Miracle-dz/UniFAR-FTUs huggingface dataset:
Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.
Prediction Models Based on Regression and Artificial Neural Network for Moduli of Layers Constituted by Open-Graded Aggregates

The impermeable cover in urban area has been growing due to rapid urbanization, which prevents stormwater from being naturally infiltrated into the ground. There is a higher chance of flooding in urban area covered with conventional concretes and asphalts. The permeable pavement is one of Low-Impact Development (LID) technologies that can reduce surface runoff and water pollution by allowing stormwater into pavement systems. Unlike traditional pavements, permeable pavement bases employ open-graded aggregates (OGAs) with highly uniform particle sizes. There is very little information on the engineering properties of compacted OGAs. In this study, the moduli of open-graded aggregates under various compaction energies are investigated based on the Plate Load Test (PLT) and Light-Weight Deflectometer (LWD). Artificial Neural Network (ANN) and Linear Regression (LR) models are employed for estimation of the moduli of the aggregates based on the material type and level of compaction. Overall, the moduli from PLT and LWD steeply increase until the number of roller passes reaches 4, and they gradually increase until the number of roller passes becomes 8. A set of simple linear equations are proposed to evaluate the moduli of open-graded aggregates from PLT and LWD based on the material type and the number of roller passes.
Statistical Copolymers of N-Vinylpyrrolidone and Isobornyl Methacrylate via Free Radical and RAFT Polymerization: Monomer Reactivity Ratios, Thermal Properties, and Kinetics of Thermal Decomposition

The synthesis of statistical copolymers of N-vinylpyrrolidone (NVP) with isobornyl methacrylate (IBMA) was conducted by free radical and reversible addition-fragmentation chain transfer (RAFT) polymerization. The reactivity ratios were estimated using the Finemann-Ross, inverted Fineman-Ross, Kelen-Tüdos, extended Kelen-Tüdos and Barson-Fenn graphical methods, along with the computer program COPOINT, modified to both the terminal and the penultimate models. According to COPOINT the reactivity ratios were found to be equal to 0.292 for NVP and 2.673 for IBMA for conventional radical polymerization, whereas for RAFT polymerization and for the penultimate model the following reactivity ratios were obtained: r11 = 4.466, r22 = 0, r21 = 14.830, and r12 = 0 (1 stands for NVP and 2 for IBMA). In all cases, the NVP reactivity ratio was significantly lower than that of IBMA. Structural parameters of the copolymers were obtained by calculating the dyad sequence fractions and the mean sequence length. The thermal properties of the copolymers were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and differential thermogravimetry (DTG). The results were compared with those of the respective homopolymers.
A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/− knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+/+, immunofluorescence showed A2A roundish aggregates, 0.3–0.4 μm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+/−, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+/−, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+/+. Finally, in Tor1a+/−, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+/−, opposite changes of A2A receptors’ expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.
Characterization of Long Non-Coding RNA Profiles in Porcine Granulosa Cells of Healthy and Atretic Antral Follicles: Implications for a Potential Role in Apoptosis

Long non-coding RNAs (lncRNAs) play important roles in multiple biological processes including ovarian follicular development. Here we aimed to gain novel information regarding lncRNAs transcriptome profiles in porcine granulosa cells of advanced atretic antral (AA) and healthy antral (HA) follicles using RNA-seq. A total of 11,321 lncRNAs including 10,813 novel and 508 annotated lncRNAs were identified, of which 173 lncRNAs were differentially expressed (DE-lncRNAs); ten of these were confirmed by qRT-PCR. Gene Ontology indicated that DE-lncRNAs associated with developmental processes were highly enriched. Pathway analysis demonstrated predicted cis- and trans-targets of DE-lncRNAs. Potential mRNA targets of up-regulated DE-lncRNAs were mainly enriched in apoptosis related pathways, while targeted genes of downregulated DE-lncRNAs were primarily enriched in metabolism and ovarian steroidogenesis pathways. Linear regression analyses showed that expression of upregulated DE-lncRNAs was significantly associated with apoptosis related genes. NOVEL_00001850 is the most-downregulated DE-lncRNA (FDR = 0.04, FC = −6.53), of which miRNA binding sites were predicted. KEGG analysis of its downregulated target genes revealed that ovarian steroidogenesis was the second most highlighted pathway. qRT-PCR and linear regression analysis confirmed the expression and correlation of its potential targeted gene, CYP19A1, a key gene involved in estradiol synthesis. Our results indicate that lncRNAs may participate in granulosa cells apoptosis and thus antral follicular atresia.
Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling

Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/∆G creating functional gene from an IFNL4 pseudogene is associated with the expression of major ISGs in the liver but impaired clearance of hepatitis C. To explain this, we compared Halo-tagged and non-tagged IFNL3 and IFNL4 signaling in liver-derived cell lines. Transfection with non-tagged IFNL3, non-tagged IFNL4 and Halo-tagged IFNL4 led to a similar degree of JAK-STAT activation and ISG induction; however, the response to transfection with Halo-tagged IFNL3 was lower and delayed. Transfection with non-tagged IFNL3 or IFNL4 induced no transcriptome change in the cells lacking either IL10R2 or IFNLR1 receptor subunits. Cytosolic overexpression of signal peptide-lacking IFNL3 or IFNL4 in wild type cells did not interfere with JAK-STAT signaling triggered by interferons in the medium. Finally, expression profile changes induced by transfection with non-tagged IFNL3 and IFNL4 were highly similar. These data do not support the hypothesis about IFNL4-specific non-canonical signaling and point out that functional studies conducted with tagged interferons should be interpreted with caution.
Roles of Brassinosteroids in Mitigating Heat Stress Damage in Cereal Crops

Heat stress causes huge losses in the yield of cereal crops. Temperature influences the rate of plant metabolic and developmental processes that ultimately determine the production of grains, with high temperatures causing a reduction in grain yield and quality. To ensure continued food security, the tolerance of high temperature is rapidly becoming necessary. Brassinosteroids (BR) are a class of plant hormones that impact tolerance to various biotic and abiotic stresses and regulate cereal growth and fertility. Fine-tuning the action of BR has the potential to increase cereals’ tolerance and acclimation to heat stress and maintain yields. Mechanistically, exogenous applications of BR protect yields through amplifying responses to heat stress and rescuing the expression of growth promoters. Varied BR compounds and differential signaling mechanisms across cereals point to a diversity of mechanisms that can be leveraged to mitigate heat stress. Further, hormone transport and BR interaction with other molecules in plants may be critical to utilizing BR as protective agrochemicals against heat stress. Understanding the interplay between heat stress responses, growth processes and hormone signaling may lead us to a comprehensive dogma of how to tune BR application for optimizing cereal growth under challenging environments in the field.
Ligand variation and metal ion binding specificity in zinc finger peptides

Three metal binding peptides with coordination sites Cys 2 His 2 , Cys 3 His, and Cys 4 have been prepared and their metal binding properties characterized. The peptides are based on a zinc finger consensus sequence and have the sequences ProTyrLysCys 4 ProGluCys 7 GlyLysSerPheSerGlnLysSerAspLeuValLysXaa 20 GlnArgThrYaa 24 ThrGly (Xaa=Yaa=His; Xaa=His, Yaa=Cys; Xaa=Yaa=Cyn).
Gene Expression Profile and Prognostic Value of m6A RNA Methylation Regulators in Hepatocellular Carcinoma

Background N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of mammalian RNA, and it is associated with tumorigenesis and cancer progression. Its regulation is mediated via m6A-related regulators, including “erasers,” “readers,” and “writers”. The present study evaluated the expression profile, risk signature and prognostic value of 13 m6A regulators in hepatocellular carcinoma (HCC) using different datasets, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and clinical samples. Methods We used 374 HCC samples derived from the TCGA database, 569 HCC samples from 2 GEO datasets, and clinical tumour and nontumour tissues derived from 60 patients with HCC who underwent surgery in Xinqiao Hospital Chongqing to assess the gene expression profiles and prognostic values of m6A-related regulators in HCC. Results Eight of 13 core m6A-related regulators were overexpressed in all databases, including TCGA, GSE, clinical tumour and nontumour tissues of HCC. Two clusters (Cluster 1 and Cluster 2) were identified via consensus clustering. Cluster 2 was associated with poorer prognosis, higher tumour grade, higher AFP levels, and worse outcome compared to Cluster 1, which indicates that these m6A-related regulators are highly correlated with HCC malignancy. We performed survival analyses using the Log rank tests and a Cox regression model. Gene enrichment analysis was used to detect the related KEGG and GO pathways. We derived a prognostic risk signature using five selected m6A-related regulators. Conclusion Our work suggested that m6A-related regulators might be key participants in the tumour progression of HCC and potential biomarkers with prognostic value.
An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.
Symptomatic and Asymptomatic Patients in the Polish Atrial Fibrillation (POL-AF) Registry

Background: Atrial fibrillation (AF) can cause severe symptoms, but it is frequently asymptomatic. We aimed to compare the clinical features of patients with asymptomatic and symptomatic AF. Methods: A prospective, observational, multicenter study was performed (the Polish Atrial Fibrillation (POL-AF) registry). Consecutive hospitalized AF patients over 18 years of age were enrolled at ten centers. The data were collected for two weeks during each month of 2019. Results: A total of 2785 patients were analyzed, of whom 1360 were asymptomatic (48.8%). Asymptomatic patients were more frequently observed to have coronary artery disease (57.5% vs. 49.1%, p < 0.0001), heart failure with preserved ejection fraction (39.8% vs. 26.5%, p < 0.0001), a previous thromboembolic event (18.2% vs. 13.1%, p = 0.0002), and paroxysmal AF (52.3% vs. 45.2%, p = 0.0002). In multivariate analysis, history of electrical cardioversion, paroxysmal AF, heart failure, coronary artery disease, previous thromboembolic event, and higher left ventricular ejection fraction were predictors of a lack of AF symptoms. First-diagnosed AF was a predictor of AF symptoms. Conclusions: In comparison to symptomatic patients, more of those hospitalized with asymptomatic AF had been previously diagnosed with this arrhythmia and other cardiovascular diseases. However, they presented with better left ventricular function and were more frequently treated with cardiovascular medicines.
Validity and Reliability of an Instrumented Treadmill with an Accelerometry System for Assessment of Spatio-Temporal Parameters and Impact Transmission

Running retraining programs focused on concurrent feedback of acceleration impacts have been demonstrated to be a good strategy to reduce running-related injuries (RRI), as well as to improve running economy and reduce acceleration impacts and injury running incidence. Traditionally, impacts have been registered by mean of accelerometers attached directly to the athletes, which is inaccessible to the entire population, because it requires laboratory conditions. This study investigated the validity and reliability of a new device integrated directly into the treadmill, compared to a traditional acceleration impact system. Thirty healthy athletes with no history of RRI were tested on two separate days over the instrumented treadmill (AccTrea) and simultaneously with an acceleration impact system attached to the participant (AccAthl). AccTrea was demonstrated to be a valid and reliable tool for measuring spatio-temporal parameters like step length (validity intraclass correlation coefficient (ICC) = 0.94; reliability ICC = 0.92), step time (validity ICC = 0.95; reliability ICC = 0.96), and step frequency (validity ICC = 0.95; reliability ICC = 0.96) during running. Peak acceleration impact variables showed a high reliability for the left (reliability ICC = 0.88) and right leg (reliability ICC = 0.85), and peak impact asymmetry showed a modest validity (ICC = 0.55). These results indicated that the AccTrea system is a valid and reliable way to assess spatio-temporal variables, and a reliable tool for measuring acceleration impacts during running.
Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a poor prognosis and a dismal survival rate. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. This review discusses multiple mechanisms responsible for the resistance of some PDACs to VSV-based OV therapy, as well multiple rational approaches to enhance permissiveness of PDACs to VSV and expand the spectrum of PDACs responsive to VSV-based oncolytic virotherapy. Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. Upregulated type I IFN signaling and constitutive expression of a subset of interferon-simulated genes (ISGs) play a major role in such resistance, while other mechanisms, such as inefficient viral attachment and resistance to VSV-mediated apoptosis, also play a role in some PDACs. Several alternative approaches have been shown to break the resistance of PDACs to VSV without compromising VSV oncoselectivity, including (i) combinations of VSV with JAK1/2 inhibitors (such as ruxolitinib); (ii) triple combinations of VSV with ruxolitinib and polycations improving both VSV replication and attachment; (iii) combinations of VSV with chemotherapeutic drugs (such as paclitaxel) arresting cells in the G2/M phase; (iv) arming VSV with p53 transgenes; (v) directed evolution approach producing more effective OVs. The latter study demonstrated impressive long-term genomic stability of complex VSV recombinants encoding large transgenes, supporting further clinical development of VSV as safe therapeutics for PDAC.
Gaussian basis sets for use in correlated molecular calculations. V. Core-valence basis sets for boron through neon

The correlation‐consistent polarized valence basis sets (cc‐pVXZ) for the atoms boron through neon have been extended to treat core and core‐valence correlation effects. Basis functions were added to the existing cc‐pVXZ sets to form correlation‐consistent polarized core‐valence sets (cc‐pCVXZ) in the usual pattern: Double zeta added (1s1p), triple zeta added (2s2p1d), quadruple zeta added (3s3p2d1f), and quintuple zeta added (4s4p3d2f1g). The exponents of the core functions were determined by minimizing the difference between all‐electron and valence‐only correlation energies obtained from HF+1+2 calculations on the ground states of the atoms. With the cc‐pCVXZ sets, core, core‐valence, and valence correlation energies all converge exponentially toward apparent complete basis set (CBS) limits, as do the corresponding all‐electron singles and doubles CI energies. Several test applications of the new sets are presented: The first two ionization potentials of boron, the 3P–5S separation in carbon, and the X.
Prediction and Activity of a Cationic α-Helix Antimicrobial Peptide ZM-804 from Maize

Antimicrobial peptides (AMPs) are small molecules consisting of less than fifty residues of amino acids. Plant AMPs establish the first barrier of defense in the innate immune system in response to invading pathogens. The purpose of this study was to isolate new AMPs from the Zea mays L. inbred line B73 and investigate their antimicrobial activities and mechanisms against certain essential plant pathogenic bacteria. In silico, the Collection of Anti-Microbial Peptides (CAMPR3), a computational AMP prediction server, was used to screen a cDNA library for AMPs. A ZM-804 peptide, isolated from the Z. mays L. inbred line B73 cDNA library, was predicted as a new cationic AMP with high prediction values. ZM-804 was tested against eleven pathogens of Gram-negative and Gram-positive bacteria and exhibited high antimicrobial activities as determined by the minimal inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs). A confocal laser scanning microscope observation showed that the ZM-804 AMP targets bacterial cell membranes. SEM and TEM images revealed the disruption and damage of the cell membrane morphology of Clavibacter michiganensis subsp. michiganensis and Pseudomonas syringae pv. tomato (Pst) DC3000 caused by ZM-804. In planta, ZM-804 demonstrated antimicrobial activity and prevented the infection of tomato plants by Pst DC3000. Moreover, four virulent phytopathogenic bacteria were prevented from inducing hypersensitive response (HR) in tobacco leaves in response to low ZM-804 concentrations. ZM-804 exhibits low hemolytic activity against mouse red blood cells (RBCs) and is relatively safe for mammalian cells. In conclusion, the ZM-804 peptide has a strong antibacterial activity and provides an alternative tool for plant disease control. Additionally, the ZM-804 peptide is considered a promising candidate for human and animal drug development.