, our findings indicate that elevated flow cytometric detection of isotypically-included B cells can identify patients with high titers of B cell-reactive VH4-34 autoantibodies and abnormal distribution of B cell subsets relevant to autoimmunity.
Practical Considerations for the Daratumumab Management in Portuguese Routine Clinical Practice: Recommendations From an Expert Panel of Hematologists

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients’ quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert panel of Portuguese hematologists. Carefully following the recommendations mentioned in daratumumab’s SmPC, and of those from other drugs used in combination regimens, along with ensuring a good communication with all healthcare professionals involved, is critical to prevent any complications arising from treatment. The risk of infection should be assessed for all patients under treatment with daratumumab and patients should be educated on the potential adverse events. Recommendations on prophylaxis and vaccination should be considered to avoid infections, and delays in the planned therapeutic schedule may be required to prevent adverse consequences of hematological toxicity. Daratumumab treatment is effective and feasible in patients with renal impairment, although careful patient monitoring and a frequent communication with the Nephrology department are of the utmost importance. Sharing clinical practice plays an important role in medical education by allowing to maximize treatment efficacy and minimize its safety risks.