Miracle-dz/UniFAR-FTUs huggingface dataset:
NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns

Despite the high morbidity and mortality among patients with extensive cutaneous burns in the intensive care unit due to the development of acute respiratory distress syndrome, effective therapeutics remain to be determined. This is primarily because the mechanisms leading to acute lung injury (ALI) in these patients remain unknown. We test the hypothesis that cutaneous chemical burns promote lung injury due to systemic activation of neutrophils, in particular, toxicity mediated by the deployment of neutrophil extracellular traps (NETs). We also demonstrate the potential benefit of a peptidyl arginine deiminase 4 (PAD4) inhibitor to prevent NETosis and to preserve microvascular endothelial barrier function, thus reducing the severity of ALI in mice. Our data demonstrated that phenylarsine oxide (PAO) treatment of neutrophils caused increased intracellular Ca2+-associated PAD4 activity. A dermal chemical burn by lewisite or PAO resulted in PAD4 activation, NETosis, and ALI. NETs disrupted the barrier function of endothelial cells in human lung microvascular endothelial cell spheroids. Citrullinated histone 3 alone caused ALI in mice. Pharmacologic or genetic abrogation of PAD4 inhibited lung injury following cutaneous chemical burns. Cutaneous burns by lewisite and PAO caused ALI by PAD4-mediated NETosis. PAD4 inhibitors may have potential as countermeasures to suppress detrimental lung injury after chemical burns.
Genome-Wide Association Study of Pelvic Organ Prolapse Using the Michigan Genomics Initiative

Supplemental digital content is available in the text. Objectives The aim of this study was to (1) replicate previously identified genetic variants significantly associated with pelvic organ prolapse and (2) identify new genetic variants associated with pelvic organ prolapse using a genome-wide association study. Methods Using our institution’s database linking genetic and clinical data, we identified 1,329 women of European ancestry with an International Classification of Diseases, Ninth Revision (ICD-9)/ICD-10 code for prolapse, 767 of whom also had Current Procedural Terminology (CPT)/ICD-9/ICD-10 procedure codes for prolapse surgery, and 16,383 women of European ancestry older than 40 years without a prolapse diagnosis code as controls. Patients were genotyped using the Illumina HumanCoreExome chip and imputed to the Haplotype Reference Consortium. We tested 20 million single nucleotide polymorphisms (SNPs) for association with pelvic organ prolapse adjusting for relatedness, age, chip version, and 4 principal components. We compared our results with 18 previously identified genome-wide significant SNPs from the UK Biobank, Commun Biol (2020;3:129), and Obstet Gynecol (2011;118:1345–1353). Results No variants achieved genome-wide significance (P = 5 × 10−8). However, we replicated 4 SNPs with biologic plausibility at nominal significance (P ≤ 0.05): rs12325192 (P = 0.002), rs9306894 (P = 0.05), rs1920568 (P = 0.034), and rs1247943 (P = 0.041), which were all intergenic and nearest the genes SALL1, GDF7, TBX5, and TBX5, respectively. Conclusions Our replication of 4 biologically plausible previously reported SNPs provides further evidence for a genetic contribution to prolapse, specifically that rs12325192, rs9306894, rs1920568, and rs1247943 may contribute to susceptibility for prolapse. These and previously reported associations that have not yet been replicated should be further explored in larger, more diverse cohorts, perhaps through meta-analysis.
Incidence Rate of COVID-19 Infection in Hemoglobinopathies: A Systematic Review and Meta-analysis

Abstract During the coronavirus-19 disease (COVID-19) pandemic, several studies were performed to determine the mortality and incidence rates of coronavirus infection among patients with hemoglobinopathies. However, there has been no systematic approach or meta-analysis to evaluate the results worldwide. This meta-analysis summarized the existing evidence of incidence and mortality rates of COVID-19 and related risk factors among patients with hemoglobinopathies with a focus on β-thalassemia (β-thal) and sickle cell disease. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Two authors independently screened the articles, extracted eligible ones, and assessed the quality of studies using the Joanna Briggs Institute (JBI) checklist. The collected data were analyzed by the Stata software. The amount of heterogeneity was demonstrated by the I2 test. The incidence of COVID-19 among patients with a hemoglobinopathy, β-thal and sickle cell disease was 4.44, 1.34, and 17.22 per 100,000 person-day, respectively, to June 15 2020. The mortality rate of COVID-19 in patients with hemoglobin (Hb) disorders was calculated as 1.07 per 1000 person-day in the same period. Our findings showed a higher incidence rate of COVID-19 in sickle cell disease patients compared to the general population. A slightly higher mortality rate was also observed in patients with hemoglobinopathies compared to the general population, possibly due to the associated risk factors and comorbidities in this vulnerable group, which underscore special care, timely diagnosis and management along with current immunization, were crucial in decreasing the frequency, disease severity and mortality of these patients.
Increased mRNA Stability and Expression Level of Croceibacter atlanticus Lipase Gene Developed through Molecular Evolution Process

In order to use an enzyme industrially, it is necessary to increase the activity of the enzyme and optimize the reaction characteristics through molecular evolution techniques. We used the error-prone PCR method to improve the reaction characteristics of LipCA lipase discovered in Antarctic Croceibacter atlanticus. Recombinant Escherichia coli colonies showing large halo zones were selected in tributyrin-containing medium. The lipase activity of one mutant strain (M3-1) was significantly increased, compared to the wild-type (WT) strain. M3-1 strain produced about three times more lipase enzyme than did WT strain. After confirming the nucleotide sequence of the M3-1 gene to be different from that of the WT gene by four bases (73, 381, 756, and 822), the secondary structures of WT and M3-1 mRNA were predicted and compared by RNAfold web program. Compared to the mean free energy (MFE) of WT mRNA, that of M3-1 mRNA was lowered by 4.4 kcal/mol, and the MFE value was significantly lowered by mutations of bases 73 and 756. Site-directed mutagenesis was performed to find out which of the four base mutations actually affected the enzyme expression level. Among them, one mutant enzyme production decreased as WT enzyme production when the base 73 was changed (T→C). These results show that one base change at position 73 can significantly affect protein expression level, and demonstrate that changing the mRNA sequence can increase the stability of mRNA, and can increase the production of foreign protein in E. coli.
Relationships among illness representations and depressive symptom severity in predominantly African-American and Caribbean-American people with epilepsy

Abstract Objective: Depression is the most common psychiatric comorbidity among people with epilepsy (PWE) and tends to be more prevalent among people of color (POC) and those with intractable seizures. However, the extent to which illness-related perceptions are associated with depressive symptom severity among POC with intractable seizures is unclear. Method: This cross-sectional study examined relationships among illness representations and self-rated depressive symptoms in 55 PWE (M Age = 41; 61.8% female) with intractable seizures (M seizures per month = 2) who identified as Black/African-American (52.7%), Black/Caribbean-American (27.3%), and/or Hispanic/Latino (21.8%). Epilepsy-related illness perceptions were assessed with the Illness Perception Questionnaire-Revised and depression was measured via the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). Results: Nearly half of the sample (41.8%) scored above the NDDI-E depression cut-off. PWE endorsing more severe depressive symptoms indicated that their epilepsy had more negative consequences, was hard to comprehend, was insufficiently controlled by treatment, and had a negative emotional impact (p’s ≤ 0.02). Controlling for sex, these four illness representations accounted for 48% of the variance in depression severity. Interestingly, participants with probable major depressive episodes were more likely to endorse several psychological causes of seizures compared to non-depressed PWE. Conclusions: Worse depression symptom severity was associated with negative illness perceptions and a tendency to attribute one’s epilepsy to psychological causes. Future research is needed to understand how the relationship between negative illness perceptions and depression symptoms unfold over time and whether interventions aimed at modifying illness representations reduce psychological distress in diverse PWE.
Theoretical model and experimental study on environmental dissipation mechanism of tapping mode atomic force microscope

The phase information reflects the energy dissipation of the probe and sample interactions in tapping mode atomic force microscopes (TM AFMs). In this paper, we use the method of tune test in TM AFM to study the contribution of external environment to energy dissipation by changing the probe position and ambient humidity. Finally, the theoretical and experimental quality factors of air viscous damping, squeeze film damping and liquid bridge force are obtained to characterise energy dissipation. The analytically predicted values of the model established on squeeze film damping, viscous damping and liquid bridge force comparing to the experimental results in this paper is rational. And the comparative analysis results show that the main mechanism of energy dissipation is different at different probe positions and different relative humidness. This result is of great significance for understanding the mechanism of phase imaging experimentally and theoretically.
Metabolomics-based predictive biomarkers of radiation injury and countermeasure efficacy: current status and future perspectives

ABSTRACT Introduction There is an urgent need for specific and sensitive bioassays to augment biodosimetric assessments of unwanted and excessive radiation exposures that originate from unexpected nuclear/radiological events, including nuclear accidents, acts of terrorism, or the use of a radiological dispersal device. If sufficiently intense, such ionizing radiation exposures are likely to impact normal metabolic processes within the cells and organs of the body, thus inducing multifaceted biological responses. Areas covered This review covers the application of metabolomics, an emerging and promising technology based on quantitative and qualitative determinations of small molecules in biological samples for the rapid assessment of an individual’s exposure to ionizing radiation. Recent advancements in the analytics of high-resolution chromatography, mass spectrometry, and bioinformatics have led to untargeted (global) and targeted (quantitative phase) approaches to identify biomarkers of radiation injury and countermeasure efficacy. Biomarkers are deemed essential for both assessing the radiation exposure levels and for extrapolative processes involved in determining scaling factors of a given radiation countering medicinal between experimental animals and humans. Expert Opinion The discipline of metabolomics appears to be highly informative in assessing radiation exposure levels and for identifying biomarkers of radiation injury and countermeasure efficacy.
The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2–infected patients by sex and age

The fact that the COVID-19 fatality rate varies by sex and age is poorly understood. Notably, the outcome of SARS-CoV-2 infections mostly depends on the control of cytokine storm and the increasingly recognized pathological role of uncontrolled neutrophil activation. Here, we used an integrative approach with publicly available RNA-Seq data sets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, according to sex and age. Female and young patients infected by SARS-CoV-2 exhibited a larger number of differentially expressed genes (DEGs) compared with male and elderly patients, indicating a stronger immune modulation. Among them, we found an association between upregulated cytokine/chemokine- and downregulated neutrophil-related DEGs. This was correlated with a closer relationship between female and young subjects, while the relationship between male and elderly patients was closer still. The association between these cytokine/chemokines and neutrophil DEGs is marked by a strongly correlated interferome network. Here, female patients exhibited reduced transcriptional levels of key proinflammatory/neutrophil-related genes, such as CXCL8 receptors (CXCR1 and CXCR2), IL-1β, S100A9, ITGAM, and DBNL, compared with male patients. These genes are well known to be protective against inflammatory damage. Therefore, our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible association between inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures.
Social aging in male and female Barbary macaques

Aging brings about notable changes in sociality, with an increasing focus on essential partners in both humans and nonhuman primates. Several studies have shown that older nonhuman primates have fewer social partners and shift their types of interactions. The majority of these studies, however, involved only female individuals. Much less is known about the trajectory of social aging in males. We collected 2180 h of focal observation data in a large age‐heterogeneous sample of 34 male and 50 female Barbary macaques (Macaca sylvanus; age range 5–30 years) living in two social groups at the outdoor enclosure at La Forêt des Singes in Rocamadour (France). To track age‐related changes in social engagement of both sexes, we used classical behavioral and social network analysis to measure age‐related variation in the number of partners, the frequency of affiliative interactions, and the position in the social network (eigenvector centrality and local clustering coefficient). We found that females were more central in most social network metrics than males, that is, had more social partners and were more engaged in affiliative interactions than males. We did not find notable sex differences with age: both sexes showed a similar decline in social activity and energy‐demanding activities like jumping or running. Our results thereby extend our knowledge of older nonhuman primates' social life and emphasize that age can have a similar impact on female and male social behavior.
Association of adenovirus 36 infection and obesity; An updated meta‐analysis of community‐based studies

As a health problem, obesity has several risk factors; it has been suggested that human adenovirus type 36 (HAdV‐36) infections may possibly be associated with obesity. This updated meta‐analysis was designed and conducted with an emphasis on articles published from 2015 to 2020. The PubMed, Web of Science, and Scopus databases were searched up to 1 December 2020. Overall, pooled prevalence and odds ratio of antibodies against HAdV‐36 in people with obesity and controls was assessed among different ages. Case‐control and cohort studies were included in the analysis. The overall prevalence of HAdV‐36 infection in obese population was 31% (CI: 0.24%–0.38%) which was 32% in cases and 27% in controls, respectively; a significant association was found between the cases and the controls (OR, 1.84; 95% CI, 1.39–2.43), especially in children younger than 18 years of age (OR, 2.44; 95% CI, 1.85–3.22). A significant association between adenovirus infection and obesity was found, especially in adolescents.
Circular RNA_0062582 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via regulation of microRNA-145/CBFB axis

ABSTRACT Osteoporosis poses a threat to human health worldwide. To date, there have been few studies regarding targeted treatment of osteoporosis. We aimed to identify the possible molecular mechanism of circular RNA (circ)_0062582 in osteogenic differentiation, and the interactions among circ_0062582, microRNA-145 (miR-145) and core-binding factor subunit β (CBFB). The proliferation of human bone marrow mesenchymal stem cells (hBMSCs) was tested with a cell counting kit-8 assay. Circ_0062582, miR-145 and CBFB were overexpressed by transient transfection. Dual-luciferase reporter assay system was used to analyze the combination among circ_0062582, miR-145 and CBFB. Additionally, the levels of circ_0062582, miR-145, CBFB, osterix (OSX), osteocalcin (OCN) and collagen type 1 (COL1) were detected by means of RT-qPCR or western blot analysis. Alkaline phosphatase and Alizarin red stainings were performed to analyze the degree of osteogenic differentiation under the control of circ_0062582, miR-145 and CBFB. The results demonstrated that circ_0062582 level was notably elvated during osteogenic differentiation of hBMSCs. Circ_0062582 overexpression significantly promoted osteogenic differentiation and upregulated the levels of osteogenic differentiation-related proteins, including OSX, OCN and COL1. In addition, miR-145, which was identified as the target gene of circ_0062582, could specifically target CBFB 3′-UTR regions. Next, these changes caused by the overexpression of circ_0062582 were reversed following the addition of miR-145 mimic. Following overexpression of CBFB, osteogenic differentiation was increased. In summary, these results demonstrated that the role of circ_0062582 in osteoporosis is mediated through regulating the expression level of CBFB via miR-145. GRAPHICAL ABSTRACT
Cardamonin Inhibited IL-1β Induced Injury by Inhibition of NLRP3 Inflammasome via Activating Nrf2/NQO-1 Signaling Pathway in Chondrocyte

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.
Periodontal Treatment Is Associated With Improvement in Gastric Helicobacter pylori Eradication: An Updated Meta-analysis of Clinical Trials

Objectives The efficacy of conventional systemic antibiotic therapy for eradication of Helicobacter pylori has been seriously challenged by antibiotic resistance. Identification of alternative therapeutic strategies might help to overcome this limitation. The aim of this study was to update previous meta-analyses that investigated the effect of periodontal treatment on gastric H. pylori eradication. Methods A systematic electronic search of the literature was conducted to identify all published clinical trials that compared the effect of adjunct periodontal treatment on conventional systemic H. pylori eradication therapy. Results The updated analysis (consisting of 541 participants representing six studies) demonstrated that, compared with conventional systemic eradication therapy alone, the addition of periodontal treatment resulted in improvements in gastric H. pylori eradication rates with OR 4.11 (P = 0.01). Moreover, not to lose any data, the previously presented Chinese results that could not be assessed by any available mechanism deduced from previously published meta-analysis and with other records were re-analysed. Similarly, the second meta-analysis adding up to a final cluster of 10 studies (909 participants) gives further credence to periodontal treatment as a useful concomitant therapy in the H. pylori eradication therapy (odds ratio [OR] = 2.65; P = 0.0002). Finally, the meta-analysis of four trials consisting of 177 cases and 161 controls showed that periodontal treatment also improved non-recurrence rates of gastric H. pylori infection, with an OR of 5.36 (P-value = 0.0002). Conclusion Although the inclusion of five additional clinical trials in this updated meta-analysis has not changed the result of the previous review, the current meta-analysis is superior for having removed one study involving the use of chlorhexidine, which did not meet appropriate criteria for inclusion. Our results strengthen the value of periodontal treatment as an adjunctive remedy. Consistency of these results suggests that the incorporation of professional periodontal treatment with systemic eradication therapy may be a wise strategy, enhancing the efficacy of H. pylori eradication therapy. Systematic review registration: in PROSPERO ID number: CRD42019119347.