Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and functional insights into a novel two-component endolysin encoded by a single gene in Enterococcus faecalis phage

Using bacteriophage-derived endolysins as an alternative strategy for fighting drug-resistant bacteria has recently been garnering renewed interest. However, their application is still hindered by their narrow spectra of activity. In our previous work, we demonstrated that the endolysin LysIME-EF1 possesses efficient bactericidal activity against multiple strains of Enterococcus faecalis (E. faecalis). Herein, we observed an 8 kDa fragment and hypothesized that it contributes to LysIME-EF1 lytic activity. To examine our hypothesis, we determined the structure of LysIME-EF1 at 1.75 Å resolution. LysIME-EF1 exhibits a unique architecture in which one full-length LysIME-EF1 forms a tetramer with three additional C-terminal cell-wall binding domains (CBDs) that correspond to the abovementioned 8 kDa fragment. Furthermore, we identified an internal ribosomal binding site (RBS) and alternative start codon within LysIME-EF1 gene, which are demonstrated to be responsible for the translation of the truncated CBD. To elucidate the molecular mechanism for the lytic activity of LysIME-EF1, we combined mutagenesis, lytic activity assays and in vivo animal infection experiments. The results confirmed that the additional LysIME-EF1 CBDs are important for LysIME-EF1 architecture and its lytic activity. To our knowledge, this is the first determined structure of multimeric endolysin encoded by a single gene in E. faecalis phages. As such, it may provide valuable insights into designing potent endolysins against the opportunistic pathogen E. faecalis.
Integrative genomic analyses identify WDR12 as a novel oncogene involved in glioblastoma

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease‐free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene‐chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM.
Determination of Submaximal and Maximal Training Zones From a 3-Stage, Variable-Duration, Perceptually Regulated Track Test.

PURPOSE To validate a new perceptually regulated, self-paced maximal oxygen consumption field test (the Running Advisor Billat Training [RABIT] test) that can be used by recreational runners to define personalized training zones. DESIGN In a cross-sectional study, male and female recreational runners (N = 12; mean [SD] age = 43 [8] y) completed 3 maximal exercise tests (2 RABIT tests and a University of Montreal Track Test), with a 48-hour interval between tests. METHODS The University of Montreal Track Test was a continuous, incremental track test with a 0.5-km·h-1 increment every minute until exhaustion. The RABIT tests were conducted at intensities of 11, 14, and 17 on the rating of perceived exertion (RPE) scale for 10, 5, and 3 minutes, respectively, with a 1-minute rest between efforts. RESULTS The 2 RABIT tests and the University of Montreal Track Test gave similar mean (SD) maximal oxygen consumption values (53.9 [6.4], 56.4 [9.1], and 55.4 [7.6] mL·kg-1·min-1, respectively, P = .722). The cardiorespiratory and speed responses were reliable as a function of the running intensity (RPE: 11, 14, and 17) and the relative time point for each RPE stage. Indeed, the oxygen consumption, heart rate, ventilation, and speed values did not differ significantly when the running time was expressed as a relative duration of 30%, 60%, or 90% (ie, at 3, 6, and 9 min of a 10-min effort at RPE 11; P = .997). CONCLUSIONS The results demonstrate that the RABIT test is a valid method for defining submaximal and maximal training zones in recreational runners.
RNA sequencing analysis of long non-coding RNA expression in ocular posterior poles of guinea pig myopia models

Purpose To detect the differential expression of long non-coding RNAs (lncRNAs) in the ocular posterior poles of two guinea pig myopia models and explore the pathogenic role of lncRNAs in myopia. Methods Form-deprived myopia (FDM) and lens-induced myopia (LIM) models were induced in guinea pig right eyes by wearing a translucent latex balloon head mask and a −10.00 diopter (D) lens, respectively. Ocular biometric parameters were measured biweekly. At 6 weeks after the induction of myopia, the guinea pig eyeballs were processed for hematoxylin and eosin staining to examine the ocular morphology. The ocular posterior poles from the normal control, FDM, and LIM groups were collected to analyze the differential expression of lncRNAs between the groups with high-throughput RNA sequencing (RNA-seq). Further, the lncRNA-mRNA colocation network was delineated to predict the functions of the differentially expressed lncRNAs. Last, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the colocated mRNAs of the differentially expressed lncRNAs. Additionally, the expression of the most differentially expressed lncRNAs in the myopia-induced eyes and the contralateral eyes was validated with quantitative real-time PCR (qPCR). Results Compared with the normal controls and the contralateral eyes, the myopia-induced eyes in the FDM and LIM groups exhibited decreased scleral and choroidal thicknesses, reduced refraction, and increased ocular axial length but without changes in the corneal curvature radius at 6 weeks after myopia was induced. RNA-seq showed that 372 and 247 lncRNAs were differentially expressed in the FDM and LIM groups, respectively, in comparison to the normal counterparts. There were 380 differentially expressed lncRNAs in the LIM group compared to the FDM group. The GO and KEGG analyses showed that the colocated mRNAs of the differentially expressed lncRNAs were enriched in cellular components such as the extracellular matrix (ECM) structural constituent; in molecular functions such as kinase activity, metabolism, and growth; as well as in pathways including ECM-receptor interaction, glycosaminoglycan degradation, and mucin type O-Glycan biosynthesis. The expression patterns of the selected lncRNAs were verified with qPCR. Conclusions High-throughput RNA-seq revealed previously undescribed lncRNA expression profiling in guinea pig FDM and LIM models. These results may shed light on the molecular pathogenesis of myopia and provide clues for interventional targets for this highly prevalent visual disorder.
Evaluating the repellent effect of four botanicals against two Bactrocera species on mangoes

Background Bactrocera dorsalis and B. correcta are economically important fruit fly pests of crops, vegetables, fruits, and nuts worldwide, especially in China. Nowadays in China, B. correcta is a second notorious pest of many fruits after B. dorsalis. Different botanicals have been tested against the B. dorsalis but in the case of B. correcta, no records were published. Methodology This study evaluated the repellency of four botanicals (Seriphidium brevifolium, Piper nigrum, Azadirachta indica and quercetin) in acetone dilutions (5%, 2.5% and 1%) against the B. dorsalis and B. correcta at the laboratory conditions (25 ± 2 °C, 60 ± 5% relative humidity, and a photoperiod of L:D 14:10 h). Results The number of visits after 24–48 h, oviposition punctures, and pupae made by both species were lower on the treated mangoes in comparison to untreated mangoes. S. brevifolium, P. nigrum, A. indica and quercetin have significantly reduced the visits, ovipositional punctures, and pupae of both species. Among botanicals, the P. nigrum was the most effective repellent against B. correcta and as well as B. dorsalis. However, the harmful effects of these botanicals against natural enemies are still unknown.
Dihydroartemisinin Prevents Distant Metastasis of Laryngeal Carcinoma by Inactivating STAT3 in Cancer Stem Cells

Background Accumulating evidence indicates that cancer stem cells (CSCs) are a minor subpopulation of cancer cells that may be the primary source of cancer invasion, migration, and widespread metastasis. Material/Methods We investigated the effects of dihydroartemisinin (DHA) on distant metastasis of laryngeal carcinoma and the relevant mechanism. In vitro, we used the Hep-2 human laryngeal squamous carcinoma cell line (Hep-2 cells) to assemble CSCs, using CD133 as the cell surface marker. Our data demonstrate that the CD133+ subpopulation of Hep-2 cells has greater invasion and migration capabilities than CD133− cells. We also evaluated the effects of DHA, a newly defined STAT3 inhibitor, on the invasion and migration of CD133+ Hep-2 cells under hypoxia and IL-6 stimulation, both of which can activate STAT3 phosphorylation. Results CSCs exhibited a significant decrease in the ability of migration and invasion upon the application of DHA, along with simultaneous alterations in related proteins, both in cultured cells and in xenograft tumors. The associated signaling proteins included phosphorylated STAT3 (p-STAT3), matrix metalloproteinase-9 (MMP-9), and E-cadherin, which are closely involved in cancer invasion and metastasis. In vivo, we found that DHA can reduce lung metastasis formation caused by CSCs and prolong survival in mice, and can inhibit STAT3 activation, downregulate MMP-9, and upregulate E-cadherin in lung metastatic tumors. Conclusions Taken together, our findings indicate that CSCs possess stronger invasive and metastatic capabilities than non-CSCs, and DHA inhibits invasion and prevents metastasis induced by CSCs by inhibiting STAT3 activation.
Interest in HIV pre-exposure prophylaxis (PrEP) among adolescents and their caregivers in Malawi

ABSTRACT Over a third of new HIV infections occur in adolescents aged 10–19 globally. Pre-exposure prophylaxis (PrEP) could be a powerful tool for prevention. Understanding more about the drivers of PrEP interest could inform implementation strategies among this age group. Moreover, family dynamics may play a uniquely critical role for this younger age group, thus it is important to gauge whether caregivers would support their children’s use of PrEP. We surveyed 2,089 adolescents (aged 10–16) and their caregivers in Malawi during 2017–2018. Data were collected on PrEP interest, factors that may facilitate PrEP use, and preferences for PrEP modality. We used multivariate logistic regression to estimate the association between the above characteristics and PrEP interest. We find that young adolescents are engaging in behaviors that would put them at substantial risk of acquiring HIV, would likely benefit from PrEP, are largely (82%) interested in using such, would prefer to get an injection over taking a daily pill, and are considerably discouraged by the prospect of side effects. Endorsement by caregivers was even greater (87%). Our findings demonstrate initial support for adolescent PrEP, and suggest parents may be a surprising advocate.
Activated pathogenic Th17 lymphocytes induce hypertension following high-fructose intake in Dahl salt-sensitive but not Dahl salt-resistant rats

ABSTRACT High-salt intake and high-fructose intake are risk factors for hypertension via oxidative stress and inflammation. T helper (Th)17 lymphocytes play an important role in the development of hypertension. Here, we tested the hypothesis that activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in Dahl salt-sensitive (SS) but not Dahl salt-resistant (SR) rats. Eight-week-old male SS and SR rats were offered 20% fructose solution or tap water only for 4 weeks. Systolic blood pressure was measured by the tail-cuff method. T lymphocyte [Th17 and T regulatory (Treg)] profiling was determined via flow cytometry. The expression of Th17-related (IL-17A, IL-17RA, IL-23R and RORγt) and Treg-related (IL-10, CD25, FOXP3 and TGFβ) factors were measured via ELISA or qRT-PCR. Th17 lymphocytes isolated from high-fructose-fed SS rats were intraperitoneally injected into recipient SS and SR rats, and recombinant IL-23 protein was subcutaneously injected into SS and SR rats to induce hypertension. High-fructose intake induced hypertension via the activation of pathogenic Th17 lymphocytes in SS but not SR rats. Injection of activated Th17 lymphocytes isolated from fructose-fed SS rats induced hypertension via increase of serum IL-17A only in recipient SS rats. In addition, injection of IL-23 induced hypertension via activation of pathogenic Th17 lymphocytes only in SS rats. Thus, activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in SS but not SR rats. These results indicate that immunologic tolerance plays an important role in protection against hypertension in SR rats. Summary: Activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in salt-sensitive rats. Immune activation plays an important role in the development of hypertension, whereas immune tolerance is protective against hypertension.
Curing Kinetics and Thermal Stability of Epoxy Composites Containing Newly Obtained Nano-Scale Aluminum Hypophosphite (AlPO2)

For the first time, nano-scale aluminum hypophosphite (AlPO2) was simply obtained in a two-step milling process and applied in preparation of epoxy nanocomposites varying concentration (0.1, 0.3, and 0.5 wt.% based on resin weight). Studying the cure kinetics and thermal stability of these nanocomposites would pave the way toward the design of high-performance nanocomposites for special applications. Scanning electron microscopy (SEM) and transmittance electron microscopy (TEM) revealed AlPO2 particles having domains less than 60 nm with high potential for agglomeration. Excellent (at heating rate of 5 °C/min) and Good (at heating rates of 10, 15 and 20 °C/min) cure states were detected for nanocomposites under nonisothermal differential scanning calorimetry (DSC). While the dimensionless curing temperature interval (ΔT*) was almost equal for epoxy/AlPO2 nanocomposites, dimensionless heat release (ΔH*) changed by densification of polymeric network. Quantitative cure analysis based on isoconversional Friedman and Kissinger methods gave rise to the kinetic parameters such as activation energy and the order of reaction as well as frequency factor. Variation of glass transition temperature (Tg) was monitored to explain the molecular interaction in the system, where Tg increased from 73.2 °C for neat epoxy to just 79.5 °C for the system containing 0.1 wt. % AlPO2. Moreover, thermogravimetric analysis (TGA) showed that nanocomposites were thermally stable.
The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein

Enterohepatic Helicobacters, such as Helicobacter hepaticus and Helicobacter pullorum, are associated with several intestinal and hepatic diseases. Their main virulence factor is the cytolethal distending toxin (CDT). In the present study, whole genome microarray-based identification of differentially expressed genes was performed in vitro in HT-29 intestinal cells while following the ectopic expression of the active CdtB subunit of H. hepaticus CDT. A CdtB-dependent upregulation of the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene encoding the MAFB oncoprotein was found, as well as the CdtB-dependent regulation of several MAFB target genes. The transduction and coculture experiments confirmed MAFB mRNA and protein induction in response to CDT and its CdtB subunit in intestinal and hepatic cell lines. An analysis of MAFB protein subcellular localization revealed a strong nuclear and perinuclear localization in the CdtB-distended nuclei in intestinal and hepatic cells. MAFB was also detected at the cell periphery of the CdtB-induced lamellipodia in some cells. The silencing of MAFB changed the cellular response to CDT with the formation of narrower lamellipodia, a reduction of the increase in nucleus size, and the formation of less γH2AX foci, the biomarker for DNA double-strand breaks. Taken together, these data show that the CDT of enterohepatic Helicobacters modulates the expression of the MAFB oncoprotein, which is translocated in the nucleus and is associated with the remodeling of the nuclei and actin cytoskeleton.
Oxidized Products of Omega-6 and Omega-3 Long Chain Fatty Acids Are Associated with Increased White Matter Hyperintensity and Poorer Executive Function Performance in a Cohort of Cognitively Normal Hypertensive Older Adults.

BACKGROUND Cerebrovascular disease is a common cause of dementia in older adults, and potentially preventable with early intervention. Oxylipins are produced from the oxidation of long-chain polyunsaturated fatty acids (PUFA) possessing potent vascular effects. Oxylipins generated from the cytochrome P450 pathway are enzymatically converted to diols by soluble epoxide hydrolase (sEH); sEH products have been associated with small vessel ischemic disease. Little is known about oxylipins' impact on markers of dementia risk. OBJECTIVE An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition. METHODS Thirty-seven non-demented participants with controlled hypertension (mean age 65.6 years) were enrolled in a dementia prevention study investigating fish oil and lipoic acid on preserving cognitive function. Baseline associations between plasma oxylipins, white matter hyperintensity (WMH), and Trails-B were examined using linear regression. P450-derived diol/epoxide ratio was an indirect measure of sEH activity. RESULTS Omega-6 derived 9-HODE was associated with increased WMH (p = 0.017) and reduced grey matter volume (p = 0.02). Omega-6 P450-derived diol/epoxide ratio 9,10-DiHOME/9,10-EpOME was associated with increased WMH (p = 0.035) and poorer performance on Trails-B (p = 0.05); ratio14,15-DHET/14,15-EET was associated with increased WMH (p = 0.045). Omega-3 P450-derived diol/epoxide ratio 19,20-DiHDPE/19,20-EpDPE was associated with increased WMH (p = 0.04) and poorer performance on Trails-B (p = 0.04). Arachidonic acid was associated with better performance on Trails-B (p = 0.012); Omega-3 derived 16,17-EpDPE was associated with decreased WMH (p = 0.005). CONCLUSIONS With the exception of arachidonic acid, it was specific oxylipin products, not their parent PUFAs, that were associated with unfavorable and favorable MRI and cognitive markers of dementia risk.
Fasting blood glucose and cerebrospinal fluid Alzheimer’s biomarkers in non-diabetic cognitively normal elders: the CABLE study

It is unclear how blood glucose levels mediate the pathology of Alzheimer's disease (AD). This study aimed to investigate whether fasting blood glucose (FBG) levels are associated with cerebrospinal fluid (CSF) biomarkers preferentially affected by AD in non-diabetic cognitively normal elders. A total of 499 non-diabetic cognitively normal elders were from the Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study. We detected the associations of FBG with individual CSF measures using multiple linear regression models controlling for age, sex, educational level, and apolipoprotein E (APOE) ε4 genotype. Fasting blood glucose level was positively correlated with CSF Aβ42 level (β = 0.045, p = 0.010), CSF Aβ42/Aβ40 ratio (β = 0.005, p < 0.001), Aβ42/P-tau ratio (β = 0.282, p = 0.013), and Aβ42/T-tau ratio (β = 0.050, p = 0.040). Interaction analysis indicated that gender affected the correlations of FBG level with CSF Aβ40 (p < 0.001) and Aβ42/Aβ40 ratio (p < 0.001). This study raises additional questions about the role of blood glucose in the predisposition to AD and supports the possibility of targeting these processes in pre-symptomatic AD trials in non-diabetic elders.
High Serum Phosphate Level as a Risk Factor to Determine Renal Prognosis in Autosomal Dominant Polycystic Kidney Disease: A Retrospective Study

Background: Serum phosphate levels, which are associated with the progression of renal dysfunction in chronic kidney disease, in patients with autosomal dominant polycystic kidney disease (ADPKD) are lower than those in patients with other kidney diseases. However, their role in ADPKD remains unclear. This study aimed to determine whether serum phosphate levels could have an association with renal prognoses among patients with ADPKD. Methods: In total, 55 patients with PKD1 or PKD2 mutations but not undergoing dialysis were evaluated. Data regarding serum phosphate levels were collected, and Cox regression analyses were used to calculate hazard ratios (HRs) with renal replacement therapy as the endpoint. Results: The median (quartile 1; quartile 3) serum phosphate concentration was 3.4 (3.1; 3.9) mg/dL, and the estimated glomerular filtration rate (eGFR) was 39.5 (17.6; 65.7) mL/min/1.73 m2. The multivariate analysis that included age, PKD1 mutation, eGFR, urinary protein excretion, hyperuricemia, and serum phosphate determined that eGFR (HR, 0.82; 95% confidence interval (CI), 0.74–0.90; p < 0.0001) and serum phosphate (HR, 6.78; 95% CI, 1.94–34.02; p = 0.0021) were independently associated with renal replacement therapy. Conclusions: We found that serum phosphate levels were significantly associated with poor renal prognoses in patients with ADPKD.
Measurement of Multi Ion Transport through Human Bronchial Epithelial Cell Line Provides an Insight into the Mechanism of Defective Water Transport in Cystic Fibrosis

We measured concentration changes of sodium, potassium, chloride ions, pH and the transepithelial potential difference by means of ion-selective electrodes, which were placed on both sides of a human bronchial epithelial 16HBE14σ cell line grown on a porous support in the presence of ion channel blockers. We found that, in the isosmotic transepithelial concentration gradient of either sodium or chloride ions, there is an electroneutral transport of the isosmotic solution of sodium chloride in both directions across the cell monolayer. The transepithelial potential difference is below 3 mV. Potassium and pH change plays a minor role in ion transport. Based on our measurements, we hypothesize that in a healthy bronchial epithelium, there is a dynamic balance between water absorption and secretion. Water absorption is caused by the action of two exchangers, Na/H and Cl/HCO3, secreting weakly dissociated carbonic acid in exchange for well dissociated NaCl and water. The water secretion phase is triggered by an apical low volume-dependent factor opening the Cystic Fibrosis Transmembrane Regulator CFTR channel and secreting anions that are accompanied by paracellular sodium and water transport.