bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Validation, and Economic Behavior of a Three-Phase Interleaved Step-Up DC–DC Converter for Electric Vehicle Application
Authors: Saravanakumar T. , Saravana kumar R.
Published: June 2022

Due to the increasing number of direct current (DC) loads in electric vehicles (EVs), DC–DC converters are widely used in EV applications. Hence, a DC distribution system with DC–DC converters is more efficient. A three-phase interleaved step-up DC–DC converter (ISC) has been proposed for use in electric vehicles. Other uses of the proposed ISC converter include aircraft, satellites, industrial, and traction drives. The proposed converter is subjected to a thorough frequency response study, which is explained in detail. The design technique recommends the proper quantity of switches to be used in the system. The reduction in the number of switches results in a 94% increase in the efficiency of this converter. The economic aspects of ISC, such as cost analysis and its procedure, have been discussed. Design models were checked using MATLAB/Simulink, which was interfaced with the real-time simulator OPAL-RT (OP5700) to ensure that they were appropriate. The results have been presented in detail.
Consensus Dispatch of Distributed Power Network Based on Multi-Access Edge Computing and Multi-Agent System
Authors: Wang Liming , Liu Yingming , Wang Xiaodong , Wang Hanbo , Guo Guoxian
Published: June 2022

This paper presents a consensus dispatch model of the distributed power network based on multi-access edge computing (MEC) and multi-agent system (MAS).MEC decentralizes the processing and storage of data in the distributed power system to the edge node combined with MAS, which reduces the amount of calculation in the dispatch center. The model formulates different objective functions for the edge nodes and the cloud center nodes of the MEC to optimally allocate the output of each unit. Meanwhile, in order to meet the consensus dispatch of distributed units, the operational benefits of flexible load, the operating cost of thermal power units, the penalty cost of abandoning wind and solar power for new energy units, and the operation of energy storage devices are utilized as consensus variables. Based on these consensus variables, an optimal dispatch method of the distributed power network is established. Compared with the traditional dispatch model, this model integrates distributed units and autonomous sub-regions through MAS and MEC, which ensures the system performs consensus dispatch under the balance of supply and demand, and also improves the proportion of new energy consumption.
Developing an Immune-Related Signature for Predicting Survival Rate and the Response to Immune Checkpoint Inhibitors in Patients With Glioma
Authors: Zhang Sibin , Xiao Xu , Wang Yu , Song Tianjun , Li Chenlong , Bao Hongbo , Liu Qing , Sun Guiyin , Sun Xiaoyang , Su Tianqi , Fu Tianjiao , Wang Yujie , Liang Peng
Published: June 2022

Background: Glioma is one of the most aggressive cancer types affecting the central nerve system, with poor overall survival (OS) rates. The present study aimed to construct a novel immune-related signature to predict prognosis and the efficiency of immunotherapy in patients with glioma.

Methods: The mRNA expression data and other clinical information of patients with glioblastoma multiforme (GBM) and low grade glioma (LGG) were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The immune-related genes were obtained from the Immunology Database and Analysis Portal database. Subsequently, an immune-related signature was created following the results obtained from the Least Absolute Shrinkage and Selection Operator regression model. To validate the predictability of the signature, Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were created. Moreover, both univariate and multivariate analyses were carried out using the OS between this signature and other clinicopathologic factors, and a nomogram was constructed. In addition, the association between signature, immune cell infiltration, tumor mutation burden and immunophenoscore were determined.

Results: Results of the present study using 118 GBM and LGG samples uncovered 15 immune-related genes that were also differently expressed in glioma samples. These were subsequently used to construct the immune-related signature. This signature exhibits the ability to predict prognosis, the infiltration of immune cells in the tumor microenvironment and the response of patients with glioma to immunotherapy.

Conclusion: Results of the present study demonstrated that the aforementioned novel immune-related signature may accurately predict prognosis and the response of patients with glioma to immunotherapy.
Serum Immunoglobulins, Pneumonia Risk, and Lung Function in Middle-Aged and Older Individuals: A Population-Based Cohort Study
Authors: Khan Samer R. , Vanoverschelde Anna , Lahousse Lies , Peeters Robin P. , van Hagen P. Martin , Brusselle Guy , Chaker Layal , Dalm Virgil A. S. H.
Published: June 2022

Introduction

Immunoglobulins (Igs) play a pivotal role in host defense and prevention of pneumonia. Aging influences serum Ig levels, but the association between Igs and pneumonia in community-dwelling older individuals remains unknown. We evaluated the association of serum IgA, IgG, and IgM with pneumonia and lung function in middle-aged and older individuals.

Methods

We performed Cox and negative binomial regression analyses for the association of Igs with incident pneumonia and pneumonia-related mortality, and recurrent pneumonia respectively. We performed logistic regression analyses for the association between Igs and lung function values. Associations were adjusted for age, sex, smoking, comorbidities, and serum C-reactive protein.

Results

We included 8,766 participants (median age 62.2 years, 57% women, median follow-up 9.8 years). Higher IgA (hazard ratio [HR]: 1.15; 95% confidence interval [95% CI]: 1.00-1.32) and IgG (HR: 1.13; 95% CI: 1.06-1.19) were associated with an increased pneumonia risk. Higher IgG was associated with an increased risk of pneumonia-related mortality (HR: 1.08; 95% CI: 1.01-1.16) and recurrent pneumonia (incidence rate ratio: 1.04; 95% CI: 1.00-1.09). Higher IgA and IgG were also associated with lower forced expiratory volume in one second (FEV1), lower forced vital capacity (FVC), and an increased odds of preserved ratio impaired spirometry (PRISm, i.e. FEV1 <80% and FEV1/FVC ratio ≥70%). No association was seen with an obstructive spirometry pattern.

Discussion

Higher serum IgA and IgG levels were associated with pneumonia, pneumonia-related mortality, and PRISm in middle-aged and older individuals from the general population. Future studies should validate our findings and elucidate underlying pathophysiology.
A Phase I Study of Locoregional High-Dose Autologous Natural Killer Cell Therapy With Hepatic Arterial Infusion Chemotherapy in Patients With Locally Advanced Hepatocellular Carcinoma
Authors: Bae Woo Kyun , Lee Byung Chan , Kim Hyeon-Jong , Lee Je-Jung , Chung Ik-Joo , Cho Sung Bum , Koh Yang Seok
Published: June 2022

Background

To explore the feasibility and safety of natural killer (NK) cell therapy in HCC, we performed a prospective, open-label, phase I trial to evaluate the synergistic effect of locoregional high-dose autologous NK cell therapy in combination with hepatic arterial infusion chemotherapy (HAIC).

Methods

Patients with locally advanced HCC who were refractory to the standard treatment were eligible for this study. Patients received expanded and activated NK cells for 5 consecutive days in a dose-escalating manner (dose 2.5×108, 5×108, 10×108 NK cells/injection) through hepatic arterial infusion following 4 cycles of HAIC with 5-fluorouracil (750 mg/m2) and cisplatin (25 mg/m2). The primary endpoint was the safety of NK cell-based immunotherapy, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immunologic responses.

Results

Of the 11 patients enrolled, the confirmed ORR was 63.6% (complete response [CR]: 36.4%, confirmed partial response [PR]: 27.3%). Stable disease (SD) and progressive disease (PD) were observed in two patients (18.2%) each, resulting in a disease control rate (DCR) of 81.8%. The median PFS and OS were 10.3 and 41.6 months, respectively. There were no incidences of decompensation or severe adverse events during HAIC, and no adverse events related to NK cell infusion were noted.

Conclusion

The combination of HAIC and locoregional high-dose NK cell therapy is a safe and effective treatment for locally advanced HCC patients who were refractory to the standard treatment. This result warrants further development of this novel treatment to establish its efficacy in HCC.

Clinical Trial Registration

cris.nih.go.kr, identifier KCT0003973.
Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses
Authors: Xia Xiaoyan , Cheng Anchun , Wang Mingshu , Ou Xumin , Sun Di , Mao Sai , Huang Juan , Yang Qiao , Wu Ying , Chen Shun , Zhang Shaqiu , Zhu Dekang , Jia Renyong , Liu Mafeng , Zhao Xin-Xin , Gao Qun , Tian Bin
Published: June 2022

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.
Diurnal Differences in Intracellular Replication Within Splenic Macrophages Correlates With the Outcome of Pneumococcal Infection
Authors: Hames Ryan G. , Jasiunaite Zydrune , Ercoli Giuseppe , Wanford Joseph J. , Carreno David , Straatman Kornelis , Martinez-Pomares Luisa , Yesilkaya Hasan , Glenn Sarah , Moxon E. Richard , Andrew Peter W. , Kyriacou Charalambos P. , Oggioni Marco R.
Published: June 2022

Circadian rhythms affect the progression and severity of bacterial infections including those caused by Streptococcus pneumoniae, but the mechanisms responsible for this phenomenon remain largely elusive. Following advances in our understanding of the role of replication of S. pneumoniae within splenic macrophages, we sought to investigate whether events within the spleen correlate with differential outcomes of invasive pneumococcal infection. Utilising murine invasive pneumococcal disease (IPD) models, here we report that infection during the murine active phase (zeitgeber time 15; 15h after start of light cycle, 3h after start of dark cycle) resulted in significantly faster onset of septicaemia compared to rest phase (zeitgeber time 3; 3h after start of light cycle) infection. This correlated with significantly higher pneumococcal burden within the spleen of active phase-infected mice at early time points compared to rest phase-infected mice. Whole-section confocal microscopy analysis of these spleens revealed that the number of pneumococci is significantly higher exclusively within marginal zone metallophilic macrophages (MMMs) known to allow intracellular pneumococcal replication as a prerequisite step to the onset of septicaemia. Pneumococcal clusters within MMMs were more abundant and increased in size over time in active phase-infected mice compared to those in rest phase-infected mice which decreased in size and were present in a lower percentage of MMMs. This phenomenon preceded significantly higher levels of bacteraemia alongside serum IL-6 and TNF-α concentrations in active phase-infected mice following re-seeding of pneumococci into the blood. These data greatly advance our fundamental knowledge of pneumococcal infection by linking susceptibility to invasive pneumococcal infection to variation in the propensity of MMMs to allow persistence and replication of phagocytosed bacteria. These findings also outline a somewhat rare scenario whereby the active phase of an organism’s circadian cycle plays a seemingly counterproductive role in the control of invasive infection.
PET/CT-Based Characterization of 18F-FDG Uptake in Various Tissues Reveals Novel Potential Contributions to Coronary Artery Disease in Psoriatic Arthritis
Authors: Schwartz Daniella M. , Parel Philip , Li Haiou , Sorokin Alexander V. , Berg Alexander R. , Chen Marcus , Dey Amit , Hong Christin G. , Playford Martin , Sylvester McKella , Teague Heather , Siegel Evan , Mehta Nehal N.
Published: June 2022

Background and Objectives

Psoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies.

Methods

In this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity.

Results

Compared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003).

Interpretation

Together, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA.
Low Protein Diets Supplemented With Alpha-Ketoglutarate Enhance the Growth Performance, Immune Response, and Intestinal Health in Common Carp (Cyprinus carpio)
Authors: Wu Di , Fan Ze , Li Jinnan , Zhang Yuanyuan , Xu Qiyou , Wang Liang , Wang Liansheng
Published: June 2022

To investigate the effects of alpha-ketoglutarate (AKG) supplementation in a low protein (LP) diet on the growth performance, immune response, and intestinal health of common carp (Cyprinus carpio), 600 carp were randomly divided into five dietary groups: a normal protein (NP) diet containing 32% crude protein, an LP diet formulated with 28% crude protein, and LP with AKG at 0.4%, 0.8%, and 1.2% (dry matter). After an 8-week trial period, the results demonstrated that an LP diet led to a decrease in performance, immune response, and intestinal barrier function. Compared with the LP group, the final body weight and weight gain rate in the LP+0.4% AKG group were significantly higher, the feed conversion ratio was significantly decreased with the addition of 0.4% and 0.8% AKG. The supplementation with 0.4% and 0.8% AKG markedly increased the activities of T-SOD and GSH-Px, as well as the expression levels of GPX1a and GPX1b relative to the LP group, whereas the MDA content was significantly decreased in the LP+0.4% AKG group. In addition, the expression levels of tight junctions including claudin-3, claudin-7, ZO-1, and MLCK were significantly up-regulated in the LP+0.4% AKG group, and the relative expression levels of the pro-inflammatory factors IL-1β and IL-6α were significantly lower with the addition of 0.4%, 0.8%, and 1.2% AKG. Moreover, the abundance of Proteobacteria in the LP+0.4% AKG group was lower than that in the LP group, and the abundance of Firmicutes and Fusobacteria was higher at the phylum level. The abundance of Citrobacter in the LP+0.4% AKG group was decreased compared to the LP group, while the abundance of Aeromonas was increased at the genus level. In short, the effects of AKG on the intestinal health of the common carp were systematically and comprehensively evaluated from the perspectives of intestinal physical barrier, chemical barrier, biological barrier, and immune barrier. We found that an LP diet supplemented with 0.4% AKG was beneficial to the growth performance and intestinal health of common carp.
Dynamic Phycobilin Pigment Variations in Diazotrophic and Non-diazotrophic Cyanobacteria Batch Cultures Under Different Initial Nitrogen Concentrations
Authors: Wang Jingyu , Wagner Nicole D. , Fulton James M. , Scott J. Thad
Published: June 2022

Increased anthropogenic nutrient loading has led to eutrophication of aquatic ecosystems, which is the major cause of harmful cyanobacteria blooms. Element stoichiometry of cyanobacteria bloom is subject to nutrient availabilities and may significantly contribute to primary production and biogeochemical cycling. Phycobilisome is the antenna of the photosynthetic pigment apparatus in cyanobacteria, which contains phycobilin pigments (PBPs) and linker proteins. This nitrogen (N)-rich protein complex has the potential to support growth as a N-storage site and may play a major role in the variability of cyanobacteria N stoichiometry. However, the regulation of PBPs during bloom formation remains unclear. We investigated the temporal variation of N allocation into PBPs and element stoichiometry for two ubiquitous cyanobacteria species, Microcystis aeruginosa and Dolichospermum flos-aquae, in a batch culture experiment with different initial N availabilities. Our results indicated that the N allocation into PBPs is species-dependent and tightly regulated by the availability of nutrients fueling population expansion. During the batch culture experiment, different nutrient uptake rates led to distinct stoichiometric imbalances of N and phosphorus (P), which substantially altered cyanobacteria C: N and C: P stoichiometry. Microcystis invested cellular N into PBPs and exhibited greater flexibility in C: N and C: P stoichiometry than D. flos-aquae. The dynamics of such N-rich macromolecules may help explain the N stoichiometry variation during a bloom and the interspecific difference between M. aeruginosa and D. flos-aquae. Our study provides a quantitative understanding of the elemental stoichiometry and the regulation of PBPs for non-diazotrophic and diazotrophic cyanobacteria blooms.
Wastewater Surveillance Detected Carbapenemase Enzymes in Clinically Relevant Gram-Negative Bacteria in Helsinki, Finland; 2011–2012
Authors: Tiwari Ananda , Paakkanen Jaana , Österblad Monica , Kirveskari Juha , Hendriksen Rene S. , Heikinheimo Annamari
Published: June 2022

Antimicrobial resistance profiling of pathogens helps to identify the emergence of rare or new resistance threats and prioritize possible actions to be taken against them. The analysis of wastewater (WW) can reveal the circulation of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARG) among the catchment communities. Here, we analyzed WW influent samples to determine the prevalence of carbapenemase genes-carrying Gram-negative bacteria (Carba-GNB) in Helsinki, Finland. This study set important historical reference points from the very early stage of the carbapenemase era, during the period 2011–2012. A total of 405 bacterial isolates grown on CHROMagarKPC (n = 195) and CHROMagarESBL (n = 210) from WW influent samples were collected between October 2011 and August 2012 and were analyzed. The bacterial DNA from the isolates was extracted, and the prevalence of carbapenemases genes blaKPC, blaNDM, blaGES, blaOXA-48, blaIMP, blaIMI, and blaVIM were screened with multiplexed PCR. All carbapenemase-positive isolates were identified taxonomically to species or genus level with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The nucleic acid extraction was successful for 399 isolates, of which 59 (14.8%) were found to carry carbapenemase genes. A total of 89.8% of the carbapenemase positive isolates (53 out of 59) were obtained from CHROMagarKPC plates and only 10.2% (six out of 59) were obtained from CHROMagar ESBL plates. Among the Carba-GNB isolates, 86.4% were blaGES (51 out of 59), 10.2% were blaKPC (six out of 59), and 3.4% were blaVIM (two out of 59). The most common carba-gene, blaGES, was carried by 10 different bacterial species, including Aeromonas spp., Enterobacter spp., and Kluyvera spp.; the blaKPC gene was carried by Escherichia coli, Klebsiella pneumoniae, and Kluyvera cryocescens; and the blaVIM gene was carried by Aeromonas hydrophila/caviae and Citrobacter amalonaticus. This study emphasizes that wastewater surveillance (WWS) can be an additional tool for monitoring antimicrobial resistance (AMR) at the population level.
Identification and Characterization of a Multifunctional Biocontrol Agent, Streptomyces griseorubiginosus LJS06, Against Cucumber Anthracnose
Authors: Chai Chien Hao , Hong Cheng-Fang , Huang Jenn-Wen
Published: June 2022

Twenty-eight bacterial strains isolated from Chinese herb extracts, beer fermentation waste, and raw oyster shells were evaluated for their efficacy in controlling cucumber anthracnose. Four bacterial strains, namely TG01, TG02, LJS06, and LJS08, were found to effectively reduce the mycelial growth of Colletotrichum orbiculare COC3 on PDA media. Spraying or drenching LJS06 spore suspension before inoculation significantly p < 0.05 reduced disease severity; thus, LJS06 was subject to further characterization. On the basis of the morphological, physiological, and biochemical characteristics and a multilocus sequence analysis of partial 16S rRNA, atpD, rpoB, and trpB genes, LJS06 was identified to be Streptomyces griseorubiginosus (Ryabova and Preobrazhenskaya) Pridham et al. Physiological and biochemical tests revealed that S. griseorubiginosus LJS06 can produce amylase, cellulase, chitinase, protease, siderophore, polyamines, and indole-3-acetic acid. Thus, a culture filtrate of LJS06 (specifically SL06) was formulated and evaluated for its efficacy against conidial germination, appressorium formation, and anthracnose management. Diluted SL06 was found to significantly (p < 0.05) inhibit conidial germination and appressorium formation, which can be attributed to impaired membrane integrity, accumulated reactive oxygen species (ROS), and impaired energy metabolism in the conidia. In addition, the spraying and drenching of diluted SL06 before inoculation consistently and significantly (p < 0.05) reduced anthracnose severity. These results jointly suggest that S. griseorubiginosus LJS06 can aid in the management of cucumber anthracnose by directly inhibiting conidial function and priming the plant defense system.
Nitrogen Removal From Nitrate-Containing Wastewaters in Hydrogen-Based Membrane Biofilm Reactors via Hydrogen Autotrophic Denitrification: Biofilm Structure, Microbial Community and Optimization Strategies
Authors: Dong Kun , Feng Xinghui , Yao Yi , Zhu Zongqiang , Lin Hua , Zhang Xuehong , Wang Dunqiu , Li Haixiang
Published: June 2022

The hydrogen-based membrane biofilm reactor (MBfR) has been widely applied in nitrate removal from wastewater, while the erratic fluctuation of treatment efficiency is in consequence of unstable operation parameters. In this study, hydrogen pressure, pH, and biofilm thickness were optimized as the key controlling parameters to operate MBfR. The results of 653.31 μm in biofilm thickness, 0.05 MPa in hydrogen pressure and pH in 7.78 suggesting high-efficiency NO3−−N removal and the NO3−−N removal flux was 1.15 g·m−2 d−1. 16S rRNA gene analysis revealed that Pseudomonas, Methyloversatilis, Thauera, Nitrospira, and Hydrogenophaga were the five most abundant bacterial genera in MBfRs after optimization. Moreover, significant increases of Pseudomonas relative abundances from 0.36 to 9.77% suggested that optimization could effectively remove nitrogen from MBfRs. Membrane pores and surfaces exhibited varying degrees of calcification during stable operation, as evinced by Ca2+ precipitation adhering to MBfR membrane surfaces based on scanning electron microscopy (SEM), atomic force microscopy (AFM) analyses. Scanning electron microscopy–energy dispersive spectrometer (SEM–EDS) analyses also confirmed that the primary elemental composition of polyvinyl chloride (PVC) membrane surfaces after response surface methodology (RSM) optimization comprised Ca, O, C, P, and Fe. Further, X-ray diffraction (XRD) analyses indicated the formation of Ca5F(PO4)3 geometry during the stable operation phase.
The Proinflammatory Role of Guanylate-Binding Protein 5 in Inflammatory Bowel Diseases
Authors: Li Yichen , Lin Xutao , Wang Wenxia , Wang Wenyu , Cheng Sijing , Huang Yibo , Zou Yifeng , Ke Jia , Zhu Lixin
Published: June 2022

NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate-binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. The expression of GBP5, NLRP3 inflammasome, and related cytokines and chemokines was examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real-time PCR. Cellular localization of GBP5 in colonic biopsies was examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that the expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, the expression of proinflammatory cytokines and chemokines was increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines, and chemokines. We conclude that GBP5 is required in the expression of many proinflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may upregulate inflammatory reactions through an inflammasome-mediated mechanism. Since GBP5 plays a proinflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.
Morphological and Spatial Heterogeneity of Microbial Communities in Pilot-Scale Autotrophic Integrated Fixed-Film Activated Sludge System Treating Coal to Ethylene Glycol Wastewater
Authors: Jia Fangxu , Chen Jiayi , Zhao Xingcheng , Liu Chenyu , Li Yiran , Ma Jinyuan , Yang Anming , Yao Hong
Published: June 2022

The understanding of microbial compositions in different dimensions is essential to achieve the successful design and operation of the partial nitritation/anammox (PN/A) process. This study investigated the microbial communities of different sludge morphologies and spatial distribution in the one-stage PN/A process of treating real coal to ethylene glycol (CtEG) wastewater at a pilot-scale integrated fixed-film activated sludge (IFAS) reactor. The results showed that ammonia-oxidizing bacteria (AOB) was mainly distributed in flocs (13.56 ± 3.16%), whereas anammox bacteria (AnAOB) was dominated in the biofilms (17.88 ± 8.05%). Furthermore, the dominant AnAOB genus in biofilms among the first three chambers was Candidatus Brocadia (6.46 ± 2.14% to 11.82 ± 6.33%), whereas it was unexpectedly transformed to Candidatus Kuenenia (9.47 ± 1.70%) and Candidatus Anammoxoglobus (8.56 ± 4.69%) in the last chamber. This demonstrated that the niche differentiation resulting from morphological (dissolved oxygen) and spatial heterogeneity (gradient distribution of nutrients and toxins) was the main reason for dominant bacterial distribution. Overall, this study presents more comprehensive information on the heterogeneous distribution and transformation of communities in PN/A processes, providing a theoretical basis for targeted culture and selection of microbial communities in practical engineering.
Efficient Detection of the Alternative Spliced Human Proteome Using Translatome Sequencing
Authors: Wu Chun , Lu Xiaolong , Lu Shaohua , Wang Hongwei , Li Dehua , Zhao Jing , Jin Jingjie , Sun Zhenghua , He Qing-Yu , Chen Yang , Zhang Gong
Published: June 2022

Alternative splicing (AS) isoforms create numerous proteoforms, expanding the complexity of the genome. Highly similar sequences, incomplete reference databases and the insufficient sequence coverage of mass spectrometry limit the identification of AS proteoforms. Here, we demonstrated full-length translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) sequencing (RNC-seq) strategy to sequence the entire translating mRNA using next-generation sequencing, including short-read and long-read technologies, to construct a protein database containing all translating AS isoforms. Taking the advantage of read length, short-read RNC-seq identified up to 15,289 genes and 15,906 AS isoforms in a single human cell line, much more than the Ribo-seq. The single-molecule long-read RNC-seq supplemented 4,429 annotated AS isoforms that were not identified by short-read datasets, and 4,525 novel AS isoforms that were not included in the public databases. Using such RNC-seq-guided database, we identified 6,766 annotated protein isoforms and 50 novel protein isoforms in mass spectrometry datasets. These results demonstrated the potential of full-length RNC-seq in investigating the proteome of AS isoforms.
Mechanism of CK2 Inhibition by a Ruthenium-Based Polyoxometalate
Authors: Fabbian Simone , Giachin Gabriele , Bellanda Massimo , Borgo Christian , Ruzzene Maria , Spuri Giacomo , Campofelice Ambra , Veneziano Laura , Bonchio Marcella , Carraro Mauro , Battistutta Roberto
Published: June 2022

CK2 is a Ser/Thr protein kinase involved in many cellular processes such as gene expression, cell cycle progression, cell growth and differentiation, embryogenesis, and apoptosis. Aberrantly high CK2 activity is widely documented in cancer, but the enzyme is also involved in several other pathologies, such as diabetes, inflammation, neurodegeneration, and viral infections, including COVID-19. Over the last years, a large number of small-molecules able to inhibit the CK2 activity have been reported, mostly acting with an ATP-competitive mechanism. Polyoxometalates (POMs), are metal-oxide polyanionic clusters of various structures and dimensions, with unique chemical and physical properties. POMs were identified as nanomolar CK2 inhibitors, but their mechanism of inhibition and CK2 binding site remained elusive. Here, we present the biochemical and biophysical characterizing of the interaction of CK2α with a ruthenium-based polyoxometalate, [Ru4(μ-OH)2(μ-O)4(H2O)4 (γ-SiW10O36)2]10− (Ru4POM), a potent inhibitor of CK2. Using analytical Size-Exclusion Chromatography (SEC), Isothermal Titration Calorimetry (ITC), and SAXS we were able to unravel the mechanism of inhibition of Ru4POM. Ru4POM binds to the positively-charged substrate binding region of the enzyme through electrostatic interactions, triggering the dimerization of the enzyme which consequently is inactivated. Ru4POM is the first non-peptide molecule showing a substrate-competitive mechanism of inhibition for CK2. On the basis of SAXS data, a structural model of the inactivated (CK2α)2(Ru4POM)2 complex is presented.
Prevalence and Prognostic Significance of Liver Fibrosis in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Li Tiangui , Wang Peng , Gong Xiao , Chong Weelic , Hai Yang , You Chao , Kang Juan , Fang Fang , Zhang Yu
Published: June 2022

Objectives

To report the prevalence, clinical associations, and prognostic consequences of liver fibrosis in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

In a retrospective study of patients with aSAH, we evaluated three validated liver fibrosis indices and modeled them as continuous-exposure variables, including the aspartate aminotransferase/platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and the Forns index. The primary outcome was mortality at 90 days. We compared the addition of fibrosis indices to the predictors of the full Subarachnoid Hemorrhage International Trialists model.

Results

A total of 3,722 patients with aSAH were included in the study. According to the APRI, FIB-4 index, and Forns index, 21.7, 17.7, and 11.4% of patients had liver fibrosis. After adjusting for potential confounding factors, liver fibrosis indices were associated with increased 90-day mortality, with odds ratios of 1.35 (95% CI 1.02–1.77) for the FIB-4 index, 1.39 (95% CI.08–1.78) for APRI, and 1.53 (95% CI 1.11–2.12) for the Forns index. Similarly, high liver fibrosis indices were associated with an increased risk of rebleeding. However, the Forns index was not significantly associated with mortality and rebleeding. The addition of FIB-4 indices and APRI into the standard model improved the mortality prediction.

Conclusions

Liver fibrosis is common in patients with aSAH, and high liver fibrosis indices are associated with mortality and rebleeding. The addition of liver fibrosis indices to a standard clinical model significantly improves risk stratification.
Age and Gender Differences in Cardiovascular Autonomic Failure in the Transgenic PLP-syn Mouse, a Model of Multiple System Atrophy
Authors: Kermorgant Marc , Fernagut Pierre-Olivier , Meissner Wassilios G. , Arvanitis Dina N. , N'Guyen Du , Senard Jean-Michel , Pavy-Le Traon Anne
Published: June 2022

Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder. Autonomic failure (AF) is one main clinical feature which has a significant impact on health-related quality of life. The neuropathological hallmark of MSA is the abnormal accumulation of α-synuclein in oligodendrocytes forming glial cytoplasmic inclusions. Only little is known about gender and age differences in AF in MSA. This study was carried out in 6 and 12 months old transgenic PLP-α-syn and WT male and female mice. Heart rate variability (HRV) was assessed both in time, frequential and non-linear domains. Baroreflex sensitivity (BRS) was estimated by the sequence method. Duration of ventricular depolarization and repolarization (QT/QTc intervals) were evaluated from the ECG signals. Three-way ANOVA (genotype x gender x age) with Sidak's method post-hoc was used to analyze data. BRS was significantly changed in PLP-α-syn mice and was age-dependent. QT and QTc intervals were not significantly modified in PLP-α-syn mice. An impaired HRV was observed at 12 months of age in PLP-α-syn female but not in male mice, indicative of cardiovascular AF.
Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage
Authors: Wan Ding , Feng Jin , Wang Peng , Yang Zhenxing , Sun Tao
Published: June 2022

The purpose of this study was to identify the biomarkers implicated in the development of intracranial hemorrhage (ICH) and potential regulatory pathways. In the transcriptomic data for patients with ICH, we identified DEmiRNAs and DEmRNAs related to hypoxia, inflammation, and their transcription factors (TFs). An ICH-based miRNA-TF-mRNA regulatory network was thus constructed, and four biomarkers (TIMP1, PLAUR, DDIT3, and CD40) were screened for their association with inflammation or hypoxia by machine learning. Following this, SP3 was found to be a transcription factor involved in hypoxia and inflammation, which regulates TIMP1 and PLAUR. From the constructed miRNA-TF-mRNA regulatory network, we identified three axes, hsa-miR-940/RUNX1/TIMP1, hsa-miR-571/SP3/TIMP1, and hsa-miR-571/SP3/PLAUR, which may be involved in the development of ICH. Upregulated TIMP1 and PLAUR were validated in an independent clinical cohort 3 days after ICH onset. According to Gene Set Enrichment Analysis (GSEA), SP3 was discovered to be important in interleukin signaling and platelet activation for hemostasis. Transcription factor SP3 associated with hypoxia or inflammation plays an important role in development of ICH. This study provides potential targets for monitoring the severity of inflammation and hypoxia in patients with ICH.
Comparison of Unilateral Middle Cerebral Artery and Bilateral Middle Cerebral Artery Monitoring for Right-to-Left Shunt Detection by Contrast-Enhanced Transcranial Doppler
Authors: Zhang Wenjie , Yang Le , Wang Shuli , Wang Lin , Li Haixian , Yang Keshi
Published: June 2022

Introduction

Contrast-enhanced transcranial Doppler (c-TCD) is a noninvasive test with high sensitivity for the detection of a right-to-left shunt (RLS). Currently, there are no reports on the outcomes of unilateral versus bilateral middle cerebral artery (MCA) monitoring. This study compared the positivity rate of bilateral MCA monitoring with unilateral MCA monitoring for RLS using c-TCD.

Methods

We enrolled 239 patients (86 women and 153 men) with a mean age of 48.54 ± 13.25 years (range, 14–79 years), who underwent c-TCD examination in the Department of Transcranial Doppler Ultrasound of our hospital between February 2018 and February 2021, due to suspicion of RLS. Bilateral MCA monitoring of 239 patients was performed using dual-channel and dual-depth c-TCD. The positive rate and shunt classification of RLS were calculated for left, right, and bilateral MCA monitoring. The differences in RLS detected by c-TCD monitoring of the left, right and bilateral MCA were compared.

Results

In the left middle cerebral artery (LMCA) monitoring, 35.56% (85 of 239) had a positive RLS result, 38 cases were permanent (44.70%), and 47 cases were latent (55.30%). In the right middle cerebral artery (RMCA) monitoring, 36.82% (88 of 239) had a positive RLS result, 38 cases were permanent (43.18%), and 50 cases were latent (56.82%). In the bilateral MCA group, 43.09% (103 of 239) had a positive RLS result, 50 cases were permanent (48.54%) and 53 were latent (51.46%). The positive rate of bilateral MCA monitoring was higher than that of LMCA and RMCA (43.09, 35.56, and 36.82%, respectively), and the difference was not statistically significant (P = 0.193). The positive rate of bilateral MCA monitoring was higher than that of LMCA and RMCA for mild and moderate shunts, but the difference was not statistically significant. The positive rate of bilateral MCA monitoring was equal to that of RMCA, but higher than that of LMCA, with no statistical significance. LMCA monitoring revealed 85 patients with RLS. The sensitivity was 82.52% (85/103). The specificity was 100%. The RMCA monitoring results showed 88 cases with RLS. The sensitivity was 85.44% (88/103). The specificity was 100%.

Conclusions

There was no significant difference in the RLS detection rate between unilateral and bilateral MCA monitoring using c-TCD. Bilateral MCA monitoring may be more advantageous for mild RLS detection.
Evaluation of Methods for the Extraction of Spatial Muscle Synergies
Authors: Zhao Kunkun , Wen Haiying , Zhang Zhisheng , Atzori Manfredo , Müller Henning , Xie Zhongqu , Scano Alessandro
Published: June 2022

Muscle synergies have been largely used in many application fields, including motor control studies, prosthesis control, movement classification, rehabilitation, and clinical studies. Due to the complexity of the motor control system, the full repertoire of the underlying synergies has been identified only for some classes of movements and scenarios. Several extraction methods have been used to extract muscle synergies. However, some of these methods may not effectively capture the nonlinear relationship between muscles and impose constraints on input signals or extracted synergies. Moreover, other approaches such as autoencoders (AEs), an unsupervised neural network, were recently introduced to study bioinspired control and movement classification. In this study, we evaluated the performance of five methods for the extraction of spatial muscle synergy, namely, principal component analysis (PCA), independent component analysis (ICA), factor analysis (FA), nonnegative matrix factorization (NMF), and AEs using simulated data and a publicly available database. To analyze the performance of the considered extraction methods with respect to several factors, we generated a comprehensive set of simulated data (ground truth), including spatial synergies and temporal coefficients. The signal-to-noise ratio (SNR) and the number of channels (NoC) varied when generating simulated data to evaluate their effects on ground truth reconstruction. This study also tested the efficacy of each synergy extraction method when coupled with standard classification methods, including K-nearest neighbors (KNN), linear discriminant analysis (LDA), support vector machines (SVM), and Random Forest (RF). The results showed that both SNR and NoC affected the outputs of the muscle synergy analysis. Although AEs showed better performance than FA in variance accounted for and PCA in synergy vector similarity and activation coefficient similarity, NMF and ICA outperformed the other three methods. Classification tasks showed that classification algorithms were sensitive to synergy extraction methods, while KNN and RF outperformed the other two methods for all extraction methods; in general, the classification accuracy of NMF and PCA was higher. Overall, the results suggest selecting suitable methods when performing muscle synergy-related analysis.
Effects of Treatment With Hypnotics on Reduced Sleep Duration and Behavior Abnormalities in a Mouse Model of Fragile X Syndrome
Authors: Saré Rachel Michelle , Lemons Abigail , Smith Carolyn Beebe
Published: June 2022

Many patients with fragile X syndrome (FXS) have sleep disturbances, and Fmr1 knockout (KO) mice (a model of FXS) have reduced sleep duration compared to wild type (WT). Sleep is important for brain development, and chronic sleep restriction during development has long-lasting behavioral effects in WT mice. We hypothesized that the sleep abnormalities in FXS may contribute to behavioral impairments and that increasing sleep duration might improve behavior. We treated adult male Fmr1 KO and WT mice subacutely with three different classes of hypnotics (DORA-22, ramelteon, and zolpidem) and caffeine, a methylxanthine stimulant, and we tested the effects of treatments on sleep duration and behavior. Behavior tests included activity response to a novel environment, anxiety-like behavior, and social behavior. As expected, all hypnotics increased, and caffeine decreased sleep duration in the circadian phase in which drugs were administered. Caffeine and DORA-22 treatment significantly reduced activity in the open field regardless of genotype. Other effects were not as apparent.
Unsupervised Black-Box Model Domain Adaptation for Brain Tumor Segmentation
Authors: Liu Xiaofeng , Yoo Chaehwa , Xing Fangxu , Kuo C.-C. Jay , El Fakhri Georges , Kang Je-Won , Woo Jonghye
Published: June 2022

Unsupervised domain adaptation (UDA) is an emerging technique that enables the transfer of domain knowledge learned from a labeled source domain to unlabeled target domains, providing a way of coping with the difficulty of labeling in new domains. The majority of prior work has relied on both source and target domain data for adaptation. However, because of privacy concerns about potential leaks in sensitive information contained in patient data, it is often challenging to share the data and labels in the source domain and trained model parameters in cross-center collaborations. To address this issue, we propose a practical framework for UDA with a black-box segmentation model trained in the source domain only, without relying on source data or a white-box source model in which the network parameters are accessible. In particular, we propose a knowledge distillation scheme to gradually learn target-specific representations. Additionally, we regularize the confidence of the labels in the target domain via unsupervised entropy minimization, leading to performance gain over UDA without entropy minimization. We extensively validated our framework on a few datasets and deep learning backbones, demonstrating the potential for our framework to be applied in challenging yet realistic clinical settings.
A Lightweight Framework for Perception Analysis Based on Multimodal Cognition-Aware Computing
Authors: Qian Xuesheng , Qiao Yihong , Wang Mianjie , Wang Xinyue , Chen Mengfan , Dai Weihui
Published: June 2022

The VUCA environment challenged neuropsychological research conducted in conventional laboratories. Researchers expected to perform complex multimodal testing tasks in natural, open, and non-laboratory settings. However, for most neuropsychological scientists, the independent construction of a multimodal laboratory in a VUCA environment, such as a construction site, was a significant and comprehensive technological challenge. This study presents a generalized lightweight framework for perception analysis based on multimodal cognition-aware computing, which provided practical updated strategies and technological guidelines for neuromanagement and automation. A real-life test experiment on a construction site was provided to illustrate the feasibility and superiority of the method. The study aimed to fill a technology gap in the application of multimodal physiological and neuropsychological techniques in an open VUCA environment. Meanwhile, it enabled the researchers to improve their systematic technological capabilities and reduce the threshold and trial-and-error costs of experiments to conform to the new trend of VUCA.
The Common Effects of Sleep Deprivation on Human Long-Term Memory and Cognitive Control Processes
Authors: Kim Taehyun , Kim Sejin , Kang Joonyoung , Kwon Minjae , Lee Sue-Hyun
Published: June 2022

Sleep deprivation is known to have adverse effects on various cognitive abilities. In particular, a lack of sleep has been reported to disrupt memory consolidation and cognitive control functions. Here, focusing on long-term memory and cognitive control processes, we review the consistency and reliability of the results of previous studies of sleep deprivation effects on behavioral performance with variations in the types of stimuli and tasks. Moreover, we examine neural response changes related to these behavioral changes induced by sleep deprivation based on human fMRI studies to determine the brain regions in which neural responses increase or decrease as a consequence of sleep deprivation. Additionally, we discuss about the possibility that light as an environmentally influential factor affects our sleep cycles and related cognitive processes.