Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

Background: TGF-β1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic β-catenin alleviated the profibrogenic effect of TGF-β1 without influencing its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results: Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing β-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-β1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of β-catenin with ICG001 suppressed TGF-β1 induced proliferation and activation of CCC-REPF-1, blocked TGF-β1 induced epithelial–mesenchymal transition (EMT) of RLE-6TN. Conclusion: Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting β-catenin specifically via inhibition of β-catenin/TCF might be a new therapeutic strategy for asthma. The reviews of this paper are available via the supplemental material section.
How do autistic adults use syntactic and prosodic cues to manage spoken discourse?

ABSTRACT Discourse studies investigating differences in the socio-communicative profiles of autistic (ASD) and neurotypical (NT) individuals have mostly relied on orthographic transcriptions, without taking prosodic information into account. However, atypical prosody is ubiquitous in ASD and a more accurate representation of their discourse abilities should also include prosodic cues. This exploratory study addresses this gap by segmenting the spoken discourse of 12 ASD and NT adults using the framework of Basic Discourse Units (BDUs). BDUs result from the mapping of syntactic boundaries on prosodic units, which can coincide in different ways and are associated with different discourse strategies. We hypothesized that the discourse of ASD adults would display more atypical strategies than NT adults, reflecting a ‘pedantic’ style and more difficulties in managing ongoing discourse. While ASD adults did not produce more discourse units associated with didactic or pedantic strategies than NT adults, they did produce less units associated with strategies of interactional regulation. This study provides initial evidence that multidimensional linguistic units, such as BDUs can help differentiate speech delivery strategies of ASD adults from those of their NT peers, even based on simple prosodic cues like silent pauses.
Quantitative proteomic analysis identified differentially expressed proteins with tail/rump fat deposition in Chinese thin- and fat-tailed lambs

Tail adipose as one of the important functional tissues can enhance hazardous environments tolerance for sheep. The objective of this study was to gain insight into the underlying development mechanisms of this trait. A quantitative analysis of protein abundance in ovine tail/rump adipose tissue was performed between Chinese local fat- (Kazakh, Hu and Lanzhou) and thin-tailed (Alpine Merino, Tibetan) sheep in the present study by using lable-free approach. Results showed that 3400 proteins were identified in the five breeds, and 804 were differentially expressed proteins, including 638 up regulated proteins and 83 down regulated proteins in the tail adipose tissues between fat- and thin-tailed sheep, and 8 clusters were distinguished for all the DEPs’ expression patterns. The differentially expressed proteins are mainly associated with metabolism pathways and peroxisome proliferator activated receptor signaling pathway. Furthermore, the proteomics results were validated by quantitative real-time PCR and Western Blot. Our research has also suggested that the up-regulated proteins ACSL1, HSD17β4, FABP4 in the tail adipose tissue might contribute to tail fat deposition by facilitating the proliferation of adipocytes and fat accumulation in tail/rump of sheep. Particularly, FABP4 highly expressed in the fat-tail will play an important role for tail fat deposition. Our study might provide a novel view to understanding fat accumulation in special parts of the body in sheep and other animals.
Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF‐associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF‐associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.
Chemical modification of polynorbornene. I. Sulfonation in dilute solution

The sulfonation of dilute solutions of polynorbornene (PN) in CCl4 has been carried out using SO3–triethylphosphate complexes of various stoichiometries dissolved in dichloroethane (DCE) or trifluoro-trichloro-ethane (TTE). This leads to an electrophilic substitution, with very few side reactions, yielding high sulfonation ratios (ca. 85%). The initial reaction is first order in both reactants (PN and SO3) and has an activation energy of 17.5 kJ mol−1. The reaction becomes diffusion-controlled after ca. 30 min at room temperature due to the precipitation of the partially sulfonated polymer. The initial rate is almost independent of the isomeric structure (cis or trans) and the molecular weight of the polymer, as well as on the stoichiometry of the SO3–TEP complex; it is higher when TTE is used as solvent. The final sulfonation ratio is strongly dependent on the concentration of SO3 and seems to be controlled by the conditions of diffusion inside the precipitated solid.
A Review of Studies of the Association of Vision-Related Quality of Life with Measures of Visual Function and Structure in Patients with Glaucoma in the United States

ABSTRACT Purpose : To investigate the association of quality of life (QoL) with ocular structure and function in glaucoma patients, and to identify which aspects of QoL are most closely tied to Visual Field (VF) and Visual Acuity (VA). Methods : We conducted a comprehensive review of studies on QoL in glaucoma patients using PubMed, Web of Science, and Google Scholar (from 1 January 1997 to 7 December 2019). A total of 21 studies in the United States that used the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ) or 51-item NEI VFQ were included. A descriptive analysis of data from the selected studies was conducted. The association between QoL scores and visual function and structure was investigated by ranking the strength of association on a scale from 1 (weakest) to 12 (strongest). Results : Studies reported correlations between QoL scores and Visual Structure. Associations were also reported between QoL and Visual Function both cross-sectionally and longitudinally, with a stronger association of VF and VA with distance activities (average ranking 9.1 and 9.6), vision-specific dependency (8.7 and 8.9), and driving (8.6 and 9.7). Vision-specific mental health (6.5 and 4.9), vision-specific social functioning (8.4 and 6.2), and vision-specific role difficulties (7.1 and 6.6) domains were more associated with VF than with VA. Conclusion : Our study was the first to quantify and rank the strength of association between visual function and QoL domains. Driving and psycho-social QoL domains tended to be most affected by glaucoma-related deterioration of visual function. QoL scores could be used for more patient-centered disease management.
Characterization of the strain-rate–dependent mechanical response of single cell–cell junctions

Significance Cell–cell junctions are essential components in multicellular structures and often experience strains of different magnitudes and rates. However, their mechanical behavior is currently underexplored due to the lack of techniques to quantitatively characterize junctional stress–strain relationships. We developed a polymeric microstructure to strain the mutual junction of a single cell pair while simultaneously recording the junction stress and observed previously unseen strain-rate–dependent junction responses. We showed that cytoskeleton growth could relax the stress buildup and prevent junction failure at low strain rates, while high strain rates led to synchronized junction failures at remarkably large strains (over 200%). We expect this platform and our biophysical understanding to form the foundation for the rate-dependent mechanics of cell–cell junctions. Cell–cell adhesions are often subjected to mechanical strains of different rates and magnitudes in normal tissue function. However, the rate-dependent mechanical behavior of individual cell–cell adhesions has not been fully characterized due to the lack of proper experimental techniques and therefore remains elusive. This is particularly true under large strain conditions, which may potentially lead to cell–cell adhesion dissociation and ultimately tissue fracture. In this study, we designed and fabricated a single-cell adhesion micro tensile tester (SCAµTT) using two-photon polymerization and performed displacement-controlled tensile tests of individual pairs of adherent epithelial cells with a mature cell–cell adhesion. Straining the cytoskeleton–cell adhesion complex system reveals a passive shear-thinning viscoelastic behavior and a rate-dependent active stress-relaxation mechanism mediated by cytoskeleton growth. Under low strain rates, stress relaxation mediated by the cytoskeleton can effectively relax junctional stress buildup and prevent adhesion bond rupture. Cadherin bond dissociation also exhibits rate-dependent strengthening, in which increased strain rate results in elevated stress levels at which cadherin bonds fail. This bond dissociation becomes a synchronized catastrophic event that leads to junction fracture at high strain rates. Even at high strain rates, a single cell–cell junction displays a remarkable tensile strength to sustain a strain as much as 200% before complete junction rupture. Collectively, the platform and the biophysical understandings in this study are expected to build a foundation for the mechanistic investigation of the adaptive viscoelasticity of the cell–cell junction.
Experimental Models for Studying HPV-Positive and HPV-Negative Penile Cancer: New Tools for An Old Disease

Simple Summary Penile cancer is an uncommon and understudied malignancy that is most commonly diagnosed in developing countries. Therapeutic advances have been slow, in part due to the lack of in vitro and in vivo models for testing new drugs before performing clinical trials. Recently, this difficulty has been partly overcome and multiple new pre-clinical models were reported. These important developments will help develop new therapies for penile cancer patients. The present review summarizes and discusses the available data concerning the pre-clinical models of penile cancer and their uses. Comparisons are drawn between different models, allowing researchers to choose the most adequate setting for their experiments. The remaining gaps in this array of penile cancer models are also discussed, in particular the lack of models for studying metastatic disease and cell lines representing tumors associated with human papillomavirus. Abstract Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.
Water Stability and Competition Effects Toward CO2 Adsorption on Metal Organic Frameworks

Metal-organic frameworks (MOFs) are compounds consisting of metal cations and organic anions organized in porous three-dimensional structures. MOFs exhibit higher selective adsorption performance for CO2-containing gas mixtures than traditional porous materials, making them promising candidates in CO2 capture. However, it is important to understand H2O effects on CO2 adsorption in MOFs before making them more applicable in the process designed to separate CO2 from wet gas mixtures. In this review, we summarize the current state of MOF development for CO2 adsorption. The stability of MOFs toward water and the strategies of enhancing the water stability for MOFs were discussed. The different effects of water on the CO2 adsorption and separation performance and the mechanism of the effects were analyzed.
The Two Faces of Exosomes in Parkinson’s Disease: From Pathology to Therapy

Accumulating evidence suggests that exosomes play a key role in Parkinson’s disease (PD). Exosomes may contribute to the PD progression facilitating the spread of pathological alpha-synuclein or activating immune cells. Glial cells also release exosomes, and transmission of exosomes derived from activated glial cells containing inflammatory mediators may contribute to the propagation of the neuroinflammatory response. Glia-to-neuron transmission of exosomes containing alpha-synuclein may contribute to alpha-synuclein propagation and neurodegeneration. Additionally, miRNAs can be transmitted among cells via exosomes inducing changes in the genetic program of the target cell contributing to PD progression. Exosomes also represent a promising drug delivery system. The brain is a difficult target for drugs of all classes because the blood-brain barrier excludes most macromolecular drugs. One of the major challenges is the development of vehicles for robust delivery to the brain. Targeted exosomes may have the potential for delivering therapeutic agents, including proteins and gene therapy molecules, into the brain. This review summarizes recent advances in the role of exosomes in PD pathology progression and their potential use as drug delivery system for PD treatment, the two faces of the exosomes in PD.
Functional Fecal Incontinence in Children: Epidemiology, Pathophysiology, Evaluation, and Management.

ABSTRACT Functional fecal incontinence (FI) is a worldwide problem in children and comprises constipation-associated fecal incontinence and nonretentive fecal incontinence. Irrespective of pathophysiology, both disorders impact negatively on the psychological well-being and quality of life of affected children. A thorough clinical history and physical examination using the Rome IV criteria is usually sufficient to diagnose these conditions in most children. Evolving investigations such as high resolution anorectal and colonic manometry have shed new light on the pathophysiology of functional FI. Although conventional interventions such as toilet training and laxatives successfully treat most children with constipation associated FI, children with nonretentive fecal incontinence need more psychologically based therapeutic options. Intrasphincteric injection of botulinum toxin, transanal irrigation and, in select cases, surgical interventions have been used in more resistant children with constipation associated FI.
Metal overlayers on self‐organized molecular assemblies. IV. Ion scattering spectroscopy of the Ag/CH3 interface

Ion scattering spectroscopy (ISS) of vacuum deposited Ag on octadecanethiol (ODT, HS(CH2)17CH3) organized molecular assemblies (OMAs) provides a means of studying interfacial structure at metal/organic interfaces under controlled conditions. The OMAs were self‐assembled onto gold films on silicon 〈100〉 substrates. ISS compositional depth profiles of the Ag/CH3 interface were performed at a number of temperatures between 113 and 293 K. Results from these experiments show clearly that Ag penetrates rapidly through ODT above ∼200 K. The changes in ISS Ag peak intensities as a function of time and temperature provide evidence for the formation of Ag clusters at the ODT/Au interface after penetration of Ag. Changes in deposition rate between 0.003 and 0.015 nm/s yielded little difference in corresponding ISS depth profiles. Over a range of ion beam current densities from 0.06 to 2.0 μA/cm2, scaled compositional depth profiles were found to be comparable within experimental error.
Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation

The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.
NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations

Overwhelming evidence suggests an association of cardiovascular disease (CVD) with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanisms remain largely speculative. It is, however, likely that common mechanisms contribute to the development of CVD and NAFLD, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits and physical inactivity being major candidates. These behavioral factors, on a predisposing genetic background, trigger changes in gut microbiota, inflammation, dyslipidemia and oxidative stress, leading to metabolic syndrome, diabetes and obesity as well as atherosclerosis. Treatment options to counteract both the progression and development of CVD and NAFLD include lifestyle interventions, optimal medical therapy of comorbid conditions and, as final possibility, bariatric surgery. As no causal pharmacotherapy of NAFLD is available, further research is urgently needed to address the unmet need of a growing population with NAFLD and CVD.
Microsatellite Instability and KRAS Mutation in Stage IV Colorectal Cancer: Prevalence, Geographic Discrepancies, and Outcomes From the National Cancer Database.

BACKGROUND This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). MATERIALS AND METHODS The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability-high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed. Overall survival (OS) was evaluated using multivariable Cox proportional hazards models in patients with complete data on both microsatellite and KRAS status and information on follow-up. RESULTS Information on microsatellite and KRAS status was available for 10,844 and 25,712 patients, respectively, and OS data were available for 5,904 patients. The overall prevalence of MSI-H status and KRAS mutation was 3.1% and 42.4%, respectively. Prevalence of MSI-H ranged between 1.6% (rectosigmoid junction) and 5.2% (transverse colon), and between 34.7% (sigmoid colon) and 58.2% (cecum) for KRAS mutation. MSI-H rates were highest in East North Central US states (4.1%), and KRAS mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with KRAS wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85-0.97; P=.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62-0.9; P=.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6-0.7; P<.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (P=.002 for interaction). CONCLUSIONS Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, and primary CRC sidedness independently affect OS and interact with distinct prognostic profiles. Generically classifying adenocarcinomas at different sites as CRC might deprecate this diversity.