Miracle-dz/UniFAR-FTUs huggingface dataset:
LyP-1-Modified Multifunctional Dendrimers for Targeted Anti-Tumor and Anti-Metastasis Therapy.

We designed and synthesized 131I-labeled dendrimers modified with LyP-1 peptide as a multifunctional platform for single-photon emission computed tomography (SPECT) imaging, radionuclide therapy and anti-metastasis therapy of cancer. The multifunctional platform was constructed by modifying amine-terminated generation 5 poly(amidoamine) dendrimers with 33.1 LyP-1 peptide and 9.2 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I via the HPAO moieties. The LyP-1-modified dendrimers showed favorable cytocompatibility in a studied concentration range of 0.1-10 μM for 24 h, and could be labeled by 131I with satisfactory radiochemical purity (>99%) and stability (>90% even at 16 h). The 131I-labeled LyP-1-modified dendrimers were capable of being utilized as a diagnostic probe for SPECT imaging and as a therapeutic agent for radionuclide therapy and anti-metastasis of cancer cells in vitro and in a subcutaneous tumor model in vivo. Based on analyses of tumor microenvironment, the anti-tumor and anti-metastasis effects could be due to the reduced levels of molecular markers associated with proliferation and metastasis, improved local hypoxia and increased apoptosis rate. The developed 131I-labeled dendrimeric nanodevice may hold great promise to be used as a nano-theranostic platform for cancer diagnosis and therapy.
Effects of Copper Oxide Nanoparticles on the Growth of Rice (Oryza Sativa L.) Seedlings and the Relevant Physiological Responses

Rice (Oryza sativa L.), a major staple food for billions of people, was assessed for its phytotoxicity of copper oxide nanoparticle (CuO NPs, size < 50 nm). Under hydroponic condition, seven days of exposure to 62.5, 125, and 250 mg/L CuO NPs significantly suppressed the growth rate of rice seedlings compared to both the control and the treatment of supernatant from 250 mg/L CuO NP suspensions. In addition, physiological indexes associated with antioxidants, including membrane damage and antioxidant enzyme activity, were also detected. Treatment with 250 mg/L CuO NPs significantly increased malondialdehyde (MDA) content and electrical conductivity of rice shoots by 83.4% and 67.0%, respectively. The activity of both catalase and superoxide dismutase decreased in rice leaves treated with CuO NPs at the concentration of 250 mg/L, while the activity of the superoxide dismutase significantly increased by 1.66 times in rice roots exposed to 125 mg/L CuO NPs. The chlorophyll, including chlorophyll a and chlorophyll b, and carotenoid content in rice leaves decreased with CuO NP exposure. Finally, to explain potential molecular mechanisms of chlorophyll variations, the expression of four related genes, namely, Magnesium chelatase D subunit, Chlorophyll synthase, Magnesium-protoporphyrin IX methyltransferase, and Chlorophyllide a oxygenase, were quantified by qRT-PCR. Overall, CuO NPs, especially at 250 mg/L concentration, could affect the growth and development of rice seedlings, probably through oxidative damage and disturbance of chlorophyll and carotenoid synthesis.
Size-Dependent Thermo- and Photoresponsive Plasmonic Properties of Liquid Crystalline Gold Nanoparticles

Achieving remotely controlled, reversibly reconfigurable assemblies of plasmonic nanoparticles is a prerequisite for the development of future photonic technologies. Here, we obtained a series of gold-nanoparticle-based materials which exhibit long-range order, and which are controlled with light or thermal stimuli. The influence of the metallic core size and organic shell composition on the switchability is considered, with emphasis on achieving light-responsive behavior at room temperature and high yield production of nanoparticles. The latter translates to a wide size distribution of metallic cores but does not prevent their assembly into various, switchable 3D and 2D long-range ordered structures. These results provide clear guidelines as to the impact of size, size distribution, and organic shell composition on self-assembly, thus enhancing the smart design process of multi-responsive nanomaterials in a condensed state, hardly attainable by other self-assembly methods which usually require solvents.
Amperometric bioplatforms to detect regional DNA methylation with single-base sensitivity.

This work reports the first bioplatform able to determine electrochemically 5-hydroxymethylcytosine (5-hmC) methylation events at localized sites and single-base sensitivity. The described bioplatform relies on a specific antibody (anti-5-hmC), further conjugated with commercial bioreagents loaded with multiple horseradish peroxidase (HRP) molecules, recognizing the epimark in a target DNA, captured through hybridization onto streptavidin-magnetic microbeads (Strep-MBs) modified with a complementary DNA capture probe. The electrochemical detection is performed by amperometry (-0.20 V vs Ag pseudoreference electrode) at disposable screen-printed carbon electrodes (SPCEs) in the presence of H2O2/hydroquinone (HQ) upon magnetic capture of the modified MBs onto the SPCE. The use of the commercial bioreagents ProtA-polyHRP80 and Histostar, very scarcely explored so far in electrochemical biosensors, provides high sensitivities for a synthetic target DNA sequence with a unique 5-hmC in the promoter region of MGMT tumor suppressor gen. Amplification factors of 43.6 and 55.2 were achieved using ProtA-polyHRP80 or Histostar, respectively, compared to the conventional secondary anti-body labeling. This amplification was crucial to detect methylation events at single-nucleotide resolution achieving limits of detection (LODs) of 23.0 and 13.2 pM, respectively, without any target DNA amplification. The ProtA-polyHRP80-based bioplatform, selected as a compromise between sensitivity and cost per determination, exhibited full discrimination towards the target 5-hmC against the closely related 5-mC. In addition, the bioplatform detected 5-hmC at regional level (MGMT promoter region) in just 10 ng of genomic DNA (gDNA, ∼2,700 genomes) extracted from cancer cells and tissues from colo-rectal cancer (CRC) patients within 60 min.
Topography in the Bursting Dynamics of Entorhinal Neurons.

Medial entorhinal cortex contains neural substrates for representing space. These substrates include grid cells that fire in repeating locations and increase in scale progressively along the dorsal-to-ventral entorhinal axis, with the physical distance between grid firing nodes increasing from tens of centimeters to several meters in rodents. Whether the temporal scale of grid cell spiking dynamics shows a similar dorsal-to-ventral organization remains unknown. Here, we report the presence of a dorsal-to-ventral gradient in the temporal spiking dynamics of grid cells in behaving mice. This gradient in bursting supports the emergence of a dorsal grid cell population with a high signal-to-noise ratio. In vitro recordings combined with a computational model point to a role for gradients in non-inactivating sodium conductances in supporting the bursting gradient in vivo. Taken together, these results reveal a complementary organization in the temporal and intrinsic properties of entorhinal cells.
Measuring objectification through the Body Inversion Paradigm: Methodological issues

Objectification occurs when a person is perceived and/or treated like an object. With the present work, we overview the available measures of objectification and present a series of studies aimed at investigating the validity of the task of inverted body recognition proposed by Bernard and colleagues (2012), which might potentially be a useful cognitive measure of objectification. We conducted three studies. Study 1 (N = 101) is a direct replication of Bernard et al.’s study: participants were presented with the same photos of sexualized male and female targets used in the original research. Study 2a (N = 100) is a conceptual replication: we used different images of scantily dressed male and female models. Finally, in Study 2b (N = 100), we investigated a boundary condition by presenting to participants photos of the same models as in Study 2a, but fully dressed and non-sexualized. Using mixed-effects models for completely-crossed classified data structures, we investigated the relationship between the inversion effect and the stimulus’ asymmetry, sexualization and attractiveness, and the perceivers’ self-objectification, sexism, and automatic woman-human association. Study 1 replicated the original results, showing a stronger inversion effect for male photos. However, no difference between male and female stimuli emerged in either Study 2a or 2b. Moreover, the impact of the other variables on the inversion effect was highly unstable across the studies. These aspects together indicate that the inversion effect depends on the specific set of stimuli and limits the generalizability of results collected using this method.
Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

Nonalcoholic fatty liver disease (NAFLD) is present in approximately 25% of the population worldwide. It is characterized by the accumulation of triacylglycerol in the liver, which can progress to steatohepatitis with different degrees of fibrosis, stages that lack approved pharmacological therapies and represent an indication for liver transplantation with consistently increasing frequency. In view that hepatic steatosis is a reversible condition, effective strategies preventing disease progression were addressed using combinations of natural products in the preclinical high-fat diet (HFD) protocol (60% of fat for 12 weeks). Among them, eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:5n-3, DHA), DHA and extra virgin olive oil (EVOO), or EPA plus hydroxytyrosol (HT) attained 66% to 83% diminution in HFD-induced steatosis, with the concomitant inhibition of the proinflammatory state associated with steatosis. These supplementations trigger different molecular mechanisms that modify antioxidant, antisteatotic, and anti-inflammatory responses, and in the case of DHA and HT co-administration, prevent NAFLD. It is concluded that future studies in NAFLD patients using combined supplementations such as DHA plus HT are warranted to prevent liver steatosis, thus avoiding its progression into more unmanageable stages of the disease.
Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins by JQ1 Unravels a Novel Epigenetic Modulation to Control Lipid Homeostasis

The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the management of lipid disorders. Here, we investigated the role of bromodomain and extraterminal domain (BET) proteins in the regulation of lipid metabolism. To reach this aim, we used a loss-of-function approach by treating HepG2 cells with JQ1, a powerful and selective BET inhibitor. The main results demonstrated that BET inhibition by JQ1 efficiently decreases intracellular lipid content, determining a significant modulation of proteins involved in lipid biosynthesis, uptake and intracellular trafficking. Importantly, the capability of BET inhibition to slow down cell proliferation is dependent on the modulation of cholesterol metabolism. Taken together, these data highlight a novel epigenetic mechanism involved in the regulation of lipid homeostasis.
A Multiplatform Decision Support Tool in Neonatology and Pediatric Care

As regards the dosage of drug, children are a much more vulnerable population than the adults. With this in mind it is extremely important the administration of the correct dosage. For this purpose, it was develop a framework, based on a prototype already tested in a real environment, with the main concern to help pediatricians in their daily tasks. Thus, this framework includes tools that can help in the preparation of Total Parenteral Nutrition prescriptions, table pediatric and neonatal emergency drugs, medical scales of morbidity and mortality, anthropometry percentiles (weight, length/height, head circumference and BMI), utilities for supporting medical decision on the treatment of neonatal jaundice and anemia and other calculators. This paper presents the architecture, their functionalities and a SWOT analysis of the solution proposed.
CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung.

BACKGROUND Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remain poorly described. METHODS We use a combination of polychromatic flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). RESULTS Using polychromatic flow cytometry, there was a 5-fold higher fraction of EpCAM-CD45-CD31-CD14- (mesenchymal) compared with EpCAM+CD45-CD31-CD14- cells (epithelial) in unaffected postnatal human lung. The mesenchymal fraction was composed primarily of single CD90+ and CD90+CD73+ cells both enriched in niche factors CXCL12 and PDGFRα. Immunofluorescence confirmed CD90+ cells in close proximity to EpCAM+ cells some co-staining for pro-SPC in the alveolar region suggestive of an alveolar unit. Contained within the CD90+ population, a subset co-expressed the pericyte marker CD146 with immunomodulatory properties able to internalize influenza virosomes, as well as live influenza virus. Postnatal CD90+CD146+ mesenchymal cells supported microvessel formation, whereas CD90+CD146+ mesenchymal cells from COPD patients failed to do so. In congenital lung lesions, cystic airspaces and dysplastic alveolar regions were marked with an expanded underlying thick interstitium of CD90+ and CD90+PDGFRα+ cells. CONCLUSION These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and track their change in diverse setting of congenital lung lesions and other airway abnormalities including COPD.
CRISPR/Cas9 engineering of albino cystinuria Type A mice

Cystinuria Type A is a relatively common genetic kidney disease occurring in 1 in 7,000 people worldwide that results from mutation of the cystine transporter rBAT encoded by Slc3a1. We used CRISPR/Cas9 technology to engineer cystinuria Type A mice via genome editing of the C57BL/6NHsd background. These mice are an improvement on currently available models as they are on a coisogenic genetic background and have a single defined mutation. In order to use albinism to track Cas9 activity, we co‐injected gRNAs targeting Slc3a1 and tyrosinase (Tyr) with Cas9 expressing plasmid DNA into mouse embryos. Two different Slc3a1 mutational alleles were derived, with homozygous mice of both demonstrating elevated urinary cystine levels, cystine crystals, and bladder stones. We used whole genome sequencing to evaluate for potential off‐target editing. No off‐target indels were observed for the top 10 predicted off‐targets for Slc3a1 or Tyr. Therefore, we used CRISPR/Cas9 to generate coisogenic albino cystinuria Type A mice that could be used for in vivo imaging, further study, or developing new treatments of cystinuria.
Enhancing Tumor Targeting Efficiency of Radiolabeled Uridine (via) Incorporation into Nanocubosomal Dispersions.

Background: Several nanosystems are currently being utilized to enhance the targeting efficiency of several cancer chemotherapeutic agents. This study was designed to improve tumor accumulation of iodine-125 (125I)-uridine via incorporation into a nanocubosomal preparation. Materials and Methods: Nanocubosomes were prepared with the aid of Glycerol mono-oleate and Pluronic F127. Each prepared nanocubosomal preparation was adequately characterized by testing their particle size, polydispersity index (PDI), zeta potential (ZP), and transmission electron microscopy. The radiolabeling of uridine with 125I was attempted using several oxidizing agents to achieve a high radiochemical yield, and the factors affecting the reaction yield were studied in detail. A comparative biodistribution study of free 125I-uridine and 125I-uridine loaded nanocubosomes was performed in normal and tumor bearing mice. The biodistribution was evaluated by intravenous injection of the sterile test solution, and animals were anesthetized and dissected at different time intervals postinjection (p.i.). Results: 125I-uridine was obtained in a high radiochemical yield (92.5% ± 0.8%). Afterward, 125I uridine was incorporated in a selected nanocubosome formulation, which showed nanosized cubic particles (178.6 ± 0.90 nm) with PDI (0.301 ± 0.04) and a ZP (34.35 ± 0.4). The biodistribution studies revealed that 125I-uridine nanocubosomes showed higher tumor localization (3.1 ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 6.2) compared with the free 125I-uridine (2.7% ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 3.3). Conclusion: The results of this study confirmed that 125I-uridine loaded nanocubosome had better efficiency in targeting the tumor site, which makes it an adequate targeting agent for tumor imaging.
Nutrition of Children With Cancer in Brazil: A Systematic Review

PURPOSE The objective of this systematic review was to describe nutrition-related publications on children and adolescents diagnosed with cancer in Brazil. METHODS The methodology followed that of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medline, LILACS (the Latin American & Caribbean Health Sciences Literature), and Embase were searched in April 2019, and data extraction and rating of methodologic study quality (according to the National Institutes of Health quality score assessment) were performed independently by reviewers. RESULTS Twenty-seven studies met the inclusion criteria, reporting on 3,509 patients from 1994 to 2018. Most of the studies (74%) were of poor quality in methodology and reporting. Different cancer diagnoses were included in 52% of studies, whereas acute leukemia was the exclusive focus in 41%. The majority of the articles (70%) were from institutions in the Southeast Region of Brazil, mainly the state of São Paulo (74%); no publications were from the North Region of the country. Twelve studies addressed nutritional status and body composition, reporting an abundance of malnourished patients in the Brazilian population of children and adolescents with cancer. Six studies on micronutrients pointed to possible deficiencies in this population, with a yet unclear but promising role for supplementation during treatment. CONCLUSION Evidence indicates that there is great interest in the impact of nutrition on childhood cancer treatment and clinical outcomes in Brazil. However, there is a need to focus on high-quality research, particularly with multicentric/national studies. This will help establish research priorities and better planned clinical interventions, adapted to each region of the country.
Circulating Immune Cell Composition and Cancer Risk: A Prospective Study Using Epigenetic Cell Count Measures

This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals. Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case–cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER− subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development. Significance: This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals. See related commentary by Song and Tworoger, p. 1801
Contagious yawning is not a signal of empathy: no evidence of familiarity, gender or prosociality biases in dogs

Contagious yawning has been suggested to be a potential signal of empathy in non-human animals. However, few studies have been able to robustly test this claim. Here, we ran a Bayesian multilevel reanalysis of six studies of contagious yawning in dogs. This provided robust support for claims that contagious yawning is present in dogs, but found no evidence that dogs display either a familiarity or gender bias in contagious yawning, two predictions made by the contagious yawning–empathy hypothesis. Furthermore, in an experiment testing the prosociality bias, a novel prediction of the contagious yawning–empathy hypothesis, dogs did not yawn more in response to a prosocial demonstrator than to an antisocial demonstrator. As such, these strands of evidence suggest that contagious yawning, although present in dogs, is not mediated by empathetic mechanisms. This calls into question claims that contagious yawning is a signal of empathy in mammals.
Advances in artificial intelligence to predict cancer immunotherapy efficacy

Tumor immunotherapy, particularly the use of immune checkpoint inhibitors, has yielded impressive clinical benefits. Therefore, it is critical to accurately screen individuals for immunotherapy sensitivity and forecast its efficacy. With the application of artificial intelligence (AI) in the medical field in recent years, an increasing number of studies have indicated that the efficacy of immunotherapy can be better anticipated with the help of AI technology to reach precision medicine. This article focuses on the current prediction models based on information from histopathological slides, imaging-omics, genomics, and proteomics, and reviews their research progress and applications. Furthermore, we also discuss the existing challenges encountered by AI in the field of immunotherapy, as well as the future directions that need to be improved, to provide a point of reference for the early implementation of AI-assisted diagnosis and treatment systems in the future.