Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs

Simple Summary Porcine epidemic diarrhea virus seriously threatens the health of suckling pigs. In this study, global mapping of H3K4me3 and transcriptomic analyses in the jejunum of porcine epidemic diarrhea virus (PEDV)-infected and healthy piglets were performed by using chromatin immunoprecipitation sequencing and RNA-seq techniques. A subset of genes and H3K4 trimethylation (H3K4me3) histone modifications that are associated with PEDV infections were identified. The results revealed previously unknown and intriguing elements involved in the regulation of genes responsive to PEDV infections, which may aid in identifying key regulators and genetic resistant markers for PEDV infections. Abstract Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.
Reply to: Older People's Loneliness in Clinical Work

1. Perissinotto C, Holt-Lundstadt J, Periyakoil VS, Covinsky K. A practical approach to assessing and mitigating loneliness and isolation in older adults. J Am Geriatr Soc. 2019;67:657-662. 2. Tilvis RS, Pitkala KH, Jolkkonen J, Strandberg TE. Social networks and dementia. Lancet. 2000;356:77-78. 3. Tilvis RS, Routasalo P, Karppinen H, Strandberg TE, Kautiainen H, Pitkala KH. Social isolation, social activity and loneliness as survival indicators in old age a nationwide survey with a 7-year follow-up. Eur Geriatr Med. 2012;3:18-22. 4. Amieva H, Stoykova R, Matharan F, Helmer C, Antonucci TC, Dartigues JF. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72:905-911. 5. Hawkley LC, Cacioppo JT. Loneliness matters: a theoretical and empirical review of consequences andmechanisms. Ann BehavMed. 2010;40:218-227. 6. Routasalo P, Tilvis RS, Kautiainen H, Pitkala KH. Effects of psychosocial group rehabilitation on social functioning, loneliness and psychological wellbeing of lonely older people: a randomized, controlled trial. J Adv Nurs. 2009;65:297-305. 7. Pitkala KH, Routasalo P, Kautiainen H, Tilvis RS. Effectiveness of psychosocial group rehabilitation on mortality and use of health services. J Gerontol. 2009;64:792-800. 8. Pitkala KH, Routasalo P, Kautiainen H, Tilvis RS. Effects of socially stimulating group intervention on lonely older people’s cogntion: a randomized controlled trial. Am J Geriatr Psychiatr. 2011;19:654-663. 9. Jansson A, Savikko N, Pitkala KH. Training professionals to implement a group model for alleviating loneliness among older people: 10-year followup study. Educ Gerontol. 2018;44:119-127. 10. Laakkonen ML, Kautiainen H, Savikko N, et al. Effects of self-management intervention on participants with dementia and their spousal caregivers. J Am Geriatr Soc. 2016;64:752-760.
Risk factors for bacteremia in children with febrile neutropenia

Background/aim Bacteremia remains an important cause of morbidity and mortality during febrile neutropenia (FN) episodes. We aimed to define the risk factors for bacteremia in febrile neutropenic children with hemato-oncological malignancies. Materials and methods The records of 150 patients aged ≤18 years who developed FN in hematology and oncology clinics were retrospectively evaluated. Patients with bacteremia were compared to patients with negative blood cultures. Results The mean age of the patients was 7.5 ± 4.8 years. Leukemia was more prevalent than solid tumors (61.3% vs. 38.7%). Bacteremia was present in 23.3% of the patients. Coagulase-negative staphylococci were the most frequently isolated microorganism. Leukopenia, severe neutropenia, positive peripheral blood and central line cultures during the previous 3 months, presence of a central line, previous FN episode(s), hypotension, tachycardia, and tachypnea were found to be risk factors for bacteremia. Positive central line cultures during the previous 3 months and presence of previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. Conclusion Presence of a bacterial growth in central line cultures during the previous 3 months and presence of any previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. These factors can predict bacteremia in children with FN.
Exosomes Are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-Regulating Early Inflammation and Angiogenesis.

Exosomes Are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-Regulating Early Inflammation and Angiogenesis Sir: W enjoyed reading the article by Chen et al.,1 and we congratulate the authors for their interest in such an important and emerging topic as extracellular vesicles in regenerative medicine applications. The data presented by Chen and colleagues are encouraging and in keeping with a potent inflammatory modulation observed in fat grafting application2 and in other contexts,. 3 The perspective of having a well-identified biological modality for enrichment of fat grafts and consequent improvement of viability and durability is at the same time appealing and challenging if we think about the efforts of the scientific community for this purpose and the huge variety of conceived methods of fat processing for improved volume retention following lipofilling. As the benefits of extracellular vesicles are promising, the question is: how far are we from the clinical translation of this intriguing tool for regenerative medicine? A Good Medical Practice method for standardized production of clinical grade extracellular vesicles has not been fully defined yet. The idea of isolating extracellular vesicles from mesenchymal stem cells instead of using mesenchymal stem cells for cell therapy is encouraging and based on the fact that the effect of these cells is considered to be likely attributable to a vesicle-mediated paracrine action. Moreover, the advantages of cell-free extracellular vesicle approaches are the absent/lower risks of tumor formation and lower immunogenicity. However, mesenchymal stem cell–derived vesicles are applied with a defined dosage, whereas mesenchymal stem cells may duplicate when transplanted, thus increasing and maintaining their effect for a longer time. A discrepancy may potentially exist between the mechanism of action of mesenchymal stem cells in vitro and in vivo, and the paracrine effects may be ascribed to both secreted vesicles and soluble factors, thus the use of only extracellular vesicles would limit mesenchymal stem cells’ stimulating and regenerative effects. When dealing with extracellular vesicles, particular attention is to be addressed to the method of isolation, which can influence efficacy and immunomodulatory activities.4 The evaluation of at least an equal or even a better efficacy of extracellular vesicles versus cells should be based on clear and specific criteria as shown by the recent review by Witwer et al.5 The topic is hot, and a number of studies are ongoing, but more knowledge is necessary to have this important technique of vesicle-based therapy available to plastic surgeons, either as an adjunct to lipofilling or as an isolated ready-off-the-shelf therapy. DOI: 10.1097/PRS.0000000000007003
Comparative Study on the Thermal-Aging Characteristics of Cellulose Insulation Polymer Immersed in New Three-Element Mixed Oil and Mineral Oil

Cellulose paper, whose main component is cellulose polymer, has been widely used in oil-immersed power transformer that gradually deteriorates during transformer operation. Thermal aging is the main degradation form for cellulose paper immersed in insulation oil (oil–paper insulation) in a transformer. One of the most challenging issues in oil–paper insulation is inhibiting the aging of cellulose paper and extending its life. In this work, a comparative study was conducted on the thermal-aging characteristics of cellulose paper immersed in a novel three-element mixed insulation oil and mineral oil at 130 °C for 150 days. The key parameters of cellulose paper were analysed, including the degree of polymerization (DP), thermal-aging rate, surface colour, and AC breakdown voltage. The furfural content and acidity of the oil, as well as the AC breakdown voltage of the insulation oil were also analysed. The results show that the cellulose paper immersed in novel three-element mixed insulation oil had much higher DP values than that immersed in mineral oil after the same thermal-aging time. The mixed insulation oil could significantly inhibit the thermal aging of cellulose paper and prolong its life. The thermal-aging rate of the cellulose insulation polymer immersed in mixed insulation oil is significantly lower than that immersed in mineral oil, whether in the process of oil–paper insulation continuous aging or in the process of aging after oil replacement with unused insulation oil. The furfural generated by cellulose degradation in the novel three-element mixed insulation oil was also less than that in the mineral oil. The mixed insulation oil had a higher acidity value during the thermal-aging process, which was mainly due to the natural esters in the components of the mixed insulation oil. However, the AC breakdown voltage of the mixed insulation oil was always higher than that of the mineral oil. This study offers a new perspective in inhibiting the thermal aging of cellulose polymer in insulation oil.
Identification of Dietary Patterns Associated with Incidence of Hyperglycemia in Middle-Aged and Older Korean Adults

Little is known about the association between dietary patterns and hyperglycemia incidence among Korean adults. Hence, we aimed to prospectively investigate the major dietary patterns associated with hyperglycemia among middle-aged and older Korean adults. In total, 55,457 adults (18,292 men and 37,165 women) aged 40 to 79 years, who were previously enrolled in the Health Examinee Study of the Korean Genome and Epidemiology Study and had no history of type 2 diabetes mellitus (T2DM) or cancer at baseline, were included. Dietary patterns were identified by a factor analysis based on dietary data, which were assessed at baseline using a validated food-frequency questionnaire. Participants were classified as having hyperglycemia if fasting blood glucose levels were ≥126 mg/dL or physician diagnosed T2DM during follow-up. Multivariable Cox proportional hazard models were used to examine the associations between each dietary pattern and future hyperglycemia risk after adjusting for potential confounders. After a mean follow-up of 4.9 years, 2574 new cases of hyperglycemia were identified. Using a factor analysis, four distinct dietary patterns were identified: “prudent;” “fatty fish, meat, and flour-based food;” “coffee and sweets;” and “whole grain (men)” or “white rice (women). ” The “prudent” pattern was inversely associated with hyperglycemia risk only in women (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.63–0.89; p for trend = 0.0003). Conversely, women in the highest quintile of the “fatty fish, meat, and flour-based food” pattern showed an increased risk of hyperglycemia (HR, 1.22; 95% CI, 1.03–1.44; p for trend = 0.0210) compared with those in the lowest quintile. The “coffee and sweets” and “white rice” patterns were not associated with hyperglycemia risk in women. The dietary patterns observed in men had no associations with hyperglycemia incidence. Our findings suggest that a diet rich in vegetables, mushrooms, seaweeds, fruits, and soy products and low in fatty fish and high-fat meat may potentially play a protective role in T2DM development with sex differences in middle-aged and older Korean adults.
Methylation of the RELA Gene is Associated with Expression of NF-κB1 in Response to TNF-α in Breast Cancer

The nuclear factor (NF)-κB family of transcriptional factors plays a critical role in inflammation, immunoregulation, cell differentiation, and tumorigenesis. This study aims to investigate the role of methylation of genes encoding for the NF-κB family in breast cancer. We analyze the DNA methylation status of the NFKB1 gene and the RELA gene in breast cancer using pyrosequencing. The expression of NF-κB1 and RELA proteins is assessed and the level of RNA transcripts in frozen tissue is determined using RT-PCR. There is no statistically significant difference in the methylation status of the NFKB1 and the RELA genes between tumors and normal tissues. The methylation status of the NFKB1 gene and the RELA gene is not significantly associated with the levels of NF-κB1 transcripts in tumor tissues. However, the methylation level of the RELA gene is significantly associated with the level of tumor necrosis factor (TNF)-α. In addition, the level of NF-κB1 transcripts was associated with the levels of TNF-α and IL-4. In tumors with positive TNF-α, the increased methylation level of the RELA gene is significantly associated with the positive expression of NF-κB1 transcripts. These results demonstrate that the level of the RELA gene methylation is related to the levels of NF-κB1 transcripts under the influence of TNF-α. Further study is needed to determine how TNF-α is involved in the methylation of the RELA gene and the subsequent expression of NF-κB1.
Natural flavones from Morus alba against MRSA via targeting the proton motive force and membrane permeability.

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency to kill diverse MRSA isolates. Based on structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase membrane permeability and to dissipate proton gradient. Meanwhile, mechanistic studies further shown that kuwanon G displayed rapid bactericidal activity in vitro with difficulty to develop drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interaction. Additionally, kuwanon G promoted wound healing in mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA associated infections through dissipating the proton motive force and disrupting the membrane permeability. The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency to kill diverse MRSA isolates. Based on structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase membrane permeability and to dissipate proton gradient. Meanwhile, mechanistic studies further shown that kuwanon G displayed rapid bactericidal activity in vitro with difficulty to develop drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interaction. Additionally, kuwanon G promoted wound healing in mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA associated infections through dissipating the proton motive force and disrupting the membrane permeability.
Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells

Arterial foam cells are central players of atherogenesis. Cholesterol acceptors, apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), take up cholesterol and phospholipids effluxed from foam cells into the circulation. Due to the high abundance of cholesterol in foam cells, most previous studies focused on apoA-I/HDL-mediated free cholesterol (FC) transport. However, recent lipidomics of human atherosclerotic plaques also identified that oxidized sterols (oxysterols) and non-sterol lipid species accumulate as atherogenesis progresses. While it is known that these lipids regulate expression of pro-inflammatory genes linked to plaque instability, how cholesterol acceptors impact the foam cell lipidome, particularly oxysterols and non-sterol lipids, remains unexplored. Using lipidomics analyses, we found cholesterol acceptors remodel foam cell lipidomes. Lipid subclass analyses revealed various oxysterols, sphingomyelins, and ceramides, species uniquely enriched in human plaques were significantly reduced by cholesterol acceptors, especially by apoA-I. These results indicate that the function of lipid-poor apoA-I is not limited to the efflux of cholesterol and phospholipids but suggest that apoA-I serves as a major regulator of the foam cell lipidome and might play an important role in reducing multiple lipid species involved in the pathogenesis of atherosclerosis.
Multimodal Device for Real-Time Monitoring of Skin Oxygen Saturation and Microcirculation Function

The present study introduces a recently developed compact hybrid device for real-time monitoring of skin oxygen saturation and temperature distribution. The prototype involves a snapshot hyperspectral camera, multi-wavelength illuminator, thermal camera, and built-in computer with custom-developed software. To validate this device in-vivo we performed upper arm vascular occlusion on eight healthy volunteers. Palm skin oxygen saturation maps were analyzed in real-time using k-means segmentation algorithm and two-layer optical diffuse model. The prototype system demonstrated a satisfying performance of skin hyperspectral measurements in the spectral range of 507–625 nm. The results confirmed the reliability of the proposed system for in-vivo assessment of skin hemoglobin saturation with oxygen and microcirculation.
MMI-0100 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Targeting MK2 Pathway

Backgrounds: This study aimed to investigate the protective effects of MMI-0100, a cell-penetrating peptide inhibitor of MAPK-activated protein kinase II (MK2), on acute colitis induced by dextran sodium sulfate (DSS). Mice were injected intraperitoneally with different doses of MMI-0100 (0.5 and 1 mg/kg per day, six days). The physiological indexes, the parameters for colonic pathological injury and the intensity of inflammatory responses were evaluated by histological staining, quantitative PCR, western blotting, and immunostaining. MMI-0100 attenuated DSS-induced body weight loss, colon length shortening, and colonic pathological injury, including decreased myeloperoxidase (MPO) and inhibited inflammatory cell infiltration. MMI-0100 suppressed DSS-induced activation of CD11b+ and F4/80 positive cell, and dramatically decreased the expression of a series of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, TGF- β, IFN-γ, IL-17A, COX-2 and iNOS. A TUNEL assay showed that MMI-0100 protected against DSS-induced apoptosis. This is consistent with the results of Western blotting assay in apoptosis-related proteins including Bcl-2, BAX, caspase-3. The anti-inflammatory effects of MMI-0100 on DSS-induced colitis were achieved by down-regulating the phosphorylation level of MK2, IκBα and p65 protein. The current study clearly demonstrates a protective role for MMI-0100 in experimental IBD.
Emotion regulation strategies in mania risk: A systematic review.

OBJECTIVES Difficulties in emotion regulation may contribute to the development of mania. This review aimed to assess how emotion regulation strategies reported by individuals at risk of mania compare with clinical and nonclinical controls. METHODS Search terms relating to mania risk and emotion regulation were entered into three databases. Sixteen studies were included. RESULTS Mania risk was typically associated with overall endorsement of emotion regulation strategies, particularly dampening, and positive and negative rumination. CONCLUSIONS Findings were limited by overall lack of evidence for individual strategies, lack of consideration of key mediating factors and reliance upon self-report designs.
Prevalence and Risk Factors for Cognitive Impairment and Dementia in Indians: A Multiethnic Perspective from a Singaporean Study.

BACKGROUND Dementia is the leading cause of dependency and disability among older persons worldwide. There remains, however, limited studies on dementia rates within the Asia-Pacific region, with little data on differences across major Asian ethnic groups. OBJECTIVE To study the prevalence of cognitive impairment (CI) and dementia in community-dwelling Indians from Singapore and to examine interethnic differences among Chinese, Malays, and Indians. METHODS Participants (>60 years) drawn from the Indian component of the multiethnic Epidemiology of Dementia in Singapore (EDIS) study were screened using the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen-positive participants underwent further detailed neuropsychological assessments. CI was classified into Cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia. RESULTS Of 961 Indian adults, 120 (12.5%) had CIND-mild, 101 (10.5%) CIND-moderate, and 12 (1.2%) dementia. The overall age-standardized prevalence of any CI was 24.6%. The prevalence of any CI increased with age (15.7% in ages 60-64 years to 30.1% in ages≥80 years), and was higher in women than men. Multivariate analysis showed that age, lower education, and hypertension were independently associated with CI. Even after demographic and cardiovascular risk factor adjustment, Indians were more likely to be cognitively impaired compared to Chinese (odds ratio [OR], 95% CI:1.37 [1.01-1.86]) but not Malays (0.89 [0.72-1.10]). CONCLUSIONS Among elderly Indians, the overall prevalence of any CI was 24.6%. Despite similar assessment protocols and risk factor adjustments, the prevalence of CI was higher in Indians compared to Chinese but similar to Malays. Further research is needed to unravel other factors that may underlie these ethnic differences.