Miracle-dz/UniFAR-FTUs huggingface dataset:
Calycosin Alleviates Injury in Airway Epithelial Cells Caused by PM 2.5 Exposure via Activation of AMPK Signalling

Methods Phospho-AMP-activated protein kinase (p-AMPK) and AMP-activated protein kinase (AMPK) were detected by western blot. Immunofluorescence staining was used to validate changes in the levels of nuclear factor kappa B (NF-кB) p65 nuclear translocation. Mice were administered intraperitoneally with calycosin one hour before anaesthesia and endotracheal instillation of PM 2.5. The extent of lung injury was evaluated in the H&E-stained lung sections. Apoptotic cells were detected by TUNEL staining. Results Administration of calycosin was increased in PM 2.5-treated B2B cells in a dose-dependent manner in vitro. Fluorescence signals from anti-NF-кB p65 were increased in nuclei of cells pretreated with calycosin. The level of p-AMPK was increased by calycosin in vitro and in vivo. After pretreatment with compound C, the inhibitory effects of calycosin on cytotoxicity, levels of inflammatory cytokines and p-AMPK, and levels of NF-кB p65 nuclear translocation were not significantly decreased in vitro or in vivo. Conclusions Calycosin effectively decreased the release of inflammatory cytokines and alleviated injury caused by PM 2.5. These effects were mediated through activation of AMPK to suppress NF-κB signalling.
Feasibility and Effectiveness of a Motion Tracking-Based Online Fitness Program for Office Workers

The development of technology-based home fitness has emerged from the booming digital healthcare market and recent demands for at-home fitness and health equipment due to the COVID-19 pandemic. Digital healthcare company Alyce Healthcare recently developed Weelo, which is a web-based online fitness program. Weelo recommends an exercise protocol through machine-learning-enabled recognition of the user’s motion and provides visual and auditory feedback. We evaluated whether Weelo improves physical and mental well-being to assess its capabilities and effectiveness. Thirty-two participants performed a total of 20 exercise sessions following the Weelo guide on a laptop. The participants were evaluated using a before and after exercise program, body composition, handgrip strength, six-minute walk test, modified star excursion balance test, short form 36, fatigue severity scale, Beck depression index, and a satisfaction survey. Overall, there was a significant improvement in muscle strength, endurance, and balance ability, as well as an improved quality of life and significant reduction in fatigue and depression. Participants showed high motivation to continue following the Weelo exercise program. In conclusion, utilizing Weelo improved physical and mental well-being and is considered to be an individual-use indoor exercise program that serves as an alternative to traditional face-to-face exercise.
Glaucoma Progression after Delivery in Patients with Open-Angle Glaucoma Who Discontinued Glaucoma Medication during Pregnancy

In this retrospective study, clinical characteristics and glaucoma progression of open-angle glaucoma (OAG) patients who discontinued intraocular pressure (IOP)-lowering medication during pregnancy were investigated. Glaucoma progression was determined using either serial visual field tests or optic disc/retinal nerve fiber layer (RNFL) photographs. Age, number of previous pregnancies, diagnosis, average IOP, IOP fluctuation, visual field mean deviation, pattern standard deviation, and RNFL thickness were examined, and their association with glaucoma progression was determined using linear regression analysis. Among 67 eyes (37 patients), 19 eyes (28.4%) exhibited glaucoma progression 13.95 ± 2.42 months after delivery. The progression group showed significantly higher mean IOP than the nonprogression group in the first, second, and third trimesters (p = 0.02, 0.001, and 0.04, respectively). The average IOP in the second, and third trimesters and IOP fluctuation during the entire pregnancy were significantly associated with glaucoma progression according to a univariate analysis (p = 0.04, 0.031, and 0.026, respectively). In conclusion, IOP elevation during pregnancy is associated with glaucoma progression after delivery in patients who had discontinued medication during pregnancy. Therefore, close monitoring of glaucoma is necessary, particularly if patients discontinue medication during pregnancy, and appropriate intervention should be considered in case of increased IOP.
The Impacts of Woolly Cupgrass on the Antioxidative System and Growth of a Maize Hybrid

Woolly cupgrass (Eriochloa villosa (Thunb.) Kunth) is a new invasive weed in Hungary. This study was conducted to elucidate the effects of this weed on the biochemistry and growth of maize (Zea mays L. cv. Armagnac) under greenhouse conditions. Activities of the antioxidative enzymes (ascorbate peroxidase (APX), guaiacol peroxidase (POD), superoxide dismutase (SOD)), the contents of malondialdehyde (MDA), and protein were measured in the shoots and roots, whereas the content of the photosynthetic pigments was measured only in the shoots. The measured growth parameters included plant height, root length, root volume, root and shoot dry weight, and stem diameter. Results showed the allelopathic effects of woolly cupgrass on maize, with significant decreases in plant height, root length, root volume, and root dry weight. Woolly cupgrass infestation (WCI) induced significantly higher activities of APX and SOD in the shoots, whereas POD was only induced in the roots. The contents of chlorophyll-a, total chlorophyll (including relative chlorophyll), carotenoids, and root protein were substantially reduced by WCI, except for the leaf chlorophyll-b. The results suggest that high APX and SOD activities in the shoots could be involved in stabilizing the leaf chlorophyll-b, chlorophyll a/b, shoot protein, and shoot dry weight because all of these parameters were not inhibited when these two enzymes were induced. In contrast, high activity of POD in the roots is not effective in counteracting allelopathy. Therefore, it would be worthwhile to further investigate if an increase in the activities of APX and SOD in the shoots of WCI maize is responsible for stabilizing leaf chlorophyll-b, shoot protein, and shoot dry weight, which could contribute to improved maize yield under WCI.
A People-Counting and Speed-Estimation System Using Wi-Fi Signals

Counting the number of people and estimating their walking speeds are essential in crowd control and flow. In this work, we propose a system that uses prevalent Wi-Fi signals to identify the number of people entering and leaving a room through a door. It selects the best subcarrier of Wi-Fi signals and applies the Hampel filter to remove outlier information first. Then, it employs a double threshold method to determine the start and end times of entering or leaving. Afterward, it compares the detected signals with the precollected database using the dynamic time-warping algorithm and determines the number of people. It uses a variance threshold method to identify the states of entering or leaving. It also employs a nonlinear fitting approach to calculate the walking speeds. The experiments show that, in a large empty laboratory, the accuracy rates in determining the number of people are 100% for one person, 81% for two persons, and 95% for three persons. In a small office, the accuracy rates for detecting the number of people are 98% for one or two persons, 82% for three persons, 93% for four, and 75% for five persons. For the walking speed estimation, the accuracy rate for a speed error of less than 0.2410 m/s is 75% for a single person.
Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein–RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing

During mRNA transcription, diverse RNA-binding proteins (RBPs) are recruited to RNA polymerase II (RNAP II) transcription machinery. These RBPs bind to distinct sites of nascent RNA to co-transcriptionally operate mRNA processing. Recent studies have revealed a close relationship between transcription and co-transcriptional RNA processing, where one affects the other’s activity, indicating an essential role of protein–RNA interactions for the fine-tuning of mRNA production. Owing to their limited amount in cells, the detection of protein–RNA interactions specifically assembled on the transcribing RNAP II machinery still remains challenging. Currently, cross-linking and immunoprecipitation (CLIP) has become a standard method to detect in vivo protein–RNA interactions, although it requires a large amount of input materials. Several improved methods, such as infrared-CLIP (irCLIP), enhanced CLIP (eCLIP), and target RNA immunoprecipitation (tRIP), have shown remarkable enhancements in the detection efficiency. Furthermore, the utilization of an RNA editing mechanism or proximity labeling strategy has achieved the detection of faint protein–RNA interactions in cells without depending on crosslinking. This review aims to explore various methods being developed to detect endogenous protein–RNA interaction sites and discusses how they may be applied to the analysis of co-transcriptional RNA processing.
Effects of L-Histidine and Sodium Acetate on β-Casein Expression in Nutrient-Restricted Bovine Mammary Epithelial Cells

Simple Summary Nutrient restriction is known to decrease the milk production and milk quality of dairy cows. However, providing cows with abundant nutrients also has a disadvantage because it will increase feed costs. Under such a situation, the use of feed additives can be a good strategy to reduce the feed cost. The objective of this study was to investigate the effects of histidine and sodium acetate on β-casein expression in nutrient-restricted bovine mammary epithelial cells. The results indicate that histidine has the potential to increase the β-casein levels in bovine mammary cells when the nutrient is restricted, suggesting that histidine is a potential feed additive for cows in a nutrient-insufficient environment. Abstract Nutrient restriction is a challenging condition for the mammary glands of dairy cows. In this condition, supplementing amino acids and energy sources might be a good strategy to improve the concentration of one of the most important caseins in bovine milk. Therefore, the objective of this study was to investigate the effects of L-histidine (His) and sodium acetate (Ace) in a nutrient-restricted (NR) immortalized bovine mammary epithelial cell line (MAC-T cells). The treatments for the MAC-T cells are as follows: experiment (1) 0–5% diluted basal medium; experiment (2) supplementation of 0–9.6 mM of His or Ace in NR or normal conditions; experiment (3) supplementation of 0–9.6 mM of Ace plus 0.15 mM of His in NR or normal conditions. The 1% diluted medium showed no significant effect on the cell viability with the basal medium; thus, it was selected as the NR condition. The relative expression of β-casein was significantly increased in the NR condition with the inclusion of 0.15 mM His alone or with Ace compared to that in control. The supplementation of Ace increased the β-casein level under normal conditions. However, it did not change the expression of β-casein under the NR condition. The results suggest that His has the potential to increase the β-casein expression under the NR condition.
Sensing of mercury and silver ions using branched Au nanoparticles prepared by hyperbranched polyethylenimine fabricated and capped AuNPs seeds

Branched AuNPs usually have two or more local surface plasmon resonance (LSPR) absorption bands due to their structural anisotropy, and the LSPR performance is more sensitive to the changes of environmental refractive index than that of spherical AuNPs. The design and preparation of branched AuNPs as colorimetric probes is expected to improve the selectivity and sensitivity of detection of targets. In this paper, branched AuNPs were innovatively synthesized via hyperbranched polyethylenimine (HPEI) fabricated and capped AuNPs as seeds and cetyltrimethylammonium bromide (CTAB) as template agent. The branched AuNPs were characterized by TEM, DLS, zeta potentials and UV–vis spectra. Using the branched AuNPs as a colorimetric probe, the detection system for Hg2+ and Ag+ showed bright color changes from blue to orange and blue to green based on the morphological evolution of branched AuNPs. The branched AuNPs could selectively detect Hg2+ and Ag+ at concentrations as low as 77 and 140 nM, respectively. Moreover, this unusual colorimetric method has been successfully used in real water samples and has great potential as a simple, rapid, sensitive and selective method for the detection of Hg2+ and Ag+.
Cryo-EM Determination of Eravacycline-Bound Structures of the Ribosome and the Multidrug Efflux Pump AdeJ of Acinetobacter baumannii

Acinetobacter baumannii has developed into a highly antibiotic-resistant Gram-negative pathogen. The prevalent AdeJ multidrug efflux pump mediates resistance to different classes of antibiotics known to inhibit the function of the 70S ribosome. ABSTRACT Antibiotic-resistant strains of the Gram-negative pathogen Acinetobacter baumannii have emerged as a significant global health threat. One successful therapeutic option to treat bacterial infections has been to target the bacterial ribosome. However, in many cases, multidrug efflux pumps within the bacterium recognize and extrude these clinically important antibiotics designed to inhibit the protein synthesis function of the bacterial ribosome. Thus, multidrug efflux within A. baumannii and other highly drug-resistant strains is a major cause of failure of drug-based treatments of infectious diseases. We here report the first structures of the Acinetobacter drug efflux (Ade)J pump in the presence of the antibiotic eravacycline, using single-particle cryo-electron microscopy (cryo-EM). We also describe cryo-EM structures of the eravacycline-bound forms of the A. baumannii ribosome, including the 70S, 50S, and 30S forms. Our data indicate that the AdeJ pump primarily uses hydrophobic interactions to bind eravacycline, while the 70S ribosome utilizes electrostatic interactions to bind this drug. Our work here highlights how an antibiotic can bind multiple bacterial targets through different mechanisms and potentially enables drug optimization by taking advantage of these different modes of ligand binding. IMPORTANCE Acinetobacter baumannii has developed into a highly antibiotic-resistant Gram-negative pathogen. The prevalent AdeJ multidrug efflux pump mediates resistance to different classes of antibiotics known to inhibit the function of the 70S ribosome. Here, we report the first structures of the A. baumannii AdeJ pump, both in the absence and presence of eravacycline. We also describe structures of the A. baumannii ribosome bound by this antibiotic. Our results indicate that AdeJ and the ribosome use very distinct binding modes for drug recognition. Our work will ultimately enable structure-based drug discovery to combat antibiotic-resistant A. baumannii infection.
Inhibiting adipose tissue M1 cytokine expression decreases DPP4 activity and insulin resistance in a type 2 diabetes mellitus mouse model

Adipose tissue inflammation is a major cause of the pathogenesis of obesity and comorbidities. To study the involvement of M1/M2 cytokine expression of adipose tissue in the regulatory mechanisms of dipeptidyl peptidase 4 (DPP4) and insulin resistance in diabetes, stromal vascular fractions (SVFs) were purified from inguinal adipose tissue of diabetic (Leprdb/db) and non-diabetic (Lepr+/+) mice followed by analysis of M1/M2 cytokine expression. SVFs of Leprdb/db mice exhibited increased TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression but decreased IL-10 mRNA expression. Plasma from Leprdb/db mice induced TNF-α, IL-6, IL-1β, CCL2, and DPP4 mRNA expression and plasma from Lepr+/+ mice induced IL-10 mRNA expression in SVFs from Leprdb/db mice. Injection of Lepr+/+ plasma into the adipose tissue of Leprdb/db mice decreased mRNA expression of TNF-α, IL-6, IL-1β, CCL2, and DPP4 and protein expression of pJNK and DPP4 in SVFs, reduced mRNA expression of ICAM, FMO3, IL-1β, iNOS, TNF-α, IL-6, and DPP4 and protein expression of ICAM, FMO3, and DPP4 in liver, and suppressed mRNA expression of TNF-α, IL-6, IL-1β, and DPP4 in Kupffer cells. Plasma from Leprdb/db mice did not induce M1 cytokine expression in SVFs from Leprdb/db-Jnk1-/- mice. Altogether, we demonstrate that diabetes induces M1 but decreases M2 cytokine expression in adipose tissue. Diabetic plasma-induced M1 expression is potentially through pJNK signaling pathways. Non-diabetic plasma reverses M1/M2 cytokine expression, plasma CCL2 levels, DPP4 activity, and Kupffer cell activation in diabetes. Our results suggest M1/M2 cytokine expression in adipose tissue is critical in diabetes-induced DPP4 activity, liver inflammation, and insulin resistance.
Sample size formula for general win ratio analysis

Originally proposed for the analysis of prioritized composite endpoints, the win ratio has now expanded into a broad class of methodology based on general pairwise comparisons. Complicated by the non‐i.i. d. structure of the test statistic, however, sample size estimation for the win ratio has lagged behind. In this article, we develop general and easy‐to‐use formulas to calculate sample size for win ratio analysis of different outcome types. In a nonparametric setting, the null variance of the test statistic is derived using U‐statistic theory in terms of a dispersion parameter called the standard rank deviation, an intrinsic characteristic of the null outcome distribution and the user‐defined rule of comparison. The effect size can be hypothesized either on the original scale of the population win ratio, or on the scale of a “usual” effect size suited to the outcome type. The latter approach allows one to measure the effect size by, for example, odds/continuation ratio for totally/partially ordered outcomes and hazard ratios for composite time‐to‐event outcomes. Simulation studies show that the derived formulas provide accurate estimates for the required sample size across different settings. As illustration, real data from two clinical studies of hepatic and cardiovascular diseases are used as pilot data to calculate sample sizes for future trials.
Retrieving high-quality genomic DNA from formalin-fixed paraffin-embedded tissues for multiple molecular analyses

Abstract Formalin-fixed paraffin-embedded (FFPE) tissues represent the biggest source of archival materials for molecular biology research and pathology investigations. Nevertheless, fixation by formalin may cause denaturation and modification of macromolecules constraining DNA quality and its downstream applications. In this study, we developed a fast, simple, and cost-effective phenol/chloroform-based protocol for the extraction of high-quality DNA from 101 FFPE colorectal cancer tissue blocks that can be used in multiple molecular studies. DNA samples extracted using this phenol/chloroform protocol and the QIAamp DNA FFPE Tissue kit were evaluated for the quantity, quality, and amplificability. Spectrophotometer analyses revealed significantly higher quality and quantity of DNA samples obtained with the phenol/chloroform protocol as compared to those of the QIAamp DNA FFPE Tissue kit. In addition, the amplificability of these samples as assessed by conventional and multiplex polymerase chain reaction (PCR), followed by sequencing and fragment analyses presented an absolute success rate. Additionally, it is able to amplify a DNA fragment of 725 base-pairs at an adequate amount for downstream applications. This fast, simple, and cost-effective method may facilitate the molecular analyses of a large number of FFPE specimens that best suits the needs of the overall study design in terms of the quality and quantity of the extracted DNA.
NEIL3 Prevents Senescence in Hepatocellular Carcinoma by Repairing Oxidative Lesions at Telomeres during Mitosis

This study describes compartmentalization of base excision repair during mitosis that is dependent on NEIL3, APE1, and POLB to repair oxidative damage accumulating at telomeres in hepatocellular carcinoma. Patients with hepatocellular carcinoma (HCC) suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for nontransformed cells. NEIL3-depleted HCC cell lines accumulated oxidative DNA lesions specifically at telomeres, resulting in telomere dysfunctional foci and 53BP1 foci formation. Following oxidative DNA damage during mitosis, NEIL3 relocated to telomeres and recruited apurinic endonuclease 1 (APE1), indicating activation of base excision repair. META-FISH revealed that NEIL3, but not NEIL1 or NEIL2, is required to initiate APE1 and polymerase beta (POLB)-dependent base excision repair at oxidized telomeres. Repeated exposure of NEIL3-depleted cells to oxidizing damage induced chromatin bridges and damaged telomeres. These results demonstrate a novel function for NEIL3 in repair of oxidative DNA damage at telomeres in mitosis, which is important to prevent senescence of HCC cells. Furthermore, these data suggest that NEIL3 could be a target for therapeutic intervention for HCC. Significance: This study describes compartmentalization of base excision repair during mitosis that is dependent on NEIL3, APE1, and POLB to repair oxidative damage accumulating at telomeres in hepatocellular carcinoma. Graphical Abstract
Chemical exchange saturation transfer imaging for epilepsy secondary to tuberous sclerosis complex at 3 T: Optimization and analysis

The homeostasis of various metabolites is impaired in epilepsy secondary to the tuberous sclerosis complex (TSC). Chemical exchange saturation transfer (CEST) imaging is an emerging molecular MRI technique that can detect various metabolites and proteins in vivo. However, the role of CEST imaging for TSC‐associated epilepsy has not been assessed. Here, we aim to investigate the feasibility of applying CEST imaging to TSC‐associated epilepsy, optimize the CEST acquisition parameters, and provide an analysis method for exploring the dominant molecular contributors to the CEST signal measured. Nine TSC epilepsy patients were scanned on a 3‐T MRI system. The CEST saturation frequencies were swept from −6 to 6 ppm with 12 different combinations of saturation power (4, 3, 2 and 1 μT) and duration (1000, 700 and 400 ms). Furthermore, a two‐stage simulation method based on the seven‐pool Bloch‐McConnell model was proposed to assess the contribution of each exchangeable pool to the CEST signal in normal‐appearing white matter and cortical tubers, which avoided the complexity and uncertainty of full Bloch‐McConnell fitting. The results showed that under the optimal saturation duration of 1000 ms, the greatest contrast between tubers and normal tissues occurred around 3, 2.5, 1.75 and 3.5 ppm for B1 of 4, 3, 2 and 1 μT, respectively. At the optimal frequency offsets, the CEST values of tubers were significantly higher than those in the normal brain tissues (P < 0.01). Furthermore, the two‐stage analysis suggested that the amine pool played a dominant role in yielding the contrast between cortical tubers and normal tissues. These results indicate that CEST MRI may serve as a potentially useful tool for identifying tubers in TSC, and the two‐stage analysis method may provide a route for investigating the molecular contributions to the CEST contrast in biological tissues.