Miracle-dz/UniFAR-FTUs huggingface dataset:
Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway

Background: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. Methods: Adult intestine-specific Cckbr-knockout mice (Cckbrfl/fl villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6–7 weeks) on intestinal Na+/H+ exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbrfl/fl villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbrfl/fl villin mice and SS13BN rats. We constructed gastrin-SiO2 microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation. Results: Gastrin-SiO2 microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na+/H+ exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na+/H+ exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2. Conclusions: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO2 microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects.
Transcriptome analysis of Epichloë strains in tall fescue in response to drought stress

ABSTRACT Epichloë coenophiala, a systemic fungal symbiont (endophyte) of tall fescue (Lolium arundinaceum), has been documented to confer to this grass better persistence than plants lacking the endophyte, especially under stress conditions such as drought. The response, if any, of the endophyte to imposition of stress on the host plant has not been characterized previously. Therefore, we investigated effects on gene expression by E. coenophiala and a related endophyte when plant-endophyte symbiota were subjected to acute water-deficit stress. Plants harboring different endophyte strains were grown in sand in the greenhouse, then half were deprived of water for 48 h and the other half were watered controls. RNA was isolated from different plant tissues, and mRNA sequencing (RNA-seq) was conducted to identify genes that were differentially expressed comparing stress treatment with control. We compared two different plants harboring the common toxic E. coenophiala strain (CTE) and two non–ergot-alkaloid-producing Epichloë strains in tall fescue pseudostems, and in a second experiment we compared responses of E. coenophiala CTE in plant pseudostem and crown tissues. The endophytes responded to the stress with increased expression of genes involved in oxidative stress response, oxygen radical detoxification, C-compound carbohydrate metabolism, heat shock, and cellular transport pathways. The magnitude of fungal gene responses during stress varied among plant-endophyte symbiota. Responses in pseudostems and crowns involved some common pathways as well as some tissue-specific pathways. The fungal response to water-deficit stress involved gene expression changes in similar pathways that have been documented for plant stress responses, indicating that Epichloë spp. and their host plants either coordinate stress responses or separately activate similar stress response mechanisms that work together for mutual protection.
Quasars Clustering at z ≈ 3 on Scales ≲10 h–1 Mpc

We test the hypothesis of whether high-redshift quasi-stellar objects (QSOs) would preferentially appear in small groups or pairs and whether they are associated with massive young clusters. We carried out a photometric search for Lyα emitters on scales ≲10 h-1 Mpc in the fields of a sample of 47 z ≈ 3 known QSOs. Wide and narrowband filter color-magnitude diagrams were generated for each of the 6. ′6 × 6. ′6 fields. A total of 13 nonresolved objects with a significant color excess were detected as QSO candidates at a redshift similar to that of the target. All the candidates are significantly fainter than the reference QSOs, with only two of them within 2 mag of the central object. Follow-up spectroscopic observations have shown that five, i.e., about 40% of the candidates, are QSOs at the same redshift of the target; four are QSOs at different z (two of them probably being a lensed pair at z = 1.47); two candidates are unresolved H II galaxies at z ~ 0.3; and one unclassified and one candidate turned out to be a CCD flaw. These data indicate that at least 10% of the QSOs at z ~ 3 do have companions. We have also detected a number of resolved, rather bright Lyα emitter candidates. Most likely, a large fraction of them might be bright galaxies with [O II] emission, at z ≈ 0.3. The fainter population of our candidates corresponds to the current expectations. Thus, there are no strong indications for the existence of an overdensity of Lyα galaxies brighter than m ≈ 25 around QSOs at z ≈ 3.
Staphylococcus aureus cell wall maintenance – the multifaceted roles of peptidoglycan hydrolases in bacterial growth, fitness, and virulence

Abstract Staphylococcus aureus is an important human and livestock pathogen that is well-protected against environmental insults by a thick cell wall. Accordingly, the wall is a major target of present-day antimicrobial therapy. Unfortunately, S. aureus has mastered the art of antimicrobial resistance, as underscored by the global spread of methicillin-resistant S. aureus (MRSA). The major cell wall component is peptidoglycan. Importantly, the peptidoglycan network is not only vital for cell wall function, but it also represents a bacterial Achilles’ heel. In particular, this network is continuously opened by no less than 18 different peptidoglycan hydrolases (PGHs) encoded by the S. aureus core genome, which facilitate bacterial growth and division. This focuses attention on the specific functions executed by these enzymes, their subcellular localization, their control at the transcriptional and post-transcriptional levels, their contributions to staphylococcal virulence and their overall importance in bacterial homeostasis. As highlighted in the present review, our understanding of the different aspects of PGH function in S. aureus has been substantially increased over recent years. This is important because it opens up new possibilities to exploit PGHs as innovative targets for next-generation antimicrobials, passive or active immunization strategies, or even to engineer them into effective antimicrobial agents.
Investigation of quinolone‐tethered aminoguanidine as novel antibacterial agents

A recent study identified quinolone‐based thiosemicarbazone with an MIC90 value of 2 µM against Mycobacterium tuberculosis (Mtb). Herein, we report further optimization of the previous hit, which led to the discovery of quinolone‐tethered aminoguanidine molecules with generally good antitubercular activity. Compounds 7f and 8e emerged as the hits of the series with submicromolar antitubercular activity, exhibiting MIC90 values of 0.49/0.90 and 0.49/0.60 µM, respectively, in the 7H9 CAS GLU Tx medium. This shows a fivefold increase in antitubercular activity compared to the previous study. Target compounds were also screened against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. However, the series generally exhibited poor antibacterial activities, with only compounds 8d and 8e demonstrating >50% growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa at 32 µg/ml. The compounds displayed selective antitubercular activity as they showed no cytotoxicity effects against two noncancerous human cell lines. In silico studies predict 7f to have good solubility, no inhibitory effect on cytochrome P450 isoenzymes, and to be a non‐pan‐assay interfering compound.
Attraction or Repelling Effects of Commercial Plant Essential Oils on the Synanthropic Cheiracanthium mildei (Araneae: Cheiracanthiidae)

Abstract The northern yellow sac spider Cheiracanthium mildei L. Koch, is expanding its range to Central Europe, especially to synanthropic habitats. The spiders become unwanted companions because of the unreasonable fear – arachnophobia, and estetic reason – silk retreats in corners, capturing dust. The most commonly used substances against spiders are pesticides, which are, however, toxic. In our work we tested the attraction or repellence of 15 essential oils (EO) from plants representing eight families to C. mildei. Our research has shown a significant repellent effect of EO from three plants, namely Syzygium aromaticum (L.) Merr. et L. M. Perry (Myrtales: Myrtaceae), Ananas comosus (L.) Merr. (Poales: Bromeliaceae) and Musa sp. (L.) (Zingiberales: Musaceae). In contrast, some EOs appeared to have an attraction effect, particularly Carum carvi L. (Apiales: Apiaceae). Zingiber officinale Roscoe (Zingiberales: Zingiberaceae) reduced the tendency of spiders to construct the silken retreat. S. aromaticum, A. sativus, Musa sp. and Z. officinale have the potential to be used as natural repellents against spiders. Graphical Abstract
Comprehensive analysis of the expression and prognosis of YPEL family members in clear cell renal cell cancer

The Yippee-like (YPEL) gene family is composed of five members encoding a protein containing a zinc finger-like metal-binding domain. Due to its structure and location in cells, this domain is considered to be involved in cell multiplication and numerous types of cancer. However, the relationship between the protein and the prognosis of clear cell renal cell carcinoma (ccRCC) remains unknown. In the present study, using pan-cancer data from the updated public database, the expression and correlation of YPEL genes in 33 types of cancer was systematically and comprehensively analyzed. The prognostic value of YPEL genes was evaluated by survival and Cox regression analysis. Considering the relationship between the tumor microenvironment and stem cell indices, the function of superoxide dismutase was evaluated. Tumor Immune Assessment Resources (TIMER) and CIBERSORT algorithm analysis were used to evaluate the correlation between YPEL genes and tumor immune infiltrating cells (TIICs). Furthermore, knockdown experiments of YPEL genes were developed to explore their effects on ccRCC cell proliferation, migration and invasion in ccRCC cell lines. Members of the YPEL family were differentially expressed in ccRCC. Increased expression levels of YPEL1, YPEL2, and YPEL5 were associated with improved overall survival and disease-specific survival. TIMER and CIBERSORT analyses showed remarkable correlation between YPEL family members and TIICs. More importantly, the results of Cell Counting Kit-8, EdU and Transwell assays revealed that the multiplication, migration and invasion abilities of ccRCC cell lines could be promoted by knocking out YPEL1, YPEL2 and YPEL5. In conclusion, the present study provided new insight into the different roles of YPEL1, YPEL2 and YPEL5 in ccRCC, and the relationship between YPEL1 and immune infiltration may offer new options for future clinical treatment.
Monocyte-to-lymphocyte ratio: a potential novel predictor for acute kidney injury in the intensive care unit

Abstract Monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) are considered as surrogate inflammatory indexes. Previous studies indicated that NLR was associated with the development of septic acute kidney injury (AKI). The objective of the present study was to explore the value of MLR and NLR in the occurrence of AKI in intensive care unit (ICU) patients. The clinical details of adult patients (n = 1500) who were admitted to the ICU from January 2016 to December 2019 were retrospectively examined. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. The development of AKI was the main outcome, and the secondary outcome was in-hospital mortality. Overall, 615 (41%) patients were diagnosed with AKI. Both MLR and NLR were positively correlated with AKI incidence (p < 0.001). Multivariate logistic regression analysis suggested that the risk value of MLR for the occurrence of AKI was nearly three-fold higher than NLR (OR = 3.904, 95% CI: 1.623‒9.391 vs. OR = 1.161, 95% CI: 1.135‒1.187, p < 0.001). The areas under the receiver operating characteristic curve (AUC) for MLR and NLR in the prediction of AKI incidence were 0.899 (95% CI: 0.881‒0.917) and 0.780 (95% CI: 0.755‒0.804) (all p < 0.001), with cutoff values of 0.693 and 12.4. However, the AUC of MLR and NLR in the prediction of in-hospital mortality was 0.583 (95% CI: 0.546‒0.620, p < 0.001) and 0.564 (95% CI: 0.528‒0.601, p = 0.001). MLR, an inexpensive and widely available parameter, is a reliable biomarker in predicting the occurrence of AKI in ICU patients.
Time-dependent seismic fragility curves for aging jacket-type offshore platforms subjected to earthquake ground motions

Abstract This paper assesses the seismic vulnerability of a recently designed jacket-type offshore platform through development of fragility curves and presents the formulation of time-dependent seismic fragility curves to capture the effects of ageing and deterioration on the seismic vulnerability of the representative platform. Among the various ageing processes, the corrosion deterioration of the structure is taken into account by applying a time-dependent model of corrosion deterioration of the tubular elements in the splash zone. Incremental dynamic analysis is performed on the initial uncorroded and corroded platforms considering soil–pile–structure interaction. A full probabilistic analysis is then performed to develop time-dependent seismic fragility curves for the immediate occupancy and collapse prevention limit states. Finally, a time variant cubic model is proposed to develop fragility curves at any point in time during platform’s service life, without need to perform a complete time-consuming fragility analyses. Results show substantial increase in probability of failure of the platform throughout its lifetime due to corrosion deterioration. The results also indicate that the time-dependent fragility curves can be used in offshore platforms to assess the seismic vulnerability of the structure and demonstrate the influence of various factors affecting the seismic vulnerability of the platform during its lifetime.
Genome architecture used to supplement species delineation in two cryptic marine ciliates

The purpose of this study is to determine which taxonomic methods can elucidate clear and quantifiable differences between two cryptic ciliate species, and to test the utility of genome architecture as a new diagnostic character in the discrimination of otherwise indistinguishable taxa. Two cryptic tintinnid ciliates, Schmidingerella arcuata and Schmidingerella meunieri, are compared via traditional taxonomic characters including lorica morphometrics, ribosomal RNA (rRNA) gene barcodes and ecophysiological traits. In addition, single‐cell ‘omics analyses (single‐cell transcriptomics and genomics) are used to elucidate and compare patterns of micronuclear genome architecture between the congeners. The results include a highly similar lorica that is larger in S. meunieri, a 0%–0.5% difference in rRNA gene barcodes, two different and nine indistinguishable growth responses among 11 prey treatments, and distinct patterns of micronuclear genomic architecture for genes detected in both ciliates. Together, these results indicate that while minor differences exist between S. arcuata and S. meunieri in common indices of taxonomic identification (i.e., lorica morphology, DNA barcode sequences and ecophysiology), differences exist in their genomic architecture, which suggests potential genetic incompatibility. Different patterns of micronuclear architecture in genes shared by both isolates also enable the design of species‐specific primers, which are used in this study as unique “architectural barcodes” to demonstrate the co‐occurrence of both ciliates in samples collected from a NW Atlantic estuary. These results support the utility of genomic architecture as a tool in species delineation, especially in ciliates that are cryptic or otherwise difficult to differentiate using traditional methods of identification.
Sex disparities and the risk of urolithiasis: a large cross-sectional study

Abstract Background Urolithiasis is one of the most common diseases in urology, with a lifetime prevalence of 14% and is more prevalent in males compared to females. We designed to explore sex disparities in the Chinese population to provide evidence for prevention measures and mechanisms of stone formation. Materials and methods A total of 98232 Chinese individuals who had undergone a comprehensive examination in 2017 were included. Fully adjusted odds ratios for kidney stones were measured using restricted cubic splines. Multiple imputations was applied for missing values. Propensity score matching was utilised for sensitivity analysis. Results Among the 98232 included participants, 42762 participants (43.53%) were females and 55470 participants (56.47%) were males. Patients’ factors might cast an influence on the development of kidney stone disease distinctly between the two genders. A risk factor for one gender might have no effect on the other gender. The risk for urolithiasis in females continuously rises as ageing, while for males the risk presents a trend to ascend until the age of around 53 and then descend. Conclusions Patients’ factors might influence the development of kidney stones distinctly between the two genders. As age grew, the risk to develop kidney stones in females continuously ascended, while the risk in males presented a trend to ascend and then descend, which was presumably related to the weakening of the androgen signals. Key messages We found that patients’ factors might cast an influence on the development of kidney stone disease distinctly between the two sexes. The association between age and urolithiasis presents distinct trends in the two sexes The results will provide evidence to explore the mechanisms underlying such differences can cast light on potential therapeutic targets and promote the development of tailored therapy strategies in prospect.
Determinants of Stress, Depression, Quality of Life, and Intent to Leave in Washington State Emergency Medical Technicians During COVID-19

Through a survey of emergency medical technicians in the Puget Sound region of Washington, we found that 67.5% of respondents reported high stress, and 35.0% had scores indicating that major depressive disorder was likely. Job demands were significantly associated with both stress and depression. Objectives This study characterizes determinants of stress, depression, quality of life, and intent to leave among emergency medical technicians (EMTs) in the Puget Sound region, Washington, during the COVID-19 pandemic and identifies areas for intervention on these outcomes. Methods A cross-sectional survey measured stress, depression, quality of life, and intent to leave among EMTs (N = 123). Regression models were developed for these outcomes. Results A total of 23.8% of respondents were very likely to leave their position in the next 6 months. Job demands predicted stress and depression, and financial security predicted stress and quality of life. Intent to leave was predicted by stress, manager support, and length of employment. Conclusions Increased exposure to hazards has impacted EMT mental health. Emergency medical technicians are vital to healthcare, so improving EMT health and well-being is important, as attrition during a pandemic could impact public health.
The visual computation of bounding contours

The problem of computing closed bounding contours from a visual image is addressed. The approach is motivated by the fact that many important image structures are heterogeneous and therefore cannot be segmented by traditional region-based methods based on homogeneity or smoothness constraints. Both psychophysical and computational aspects of the problem are studied. Psychophysical evidence is presented which shows that properties of bounding contour such as closure act as binding features for the segmentation of 2-D shapes, whereas texture (a region property) does not. These psychological results motivate an investigation of local and global issues in the computation of bounding contours for the purpose of figure/ground segmentation. Novel techniques for the local analysis of contour are presented which allow edges to be reliably detected and localized over a broad range of blur scale and contrast in images with shallow depth-of-field and shadows. Local estimates of contour blur are shown to be useful for computing depth segmentation from focal blur in complex images where the continuity assumptions required by existing Fourier techniques do not apply. It is hypothesized that in order to integrate contours fragmented by occlusion and insufficient contrast, the human visual system exploits a measure of geometric contour closure. The results of psychophysical experiments show that a measure for closure based on $L\sb2$ norm of contour gaps in psychophysically consistent. The existence of this measure is evidence for the computation of geometric closure by the human visual system. These psychophysical findings motivate an algorithm for computing closed bounding contours as cycles of curve tangents. Tangent cycles extracted from a variety of real images are shown to correspond to the bounding contours of 2-D image structures, many of which are heterogeneous over their interior. Thus closure computations are seen to complement region-grouping methods by extending the class of structures which may be segmented to include heterogeneous image structures.
SiO 2 and ZnO Dopants in 3D Printed TCP Scaffolds Enhances Osteogenesis and Angiogenesis in vivo

Calcium phosphate (CaP) scaffolds with three dimensionally (3D) interconnected pores play an important role in mechanical interlocking and biological fixation in bone implant applications. CaPs alone, however, are only osteoconductive (ability to guide bone growth). Much attention has been given to the incorporation of biologics and pharmacologics to add osteoinductive (ability to cause new bone growth) properties to CaP materials. Because biologics and pharmacologics are generally delicate compounds and also subject to increased regulatory scrutiny, there is a need to investigate alternative methods to introduce osteoinductivity to CaP materials. In this study silica (SiO 2 ) and zinc oxide (ZnO) have been incorporated in to 3D printed β -tricalcium phosphate (TCP) scaffolds to investigate their potential to trigger osteoinduction in vivo. Silicon and zinc are trace elements that are common to bone and have also been shown to have many beneficial properties from increased bone regeneration to angiogenesis. Implants were placed in bicortical femur defects introduced to a murine model for up to 16 weeks. Addition of dopants into TCP increased the capacity for new early bone formation by modulating collagen I production and osteocalcin production. Neovascularization was found to be up to three times more than the pure TCP control group. The findings from this study indicate that the combination of SiO 2 and ZnO dopants in TCP may be a viable alternative to introduce osteoinductive properties to CaPs.