bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carvedilol ameliorates experimental atherosclerosis by inhibiting the NLRP3 inflammasome
Authors: Xu Rui , Yan KaiXin , Bu Juan , Zhou Ling , Xu Hong 
Published: January 2024

Abstract
Objective: To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome.
Methods：In vitro experiments, human umbilical vein endothelial cells(HUVEC) were divided into the control group, ox-LDL group, carvedilol 5μM group, carvedilol 10μM group, and carvedilol 20μM group. The optimal concentration of carvedilol was determined using the CCK-8 method to assess cell proliferation levels and oil red O staining to observe intracellular lipid droplet formation. Subsequently, the cells were further divided into the control group, ox-LDL group, carvedilol 5μM (optimal concentration) group, and MCC950 (inhibitor of NLRP3 Inflammasome) group. The expression levels of intracellular proteins NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65, GSDMD, and N-GSDMD were detected by ELISA, or Western Blotting.
Results: Compared to the control group, the ox-LDL group exhibited a significant reduction in cell proliferation level (P<0.05), accompanied by an increase in lipid droplet formation upon induction. In contrast, pretreatment with carvedilol at concentrations of 5μM, 10μM, and 20μM effectively promoted cell proliferation (P<0.05) and inhibited intracellular lipid droplet formation. Notably, the most pronounced effect was observed with carvedilol pretreatment at a concentration of 5μM. Furthermore, compared to the control group, HUVEC cells in the ox-LDL group demonstrated substantial upregulation of NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65 GSDMD and N-GSDMD; however, these markers were downregulated following treatment with carvedilol and MCC950 administration-particularly evident in the carvedilol group.
Conclusion: Carvedilol effectively inhibits the progression of atherosclerosisby targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.
Stimuli-specific senescence of primary human lung fibroblasts modulates alveolar stem cell function
Authors: Bramey Nora , Melo-Narvaez Maria Camila , See Fenja , Ballester-Lllobell Beatriz , Steinchen Carina , Jain Eshita , Hafner Kathrin , Yildirim Ali Önder , Königshoff Melanie , Lehmann Mareike 
Published: January 2024

Abstract
Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging such as cellular senescence are present in different lung cell types such as fibroblasts in these patients. However, whether the senescent phenotype of fibroblasts derived from IPF or COPD patients differs is still unknown. Therefore, we characterized senescence at baseline and after exposure to disease-relevant insults (H2O2, bleomycin, and TGF-β1) in cultured primary human lung fibroblasts (phLF) from control donors, IPF, or COPD patients. We found that phLF from different disease-origins have a low baseline senescence. H2O2 and bleomycin treatment induced a senescent phenotype in phLF, whereas TGF-β1 had primarily a pro-fibrotic effect. Notably, we did not observe any differences in susceptibility to senescence induction in phLF based on disease origin, while exposure to different stimuli resulted in distinct senescence programs in phLF. Moreover, senescent phLF reduced colony formation efficiency of distal alveolar epithelial progenitor cells in a stimuli-dependent manner. In conclusion, the senescent phenotype of phLF is mainly determined by the senescence inducer and impairs alveolar epithelial progenitor capacity in vitro.
A Study on Expression Recognition Based on Improved MobileNetV2 Network
Authors: Zhu Qiming , Zhuang Hongwei , Zhao Mi , Xu Shuangchao , Meng Rui 
Published: January 2024

Abstract
This paper proposes an improved strategy for the MobileNetV2 neural network(I-MobileNetV2) in response to problems such as large parameter quantities in existing deep convolutional neural networks and the shortcomings of the lightweight neural network MobileNetV2 such as easy loss of feature information, poor real-time performance, and low accuracy rate in facial emotion recognition tasks. The network inherits the characteristics of MobilenetV2 depthwise separated convolution, signifying a reduction in computational load while maintaining a lightweight profile. It utilizes a reverse fusion mechanism to retain negative features, which makes the information less likely to be lost. The SELU activation function is used to replace the RELU6 activation function to avoid gradient vanishing. Meanwhile, to improve the feature recognition capability, the channel attention mechanism (Squeeze-and-Excitation Networks (SE-Net)) is integrated into the MobilenetV2 network. Experiments conducted on the facial expression datasets FER2013 and CK + showed that the proposed network model achieved facial expression recognition accuracies of 68.62% and 95.96%, improving upon the MobileNetV2 model by 0.72% and 6.14% respectively, and the parameter count decreased by 83.8%. These results empirically verify the effectiveness of the improvements made to the network model.
Computational analysis of substituent effects on proton affinity and gas-phase basicity of TEMPO derivatives, and their hydrogen bonding interactions with water molecules
Authors: Shiroudi Abolfazl , Śmiechowski Maciej , Czub Jacek , Abdel-Rahman Mohamed A. 
Published: January 2024

Abstract
The molecular structure of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives (X: CH3, NH2, CHO, and NO2) in the gas phase, as well as their hydration, is investigated using the B3LYP method and the 6-311 + + G(d,p) basis set. Intermolecular interactions are analyzed using the natural bond orbital (NBO) and atoms in molecules (AIM) techniques. NBO analysis reveals the stability and formation of compounds, while AIM calculations show all hydrogen bonding interactions in the hydrated forms of TEMPO derivatives. The chemical reactivity parameters show that NO2-substituted TEMPO, with a small HOMO-LUMO energy gap, is more reactive, less stable, and exhibits softer qualities. Furthermore, the NBO results show that the stability of the investigated TEMPO derivatives is mainly influenced by LP(e)→σ∗ electronic delocalization effects, with the highest stabilization observed on the oxygen atom of the nitroxide moiety. The study considers electron density, atomic charges, and energetic and thermodynamic properties of the studied nitroxide radicals and their relative stability. The study computed the proton affinity (PA) and gas-phase basicity (GB) of TEMPO derivatives at T = 298 K for the O-protonation and N-protonation.The computed PA values in case of O-protonation of TEMPO derivatives (X: H, CH3, NH2, CHO, NO2) are 896.04, 894.17, 892.57, 870.36, and 851.29 kJ/mol, respectively, while the corresponding values for N-protonation are 806.50, 806.92, 804.08, 787.45, and 763.11 kJ/mol, respectively. The AIM analysis reveals that the N−O…H interaction in H2O complexes has the most favorable H-bond energy. The electronic structure characterization of N−O…H bonds in stable conformers of studied TEMPO derivatives revealed H-bond energies of 6.90, 6.90, 6.87, 6.62, and 6.46 kcal/mol for H, CH3, NH2, CHO, and NO2 substitutions, computed at bond critical points (3,−1).
Gripping Insights: Relative Muscle Strength and Its Association with Hypertension and Prehypertension: A Cross-Sectional Study
Authors: M Yogesh , Nagda Jay , Patel Nirmalkumar Shaileshbhai , Varu Jay 
Published: January 2024

Abstract

Background: Hypertension and muscle strength are known to be associated; however, identifying simple clinical indicators of this relationship ischallenging. Relative muscle strength (RMS), defined as strength per unit muscle mass, has been proposed as a potential indicator, but its association with hypertension is unclear. This study aimed to investigate the relationship between RMS and hypertension in middle-aged and older adults.
Methods: This hospital-based cross-sectional study included 430 adults attending outpatient medicine clinics from January to October 2023. Grip strength and appendicular skeletal muscle mass (ASM), estimated using a validated formula, were also measured. The RMS was calculated as grip strength/ASM. Hypertension was defined using standard criteria. Logistic regression was used to analyse the relationship between RMS and hypertension, adjusting for confounders.
Results: The prevalence of prehypertension and hypertension was 43% and 23%, respectively. According to the adjusted analysis, a higher RMS was associated with 33% lower odds of prehypertension (OR=0.67, 95% CI=0.49-0.91) and 26% lower odds of hypertension (OR=0.74, 95% CI=0.59-0.89) than was the lowest RMS tertile. RMS also showed strong negative correlations with systolic and diastolic blood pressure (r=-0.549 and -0.418, respectively; p<0.001).
Conclusion: Increased relative muscle strength was significantly protective against prehypertension and hypertension. Maintaining muscle quality through resistance exercise or other approaches may promote hypertension prevention.
Breast-conserving surgery with partial resection of the nipple and areola considering the anatomy of the mammary gland
Authors: Ogawa Akio , Ito Yuko , Nojiri Motoi , Yoshihara Motoi 
Published: January 2024

Abstract

Background
For breast cancer in or near the nipple–areolar region, the nipple–areolar complex (NAC) is generally resected. The NAC is important for the appearance of the breast. By embryological mechanism, each glandular lobe system is independent until the ductal opening on the nipple surface.
Methods
Breast-conserving surgery was performed with quadrantectomy of the nipple, including the target duct, by adding a full-layer excision of the areolar region, and further resection, including the main breast cancer lesion. Sixty patients underwent the procedure. The main lesion occupied a subsite other than the nipple–areolar region in 43 patients. The degree of intraductal growth toward the nipple was determined using preoperative contrast-enhanced magnetic resonance imaging in the prone position. The diagnosis was made based on the pathology results of postoperative resection specimens.
Results
The shape of the excised mammary gland appeared like a whole cake cutting. Eight cases had positive resection margins. Two cases were positive at the nipple-side dissecting edge. Eight patients had no lesions in the nipple–areolar region. Deformation of the NAC was slight. The postoperative breast morphology was similar to that of other conservative techniques. This technique allows for partial excision of the nipple to preserve the NAC and safely perform breast-conserving surgery.
Conclusion
Breast-conserving surgery with partial nipple and areola resection is an option for early-stage breast cancer with possible intraductal growth to the nipple–areolar region.
Integrated analyses of the intestinal microbiome and transcriptome in NingXiang piglets
Authors: Hu Zhenguo , Yao Yuezhou , Chen Feiyue , Feng Luya , Yuan Zian , Deng Junhao , Huang Lang , Tang Xiongzhuo , Yin Yulong 
Published: January 2024

Abstract

Background
NingXiang (NX) pig has been characterized as one of the best Chinese indigenous pig breeds, with high fertility and disease resistance.
However, its intestinal gene expression and gut microbial characteristics have not been studied.
Results
Here, we delineated and compared the profile of intestinal microbiome and transcriptome between NX and Duroc × Landrace × Large white (DLY) piglets by integrating metagenomic and transcriptomic analyses. We found that the abundance of several colonic Bacteroides species (B. fragilis, B. thetaiotaomicron and B. sp_PHL_2737), Prevotella species (P. intermedia, P. dentalis and P. enoeca), Clostridium species (C. scindens, C. butyricum and C. botulinum), Anaerrobutyricum and Lactobacillus_saerimneri are significantly increased in NX piglets than DLY piglets. Additionally, several archaea and fungal species were also dominantly enriched in the colon of NX piglets. Then, we identified some unique colonic bacterial species that may act as characteristics of these two pig breeds. Functional analyses of NX piglets-enriched microbes revealed their dominant function in methane, glycolysis and gluconeogenesis metabolism. Strikingly, the composition and function of the gut microbiota were significantly correlated with growth performance both in NX and DLY piglets. Finally, our mRNA-sequencing revealed the distinct intestinal gene expression pattern between NX and DLY piglets, and NX piglets exhibit improved intestinal barrier function and varied immune features than DLY piglets.
Conclusion
Together, our study revealed the characteristics of the gut microbiota and intestinal gene expression in NX piglets, providing the potential to explore its mechanisms in disease resistance and gut development.
Unveiling Digenic Pathogenic Variants and Mutation Susceptibility in Chinese Patients with Suspected Retinitis Pigmentosa
Authors: Ziwei Wang , Han Dongming , li Jiankang 
Published: January 2024

Abstract

Background
Retinitis pigmentosa (RP; MIM: #268000) is a type of inherited retinal dystrophy (IRD) characterized by the progressive loss of retinal photoreceptors. In recent years, the field of bioinformatics has made significant advancements, enabling us to uncover new digenic disease variants associated with RP. Additionally, there is increasing attention given to identifying prevalent founder mutations, as they have the potential to be targeted by mutation-specific therapies that focus on specific regions of the genome.
Methods
We conducted a retrospective study involving 450 patients who were diagnosed with suspected RP as the study cohort. To serve as a control cohort, we included their family members. In this study, we aimed to establish a genotype-phenotype correlation among all participants. For patients who did not have any identified pathogenic variants, we performed digenic pathogenicity prediction along with Sanger sequencing validation. Furthermore, we conducted transmission linkage disequilibrium analysis to identify susceptibility loci for all patients.
Result
In our study, we achieved a molecular diagnosis in 67.8% of the patients, with the top 17 genes accounting for 75.63% of the 305 diagnosed cases. We identified a total of 464 known pathogenic loci, consisting of 103 different variants, as well as 73 novel pathogenic loci with 43 different variants. Among these findings, we discovered 12 suspected pathogenic digenic loci pairs, and two of them were successfully validated through Sanger sequencing - PDE6A c.1744C > T/RP1 c.607G > T and CRB1 c.2714G > A/PROM1 c.1438G > A. After applying the Bonferroni correction, we identified eight significant mutations associated with suspected RP. These mutations include MSH2 c.212-16delT, LRP5 c.58-60del, FOXE3 c.211A > G, PRX c.4077-4079del, DMD c.8810A > A, GP1BA c.1322-1344del, SYNE2 c.1170A > C, and SMPD1 c.573T > C. Additionally, our study unveiled 26 combinations of highly correlated susceptible loci involving 31 genes. Among these combinations, MSH2 c.212-16delT and WFS1 c.1832G > A were identified as susceptible interaction hotspots.
Conclusion
In conclusion, this retrospective study demonstrated that a considerable number of patients achieved a molecular diagnosis. Furthermore, the study aimed to identify novel digenic disease variants in patients with suspected RP utilizing bioinformatics methods. The findings of the study also unveiled significant susceptible mutations associated with suspected RP, shedding light on potential targets for mutation-specific therapy in the future.
Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach
Authors: Singh Khushboo , Patten J. J. , Dimet Andrea , Davey Robert A. , Watowich Stanley J. , Chandra Amit , Leverett Jesse 
Published: January 2024

Abstract
The main protease (MPro) of SARS-CoV-2 plays a crucial role in viral replication and is a prime target for therapeutic interventions. Phytochemicals, known for their antiviral properties, have been previously identified as potential MPro inhibitors in several in silico studies. However, the efficacy of these remains in question owing to the inherent flexibility of the MPro binding site, posing challenges in selecting suitable protein structures for virtual screening. In this study, we conducted an extensive analysis of the MPro binding pocket, utilizing molecular dynamics (MD) simulations to explore its conformational diversity. Based on pocket volume and shape-based clustering, five representative protein conformations were selected for virtual screening. Virtual screening of a library of ~ 48,000 phytochemicals suggested 39 phytochemicals as potential MPro inhibitors. Based on subsequent MM-GBSA binding energy calculations and ADMET property predictions, five compounds were advanced to cell-based viral replication inhibition assays, with three compounds (demethoxycurcumin, shikonin, and withaferin A) exhibiting significant (EC50 < 10 uM) inhibition of SARS-CoV-2 replication. Our study provides an understanding of the binding interactions between these phytochemicals and MPro, contributing significantly to the identification of promising MPro inhibitors. Furthermore, beyond its impact on therapeutic development against SARS-CoV-2, this research highlights a crucial role of proper nutrition in the fight against viral infections.
Nonreciprocal feedback induces migrating oblique and horizontal banded vegetation patterns in hyperarid landscapes
Authors: Hidalgo Belen , Pinto David , Tlidi Mustapha , Clerc Marcel 
Published: January 2024

Abstract
In hyperarid environments, vegetation is highly fragmented, with plant populations exhibiting non-random biphasic structures where regions of high biomass density are separated by bare soil. In the Atacama Desert of northern Chile, rainfall is virtually nonexistent, but fog pushed in from the interior sustains patches of vegetation in a barren environment. Tillandsia landbeckii, a plant with no functional roots, survives entirely on fog corridors as a water source. Their origin is attributed to interaction feedback among the ecosystem agents, which have different spatial scales, ultimately generating banded patterns as a self-organising response to resource scarcity. The interaction feedback between the plants can be nonreciprocal due to the fact that the fog flows in a well-defined direction. Using remote sensing analysis and mathematical modelling, we characterise the orientation angle of banded vegetation patterns with respect to fog direction and topographic slope gradient. We show that banded vegetation patterns can be either oblique or horizontal to the fog flow rather than topography. The initial and boundary conditions determine the type of the pattern. The bifurcation diagram for both patterns is established. The theoretical predictions are in agreement with observations from remote sensing image analysis.
Developing a scoring framework for curriculum viability indicators to assess the survival of a curriculum
Authors: Sikander Fatima , Khan Rehan A , Batool Saima 
Published: January 2024

Abstract

Background:
Curriculum viability indicators are crucial in the success of a curriculum. In our study, curriculum viability within the context of medical education was undertaken, with a particular focus on the development and validation of a scoring framework.
Methods:
The study spans two phases, beginning with the creation of norm tables using the Median split method for Curriculum viability student questionnaire and Curriculum viability teacher questionnaire. These norm tables serve to categorize curriculum viability into high, satisfactory, and poor levels. The scoring framework undergoes refinement through validation using the Modified Angoff method and Receiver Operating Characteristic (ROC) analysis.
Results:
Results indicate a cut-off score range for CVTQ (51-75 by norm table, 69.5 via ROC, and 42 through expert consensus) and for CVSQ (29-42 by norm table and 46 via Modified Angoff).
Conclusion:
Our study offers a comprehensive diagnostic tool for curriculum viability and a basis for informed decision-making in educational planning and improvement.
Uncovering the neural control of laryngeal activity and subglottic pressure in anaesthetized rats: insights from mesencephalic regions
Authors: Marta González-García , Laura Carrillo-Franco , Carmen Morales-Luque , Marina Ponce-Velasco , Belén Gago , Stefan Dawid-Milner Marc , Víctor López-González Manuel 
Published: January 2024

Abstract
To assess the possible interactions between the dorsolateral Periaqueductal Gray matter (dlPAG) and the laryngeal motor neurons of the nucleus Ambiguus (nA), we have examined the pattern of double staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/Fox-P2-ir) and Tyrosine Hydroxylase (TH) throughout the rostro-caudal extent of nA in spontaneously breathing anaesthetised male Sprague–Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p<0.05) and compact formation (p<0.01) within the nA and confirm the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stmulations evoked a significant decrease of laryngeal resistance (subglottal pressure) (p<0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute with new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.
P-GeT Assay: An Innovative Frontier in CircRNA Enrichment
Authors: Sharma Priyanka , Guria Ashirbad , Pandi Gopal 
Published: January 2024

Abstract

Circular RNAs have garnered attention as essential regulators of gene expression and potential biomarkers in various biological processes and diseases. However, their reliable enrichment from complex RNA pool remains a critical challenge and a costlier approach. Here, we present the "Plug-Gel Trap (P-GeT) assay," as a novel, cost-efficient, and innovative way that bypass the existing exorbitant techniques for circRNA enrichment. By greatly modifying the existing (circular DNA) gel-trap method, the principles of P-GeT assay capitalize on efficient entrapment of unique covalently-closed circular characteristics of RNAs while excluding linear counterparts. In this article, we sketch the fundamental principles behind the P-GeT assay, detailing its workflow and highlighting specificity and efficiency in aggrandizing circRNAs. We compared the competence of two regularly used gel sieves composed of either acrylamides or agarose to significantly trap circular transcripts. The selective trapping by P-GeT assay is validated using the divergent and convergent oligo-nucleotides specific to circular and linear transcripts respectively, and subsequently by northern hybridization. Both the validations are greatly able to detect only the circular form rather than linear transcript. Our study not only introduces an innovative approach for circRNA enrichment but also underscores its versatility and cost-effectiveness, making it accessible to a broader research community. The P-GeT assay represents a significant step towards advancing circRNA studies, unlocking their full potential in deciphering complex biological processes and disease mechanisms.