syedzayyan/paper_mill_benchmark huggingface dataset:
Liver-adipose tissue crosstalk in alcohol-associated liver disease: The role of mTOR.

Alcohol-associated liver disease (ald) is a major chronic liver disease around the world without successful treatment.Acute alcoholic hepatitis is one of the most severe forms of ald with high mortality, which is often associated with binge drinking.Alcohol drinking dysregulates lipid metabolism, increases adipose tissue lipolysis, and induces liver steatosis and adipose tissue atrophy.Increasing evidence implicates that crosstalk of liver and adipose tissue in the pathogenesis of ald.Mechanistic target of rapamycin (m tor) is a phosphatidylinositol 3-kinase (pi3k)-like serine/threonine protein kinase that regulates lipid metabolism, cell proliferation and autophagy.However, the role of m tor in regulating adipose-liver crosstalk in binge drinking-induced organ damage remains unclear.Methods we generated liver-specific and adipocyte-specific regulatory-associated protein of m tor (rptor) knockout (rptor lkoand rptor ako) as well as mtorknockout (mtor lkoand mtor ako) mice, by crossing rptorfloxand mtorfloxmice with albumin cre or adiponectin cre mice, respectively.In addition, we generated liver and adipocyte double deletion of rptoror mtor(mtor lakoand rptor lako) mice.The knockout mice with their matched wild-type littermates (rptor wtand mtor wt) were subjected to acute gavage of 7 g/kg ethanol.Results mice with adipocyte deletion of rptoror mtordeveloped hepatomegaly and adipose tissue atrophy.Alcohol gavage increased liver injury, hepatic steatosis and inflammation in mouse livers as demonstrated by elevated serum alanine aminotransferase activities, increased hepatic levels of triglyceride and increased hepatic numbers of cd68 positive macrophages in mouse livers after alcohol gavage.Liver injury was further exacerbated by deletion of adipocyte rptoror mtor.Serum adipokine array analysis revealed that increased levels of pro-inflammatory cytokines il-6 and tnfα as well as chemokine mcp-1 following acute alcohol gavage in wild-type mice, which were further increased in adipocyte-specific mtoror rptorknockout mice.Conversely, levels of anti-inflammatory cytokine il-10 decreased in adipocyte-specific mtoror rptorknockout mice.The levels of circulating fibroblast growth factor 21 (fgf21) increased whereas levels of circulating adiponectin and fetuin a decreased in wild-type mice after alcohol gavage.Intriguingly, adipocyte-specific mtoror rptorknockout mice already had decreased basal level of fgf21 which increased by alcohol gavage.Moreover, adipocyte-specific mtoror rptorknockout mice already had increased basal level of adiponectin and decreased fetuin a which were not further changed by alcohol gavage.Conclusions adipocyte but not hepatocyte ablation of mtorpathway contributes to acute alcohol-induced liver injury with increased inflammation.Our results demonstrate the critical role of adipocyte m tor in regulating the adipose-liver crosstalk in ald.

Journal: Liver research (2022)
Publication types: Journal Article
Cold Exposure Drives Weight Gain and Adiposity following Chronic Suppression of Brown Adipose Tissue.

Therapeutic activation of thermogenic brown adipose tissue (bat) may be feasible to prevent, or treat, cardiometabolic disease.However, rodents are commonly housed below thermoneutrality (~20 °c) which can modulate their metabolism and physiology including the hyperactivation of brown (bat) and beige white adipose tissue.We housed animals at thermoneutrality from weaning to chronically supress bat, mimic human physiology and explore the efficacy of chronic, mild cold exposure (20 °c) and β3-adrenoreceptor agonism (ym-178) under these conditions.Using metabolic phenotyping and exploratory proteomics we show that transfer from 28 °c to 20 °c drives weight gain and a 125% increase in subcutaneous fat mass, an effect not seen with ym-178 administration, thus suggesting a direct effect of a cool ambient temperature in promoting weight gain and further adiposity in obese rats.Following chronic suppression of bat, uncoupling protein 1 m rna was undetectable in the subcutaneous inguinal white adipose tissue (iwat) in all groups.Using exploratory adipose tissue proteomics, we reveal novel gene ontology terms associated with cold-induced weight gain in bat and iwat whilst reactome pathway analysis highlights the regulation of mitotic (i.e., g2/m transition) and metabolism of amino acids and derivatives pathways.Conversely, ym-178 had minimal metabolic-related effects but modified pathways involved in proteolysis (i.e., eukaryotic translation initiation) and rna surveillance across both tissues.Taken together these findings are indicative of a novel mechanism whereby animals increase body weight and fat mass following chronic suppression of adaptive thermogenesis from weaning.In addition, treatment with a b3-adrenoreceptor agonist did not improve metabolic health in obese animals raised at thermoneutrality.

Journal: International journal of molecular sciences (2022)
Publication types: Journal Article
Genetic analysis of the first mcr-1 positive Escherichia coli isolate collected from an outpatient in Chile.

Global dissemination of mcr-like genes represents a serious threat to public health since it jeopardizes the effectiveness of colistin, an antibiotic used as a last-resort treatment against highly antibiotic-resistant bacteria.In 2017, a mcr-1-positive isolate of escherichia coli was found in chile for the first time.Herein we report the genetic features of this strain (uco-457) by whole-genome sequencing (wgs) and conjugation experiments.The uco-457 strain belonged to st4204 and carried a 285 kb inc i2-type plasmid containing the mcr-1 gene.Moreover, this plasmid was transferred by conjugation to an e.Coli j53 strain at high frequency.The isolate harbored the cma, iro n, and iss virulence genes and did carry resistance genes to trimethoprim/sulfamethoxazole and fluoroquinolones.Other antibiotic resistance determinants such as β-lactamases-encoding genes were not detected, making the isolate highly susceptible to these antibiotics.Our results revealed that such susceptible isolates could be acting as platforms to disseminate plasmid-mediated colistin resistance.Based on this evidence, we consider that mcr-like prevalence deserves urgent attention and should be examined not only in highly resistant bacteria but also in susceptible isolates.

Journal: The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases (2019)
Publication types: Journal Article
Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions.This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (pcos).This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with pcos aged 18-40 years old.Patients were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, or placebo for 8 weeks.Fasting blood samples were taken at baseline and after the intervention to quantify related variables.After the 8-week intervention, an insignificant marginal difference was seen in waist circumference (wc) between groups (p = 0.085).Magnesium-melatonin co-supplementation resulted in more reductions in hirsutism compared with other groups (p < 0.001).Serum levels of tumor necrosis factor-α (tnf-α) declined significantly in the melatonin and co-supplementation groups compared to baseline (p < 0.05).Also, magnesium plus melatonin was associated with a more increase in total antioxidant capacity (tac) levels, as compared to the other treatment groups (p = 0.001).Overall, we found a favorable effect of co-supplementation of magnesium and melatonin for 8 weeks in women with pcos on hirsutism, serum tnf-α, and tac levels.Furthermore, melatonin independently contributed to decreased serum values of tnf-α.clinical trial registration number : irct20191130045556n1, january 2020.

Journal: Biological trace element research (2022)
Publication types: Journal Article;Randomized Controlled Trial
The associations between sleep behaviors, lifestyle factors, genetic risk and mental disorders: A cohort study of 402 290 UK Biobank participants.

Sleep behaviors were believed to be associated with mental disorders (md).However, the underlying mechanism of such association relationship, especially the role of multiple lifestyle factors in it remains unclear.Methods a total of 402,290 participants from uk biobank who don't have md at baseline were included.They were divided into poor, intermediate and healthy sleep patterns according to the sleep score, which was calculated based on the data collecting from five sleep behaviors.Cox proportional hazard model was used to estimate the associations between sleep behaviors and md.The associations were further estimated when taking lifestyle factors such as physical activity, coffee intake, tea intake and genetic susceptibility into account.Results healthy sleep pattern was associated with lower risk of overall md status (hr,0.41, 95%ci,0.39-0.43), depressive disorders (hr,0.34, 95%ci,0.31-0.37) and anxiety disorders (hr,0.46, 95%ci,0.41-0.79), compared with poor sleep pattern.And in each subgroup of physical activity, tea intake, coffee intake, age and genetic risk scores (grs), healthy sleep pattern could partly offset the risk of diseases.Conclusions our study suggested healthy sleep behaviors could diminish the negative effect from genetic predisposition and lifestyle factors on the risk of md, highlighting the benefit of healthy sleep pattern.

Journal: Psychiatry research (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Single-type reporter multiplexing with A single droplet through bead-based digital microfluidics.

With the limited sample volume, the droplet-based microfluidic becomes attractive in biomedical diagnosis, especially for measuring multiple analytes.Usually, for multiplexing by parallel processing, a larger sample volume is required.In our previous study, simultaneously detecting two analytes from a single droplet was first achieved by measuring different fluorescence wavelengths for different analytes.However, the number of detectable analytes could be limited by the spectral resolution of fluorescence.Here a different approach is proposed for multiplexing by sharing a single droplet in multiple sub-assays.Therefore, only a single-type reporter, i.e., the fluorescence with the same wavelength, is needed for detection of different analytes from a single sample droplet, called single-type reporter multiplexing (strm).The standard curves of two analytes, human il-1β and human tnf-α, are demonstrated.The required sample volume for one measurement is only 520 n l; the total duration of the on-chip process is less than 50 min.The limits of detection (lod) of human il-1β and human tnf-α are about 1.14 and 0.97 pg/m l, respectively.It is shown that the proposed bead-based digital microfluidic immunoassay can achieve multiple analytes detection with low lod from a single sample droplet using the single-type reporter, which has never been achieved before.

Journal: Journal of pharmaceutical and biomedical analysis (2022)
Publication types: Journal Article
Comparison of free breathing and respiratory triggered diffusion-weighted imaging sequences for liver imaging.

Diffusion-weighted imaging (dwi) has become a useful tool in the detection, characterization, and evaluation of response to treatment of many cancers, including malignant liver lesions.Dwi offers higher image contrast between lesions and normal liver tissue than other sequences.Dwi images acquired at two or more b-values can be used to derive an apparent diffusion coefficient (adc).Dwi in the body has several technical challenges.This include ghosting artifacts, mis-registration and susceptibility artifacts.New dwi sequences have been developed to overcome some of these challenges.Our goal is to evaluate 3 new dwi sequences for liver imaging.Aim to qualitatively and quantitatively compare 3 dwi sequences for liver imaging: free-breathing (fb), simultaneous multislice (sms), and prospective acquisition correction (pace).Methods magnetic resonance imaging (mri) was performed in 20 patients in this prospective study.The mr study included 3 separate dwi sequences: fb-dwi, sms-dwi, and pace-dwi.The image quality, mean adc, standard deviations (sd) of adc, and adc histogram were compared.Wilcoxon signed-rank tests were used to compare qualitative image quality.A linear mixed model was used to compare the mean adc and the sds of the adc values.All tests were 2-sided and pvalues of < 0.05 were considered statistically significant.Results there were 56 lesions (50 malignant) evaluated in this study.The mean qualitative image quality score of pace-dwi was 4.48.This was significantly better than that of sms-dwi (4.22) and fb-dwi (3.15) (p< 0.05).Quantitatively, the mean adc values from the 3 different sequences did not significantly differ for each liver lesion.Fb-dwi had a markedly higher variation in the sd of the adc values than did sms-dwi and pace-dwi.We found statistically significant differences in the sds of the adc values for fb-dwivs pace-dwi (p< 0.0001) and for fb-dwivs sms-dwi (p= 0.03).The sd of the adc values was not statistically significant for pace-dwi and sms-dwi (p= 0.18).The quality of the pace-dwi adc histograms were considered better than the sms-dwi and fb-dwi.Conclusion compared to fb-dwi, both pace-dwi and sms-dwi provide better image quality and decreased quantitative variability in the measurement of adc values of liver lesions.

Journal: World journal of radiology (2019)
Publication types: Journal Article
Pharmacological Approaches to Studying Potassium Channels.

In this review, we consider the pharmacology of potassium channels from the perspective of these channels as therapeutic targets.Firstly, we describe the three main families of potassium channels in humans and disease states where they are implicated.Secondly, we describe the existing therapeutic agents which act on potassium channels and outline why these channels represent an under-exploited therapeutic target with potential for future drug development.Thirdly, we consider the evidence desired in order to embark on a drug discovery programme targeting a particular potassium channel.We have chosen two "case studies": activators of the two-pore domain potassium (k2p) channel trek-2 (k2p10.1), for the treatment of pain and inhibitors of the voltage-gated potassium channel kv1.3, for use in autoimmune diseases such as multiple sclerosis.We describe the evidence base to suggest why these are viable therapeutic targets.Finally, we detail the main technical approaches available to characterise the pharmacology of potassium channels and identify novel regulatory compounds.We draw particular attention to the comprehensive in vitro proarrhythmia assay initiative (ci pa, ) project for cardiac safety, as an example of what might be both desirable and possible in the future, for ion channel regulator discovery projects.

Journal: Handbook of experimental pharmacology (2021)
Publication types: Journal Article;Review
Optimizing Flap Harvest in Auricular Reconstruction.

Introduction the temporoparietal fascial (tpf) and occipital cranial fascial (ocp) flaps are the mainstay of implant coverage in alloplastic auricular reconstruction.Their optimal design is critical for elevating a robust flap that ultimately leads to favorable outcomes.Materials and methods sixteen tpf and ocp dissections were performed on 8 cadaveric specimens.Vascular anatomy and key landmarks were documented.The minimum flap size that incorporated ideal vasculature and would appropriately cover a porous polyethylene implant was measured.Results the minimum flap dimensions (length × width × base width) to cover a standard ppe auricular implants were on average 11×8.3×6.4 cm for tpf and 13.1×8.6×6.5 cm for ocp.The average axial length of the superficial temporal artery and occipital artery were 12.51 and 13.2 cm, respectively.An "occipital elbow" was located on average 8.2 cm posterior to the external acoustic canal.The postauricular fascia contained additional contributions from the occipital artery and mastoid emissary vein, which was located on average 5.9 cm posterior to the superficial temporal artery.Conclusions this study highlights the anatomic features behind optimal tpf and ocp flap design for auricular reconstruction.Contributions to axial length and anatomic relationships of their primary arterial supply, significance of the occipital elbow as a reliable landmark for fascial dissection, and importance of the postauricular fascia and its vascular supply for flap viability are emphasized.Ultimately, the authors provide minimal dimensions for both tpf and ocp flaps to obtain adequate alloplastic implant coverage.

Journal: The Journal of craniofacial surgery (2022)
Publication types: Journal Article
The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice.

And aims the conserved hippo pathway regulates organ size, tissue homeostasis, and tumorigenesis.Interferon regulatory factor 2 binding protein 2 (irf2bp2) was originally identified as a transcriptional corepressor.However, the association between irf2bp2 and the hippo pathway remains largely unknown.In addition, the biological function and regulation mechanism of irf2bp2 in liver cancer are poorly understood.Approach and results in this study, we uncovered the clinical significance of irf2bp2 in suppressing hepatocellular carcinogenesis.We showed that irf2bp2, a direct target repressed by the yes-associated protein (yap)/tea domain transcription factor 4 (tead4) transcriptional complex, inhibited yap activity through a feedback loop.Irf2bp2 stabilized vestigial-like family member 4 (vgll4) and further enhanced vgll4's inhibitory function on yap.Moreover, liver-specific irf2bp2 overexpression suppressed tumor formation induced by hippo pathway inactivation.Conclusions these results revealed the important role of irf2bp2 in repressing liver cancer progression and highlighted a feedback loop underlying the hippo pathway in organ-size control and tumorigenesis.

Journal: Hepatology (Baltimore, Md.) (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Effects of a high-intensity interval training session and chocolate milk on appetite and cognitive performance in youth aged 9-13 years.

/objectives to investigate the separate and combined effects of a single session of high intensity interval training (hiit) and chocolate milk on appetite and cognitive performance in youth aged 9-13 years.Blood glucose, salivary cortisol, and subjective emotions were measured to evaluate potential underlying mechanisms contributing to changes in appetite and cognitive performance.Subjects/methods using a 2 × 2 repeated measures design, 20 youth (n = 12 girls and n = 8 boys; age = 11.4 ± 0.3 years) performed hiit on a cycle ergometer (7 × 60 s bouts, interspersed by 60 s active recovery) or sitting, followed by consumption of 163 kcal chocolate milk or water.Capillary blood glucose, salivary cortisol, cognitive performance, and subjective appetite and emotions were assessed at baseline and at several time points post-treatment.Results subjective appetite decreased from baseline following chocolate milk consumption compared water (p = 0.04), and increased from baseline after hiit compared to sitting (p = 0.01).Participants recalled more words during a short-term memory task and had faster reaction times during an attention task following hiit compared to sitting (δ = 1.1 ± 0.02 words, p = 0.03; and δ = 117.9 ± 23.1 ms, p = 0.01, respectively).Blood glucose increased from baseline following chocolate milk consumption compared to water (at 10 min: δ = 1.0 ± 0.33 vs.Δ = 0.29 ± 0.060 mmol/l; p < 0.0001).Conclusions our findings that hiit may have a positive effect on aspects of cognitive performance suggest that youth should engage in hiit-like exercise during recesses and lunch at school to attenuate declines in cognitive performance throughout the day.Registered at (nct03305107).

Journal: European journal of clinical nutrition (2021)
Publication types: Clinical Study;Journal Article;Research Support, Non-U.S. Gov't
Translational remodeling by RNA-binding proteins and noncoding RNAs.

Responsible for generating the proteome that controls phenotype, translation is the ultimate convergence point for myriad upstream signals that influence gene expression.System-wide adaptive translational reprogramming has recently emerged as a pillar of cellular adaptation.As classic regulators of m rna stability and translation efficiency, foundational studies established the concept of collaboration and competition between rna-binding proteins (rbps) and noncoding rnas (nc rnas) on individual m rnas.Fresh conceptual innovations now highlight stress-activated, evolutionarily conserved rbp networks and nc rnas that increase the translation efficiency of populations of transcripts encoding proteins that participate in a common cellular process.The discovery of post-transcriptional functions for long noncoding rnas (lnc rnas) was particularly intriguing given their cell-type-specificity and historical definition as nuclear-functioning epigenetic regulators.The convergence of rbps, lnc rnas, and micro rnas on functionally related m rnas to enable adaptive protein synthesis is a newer biological paradigm that highlights their role as "translatome (protein output) remodelers" and reinvigorates the paradigm of "rna operons." together, these concepts modernize our understanding of cellular stress adaptation and strategies for therapeutic development.This article is categorized under: rna interactions with proteins and other molecules > protein-rna interactions: functional implications translation > translation regulation regulatory rnas/rnai/riboswitches > regulatory rnas.

Journal: Wiley interdisciplinary reviews. RNA (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review