Miracle-dz/UniFAR-FTUs huggingface dataset:
Directed Differentiation of Human Pluripotent Stem Cells towards Corneal Endothelial-Like Cells under Defined Conditions

The most crucial function of corneal endothelial cells (CEnCs) is to maintain optical transparency by transporting excess fluid out of stroma. Unfortunately, CEnCs are not able to proliferate in vivo in the case of trauma or dystrophy. Visually impaired patients with corneal endothelial deficiencies that are waiting for transplantation due to massive global shortage of cadaveric corneal transplants are in a great need of help. In this study, our goal was to develop a defined, clinically applicable protocol for direct differentiation of CEnCs from human pluripotent stem cells (hPSCs). To produce feeder-free hPSC-CEnCs, we used small molecule induction with transforming growth factor (TGF) beta receptor inhibitor SB431542, GSK-3-specific inhibitor CHIR99021 and retinoic acid to guide differentiation through the neural crest and periocular mesenchyme (POM). Cells were characterized by the morphology and expression of human (h)CEnC markers with immunocytochemistry and RT-qPCR. After one week of induction, we observed the upregulation of POM markers paired-like homeodomain transcription factor 2 (PITX2) and Forkhead box C1 (FOXC1) and polygonal-shaped cells expressing CEnC-associated markers Zona Occludens-1 (ZO-1), sodium-potassium (Na+/K+)-ATPase, CD166, sodium bicarbonate cotransporter 1 (SLC4A4), aquaporin 1 (AQP1) and N-cadherin (NCAD). Furthermore, we showed that retinoic acid induced a dome formation in the cell culture, with a possible indication of fluid transport by the differentiated cells. Thus, we successfully generated CEnC-like cells from hPSCs with a defined, simple and fast differentiation method.
Penetration and Break-Up Behaviour of a Discrete Liquid Jet in a Cross Flowing Airstream: A Further Study

Penetration and break-up characteristics of a discrete liquid jet injected into a high velocity cross flowing airstream were examined as a basis of plain-jet airblast atomizer design. The first results of this program, detailed in (4), covered the effects of liquid jet/airstream velocities and the injection orifice diameter. The results presented here cover the effects of liquid viscosity (0.001 to 0.125 Ns/m2), liquid surface tension (0.027 to 0.074 N/m), liquid density (812 to 1830 Kg/m3), the liquid jet injection angle (30 to 90 degrees) and the orifice length-to-diameter ratio (5 to 14). These tests were carried out under normal atmospheric pressure and temperature conditions using still photography for penetration profile and a laser light scattering technique for mean dropsize determination. The experimental penetration data is shown to agree reasonably accurately, with the simple model developed before (see (4)). The analysis of the experimental mean dropsize data collected in this study leads to the development of the following correlationDisplay FormulaSMD=1. 206σlVa20. 6djo0.4+0. 072μl2σlρl0. 45djo0.55Copyright © 1983 by ASME
Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b+ platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti–mouse CD49b-PE (phycoerythrin) antibody. Platelet–endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b+ platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism.
Herpes Simplex Virus 1 Manipulates Host Cell Antiviral and Proviral DNA Damage Responses

We investigated the relationship between the DNA damage response, a collection of vital cellular pathways that repair potentially lethal damage to the genome, and the DNA virus herpes simplex virus 1. We found that infection by the virus triggers the DNA damage response and key proteins that mediate this response have opposing effects on the replication and production of progeny viruses. ABSTRACT Cells activate their DNA damage response (DDR) in response to DNA virus infection, including adenoviruses, papillomaviruses, polyomaviruses, and herpesviruses. In this study, we found that the DDR kinase pathways activated in normal human fibroblasts by herpes simplex virus 1 (HSV-1) input genomic DNA, HSV-1 replicating DNA, and progeny DNA and in uninfected cells treated with etoposide are different. We also found using clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 technology that different host gene products are required for the DDR in uninfected versus infected cells. Individual DDR components can be proviral or antiviral in that ataxia-telangiectasia mutated (ATM) and p53 promote and Mre11 restricts replication of ICP0-null HSV-1, but ICP0 expression eliminates these DDR effects. Thus, in total, these results argue that HSV-1 manipulates the host cell DDR to utilize specific components for its optimal replication while inactivating the antiviral aspects of the DDR. IMPORTANCE We investigated the relationship between the DNA damage response, a collection of vital cellular pathways that repair potentially lethal damage to the genome, and the DNA virus herpes simplex virus 1. We found that infection by the virus triggers the DNA damage response, and key proteins that mediate this response have opposing effects on the replication and production of progeny viruses. Our work provides novel insights into the relationship between DNA virus infection and the cellular response to the viral genome. We speculate that viral gene products modulate this response, providing potentially novel targets for therapeutic intervention against the virus.
Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue

This study has extended previous metabolic measures in postmortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37-year-old male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathologic characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n = 2-4) approximately age-matched controls. Examination of mass and molar composition of major phospholipid classes showed decreases in phospholipids enriched in myelin, such as phosphatidylserine, sphingomyelin, and ethanolamine plasmalogen. Evaluation of gene expression (RT2 Profiler PCR Arrays, GABA, glutamate; Qiagen) revealed dysregulation in 14/15 GABAA receptor subunits in cerebellum, parietal, and frontal lobes with the most significant downregulation in ∊, θ, ρ1, and ρ2 subunits (7.7-9.9-fold). GABAB receptor subunits were largely unaffected, as were ionotropic glutamate receptors. The metabotropic glutamate receptor 6 was consistently downregulated (maximum 5.9-fold) as was the neurotransmitter transporter (GABA), member 13 (maximum 7.3-fold). For other genes, consistent dysregulation was seen for interleukin 1β (maximum downregulation 9.9-fold) and synuclein α (maximal upregulation 6.5-fold). Our data provide unique insight into SSADHD brain function, confirming astrogliosis and lipid abnormalities previously observed in the null mouse model while highlighting long-term effects on GABAergic/glutamatergic gene expression in this disorder.
In situ preparation of zinc salts of unsaturated carboxylic acids to reinforce NBR

Through the neutralization reaction of zinc oxide (ZnO) and methacrylic acid (MAA) or acrylic acid (AA), zinc methacrylate (ZMA) or zinc acrylate (ZA) was in situ prepared in nitrile rubber (NBR). The mechanical properties and crosslinking structure of the resulting peroxide-cured NBR vulcanizates were studied. The results showed that ZnO/MAA (AA) had a great reinforcing effect for NBR, and their amounts and ratio played important roles in influencing the mechanical properties. Such vulcanizate contains both covalent crosslinks and salt crosslinks, and the change in the tensile strength of the vulcanizate was related to the variation of the salt crosslink density. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 2740–2748, 2000
Influence of Soil and Water Conservation Measures on Soil Microbial Communities in a Citrus Orchard of Southeast China

Soil microbes play a crucial role in ecosystem function. Here, the effects of soil and water conservation measures on soil microbial community structures, biodiversity, and co-occurrence networks are investigated and compared. We sampled soils at three different depths (0–10 cm, 10–20 cm and 20–40 cm) in a citrus orchard that uses long-term soil and water conservation measures, which includes Bermuda grass strip intercropping (BS), Bermuda grass full coverage (BF), Radish–soybean crop rotation strip intercropping (RS) and clear tillage orchards (CT). Results demonstrated that BS and BF yields a significant increase in bacterial richness and diversity of fungal in soils, while BF contains more beneficial microbial taxa, especially those with degrading and nutrient cycling capabilities. Microbial community structures differed significantly among the applied measures. In addition, co-occurrence networks under BS, BF and RS were more complex and robust than that of CT, and the stability of the network in BF was the highest. Microbial interactive stability and potential interactions in bacterial networks were stronger than those of fungi. The distribution of dominant phyla showed that Chloroflexi and Ascomycota dominated the different soil and water conservation measures. Proteobacteria and Ascomycota are revealed to be keystone species in bacterial networks and fungal networks, respectively, while Proteobacteria was the keystone species in microbial networks. Though the relative abundance of Chloroflexi turned out to have increased among the four measures, the relative abundance for Proteobacteria, Acidobacteria and Actinobacteria all decreased along the soil profile, with Acidobacteria under BS to be an exception. Soils under BS and BF had higher total nitrogen, microbial biomass carbon and organic carbon than CT and RS. Organic carbon(C) and total nitrogen(N) in soil were the major drivers of these bacterial community patterns, while there was no significant correlation between them and fungi. Overall, BF increases soil nutrients and microbial diversity, and also promotes ecological stability and interrelations among microbial taxa that collectively improve soil quality in the citrus orchard studied. Therefore, we recommended BF to be an ideal application for citrus orchards of southeast China.
Deuterium Oxide (D2O) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma

Simple Summary Systemic administration of deuterium oxide (‘heavy water’) has shown promise in suppressing tumor growth and metastasis in mammalian cancer models, but no detailed molecular studies have revealed specific molecular pathways mediating cancer-cell-directed activities. Here, for the first time, transcriptomic analysis complemented by in vivo efficacy experiments have addressed this unresolved topic. Abstract There are two stable isotopes of hydrogen, protium (1H) and deuterium (2H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (2H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (D2O; ‘heavy water’) together with stress response gene expression profiling in panels of malignant melanoma (A375V600E, A375NRAS, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts. Moreover, we have examined the efficacy of D2O-based pharmacological intervention in murine models of human melanoma tumor growth and metastasis. D2O-induction of apoptosis was substantiated by AV-PI flow cytometry, immunodetection of PARP-1, and pro-caspase 3 cleavage, and rescue by pan-caspase inhibition. Differential array analysis revealed early modulation of stress response gene expression in both A375 melanoma and PANC-1 adenocarcinoma cells elicited by D2O (90%; ≤6 h) (upregulated: CDKN1A, DDIT3, EGR1, GADD45A, HMOX1, NFKBIA, or SOD2 (up to 9-fold; p < 0.01)) confirmed by independent RT-qPCR analysis. Immunoblot analysis revealed rapid onset of D2O-induced stress response phospho-protein activation (p-ERK, p-JNK, p-eIF2α, or p-H2AX) or attenuation (p-AKT). Feasibility of D2O-based chemotherapeutic intervention (drinking water (30% w/w)) was demonstrated in a severe combined immunodeficiency (SCID) mouse melanoma metastasis model using luciferase-expressing A375-Luc2 cells. Lung tumor burden (visualized by bioluminescence imaging) was attenuated by D2O, and inhibition of invasiveness was also confirmed in an in vitro Matrigel transwell invasion assay. D2O supplementation also suppressed tumor growth in a murine xenograft model of human melanoma, and median survival was significantly increased without causing adverse effects. These data demonstrate for the first time that systemic D2O administration impairs growth and metastasis of malignant melanoma through the pharmacological induction of deuterium (2H)-stress.
The association between self-perceived walking pace with the incidence of hypertension: the ‘Seguimiento Universidad de Navarra’ cohort

Supplemental Digital Content is available in the text Objective: Although available evidence supports the protective effects of walking on hypertension – a major risk factor for cardiovascular disease and stroke – more information is needed in determining whether walking pace independently provides additional hypertension risk reductions. This prospective study determined the association between self-reported walking pace and the incidence of hypertension in the ‘Seguimiento Universidad de Navarra’ (SUN) cohort in Spain. Methods: Our population sample consisted of 15 357 university graduates initially free of chronic disease or hypertension. During an average follow-up time of 10.9 years, 1673 incident cases of hypertension were observed. Hazard ratios and 95% confidence intervals (95% CIs) for hypertension risk of each walking pace [slow (reference), normal, brisk and very brisk] were estimated using Cox regression models, adjusted for multiple possible confounders. Data were collected from 1999 to 2019, and analysed in 2020. Results: Participants who walked at a very brisk pace at baseline had a substantially lower risk of developing hypertension during follow-up than those who walked at a slow pace (multivariable-adjusted hazard ratio: 0.64; 95% CI: 0.41–0.99). Inverse associations were observed also for normal (HR: 0.64; 95% CI: 0.46–0.90) and brisk walking pace (0.69; 95% CI: 0.50–0.97) as compared to slow pace, independent of other risk factors. Conclusion: Our results support that an increase in walking pace, even slightly, is inversely associated with the development of hypertension, independent of total time spent walking and other factors associated with hypertension.
Roles of NANOGP8 in cancer metastasis and cancer stem cell invasion during development of castration-resistant prostate cancer

Background Prostate cancer (PCa) is one of the most common types of cancer and the emerging resistance to androgen deprivation therapy in PCa aggravates disease progression. In this study, we examined the potential pro-tumorigenic functions of NANOGP8 in prostate cancer development. Methods Quantitative RT-PCR confirmed higher NANOGP8 expression in androgen independent tumors, as well as a recurrent prostate tumor in patient samples. We then established a novel two-way inducible NANOGP8-short hairpin RNA experimental system, in which the NANOGP8 expression was transiently induced by adding doxycycline in the diet of NOD/SCID mice. Results The knockdown of NANOGP8 inhibited implanted tumor growth and the progression of castration-resistant PCa. NANOGP8-deficient PCa cells lost their cancer stem cell and gene expression programs. To further investigate the functions of NANOGP8 in PCa stem cells, real-time cell tracking was used to monitor the cell division modes and differentiation patterns of NANOGP8+ cells. The expression level of NANOGP8 markedly influenced the cell division mode of NANOGP8+ PCa cells and was strongly correlated with their pluripotency, reflected by robust telomerase activity and longer telomere length. NANOGP8 expression was also associated with the metastatic capacity of PCa cells. Conclusions Based on these findings, we propose that NANOGP8 could serve as an effective therapeutic target for the treatment of PCa.
Cultural race-related stress and cannabis use among incarcerated African American men.

OBJECTIVE Research suggests African American men use cannabis to cope with racial discrimination. This conjecture may also be true for incarcerated African American men, who report high rates of cannabis use prior to and after incarceration. However, no studies to date have examined the association between race-related stress and chronic cannabis use among incarcerated African American men. As this population encounters pervasive negative cultural stereotypes and devaluation from larger society, cultural race-related stress may predict cannabis use among this population. Therefore, the purpose of this brief report was to examine the relationship between cultural race-related stress and years of regular cannabis use among a sample of incarcerated African American men. METHOD Study staff completed interviews with N = 177 African American men nearing release from four prisons in Kentucky. The interviews focused on mental health, drug use, and HIV risk behaviors. Participants provided their demographics (e.g., age, years of education, and length of incarceration), self-reported their years of regular cannabis use (3 times or more per week), and completed the Brief Index of Race-Related Stress (IRRS-B; Utsey, Measurement & Evaluation in Counseling & Development, 1999, 32, 149). RESULTS Multivariate regression analyses demonstrated cultural race-related stress was significant and positively associated with the number of years of regular cannabis use (p = .003) among this population. CONCLUSIONS This finding has implications for culturally tailored substance abuse treatment, specifically for cannabis use, with African American men upon their community re-entry from prison. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Artificial hair implantation for hair restoration

Abstract Background Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Artificial hair implantation is considered an alternative treatment when the donor area is depleted or unsuitable for hair transplantation. The use of artificial hair implants remains controversial, particularly because this practice has been banned by the US FDA. Objective To summarize various aspects of artificial hair implantation. Methods We discuss the history of artificial hair implantation, development of new biocompatible fibers (Biofibre®, Nido Z-type), patient eligibility for this treatment, implantation technique, follow-up, immune response to the implanted fibers, and post-implantation complications. We performed a methodological quality assessment of the clinical studies that investigated artificial hair implantation using the Canadian Institute of Health Economics (IHE) Quality Appraisal Tool for Case Series (Interventional). Results Although the studies evaluating the use of artificial hair fibers appear promising, the methodological quality of most of them was between ‘poor’ and ‘fair’, due to lack of randomization, absence of control groups, improper study design, and inappropriate outcome measures. Conclusions Artificial hair implantation has been received with skepticism among physicians due to the complications reported. Further high-quality research needs to be performed to ascertain the safety and efficacy of artificial hair implantation.
Oligodendroglial Heterogeneity in Neuropsychiatric Disease

Oligodendroglia interact with neurons to support their health and maintain the normal functioning of the central nervous system (CNS). Human oligodendroglia are a highly heterogeneous population characterised by distinct developmental origins and regional differences, as well as variation in cellular states, as evidenced by recent analysis at single-nuclei resolution. Increasingly, there is evidence to suggest that the highly heterogeneous nature of oligodendroglia might underpin their role in a range of CNS disorders, including those with neuropsychiatric symptoms. Understanding the role of oligodendroglial heterogeneity in this group of disorders might pave the way for novel approaches to identify biomarkers and develop treatments.