bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Surface Data Simulation Performance with the Brazilian Global Atmospheric Model (BAM)
Authors: Herdies Dirceu Luis , Silva Fabrício Daniel dos Santos , Gomes Helber Barros , Silva Maria Cristina Lemos da , Gomes Heliofábio Barros , Costa Rafaela Lisboa , Lins Mayara Christine Correia , Reis Jean Souza dos , Kubota Paulo Yoshio , Souza Dayana Castilho de , Melo Maria Luciene Dias de , Mariano Glauber Lopes
Published: January 2023

In this study, we evaluated the performance of the Brazilian Global Atmospheric Model (BAM), in its version 2.2.1, in the representation of the surface variables solar radiation, temperature (maximum, minimum, and average), and wind speed. Three experiments were carried out for the period from 2016 to 2022 under three different aerosol conditions (constant (CTE), climatological (CLIM), and equal to zero (ZERO)), discarding the first year as a spin-up period. The observations came from a high-resolution gridded analysis that provides Brazil with robust data based on observations from surface stations on a daily scale from 1961 to 2020; therefore, combining the BAM outputs with the observations, our intercomparison period took place from 2017 to 2020, for three timescales: daily, 10-day average, and monthly, targeting different applications. In its different simulations, BAM overestimated solar radiation throughout Brazil, especially in the Amazon; underestimated temperature in most of the northeast, southeast, and south regions; and overestimated in parts of the north and mid-west; while wind speed was only not overestimated in the Amazon region. In relative terms, the simulations with constant aerosol showed better performance than the others, followed by climatological conditions and zero aerosol. The dexterity indices applied in the intercomparison between BAM and observations indicate that BAM needs adjustments and calibration to better represent these surface variables. Where model deficiencies have been identified, these can be used to drive model development and further improve the predictive capabilities.
An Experimental Method for Evaluating Ammonia Emission Rates of Bio-Curtain
Authors: Halder Joshua Nizel , Park Jun Su , Park So Yean , Kwon Kyeong Seok , Hwang Ok Hwa
Published: January 2023

Bio-curtain (i.e., curtain) is a permeable cover equipped with a spraying system for ammonia (NH3) control in a swine facility. Previous studies investigated the NH3 reduction effects primarily based on concentration units. It is challenging to determine the actual efficiency because of the large amount of air discharged through the large surface of the curtain, and external wind rapidly dilutes and disperses the exhausted air. Therefore, this study investigates a technique to evaluate the NH3 reduction effect of the curtain in terms of emission rate. We constructed a metallic cover with a single hole around the curtain to gather the air discharged through it. The NH3 reduction effect was calculated by comparing the NH3 emission rate that was monitored in the barn exhaust fan and at the single hole of metallic cover during the non-spray and spray treatments inside the curtain at the maximum and minimum operating rate of the barn’s exhaust fan. NH3 emission rates declined both non-spray and spray at the minimum operation rate of the barn exhaust fan, but the reduction effect was higher in spray conditions than non-spray. Accumulating NH3-absorbed water inside the curtain under the low ventilation of the exhaust fan caused these circumstances.
Statistical Characteristics of Blocking High in the Ural Mountains during Winters and Relationship with Changes in Sea Surface Temperature and Sea Ice
Authors: Liu Yingying , Zhang Yuanzhi
Published: January 2023

A blocking high in the Ural Mountains, which is recognized as the third major blocking high area in the northern hemisphere, describes a deep warm high-pressure system superimposed on the westerly belt. Based on the ERA-5 daily reanalysis data (the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis global climate dataset) and using the Tibaldi and Molteni (TM) method, we selected 43 blocking high events in the Ural Mountains during the extended winters of 1979–2020 and analyzed their atmospheric circulation characteristics and influencing factors. Our findings revealed a downward trend in the frequency of occurrence of blocking highs in the Ural Mountains in winter, most of them were short-lived; furthermore, the frequency and duration of these occurrences generally followed a 3–4 years oscillating cycle. The synthetic results of the geopotential height (HGT) anomaly field and the surface air temperature (SAT) anomaly field of these 43 extended wintertime blocking high events in the Ural Mountains region showed that during the development of a blocking high, the central intensity of the positive anomalies in the Ural Mountains region first increased and then weakened, while the central intensity and meridional span of the negative anomalies in the Eurasian mid-latitudes of the SAT anomaly field increased continuously. In addition, abnormally high sea surface temperature (SST) in the North Atlantic sea area and abnormal reduction of sea ice (SI) in the Barents-Kara Sea and the Chukchi Sea in autumn had a significant impact on the wintertime formation of Ural Mountains blocking highs. In contrast, in autumn, the abnormal reduction of SI in the Barents-Kara and Chukchi Seas might also have led to the westward positioning of Ural Mountains blocking highs.
Manganese Slag Amendment Reduces Greenhouse Gas Emissions from Paddy Soil
Authors: Bai Yinping , Dai Qianli , Hai Jiangbo , Wang Qing , Liao Dahang , Liu Guotong , Wang Yinjia , Huang Jing , Zhang Rongping , Siddig Ahmed Ali Hassabelkreem , Bao Wanting , Yang Gang
Published: January 2023

Increasing crop productivity and minimizing greenhouse gas emissions from paddy fields are increasingly receiving attention. Slag application not only can maximize the use of solid wastes as beneficial resources for agricultural production, but it also reduces greenhouse gas emissions. In order to determine the most effective slags as soil amendments for greenhouse gas emission reduction, three major slags, i.e., steel, titanium and manganese slags, were applied as soil amendments to paddy soils; correspondingly, the greenhouse gas emissions, cumulative emissions and global warming potential of the soils during one growing season were measured. It was found that applying all these three slags could reduce the methane emission rates and the cumulative methane emissions. Manganese slag significantly decreased methane emissions by 55% compared with the control. Carbon dioxide caused no significant changes among different slag treatments; however, the cumulative carbon dioxide emissions from fields treated with steel and manganese slags were lower than those from control fields. The global warming potential of paddy soil with manganese application was 63% lower than that of the control. Finally, manganese oxide was found to have a negative relation with greenhouse gas emissions. It was inferred that the electron acceptors and the photocatalysis of manganese oxide minerals might have been the main reasons for greenhouse gas reduction. This preliminary result could be further applied to utilizing solid wastes as beneficial resources and to developing carbon fixation and greenhouse gas reduction fertilizers.
Investigation of Water and Soil Migration and Mud Pumping of Subgrades under Traffic Load
Authors: Wang Lin , Zhang Lixin , Wang Tianliang , Zhang Shengjie
Published: January 2023

Atmospheric precipitation leads to the increase of moisture in the subgrade. The moisture and soil migration in subgrade is a key scientific problem in evaluating the service performance of the subgrade and resolving or preventing mud pumping. Using a self-developed testing system as well as a numerical simulation model, a detailed study of the dynamic hydraulic characteristics, water migration mechanism, fine soil migration mechanism, and mud pumping properties of the subgrade was conducted. The results showed that water migrated into the upper layer of the subgrade under traffic load. Meanwhile, a pressure gradient for the pore water was generated in the subgrade. This kind of pressure gradient is beneficial for the moisture and fine soil migration. With rising groundwater level and increasing traffic load, the porosity of the subgrade soil differs at different depths. The fine soil migration is caused by water migration, which causes new migration channel for water in the subgrade. Then, a circulating system of moisture and fine soil is formed in the subgrade under a traffic load. After that, the upper layer subgrade soil is nearly saturated under the action of traffic load. Then, the nearly saturated soil liquefies instantaneously, becoming mud, under the action of traffic load. However, as the loading time progresses, the moisture and fine soil in the subgrade continue to migrate upward, resulting in the mud being pumped into the ballast and the gradual disappearance of liquefied soils at different depths.
Characters of Particulate Matter and Their Relationship with Meteorological Factors during Winter Nanyang 2021–2022
Authors: Zhang Miao , Chen Shiyong , Zhang Xingang , Guo Si , Wang Yunuo , Zhao Feifei , Chen Jinhan , Qi Pengcheng , Lu Fengxian , Chen Mingchun , Bilal Muhammad
Published: January 2023

The purpose of this study is to investigate the air quality levels of Nanyang city according to Chinese air quality standards. Therefore, in this study, fine particulate matter (PM2.5), coarse particulate matter (PM10), and total suspended particulate (TSP) were analyzed from 19 November 2021 to 19 March 2022 in Nanyang city. The results show that the average concentrations of PM2.5, PM10, and TSP were 106.47 µg/m3, 137.32 µg/m3, and 283.40 µg/m3, respectively. The numbers of days that meet the national secondary air quality standard of 24-h average concentrations were 29.75% for PM2.5, 63.64% for PM10, and 63.64% for TSP, indicating that most of the time, the air quality of Nanyang city remains polluted in winter, especially with more contributions of PM2.5 compared to PM10 and TSP. The higher concentrations were observed between 07:00 and 08:00, suggesting that vehicular emissions can be a major cause of air pollution in Nanyang city. The results also show a significant positive correlation between particulate matter and relative humidity, and a weak correlation with temperature and wind speed, which suggests that higher relative humidity increases the formation of particulate matter. This study can provide theoretical support for the local government to formulate air pollution prevention and control policies for Nanyang city.
Spatial Patterns in the Extreme Dependence of Ozone Pollution between Cities in China’s BTH Region
Authors: Deng Lu , Sheng Siqi
Published: January 2023

Ozone pollution in China has become increasingly severe in recent years. Considering the damage that extreme ozone pollution may cause and the fact that the occurrence of extreme ozone pollution among different locations may be related, this paper uses hourly ozone concentration data from national monitoring stations to investigate the co-movement of extreme ozone pollution in the Beijing-Tianjin-Hebei (BTH) Region. The extreme dependence analysis is adopted to assess such extreme co-movements between different cities. The co-occurrences of extreme ozone pollution at the same time or with certain time differences in the region are analyzed. City groups suffering simultaneous extreme pollution and those where the pollution occurs with certain time differences are identified under certain criteria. Furthermore, the order in which cities experience extreme ozone pollution is determined. With the publication of the New Three-year Action Plan for Winning the Blue Sky War, our results may be important for improving the joint early-warning and emergency response mechanism at city levels in the BTH Region.
Heterogenous Canopy in a Lagrangian-Stochastic Dispersion Model for Particulate Matter from Multiple Sources over the Haifa Bay Area
Authors: Fattal Eyal , David-Saroussi Hadas , Buchman Omri , Tas Eran , Klausner Ziv
Published: January 2023

The Haifa Bay area (HBA) is a major metropolitan area in Israel, which consists of high volume transportation routes, major industrial complexes, and the largest international seaport in Israel. These, which lie relatively near densely populated residential areas, result in a multitude of air pollution sources, many of whose emissions are in the form of particulate matter (PM). Previous studies have associated exposure to such PM with adverse health effects. This potential consequence serves as the motivation for this study whose aim is to provide a realistic and detailed three-dimensional concentration field of PM, originating simultaneously from multiple sources. The IIBR in-house Lagrangian stochastic pollutant dispersion model (LSM) is suitable for this endeavor, as it describes the dispersion of a scalar by solving the velocity fluctuations in high Reynolds number flows. Moreover, the LSM was validated in urban field experiments, including in the HBA. However, due to the fact that the multiple urban sources reside within the canopy layer, it was necessary to integrate into the LSM a realistic canopy layer model that depicts the actual effect of the roughness elements’ drag on the flow and turbulent exchange of the urban morphology. This was achieved by an approach which treats the canopy as patches of porous media. The LSM was used to calculate the three-dimensional fields of PM10 and PM2.5 concentrations during the typical conditions of the two workday rush-hour periods. These were compared to three air quality monitoring stations located downstream of the PM sources in the HBA. The LSM predictions for PM2.5 satisfy all acceptance criteria. Regarding the PM10 predictions, the LSM results comply with three out of four acceptance criteria. The analysis of the calculated concentration fields has shown that the PM concentrations up to 105 m AGL exhibit a spatial pattern similar to the ground level. However, it decreases by a factor of two at 45 m AGL, while, at 105 m, the concentration values are close to the background concentrations.
On the Use of the Generalized Littlewood Theorem Concerning Integrals of the Logarithm of Analytical Functions for the Calculation of Infinite Sums and the Analysis of Zeroes of Analytical Functions
Authors: Sekatskii Sergey
Published: January 2023

Recently, we have established and used the generalized Littlewood theorem concerning contour integrals of the logarithm of an analytical function to obtain a few new criteria equivalent to the Riemann hypothesis. Here, the same theorem is applied to calculate certain infinite sums and study the properties of zeroes of a few analytical functions. On many occasions, this enables to facilitate the obtaining of known results thus having important methodological meaning. Additionally, some new results, to the best of our knowledge, are also obtained in this way. For example, we established new properties of the sum of inverse zeroes of a digamma function, new formulae for the sums ∑kiρi2 for zeroes ρi of incomplete gamma and Riemann zeta functions having the order ki (These results can be straightforwardly generalized for the sums ∑kiρin with integer n > 2, and so on.)
Collinearity and Dimensionality Reduction in Radiomics: Effect of Preprocessing Parameters in Hypertrophic Cardiomyopathy Magnetic Resonance T1 and T2 Mapping
Authors: Marzi Chiara , Marfisi Daniela , Barucci Andrea , Del Meglio Jacopo , Lilli Alessio , Vignali Claudio , Mascalchi Mario , Casolo Giancarlo , Diciotti Stefano , Traino Antonio Claudio , Tessa Carlo , Giannelli Marco
Published: January 2023

Radiomics and artificial intelligence have the potential to become a valuable tool in clinical applications. Frequently, radiomic analyses through machine learning methods present issues caused by high dimensionality and multicollinearity, and redundant radiomic features are usually removed based on correlation analysis. We assessed the effect of preprocessing—in terms of voxel size resampling, discretization, and filtering—on correlation-based dimensionality reduction in radiomic features from cardiac T1 and T2 maps of patients with hypertrophic cardiomyopathy. For different combinations of preprocessing parameters, we performed a dimensionality reduction of radiomic features based on either Pearson’s or Spearman’s correlation coefficient, followed by the computation of the stability index. With varying resampling voxel size and discretization bin width, for both T1 and T2 maps, Pearson’s and Spearman’s dimensionality reduction produced a slightly different percentage of remaining radiomic features, with a relatively high stability index. For different filters, the remaining features’ stability was instead relatively low. Overall, the percentage of eliminated radiomic features through correlation-based dimensionality reduction was more dependent on resampling voxel size and discretization bin width for textural features than for shape or first-order features. Notably, correlation-based dimensionality reduction was less sensitive to preprocessing when considering radiomic features from T2 compared with T1 maps.
Attenuation of SCI-Induced Hypersensitivity by Intensive Locomotor Training and Recombinant GABAergic Cells
Authors: Jergova Stanislava , Dugan Elizabeth A. , Sagen Jacqueline
Published: January 2023

The underlying mechanisms of spinal cord injury (SCI)-induced chronic pain involve dysfunctional GABAergic signaling and enhanced NMDA signaling. Our previous studies showed that SCI hypersensitivity in rats can be attenuated by recombinant rat GABAergic cells releasing NMDA blocker serine-histogranin (SHG) and by intensive locomotor training (ILT). The current study combines these approaches and evaluates their analgesic effects on a model of SCI pain in rats. Cells were grafted into the spinal cord at 4 weeks post-SCI to target the chronic pain, and ILT was initiated 5 weeks post-SCI. The hypersensitivity was evaluated weekly, which was followed by histological and biochemical assays. Prolonged effects of the treatment were evaluated in subgroups of animals after we discontinued ILT. The results show attenuation of tactile, heat and cold hypersensitivity in all of the treated animals and reduced levels of proinflammatory cytokines IL1β and TNFα in the spinal tissue and CSF. Animals with recombinant grafts and ILT showed the preservation of analgesic effects even during sedentary periods when the ILT was discontinued. Retraining helped to re-establish the effect of long-term training in all of the groups, with the greatest impact being in animals with recombinant grafts. These findings suggest that intermittent training in combination with cell therapy might be an efficient approach to manage chronic pain in SCI patients.
Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Extranodal Marginal Zone Lymphoma
Authors: Wolf Julian , Reinhard Thomas , Hajdu Rozina Ida , Schlunck Günther , Auw-Haedrich Claudia , Lange Clemens
Published: January 2023

This study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival extranodal marginal zone lymphoma (EMZL) and identifies prognostically relevant biomarkers. Ten formalin-fixed and paraffin-embedded conjunctival EMZL and eight healthy conjunctival specimens were analyzed by Massive Analysis of cDNA Ends (MACE) RNA sequencing. The 3417 upregulated genes in conjunctival EMZL were involved in processes such as B cell proliferation and Rac protein signaling, whereas the 1188 downregulated genes contributed most significantly to oxidative phosphorylation and UV protection. The tumor microenvironment, as determined by deconvolution analysis, was mainly composed of multiple B cell subtypes which reflects the tumor’s B cell lineage. However, several T cell types, including T helper 2 cells and regulatory T cells, as well as innate immune cell types, such as anti-inflammatory macrophages and plasmacytoid dendritic cells, were also strongly enriched in conjunctival EMZL. A 13-biomarker prognostic panel, including S100A8 and S100A9, classified ocular and extraocular tumor recurrence, exceeded prognostic accuracy of Ann Arbor and American Joint Committee on Cancer (AJCC) staging, and demonstrated prognostic value for patient survival in 21 different cancer types in a database of 12,332 tumor patients. These findings may lead to new options of targeted therapy and may improve prognostic prediction for conjunctival EMZL.
The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms
Authors: Liu Jia , Wang Faping , Luo Fengming
Published: January 2023

There are four members of the JAK family and seven of the STAT family in mammals. The JAK/STAT molecular pathway could be activated by broad hormones, cytokines, growth factors, and more. The JAK/STAT signaling pathway extensively mediates various biological processes such as cell proliferation, differentiation, migration, apoptosis, and immune regulation. JAK/STAT activation is closely related to growth and development, homeostasis, various solid tumors, inflammatory illness, and autoimmune diseases. Recently, with the deepening understanding of the JAK/STAT pathway, the relationship between JAK/STAT and the pathophysiology of fibrotic diseases was noticed, including the liver, renal, heart, bone marrow, and lung. JAK inhibitor has been approved for myelofibrosis, and subsequently, JAK/STAT may serve as a promising target for fibrosis in other organs. Therefore, this article reviews the roles and mechanisms of the JAK/STAT signaling pathway in fibrotic diseases.
MetaScore: A Novel Machine-Learning-Based Approach to Improve Traditional Scoring Functions for Scoring Protein–Protein Docking Conformations
Authors: Jung Yong , Geng Cunliang , Bonvin Alexandre M. J. J. , Xue Li C. , Honavar Vasant G.
Published: January 2023

Protein–protein interactions play a ubiquitous role in biological function. Knowledge of the three-dimensional (3D) structures of the complexes they form is essential for understanding the structural basis of those interactions and how they orchestrate key cellular processes. Computational docking has become an indispensable alternative to the expensive and time-consuming experimental approaches for determining the 3D structures of protein complexes. Despite recent progress, identifying near-native models from a large set of conformations sampled by docking—the so-called scoring problem—still has considerable room for improvement. We present MetaScore, a new machine-learning-based approach to improve the scoring of docked conformations. MetaScore utilizes a random forest (RF) classifier trained to distinguish near-native from non-native conformations using their protein–protein interfacial features. The features include physicochemical properties, energy terms, interaction-propensity-based features, geometric properties, interface topology features, evolutionary conservation, and also scores produced by traditional scoring functions (SFs). MetaScore scores docked conformations by simply averaging the score produced by the RF classifier with that produced by any traditional SF. We demonstrate that (i) MetaScore consistently outperforms each of the nine traditional SFs included in this work in terms of success rate and hit rate evaluated over conformations ranked among the top 10; (ii) an ensemble method, MetaScore-Ensemble, that combines 10 variants of MetaScore obtained by combining the RF score with each of the traditional SFs outperforms each of the MetaScore variants. We conclude that the performance of traditional SFs can be improved upon by using machine learning to judiciously leverage protein–protein interfacial features and by using ensemble methods to combine multiple scoring functions.
Decellularized Matrix Induced Spontaneous Odontogenic and Osteogenic Differentiation in Periodontal Cells
Authors: Ivanov Alexey A. , Danilova Tamara I. , Kuznetsova Alla V. , Popova Olga P. , Yanushevich Oleg O.
Published: January 2023

The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells.
Beeswax Alcohol and Fermented Black Rice Bran Synergistically Ameliorated Hepatic Injury and Dyslipidemia to Exert Antioxidant and Anti-Inflammatory Activity in Ethanol-Supplemented Zebrafish
Authors: Han Youngji , Zee Seonggeun , Cho Kyung-Hyun
Published: January 2023

Alcohol abuse, a global health problem, is closely associated with many pathological processes, such as dyslipidemia and cardiovascular disease. In particular, excessive alcohol consumption promotes dyslipidemia and liver damage, such as hepatic steatosis, fibrosis, and cirrhosis. Beeswax alcohol (BWA) is a natural product used for its antioxidant properties that has not been evaluated for its efficacy in alcohol-induced liver injury. In the present study, zebrafish were exposed to 1% ethanol with supplementation of 10% fermented black rice bran (BRB-F), 10% BWA, or 10% mixtures of BWA+BRB-F (MIX). The BRB-F, BWA, and MIX supplementation increased the survival rate dramatically without affecting the body weight changes. In histology of hepatic tissue, alcoholic foamy degeneration was ameliorated by the BWA or MIX supplements. Moreover, dihydroethidium (DHE) and immunohistochemistry staining suggested that the MIX supplement decreased the hepatic ROS production and interleukin-6 expression significantly owing to the enhanced antioxidant properties, such as paraoxonase. Furthermore, the MIX supplement improved alcohol-induced dyslipidemia and oxidative stress. The BWA and MIX groups showed lower blood total cholesterol (TC) and triglyceride (TG) levels with higher high-density lipoprotein-cholesterol (HDL-C) than the alcohol-alone group. The MIX group showed the highest HDL-C/TC ratio and HDL-C/TG ratio with the lowest low-density lipoprotein (LDL)-C/HDL-C ratio. In conclusion, BWA and BRB-F showed efficacy to treat alcohol-related metabolic disorders, but the MIX supplement was more effective in ameliorating the liver damage and dyslipidemia, which agrees with an enhanced antioxidant and anti-inflammatory activity exhibited by BWA/BRB-F in a synergistic manner.
Prediction of Protein Function from Tertiary Structure of the Active Site in Heme Proteins by Convolutional Neural Network
Authors: Kondo Hiroko X. , Iizuka Hiroyuki , Masumoto Gen , Kabaya Yuichi , Kanematsu Yusuke , Takano Yu
Published: January 2023

Structure–function relationships in proteins have been one of the crucial scientific topics in recent research. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure–function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure–function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB–OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with quite different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure–function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions.
Gene-Function-Based Clusters Explore Intricate Networks of Gene Expression of Circulating Tumor Cells in Patients with Colorectal Cancer
Authors: Huang Chi-Shuan , Terng Harn-Jing , Hwang Yi-Ting
Published: January 2023

Colorectal cancer (CRC) is a complex disease characterized by dynamically deregulated gene expression and crosstalk between signaling pathways. In this study, a new approach based on gene-function-based clusters was introduced to explore the CRC-associated networks of gene expression. Each cluster contained genes involved in coordinated regulatory activity, such as RAS signaling, the cell cycle process, transcription, or translation. A retrospective case–control study was conducted with the inclusion of 119 patients with histologically confirmed colorectal cancer and 308 controls. The quantitative expression data of 15 genes were obtained from the peripheral blood samples of all participants to investigate cluster–gene and gene–gene interactions. DUSP6, MDM2, and EIF2S3 were consistently selected as CRC-associated factors with high significance in all logistic models. CPEB4 became an insignificant factor only when combined with the clusters for cell cycle processes and for transcription. The CPEB4/DUSP6 complex was a prerequisite for the significance of MMD, whereas EXT2, RNF4, ZNF264, WEE1, and MCM4 were affected by more than two clusters. Intricate networks among MMD, RAS signaling factors (DUSP6, GRB2, and NF1), and translation factors (EIF2S3, CPEB4, and EXT2) were also revealed. Our results suggest that limited G1/S transition, uncontrolled DNA replication, and the cap-independent initiation of translation may be dominant and concurrent scenarios in circulating tumor cells derived from colorectal cancer. This gene-function-based cluster approach is simple and useful for revealing intricate CRC-associated gene expression networks. These findings may provide clues to the metastatic mechanisms of circulating tumor cells in patients with colorectal cancer.
Mechanistic Insights and Potential Therapeutic Approaches in PolyQ Diseases via Autophagy
Authors: Jain Mukul , Patil Nil , Abdi Gholamreza , Abbasi Tarighat Maryam , Mohammed Arifullah , Ahmad Mohd Zain Muhammad Rajaei , Goh Khang Wen
Published: January 2023

Polyglutamine diseases are a group of congenital neurodegenerative diseases categorized with genomic abnormalities in the expansion of CAG triplet repeats in coding regions of specific disease-related genes. Protein aggregates are the toxic hallmark for polyQ diseases and initiate neuronal death. Autophagy is a catabolic process that aids in the removal of damaged organelles or toxic protein aggregates, a process required to maintain cellular homeostasis that has the potential to fight against neurodegenerative diseases, but this pathway gets affected under diseased conditions, as there is a direct impact on autophagy-related gene expression. The increase in the accumulation of autophagy vesicles reported in neurodegenerative diseases was due to an increase in autophagy or may have been due to a decrease in autophagy flux. These reports suggested that there is a contribution of autophagy in the pathology of diseases and regulation in the process of autophagy. It was demonstrated in various disease models of polyQ diseases that autophagy upregulation by using modulators can enhance the dissolution of toxic aggregates and delay disease progression. In this review, interaction of the autophagy pathway with polyQ diseases was analyzed, and a therapeutic approach with autophagy inducing drugs was established for disease pathogenesis.
Role of Ferroptosis in Regulating the Epithelial–Mesenchymal Transition in Pulmonary Fibrosis
Authors: Ling Hong , Xiao Hong , Luo Ting , Lin Huicai , Deng Jiang
Published: January 2023

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease whose pathogenesis involves a complex interaction of cell types and signaling pathways. Lung epithelial cells responding to repeated injury experience persistent inflammation and sustained epithelial–mesenchymal transition (EMT). The persistence of EMT-induced signals generates extracellular matrix accumulation, thereby causing fibrosis. Ferroptosis is a newly characterized iron-dependent non-apoptotic regulated cell death. Increased iron accumulation can increase iron-induced oxidant damage in alveolar epithelial cells. Studies have demonstrated that iron steady states and oxidation steady states play an important role in the iron death regulation of EMT. This review summarizes the role of ferroptosis in regulating EMT in pulmonary fibrosis, aiming to provide a new idea for the prevention and treatment of this disease.
A Preliminary Technology Readiness Assessment of Morphing Technology Applied to Case Studies
Authors: Miceli Marco Fabio , Ameduri Salvatore , Dimino Ignazio , Pecora Rosario , Concilio Antonio
Published: January 2023

In an innovative system, it is essential to keep under control the crucial development phases, which should consider several aspects involving, for instance, the modeling or the assessment of suitable analytical representations. Aiming to pursue a final demonstration to verify the actual capability of an engineering idea, however, some fundamental elements may have been partially considered. Many projects state the initial and final technology readiness level based on the famous scale introduced by the US National and Aeronautics Space Administration (NASA) many years ago and now widespread in many fields of technology innovation. Its nine-step definition provides a high-level indication of the maturity of the observed innovative system. Trivially, the resolution of that macroscopic meter is not made for catching advancement details, but it rather provides comprehensive information on the examined technology. It is, therefore, necessary to refer to more sophisticated analysis tools that can show a more accurate picture of the development stage and helps designers to highlight points that deserve further attention and deeper analysis. The risk is to perform a very good demonstration test that can miss generality and remain confined only to that specific experimental campaign. Moving on to these assumptions, the authors expose three realizations of theirs concerning aeronautic morphing systems, to the analysis of a well-assessed Technology Readiness Level instrument. The aim is to define the aspects to be further assessed, the aspect to be considered fully mature, and even aspects that could miss some elementary point to attain full maturation. Such studies are not so frequent in the literature, and the authors believe to give a valuable, yet preliminary, contribution to the engineering of breakthrough systems. Without losing generality, the paper refers to the 2.2 version of a tool set up by the US Air Force Research Laboratory (AFRL), and NASA, with the aim to standardize the evaluation process of the mentioned nine-step TRL.
Towards a Novel Cost-Effective and Versatile Bioink for 3D-Bioprinting in Tissue Engineering
Authors: Züger Fabian , Berner Natascha , Gullo Maurizio R.
Published: January 2023

3D-bioprinting for tissue regeneration relies on, among other things, hydrogels with favorable rheological properties. These include shear thinning for cell-friendly extrusion, post-printing structural stability as well as physiologically relevant elastic moduli needed for optimal cell attachment, proliferation, differentiation and tissue maturation. This work introduces a cost-efficient gelatin-methylcellulose based hydrogel whose rheological properties can be independently optimized for optimal printability and tissue engineering. Hydrogel viscosities were designed to present three different temperature regimes: low viscosity for eased cell suspension and printing with minimal shear stress, form fidelity directly after printing and long term structural stability during incubation. Enzymatically crosslinked hydrogel scaffolds with stiffnesses ranging from 5 to 50 kPa were produced, enabling the hydrogel to biomimic cell environments for different types of tissues. The bioink showed high intrinsic cytocompatibility and tissues fabricated by embedding and bioprinting NIH 3T3 fibroblasts showed satisfactory viability. This novel hydrogel uses robust and inexpensive technology, which can be adjusted for implementation in tissue regeneration, e.g., in myocardial or neural tissue engineering.
Application of Various Optical and Electrochemical Nanobiosensors for Detecting Cancer Antigen 125 (CA-125): A Review
Authors: Pourmadadi Mehrab , Moammeri Ali , Shamsabadipour Amin , Moghaddam Yasamin Farahanian , Rahdar Abbas , Pandey Sadanand
Published: January 2023

Nowadays, diagnosing early-stage cancers can be vital for saving patients and dramatically decreases mortality rates. Therefore, specificity and sensitivity in the detection of cancer antigens should be elaborately ensured. Some early-stage cancers can be diagnosed via detecting the cancer antigen CA-125, such as ovarian cancer, and required treatments can be applied more efficiently. Thus, detection of CA-125 by employing various optical or electrochemical biosensors is a preliminary and crucial step to treating cancers. In this review, a diverse range of optical and electrochemical means of detecting CA-125 are reviewed. Furthermore, an applicable comparison of their performance and sensitivity is provided, several commercial detection kits are investigated, and their applications are compared and discussed to determine whether they are applicable and accurate enough.
Engineering At-Home Dilution and Filtration Methods to Enable Paper-Based Colorimetric Biosensing in Human Blood with Cell-Free Protein Synthesis
Authors: Free Tyler J. , Tucker Ryan W. , Simonson Katelyn M. , Smith Sydney A. , Lindgren Caleb M. , Pitt William G. , Bundy Bradley C.
Published: January 2023

Diagnostic blood tests can guide the administration of healthcare to save and improve lives. Most clinical biosensing blood tests require a trained technician and specialized equipment to process samples and interpret results, which greatly limits test accessibility. Colorimetric paper-based diagnostics have an equipment-free readout, but raw blood obscures a colorimetric response which has motivated diverse efforts to develop blood sample processing techniques. This work uses inexpensive readily-available materials to engineer user-friendly dilution and filtration methods for blood sample collection and processing to enable a proof-of-concept colorimetric biosensor that is responsive to glutamine in 50 µL blood drop samples in less than 30 min. Paper-based user-friendly blood sample collection and processing combined with CFPS biosensing technology represents important progress towards the development of at-home biosensors that could be broadly applicable to personalized healthcare.
A Dual-Function Wearable Electrochemical Sensor for Uric Acid and Glucose Sensing in Sweat
Authors: Li Zhanhong , Wang Yuwei , Fan Zheyuan , Sun Yufan , Sun Yue , Yang Yiduo , Zhang Yifan , Ma Junjie , Wang Zifeng , Zhu Zhigang
Published: January 2023

Simultaneous detection of uric acid and glucose using a non-invasive approach can be a promising strategy for related diseases, e.g., diabetes, gout, kidney disease, and cardiovascular disease. In this study, we have proposed a dual-function wearable electrochemical sensor for uric acid and glucose detection in sweat. The sensor with a four-electrode system was prepared by printing the ink on a common rubber glove. CV and chronoamperometry were used to characterize the prepared sensor’s electrochemical sensing performance. The sensors exhibited the linear range from 0 to 1.6 mM and 0 to 3.7 mM towards uric acid and glucose electrochemical sensing in phosphate-buffered solution, with the corresponding limit of detection of 3.58 μM and 9.10 μM obtained, respectively. Moreover, the sensors had shown their feasibility of real sample sensing in sweat. The linear detection range for uric acid (0 to 40 μM) and glucose (0 to 1.6 mM) in the sweat can well cover their concentration range in physiological conditions. The prepared dual-function wearable electrochemical sensor features easy preparation, fast detection, high sensitivity, high selectivity, and the practical application potential in uric acid and glucose sensing.
A Designed Vessel Using Dissolvable Polyvinyl Alcohol Membrane as Automatic Valve to Couple LAMP with CRISPR/Cas12a System for Visual Detection
Authors: Yang Tianyi , Chen Yanju , He Jinsong , Wu Jian , Wang Meixia , Zhong Xiaoping
Published: January 2023

A rapid and intuitive method for detecting Vibrio parahaemolyticus (VP) was established by a designed reaction vessel which coupled CRISPR/Cas12a with loop-mediated isothermal nucleic acid amplification (LAMP). There were two spaces in the vessel-holding LAMP reaction solution and CRISPR reaction solution, respectively, which were separated with a polyvinyl alcohol (PVA) membrane. The PVA membrane could be dissolved with a water solution. The thermolabile hemolysin (TLH) gene of VP was employed as the detection target. After the target sequence of the TLH gene was amplified with LAMP, the PVA membrane would be dissolved and the CRISPR reaction solution mixed with the LAMP reaction solution. In this way, amplicons could be detected with CRISPR/Cas12a in the reaction vessel. The fluorescent signals produced by the positive samples were clearly identified by the naked eye under a UV light, while the negative samples were dark. The whole detection procedure could be finished within 35 min with a detection limit of 100 copies/µL. The designed reaction vessel is easy to produce and can effectively prevent contamination due to the opening of the reaction vessel after the LAMP reaction. Thus, it will have the potential to provide a new solution for rapid detection in the field.
High-Performance Zwitterionic Organohydrogel Fiber in Bioelectronics for Monitoring Bioinformation
Authors: Xia Jun , Luo Jiabei , Chang Boya , Sun Chuanyue , Li Kerui , Zhang Qinghong , Li Yaogang , Wang Hongzhi , Hou Chengyi
Published: January 2023

Bioinformation plays an imperative role in day-to-day life. Wearable bioelectronics are important for sensing bioinformation in real-time and conductive hydrogel fibers are a key component in next generation wearable bioelectronics. However, current conductive hydrogel fibers have remarkable disadvantages such as insufficient conductivity, stability, and bioinformation sensing ability. Here, we report the synthesis of a zwitterionic organohydrogel (ZOH) fiber by the combination of the mold method and solvent replacement strategy. The ZOH fiber shows transparency (92.1%), stretchability (905.8%), long-term stability, anti-freezing ability (−35–60 °C), and low light transmission loss (0.17 dB/cm). Then, we integrate the ZOH fiber into fabric for use as a bioinformation sensor, the results prove its capability as a bioinformation monitor, monitoring information such as motion and bioelectric signals. In addition, the potential of the ZOH fiber in optogenetic applications is also confirmed.
Health-Related Quality of Life in Spinal Muscular Atrophy Patients and Their Caregivers—A Prospective, Cross-Sectional, Multi-Center Analysis
Authors: Wohnrade Camilla , Velling Ann-Kathrin , Mix Lucas , Wurster Claudia D. , Cordts Isabell , Stolte Benjamin , Zeller Daniel , Uzelac Zeljko , Platen Sophia , Hagenacker Tim , Deschauer Marcus , Lingor Paul , Ludolph Albert C. , Lulé Dorothée , Petri Susanne , Osmanovic Alma , Schreiber-Katz Olivia
Published: January 2023

Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient’s health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA patient/caregiver couples (n = 49) filled in the EuroQoL Five Dimension Five Level Scale (EQ-5D-5L) and the Short Form Health Survey 36 (SF-36). Caregivers (CGs) additionally answered the Zarit Burden Interview (ZBI) and the Hospital Anxiety and Depression Scale (HADS). Patients were clustered into two groups with either low or high HRQoL (EQ-5D-5L index value <0.259 or >0.679). The latter group was mostly composed of ambulatory type III patients with higher motor/functional scores. More severely affected patients reported low physical functioning but good mental health and vitality. The CGB (mean ZBI = 22/88) correlated negatively with patients’ motor/functional scores and age. Higher CGB was associated with a lower HRQoL, higher depression and anxiety, and more health impairments of the CGs. We conclude that patient and CG well-being levels interact closely, which highlights the need to consider the health of both parties while evaluating novel treatments.
The Photic Stimulation Has an Impact on the Reproduction of 10 s Intervals Only in Healthy Controls but Not in Patients with Schizophrenia: The EEG Study
Authors: Portnova Galina V. , Maslennikova Aleksandra V.
Published: January 2023

Schizophrenia is a mental disorder characterized by both abnormal time perception and atypical relationships with external factors. Here we compare the influence of external photic stimulation on time production between healthy subjects (n = 24) and patients with schizophrenia (n = 22). To delve into neuropsychological mechanisms of such a relationship, the EEG was recorded during variable conditions: during production of 10 s intervals; during photic stimulation of 4, 9, 16, and 25 Hz; and during combinations of these conditions. We found that the higher frequency of photic stimulation influenced the production of time intervals in healthy volunteers, which became significantly longer and were accompanied by corresponding EEG changes. The impact of photic stimulation was absent in patients with schizophrenia. In addition, the time production was characterized by less accuracy and the absence of EEG dynamics typical for healthy controls that included an increase in alpha2 power and envelope frequency. Our findings indicated that the time perception was not adjusted by external factors in patients with schizophrenia and might have involved cognitive and mental processes different from those of healthy volunteers.