bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals in vivo osteoimmunology interactions between the immune and skeletal systems
Authors: Wang Shengran , Greenbaum Jonathan , Qiu Chuan , Gong Yun , Wang Zun , Lin Xu , Liu Yong , He Pei , Meng Xianghe , Zhang Qiang , Shen Hui , Vemulapalli Krishna Chandra , Sanchez Fernando L. , Schiller Martin R. , Xiao Hongmei , Deng Hongwen 
Published: March 2023

BackgroundWhile osteoimmunology interactions between the immune and skeletal systems are known to play an important role in osteoblast development, differentiation and bone metabolism related disease like osteoporosis, such interactions in either bone microenvironment or peripheral circulation in vivo at the single-cell resolution have not yet been characterized.MethodsWe explored the osteoimmunology communications between immune cells and osteoblastic lineage cells (OBCs) by performing CellphoneDB and CellChat analyses with single-cell RNA sequencing (scRNA-seq) data from human femoral head. We also explored the osteoimmunology effects of immune cells in peripheral circulation on skeletal phenotypes. We used a scRNA-seq dataset of peripheral blood monocytes (PBMs) to perform deconvolution analysis. Then weighted gene co-expression network analysis (WGCNA) was used to identify monocyte subtype-specific subnetworks. We next used cell-specific network (CSN) and the least absolute shrinkage and selection operator (LASSO) to analyze the correlation of a gene subnetwork identified by WGCNA with bone mineral density (BMD).ResultsWe constructed immune cell and OBC communication networks and further identified L-R genes, such as JAG1 and NOTCH1/2, with ossification related functions. We also found a Mono4 related subnetwork that may relate to BMD variation in both older males and postmenopausal female subjects.ConclusionsThis is the first study to identify numerous ligand-receptor pairs that likely mediate signals between immune cells and osteoblastic lineage cells. This establishes a foundation to reveal advanced and in-depth osteoimmunology interactions to better understand the relationship between local bone microenvironment and immune cells in peripheral blood and the impact on bone phenotypes.
Experimental study on the rotating detonation engine based on a gas mixture
Authors: Xue Sainan , Zhang Xin , Yang Jianlu , Liu Denghang , Ma Hu , Zhou Changsheng 
Published: March 2023

A direct connection test of a rotating detonation engine was conducted. The outer and inner diameters of the annular combustors were 206 and 166 mm, respectively. High enthalpy air was used as an oxidizer, and a mixture of hydrogen, carbon monoxide, and methane was used as fuel with a volume fraction of 5/4/1. The mixture was injected through small holes, and air was injected through annular slots. The effects of combustor length, width of annular slots, and the equivalent ratio on formation, development, propagation, and flameout of rotating detonation waves were analyzed, and several modes of rotating detonation were observed. It was found that when the width of the air annular slot was within the range of 3–5 mm, the pressure of the detonation wave was augmented with an increased slot width. As width increased, detonation waves became unstable. In study test conditions, an annular slot width of 6 mm was the critical condition for the formation of stable detonation. When the slot width was 4 mm and combustor length 160 mm, the phenomena of the conversion between single and double waves, double-wave collision, and conversion of the propagation direction occurred at different equivalent ratios. When the equivalent ratio was 1.2/1 and the slot width was within the range of 3–6 mm, the slot width was inversely related to the detonation wave velocity. When the slot width was 4 mm and the equivalent ratio was 1.0/1–1.2/1, the slot width was positively correlated with the detonation wave velocity. When the combustor length was shortened to 80 mm, the propagation mode of the detonation wave was changed to a single wave first and then to a double wave in the same direction, and the velocity reduced from 1130.69 to 1024.16 m/s. The injector used in the test inhibited the propagation of back pressure from the combustor.
Impaired tolerance to the autoantigen LL-37 in acute coronary syndrome
Authors: Chernomordik Fernando , Cercek Bojan , Zhou Jianchang , Zhao Xiaoning , Lio Nicole Wai Man , Chyu Kuang-Yuh , Shah Prediman K. , Dimayuga Paul C. 
Published: March 2023

BackgroundLL-37 is the only member of the cathelicidin family of antimicrobial peptides in humans and is an autoantigen in several autoimmune diseases and in acute coronary syndrome (ACS). In this report, we profiled the specific T cell response to the autoimmune self-antigen LL-37 and investigated the factors modulating the response in peripheral blood mononuclear cells (PBMCs) of healthy subjects and ACS patients.Methods and resultsThe activation induced marker (AIM) assay demonstrated differential T cell profiles characterized by the persistence of CD134 and CD137, markers that impair tolerance and promote immune effector and memory response, in ACS compared to Controls. Specifically, CD8+CD69+CD137+ T cells were significantly increased by LL-37 stimulation in ACS PBMCs. T effector cell response to LL-37 were either HLA dependent or independent as determined by blocking with monoclonal antibody to either Class-I HLA or Class-II HLA. Blocking of immune checkpoints PD-1 and CTLA-4 demonstrated the control of self-reactive T cell response to LL-37 was modulated predominantly by CTLA-4. Platelets from healthy controls down-modulated CD8+CD69+CD137+ T cell response to LL-37 in autologous PBMCs. CD8+CD69+CD137+ T cell AIM profile negatively correlated with platelet count in ACS patients.ConclusionsOur report demonstrates that the immune response to the autoantigen LL-37 in ACS patients is characterized specifically by CD8+CD69+CD137+ T cell AIM profile with persistent T cell activation and the generation of immunologic memory. The results provide potentially novel insight into mechanistic pathways of antigen-specific immune signaling in ACS.
Analysis of necroptosis-related prognostic genes and immune infiltration in idiopathic pulmonary fibrosis
Authors: Chen Hongzuo , Xia Zhenkun , Qing Bei , Wang Wei , Gu Linguo , Chen Ying , Wang Juan , Yuan Yunchang 
Published: March 2023

BackgroundIPF is an undetermined, progressive lung disease. Necroptosis is a type of programmed apoptosis, which involved in the pathogenesis of lung diseases like COPD and ARDS. However, necroptosis in IPF have not been adequately studied. This study aimed to investigate the necroptosis in IPF and the relationship between necroptosis and immune infiltration, to construct a prognostic prediction model of IPF based on necroptosis-related genes.MethodsGSE110147 was downloaded from the GEO database and utilized to analyze the expression of necroptosis-related differentially expressed genes (NRDEGs). Then NRDEGs were used to construct protein-protein interaction (PPI) networks in the STRING database, and Cytoscape software was used to identify and visualize hub genes. Necroptosis-related prognosticgenes were explored in GSE70866, and a prognostic prediction model was constructed. The ImmuCellAI algorithm was utilized to analyze the landscape of immune infiltration in GSE110147. The single-cell RNA sequencing dataset GSE122960 was used to explore the association between necroptosis and type II alveolar epithelial cells (AT II) in IPF. The GSE213001 and GSE93606 were used for external validation. The expression of prognostic genes was quantified using RT-qPCRin the IPF A549 cell model, and was further verified by western blotting in the bleomycin-induced pulmonary fibrosis mouse model.ResultsIt was observed that necroptosis-related signaling pathways were abundantly enriched in IPF. 29 NRDEGs were screened, of which 12 showed consistent expression trends in GSE213001. Spearman correlation analysis showed that the expression of NRDEGs was positively correlated with the infiltration of proinflammatory immune cells, and negatively correlated with the infiltration of anti-inflammatory immune cells. NRDEGs, including MLKL, were highly expressed in AT II of fibrotic lung tissue. A necroptosis-related prediction model was constructed based on 4 NRDEGsby the cox stepwise regression. In the validation dataset GSE93606, the prognostic prediction model showed good applicability. The verification results of RT-qPCR and western blotting showed the reliability of most of the conclusions.ConclusionsThis study revealed that necroptosis existed in IPF and might occur in AT II. Necroptosis was associated with immune infiltration, suggesting that necroptosis of AT II might involve in IPF by activating immune infiltration and immune response.
Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of sepsis-induced ALI/ARDS
Authors: Liu Chenchen , Zhou Yu , Tu Qing , Yao Liangfang , Li Jinbao , Yang Zhongwei 
Published: March 2023

BackgroundNeutrophil extracellular traps (NETs) can cause acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage pyroptosis. The purpose of this study was to find out whether pretreatment of alpha-linolenic acid (ALA) could inhibit NETs-induced macrophage pyroptosis in sepsis-induced ALI/ARDS, as well as to identify which inflammasome is involved in this process.MethodsLPS was instilled into the trachea to establish sepsis-induced ALI/ARDS in a mouse model. ​Lung injury was assessed by microscopic examination of lung tissue after hematoxylin and eosin staining, pathology score, and bronchoalveolar lavage fluid (BALF) total protein concentration. The level of NETs in lung tissue was detected by MPO-DNA ELISA. Purified NETs, extracted from peritoneal neutrophils, induced macrophage pyroptosis in vitro. Expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in the lung tissue and bone marrow-derived macrophages (BMDMs) were determined by western blotting or ELISA. Specks of Pyrin/ASC were examined by confocal immunofluorescence microscopy. Mefv (Pyrin)-/- mice were used to study the role of Pyrin in the process of sepsis-induced ALI/ARDS.ResultsALA alleviated LPS-induced lung injury. ALA reduced the level of NETs, pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC), and IL-1β in the lung tissue of sepsis mice. In vitro, NETs increased the expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β significantly in BMDMs. Pyrin protein was found to be higher and form the inflammasome with ASC in NETs challenged-BMDMs. Knockout of Mefv (Pyrin) gene fully restored the increased expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in vitro and in vivo. Lung injury was alleviated significantly in Mefv (Pyrin)-/- mice as well.​ ALA suppresses all the NETs-induced changes as mentioned above.ConclusionOur study is the first to demonstrate Pyrin inflammasome driving NETs-induced macrophage pyroptosis, and ALA may reduce ALI/ARDS by inhibiting the activation of the Pyrin inflammasome-driven macrophage pyroptosis.
FGL2 deficiency alleviates maternal inflammation-induced blood-brain barrier damage by blocking PI3K/NF-κB mediated endothelial oxidative stress
Authors: Huang Lianjing , Zhan Di , Xing Ying , Yan Yaqin , Li Qing , Zhang Jingyi , Li Sujuan , Ning Qin , Zhang Cai , Luo Xiaoping 
Published: March 2023

IntroductionThe impairment of blood-brain barrier (BBB) is one of the key contributors to maternal inflammation induced brain damage in offspring. Our previous studies showed Fibrinogen-like protein 2 (FGL2) deficiency alleviated maternal inflammation induced perinatal brain damage. However, its role in BBB remains undefined.MethodsLipopolysaccharide (LPS) was intraperitoneally injected to dams at Embryonic day 17 to establish maternal inflammation model. FGL2 knockout mice and primary brain microvascular endothelial cells (BMECs) were used for the in-vivo and in-vitro experiments. BBB integrity was assessed by sodium fluorescein extravasation and tight junction (TJ) protein expression. Oxidative stress and the activation of PI3K/NF-κB pathway were evaluated to explore the mechanisms underlying.ResultsUpon maternal inflammation, BBB integrity was remarkedly reduced in neonatal mice. Meanwhile, FGL2 expression was consistently increased in BBB-impaired brain as well as in LPS-treated BMECs. Moreover, FGL2 deficiency attenuated the hyperpermeability of BBB, prevented the decline of TJ proteins, and reduced the cytokine expressions in LPS-exposed pups. Mechanistically, the indicators of oxidative stress, as well as the activation of PI3K/NF-κB pathway, were upregulated after LPS exposure in vivo and in vitro. FGL2 deletion decreased the generation of ROS and NO, reduced the endothelial iNOS and NOX2 expressions, and suppressed the PI3K/NF-κB pathway activation. Besides, inhibition of PI3K by LY294002 decreased the oxidative stress in LPS-treated wild-type BMECs. While, overexpression of PI3K by lentivirus reemerged the induction of NOX2 and iNOS as well as NF-κB activation in FGL2-deleted BMECs.ConclusionOur findings indicate that FGL2 deficiency alleviates the maternal inflammation-induced BBB disruption by inhibiting PI3K/NF-κB mediated oxidative stress in BMECs. Targeting FGL2 may provide a new therapy for prenatal brain damage of offspring.
Elevated serum platelet count inhibits the effects of brain functional changes on cognitive function in patients with mild cognitive impairment: A resting-state functional magnetic resonance imaging study
Authors: Zhang Yuechan , Liu Jing , Wei Zijun , Mei Jianing , Li Qianqian , Zhen Xiaomin , Zhang Yunyun 
Published: March 2023

ObjectiveBrain function remodeling has been observed in patients with mild cognitive impairment (MCI) and is closely associated with cognitive performance. However, it is not clear if this relationship is influenced by complete blood counts. This study investigated the role of complete blood counts in the relationship between brain function and cognitive performance.MethodsTwenty-two MCI patients and eighteen controls were enrolled. All subjects underwent resting-state functional magnetic resonance imaging. A neuropsychological battery [Mini-Mental Status Examination, Auditory Verbal Learning Test (AVLT), Symbol Digit Modalities Test, Boston Naming Test (BNT), Shape Trails Test B (STT-B), Rey Complex Figure Test (RCFT), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Scale] was used to assess cognitive function, and MCI patients received complete blood counts tests for red blood cells (RBC), white blood cells, hemoglobin (HGB), monocytes, and platelet counts (PLT).ResultsCompared with controls, MCI patients demonstrated significantly decreased amplitude of low-frequency fluctuation (ALFF) values in the left dorsolateral superior frontal gyrus, left post orbitofrontal cortex, right medial superior frontal gyrus, right insula, and left triangular inferior frontal gyrus. In the MCI group, there were associations between ALFF values of the left hippocampus (HIP.L) and AVLT (p = 0.003) and AVLT-N5 scores (p = 0.001); ALFF values of the right supramarginal gyrus (SMG.R) and BNT scores (p = 0.044); ALFF values of the right superior temporal gyrus (STG.R) and BNT scores (p = 0.022); ALFF values of the left precuneus (PCUN.L) and STT-B time (p = 0.012); and ALFF values of the left caudate nucleus (CAU.L) and RCFT-time (p = 0.036). Moreover, the HAMA scores were negatively correlated with RBC and HGB levels, and positively correlated with monocyte count. The PLT count was positively correlated with STT-B time. Additionally, high PLT count inhibited the effect of ALFF values of the PCUN. L on STT-B performance in MCI patients (p = 0.0207).ConclusionALFF values of the HIP. L, SMG.R, STG. R, PCUN.L, and CAU. L were associated with decreased memory, language, executive function, and visuospatial ability in MCI patients. Notably, elevated PLT count could inhibit the effect of brain functional changes in the PCUN.L on executive function in MCI patients.
The signs of computer tomography combined with artificial intelligence can indicate the correlation between status of consciousness and primary brainstem hemorrhage of patients
Authors: Liu Guofang , Sun Juan , Zuo Shiyi , Zhang Lei , Cai Hanxu , Zhang Xiaolong , Hu Zhian , Liu Yong , Yao Zhongxiang 
Published: March 2023

BackgroundFor patients of primary brainstem hemorrhage (PBH), it is crucial to find a method that can quickly and accurately predict the correlation between status of consciousness and PBH.ObjectiveTo analyze the value of computer tomography (CT) signs in combination with artificial intelligence (AI) technique in predicting the correlation between status of consciousness and PBH.MethodsA total of 120 patients with PBH were enrolled from August 2011 to March 2021 according to the criteria. Patients were divided into three groups [consciousness, minimally conscious state (MCS) and coma] based on the status of consciousness. Then, first, Mann–Whitney U test and Spearman rank correlation test were used on the factors: gender, age, stages of intracerebral hemorrhage, CT signs with AI or radiology physicians, hemorrhage involving the midbrain or ventricular system. We collected hemorrhage volumes and mean CT values with AI. Second, those significant factors were screened out by the Mann–Whitney U test and those highly or moderately correlated by Spearman’s rank correlation test, and a further ordinal multinomial logistic regression analysis was performed to find independent predictors of the status of consciousness. At last, receiver operating characteristic (ROC) curves were drawn to calculate the hemorrhage volume for predictively assessing the status of consciousness.ResultsPreliminary meaningful variables include hemorrhage involving the midbrain or ventricular system, hemorrhage volume, grade of hematoma shape and density, and CT value from Mann–Whitney U test and Spearman rank correlation test. It is further shown by ordinal multinomial logistic regression analysis that hemorrhage volume and hemorrhage involving the ventricular system are two major predictors of the status of consciousness. It showed from ROC that the hemorrhage volumes of &lt;3.040 mL, 3.040 ~ 6.225 mL and &gt;6.225 mL correspond to consciousness, MCS or coma, respectively. If the hemorrhage volume is the same, hemorrhage involving the ventricular system should be correlated with more severe disorders of consciousness (DOC).ConclusionCT signs combined with AI can predict the correlation between status of consciousness and PBH. Hemorrhage volume and hemorrhage involving the ventricular system are two independent factors, with hemorrhage volume in particular reaching quantitative predictions.
Retinal ganglion cells adapt to ionic stress in experimental glaucoma
Authors: Boal Andrew M. , McGrady Nolan R. , Holden Joseph M. , Risner Michael L. , Calkins David J. 
Published: March 2023

IntroductionIdentification of early adaptive and maladaptive neuronal stress responses is an important step in developing targeted neuroprotective therapies for degenerative disease. In glaucoma, retinal ganglion cells (RGCs) and their axons undergo progressive degeneration resulting from stress driven by sensitivity to intraocular pressure (IOP). Despite therapies that can effectively manage IOP many patients progress to vision loss, necessitating development of neuronal-based therapies. Evidence from experimental models of glaucoma indicates that early in the disease RGCs experience altered excitability and are challenged with dysregulated potassium (K+) homeostasis. Previously we demonstrated that certain RGC types have distinct excitability profiles and thresholds for depolarization block, which are associated with sensitivity to extracellular K+.MethodsHere, we used our inducible mouse model of glaucoma to investigate how RGC sensitivity to K+ changes with exposure to elevated IOP.ResultsIn controls, conditions of increased K+ enhanced membrane depolarization, reduced action potential generation, and widened action potentials. Consistent with our previous work, 4 weeks of IOP elevation diminished RGC light-and current-evoked responses. Compared to controls, we found that IOP elevation reduced the effects of increased K+ on depolarization block threshold, with IOP-exposed cells maintaining greater excitability. Finally, IOP elevation did not alter axon initial segment dimensions, suggesting that structural plasticity alone cannot explain decreased K+ sensitivity.DiscussionThus, in response to prolonged IOP elevation RGCs undergo an adaptive process that reduces sensitivity to changes in K+ while diminishing excitability. These experiments give insight into the RGC response to IOP stress and lay the groundwork for mechanistic investigation into targets for neuroprotective therapy.
Eye movement characteristics in a mental rotation task presented in virtual reality
Authors: Tang Zhili , Liu Xiaoyu , Huo Hongqiang , Tang Min , Qiao Xiaofeng , Chen Duo , Dong Ying , Fan Linyuan , Wang Jinghui , Du Xin , Guo Jieyi , Tian Shan , Fan Yubo 
Published: March 2023

IntroductionEye-tracking technology provides a reliable and cost-effective approach to characterize mental representation according to specific patterns. Mental rotation tasks, referring to the mental representation and transformation of visual information, have been widely used to examine visuospatial ability. In these tasks, participants visually perceive three-dimensional (3D) objects and mentally rotate them until they identify whether the paired objects are identical or mirrored. In most studies, 3D objects are presented using two-dimensional (2D) images on a computer screen. Currently, visual neuroscience tends to investigate visual behavior responding to naturalistic stimuli rather than image stimuli. Virtual reality (VR) is an emerging technology used to provide naturalistic stimuli, allowing the investigation of behavioral features in an immersive environment similar to the real world. However, mental rotation tasks using 3D objects in immersive VR have been rarely reported.MethodsHere, we designed a VR mental rotation task using 3D stimuli presented in a head-mounted display (HMD). An eye tracker incorporated into the HMD was used to examine eye movement characteristics during the task synchronically. The stimuli were virtual paired objects oriented at specific angular disparities (0, 60, 120, and 180°). We recruited thirty-three participants who were required to determine whether the paired 3D objects were identical or mirrored.ResultsBehavioral results demonstrated that the response times when comparing mirrored objects were longer than identical objects. Eye-movement results showed that the percent fixation time, the number of within-object fixations, and the number of saccades for the mirrored objects were significantly lower than that for the identical objects, providing further explanations for the behavioral results.DiscussionIn the present work, we examined behavioral and eye movement characteristics during a VR mental rotation task using 3D stimuli. Significant differences were observed in response times and eye movement metrics between identical and mirrored objects. The eye movement data provided further explanation for the behavioral results in the VR mental rotation task.