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Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression-free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high-risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1-year, 3-year, and 5-year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single-cell RNA sequencing to two castration-related prostate cancer (CRPC) samples and two hormone-related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression-related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.
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Biología Computacional , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , Masculino , Humanos , Biología Computacional/métodos , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Factores de Riesgo , Línea Celular TumoralRESUMEN
Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
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Accelerating the migration of interfacial carriers in heterojunctions is crucial for achieving highly sensitive photoelectrochemical (PEC) sensing. In this study, we developed three-dimensional (3D)/two-dimensional (2D) CuInS2/red phosphorus nanosheet (CuInS2/RP NS) n-n heterojunction functional materials with enhanced interfacial charge transfer capabilities for PEC sensing. The 3D CuInS2 serves as a conductive layer, providing excellent electronic conductivity and superior electron absorption and transport properties. In contrast, the ultrathin RP NS acts as a transport layer that enhances carrier mobility. The 3D/2D heterojunction ensures a large interface contact surface, shortening the carrier transport distance. A well-aligned band position generates a substantial built-in electric field, providing a significant driving force for efficient carrier separation and migration, thereby improving response sensitivity. A PEC aptamer sensor was constructed based on the synthesized heterostructure for ciprofloxacin detection. The detection limit of the CuInS2/RP NS aptamer sensor for ciprofloxacin is 2.03 × 10-15 mg·mL-1, with a linear range from 1.0 × 10-14 to 1.0 × 10-5 mg·mL-1. This work presents a strategy for enhancing the photoelectric response by modulating the interface structure of heterojunctions, thereby opening new prospects for the application of highly sensitive PEC sensors in antibiotic detection.
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Point-of-care testing (POCT) has attracted great interest because of its prominent advantages of rapidness, precision, portability, and real-time monitoring, thus becoming a powerful biomedical device in early clinical diagnosis and convenient medical treatments. However, its complicated manufacturing process and high expense severely impede mass production and broad applications. Herein, an innovative but inexpensive integrated sandwich-paper three-dimensional (3D) cell sensing device is fabricated to in situ wirelessly detect H2O2 released from living cells. The paper-based electrochemical sensing device was constructed by a sealed sandwiched bottom plastic film/fiber paper/top hole-centered plastic film that was printed with patterned electrodes. A new (Fe, Mn)3(PO4)2/N-doped carbon nanorod was developed and immobilized on the sensing carbon electrode while cell culture solution filled the exposed fiber paper, allowing living cells to grow on the fiber paper surrounding the electrode. Due to the significantly shortening diffusion distance to access the sensing sites by such a unique device and a rationally tuned ratio of Fe2+/Mn2+, the device exhibits a fast response time (0.2 s), a low detection limit (0.4 µM), and a wide detection range (2-3200 µM). This work offers great promise for a low-cost and highly sensitive POCT device for practical clinic diagnosis and broad POCT biomedical applications.
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As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.
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Algoritmos , Aprendizaje Profundo , Psoriasis , Índice de Severidad de la Enfermedad , Psoriasis/patología , Humanos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.
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Transición de Fase , Polienos/química , Cristalización , Temperatura , Polímeros/química , Resistencia al CorteRESUMEN
Cobalt-bridged organometallic molecular wires (p-Co-p, p-Co-m and m-Co-m) are synthesized, and their charge transport properties are studied. The experimental results show that the quantum interference (QI) effects of cobalt-bridged organometallic wires are determined by the anchoring group. Interestingly, the cobalt-bridge reduces the conductance of the junctions and tunes the QI effect of the wires. These results demonstrate the unique property of metal-bridged organometallic molecular wires and their potential applications in molecular electronics.
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Using line structured light to measure metal surface topography, the extraction error of the stripe center is significant due to the influence of the optical characteristics of the metal surface and the scattering noise. This paper proposes a sub-pixel stripe center extraction method based on adaptive threshold segmentation and a gradient weighting strategy to address this issue. First, we analyze the characteristics of the stripe image of the measured metal's surface morphology. Relying on the morphological features of the image, the image is segmented to remove the effect of background noise and to obtain the region of interest in the image. Then, we use the gray-gravity method to get the rough center coordinates of the stripes. We extend the stripes in the width direction using the rough center coordinates as a reference to determine the center of the stripes for extraction after segmentation. Next, we adaptively determine the boundary threshold utilizing the region's grayscale. Finally, we use the gradient weighting strategy to extract the sub-pixel stripe center. The experimental results show that the proposed method effectively eliminates the interference of metal surface scattering on 3D reconstruction. The average height error of the measured standard block is 0.025 mm, and the repeatability of the measurement accuracy is 0.026 mm.
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Exposure to arsenic (As) induces adverse effects on human health. Vitamins B1, B6, and C, as indispensable micronutrients for humans, have been proven to influence the metabolism and toxicity of ingested As. To determine the effect of vitamins on health risks associated with soil exposure, As bioaccessibility in 14 soil samples using four in vitro methods of IVG, PBET, SBRC, and UBM was measured with the addition of vitamins B1, B6, and C. With vitamins B1 and B6 addition, the gastric As bioaccessibility in 14 soil samples was reduced by 1.14-3.52 and 1.14-5.02 fold, respectively, and instead an increase in the intestinal bioaccessibility was presented in some cases. Vitamin C supplementation yielded higher As bioaccessibility in the gastric (1.13-13.02 fold) and small intestinal (1.21-33.35 fold) phases, respectively. As evidenced by the X-ray absorption near-edge spectroscopy (XANES) and Fourier transform infrared spectroscopy (FTIR) analysis, arsenic dissolution was promoted by Fe-As and hindered by the formation of Al-As fractions. Soil As dissolution in the simulated gastrointestinal tract was strongly influenced by soil minerals and ingested vitamins, due to the chelation of arsenic with vitamins and soil minerals such as Fe (hydr)oxides, and Fe(III) reductive dissolution to enhance As release by vitamin C as an iron reducer. These findings will expand the knowledge of health risks of exposure to As-contaminated soils and nutritional interventions aiming at the mitigation of As toxicity.
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PEDOT: PSS has been used as a biomimetic uric acid (UA) sensor but suffers from unfortunate low detection limit (LOD), narrow detection range and poor stability. Herein, we get graphdiyne (GDY) marry PEDOT:PSS to create a very stable GDY@PEDOT:PSS heterostructure for a biomimetic UA sensor, which accomplishes the lowest LOD (6 nM), the widest detection range (0.03 µM-7 mM) and the longest stability (98.1% for 35 days) among the related UA sensors. The sensor was successfully used to in situ real-time detection of UA in sweat. The enhancement mechanisms of the sensor were investigated, and results discover that C≡C of GDY and C = C of PEDOT:PSS can cross-link each other by π-π interactions, making not only the former strongly resistant against oxidation deterioration, but also causes the latter to efficiently prevent water swelling of polymer for poor conductivity, thereby leading to high stability from both components. While the stabilized heterostructure can also offer more active sites by enhanced absorption of UA via π-π interactions for highly sensitive detection of UA. This work holds great promise for a practical sweat UA sensor while providing scientific insight to design a stable and electrocatalytically active structure from two unstable components.
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Grafito , Sudor , Ácido Úrico , Límite de DetecciónRESUMEN
The performance of the capacitive gap-sensing system plays a critical role in a satellite-based gravity gradiometer that is developed using an electrostatic accelerometer. The capacitive sensing gain mainly depends on the stabilized injection bias amplitude, the gain of the transformer bridge, and the trans-impedance amplifier. Previous studies have indicated that amplitude noise is the main factor influencing the noise of capacitive displacement detection. Analyzing the capacitive gap-sensing system indicates that the amplitude, frequency, phase, and broadband noises of the stabilized injection bias have varying levels of influence on the performance of the detection system. This paper establishes a model to clarify the mentioned effects. The validation of the sub-tests demonstrates that the analysis and evaluation results of various noise coefficients are highly consistent with the model's predicted outcomes.
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BACKGROUND: Ferroptosis has excellent potential in glioblastoma (GBM) therapy. In this study, we attempted to explore the effect of miR 491-5p on ferroptosis in GBM. METHODS: In this study, publicly available ferroptosis-related genome maps were used to screen genes upregulated in GBM and their target genes. The Spearman correlation coefficient was applied to analyze the correlation between the tumor protein p53 gene (TP53) and miR-491-5p. The expressions of miR-491-5p and TP53 were determined. The protein abundances of the TP53-encoded factors p53 and p21 were measured. Cell proliferation, migration and invasion were assessed. We pretreated U251MG cells and GBM mice with a ferroptosis inducer (erastin). The mitochondrial state was observed. The contents of reactive oxygen species (ROS), total Fe and Fe2+ were calculated. RESULTS: The level of TP53 was significantly increased in GBM and negatively correlated with miR-491-5p. miR-491-5p overexpression promoted U251MG cell proliferation, migration and invasion and interfered with the p53/p21 pathway. TP53 supplement reversed the effects of miR-491-5p. U251MG cells and GBM mice exhibited significant accumulations of ROS and iron. Erastin promoted the expression of TP53. Inhibition of TP53 reversed erastin-induced physiological phenotypes. Moreover, miR-491-5p overexpression caused a decrease in the number of damaged mitochondria and the contents of ROS, total Fe and Fe2+. TP53 supplement disrupted miR-491-5p-repressed ferroptosis. Erastin could inhibit GBM growth, and miR-491-5p overexpression impeded the therapeutic effect of erastin. CONCLUSIONS: Our findings reveal the functional diversity of miR-491-5p in GBM and suggest that miR-491-5p/TP53 signaling hinders the sensitivity of GBM to ferroptosis through the p53/p21 pathway.
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Neoplasias Encefálicas , Ferroptosis , Glioblastoma , MicroARNs , Animales , Ratones , Glioblastoma/patología , MicroARNs/genética , MicroARNs/metabolismo , Ferroptosis/genética , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Encefálicas/patología , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
Rotation axis calibration is crucial for high-precision automatic point cloud stitching in turntable-based 3D scanning systems. To achieve a 360° sampling with a 2D calibrator in rotation axis calibration, this paper proposes a dual-turntable angle cancellation (DTAC) method. DTAC introduces an auxiliary turntable to keep a proper relative angle between the 3D sensor and the calibrator during the calibration process. The auxiliary turntable rotates at the same and opposite angle as the main turntable and cancels the increment of the relative angle. By projecting the feature points on the planar calibrator from real-world space to virtual calibration space, the projected points all share the same rotation axis of the main turntable. Further, a layered circle center extraction (LCCE) algorithm is applied to deal with outlier data points. The algorithm uses a two-step robust estimation strategy combining RANSAC circle fitting with a median noise filter for circle center selection. The standard ball reconstruction experiment shows that the 3D system calibrated by the method achieves a mean absolute error of 0.022 mm and root mean square error of 0.025 mm within the measurement distance of 60-70 cm. Point cloud stitching experiments of different types of objects show that our method outperforms other state-of-the-art methods in stitching accuracy. The DTAC method and LCCE algorithm can improve turntable-based 3D scanning systems.
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Microglial activation is a key event in neuroinflammation, which, in turn, is a central process in neurological disorders. In this study, we investigated the protective effects of D-beta-hydroxybutyrate (BHB) against microglial activation in lipopolysaccharide (LPS)-treated mice and BV-2 cells. The effects of BHB in mice were assessed using behavioral testing, morphological analysis and immunofluorescence labeling for the microglial marker ionizing calcium-binding adaptor molecule 1 (IBA-1) and the inflammatory cytokine interleukin-6 (IL-6) in the hippocampus. Moreover, we examined the levels of the inflammatory IL-6 and tumor necrosis factor-α (TNF-α), as well as those of the neuroprotective brain-derived neurotrophic factor (BDNF) and transforming growth factor-ß (TGF-ß) in the brain. In addition, we examined the effects of BHB on IL-6, TNF-α, BDNF, TGF-ß, reactive oxygen species (ROS) level and cell viability in LPS-stimulated BV-2 cells. BHB treatments attenuated behavioral abnormalities, reduced the number of IBA-1-positive cells and the intensity of IL-6 fluorescence in the hippocampus, with amelioration of microglia morphological changes in the LPS-treated mice. Furthermore, BHB inhibited IL-6 and TNF-α generation, but promoted BDNF and TGF-ß production in the brain of LPS-treated mice. In vitro, BHB inhibited IL-6 and TNF-α generation, increased BDNF and TGF-ß production, reduced ROS level, ameliorated morphological changes and elevated cell viability of LPS-stimulated BV-2 cells. Together, our findings suggest that BHB exerts protective effects against microglial activation in vitro and in vivo, thereby reducing neuroinflammation.
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Lipopolisacáridos , Microglía , Ratones , Animales , Lipopolisacáridos/farmacología , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo , Factor de Necrosis Tumoral alfa , Interleucina-6 , Especies Reactivas de Oxígeno , Enfermedades Neuroinflamatorias , Factor de Crecimiento Transformador beta/farmacología , Inflamación/tratamiento farmacológicoRESUMEN
Abernethy malformation, also known as congenital extrahepatic shunt, is a rare anomaly, which is characterized by partial or complete diversion of the portal blood into the systemic venous circulation. The clinical manifestations of Abernethy malformation during childhood include neonatal cholestasis, failure to thrive, mental retardation, and other congenital defects. We report a case of Abernethy malformation Type II in a 9-year-old boy, whose left ventricle was slightly enlarged because of several major aortopulmonary collateral arteries (MAPCAs) but laboratory examinations were normal 5 years earlier. The characteristics of congenital heart disease in patients with Abernethy malformation are discussed. We propose that physicians should be aware of the possibility of Abernethy malformation in children with enlargement of the left ventricular due to systemic-pulmonary collateral circulation.
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Cardiopatías Congénitas , Malformaciones Vasculares , Masculino , Niño , Humanos , Recién Nacido , Vena Porta/anomalías , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/diagnóstico por imagen , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagenRESUMEN
Given the digitalization trends within the field of engineering, we propose a practical approach to engineering digitization. This method is established based on a physical sandbox model, camera equipment and simulation technology. We propose an image processing modeling method to establish high-precision continuous mathematical models of transmission towers. The calculation of the wind field is realized by using wind speed calculations, a load-wind-direction-time algorithm and the Continuum-Discontinuum Element Method (CDEM). The sensitivity analysis of displacement- and acceleration-controlled transmission tower loads under two different wind direction conditions is conducted. The results show that the digital model exhibits a proportional relationship with the physical dimensions of the transmission tower model. The error between the numerical simulation results and the experimental results falls within a reasonable range. Nodes at higher positions of the transmission tower experience significantly higher forces compared to those at lower positions, and the structural forms with larger windward projected areas yield similar simulation results. The proposed digital twin system can help monitor the performance of structural bodies and assess the disaster degree in extreme conditions. It can guide specific maintenance and repair tasks.
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While restricting nutrition can improve diseases related to the digestive tract, excessive restriction of food intake can also lead to malnutrition and delayed physical growth. Therefore, this brings the demand to study the effect and potential mechanism of restricted feeding on skeletal muscle development in rabbits. This study utilized hematoxylin-eosin (HE) staining to detect muscle fiber area which depicted significant reduction in skeletal muscle fiber upon 30% feed restriction (p < 0.05). The control group and 30% feed restricted group showed 615 deferentially expressed genes (DEGs). Through the GO and KEGG functional enrichment analysis demonstrated 28 DEGs related to muscle development. KEGG analysis showed enrichment of pathways including PI3K/Akt signaling pathway, MAPK signaling pathway, and Hedgehog signaling pathway. Further, the full length of troponin I1, slow skeletal type (TNNI1) was cloned. We studied the expression of skeletal muscle differentiation-related genes such as MyoD, Myf5 gene and Desmin. Specifically, the TNNI1 gene overexpression and knockdown studies were conducted. The over-expression of TNNI1 significantly enhanced the expression of the skeletal muscle development-related genes. Contrastingly, the silencing of TNNI1 gene reduced the expression significantly. These findings showed that TNNI1 may be a regulator for regulating the expression of muscle development-related genes.
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After more than a century of development, autologous fat transplantation (AFT), a repair method for soft tissue defects and deformities, has the advantages of being simple, rapid, effective and safe, and it is increasingly favoured by plastic surgeons. This article reviews the developmental history of AFT, analyses its clinical application status in the oral and maxillofacial regions, and provides a preliminary summary and discussion of the research progress related to AFT. The hope is that that this technique could be widely applied for oral and maxillofacial diseases as well as facial rejuvenation indications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Tejido Adiposo , Rejuvenecimiento , Tejido Adiposo/trasplante , Cara , Humanos , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
Understanding the impact of climate change on terrestrial wet and dry changes and the relationship between the two is of great significance to the sustainable development of terrestrial ecosystems. The farming-pastoral ecotone of northern China (FPENC) is an area that is sensitive to climate change, suffering from perennial drought and a clear aridification trend. Unlike previous single-factor, single-timescale studies, we identified aridification in the region based on a dataset established by remote sensing and ground-based monitoring stations from a combination of two perspectives: climate and soil. The results show that, in terms of climate, the period from 2000 to 2019 was the driest in the region during the last 120 years , and the summer drought was the most severe and shifted from a summer to spring drought; in terms of soil, the soil aridification trend in the region was severe, with 16.1% of the areas becoming significantly drier (P < 0.1) among the years and 41.6% in spring, respectively. Similar to climate change, soils exhibited recessive aridification due to the counterbalancing effect of the dry and wet seasons within the year. Then the coupling relationship between climate change and soil aridification was established in time and space. Moreover, the spatiotemporal response patterns of both were obtained. The results showed that the frequency of soil drought under meteorological drought conditions showed an increasing trend and that the sensitivity of soil drought occurrence increased. Among them, the effect of precipitation on relative soil moisture (RSM) was immediate, and the effect of prolonged warming on RSM is greater. The area of soil aridification that was caused by climatic aridification in spring accounted for 13.7% of the entire area. The regional aridification research mode proposed in this paper can provide ideas for subsequent studies.
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Ecosistema , Suelo , Agricultura , China , Cambio ClimáticoRESUMEN
It is challenging to realize stereo matching in dynamic stereo vision systems. We present an epipolar guided optical flow network (EGOF-Net) for unrectified stereo matching by estimating robust epipolar geometry with a deep cross-checking-based fundamental matrix estimation method (DCCM) and then surpassing false matches with a 4D epipolar modulator (4D-EM) module. On synthetic and real-scene datasets, our network outperforms the state-of-the-art methods by a substantial margin. Also, we test the network in an existing dynamic stereo system and successfully reconstruct the 3D point clouds. The technique can simplify the stereo vision pipeline by ticking out rectification operations. Moreover, it suggests a new opportunity for combining heuristic algorithms with neural networks. The code is available on https://github.com/psyrocloud/EGOF-Net.