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Recent experiments reported that quantum Hall chiral edge state-mediated Josephson junctions (chiral Josephson junctions) could exhibit Fraunhofer oscillations with a periodicity of either h/e [Vignaud et al., Nature (London) 624, 545 (2023)NATUAS0028-083610.1038/s41586-023-06764-4] or h/2e [Amet et al., Science 352, 966 (2016)SCIEAS0036-807510.1126/science.aad6203]. While the h/e-periodic component of the supercurrent had been anticipated theoretically before, the emergence of the h/2e periodicity is still not fully understood. In this Letter, we systematically study the Fraunhofer oscillations of chiral Josephson junctions. In chiral Josephson junctions, the chiral edge states coupled to the superconductors become chiral Andreev edge states. We find that in short junctions, the coupling of the chiral Andreev edge states can trigger the h/2e-magnetic flux periodicity. Our theory resolves the important puzzle concerning the appearance of the h/2e periodicity in chiral Josephson junctions. Furthermore, we explain that when the chiral Andreev edge states couple, a pair of localized Majorana zero modes appear at the ends of the Josephson junction, which are robust and independent of the phase difference between the two superconductors. As the h/2e periodicity and the Majorana zero modes have the same physical origin in the wide junction limit, the Fraunhofer oscillation period could be useful in identifying the regime with Majorana zero modes.
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This paper addresses the issue of how to endow robots with motion skills, flexibility, and adaptability similar to human arms. It innovatively proposes a hybrid-primitive-frame-based robot skill learning algorithm and utilizes the policy improvement with a path integral algorithm to optimize the parameters of the hybrid primitive framework, enabling robots to possess skills similar to human arms. Firstly, the end of the robot is dynamically modeled using an admittance control model to give the robot flexibility. Secondly, the dynamic movement primitives are employed to model the robot's motion trajectory. Additionally, novel stiffness primitives and damping primitives are introduced to model the stiffness and damping parameters in the impedance model. The combination of the dynamic movement primitives, stiffness primitives, and damping primitives is called the hybrid primitive framework. Simulated experiments are designed to validate the effectiveness of the hybrid-primitive-frame-based robot skill learning algorithm, including point-to-point motion under external force disturbance and trajectory tracking under variable stiffness conditions.
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PURPOSE: To develop a novel classification of sagittal en bloc resection (SEBR) based on anatomical locations for thoracolumbar spine tumors and assess the clinical outcomes of this surgical procedure. METHODS: 31 patients with thoracolumbar tumours treated with SEBR were enrolled in this study. The individualized surgical strategy was adopted based on our surgical classification. Demographics, perioperative outcomes, complications and postoperative outcomes were assessed. RESULTS: Based on our surgical classifications, patients were divided into four types. All bony resection margins were negative, wide resection was achieved in 25 patients, marginal resection in four, and intralesional resection in two. 18 patients underwent anterior reconstruction. Complications were encountered in five patients, and instrumentation failure occurred in one patient. The median follow-up was 24 (range, 6-72) months and recurrence was found in only one patient. CONCLUSION: SEBR is a safe and effective surgical procedure for patients with thoracolumbar spinal tumours in specific anatomical locations. The proposed surgical classification covers all SEBR types and is easy to apply, it may assist surgical decision-making in patients with spinal tumours.
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Vértebras Lombares , Neoplasias da Coluna Vertebral , Vértebras Torácicas , Humanos , Vértebras Torácicas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Adulto , Vértebras Lombares/cirurgia , Adulto Jovem , Adolescente , Resultado do Tratamento , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Recently, the Josephson diode effect (JDE), in which the superconducting critical current magnitudes differ when the currents flow in opposite directions, has attracted great interest. In particular, it was demonstrated that gate-defined Josephson junctions based on magic-angle twisted bilayer graphene showed a strong nonreciprocal effect when the weak-link region is gated to a correlated insulating state at half filling (two holes per moiré cell). However, the mechanism behind such a phenomenon is not yet understood. In this Letter, we show that the interaction-driven valley polarization, together with the trigonal warping of the Fermi surface, induce the JDE. The valley polarization, which lifts the degeneracy of the states in the two valleys, induces a relative phase difference between the first and the second harmonics of the supercurrent and results in the JDE. We further show that the nontrivial current phase relation, which is responsible for the JDE, also generates the asymmetric Shapiro steps.
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Grafite , Meio AmbienteRESUMO
BACKGROUND: The outcomes of patients with tumors of the thoracolumbar spine treated with en bloc resection (EBR) using three-dimensional (3D)-printed endoprostheses are underreported. METHODS: We retrospectively evaluated patients with thoracolumbar tumors who underwent surgery at our institution. Logistic regression analysis was performed to identify the potential risk factors for surgical complications. Nomograms to predict complications were constructed and validated. RESULTS: A total of 53 patients with spinal tumors underwent EBR at our hospital; of these, 2 were lost to follow-up, 45 underwent total en bloc spondylectomy, and 6 were treated with sagittal en bloc spondylectomy. The anterior reconstruction materials included a customized 3D-printed artificial vertebral body (AVB) in 10 cases and an off-the-shelf 3D-printed AVB in 41 cases, and prosthesis mismatch occurred in 2 patients reconstructed with the off-the-shelf 3D-printed AVB. The median follow-up period was 21 months (range, 7-57 months). Three patients experienced local recurrence, and 5 patients died at the final follow-up. A total of 50 perioperative complications were encountered in 29 patients, including 25 major and 25 minor complications. Instrumentation failure occurred in 1 patient, and no prosthesis subsidence was observed. Using a combined surgical approach was a dependent predictor of overall complications, while Karnofsky performance status score, lumbar spine lesion, and intraoperative blood loss ≥ 2000 mL were predictors of major complications. Nomograms for the overall and major complications were constructed using these factors, with C-indices of 0.850 and 0.891, respectively. CONCLUSIONS: EBR is essential for the management of thoracolumbar tumors; however, EBR has a steep learning curve and a high complication rate. A 3D-printed AVB is an effective and feasible reconstruction option for patients treated with EBR.
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Neoplasias da Coluna Vertebral , Corpo Vertebral , Humanos , Corpo Vertebral/patologia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Resultado do Tratamento , Impressão TridimensionalRESUMO
Integration of light signaling and diverse abiotic stress responses contribute to plant survival in a changing environment. Some reports have indicated that light signals contribute a plant's ability to deal with heat, cold, and stress. However, the molecular link between light signaling and the salt-response pathways remains unclear. We demonstrate here that increasing light intensity elevates the salt stress tolerance of plants. Depletion of HY5, a key component of light signaling, causes Arabidopsis thaliana to become salinity sensitive. Interestingly, the small heat shock protein (sHsp) family genes are upregulated in hy5-215 mutant plants, and HsfA2 is commonly involved in the regulation of these sHsps. We found that HY5 directly binds to the G-box motifs in the HsfA2 promoter, with the cooperation of HISTONE DEACETYLASE 9 (HDA9), to repress its expression. Furthermore, the accumulation of HDA9 and the interaction between HY5 and HDA9 are significantly enhanced by salt stress. On the contrary, high temperature triggers HY5 and HDA9 degradation, which leads to dissociation of HY5-HDA9 from the HsfA2 promoter, thereby reducing salt tolerance. Under salt and heat stress conditions, fine tuning of protein accumulation and an interaction between HY5 and HDA9 regulate HsfA2 expression. This implies that HY5, HDA9, and HsfA2 play important roles in the integration of light signaling with salt stress and heat shock response.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Histona Desacetilases/metabolismo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição de Zíper de Leucina Básica/metabolismoRESUMO
Moiré heterobilayer transition metal dichalcogenides (TMDs) emerge as an ideal system for simulating the single-band Hubbard model and interesting correlated phases have been observed in these systems. Nevertheless, the moiré bands in heterobilayer TMDs were believed to be topologically trivial. Recently, it was reported that both a quantum valley Hall insulating state at filling ν=2 (two holes per moiré unit cell) and a valley-polarized quantum anomalous Hall state at filling ν=1 were observed in AB stacked moiré MoTe_{2}/WSe_{2} heterobilayers. However, how the topologically nontrivial states emerge is not known. In this Letter, we propose that the pseudomagnetic fields induced by lattice relaxation in moiré MoTe_{2}/WSe_{2} heterobilayers could naturally give rise to moiré bands with finite Chern numbers. We show that a time-reversal invariant quantum valley Hall insulator is formed at full filling ν=2, when two moiré bands with opposite Chern numbers are filled. At half filling ν=1, the Coulomb interaction lifts the valley degeneracy and results in a valley-polarized quantum anomalous Hall state, as observed in the experiment. Our theory identifies a new way to achieve topologically nontrivial states in heterobilayer TMD materials.
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BACKGROUND: A history of prior cancer commonly results in exclusion from cancer clinical trials. However, whether a prior cancer history has an adversely impact on clinical outcomes for patients with advanced prostate cancer (APC) remains largely unknown. We therefore aimed to investigate the impact of prior cancer history on these patients. METHODS: We identified patients with advanced prostate cancer diagnosed from 2004 to 2010 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance baseline characteristics. Kaplan-Meier method and the Cox proportional hazard model were utilized for survival analysis. RESULTS: A total of 19,772 eligible APC patients were included, of whom 887 (4.5 %) had a history of prior cancer. Urinary bladder (19 %), colon and cecum (16 %), melanoma of the skin (9 %) malignancies, and non-hodgkin lymphoma (9 %) were the most common types of prior cancer. Patients with a history of prior cancer had slightly inferior overall survival (OS) (AHR = 1.13; 95 % CI [1.02-1.26]; P = 0.017) as compared with that of patients without a prior cancer diagnosis. Subgroup analysis further indicated that a history of prior cancer didn't adversely impact patients' clinical outcomes, except in patients with a prior cancer diagnosed within 2 years, at advanced stage, or originating from specific sites, including bladder, colon and cecum, or lung and bronchus, or prior chronic lymphocytic leukemia. CONCLUSIONS: A large proportion of APC patients with a prior cancer history had non-inferior survival to that of patients without a prior cancer diagnosis. These patients may be candidates for relevant cancer trials.
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Segunda Neoplasia Primária/mortalidade , Neoplasias da Próstata/mortalidade , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Dynamic interaction seriously limits the overall performance of a Dual-Stage Actuator (DSA) system. This paper aims to identify and compensate for the dynamic interaction in a non-contact DSA system. The effects of the interaction in the non-contact DSA system are initially classified as non-contact position-dependent disturbance forces (PDDFs) and velocity-dependent disturbance forces (VDDFs). The PDDFs in the three degrees of freedom (DoFs) motion space between the two stages of the DSA system are directly identified in the time domain, and VDDFs are indirectly identified in the form of damping values in frequency domains. The feedforward networks of the force are subsequently applied to compensate the PDDFs and VDDFs, which are indexed with relative displacement and velocity, respectively. Experiments are finally conducted to investigate the effectiveness of compensation, which infers that the final positioning error in the time domain can be reduced from 260 nm to 130 nm with PDDFs and VDDFs compensation. The gain of the interaction transfer is decreased in the frequency range of up to 45 Hz with PDDFs and VDDFs compensation. With this method, some weak dynamic interaction can be completely compensated for by the force feedforward compensation, and the positioning accuracy of non-contact DSA systems can be greatly improved.
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Endothelial dysfunction (ED) is an initiating trigger and key factor in vascular complications, leading to disability and mortality in individuals with diabetes. The research concerning therapeutic interventions for ED has gained considerable interest. Fenugreek, a commonly used edible plant in dietary consumption, has attracted significant attention due to its management of diabetes and its associated complications. The research presented in this study examines the potential therapeutic benefits of fenugreek in treating ED and investigates the underlying mechanism associated with its effects. The analysis on fenugreek was performed using 70% ethanol extract, and its chemical composition was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). In total, we identified 49 compounds present in the fenugreek extract. These compounds encompass flavonoids, saponins, and phospholipids. Then, the models of ED in streptozotocin-induced diabetic mice and high glucose-induced isolated rat aortas were established for research. Through vascular function testing, it was observed that fenugreek extract effectively improved ED induced by diabetes or high glucose. By analyzing the protein expression of arginase 1 (Arg1), Arg activity, Arg1 immunohistochemistry, nitric oxide (NO) level, and the protein expression of endothelial nitric oxide synthase (eNOS), p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK in aortas, this study revealed that the potential mechanism of fenugreek extract in anti-ED involves the downregulation of Arg1, leading to enhanced NO production. Furthermore, analysis of serum exosomes carrying Arg activity indicates that fenugreek may decrease the activity of Arg transported by serum exosomes, potentially preventing the increase in Arg levels triggered by the uptake of serum exosomes by vascular endothelial cells. In general, this investigation offers valuable observations regarding the curative impact of fenugreek extract on anti-ED in diabetes, revealing the involvement of the Arg1 pathway in its mechanism.
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Diabetes Mellitus Experimental , Células Endoteliais , Extratos Vegetais , Trigonella , Ratos , Camundongos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Arginase , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Glucose/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
Aims: The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. Methods: We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital. Results: In all, 17 patients with locally aggressive bone tumours (Enneking stage IIB) located in the femoral shaft underwent JSLSS and reconstruction with 3D-printed modular prostheses between January 2020 and June 2022. The median surgical time was 153 minutes (interquartile range (IQR) 117 to 248), and the median estimated blood loss was 200ml (IQR 125 to 400). Osteosarcoma was the most common pathological type (n = 12; 70.6%). The mean osteotomy length was 197.53 mm (SD 12.34), and the median follow-up was 25 months (IQR 19 to 38). Two patients experienced local recurrence and three developed distant metastases. Postoperative complications included wound infection in one patient and screw loosening in another, both of which were treated successfully with revision surgery. The median Musculoskeletal Tumor Society score at the final follow-up was 28 (IQR 27 to 28). Conclusion: The 3D-printed modular prosthesis is a reliable and feasible reconstruction option for patients with malignant femoral diaphyseal tumours. It helps to improve the limb salvage rate, restore limb function, and achieve better short-term effectiveness.
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Background: All available methods for reconstruction after proximal humerus tumor resection have disadvantages, and the optimal reconstruction method remains uncertain. This study aimed to design a novel 3D-printed glenohumeral fusion prosthesis and verify its feasibility and safety using biomechanical methods. Methods: We verified the feasibility and safety of the 3D-printed glenohumeral fusion prosthesis by finite element analysis and biomechanical experimentation. In the finite element analysis, three reconstruction methods were used, and displacement and von Mises stress were observed; on this basis, in the biomechanical experiment, models constructed with sawbones were classified into two groups. The forceâdisplacement curve of the 3D-printed prosthesis was evaluated. Results: In terms of displacement, the finite element analysis showed greater overall stability for the novel prosthesis than traditional glenohumeral joint arthrodesis. There was no obvious stress concentration in the internal part of the 3D-printed glenohumeral fusion prosthesis; the stable structure bore most of the stress, and the force was well distributed. Adding lateral plate fixation improved the stability and mechanical properties of the prosthesis. Furthermore, the biomechanical results showed that without lateral plate fixation, the total displacement of the prosthesis doubled; adding lateral plate fixation could reduce and disperse strain on the glenoid. Conclusion: The design of the 3D-printed glenohumeral fusion prosthesis was rational, and its stability and mechanical properties were better than those of traditional glenohumeral joint arthrodesis. Biomechanical verification demonstrated the feasibility and safety of this prosthesis, indicating its potential for proximal humerus bone defect reconstruction after tumor resection.
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Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM. IMPLICATIONS: SB9 as a therapeutic target for LCBM.
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Neoplasias Ósseas , Neoplasias Pulmonares , Serpinas , Humanos , Camundongos , Animais , Neoplasias Pulmonares/patologia , Serpinas/genética , Serpinas/metabolismo , Proteômica , Linhagem Celular , Neoplasias Ósseas/genéticaRESUMO
Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.
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Quimiocinas CXC , Integrinas , Neoplasias Pulmonares , Osteossarcoma , Microambiente Tumoral , Humanos , Linhagem Celular Tumoral , Quimiocinas CXC/metabolismo , Fibroblastos/metabolismo , Integrinas/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Receptores de Colágeno , Fator de Crescimento Transformador beta/metabolismoRESUMO
Treatments for osteosarcoma (OS) with pulmonary metastases reach a bottleneck with a survival rate of 10-20%. The suppressive tumor associated macrophages(TAMs) and CD47 over-expression greatly lead to the treatment failure. Sonodynamic therapy (SDT) can generate ROS with deep tumor penetration to induce tumor cell apoptosis, which is reported to further induce M1 macrophage polarization. CD47 inhibition combined with SDT to synergistically modulate TAMs may induce superior effects for OS treatment. In this work, for the first time, a biomimetic nanodrug named MPIRx was deveploped by loading IR780 (a sonosensitizer) and RRx-001 (a CD47 inhibitor) in PEG-PCL nanomicelles and then coating with OS cell membranes. After ultrasound activation, the nanodrug significantly inhibited OS proliferation and migration, induced apoptosis and immunogenic cell death in OS cells. Furthermore, MPIRx could guide macrophage migrating towards tumor cells and promote M1-type polarization while increasing the phagocytosis activity of macrophages on OS cells. Ultimately, MPIRx showed good tumor accumulation in vivo and successfully inhibited subcutaneous OS and orthotopic tumor with deterioration of pulmonary metastasis. Overall, by creating a local oxidative microenvironment and modulating the TAMs/CD47 in tumor tissue, the MPIRx nanodrug presents a novel strategy for macrophage-related immunotherapy to successfully eliminate OS and inhibit the intractable pulmonary metastasis.
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Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Humanos , Antígeno CD47 , Fagocitose , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The recently discovered nonlinear Hall effect (NHE) in a few non-interacting systems provides a novel mechanism for generating second-harmonic electrical Hall signals under time-reversal-symmetric conditions. Here, we introduce a new approach to engineering an NHE by using twisted moiré structures. We found that the twisted WSe2 bilayer exhibited an NHE when the Fermi level was tuned to the moiré flat bands. When the first moiré band was half-filled, the nonlinear Hall signal exhibited a sharp peak with a generation efficiency that was at least two orders of magnitude greater than those obtained in previous experiments. We discuss the possible origins of the diverging generation efficiency in twisted WSe2 based on resistivity measurements, such as moiré-interface-induced correlation effects and mass-diverging-type continuous Mott transition. This study demonstrates not only how interaction effects can combine with Berry curvature dipoles to produce novel quantum phenomena, but also the potential of NHE measurements as a new tool for studying quantum criticality.
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Inflammation of chondrocytes plays a critical role in the occurrence and development of osteoarthritis (OA). Recent evidence indicated exosomes derived from mesenchymal stem cells (MSCs-Exos) exhibit excellent anti-inflammatory ability in many troublesome inflammatory diseases including OA. In the present study, we aimed to explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms. Ultracentrifugation was applied to isolate hUC-MSCs-Exos from the culture supernatant of hUC-MSCs. Two OA-like in vitro inflammation models of human articular chondrocytes induced with interleukin 1ß (IL-1ß) and co-incubation with macrophage utilizing transwell cell culture inserts were both used to evaluate the anti-inflammatory effects of hUC-MSCs-Exos. The mRNA sequencing of chondrocytes after treatment and microRNA (miRNA) sequencing of hUC-MSCs-Exos were detected and analyzed for possible mechanism analysis. The results of the study confirmed that hUC-MSCs-Exos had a reversed effect of IL-1ß on chondrocytes in the expression of collagen type II alpha 1 (COL2A1) and matrix metalloproteinase 13 (MMP13). The addition of hUC-MSCs-Exos to M1 macrophages in the upper chamber showed down-regulation of IL-1ß and tumor necrosis factor α (TNF-α), up-regulation of IL-10 and arginase1 (ARG1), and reversed the gene and protein expression of COL2A1 and MMP13 of the chondrocytes seeded in the lower chamber. The results of this study confirmed the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. hUC-MSCs-Exos may be used as a potential cell-free treatment strategy for chondrocyte inflammation in OA.
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Wheat protein disulfide isomerase (PDI) is involved in the formation of glutenin macropolymers (GMP) and the correct folding and accumulation of storage proteins in endosperm. In present study, seven types of homozygous TaPDI gene edited mutants were obtained by CRISPR/Cas9 technology, which were confirmed by PCR-RE and sequencing. Compared with other mutants and wild type (WT), the grain length and width in mutant PDI-abd-6 which was edited for the three TaPDI homoeologous genes were reduced, and the grain middle parts were slumped. The GMP size in PDI-abd-6 was not significantly different from that in WT, whereas the accumulation of protein bodies (PBs) increased during grain development. The endosperm cells became denser in PDI-abd-6 without sheet-like structure, and the expression level of TaBiP gene was significantly decreased. Particularly, the GMP content in PDI-abd-6 is also decreased significantly. The basic bread and flour rheological parameters in the mutant were negatively changed compared with those in WT. Our results indicated that TaPDI genes affects wheat flour-processing quality by the order of TaPDI-4B, TaPDI-4D, and TaPDI-4A from high to low; the expression of either one TaPDI could be enough to maintain the GMP accumulation and processing properties of wheat dough.
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Sistemas CRISPR-Cas , Edição de Genes , Mutação , Proteínas de Plantas/genética , Isomerases de Dissulfetos de Proteínas/genética , Triticum/genética , Grão Comestível , Regulação da Expressão Gênica de Plantas , Mutação INDEL , Fenótipo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Isomerases de Dissulfetos de Proteínas/metabolismo , Transformação Genética , Triticum/química , Triticum/metabolismoRESUMO
Samples of 23 seafood products were obtained internationally in processing plants and subjected to controlled decomposition to produce seven discrete quality increments. A sensory expert evaluated each sample for decomposition, using a scale of 1-100. Samples were then extracted and analyzed by liquid chromatography with high-resolution mass spectrometry (LC-HRMS). Untargeted data processing was performed, and a sensory-driven Random Forest model in the R programming language for each product was created. Five samples of each quality increment were analyzed in duplicate on separate days. Scores analogous to those obtained through sensory analysis were calculated by this approach, and these were compared to the original sensory findings. Correlation values (r) were calculated from these plots and ranged from 0.971 to 0.999. The finding of decomposition state of each sample was consistent with sensory for 548 of 550 test samples (99.6%). Of the two misidentified samples, one was a false negative, and one false positive (0.2% each). One additional sample from each of the 1st, 4th, and 7th increments of each product was extracted and analyzed on a third separate day to evaluate reproducibility. The range of these triplicate calculated scores was 15 or less for all samples tested, 10 or less for 63 of the 69 triplicate tests (91%), and five or less for 41 (59%). From the models, the most predictive compounds of interest were selected, and many of these were identified using MS2 data with standard or database comparison, allowing identification of compounds indicative of decomposition in these products which have not previously been explored for this purpose.
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The sequencing, assembly, and analysis of bacterial genomes is central to tracking and characterizing foodborne pathogens. The bulk of bacterial genome sequencing at the US Food and Drug Administration is performed using short-read Illumina MiSeq technology, resulting in highly accurate but fragmented genomic sequences. The MinION sequencer from Oxford Nanopore is an evolving technology that produces long-read sequencing data with low equipment cost. The goal of this study was to compare Campylobacter genome assemblies generated from MiSeq and MinION data independently, as well as hybrid genome assemblies combining both data types. Two reference strains and two field isolates of C. jejuni were sequenced using MiSeq and MinION, and the sequence data were assembled using the software programs SPAdes and Canu, respectively. Hybrid genome assembly was performed using the program Unicycler. Comparison of the C. jejuni 81-176 and RM1221 genome assemblies to the PacBio reference genomes revealed that the SPAdes assemblies had the most accurate nucleotide identity, while the hybrid assemblies were the most contiguous. Assemblies generated only from MinION data using Canu were the least accurate, containing many indels and substitutions that affected downstream analyses. The hybrid sequencing approach was the most useful for detecting plasmids, large genome rearrangements, and repetitive elements such as rRNA and tRNA genes. The full genomes of both C. jejuni field isolates were completed and circularized using hybrid sequencing, and a plasmid was detected in one isolate. Continued development of nanopore sequencing technologies will likely enhance the accuracy of hybrid genome assemblies and enable public health laboratories to routinely generate complete circularized bacterial genome sequences.