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N-methyl-D-aspartate receptors (NMDARs) are members of the glutamate receptor family and participate in excitatory postsynaptic transmission throughout the central nervous system. Genetic variants in GRIN genes encoding NMDAR subunits are associated with a spectrum of neurological disorders. The M3 transmembrane helices of the NMDAR couple directly to the agonist-binding domains and form a helical bundle crossing in the closed receptors that occludes the pore. The M3 functions as a transduction element whose conformational change couples ligand binding to opening of an ion conducting pore. In this study, we report the functional consequences of 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M3 transmembrane helix. These de novo variants were identified in children with neurological and neuropsychiatric disorders including epilepsy, developmental delay, intellectual disability, hypotonia and attention deficit hyperactivity disorder. All 48 variants in M3 for which comprehensive testing was completed produce a gain-of-function (28/48) compared to loss-of-function (9/48); 11 variants had an indeterminant phenotype. This supports the idea that a key structural feature of the M3 gate exists to stabilize the closed state so that agonist binding can drive channel opening. Given that most M3 variants enhance channel gating, we assessed the potency of FDA-approved NMDAR channel blockers on these variant receptors. These data provide new insight into the structure-function relationship of the NMDAR gate, and suggest that variants within the M3 transmembrane helix produce a gain-of-function.
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Epilepsia , Receptores de N-Metil-D-Aspartato , Niño , Humanos , Epilepsia/genética , Mutación Missense , Fenotipo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de SeñalRESUMEN
Methyl jasmonate (MeJA)-regulated postharvest quality retention of Agaricus bisporus fruiting bodies is associated with arginine catabolism. However, the mechanism of MeJA-regulated arginine catabolism in edible mushrooms is still unclear. This study aimed to investigate the regulatory modes of MeJA on the expression of arginine catabolism-related genes and proteins in intact and different tissues of A. bisporus mushrooms during storage. Results showed that exogenous MeJA treatment activated endogenous JA biosynthesis in A. bisporus mushrooms, and differentially and tissue-specifically regulated the expression of arginine catabolism-related genes (AbARG, AbODC, AbSPE-SDH, AbSPDS, AbSAMDC, and AbASL) and proteins (AbARG, AbSPE-SDH, AbASL, and AbASS). MeJA caused no significant change in AbASS expression but resulted in a dramatic increase in AbASS protein level. Neither the expression of the AbSAMS gene nor the AbSAMS protein was conspicuously altered upon MeJA treatment. Additionally, MeJA reduced the contents of arginine and ornithine and induced the accumulation of free putrescine and spermidine, which was closely correlated with MeJA-regulated arginine catabolism-related genes and proteins. Hence, the results suggested that the differential and tissue-specific regulation of arginine catabolism-related genes and proteins by MeJA contributed to their selective involvement in the postharvest continuing development and quality retention of button mushrooms.
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Agaricus , Agaricus/genética , Acetatos/farmacología , Ciclopentanos/farmacología , Oxilipinas/farmacologíaRESUMEN
The mpox outbreak has subdued with fewer reported cases at the present in high-income countries. It is known that mpox virus (MPXV) infection has been epidemic for more than 50 years in African countries. The ancestral MPXV strain has changed into multiple clades, indicating the ongoing evolution of MPXV, which reflects the historical neglect of mpox in Africa, especially after smallpox eradication, and bestows the danger of more severe mpox epidemics in the future. It is thus imperative to continue the development of mpox diagnostics and treatments so we can be prepared in the event of a new mpox epidemic. In this study, we have developed an MPXV detection tool that leverages the recombinase-aid amplification assay by integrating lateral flow strips (RAA-LF) and one-step sample DNA preparation, with visible readout, no need of laboratory instrument, and ready for field deployment. The detection limit reaches 10 copies per reaction. The performance of our RAA-FL assay in diagnosing mpox clinical samples is on par with that of the quantitative polymerase chain reaction (PCR) assay. Taken together, we have developed a point-of-care RAA-LF method of high accuracy and sensitivity, readily deployable for field detection of MPXV. This diagnostic tool is expected to improve and accelerate field- and self-diagnosis, allow timely isolation and treatment, reduce the spread of MPXV, thus effectively mitigate MPXV outbreak in the future.
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Monkeypox virus , Mpox , Humanos , África , Bioensayo , Brotes de EnfermedadesRESUMEN
PURPOSE: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood. METHODS: We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89Zr-αPD-L1/Fab. RESULTS: The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer. CONCLUSION: The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects.
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BACKGROUND & AIMS: Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear. METHODS: We analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight-adjusted multivariable Cox proportional model was used to study the mortality over three terms. RESULTS: The prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow-up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04-1.33 and 1.19, 1.06-1.34, respectively), this association was mainly observed in NAFLD-/MASLD+ subgroups. NAFLD was not associated with all-cause mortality. However, all three terms were associated with an increased risk of all-cause mortality in individuals with advanced fibrosis (aHR: 1.71-1.81). Subgroup analyses showed that higher risk of all-cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non-Hispanic whites and those without diabetes. CONCLUSIONS: Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.
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Enfermedades Metabólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Anciano , BlancoRESUMEN
Cervical squamous cell carcinoma (CESC) is a significant threat to women's health. Resistance to cisplatin (DDP), a common treatment, hinders the therapeutic efficacy. Understanding the molecular basis of DDP resistance in CESC is imperative. Cyclin-dependent kinase inhibitor 2A (CDKN2A) expression was evaluated through quantitative real-time-PCR and western blot in clinical samples from 30 CESC patients and human cervical epithelial cells and CESC cell lines (SiHa, C33A, and Caski). It was also evaluated through bioinformatics analysis in Timer, Ualcan, and GEPIA database. Cell viability was detected by CCK-8. Apoptosis was detected by Calcein AM/PI assay. Lipid reactive oxygen species (ROS), malondialdehyde, glutathione, Fe 2+ , and iron level were detected by kits. Protein level of JAK2, STAT3, p-JAK2, p-STAT3, ACSL4, GPX4, SLC7A11, and FTL were detected by western blot. In CESC, elevated CDKN2A expression was observed. Cisplatin exhibited a dual effect, inhibiting cell proliferation and inducing ferroptosis in CESC. CDKN2A knockdown in a cisplatin-resistant cell line suppressed proliferation and induced ferroptosis. Moreover, CDKN2A was identified as an inhibitor of erastin-induced ferroptosis. Additionally, targeting the JAK2/STAT3 pathway enhanced ferroptosis in cisplatin-resistant cells. CDKN2A could inhibit ferroptosis in CESC through activating JAK2/STAT3 pathway to modulate cisplatin resistance.
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Carcinoma de Células Escamosas , Cisplatino , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Resistencia a Antineoplásicos , Ferroptosis , Janus Quinasa 2 , Factor de Transcripción STAT3 , Neoplasias del Cuello Uterino , Humanos , Cisplatino/farmacología , Ferroptosis/efectos de los fármacos , Janus Quinasa 2/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Factor de Transcripción STAT3/metabolismo , Femenino , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones , Animales , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Transducción de Señal/efectos de los fármacosRESUMEN
RATIONALE: The chemical constituents of traditional Tibetan medicines (TTM) can be identified using high-performance liquid chromatography and high-resolution mass spectrometry (HPLC-MS/MS) technique. However, the HPLC-MS/MS technique requires the sample to be pretreated and then separated using the specific liquid chromatography method, which is time consuming. This study developed a ballpoint electrospray ionization (BPESI) technique for analyzing the chemical constituents of Sbyor-bzo-ghi-wang. This technique is a simple and inexpensive method for the rapid identification of the chemical constituents of TTMs. METHODS: After the important parameters of the homemade BPESI device were optimized, the chemical constituents of Sbyor-bzo-ghi-wang were quickly identified without sample pretreatment. The raw data were converted to mzML file using MSConvert and then identified using SIRIUS 5 software. RESULTS: The results showed that 30 compounds were identified from Sbyor-bzo-ghi-wang, namely eight bile acids, six flavonoids, four alkaloids, three amino acids, and nine others. Compared to the ultra-high-performance liquid chromatography-Q/Orbitrap and high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) technique, the BPESI technique identified almost similar types of compounds and also a comparable number of compounds. CONCLUSIONS: Compared with the traditional HPLC-MS/MS methods, the BPESI technique does not require complex sample pretreatment and subsequent chromatographic separation steps; also it consumes a small quantity of samples. Therefore, BPESI can be used for the qualitative analysis of the chemical constituents of Sbyor-bzo-ghi-wang.
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Medicina Tradicional Tibetana , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Flavonoides/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Alcaloides/análisis , Alcaloides/química , Ácidos y Sales Biliares/análisis , Ácidos y Sales Biliares/química , Aminoácidos/análisis , Aminoácidos/química , Extractos Vegetales/químicaRESUMEN
Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus. Fish were subjected to varying concentrations of NIC, including a control group (0⯵g/L), a low NIC group (15% 96â¯h LC50, LNG, 9.8⯵g/L), and a high NIC group (80% 96â¯h LC50, HNG, 52.5⯵g/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC50 for NIC was determined to be 65.7⯵g/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3, c9, tnfα, il6, il8, and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein (nramp) mRNA increased, and liver-expressed antimicrobial peptide 2 (leap2) mRNA decreased in gill and gut tissues. And hepcidin (hepc) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.
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Branquias , Animales , Branquias/efectos de los fármacos , Branquias/inmunología , Contaminantes Químicos del Agua/toxicidad , Larva/efectos de los fármacos , Carpas/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Insecticidas/toxicidad , Microbiota/efectos de los fármacosRESUMEN
The natural antimicrobial peptide, epsilon-poly-l-lysine (ε-PL), is widely acknowledged as a food preservative. However, its potential in managing bacterial brown blotch disease in postharvest edible mushrooms and the associated mechanism remain unexplored. In this study, concentrations of ε-PL ≥ 150 mg L-1 demonstrated significant inhibition effects, restraining over 80% of growth and killed over 99% of Pseudomonas tolaasii (P. tolaasii). This inhibition effect occurred in a concentration-dependent manner. The in vivo findings revealed that treatment with 150 mg L-1 ε-PL effectively inhibited P. tolaasii-caused brown blotch disease in Agaricus bisporus (A. bisporus) mushrooms. Plausible mechanisms underlying ε-PL's action against P. tolaasii in A. bisporus involve: (i) damaging the cell morphology and membrane integrity, and increasing uptake of propidium iodide and leakage of cellular components of P. tolaasii; (ii) interaction with intracellular proteins and DNA of P. tolaasii; (iii) inhibition of P. tolaasii-induced activation of polyphenol oxidase, elevation of antioxidative enzyme activities, stimulation of phenylpropanoid biosynthetic enzyme activities and metabolite production, and augmentation of pathogenesis-related protein contents in A. bisporus mushrooms. These findings suggest promising prospects for the application of ε-PL in controlling bacterial brown blotch disease in A. bisporus.
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Agaricus , Polilisina , Pseudomonas , Polilisina/farmacología , Resistencia a la EnfermedadRESUMEN
The most critical aspect of panorama generation is maintaining local semantic consistency. Objects may be projected from different depths in the captured image. When warping the image to a unified canvas, pixels at the semantic boundaries of the different views are significantly misaligned. We propose two lightweight strategies to address this challenge efficiently. First, the original image is segmented as superpixels rather than regular grids to preserve the structure of each cell. We propose effective cost functions to generate the warp matrix for each superpixel. The warp matrix varies progressively for smooth projection, which contributes to a more faithful reconstruction of object structures. Second, to deal with artifacts introduced by stitching, we use a seam line method tailored to superpixels. The algorithm takes into account the feature similarity of neighborhood superpixels, including color difference, structure and entropy. We also consider the semantic information to avoid semantic misalignment. The optimal solution constrained by the cost functions is obtained under a graph model. The resulting stitched images exhibit improved naturalness. Extensive testing on common panorama stitching datasets is performed on the algorithm. Experimental results show that the proposed algorithm effectively mitigates artifacts, preserves the completeness of semantics and produces panoramic images with a subjective quality that is superior to that of alternative methods.
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Taking the AquaCrop crop model as the research object, considering the complexity and uncertainty of the crop growth process, the crop model can only achieve more accurate simulation on a single point scale. In order to improve the application scale of the crop model, this study inverted the canopy coverage of a tea garden based on UAV multispectral technology, adopted the particle swarm optimization algorithm to assimilate the canopy coverage and crop model, constructed the AquaCrop-PSO assimilation model, and compared the canopy coverage and yield simulation results with the localized model simulation results. It is found that there is a significant regression relationship between all vegetation indices and canopy coverage. Among the single vegetation index regression models, the logarithmic model constructed by OSAVI has the highest inversion accuracy, with an R2 of 0.855 and RMSE of 5.75. The tea yield was simulated by the AquaCrop-PSO model and the measured values of R2 and RMSE were 0.927 and 0.12, respectively. The canopy coverage R2 of each simulated growth period basically exceeded 0.9, and the accuracy of the simulation results was improved by about 19.8% compared with that of the localized model. The results show that the accuracy of crop model simulation can be improved effectively by retrieving crop parameters and assimilating crop models through UAV remote sensing.
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Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS (eICSS), an electrode is surgically implanted into the medial forebrain bundle (MFB) in the lateral hypothalamus or the ventral tegmental area (VTA) in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the eICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of eICSS is the lack of cellular selectivity in understanding the neural substrates underlying this behavior. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models-dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable stimulation frequency-lever response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in oICSS have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel behavioral model in preclinical medication development for treating substance use disorders.
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Roedores , Autoestimulación , Animales , Recompensa , Mesencéfalo , Haz Prosencefálico Medial , Estimulación EléctricaRESUMEN
Heart failure (HF) is a clinical syndrome caused by the progression of various cardiac diseases to severe stages, and exercise training plays a positive role in the development of HF. This study aimed to investigate the impact of different intensities of exercise training on HF rats.In this study, we established two HF rat models by intraperitoneal injection of isoproterenol at 2.5 mg/kg/day and abdominal aortic coarctation. After exercise training for 4 weeks, the heart weight/body weight ratio and echocardiography results were measured. Moreover, the regulatory effect of different exercise intensities on myocardial function in HF model rats was verified using tissue staining, western blotting, and reagent kits.Exercise training had a bidirectional adjust effect on HF. A running training program of 20 minutes/time had the most significant effect on improving myocardial function in HF rats, whereas exercise intensity of 40 minutes/time or 50 minutes/time did not significantly improve myocardial function in HF rats. Moreover, exercise intensities of 20 minutes/time and 30 minutes/time could reduce the expression levels of the HF markers NT-proBNP and BNP in rats, but the effect was more significant at a duration of 20 minutes/time. We also found that compared with other exercise intensities, 20 minutes/time exercise intensity could significantly improve myocardial fibrosis, promote cardiomyocyte autophagy, and reduce apoptosis in combating HF.Furthermore, an exercise intensity of 20 minutes/time can significantly ameliorate the progression of HF. However, the degree of significance of increasing exercise intensity in improving HF progression is weakened or has no significant effect.
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Modelos Animales de Enfermedad , Insuficiencia Cardíaca , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Animales , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Ratas , Condicionamiento Físico Animal/fisiología , Masculino , Apoptosis , Péptido Natriurético Encefálico/metabolismo , Péptido Natriurético Encefálico/sangre , Ecocardiografía , Miocitos Cardíacos/metabolismo , Isoproterenol/farmacología , Miocardio/metabolismo , Miocardio/patología , Autofagia/fisiologíaRESUMEN
BACKGROUND: Numerous observational studies have suggested a correlation between sarcopenia and depression, but the nature of this relationship requires further investigation. METHODS: This study employed bidirectional Mendelian randomization to explore this connection. Data from genome-wide association studies were used, encompassing measures of sarcopenia and mental factors, including depression and emotional states. The initial analysis concentrated on the impact of depression on sarcopenia, and then it examined the reverse relationship. The same methodology was applied to emotional data for validation. RESULTS: The results indicated a reciprocal causation between sarcopenia and depression, even when emotional state data were considered. Various emotions can impact sarcopenia, and in turn, sarcopenia can affect emotions, except subjective well-being. These findings highlight a cyclic deterioration between sarcopenia and depression, with a link to negative emotions and a partially ameliorative effect of subjective well-being on sarcopenia. CONCLUSIONS: In summary, this study sheds light on the interplay between psychiatric factors and sarcopenia, offering insights into intervention and prevention strategies.
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Depresión , Análisis de la Aleatorización Mendeliana , Sarcopenia , Humanos , Sarcopenia/genética , Depresión/genética , Depresión/epidemiología , Estudio de Asociación del Genoma Completo , CausalidadRESUMEN
A robot screwing skill learning framework based on teaching-learning is proposed to improve the generalization ability of robots for different scenarios and objects, combined with the experience of a human operation. This framework includes task-based teaching, learning, and summarization. We teach a robot to twist and gather the operation's trajectories, define the obstacles with potential functions, and counter the twisting of the robot using a skill-learning-based dynamic movement primitive (DMP) and Gaussian mixture model-Gaussian mixture regression (GMM-GMR). The hole-finding and screwing stages of the process are modeled. In order to verify the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios, obstacle avoidance trends and tightening experiments were conducted. Obstacle avoidance and tightening experiments were conducted on the robot tightening platform for bolts, plastic bottle caps, and faucets. The robot successfully avoided obstacles and completed the twisting task, verifying the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios.
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The high-altitude imaging capabilities of Unmanned Aerial Vehicles (UAVs) offer an effective solution for maritime Search and Rescue (SAR) operations. In such missions, the accurate identification of boats, personnel, and objects within images is crucial. While object detection models trained on general image datasets can be directly applied to these tasks, their effectiveness is limited due to the unique challenges posed by the specific characteristics of maritime SAR scenarios. Addressing this challenge, our study leverages the large-scale benchmark dataset SeaDronesSee, specific to UAV-based maritime SAR, to analyze and explore the unique attributes of image data in this scenario. We identify the need for optimization in detecting specific categories of difficult-to-detect objects within this context. Building on this, an anchor box optimization strategy is proposed based on clustering analysis, aimed at enhancing the performance of the renowned two-stage object detection models in this specialized task. Experiments were conducted to validate the proposed anchor box optimization method and to explore the underlying reasons for its effectiveness. The experimental results show our optimization method achieved a 45.8% and a 10% increase in average precision over the default anchor box configurations of torchvision and the SeaDronesSee official sample code configuration respectively. This enhancement was particularly evident in the model's significantly improved ability to detect swimmers, floaters, and life jackets on boats within the SeaDronesSee dataset's SAR scenarios. The methods and findings of this study are anticipated to provide the UAV-based maritime SAR research community with valuable insights into data characteristics and model optimization, offering a meaningful reference for future research.
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Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.
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Introduction: Continuous cropping affected the stability of soil enzyme activity and the structural characteristics of microbial community. Owing to challenges in the study of complex rhizosphere microbial communities, the composition and function of these microbial communities in farmland ecosystems remain elusive. Here, we studied the microbial communities of the rhizosphere of wine grapes with different years of continuous cropping and investigated their relationships with soil enzyme activity. Methods: Metagenomic sequencing was conducted on the rhizosphere soils from one uncultivated wasteland and four vineyards with varying durations of continuous cropping. Results: The predominant microbial were bacteria (98.39%), followed by archaea (1.15%) and eukaryotes (0.45%). Continuous cropping caused a significant increase in the relative abundance of Rhizobiales and Micrococcales but a marked decrease in Solirubrobacterales. At the genus level, 75, 88, 65, 132, and 128 microbial genera were unique to uncultivated wasteland, 5, 10, 15, and 20 years of continuous cropping, respectively. The relative abundance of genes with signal transduction function was the highest. The activity of all enzymes measured in this study peaked at 5 years of continuous cropping, and then decreased with 10 to 15 year of continuous cropping, but increased at 20 years again. In addition, soil enzyme activity, especially of alkaline phosphatase was significantly correlated with the diversity of the dominant microorganisms at the genus level. Moreover, the coupled enzyme activities had a greater impact on the diversity of the microbial community than that of individual enzymes. Conclusion: Our findings reveal the composition and function of the soil microbial communities and enzymes activity in response to changes in cropping years, which has important implications for overcoming continuous cropping obstacles and optimizing land use.
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Objective. To enable the registration network to be trained only once, achieving fast regularization hyperparameter selection during the inference phase, and to improve registration accuracy and deformation field regularity.Approach. Hyperparameter tuning is an essential process for deep learning deformable image registration (DLDIR). Most DLDIR methods usually perform a large number of independent experiments to select the appropriate regularization hyperparameters, which are time-consuming and resource-consuming. To address this issue, we propose a novel dynamic hyperparameter block, which comprises a distributed mapping network, dynamic convolution, attention feature extraction layer, and instance normalization layer. The dynamic hyperparameter block encodes the input feature vectors and regularization hyperparameters into learnable feature variables and dynamic convolution parameters which changes the feature statistics of the high-dimensional features layer feature variables, respectively. In addition, the proposed method replaced the single-level structure residual blocks in LapIRN with a hierarchical multi-level architecture for the dynamic hyperparameter block in order to improve registration performance.Main results. On the OASIS dataset, the proposed method reduced the percentage of|JÏ|⩽0by 28.01%, 9.78%and improved Dice similarity coefficient by 1.17%, 1.17%, compared with LapIRN and CIR, respectively. On the DIR-Lab dataset, the proposed method reduced the percentage of|JÏ|⩽0by 10.00%, 5.70%and reduced target registration error by 10.84%, 10.05%, compared with LapIRN and CIR, respectively.Significance. The proposed method can fast achieve the corresponding registration deformation field for arbitrary hyperparameter value during the inference phase. Extensive experiments demonstrate that the proposed method reduces training time compared to DLDIR with fixed regularization hyperparameters while outperforming the state-of-the-art registration methods concerning registration accuracy and deformation smoothness on brain dataset OASIS and lung dataset DIR-Lab.