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In the past few decades, tremendous efforts have been made toward understanding the exotic physics emerging from competition between various ordering tendencies in strongly correlated systems. Employing state-of-the-art quantum Monte Carlo simulation, we investigate an interacting SU(N) fermionic model with varying interaction strength and value of N, and we unveil the ground-state phase diagram of the model exhibiting a plethora of exotic phases. For small values of N-namely, N=2, 3-the ground state is an antiferromagnetic (AFM) phase, whereas in the large-N limit, a staggered valence bond solid (VBS) order is dominant. For intermediate values of N such as N=4, 5, remarkably, our study reveals that distinct VBS orders appear in the weak and strong coupling regimes. More fantastically, the competition between staggered and columnar VBS ordering tendencies gives rise to a Mott insulating phase without spontaneous symmetry breaking (SSB), existing in a large interacting parameter regime, which is consistent with a gapped quantum spin liquid. Our study not only provides a platform to investigate the fundamental physics of quantum many-body systems-it also offers a novel route toward searching for exotic states of matter such as quantum spin liquid in realistic quantum materials.
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Arsenic (As) has been widely detected in surface media on the Qinghai-Tibetan Plateau (QTP); however, the differences in the As distribution and partitioning characteristics between freshwater and saltwater lakes remain poorly understood. To determine the distribution and partitioning characteristics of As, multimedia environmental samples were collected from a typical small watershed consisting of a river, wetland, and both freshwater and saltwater lakes on the QTP. Results showed that freshwater systems, represented by Hurleg Lake, were high in particulate arsenic (PAs) and low in dissolved arsenic (DAs), whereas the saltwater system represented by Tosen Lake, exhibited the reverse distribution. This discrepancy in As distribution was primarily attributed to evaporation enrichment, competitive adsorption of HCO3- and pH variations, as suggested by correlation analysis and stable isotopic composition of water. In the stratified Tosen Lake, an increasing trend of DAs in the water column was observed, potentially driven by the reductive dissolution of Fe (hydr)oxides and bacterial sulfate reduction in the anoxic bottom hypolimnion. Conversely, Hurleg Lake maintained oxic conditions with stable DAs concentrations. Notably, PAs was elevated in the bottom layer of both lakes, possibly due to uptake/adsorption by biogenic particles, as indicated by high levels of chl.α and suspended particulate matter. These findings offer insights into the potential future impact of climate change on As mobilization/redistribution in arid plateau lakes, with implications for management policies that regulate As pollution.
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Arsénico , Lagos , Lagos/química , Arsénico/análisis , Tibet , Monitoreo del Ambiente/métodos , Agua , ChinaRESUMEN
Endocervical adenocarcinoma (ECA), harboring poor prognosis, is divided into human papilloma virus (HPV)-associated adenocarcinoma (HPVA) and non-HPVA (NHPVA), each consisting of a heterogeneous immune microenvironment. We aim to examine the effect of CKLF-like MARVEL transmembrane domain 6 (CMTM6), a key regulator of PD-L1, on ECA. Immunohistochemistry and RNA-sequencing (RNA-seq) were used to detect CMTM6, Programmed death ligand 1 (PD-L1), and immune cells biomarkers levels in tumors. RT-qPCR and Western Blotting were used to detect the mRNA and protein level changed in cells. The expression of CMTM6 in ECA is upregulated compared to cervical squamous cell carcinoma tissues. More infiltrating T cells were observed in CMTM6high ECA tissues, especially in CMTM6high HPVA. Higher expression of CMTM6 is associated with a higher rate of infiltrating CD8+ T cells in HPVA, but not in NHPVA. ECA patients were divided into three groups according to the co-expression status of CMTM6 and PD-L1(CPS) . Patients with CMTM6high /PD-L1(CPS+) had the longest OS and DFS, especially in NHPVA patients. Moreover, knock down of CMTM6 promotes ECA cell proliferation via the p53 pathway. CMTM6 recruits T cells, suppresses ECA cell proliferation via the p53 pathway and can be used as a novel prognostic indicator for ECA patients.
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Adenocarcinoma , Neoplasias del Cuello Uterino , Femenino , Humanos , Antígeno B7-H1/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/análisis , Linfocitos T CD8-positivos , Proliferación Celular , Microambiente TumoralRESUMEN
BACKGROUND: Myofascial pain syndrome (MPS) is a common musculoskeletal pain and dysfunction, which is characterised by myofascial trigger points. Therapeutic physical modalities, as potentially effective treatment options, are commonly used in the clinical setting for the patients with MPS. OBJECTIVE: This systematic review aimed to evaluate the safety and effectiveness of therapeutic physical modalities in the treatment of MPS, investigate its therapeutic mechanisms and provide a scientific evidence-based decision. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Cochrane Central Library, Embase, and CINAHL databases were searched for randomized controlled clinical studies published from database inception to October 30, 2022. A total of 25 articles met the study inclusion criteria. Data were extracted from these studies and a qualitative analysis was performed. RESULTS: Transcutaneous electrical nerve stimulation therapy, extracorporeal shock wave therapy, laser therapy, and other therapeutic physical modalities have been demonstrated to improve the pain symptoms, joint mobility, psychological state, and quality of life in the patients with MPS and no side effects have been reported. The curative effect of therapeutic physical modalities was found to be possibly associated with increased blood perfusion and oxygen supply in ischaemic tissues, reduced hyperalgesia in the peripheral and central nerves, and decreased involuntary muscle contractions. CONCLUSION: The systematic review has shown that therapeutic physical modalities could provide a safe and effective therapeutic option for MPS. However, the consensus is currently lacking regarding the optimal treatment paradigm, therapeutic parameters, and mutual combination of therapeutic physical modalities. The clinical trials with robust quality are required to further promote the evidence-based application of therapeutic physical modalities for MPS.
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Fibromialgia , Dolor Musculoesquelético , Síndromes del Dolor Miofascial , Humanos , Calidad de Vida , Síndromes del Dolor Miofascial/diagnóstico , Síndromes del Dolor Miofascial/terapia , Modalidades de Fisioterapia , Puntos DisparadoresRESUMEN
BACKGROUND: Precise diagnosis and early appropriate treatment are of importance to reduce neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) morbidity. Distinguishing NMOSD from MS based on clinical manifestations and neuroimaging remains challenging. PURPOSE: To investigate radiomic signatures as potential imaging biomarkers for distinguishing NMOSD from MS, and to develop and validate a diagnostic radiomic-signature-based nomogram for individualized disease discrimination. STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Seventy-seven NMOSD patients and 73 MS patients. FIELD STRENGTH/SEQUENCE: 3T/T2 -weighted imaging. ASSESSMENT: Eighty-eight patients and 62 patients were respectively enrolled in the primary and validation cohorts. Quantitative radiomic features were automatically extracted from lesioned regions on T2 -weighted imaging. A least absolute shrinkage and selection operator analysis was used to reduce the dimensionality of features. Finally, we constructed a radiomic nomogram for disease discrimination. STATISTICAL TESTS: Features were compared using the Mann-Whitney U-test with a nonnormal distribution. We depicted the nomogram on the basis of the results of the logistic regression using the rms package in R. The Hmisc package was used to investigate the performance of the nomogram via Harrell's C-index. RESULTS: A total of 273 quantitative radiomic features were extracted from lesions. A multivariable analysis selected 11 radiomic features and five clinical features to be included in the model. The radiomic signature (P < 0.001 for both the primary and validation cohorts) showed good potential for building a classification model for disease discrimination. The area under the receiver operating characteristic curve was 0.9880 for the training cohort and 0.9363 for the validation cohort. The nomogram exhibited good discrimination, a concordance index of 0.9363, and good calibration in the primary cohort. The nomogram showed similar discrimination, concordance (0.9940), and calibration in the validation cohort. DATA CONCLUSION: The diagnostic radiomic-signature-based nomogram has potential utility for individualized disease discrimination of NMOSD from MS in clinical practice. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1113-1121.
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Biomarcadores , Esclerosis Múltiple/diagnóstico por imagen , Neuroimagen , Neuromielitis Óptica/diagnóstico por imagen , Adulto , Área Bajo la Curva , Calibración , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nomogramas , Fenotipo , Inducción de Remisión , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Qinanmer (1), a new compound comprising 2-(2-phenylethyl)chromone and sesquiterpene moieties, together with two known 2-(2-phenylethyl)chromone derivatives (2-3), was isolated from the high-quality Chinese agarwood "Qi-Nan" originating from Aquilaria sinensis (Lour.) Glig. The structure of 1 was elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR), MS analyses, ECD spectra analyses, and quantum 13C NMR calculations.
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Sesquiterpenos/aislamiento & purificación , Inhibidores de la Colinesterasa/química , Cromonas/química , Medicamentos Herbarios Chinos/química , Flavonoides , Estructura Molecular , Sesquiterpenos/química , Thymelaeaceae/química , Madera/químicaRESUMEN
A new 2-(2-phenylethyl)chromone glycoside, 2-[2-(4-glucosyloxy-3-methoxyphenyl)ethyl]chromone (1), was isolated from the high-quality Chinese agarwood "Qi-Nan" originating from Aquilaria sinensis (Lour.) Glig. The structure including the absolute configuration of the sugar moiety was elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR), MS analysis, PMP-labeling HPLC analysis methods, as well as comparison with literature data. To the best of our knowledge, it is the first time that chromone glycoside was discovered in agarwood, or even in the whole Aquilaria plants.
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Cromonas/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Thymelaeaceae/química , Inhibidores de la Colinesterasa/química , Cromatografía Líquida de Alta Presión , Cromonas/química , Medicamentos Herbarios Chinos/química , Glucósidos/química , Glicósidos/química , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Three new2-(2-phenylethyl)chromone derivatives (1-3) and a new2-(2-phenylethenyl)chromone derivative (4), together with two known 2-(2-phenylethyl)chromone derivatives (5-6), were isolated from agarwood originating from Gyrinops salicifolia Ridl. The structures of compounds 1-4 were elucidated by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS analysis, as well as by comparison with the literature. Compounds 1, 2, and 5 showed moderate cytotoxicity against human tumor K562, BEL-7402, and SGC-7901 cell lines with IC50 values of 5.76 to 20.1 µM.
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Antineoplásicos/química , Cromonas/química , Flavonoides/química , Magnoliopsida/química , Extractos Vegetales/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Cromonas/aislamiento & purificación , Cromonas/farmacología , Flavonoides/farmacología , Humanos , Células K562 , Estructura MolecularRESUMEN
BACKGROUND: Hepatitis B virus (HBV) DNA levels are crucial for managing chronic hepatitis B (CHB). It was unclear whether Daan real-time polymerase chain reaction test (Daan test) or COBAS TaqMan HBV DNA Test (Cobas TaqMan) was superior in measuring different HBV DNA levels in clinical specimens. METHODS: We enrolled 67 treatment-naïve, HBV surface antigen-positive CHB patients (high baseline viral levels) who received either lamivudine/adefovir or entecavir. Serum samples were tested at baseline and treatment week 24 using the Daan test and Cobas TaqMan. RESULTS: In the 67-baseline samples, the HBV DNA levels with the Cobas TaqMan (7.90 ± 0.73 log10 IU/mL) were significantly greater than those of the Daan test (7.11 ± 0.44 log10 IU/mL; P < 0.001). Of the 67 24-week samples (low viral levels), the Cobas TaqMan detected 59 (88.1%; 8 undetected); the Daan test detected 33 (49.3%; 34 undetected; P < 0.001). The Cobas TaqMan detected HBV DNA in 26 of 34 samples undetectable by the Daan test (range, 1.4-3.7 log10 IU/mL) or 38% of samples (26/67). The reductions in viral load after 24 weeks of oral antiviral treatment in the 33 samples that were positive for both the Daan test and the Cobas TaqMan test were significantly different (3.59 ± 1.11 log10 IU/mL versus 4.87 ± 1.58 log10 IU/mL, respectively; P = 0.001). Spearman correlation analysis showed positive correlation between results from two tests (rp = 0.602,P<0.001). The HBV genotypes and the anti-viral treatment did not affect the measurements of the HBV DNA by the Daan assay and the Cobas Taqman assay. CONCLUSION: The Cobas Taqman was more sensitive at low viral loads than the Daan test and the change from complete to partial virological response could affect clinical decisions. The Cobas Taqman may be more appropriate for detection of HBV DNA levels.
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ADN Viral/sangre , Hepatitis B Crónica/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Carga Viral , Adenina/análogos & derivados , Adenina/uso terapéutico , Adolescente , Adulto , Antivirales/uso terapéutico , Femenino , Guanina/análogos & derivados , Guanina/uso terapéutico , Virus de la Hepatitis B , Humanos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Organofosfonatos/uso terapéutico , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Objective:To evaluate the diagnostic efficacy of traditional radiomics, deep learning, and deep learning radiomics in differentiating normal and inner ear malformations on temporal bone computed tomographyï¼CTï¼. Methods:A total of 572 temporal bone CT data were retrospectively collected, including 201 cases of inner ear malformation and 371 cases of normal inner ear, and randomly divided into a training cohortï¼n=458ï¼ and a test cohortï¼n=114ï¼ in a ratio of 4â¶1. Deep transfer learning features and radiomics features were extracted from the CT images and feature fusion was performed to establish the least absolute shrinkage and selection operator. The CT results interpretated by two chief otologists from the National Clinical Research Center for Otorhinolaryngological Diseases served as the gold standard for diagnosis. The model performance was evaluated using receiver operating characteristicï¼ROCï¼, and the accuracy, sensitivity, specificity, and other indicators of the models were calculated. The predictive power of each model was compared using the Delong test. Results:1 179 radiomics features were obtained from traditional radiomics, 2 048 deep learning features were obtained from deep learning, and 137 features fusion were obtained after feature screening and fusion of the two. The area under the curveï¼AUCï¼ of the deep learning radiomics model on the test cohort was 0.964 0ï¼95%CI 0.931 4-0.996 8ï¼, with an accuracy of 0.922, sensitivity of 0.881, and specificity of 0.945. The AUC of the radiomics features alone on the test cohort was 0.929 0ï¼95%CI 0.882 2-0.974 9ï¼, with an accuracy of 0.878, sensitivity of 0.881, and specificity of 0.877. The AUC of the deep learning features alone on the test cohort was 0.947 0ï¼95%CI 0.898 2-0.994 8ï¼, with an accuracy of 0.913, sensitivity of 0.810, and specificity of 0.973. The results indicated that the prediction accuracy and AUC of the deep learning radiomics model are the highest. The Delong test showed that the differences between any two models did not reach statistical significance. Conclusion:The feature fusion model can be used for the differential diagnosis of normal and inner ear malformations, and its diagnostic performance is superior to radiomics or deep learning models alone.
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Aprendizaje Profundo , Oído Interno , Hueso Temporal , Tomografía Computarizada por Rayos X , Humanos , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/anomalías , Oído Interno/diagnóstico por imagen , Oído Interno/anomalías , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Sensibilidad y Especificidad , Curva ROC , RadiómicaRESUMEN
Remote noncontact respiratory rate estimation by facial visual information has great research significance, providing valuable priors for health monitoring, clinical diagnosis, and anti-fraud. However, existing studies suffer from disturbances in epidermal specular reflections induced by head movements and facial expressions. Furthermore, diffuse reflections of light in the skin-colored subcutaneous tissue caused by multiple time-varying physiological signals independent of breathing are entangled with the intention of the respiratory process, leading to confusion in current research. To address these issues, this article proposes a novel network for natural light video-based remote respiration estimation. Specifically, our model consists of a two-stage architecture that progressively implements vital measurements. The first stage adopts an encoder-decoder structure to recharacterize the facial motion frame differences of the input video based on the gradient binary state of the respiratory signal during inspiration and expiration. Then, the obtained generative mapping, which is disentangled from various time-varying interferences and is only linearly related to the respiratory state, is combined with the facial appearance in the second stage. To further improve the robustness of our algorithm, we design a targeted long-term temporal attention module and embed it between the two stages to enhance the network's ability to model the breathing cycle that occupies ultra many frames and to mine hidden timing change clues. We train and validate the proposed network on a series of publicly available respiration estimation datasets, and the experimental results demonstrate its competitiveness against the state-of-the-art breathing and physiological prediction frameworks.
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PURPOSE: To evaluate a system for otomicrosurgery based on 4K three-dimensional (3D) exoscope technology and apply it to cochlear implantation. METHODS: An open stereoscopic vision-based surgical system, which differs from traditional surgical microscopes, was created by utilizing 4K stereo imaging technology and combining it with low-latency 4K ultra-high-definition 3D display. The system underwent evaluation based on 57 cochlear implantation operations, three designed microscopic manipulations, and a questionnaire survey. RESULTS: The surgical images displayed by the 4K-3D exoscope system (4K-3D-ES) are stereoscopic, clear, and smooth. The use of 4K-3D-ES in cochlear implantation is not inferior to traditional microscopes in terms of intraoperative bleeding and surgical complications, and the surgical duration is not slower or may even be faster than when using traditional microscopes. The results of micromanipulation experiments conducted on 16 students also confirmed this and demonstrated that 4K-3D-ES can be easily adapted. Furthermore, additional advantages of 4K-3D-ES were gathered. Significantly enlarged and high-definition stereoscopic images contribute to the visualization of finer anatomical microstructures such as chordae tympani, ensuring safer surgery. Users feel more comfortable in their necks, shoulders, waists, and backs. Real-time shared stereoscopic view for multiple people, convenient for collaboration and teaching. The ear endoscope and 4K-3D-ES enable seamless switching on the same screen. High-definition 3D images and videos can be saved with just one click, making future publication and communication convenient. CONCLUSION: The feasibility and safety of 4K-3D-ES for cochlear implantation surgery have been demonstrated. The 4K-3D-ES also offers numerous unique advantages and holds clinical application and promotional value.
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Implantación Coclear , Humanos , Implantación Coclear/métodos , Implantación Coclear/instrumentación , Masculino , Femenino , Niño , Imagenología Tridimensional/métodos , Adulto , Persona de Mediana Edad , Microcirugia/métodos , Microcirugia/instrumentación , Preescolar , Adolescente , Adulto Joven , Anciano , LactanteRESUMEN
Objectives: Lung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival. Methods: Here, quantitative mass spectrometry was conducted for comparing protein expression profiles among various histological subtypes, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (including acinar and micropapillary [MIP] types). To determine the mechanism of MIP-associated metastasis, we identified a protein that was highly expressed in MIP. The expression of the selected highly expressed MIP protein was verified via immunohistochemical (IHC) analysis and its function was validated by an in vitro migration assay. Results: Proteomic data revealed that low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) was highly expressed in MIP group, which was confirmed by IHC. The co-expressed proteins in this study, PSMD1 and HSP90AB1, have been reported to be highly expressed in different cancers and play an essential role in metastasis. We observed that LRPAP1 promoted lung cancer progression, including metastasis, invasion and proliferation in vitro and in vivo. Conclusion: LRPAP1 is necessary for MIP-associated metastasis and is the candidate novel anti-metastasis therapeutic target.
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BACKGROUND: Emerging three-dimensional digital visualization technology (DVT) provides more advantages than traditional microscopy in microsurgery; however, its impact on microsurgeons' visual and nervous systems and delicate microsurgery is still unclear, which hinders the wider implementation of DVT in digital visualization for microsurgery. METHODS AND MATERIAL: Forty-two microsurgeons from the Zhongshan Ophthalmic Center were enrolled in this prospective self-controlled study. Each microsurgeon consecutively performed 30 min conjunctival sutures using a three-dimensional digital display and a microscope, respectively. Visual function, autonomic nerve activity, and subjective symptoms were evaluated before and immediately after the operation. Visual functions, including accommodative lag, accommodative amplitude, near point of convergence and contrast sensitivity function (CSF), were measured by an expert optometrist. Heart rate variability was recorded by a wearable device for monitoring autonomic nervous activity. Subjective symptoms were evaluated by questionnaires. Microsurgical performance was assessed by the video-based Objective Structured Assessment of Technical Skill (OSATS) tool. RESULTS: Accommodative lag decreased from 0.63 (0.18) diopters (D) to 0.55 (0.16) D ( P =0.014), area under the log contrast sensitivity function increased from 1.49 (0.15) to 1.52 (0.14) ( P =0.037), and heart rate variability decreased from 36.00 (13.54) milliseconds (ms) to 32.26 (12.35) ms ( P =0.004) after using the DVT, but the changes showed no differences compared to traditional microscopy ( P >0.05). No statistical significance was observed for global OSATS scores between the two rounds of operations [mean difference, 0.05 (95% CI: -1.17 to 1.08) points; P =0.95]. Subjective symptoms were quite mild after using both techniques. CONCLUSIONS: The impact of DVT-based procedures on microsurgeons includes enhanced accommodation and sympathetic activity, but the changes and surgical performance are not significantly different from those of microscopy-based microsurgery. Our findings indicate that short-term use of DVT is reliable for microsurgery and the long-term effect of using DVT deserve more consideration.
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Microscopía , Dispositivos Electrónicos Vestibles , Humanos , Microcirugia/métodos , Estudios Prospectivos , TecnologíaRESUMEN
This paper presents an improved solution for the airflow energy harvester based on the push-pull diamagnetic levitation structure. A four-notch rotor is adopted to eliminate the offset of the floating rotor and substantially increase the energy conversion rate. The new rotor is a centrally symmetrical-shaped magnet, which ensures that it is not subjected to cyclically varying unbalanced radial forces, thus avoiding the rotor's offset. Considering the output voltage and power of several types of rotors, the four-notch rotor was found to be optimal. Furthermore, with the four-notch rotor, the overall average increase in axial magnetic spring stiffness is 9.666% and the average increase in maximum monostable levitation space is 1.67%, but the horizontal recovery force is reduced by 3.97%. The experimental results show that at an airflow rate of 3000 sccm, the peak voltage and rotation speed of the four-notch rotor are 2.709 V and 21,367 rpm, respectively, which are 40.80% and 5.99% higher compared to the three-notch rotor. The experimental results were consistent with the analytical simulation. Based on the improvement, the energy conversion factor of the airflow energy harvester increased to 0.127 mV/rpm, the output power increased to 138.47 mW and the energy conversion rate increased to 58.14%, while the trend of the levitation characteristics also matched the simulation results. In summary, the solution proposed in this paper significantly improves the performance of the airflow energy harvester.
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INTRODUCTION: We studied the correlation of central macular fluid volume (CMFV) and central subfield thickness (CST) with best-corrected visual acuity (BCVA) in treatment-naïve eyes with diabetic macular edema (DME) 1 month after anti-vascular endothelial growth factor (VEGF) therapy. METHODS: This retrospective cohort study investigated eyes that received anti-VEGF therapy. All participants underwent comprehensive examinations and optical coherence tomography (OCT) volume scans at baseline (M0) and 1 month after the first treatment (M1). Two deep learning models were separately developed to automatically measure the CMFV and the CST. Correlations were analyzed between the CMFV and the logMAR BCVA at M0 and logMAR BCVA at M1. The area under the receiver operating characteristic curve (AUROC) of CMFV and CST for predicting eyes with BCVA [Formula: see text] 20/40 at M1 was analyzed. RESULTS: This study included 156 DME eyes from 89 patients. The median CMFV decreased from 0.272 (0.061-0.568) at M0 to 0.096 (0.018-0.307) mm3 at M1. The CST decreased from 414 (293-575) to 322 (252-430) µm. The logMAR BCVA decreased from 0.523 (0.301-0.817) to 0.398 (0.222-0.699). Multivariate analysis demonstrated that the CMFV was the only significant factor for logMAR BCVA at both M0 (ß = 0.199, p = 0.047) and M1 (ß = 0.279, p = 0.004). The AUROC of CMFV for predicting eyes with BCVA [Formula: see text] 20/40 at M1 was 0.72, and the AUROC of CST was 0.69. CONCLUSIONS: Anti-VEGF therapy is an effective treatment for DME. Automated measured CMFV is a more accurate prognostic factor than CST for the initial anti-VEGF treatment outcome of DME.
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Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a quarantine disease that seriously affects citrus production worldwide. The use of microorganisms and their products for biological control has been proven to be effective in controlling Xanthomonas disease. In this study, a novel Xcc antagonistic strain was isolated and identified as Bacillus amyloliquefaciens F9 by morphological and molecular analysis. The lipopeptide extract of B. amyloliquefaciens F9 (F9LE) effectively inhibited the growth of Xcc in an agar diffusion assay and restrained the occurrence of canker lesions in a pathogenicity test under greenhouse conditions. Consistent with these findings, F9LE treatment significantly inhibited the production of extracellular enzymes in Xcc cells and induced cell wall damage, with leakage of bacterial contents revealed by scanning electron microscopy and transmission electron microscopy analyses. In addition, F9LE also showed strong antagonistic activity against a wide spectrum of plant pathogenic bacteria and fungi. Furthermore, using electrospray ionization mass spectrometry analysis, the main antimicrobial compounds of strain F9 were identified as three kinds of lipopeptides, including homologues of surfactin, fengycin, and iturin. Taken together, our results show that B. amyloliquefaciens F9 and its lipopeptide components have the potential to be used as biocontrol agents against Xcc, and other plant pathogenic bacteria and fungi.
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Lipid accumulation exacerbates tumor development, as it fuels the proliferative growth of cancer cells. The role of medium-chain acyl-CoA dehydrogenase (ACADM), an enzyme that catalyzes the first step of mitochondrial fatty acid oxidation, in tumor biology remains elusive. Therefore, investigating its mode of dysregulation can shed light on metabolic dependencies in cancer development. In hepatocellular carcinoma (HCC), ACADM was significantly underexpressed, correlating with several aggressive clinicopathologic features observed in patients. Functionally, suppression of ACADM promoted HCC cell motility with elevated triglyceride, phospholipid, and cellular lipid droplet levels, indicating the tumor suppressive ability of ACADM in HCC. Sterol regulatory element-binding protein-1 (SREBP1) was identified as a negative transcriptional regulator of ACADM. Subsequently, high levels of caveolin-1 (CAV1) were observed to inhibit fatty acid oxidation, which revealed its role in regulating lipid metabolism. CAV1 expression negatively correlated with ACADM and its upregulation enhanced nuclear accumulation of SREBP1, resulting in suppressed ACADM activity and contributing to increased HCC cell aggressiveness. Administration of an SREBP1 inhibitor in combination with sorafenib elicited a synergistic antitumor effect and significantly reduced HCC tumor growth in vivo. These findings indicate that deregulation of fatty acid oxidation mediated by the CAV1/SREBP1/ACADM axis results in HCC progression, which implicates targeting fatty acid metabolism to improve HCC treatment. SIGNIFICANCE: This study identifies tumor suppressive effects of ACADM in hepatocellular carcinoma and suggests promotion of ß-oxidation to diminish fatty acid availability to cancer cells could be used as a therapeutic strategy.
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Acil-CoA Deshidrogenasa/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Caveolina 1/metabolismo , Ácidos Grasos/química , Regulación Neoplásica de la Expresión Génica , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Acil-CoA Deshidrogenasa/genética , Acil-CoA Deshidrogenasa/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Caveolina 1/genética , Proliferación Celular , Humanos , Metabolismo de los Lípidos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Oxidación-Reducción , Pronóstico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Rab GTPases are major mediators that ensure the proper spatiotemporal regulation of intracellular trafficking. Functional impairment and altered expression of Rab proteins have been revealed in various human cancers. There is an emerging evidence about the role of Rab proteins in the biogenesis of extracellular vesicles (EVs). In hepatocellular carcinoma (HCC), using RNA sequencing comparing expression profiles of adjacent non-tumorous tissues and HCC, Rab20 is identified to be the most frequently downregulated Rab member in HCC. Functionally, restoration of Rab20 in metastatic HCC cells results in the release of EVs with a diminished activity to promote cell growth, motility and metastasis. Conversely, EVs released from normal liver cells with Rab20 knockdown loses suppressive effect on HCC cell growth and motility. Proteomic profiling revealed the level of triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, in EVs to be positively associated with Rab20 expression of the releasing cells. TPI1 targeted to be expressed in EVs released by Rab20 knockdown cells compromises the oncogenic activity of EVs. Besides, EVs released by TPI1 knockdown cells recapitulates the promoting effect of EVs derived from HCC cells with Rab20 underexpression. Aerobic glycolysis is beneficial to the survival and proliferation of tumour cells. Here, we observed that the enhanced cell growth and motility are driven by the enhanced aerobic glycolysis induced by EVs with reduced TPI1. The addition of glycolytic inhibitor blocks the promoting effect of EVs with reduced TPI1. Taken together, our study provides a mechanistic link among tumour cell-derived EVs and glucose metabolism in HCC with Rab20 deregulation.
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Carcinogénesis/metabolismo , Carcinoma Hepatocelular/metabolismo , Vesículas Extracelulares/metabolismo , Glucólisis , Neoplasias Hepáticas/metabolismo , Triosa-Fosfato Isomerasa/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Hepáticas/genética , Análisis de Secuencia de ARN , Triosa-Fosfato Isomerasa/genética , Proteínas de Unión al GTP rab/genéticaRESUMEN
BACKGROUND: It is well established that obesity is a disease of sustained low-grade inflammation. However, it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this study, we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2. METHODS: This is a retrospective multicenter clinical study. A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People's Hospital, Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020. Demographic and clinical data were extracted from medical records. Acute respiratory distress syndrome (ARDS) was defined as oxygenation index (PaO2/FiO2) ≤ 300 mmHg. We grouped patients through the body mass index (BMI). Associations were examined using the t test, χ2 test and multivariate logistic forward regression test. RESULTS: Patients with BMI < 24 were significantly younger (P = 0.025) with lower creatine kinase (P = 0.013), lower diastolic pressure blood (P = 0.035), lower serum creatinine (P = 0.012), lower lactate dehydrogenase (P = 0.001) and higher platelet count (P = 0.002). The BMI level was 20.78 ± 3.15 in patients without pneumonia compared with the patients with pneumonia (23.81 ± 3.49, P = 0.001). For patients without ARDS, an average BMI level of 22.65 ± 3.53 was observed, significantly lower than patients with ARDS (24.57 ± 3.59, P = 0.022). The mean BMI was 22.35 ± 3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests, lower than patients with disease exacerbation with 24.89 ± 3.17 (P = 0.001). In addition, lymphocyte count (r = - 0.23, P = 0.027) and platelet count (r = - 0.44, P < 0.001) were negatively correlated with BMI. While hemoglobin (r = 0.267, P = 0.008), creatine kinase (r = 0.331, P = 0.001), serum creatinine (r = 0.424, P < 0.001) and lactate dehydrogenase (r = 0.343, P = 0.001) were significantly positive correlated with BMI. Multivariate analysis showed that older age (OR = 1.046, P = 0.009) and BMI ≥ 24 (OR = 1.258, P = 0.005) were independent risk factors associated ICU admission while BMI ≥ 24 (OR = 4.219, P = 0.007) was independent risk factor associated with radiographic disease exacerbation. CONCLUSIONS: Our study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection. For patients with increased risk, clinicians should intervene promptly to avoid disease progression.