Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells

In humans, Factor VIII (F8) deficiency leads to hemophilia A and F8 is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the specificity and characteristics of these cells in comparison to other endothelial cells is not well known. In this study, we performed genome wide expression and CpG methylation profiling of fetal and adult human primary LSECs together with other fetal primary endothelial cells from lung (micro-vascular and arterial), and heart (micro-vascular). Our results reveal expression and methylation markers distinguishing LSECs at both fetal and adult stages. Differential gene expression of fetal LSECs in comparison to other fetal endothelial cells pointed to several differentially regulated pathways and biofunctions in fetal LSECs. We used targeted bisulfite resequencing to confirm selected top differentially methylated regions. We further designed an assay where we used the selected methylation markers to test the degree of similarity of in-house iPS generated vascular endothelial cells to primary LSECs; a higher similarity was found to fetal than to adult LSECs. In this study, we provide a detailed molecular profile of LSECs and a guide to testing the effectiveness of production of in vitro differentiated LSECs.
DNA fingerprinting sets for four southern pines

DNA markers can provide valuable genetic information for forest tree research, breeding, conservation, and restoration programs. When properly evaluated, selected sets of DNA markers can be used to efficiently get information about genetic diversity in regions, forests, or stands, or in seed lots and orchards. Selected markers also can be used to determine parentage or verify clonal identity of individual trees in tree improvement programs and seed production orchards. With these purposes in mind, we developed sets of informative markers for four species of southern pines: shortleaf pine (Pinus echinata Mill.), slash pine (P. elliottii Englem.), longleaf pine (P. palustris Mill.), and loblolly pine (P. taeda L.). We selected 38 markers for all 4 species and then selected markers within each species: 9 for shortleaf pine, 16 for slash pine, 10 for longleaf pine, and 11 for loblolly pine. All markers were originally developed for use in loblolly pine. Once we optimized marker sets for each species, however, there were few markers left in common between the different marker sets. In this report, we provide all the methods and information needed for any molecular biology lab to use the markers in any of the four pine species.
Influence of vitamin E and carcass feeding supplementation on fecal glucocorticoid and androgen metabolites in male black-footed ferrets (Mustela nigripes)

In recent years, the ex situ population of the endangered black-footed ferret (Mustela nigripes; ferret) has experienced a decline in normal sperm morphology (from 50% to 20%), which may be linked to inbreeding depression and/or a dietary change. We examined the effects of adding carcass and vitamin E to the diet on stress and reproductive biomarkers in male ferrets (n = 42 males including 16 juveniles and 26 adults) housed at the U.S. Fish and Wildlife National Black-footed Ferret Conservation Center (Carr, CO, USA). Fecal samples (3x/week) were collected from November and December (pre-breeding season, no diet change), February through May (breeding season, diet change) and June (post-breeding season, diet change) and analyzed for fecal glucocorticoid metabolites (FGM) via a corticosterone enzyme immunoassay (EIA). A subset of samples from adult males (n = 15) were analyzed for fecal androgen metabolites (FAM) via a testosterone EIA. We first used a linear mixed effects model to identify the important fixed effects among meat treatment, vitamin E treatment, age class (juvenile or adult), and all possible interactions on each hormone. We then examined the important factor’s effects across seasons using the non-parametric Friedman test. We found that age did not influence (p = 0.33) FGMs; however there was a significant effect of meat treatment on FGM (p = 0.04) and an effect of vitamin E on FAMs (p<0.10). When fed carcass, FGMs declined (p<0.001) from pre- to the during the breeding season time period, but was similar (p>0.05) between during and post-breeding season periods. Males that were not fed carcass had higher (p<0.05) FGMs during the breeding season compared to pre- and post-breeding season and FGMs were lower (p<0.05) in the post-breeding season compared to pre-breeding season. Males fed with carcass had lower (p<0.001) FGM than males that were not fed carcass during both the pre-breeding and the breeding season but not during the post-breeding season (p>0.05). Males supplemented with vitamin E had higher (p<0.001) FAM than non-supplemented males during the breeding season only. For both groups, FAM was highest (p<0.05) during the breeding season. In conclusion, adding carcass to the diet can reduce glucocorticoid production and adding vitamin E can increase testosterone during the breeding season, which may influence reproductive success.
Antibacterial Activity of Chromomycins from a Marine-Derived Streptomyces microflavus

A marine-derived actinomycete (Streptomyces sp. MBTI36) exhibiting antibacterial activities was investigated in the present study. The strain was identified using genetic techniques. The 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces microflavus. Furthermore, a new chromomycin A9 (1), along with chromomycin Ap (2), chromomycin A2 (3), and chromomycin A3 (4), were isolated from the ethyl acetate extract. Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, and HRMS, as well as comparisons with previously reported data. Compounds 1–4 showed potent antibacterial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). During a passage experiment, minimum inhibitory concentration (MIC) values for compounds 1–4 showed no more than a 4-fold increase from the starting MIC value, indicating that no resistance was detected over the 21 passages.
Speech and Language Skills of Low-Risk Preterm and Full-Term Late Talkers: The Role of Child Factors and Parent Input

Among children in the third year of life, late talkers comprise from 9% to 20%. This range seems to increase when addressing preterm children. This study examined video-recorded child spontaneous speech during parent–child book sharing as well as linguistic skills reported through the MacArthur Bates Communicative Development Inventories (MB-CDI) Short Form in 61 late talkers aged 30 months old (26 low-risk preterm, 8 females; 35 full-term, 12 females). Differences between low-risk preterm and full-term late talkers in child language measures and parental speech input were tested, as were the roles of child and parent factors on child language. Low-risk preterm and full-term late talkers showed similar speech and language skills. Similarly, no differences were found in measures of parental speech between groups. Child cognitive score, chronological age, and low-risk preterm status were positively associated with lexical diversity, rate, and composition of child speech production, whereas family history for language and/or learning disorders as well as parent measures of lexical diversity, rate, and grammatical complexity were negatively associated with the above child variables. In addition, child cognitive score and low-risk preterm status were positively associated with the MB-CDI measures of word and sentence production. Findings are discussed in terms of the need of good practices when following up on low-risk preterm children and of interventions targeting parents’ input to preterm and full-term late talkers.
The exosomal surface phenotype and inflamma‐miR cargo correlate with MDS diagnosis

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Vaccination with Intradermal Bacillus Calmette–Guérin Provides Robust Protection against Extrapulmonary Tuberculosis but Not Pulmonary Infection in Cynomolgus Macaques

Key Points Intradermal BCG vaccination cannot protect cynomolgus macaques against pulmonary TB. Extrapulmonary TB is strongly controlled in intradermal BCG–vaccinated monkeys. Recently, the efficacy of Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccination is being reassessed in accordance with the achievements of clinical tuberculosis (TB) vaccine research. However, the mechanisms ultimately determining the success or failure of BCG vaccination to prevent pulmonary TB remain poorly understood. In this study, we analyzed the protective effects of intradermal BCG vaccination by using specific pathogen–free cynomolgus macaques of Asian origin that were intradermally vaccinated with BCG (Tokyo strain) followed by Mycobacterium tuberculosis (Erdman strain) infection. Intradermal BCG administration generated TB Ag-specific multifunctional CD4 T cell responses in peripheral blood and bronchoalveolar lavage and almost completely protected against the development of TB pathogenesis with aggravation of clinical parameters and high levels of bacterial burdens in extrapulmonary organs. However, interestingly, there were no differences in bacterial quantitation and pathology of extensive granulomas in the lungs between BCG-vaccinated monkeys and control animals. These results indicated that the changes in clinical parameters, immunological responses, and quantitative gross pathology that are used routinely to determine the efficacy of TB vaccines in nonhuman primate models might not correlate with the bacterial burden and histopathological score in the lung as measured in this study.
Does acute soccer heading cause an increase in plasma S100B? A randomized controlled trial

The purpose of this study was to test the effect of subconcussive head impacts on acute changes in plasma S100B. In this randomized controlled trial, 79 healthy adult soccer players were randomly assigned to either the heading (n = 41) or kicking-control groups (n = 38). The heading group executed 10 headers with soccer balls projected at a speed of 25 mph, whereas the kicking-control group performed 10 kicks. Plasma samples were obtained at pre-, 0h post-, 2h post- and 24h post-intervention and measured for S100B. The primary hypothesis was that there would be a significant group difference (group-by-time interaction) in plasma S100B at 2h post-intervention. Secondary hypotheses included (1) no significant group differences in plasma S100B concentrations at 0h post- and 24h post-intervention; (2) a significant within-group increase in S100B concentrations in the heading group at 2h post-intervention compared to pre-intervention; and (3) no significant within-group changes in plasma S100B in the kicking-control group. Data from 68 subjects were available for analysis (heading n = 37, kicking n = 31). There were no differences in S100B concentrations between heading and kicking groups over time, as evidenced by nonsignificant group-by-time interaction at 2h post-intervention (B = 2.20, 95%CI [-22.22, 26.63], p = 0.86) and at all the other time points (0h post: B = -11.05, 95%CI [-35.37, 13.28], p = 0.38; 24h post: B = 16.11, 95%CI [-8.29, 40.51], p = 0.20). Part of the secondary outcome, the heading group showed elevation in plasma S100B concentrations at 24h post-intervention compared to pre-heading baseline (B = 19.57, 95%CI [3.13, 36.02], p = 0.02), whereas all other within-group comparisons in both remained nonsignificant. The data suggest that 10 bouts of acute controlled soccer headings do not elevate S100B concentrations up to 24-hour post-heading. Further dose-response studies with longer follow-up time points may help determine thresholds of acute soccer heading exposure that are related to astrocyte activation. The protocol was registered under ClinicalTrials.gov (NCT03488381; retrospectively registered.).
Nanoparticle Delivery Systems with Cell-specific Targeting for Pulmonary Diseases.

Respiratory disorders are among the most important medical problems threatening human life. The conventional therapeutics for respiratory disorders are hindered by insufficient drug concentrations at pathological lesions, lack of cell-specific targeting, and various bio-barriers in the conducting airways and alveoli. To address these critical issues, various nanoparticle delivery systems have been developed to serve as carriers of specific drugs, DNA expression vectors and RNAs. The unique properties of nanoparticles, such as controlled size and distribution, surface functional groups, high payload capacity, and drug release triggering capabilities, are tailored to specific requirements in drug/gene delivery to overcome major delivery barriers in pulmonary diseases. To avoid off-target effects and improve therapeutic efficacy, nanoparticles with high cell-targeting specificity are essential for successful nanoparticle therapies. Furthermore, low toxicity and high degradability of the nanoparticles are among the most important requirements in the nanoparticle designs. In this review, we provide the most up-to-date research and clinical outcomes in nanoparticle therapies for pulmonary diseases. We also address the current critical issues in key areas of pulmonary cell targeting, bio-safety and compatibility, and molecular mechanisms for selective cellular uptake.
MKK7 deficiency in mature neurons impairs parental behavior in mice

c‐Jun N‐terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7flox/floxSyn‐Cre mice) give birth to a normal number of pups but fail to raise them due to a defect in pup retrieval. To explore the mechanism underlying this abnormality, we performed comprehensive behavioral tests. Mkk7flox/floxSyn‐Cre mice showed normal locomotor functions and cognitive ability but exhibited depression‐like behavior. cDNA microarray analysis of mutant brain revealed an altered gene expression pattern. Quantitative RT‐PCR analysis demonstrated that mRNA expression levels of genes related to neural signaling pathways and a calcium channel were significantly different from controls. In addition, loss of neural MKK7 had unexpected regulatory effects on gene expression patterns in oligodendrocytes. These findings indicate that MKK7 has an important role in regulating the gene expression patterns responsible for promoting normal social behavior and staving off depression.
Lazily Aggregated Quantized Gradient Innovation for Communication-Efficient Federated Learning

This paper focuses on communication-efficient federated learning problem, and develops a novel distributed quantized gradient approach, which is characterized by adaptive communications of the quantized gradients. Specifically, the federated learning builds upon the server-worker infrastructure, where the workers calculate local gradients and upload them to the server; then the server obtain the global gradient by aggregating all the local gradients and utilizes it to update the model parameter. The key idea to save communications from the worker to the server is to quantize gradients as well as skip less informative quantized gradient communications by reusing previous gradients. Quantizing and skipping result in ‘lazy’ worker-server communications, which justifies the term Lazily Aggregated Quantized (LAQ) gradient. Theoretically, the LAQ algorithm achieves the same linear convergence as the gradient descent in the strongly convex case, while effecting major savings in the communication in terms of transmitted bits and communication rounds. Empirically, extensive experiments using realistic data corroborate a significant communication reduction compared with state-of-the-art gradient- and stochastic gradient-based algorithms.
Flavone effects on the proteome and transcriptome of colonocytes in vitro and in vivo and its relevance for cancer prevention and therapy

Flavone is a secondary plant compound that has been shown in the present thesis to exert profound effects on the mRNA and protein expression of colonic cells in cultures and in mice treated with a chemical carcinogen for tumor induction. Flavone is able to selectively induce apoptosis in transformed cells but not in normal colonocytes. Its main action appears the induction of apoptosis in tumor cells by forcing them to conduct oxidative metabolism rather than aerobic glycolysis and this leads to increased production of reactive oxygen species and in turn to mitochondria-driven apoptosis. Flavone may therefore be considered as an effective adjuvant in colon cancer therapy.
Multimodal imaging of brain reorganization in hearing late learners of sign language

The neural plasticity underlying language learning is a process rather than a single event. However, the dynamics of training‐induced brain reorganization have rarely been examined, especially using a multimodal magnetic resonance imaging approach, which allows us to study the relationship between functional and structural changes. We focus on sign language acquisition in hearing adults who underwent an 8‐month long course and five neuroimaging sessions. We assessed what neural changes occurred as participants learned a new language in a different modality—as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Major changes in the activity pattern appeared after just 3 months of learning, as indicated by increases in activation within the modality‐independent perisylvian language network, together with increased activation in modality‐dependent parieto‐occipital, visuospatial and motion‐sensitive regions. Despite further learning, no alterations in activation were detected during the following months. However, enhanced coupling between left‐lateralized occipital and inferior frontal regions was observed as the proficiency increased. Furthermore, an increase in gray matter volume was detected in the left inferior frontal gyrus which peaked at the end of learning. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality.
Impacts of Environmental Regulation on the Green Transformation and Upgrading of Manufacturing Enterprises

Since environmental problems are becoming increasingly prominent, macro policies and social development have placed higher requirements on manufacturing enterprises to promote green transformation and upgrading (GTU) in China. Considering that different manufacturing enterprises choose different green technology innovation levels for GTU under environmental regulation, a game model between manufacturing enterprises and the government is constructed. The relationship between the green technology innovation level (GTIL) and the environmental regulation intensity is analyzed. Through numerical examples, the influences of environmental regulation and consumer preference on system decisions are further examined. Moreover, an econometric model is constructed to explore the influence that the environmental regulation exerts on the GTIL using panel data from the Chinese manufacturing industry. Our results show that the increase in environmental regulation intensity contributes to improving GTIL and promoting the GTU of manufacturing enterprises. Furthermore, as the environmental regulation is enhanced, the sales price decreases, benefiting consumers. Consumers’ preference for high-GTIL products is conducive to GTU under environmental regulation. Empirical analysis shows that there is a U-shaped relationship between environmental regulation and the GTIL. Only when the intensity reaches a threshold can the environmental regulation be beneficial to improve the GTIL and promote the GTU of Chinese manufacturing enterprises.