bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
Authors: Wu Fanglong , Wang Shimeng , Zeng Qingxiang , Liu Junjiang , Yang Jin , Mu Jingtian , Xu Hongdang , Wu Lanyan , Gao Qinghong , He Xin , Liu Ying , Zhou Hongmei
Published: January 2022

Cancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake of glucose for conversion into lactate under sufficient oxygen conditions, and this metabolic process occurs at the site of energy exchange between CAFs and cancer cells. As a hallmark of cancer, metabolic reprogramming of CAFs is defined as reverse Warburg effect (RWE), characterized by increased lactate, glutamine, and pyruvate, etc. derived from aerobic glycolysis. Given that the TGF-β signal cascade plays a critical role in RWE mainly through metabolic reprogramming related proteins including pyruvate kinase muscle isozyme 2 (PKM2), however, the role of nuclear PKM2 in modifying glycolysis remains largely unknown. In this study, using a series of in vitro and in vivo experiments, we provide evidence that TGF-βRII overexpression suppresses glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth. This study highlights a novel pathway that explains the role of TGF-βRII in CAFs glucose metabolism and suggests that targeting TGF-βRII in CAFs might represent a therapeutic approach for oral cancer.
Impairment of μ-calpain activation by rhTNFR:Fc reduces severe burn-induced membrane disruption in the heart
Authors: Cao Meng-Shu , Zhao Ting-Yan , Song Zhi-Long , Lu Hong-Ting , Zheng Yun , Gu Xiao-Ming , Lu Tao , Wang Qiong , Zhou Jing-Jun
Published: January 2022

Stress cardiomyopathy is a major clinical complication after severe burn. Multiple upstream initiators have been identified; however, the downstream targets are not fully understood. This study assessed the role of the plasma membrane in this process and its relationship with the protease μ-calpain and tumor necrosis factor-alpha (TNF-α). Here, third-degree burn injury of approximately 40% of the total body surface area was established in rats. Plasma levels of LDH and cTnI and cardiac cell apoptosis increased at 0.5 h post burn, reached a peak at 6 h, and gradually declined at 24 h. This effect correlated well with not only the disruption of cytoskeletal proteins, including dystrophin and ankyrin-B, but also with the activation of μ-calpain, as indicated by the cleaved fragments of α-spectrin and membrane recruitment of the catalytic subunit CAPN1. More importantly, these alterations were diminished by blocking calpain activity with MDL28170. Burn injury markedly increased the cellular uptake of Evans blue, indicating membrane integrity disruption, and this effect was also reversed by MDL28170. Compared with those in the control group, cardiac cells in the burn plasma-treated group were more prone to damage, as indicated by a marked decrease in cell viability and increases in LDH release and apoptosis. Of note, these alterations were mitigated by CAPN1 siRNA. Moreover, after neutralizing TNF-α with rhTNFR:Fc, calpain activity was blocked, and heart function was improved. In conclusion, we identified μ-calpain as a trigger for severe burn-induced membrane disruption in the heart and provided evidence for the application of rhTNFR:Fc to inhibit calpain for cardioprotection.
Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy
Authors: Särchen Vinzenz , Shanmugalingam Senthan , Kehr Sarah , Reindl Lisa Marie , Greze Victoria , Wiedemann Sara , Boedicker Cathinka , Jacob Maureen , Bankov Katrin , Becker Nina , Wehner Sibylle , Theilen Till M. , Gretser Steffen , Gradhand Elise , Kummerow Carsten , Ullrich Evelyn , Vogler Meike
Published: January 2022

The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-XL inhibitor A1331852 or the Mcl-1 inhibitor S63845 increased the cytotoxicity of NK cells and reduced spheroid size, while the Bcl-2 inhibitor ABT-199 had no effect on NK cell-mediated killing. Taken together, this is the first study to describe the combination of BH3 mimetics targeting Bcl-XL or Mcl-1 with NK cell-based immunotherapy, highlighting the potential of BH3 mimetics in immunotherapy.
Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters
Authors: Yan Wei , Hall A. Brantley , Jiang Xiaofang
Published: January 2022

Antibiotic-resistance genes (ARGs) regulated by invertible promoters can mitigate the fitness cost of maintaining ARGs in the absence of antibiotics and could potentially prolong the persistence of ARGs in bacterial populations. However, the origin, prevalence, and distribution of these ARGs regulated by invertible promoters remains poorly understood. Here, we sought to assess the threat posed by ARGs regulated by invertible promoters by systematically searching for ARGs regulated by invertible promoters in the human gut microbiome and examining their origin, prevalence, and distribution. Through metagenomic assembly of 2227 human gut metagenomes and genomic analysis of the Unified Human Gastrointestinal Genome (UHGG) collection, we identified ARGs regulated by invertible promoters and categorized them into three classes based on the invertase-regulating phase variation. In the human gut microbiome, ARGs regulated by invertible promoters are exclusively found in Bacteroidales species. Through genomic analysis, we observed that ARGs regulated by invertible promoters have convergently originated from ARG insertions into glycan-synthesis loci that were regulated by invertible promoters at least three times. Moreover, all three classes of invertible promoters regulating ARGs are located within integrative conjugative elements (ICEs). Therefore, horizontal transfer via ICEs could explain the wide taxonomic distribution of ARGs regulated by invertible promoters. Overall, these findings reveal that glycan-synthesis loci regulated by invertible promoters in Bacteroidales species are an important hotspot for the emergence of clinically-relevant ARGs regulated by invertible promoters.
Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression
Authors: Bhome R. , Zarkali A. , Thomas G. E. C. , Iglesias J. E. , Cole J. H. , Weil R. S.
Published: January 2022

Depression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.
Specific immune status in Parkinson’s disease at different ages of onset
Authors: Tian Jun , Dai Shao-Bing , Jiang Si-Si , Yang Wen-Yi , Yan Yi-Qun , Lin Zhi-Hao , Dong Jia-Xian , Liu Yi , Zheng Ran , Chen Ying , Zhang Bao-Rong , Pu Jia-Li
Published: January 2022

Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively.Ttest and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8+T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8+T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.
Biallelic expansion in RFC1 as a rare cause of Parkinson’s disease
Authors: Kytövuori Laura , Sipilä Jussi , Doi Hiroshi , Hurme-Niiranen Anri , Siitonen Ari , Koshimizu Eriko , Miyatake Satoko , Matsumoto Naomichi , Tanaka Fumiaki , Majamaa Kari
Published: January 2022

An intronic expansion (AAGGG)exp in the RFC1 gene has recently been shown to cause recessively inherited cerebellar ataxia, neuropathy, and vestibular areflexia syndrome and, furthermore, a few patients with ataxia and parkinsonism have been reported. We investigated 569 Finnish patients with medicated parkinsonism for RFC1 and found biallelic (AAGGG)exp in three non-consanguineous patients with clinically confirmed Parkinson’s disease without ataxia suggesting that RFC1-related disorders include Parkinson’s disease as well.
Confirming the trilinear form of the optical magnetoelectric effect in the polar honeycomb antiferromagnet Co2Mo3O8
Authors: Reschke S. , Farkas D. G. , Strinić A. , Ghara S. , Guratinder K. , Zaharko O. , Prodan L. , Tsurkan V. , Szaller D. , Bordács S. , Deisenhofer J. , Kézsmárki I.
Published: January 2022

Magnetoelectric phenomena are intimately linked to relativistic effects and also require the material to break spatial inversion symmetry and time-reversal invariance. Magnetoelectric coupling can substantially affect light–matter interaction and lead to non-reciprocal light propagation. Here, we confirm on a fully experimental basis, without invoking either symmetry-based or material-specific assumptions, that the optical magnetoelectric effect in materials with non-parallel magnetization (M) and electric polarization (P) generates a trilinear term in the refractive index, δn ∝ k ⋅ (P × M), where k is the propagation vector of light. Its sharp magnetoelectric resonances in the terahertz regime, which are simultaneously electric and magnetic dipole active excitations, make Co2Mo3O8 an ideal compound to demonstrate this fundamental relation via independent variation of M, P, and k. Remarkably, the material shows almost perfect one-way transparency in moderate magnetic fields for one of these magnetoelectric resonances.
The clinical potential of articular cartilage-derived progenitor cells: a systematic review
Authors: Rikkers Margot , Korpershoek Jasmijn V. , Levato Riccardo , Malda Jos , Vonk Lucienne A.
Published: January 2022

Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).
Human EEG recordings for 1,854 concepts presented in rapid serial visual presentation streams
Authors: Grootswagers Tijl , Zhou Ivy , Robinson Amanda K. , Hebart Martin N. , Carlson Thomas A.
Published: January 2022

The neural basis of object recognition and semantic knowledge has been extensively studied but the high dimensionality of object space makes it challenging to develop overarching theories on how the brain organises object knowledge. To help understand how the brain allows us to recognise, categorise, and represent objects and object categories, there is a growing interest in using large-scale image databases for neuroimaging experiments. In the current paper, we present THINGS-EEG, a dataset containing human electroencephalography responses from 50 subjects to 1,854 object concepts and 22,248 images in the THINGS stimulus set, a manually curated and high-quality image database that was specifically designed for studying human vision. The THINGS-EEG dataset provides neuroimaging recordings to a systematic collection of objects and concepts and can therefore support a wide array of research to understand visual object processing in the human brain.
Response of atomic spin-based sensors to magnetic and nonmagnetic perturbations
Authors: Padniuk Mikhail , Kopciuch Marek , Cipolletti Riccardo , Wickenbrock Arne , Budker Dmitry , Pustelny Szymon
Published: January 2022

Searches for pseudo-magnetic spin couplings require implementation of techniques capable of sensitive detection of such interactions. While Spin-Exchange Relaxation Free (SERF) magnetometry is one of the most powerful approaches enabling the searches, it suffers from a strong magnetic coupling, deteriorating the pseudo-magnetic coupling sensitivity. To address this problem, here, we compare, via numerical simulations, the performance of SERF magnetometer and noble-gas-alkali-metal co-magnetometer, operating in a so-called self-compensating regime. We demonstrate that the co-magnetometer allows reduction of the sensitivity to low-frequency magnetic fields without loss of the sensitivity to nonmagnetic couplings. Based on that we investigate the responses of both systems to the oscillating and transient spin perturbations. Our simulations reveal about five orders of magnitude stronger response to the neutron pseudo-magnetic coupling and about three orders of magnitude stronger response to the proton pseudo-magnetic coupling of the co-magnetometer than those of the SERF magnetometer. Different frequency responses of the co-magnetometer to magnetic and nonmagnetic perturbations enables differentiation between these two types of interactions. This outlines the ability to implement the co-magnetometer as an advanced sensor for the Global Network of Optical Magnetometer for Exotic Physics searches (GNOME), aiming at detection of ultra-light bosons (e.g., axion-like particles).
Prediction of steady flows passing fixed cylinders using deep learning
Authors: Ozaki Hiroto , Aoyagi Takeshi
Published: January 2022

Considerable attention has been given to deep-learning and machine-learning techniques in an effort to reduce the computational cost of computational fluid dynamics simulation. The present paper addresses the prediction of steady flows passing many fixed cylinders using a deep-learning model and investigates the accuracy of the predicted velocity field. The deep-learning model outputs the x- and y-components of the flow velocity field when the cylinder arrangement is input. The accuracy of the predicted velocity field is investigated, focusing on the velocity profile of the fluid flow and the fluid force acting on the cylinders. The present model accurately predicts the flow when the number of cylinders is equal to or close to that set in the training dataset. The extrapolation of the prediction to a smaller number of cylinders results in error, which can be interpreted as internal friction of the fluid. The results of the fluid force acting on the cylinders suggest that the present deep-learning model has good generalization performance for systems with a larger number of cylinders.
Machine learning for emerging infectious disease field responses
Authors: Chiu Han-Yi Robert , Hwang Chun-Kai , Chen Shey-Ying , Shih Fuh-Yuan , Han Hsieh-Cheng , King Chwan-Chuen , Gilbert John Reuben , Fang Cheng-Chung , Oyang Yen-Jen
Published: January 2022

Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.
Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses
Authors: Mainguy-Seers Sophie , Boivin Roxane , Pourali Dogaheh Sheila , Beaudry Francis , Hélie Pierre , Bonilla Alvaro G. , Martin James G. , Lavoie Jean-Pierre
Published: January 2022

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.
Susceptibility artifacts induced by crowns of different materials with prepared teeth and titanium implants in magnetic resonance imaging
Authors: Gao Xiaomeng , Wan Qianbing , Gao Qingping
Published: January 2022

This study aimed to investigate the artifacts induced by crowns composed of different materials with prepared teeth and titanium implants. Resin, metal-ceramic, ceramic and zirconia crowns were fabricated and placed onto the prepared teeth on a human cadaver head or titanium implants with prosthesis abutments on a dry human mandible. The samples were scanned on a 1.5 T MRI apparatus, and artifact areas were defined as the signal intensity and signal loss adjacent to the prosthesis and measured by a threshold tool with ImageJ2x. Data were analyzed using SPSS 22.0. Resin, ceramic, zirconia, and precious metal-ceramic crowns barely produced artifacts on the cadaver skull (p > 0.999). By contrast, pure Ti and nonprecious metal-ceramic crowns created significant artifacts (p < 0.001). The average artifacts reduction of double Au-Pt and Ag-Pd metal-ceramic crowns combined with titanium implants and abutments was 79.49 mm2 (p < 0.001) and 74.17 mm2 (p < 0.001) respectively, while artifact areas were increased in double Co-Cr and Ni–Cr metal-ceramic crowns by 150.10 mm2 (p < 0.001) and 175.50 mm2 (p < 0.001) respectively. Zirconia, ceramic and precious metal-ceramic crowns induce less MRI artifacts after tooth preparation while precious metal-ceramic crowns alleviate artifacts in combination with titanium implants.
The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism
Authors: Pitman Melissa R. , Lewis Alexander C. , Davies Lorena T. , Moretti Paul A. B. , Anderson Dovile , Creek Darren J. , Powell Jason A. , Pitson Stuart M.
Published: January 2022

Sphingosine 1-phosphate (S1P) is a signaling lipid that has broad roles, working either intracellularly through various protein targets, or extracellularly via a family of five G-protein coupled receptors. Agents that selectively and specifically target each of the S1P receptors have been sought as both biological tools and potential therapeutics. JTE-013, a small molecule antagonist of S1P receptors 2 and 4 (S1P2 and S1P4) has been widely used in defining the roles of these receptors in various biological processes. Indeed, our previous studies showed that JTE-013 had anti-acute myeloid leukaemia (AML) activity, supporting a role for S1P2 in the biology and therapeutic targeting of AML. Here we examined this further and describe lipidomic analysis of AML cells that revealed JTE-013 caused alterations in sphingolipid metabolism, increasing cellular ceramides, dihydroceramides, sphingosine and dihydrosphingosine. Further examination of the mechanisms behind these observations showed that JTE-013, at concentrations frequently used in the literature to target S1P2/4, inhibits several sphingolipid metabolic enzymes, including dihydroceramide desaturase 1 and both sphingosine kinases. Collectively, these findings demonstrate that JTE-013 can have broad off-target effects on sphingolipid metabolism and highlight that caution must be employed in interpreting the use of this reagent in defining the roles of S1P2/4.
Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson’s disease
Authors: Hideshima Makoto , Kimura Yasuyoshi , Aguirre César , Kakuda Keita , Takeuchi Toshihide , Choong Chi-Jing , Doi Junko , Nabekura Kei , Yamaguchi Keiichi , Nakajima Kichitaro , Baba Kousuke , Nagano Seiichi , Goto Yuji , Nagai Yoshitaka , Mochizuki Hideki , Ikenaka Kensuke
Published: January 2022

Parkinson’s disease is a neurodegenerative disease characterized by the formation of neuronal inclusions of α-synuclein in patient brains. As the disease progresses, toxic α-synuclein aggregates transmit throughout the nervous system. No effective disease-modifying therapy has been established, and preventing α-synuclein aggregation is thought to be one of the most promising approaches to ameliorate the disease. In this study, we performed a two-step screening using the thioflavin T assay and a cell-based assay to identify α-synuclein aggregation inhibitors. The first screening, thioflavin T assay, allowed the identification of 30 molecules, among a total of 1262 FDA-approved small compounds, which showed inhibitory effects on α-synuclein fibrilization. In the second screening, a cell-based aggregation assay, seven out of these 30 candidates were found to prevent α-synuclein aggregation without causing substantial toxicity. Of the seven final candidates, tannic acid was the most promising compound. The robustness of our screening method was validated by a primary neuronal cell model and a Caenorhabditis elegans model, which demonstrated the effect of tannic acid against α-synuclein aggregation. In conclusion, our two-step screening system is a powerful method for the identification of α-synuclein aggregation inhibitors, and tannic acid is a promising candidate as a disease-modifying drug for Parkinson’s disease.
Fucoidan from Sargassum hemiphyllum inhibits infection and inflammation of Helicobacter pylori
Authors: Chen Bo-Rui , Li Wei-Ming , Li Tsung-Lin , Chan Yi-Lin , Wu Chang-Jer
Published: January 2022

Having infected byHelicobacter pylori, the infection often leads to gastritis, gastric ulcer, or even gastric cancer. The disease is typically treated with antibiotics as they used to effectively inhibit or killH. pylori, thus reducing the incidence of gastric adenoma and cancer to significant extent.H. pylori, however, has developed drug resistance to many clinically used antibiotics over the years, highlighting the crisis of antibiotic failure during theH. pyloritreatment. We report here that the fucoidan fromSargassum hemiphyllumcan significantly reduce the infection ofH. pyloriwithout developing to drug resistance. Fucoidan appears to be a strong anti-inflammation agent as manifested by the RAW264.7 cell model examination. Fucoidan can prohibitH. pyloriadhesion to host cells, thereby reducing the infection rate by 60%, especially in post treatment in the AGS cell model assay. Mechanistically, fucoidan intervenes the adhesion of BabA and AlpA ofH. pylorisignificantly lowering the total count ofH. pyloriand the level of IL-6 and TNF-α in vivo. These results all converge on the same fact that fucoidan is an effective agent in a position to protect the stomach from theH. pyloriinfection by reducing both the total count and induced inflammation.
Cortical traveling waves reflect state-dependent hierarchical sequencing of local regions in the human connectome network
Authors: Sato Naoyuki
Published: January 2022

Recent human studies using electrocorticography have demonstrated that alpha and theta band oscillations form traveling waves on the cortical surface. According to neural synchronization theories, the cortical traveling waves may group local cortical regions and sequence them by phase synchronization; however these contributions have not yet been assessed. This study aimed to evaluate the functional contributions of traveling waves using connectome-based network modeling. In the simulation, we observed stable traveling waves on the entire cortical surface wherein the topographical pattern of these phases was substantially correlated with the empirically obtained resting-state networks, and local radial waves also appeared within the size of the empirical networks (< 50 mm). Importantly, individual regions in the entire network were instantaneously sequenced by their internal frequencies, and regions with higher intrinsic frequency were seen in the earlier phases of the traveling waves. Based on the communication-through-coherence theory, this phase configuration produced a hierarchical organization of each region by unidirectional communication between the arbitrarily paired regions. In conclusion, cortical traveling waves reflect the intrinsic frequency-dependent hierarchical sequencing of local regions, global traveling waves sequence the set of large-scale cortical networks, and local traveling waves sequence local regions within individual cortical networks.
Hydrodynamic and heat transfer analysis of dissimilar shaped nanoparticles-based hybrid nanofluids in a rotating frame with convective boundary condition
Authors: Ramzan Muhammad , Shahmir Nazia , Ghazwani Hassan Ali S. , Nisar Kottakkaran Sooppy , Alharbi Faizah M. , Yahia I. S.
Published: January 2022

Solar thermal systems have low efficiency due to the working fluid's weak thermophysical characteristics. Thermo-physical characteristics of base fluid depend on particle concentration, diameter, and shapes. To assess a nanofluid's thermal performance in a solar collector, it is important to first understand the thermophysical changes that occur when nanoparticles are introduced to the base fluid. The aim of this study is, therefore, to analyze the hydrodynamic and heat characteristics of two different water-based hybrid nanofluids (used as a solar energy absorber) with varied particle shapes in a porous medium. As the heat transfer surface is exposed to the surrounding environment, the convective boundary condition is employed. Additionally, the flow of nanoliquid between two plates (in parallel) is observed influenced by velocity slip, non-uniform heat source-sink, linear thermal radiation. To make two targeted hybrid nanofluids, graphene is added as a cylindrical particle to water to make a nanofluid, and then silver is added as a platelet particle to the graphene/water nanofluid. For the second hybrid nanofluid, CuO spherical shape particles are introduced to the graphene/water nanofluid. The entropy of the system is also assessed. The Tiwari-Das nanofluid model is used. The translated mathematical formulations are then solved numerically. The physical and graphical behavior of significant parameters is studied.
Gray matter volume alterations in patients with strabismus and amblyopia: voxel-based morphometry study
Authors: Su Ting , Zhu Pei-Wen , Li Biao , Shi Wen-Qing , Lin Qi , Yuan Qing , Jiang Nan , Pei Chong-Gang , Shao Yi
Published: January 2022

This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.
Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound
Authors: Zacharopoulou P. , Marchi E. , Ogbe A. , Robinson N. , Brown H. , Jones M. , Parolini L. , Pace M. , Grayson N. , Kaleebu P. , Rees H. , Fidler S. , Goulder P. , Klenerman P. , Frater J.
Published: January 2022

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning ‘post-treatment control’ remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.
Effect of storage conditions on the shelf-life extension of fungus-colonized substrates based on Metarhizium anisopliae using modified atmosphere packaging
Authors: Jeong Seul-Gi , Kim Ho Myeong , Kim Junheon , Kim Jae Su , Park Hae Woong
Published: January 2022

Metarhizium anisopliae is a promising alternative to chemical pesticides against pine wilt disease caused by Bursaphelenchus xylophilus. Herein, we investigated the efficacy of modified atmosphere packaging (MAP) to prolong the shelf-life of the M. anisopliae conidia. The effects of various conditions on its stability were also examined. M. anisopliae-inoculated millet grains were treated in a MAP system with different packaging materials (polypropylene, PP; polyethylene terephthalate, PET; ethylene vinyl alcohol, EVOH), gas compositions (high CO2 atmosphere, ≈ 90%; high O2 atmosphere, > 95%; high N2 atmosphere, > 95%; 30% CO2 + 70% N2; 50% CO2 + 50% N2; 70% CO2 + 30% N2), and storage temperatures (4 and 25 °C). Results revealed EVOH film as the best for the preservation of gases at all concentrations for 28 days. MAP treatment in the high-barrier EVOH film under an atmosphere of 30% CO2 + 70% N2 achieved 80.5% viability of dried conidia (7.4% moisture content), with 44.2–64.9% viability recorded with the other treatments. Cold storage for technical concentrates formulation promoted extension of shelf-life of MAP-treated conidia. These results imply that MAP under optimized conditions could enhance the shelf-life of fungus-based biopesticides in fungus-colonized substrates formulations.
Structure-guided development of Pb2+-binding DNA aptamers
Authors: Liu Hehua , Gao Yanqing , Mathivanan Johnsi , Shen Fusheng , Chen Xi , Li Yangyang , Shao Zhiwei , Zhang Yixi , Shao Qiyuan , Sheng Jia , Gan Jianhua
Published: January 2022

Owing to its great threat to human health and environment, Pb2+ pollution has been recognized as a major public problem by the World Health Organization (WHO). Many DNA aptamers have been utilized in the development of Pb2+-detection sensors, but the underlying mechanisms remain elusive. Here, we report three Pb2+-complexed structures of the thrombin binding aptamer (TBA). These high-resolution crystal structures showed that TBA forms intramolecular G-quadruplex and Pb2+ is bound by the two G-tetrads in the center. Compared to K+-stabilized G-quadruplexes, the coordinating distance between Pb2+ and the G-tetrads are much shorter. The T3T4 and T12T13 linkers play important roles in dimerization and crystallization of TBA, but they are changeable for Pb2+-binding. In combination with mutagenesis and CD spectra, the G8C mutant structure unraveled that the T7G8T9 linker of TBA is also variable. In addition to expansion of the Pb2+-binding aptamer sequences, our study also set up one great example for quick and rational development of other aptamers with similar or optimized binding activity.
Tissue specific expression of UMAMIT amino acid transporters in wheat
Authors: Fang Ze Tian , Kapoor Rajan , Datta Aniruddha , Okumoto Sakiko
Published: January 2022

Wheat grain protein content and composition are important for its end-use quality. Protein synthesis during the grain filling phase is supported by the amino acids remobilized from the vegetative tissue, the process in which both amino acid importers and exporters are expected to be involved. Previous studies identified amino acid importers that might function in the amino acid remobilization in wheat. However, the amino acid exporters involved in this process have been unexplored so far. In this study, we have curated the Usually Multiple Amino acids Move In and out Transporter (UMAMIT) family of transporters in wheat. As expected, the majority of UMAMITs were found as triads in the A, B, and D genomes of wheat. Expression analysis using publicly available data sets identified groups of TaUMAMITs expressed in root, leaf, spike, stem and grain tissues, many of which were temporarily regulated. Strong expression of TaUMAMITs was detected in the late senescing leaves and transfer cells in grains, both of which are the expected site of apoplastic amino acid transport during grain filling. Biochemical characterization of selected TaUMAMITs revealed that TaUMAMIT17 shows a strong amino acid export activity and might play a role in amino acid transfer to the grains.
Effects of Te- and Fe-doping on the superconducting properties in FeySe1−xTex thin films
Authors: Zhang Yalin , Wang Tong , Wang Zhihe , Xing Zhongwen
Published: January 2022

High quality FeySe1−xTex epitaxial thin films have been fabricated on TiO2-buffered SrTiO3 substrates by pulsed laser deposition technology. There is a significant composition deviation between the nominal target and the thin film. Te doping can affect the Se/Te ratio and Fe content in chemical composition. The superconducting transition temperature Tc is closely related to the chemical composition. Fe vacancies are beneficial for the FeySe1−xTex films to exhibit the higher Tc. A 3D phase diagram is given that the optimize range is x = 0.13–0.15 and y = 0.73–0.78 for FeySe1−xTex films. The anisotropic, effective pining energy, and critical current density for the Fe0.72Se0.94Te0.06, Fe0.76Se0.87Te0.13 and Fe0.91Se0.77Te0.23 films were studied in detail. The scanning transmission electron microscopy images display a regular atomic arrangement at the interfacial structure.
Quantitative imaging of ultrasound backscattered signals with information entropy for bone microstructure characterization
Authors: Wang Chiao-Yin , Chu Sung-Yu , Lin Yu-Ching , Tsai Yu-Wei , Tai Ching-Lung , Yang Kuen-Cheh , Tsui Po-Hsiang
Published: January 2022

Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient rs, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (rs = − 0.83; p < 0.05). Small-window entropy imaging also performed well in discriminating young and old participants (p < 0.05) and postmenopausal women with low versus moderate-to-high osteoporosis risk (the area under the ROC curve = 0.80; cut-off value = 2.65; accuracy = 86.00%; sensitivity = 71.43%; specificity = 88.37%). Ultrasound small-window entropy imaging has great potential in bone tissue characterization and osteoporosis assessment.
Linkage mapping and QTL analysis of growth traits in Rhopilema esculentum
Authors: Chen Bailing , Li Yulong , Tian Meilin , Su Hao , Sun Wei , Li Yunfeng
Published: January 2022

R. esculentumis a popular seafood in Asian countries and an economic marine fishery resource in China. However, the genetic linkage map and growth-related molecular markers are still lacking, hindering marker assisted selection (MAS) for genetic improvement ofR. esculentum. Therefore, we firstly used 2b-restriction site-associated DNA (2b-RAD) method to sequence 152R. esculentumspecimens and obtained 9100 single nucleotide polymorphism (SNP) markers. A 1456.34 cM linkage map was constructed using 2508 SNP markers with an average interval of 0.58 cM. Then, six quantitative trait loci (QTLs) for umbrella diameter and body weight were detected by QTL analysis based on the new linkage map. The six QTLs are located on four linkage groups (LGs), LG4, LG13, LG14 and LG15, explaining 9.4% to 13.4% of the phenotypic variation. Finally, 27 candidate genes in QTLs regions of LG 14 and 15 were found associated with growth and one gene namedRE13670(sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1-like) may play an important role in controlling the growth ofR. esculentum. This study provides valuable information for investigating the growth mechanism and MAS breeding inR. esculentum.
The over-estimation of distance for self-voice versus other-voice
Authors: Wen Wen , Okon Yuta , Yamashita Atsushi , Asama Hajime
Published: January 2022

Self-related stimuli are important cues for people to recognize themselves in the external world and hold a special status in our perceptual system. Self-voice plays an important role in daily social communication and is also a frequent input for self-identification. Although many studies have been conducted on the acoustic features of self-voice, no research has ever examined the spatial aspect, although the spatial perception of voice is important for humans. This study proposes a novel perspective for studying self-voice. We investigated people’s distance perception of their own voice when the voice was heard from an external position. Participants heard their own voice from one of four speakers located either 90 or 180 cm from their sitting position, either immediately after uttering a short vowel (i.e., active session) or hearing the replay of their own pronunciation (i.e., replay session). They were then asked to indicate which speaker they heard the voice from. Their voices were either pitch-shifted by ± 4 semitones (i.e., other-voice condition) or unaltered (i.e., self-voice condition). The results of spatial judgment showed that self-voice from the closer speakers was misattributed to that from the speakers further away at a significantly higher proportion than other-voice. This phenomenon was also observed when the participants remained silent and heard prerecorded voices. Additional structural equation modeling using participants’ schizotypal scores showed that the effect of self-voice on distance perception was significantly associated with the score of delusional thoughts (Peters Delusion Inventory) and distorted body image (Perceptual Aberration Scale) in the active speaking session but not in the replay session. The findings of this study provide important insights for understanding how people process self-related stimuli when there is a small distortion and how this may be linked to the risk of psychosis.
Quality factor control of mechanical resonators using variable phononic bandgap on periodic microstructures
Authors: Inomata Naoki , Tonsho Yuka , Ono Takahito
Published: January 2022

The quality factor (Q-factor) is an important parameter for mechanical resonant sensors, and the optimal values depend on its application. Therefore, Q-factor control is essential for microelectromechanical systems (MEMS). Conventional methods have some restrictions, such as additional and complicated equipment or nanoscale dimensions; thus, structural methods are one of the reasonable solutions for simplifying the system. In this study, we demonstrate Q-factor control using a variable phononic bandgap by changing the length of the periodic microstructure. For this, silicon microstructure is used because it has both periodicity and a spring structure. The bandgap change is experimentally confirmed by measuring the Q-factors of mechanical resonators with different resonant frequencies. The bandgap range varies depending on the extended structure length, followed by a change in the Q-factor value. In addition, the effects of the periodic structure on the Q-factor enhancement and the influence of stress on the structural length were evaluated. Although microstructures can improve the Q-factors irrespective of periodicity; the result of the periodic microstructure is found to be efficient. The proposed method is feasible as the novel Q-factor control technique has good compatibility with conventional MEMS.