bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Method to Develop the Primate Model of Knee Osteoarthritis With Focal Cartilage Defect
Authors: Bi Xin , Li Tao , Li Min , Xiang Shutian , Li Junhong , Ling Bin , Wu Zhaoxiang , Chen Zhong
Published: November 2021

Objective: Osteoarthritis (OA) is a common degenerative joint disease, and animal models have proven pivotal in investigating this disease. This study aimed to develop a primate model of OA that may be more relevant to research studies on OA in humans.

Method: Twelve female rhesus macaques were randomly divided into three groups. Four animals were untreated (Control group); four were subjected to the modified Hulth method, involving cutting of the anterior and posterior cruciate ligaments, and transecting the meniscus (Hulth group); and four were subjected to the modified Hulth method combined with cartilage defect (MHCD group). Each primate was subjected to motor ability tests, and underwent arthroscopic, radiographic, morphological, and pathological observation of the knee joints at various times for up to 180 days.

Results: Motor ability on Day 180 was significantly lower in the MHCD group than in the Control (p＜0.01) and Hulth (p＜0.05) groups. Radiographic and morphological examination showed that the severity of knee joint deformity and articular cartilage injury were greater in the MHCD group than in the other groups. Pathological examination showed that cartilage thickness was significantly lower in the MHCD group than in the other groups at the same time points. The Mankin score on Day 180 was markedly higher in the MHCD group than in the Hulth (p＜0.05) and Control (p＜0.001) groups.

Conclusion: The MHCD model of OA closely resembles the pathophysiological processes of spontaneous knee OA in humans. The time required to develop knee OA is shorter using the MHCD model than using the Hulth method.
Comparison of Gait Symmetry and Joint Moments in Unilateral and Bilateral Hip Osteoarthritis Patients and Healthy Controls
Authors: van Drongelen S. , Braun S. , Stief F. , Meurer A.
Published: November 2021

Patients with unilateral hip osteoarthritis show a characteristic gait pattern in which they unload the affected leg and overload the unaffected leg. Information on the gait characteristics of patients with bilateral hip osteoarthritis is very limited. The main purposes of this study were to investigate whether the gait pattern of both legs of patients with bilateral hip osteoarthritis deviates from healthy controls and whether bilateral hip osteoarthritis patients show a more symmetrical joint load compared to unilateral hip osteoarthritis patients. In this prospective study, 26 patients with bilateral hip osteoarthritis, 26 patients with unilateral hip osteoarthritis and 26 healthy controls were included. The three groups were matched for gender, age and walking speed. Patients were scheduled for a unilateral total hip arthroplasty on the more affected/more painful side. All participants underwent a three-dimensional gait analysis. Gait kinematics and gait kinetics of patients and controls were compared using Statistical Parametric Mapping. Corrected for speed, the gait kinematics and kinetics of both legs of patients with bilateral hip osteoarthritis differed from healthy controls. Bilateral patients had symmetrical knee joint loading, in contrast to the asymmetrical knee joint loading in unilateral hip osteoarthritis patients. The ipsilateral leg of the bilateral patients could be included in studies in addition to unilateral hip osteoarthritis patients as no differences were found. Although patients with bilateral hip osteoarthritis show more symmetrical frontal plane knee joint moments, a pathological external knee adduction moment in the second half of stance was present in the ipsilateral leg in patients with unilateral and bilateral hip osteoarthritis. The lateral adjustment of the knee adduction moment may initiate or accelerate progression of degenerative changes in the lateral compartment of the knee.
From Stoop to Squat: A Comprehensive Analysis of Lumbar Loading Among Different Lifting Styles
Authors: von Arx Michael , Liechti Melanie , Connolly Lukas , Bangerter Christian , Meier Michael L. , Schmid Stefan
Published: November 2021

Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher loads in the lumbar spine. Even though recent biomechanical studies challenge these assumptions, conclusive evidence is still lacking. This study therefore aimed at comparing lumbar loads among different lifting styles using a comprehensive state-of-the-art motion capture-driven musculoskeletal modeling approach. Thirty healthy pain-free individuals were enrolled in this study and asked to repetitively lift a 15 kg-box by applying 1) a freestyle, 2) a squat and 3) a stoop lifting technique. Whole-body kinematics were recorded using a 16-camera optical motion capture system and used to drive a full-body musculoskeletal model including a detailed thoracolumbar spine. Continuous as well as peak compressive, anterior-posterior shear and total loads (resultant load vector of the compressive and shear load vectors) were calculated based on a static optimization approach and expressed as factor body weight (BW). In addition, lumbar lordosis angles and total lifting time were calculated. All parameters were compared among the lifting styles using a repeated measures design. For each lifting style, loads increased towards the caudal end of the lumbar spine. For all lumbar segments, stoop lifting showed significantly lower compressive and total loads (−0.3 to −1.0BW) when compared to freestyle and squat lifting. Stoop lifting produced higher shear loads (+0.1 to +0.8BW) in the segments T12/L1 to L4/L5, but lower loads in L5/S1 (−0.2 to −0.4BW). Peak compressive and total loads during squat lifting occurred approximately 30% earlier in the lifting cycle compared to stoop lifting. Stoop lifting showed larger lumbar lordosis range of motion (35.9 ± 10.1°) than freestyle (24.2 ± 7.3°) and squat (25.1 ± 8.2°) lifting. Lifting time differed significantly with freestyle being executed the fastest (4.6 ± 0.7 s), followed by squat (4.9 ± 0.7 s) and stoop (5.9 ± 1.1 s). Stoop lifting produced lower total and compressive lumbar loads than squat lifting. Shear loads were generally higher during stoop lifting, except for the L5/S1 segment, where anterior shear loads were higher during squat lifting. Lifting time was identified as another important factor, considering that slower speeds seem to result in lower loads.
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Gilbert Guillaume , Kadur Nagaraju Chandan , Duelen Robin , Amoni Matthew , Bobin Pierre , Eschenhagen Thomas , Roderick H. Llewelyn , Sampaolesi Maurilio , Sipido Karin R.
Published: November 2021

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex. We examined the expression of DAPC components in hiPSC-CM, which underwent maturation in 2D and 3D culture protocols. The results were compared with human adult cardiac tissue and isolated cardiomyocytes. We found that similarly to adult cardiomyocytes, hiPSC-CM express dystrophin, in line with previous studies on Duchenne’s disease. β-dystroglycan was also expressed, but, contrary to findings in adult cardiomyocytes, none of the sarcoglycans nor α-dystroglycan were, despite the presence of their mRNA. In conclusion, despite the robust expression of dystrophin, the absence of several other DAPC protein components cautions for reliance on commonly used protocols for hiPSC-CM maturation for functional assessment of the complete DAPC.
Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma
Authors: Wu Jing , Zhou Jiawei , Xu Qian , Foley Ruth , Guo Jianqiang , Zhang Xin , Tian Chang , Mu Min , Xing Yingru , Liu Yafeng , Wang Xueqin , Hu Dong
Published: November 2021

The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment.
Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
Authors: Zhang Jingtian , Uchiyama Junki , Imami Koshi , Ishihama Yasushi , Kageyama Ryoichiro , Kobayashi Taeko
Published: November 2021

Neural stem cell (NSC) quiescence plays pivotal roles in avoiding exhaustion of NSCs and securing sustainable neurogenesis in the adult brain. The maintenance of quiescence and transition between proliferation and quiescence are complex processes associated with multiple niche signals and environmental stimuli. Exosomes are small extracellular vesicles (sEVs) containing functional cargos such as proteins, microRNAs, and mRNAs. The role of sEVs in NSC quiescence has not been fully investigated. Here, we applied proteomics to analyze the protein cargos of sEVs derived from proliferating, quiescent, and reactivating NSCs. Our findings revealed fluctuation of expression levels and functional clusters of gene ontology annotations of differentially expressed proteins especially in protein translation and vesicular transport among three sources of exosomes. Moreover, the use of exosome inhibitors revealed exosome contribution to entrance into as well as maintenance of quiescence. Exosome inhibition delayed entrance into quiescence, induced quiescent NSCs to exit from the G0 phase of the cell cycle, and significantly upregulated protein translation in quiescent NSCs. Our results suggest that NSC exosomes are involved in attenuating protein synthesis and thereby regulating the quiescence of NSCs.
A Novel Prognostic Model Based on the Serum Iron Level for Patients With Early-Stage Triple-Negative Breast Cancer
Authors: Hua Xin , Duan Fangfang , Huang Jiajia , Bi Xiwen , Xia Wen , Song Chenge , Wang Li , Jiang Chang , Yuan Zhongyu
Published: November 2021

The dysregulation of iron homeostasis has been explored in malignancies. However, studies focusing on the association between the serum iron level and prognosis of patients with early-stage triple-negative breast cancer (TNBC) are scarce. Accordingly, in current study, 272 patients with early-stage TNBC treated at Sun Yat-sen University Cancer Center (SYSUCC) between September 2005 and October 2016 were included as a training cohort, another 86 patients from a previous randomized trial, SYSUCC-001, were analyzed as a validation cohort (SYSUCC-001 cohort). We retrospectively collected their clinicopathological data and tested the serum iron level using blood samples at the diagnosis. In the training cohort, patients were divided into low-iron and high-iron groups according to the serum iron level cut-off of 17.84 μmol/L determined by maximally selected rank statistics. After a median follow-up of 87.10 months, patients with a low iron had a significantly longer median disease-free survival (DFS) of 89.13 [interquartile range (IQR): 66.88–117.38] months and median overall survival (OS) of 92.85 (IQR: 68.83–117.38) months than those in the high-iron group (median DFS: 75.25, IQR: 39.76–105.70 months, P = 0.015; median OS: 77.17, IQR: 59.38–110.28 months, P = 0.015). Univariate and multivariate Cox analysis demonstrated the serum iron level to be an independent predictor for DFS and OS. Then, a prognostic nomogram incorporating the serum iron level, T stage and N stage was developed for individualized prognosis predictions. It had good discriminative ability with a C-index of DFS (0.729; 95% CI 0.666–0.792) and OS (0.739; 95% CI 0.666–0.812), respectively. Furtherly, we validated the predictive model in the SYSUCC-001 cohort, which also showed excellent predictive performance with a C-index of DFS (0.735; 95% CI 0.614–0.855) and OS (0.722; 95% CI 0.577–0.867), respectively. All these suggested that the serum iron level might be a potential prognostic biomarker for patients with early-stage TNBC, the predictive model based on it might be served as a practical tool for individualized survival predictions.
USP25 Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Modulating the PI3K/AKT Pathway via Deubiquitinating PTEN
Authors: Gao Yue , Chen Jiao , Ji Rui , Ding Jinli , Zhang Yan , Yang Jing
Published: November 2021

Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.

Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.

Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.

Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.
Lipoic Acid Metabolism as a Potential Chemotherapeutic Target Against Plasmodium falciparum and Staphylococcus aureus
Authors: Rei Yan Sun Liu , Wakasuqui Felipe , Du Xiaochen , Groves Matthew R. , Wrenger Carsten
Published: November 2021

Lipoic acid (LA) is an organic compound that plays a key role in cellular metabolism. It participates in a posttranslational modification (PTM) named lipoylation, an event that is highly conserved and that occurs in multimeric metabolic enzymes of very distinct microorganisms such as Plasmodium sp. and Staphylococcus aureus, including pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KDH). In this mini review, we revisit the recent literature regarding LA metabolism in Plasmodium sp. and Staphylococcus aureus, by covering the lipoate ligase proteins in both microorganisms, the role of lipoate ligase proteins and insights for possible inhibitors of lipoate ligases.
A Homogeneous Label-Free Electrochemical microRNA Biosensor Coupling With G-Triplex/Methylene Blue Complex and λ-Exonuclease-Assisted Recycling Amplification
Authors: Meng Yao , Chen Fangming , Jiang Mingrui , Guo Qin , Wang Yaqiong , Wang Jian , Zhang De-Wen
Published: November 2021

A novel homogeneous label-free electrochemical biosensor using G-triplex/methylene blue (G3/MB) complex as the signal generator together with an amplification assisted by the λ-exonuclease (λ-Exo) has been successfully constructed for ultrasensitive microRNA (miRNA) detection. An integrated microelectrode was designed to realize the miniaturization of the homogeneous electrochemical assay. Taking advantage of G3, that can specifically bind with MB and decrease its diffusion current, a single-stranded functional DNA hairpin structure was designed as the bio-recognition probe. The probe consisted of G3, eight bases to block G3, and the complementary sequences of the target miRNA. Here we chose miRNA141—a potentially diagnostic biomarker of prostate cancer as the model target. The presence of miRNA141 could hybridize with the probe DNA to form a double-stranded structure with a 5′-phosphorylated terminus. Then λ-Exo was adopted to digest mononucleotides from the 5′-end, leading to the release of G3 part and miRNA141. The released miRNA could hybridize with another probe to trigger the cycling process, while the released G3 could therefore interact with MB to cause a detectable decrease of diffusion current. The proposed strategy showed a low detection limit of 16 fM and an excellent specificity to discriminate single-base mismatches. Furthermore, this sensor was applied to detect miRNA141 from diluted human serum samples, indicating that it has great potential in the application of nucleic acid detection in real samples.
Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment
Authors: Huang Jiayue , Yang Fan , Gutiérrez-Chico Juan Luis , Xu Tianxiao , Wu Jigang , Wang Liang , Lv Rui , Lai Yan , Liu Xuebo , Onuma Yoshinobu , Tang Dalin , Serruys Patrick W. , Wijns William , Tu Shengxian
Published: November 2021

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.

Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.

Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p < 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p < 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).

Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.
Extracellular Vesicles Are Associated With Outcome in Veno-Arterial Extracorporeal Membrane Oxygenation and Myocardial Infarction
Authors: Siegel Patrick M. , Bender Ileana , Chalupsky Julia , Heger Lukas A. , Rieder Marina , Trummer Georg , Wengenmayer Tobias , Duerschmied Daniel , Bode Christoph , Diehl Philipp
Published: November 2021

Background:Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is being increasingly applied in patients with circulatory failure, but mortality remains high. An inflammatory response syndrome initiated by activation of blood components in the extracorporeal circuit may be an important contributing factor. Patients with ST-elevation myocardial infarction (STEMI) may also experience a systemic inflammatory response syndrome and are at risk of developing cardiogenic shock and cardiac arrest, both indications for VA-ECMO. Extracellular vesicles (EV) are released by activated cells as mediators of intercellular communication and may serve as prognostic biomarkers. Cardiomyocyte EV, released upon myocardial ischemia, hold strong potential for this purpose. The aim of this study was to assess the EV-profile in VA-ECMO and STEMI patients and the association with outcome.

Methods:In this prospective observational study, blood was sampled on day 1 after VA-ECMO initiation or myocardial reperfusion (STEMI patients). EV were isolated by differential centrifugation. Leukocyte, platelet, endothelial, erythrocyte and cardiomyocyte (caveolin-3+) Annexin V+EV were identified by flow cytometry. EV were assessed in survivors vs. non-survivors of VA-ECMO and in STEMI patients with normal-lightly vs. moderately-severely reduced left ventricular function. Logistic regression was conducted to determine the predictive accuracy of EV. Pearson correlation analysis of EV with clinical parameters was performed.

Results:Eighteen VA-ECMO and 19 STEMI patients were recruited. Total Annexin V+, cardiomyocyte and erythrocyte EV concentrations were lower (p≤ 0.005) while the percentage of platelet EV was increased in VA-ECMO compared to STEMI patients (p= 0.002). Total Annexin V+EV were increased in non-survivors of VA-ECMO (p= 0.01), and higher levels were predictive of mortality (AUC = 0.79,p= 0.05). Cardiomyocyte EV were increased in STEMI patients with moderately-severely reduced left ventricular function (p= 0.03), correlated with CK-MBmax(r= 0.57,p= 0.02) and time from reperfusion to blood sampling (r= 0.58,p= 0.01). Leukocyte EV correlated with the number of coronary stents placed (r= 0.60,p= 0.02).

Conclusions:Elevated total Annexin V+EV on day 1 of VA-ECMO are predictive of mortality. Increased cardiomyocyte EV on day 1 after STEMI correlate with infarct size and are associated with poor outcome. These EV may aid in the early identification of patients at risk of poor outcome, helping to guide clinical management.
Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of hiPSC-CMs After Myocardial Infarction
Authors: Wu Xun , Wang Di , Qin Kele , Iroegbu Chukwuemeka Daniel , Xiang Kun , Zhou Yuanjing , Guan Qing , Tang Weijie , Peng Jun , Guo Jianjun , Yang Jinfu , Fan Chengming
Published: November 2021

Objective: We investigated the potency of cardiac repair based on echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) after myocardial infarction (MI).

Methods: Mice with surgically induced MI were randomly divided into three groups (n = 8 in each group) and subjected to echocardiography-guided percutaneous left ventricular infarcted border injection of hiPSC-CMs (single dose; 10 μl 3 × 105 cells) or repeated injections of hiPSC-CMs at post-MI weeks 1 and 2 (multiple doses). The sham group of animals underwent all surgical procedures necessary for MI induction except for ligation. Then 4 weeks after MI, heart function was measured with transthoracic echocardiography. Engraftment was evaluated through the detection of human-specific cardiac troponin T. Infarct size and collagen volume were calculated with Sirius Red/Fast Green staining. Angiogenesis was evaluated with isolectin B4 staining. Cardiac remodeling was evaluated from the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected via TdT-mediated dUTP Nick-End Labeling (TUNEL) staining in cardiomyocytes from the infarcted border zone.

Results: No mice died after echocardiography-guided percutaneous left ventricular intramyocardial injection. hiPSC-CMs were about nine-fold higher in the multiple-dose group at week 4 compared to the single-dose group. Multiple-dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis.

Conclusion: Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive, and effective method of delivering cell therapy. The delivery of hiPSC-CMs indicates a novel therapy for MI.
An Active Balancing Method Based on SOC and Capacitance for Lithium-Ion Batteries in Electric Vehicles
Authors: Liu Renxiong , Zhang Chaolong
Published: November 2021

An active balancing method based on the state of charge (SOC) and capacitance is presented in this article to solve the inconsistency problem of lithium-ion batteries in electric vehicles. The terminal voltage of each battery is collected first. Then, each battery SOC is accurately estimated by an extended Kalman filter (EKF) algorithm. In the experiment, the maximum absolute error of SOC evaluation is only 0.0061, and the mean absolute error is 0.0013 when the initial battery SOC is clear. Meanwhile, the maximum absolute error of SOC evaluation is 0.5 and the average absolute error of SOC is 0.0015 when the initial battery SOC is not clear. Afterward, an active balancing circuit based on the estimated battery SOC and capacitance is designed. The energy of capacitance is charged by the battery whose SOC is higher than the other batteries through the circuit to avoid the battery being overcharged. Then, the SOC of batteries gradually turn consistent. In the simulation experiment, the SOC difference of batteries is 7% before the balancing. Meanwhile, the SOC difference of batteries reduces to 0.02% after the balancing and the consuming time is merely 272s, which manifests that the proposed balancing method has a fast balancing speed and better balancing efficiency.
Optimization of a Low Volume Extraction Method to Determine Polycyclic Aromatic Hydrocarbons in Aerosol Samples
Authors: Scaramboni Caroline , Neris Jordan Brizi , do Nascimento Rita de Kássia Silva , Chiaranda da Rosa Natasha Leandra , Carvalho Jonatas Schadeck , Grosseli Guilherme Martins , Campos Maria Lucia Arruda Moura , Fadini Pedro Sérgio , Urban Roberta Cerasi
Published: November 2021

This work describes the optimization of an extraction method for the determination of polycyclic aromatic hydrocarbons (PAHs) and their nitro- and oxy-PAH derivatives in atmospheric particulate matter (PM) samples, and demonstrates that this method is also effective for the determination of levoglucosan. The optimization of the extraction solvents was performed using a three-component mixture design with the solvents dichloromethane, methanol, and acetonitrile. The number of extractions, volume of solvent, and duration of extraction in an ultrasonic bath were optimized using a full factorial design followed by a central composite design. The analyses were performed by gas chromatography coupled with mass spectrometry. The optimized conditions of the method were three extractions using 4.0 ml of acetonitrile, with ultrasonication for 34 min. The proposed method presented good linearity (r > 0.990) and acceptable precision for low (100 ng ml−1, RSD: 1–16%), medium (300 ng ml−1, RSD: 1–19%), and high (500 ng ml−1, RSD: 2–16%) concentrations of PAHs. The limits of quantification for different PAHs ranged from 10 to 50 ng ml−1, which were suitable for atmospheric PM. Assessment of the method using sample matrix spiking/recovery assays, as well as use of a reference method, showed good recoveries for levoglucosan and for most of the PAHs and their derivatives, except for the most volatile compounds, which were lost during the evaporation of the solvent. The results for PM samples extracted by the optimized method and the reference method were in good agreement. The proposed method required 97% less solvent than the reference method, shortened the analysis time by 85%, and proved to be accurate and precise for the determination of at least 27 PAHs and their derivatives present in PM samples collected with a low-volume sampler.
Threshold Reaction of Soil Arthropods to Simulative Nitrogen Deposition in Urban Green Spaces
Authors: Mo Lingzi , Xu Guoliang , Zhang Jiaen , Wu Zhifeng , Yu Shiqin , Chen Xiaohua , Peng Bin , Squartini Andrea , Zanella Augusto
Published: November 2021

Sustained nitrogen (N) deposition has a wide-ranging impact on terrestrial ecosystems. However, still little attention has been paid to responses of urban soil fauna to the increasing N deposition. To clarify such effects on the soil properties and soil fauna in typical urban lawns (featuring Cynodon dactylon vegetation), a control experiment was conducted for 1 year, in which NH4NO3 was added as the external N source with four treatments of N addition: N0 (i.e., only water), N1 (50 kg N ha–1 yr–1), N2 (100 kg N ha–1 yr–1), N3 (150 kg N ha–1 yr–1). Results showed that N additions influence soil faunal communities in the urban lawns soil. The relative abundance of Oribatida increased with the N treatment level, partially replacing the more sensitive Collembola. Significant differences in the Shannon-Wiener and Margalef indices (p < 0.01) supported this statement. Although higher doses of N addition showed adverse effects on soil fauna communities, low N inputs increased the soil fauna diversity and richness, especially at 5–10 cm depth. A threshold effect appears to exist: low N addition (<25 kg N ha–1) did not negatively affect pedofauna structure and composition, while in the range from these values up to 50 kg N ha–1, the composition of the soil fauna underwent major changes which were confirmed by the decline of biodiversity indices. These changes are accompanied by the decreased pH values with increasing N inputs.
Nematodes Follow a Leader
Authors: Erdogan Hilal , Cruzado-Gutierrez Karin , Stevens Glen , Shapiro-Ilan David , Kaplan Fatma , Alborn Hans , Lewis Edwin
Published: November 2021

Aggregated movement and population structure are known in entomopathogenic nematodes, which are obligate insect parasites. Aggregation behavior in the absence of external stimuli suggests communication among individuals, often in the form of trail-following, which has not been shown by nematodes of any kind. Interactions among individuals are an essential basis of following behaviors and can have significant fitness consequences. We explored intraspecific and interspecific interactions among three Steinernema species (S. glaseri, S. carpocapsae, and S. feltiae) in terms of trail following, and fitness outcomes of following heterospecific individuals. We found that the following behavior is context dependent. Following behavior among conspecifics was significantly increased when the lead nematode had prior contact with host cuticle. However, we did not find a clear association between the following response to heterospecific IJs and their reproductive success in a co-infected host.
TreeNet–The Biological Drought and Growth Indicator Network
Authors: Zweifel Roman , Etzold Sophia , Basler David , Bischoff Reinhard , Braun Sabine , Buchmann Nina , Conedera Marco , Fonti Patrick , Gessler Arthur , Haeni Matthias , Hoch Günter , Kahmen Ansgar , Köchli Roger , Maeder Marcus , Nievergelt Daniel , Peter Martina , Peters Richard L. , Schaub Marcus , Trotsiuk Volodymyr , Walthert Lorenz , Wilhelm Micah , Eugster Werner
Published: November 2021

The TreeNet research and monitoring network has been continuously collecting data from point dendrometers and air and soil microclimate using an automated system since 2011. The goal of TreeNet is to generate high temporal resolution datasets of tree growth and tree water dynamics for research and to provide near real-time indicators of forest growth performance and drought stress to a wide audience. This paper explains the key working steps from the installation of sensors in the field to data acquisition, data transmission, data processing, and online visualization. Moreover, we discuss the underlying premises to convert dynamic stem size changes into relevant biological information. Every 10 min, the stem radii of about 420 trees from 13 species at 61 sites in Switzerland are measured electronically with micrometer precision, in parallel with the environmental conditions above and below ground. The data are automatically transmitted, processed and stored on a central server. Automated data processing (R-based functions) includes screening of outliers, interpolation of data gaps, and extraction of radial stem growth and water deficit for each tree. These long-term data are used for scientific investigations as well as to calculate and display daily indicators of growth trends and drought levels in Switzerland based on historical and current data. The current collection of over 100 million data points forms the basis for identifying dynamics of tree-, site- and species-specific processes along environmental gradients. TreeNet is one of the few forest networks capable of tracking the diurnal and seasonal cycles of tree physiology in near real-time, covering a wide range of temperate forest species and their respective environmental conditions.
Copy Number Variation Identification on 3,800 Alzheimer’s Disease Whole Genome Sequencing Data from the Alzheimer’s Disease Sequencing Project
Authors: Lee Wan-Ping , Tucci Albert A. , Conery Mitchell , Leung Yuk Yee , Kuzma Amanda B. , Valladares Otto , Chou Yi-Fan , Lu Wenbin , Wang Li-San , Schellenberg Gerard D. , Tzeng Jung-Ying
Published: November 2021

Alzheimer’s Disease (AD) is a progressive neurologic disease and the most common form of dementia. While the causes of AD are not completely understood, genetics plays a key role in the etiology of AD, and thus finding genetic factors holds the potential to uncover novel AD mechanisms. For this study, we focus on copy number variation (CNV) detection and burden analysis. Leveraging whole-genome sequence (WGS) data released by Alzheimer’s Disease Sequencing Project (ADSP), we developed a scalable bioinformatics pipeline to identify CNVs. This pipeline was applied to 1,737 AD cases and 2,063 cognitively normal controls. As a result, we observed 237,306 and 42,767 deletions and duplications, respectively, with an average of 2,255 deletions and 1,820 duplications per subject. The burden tests show that Non-Hispanic-White cases on average have 16 more duplications than controls do (p-value 2e-6), and Hispanic cases have larger deletions than controls do (p-value 6.8e-5).
Transcriptomic and Proteomic Profiling of Human Stable and Unstable Carotid Atherosclerotic Plaques
Authors: Bao Mei-hua , Zhang Ruo-qi , Huang Xiao-shan , Zhou Ji , Guo Zhen , Xu Bao-feng , Liu Rui
Published: November 2021

Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity
Authors: Leenders Floris , Groen Nathalie , de Graaf Natascha , Engelse Marten A. , Rabelink Ton J. , de Koning Eelco J. P. , Carlotti Françoise
Published: November 2021

Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human β-cells. We show that primary human β-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of β-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced β-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional β-cell mass in early stages of development of T1D.
Maternal IgA2 Recognizes Similar Fractions of Colostrum and Fecal Neonatal Microbiota
Authors: Sánchez-Salguero Erick , Corona-Cervantes Karina , Guzmán-Aquino Hector Armando , de la Borbolla-Cruz María Fernanda , Contreras-Vargas Víctor , Piña-Escobedo Alberto , García-Mena Jaime , Santos-Argumedo Leopoldo
Published: November 2021

Microbiota acquired during labor and through the first days of life contributes to the newborn’s immune maturation and development. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is coating a fraction of maternal microbiota. Thus, to better characterize this IgA-microbiota association, we used flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in human colostrum and neonatal feces. We identified IgA bound bacteria (IgA+) and characterized their diversity and composition shared in colostrum fractions and neonatal fecal bacteria. We found that IgA2 is mainly associated withBifidobacterium,Pseudomonas, Lactobacillus, andParacoccus, among other genera shared in colostrum and neonatal fecal samples. We found that metabolic pathways related to epithelial adhesion and carbohydrate consumption are enriched within the IgA2+ fecal microbiota. The association of IgA2 with specific bacteria could be explained because these antibodies recognize common antigens expressed on the surface of these bacterial genera. Our data suggest a preferential targeting of commensal bacteria by IgA2, revealing a possible function of maternal IgA2 in the shaping of the fecal microbial composition in the neonate during the first days of life.
Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort
Authors: Chong Amanda H. W. , Mitchell Ruth E. , Hemani Gibran , Davey Smith George , Yolken Robert H. , Richmond Rebecca C. , Paternoster Lavinia
Published: November 2021

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler’s virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 – 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.
Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies
Authors: Li Hua , Li Xiaofan , Chen Yiling , Li Duihong , Chen Xianling , Zhu Zhijuan , Wang Yiting , Huang Jiafu , Chen Ping , Chen Yuanzhong , Li Nainong
Published: November 2021

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p>0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175–0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p<0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.
Identification of Methylation Immune Subtypes and Establishment of a Prognostic Signature for Gliomas Using Immune-Related Genes
Authors: Hu Zhengang , Zhang Hao , Fan Fan , Wang Zeyu , Xu Jiahao , Huang Yunying , Dai Ziyu , Cao Hui , Zhang Xun , Liu Zhixiong , Cheng Quan
Published: November 2021

DNA methylation patterns are essential in understanding carcinogenesis. However, the relationship between DNA methylation and the immune process has not been clearly established—this study aimed at elucidating the interaction between glioma and DNA methylation, consolidating glioma classification and prognosis. A total of 2,483 immune-related genes and 24,556 corresponding immune-related methylation probes were identified. From the Cancer Genome Atlas (TCGA) glioma cohort, a total of 683 methylation samples were stratified into two different clusters using unsupervised clustering, and eight types of other cancer samples from the TCGA database were shown to exhibit excellent distributions. A total of 3,562 differentially methylated probes (DMPs) were selected and used for machine learning. A five-probe signature was established to evaluate the prognosis of glioma as well as the potential benefits of radiotherapy and Procarbazine, CCNU, Vincristine (PCV) treatment. Other prognostic clinical models, such as nomogram and decision tree, were also evaluated. Our findings confirmed the interactions between immune-related methylation patterns and glioma. This novel approach for cancer molecular characterization and prognosis should be validated in further studies.
Receptor-Mediated NETosis on Neutrophils
Authors: Chen Tao , Li Yanhong , Sun Rui , Hu Huifang , Liu Yi , Herrmann Martin , Zhao Yi , Muñoz Luis E.
Published: November 2021

Neutrophil extracellular traps (NETs), a web-like structures containing chromatin, have a significant role in assisting the capture and killing of microorganisms by neutrophils during infection. The specific engagement of cell-surface receptors by extracellular signaling molecules activates diverse intracellular signaling cascades and regulates neutrophil effector functions, including phagocytosis, reactive oxygen species release, degranulation, and NET formation. However, overproduction of NETs is closely related to the occurrence of inflammation, autoimmune disorders, non-canonical thrombosis and tumor metastasis. Therefore, it is necessary to understand neutrophil activation signals and the subsequent formation of NETs, as well as the related immune regulation. In this review, we provide an overview of the immunoreceptor-mediated regulation of NETosis. The pathways involved in the release of NETs during infection or stimulation by noninfectious substances are discussed in detail. The mechanisms by which neutrophils undergo NETosis help to refine our views on the roles of NETs in immune protection and autoimmune diseases, providing a theoretical basis for research on the immune regulation of NETs.