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Adeno-associated viruses (AAVs) have emerged as promising tools for gene therapy due to their safety and efficacy in delivering therapeutic genes or gene editing sequences to various tissues and organs. AAV serotype 9 (AAV9), among AAV serotypes, stands out for its ability to efficiently target multiple tissues, thus holding significant potential for clinical applications. However, existing methods for purifying AAVs are cumbersome, expensive, and often yield inconsistent results. In this study, we explore a novel purification strategy utilizing Dynabeads™ CaptureSelect™ magnetic beads. The AAV9 magnetic beads capture AAV9 with high specificity and recovery between 70 and 90%, whereas the AAVX magnetic beads did not bind to the AAV9. Through continuous interaction with AAVs in solution, these beads offer enhanced clearance of genomic DNA and plasmids even in the absence of endonuclease. The beads could be regenerated at least eight times, and the used beads could be stored for up to six months and reused without a significant reduction in recovery. The potency of the AAV9-purified vectors in vivo was comparable to that of iodixanol purified vectors.
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Dependovirus , Vectores Genéticos , Dependovirus/genética , Dependovirus/aislamiento & purificación , Humanos , Vectores Genéticos/genética , Animales , Células HEK293 , Ratones , Terapia Genética/métodosRESUMEN
Assessment and monitoring of the quality of the ecological environment in the area is a very important fundamental task in the development of ecological civilization in the Xiaojiang River Basin in Yunnan Province, which serves as a demonstration area for ecological restoration in the upper reaches of the Yangtze River. The Landsat remote sensing images from 1990, 1995, 2000, 2005, 2010, 2014, 2018, and 2022 were chosen, and the four indexes of greenness ï¼NDMVIï¼, humidity ï¼WETï¼, dryness ï¼NDBSIï¼, and heat ï¼LSTï¼ were extracted. The remote sensing ecological index ï¼RSEIï¼ was created using the principal component analysis method, then the spatial and temporal patterns and trends of ecological quality in the Xiaojiang River Basin between 1990 and 2022 were examined using the GEE platform, ArcGIS 10.7 platform, and Python platform, combining the analysis methods of geographic information mapping, coefficient of variation, Mann-Kendall trend test, Sen's slope estimation, and Hurst's index. The findings demonstrated thatï¼ â the ecological quality of the study area had more obvious geographic differentiation spatially, and by 2022, the areas with excellent and good ecological quality grades were primarily distributed in the areas with better alpine vegetation cover, and those with poor ecological quality were primarily distributed in the areas of the mudslide ravines with relatively low terrain. On a time scale, the study area's RSEI index increased from 0.41 in 1990 to 0.55 in 2022, with a fluctuating overall trend of ecological quality improvement and an average increase of 0.048ï¼10 aï¼ -1ï¼ this progress was directly related to a number of ecological construction initiatives that have been energetically carried out, such as converting farms to forests, preventing mudslides, saving soil and water, managing heavy metal contamination, etc. â¡ The RSEI was more appropriate for the evaluation of ecological quality in alpine ravine areas because, in comparison to the NDVI index, the NDVMI adopted in this study was more sensitive to vegetation information in topographic undulation areas, especially in shaded areas, and could more accurately and quantitatively describe the vegetation information. ⢠The RSEI in the Xiaojiang River Basin had a mean coefficient of variation of 0.202. Overall, its volatility was low, and its high volatility was mostly concentrated in the mudslide gully area along both sides of the Xiaojiang River fracture zone, where the surface was made up of bare rocks and sediment that was easily impacted by the changing of the seasons, the climate, and human activity. ⣠The quality of the ecological environment in the region was significantly improving, with the rising area reaching 85.72% of the total area and the declining area accounting for approximately 10.15% of the total area. The future trend of change will be dominated by ongoing improvement and future degradation, accounting for 44.75% and 39.97%, respectively. It is important to pay close attention to areas that could potentially degrade. The findings of this study can serve as a theoretical foundation for additional ecological environmental conservation, management, and sustainable development in the Xiaojiang River Basin.
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In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.
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Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Mediciones Luminiscentes , MicroARNs , Puntos Cuánticos , Resonancia por Plasmón de Superficie , MicroARNs/análisis , MicroARNs/sangre , Humanos , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , ADN/química , Puntos Cuánticos/química , Resonancia por Plasmón de Superficie/métodos , Mediciones Luminiscentes/métodos , Oro/química , Límite de Detección , Transferencia de Energía , Nanopartículas del Metal/químicaRESUMEN
Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.
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BACKGROUND: Sotn ureteroscopy is a new lithotripsy procedure developed on the basis of ureteroscopy and includes a rigid ureteral access sheath, standard mirror, lithotripsy mirror, and Sotn perfusion aspirator. Thus, we performed a prospective multicenter randomized controlled trial comparing the safety and efficacy of Sotn ureteroscopy in the treatment of renal and upper ureteral calculi. METHODS: In this study, 224 patients with renal and upper ureteral calculi were randomly divided equally into study and control groups from March 2018 to March 2022. All the patients were approved by the hospital ethics committee (proof number: ZF-2018-164-01 and ZF-2018-165-01) of the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and month after treatment and operation duration. The secondary outcome was postoperative complication rate. RESULTS: In total, for upper ureteral calculi, the SFR of 1 day after operation of the Sotn ureteroscopy group was significantly higher than the rigid ureteroscopy group (83.6% vs. 60%, P=0.006). Moreover, operative time (33.7±1.80 vs. 52.9±2.73 min, P<0.005) of the Sotn ureteroscopy group was significantly lower than the rigid ureteroscopy group. Additionally, the SFR of 1 day after operation and operative time for the study group (Sotn ureteroscopy combined with flexible ureteroscopy) and the control group (flexible ureteroscopy alone) were 63.2% and 36.8% (P=0.005), 65.6±4.06 and 80.3±4.91 (P=0.023), respectively. However, there were no significant differences in the SFR of 1 month after operation, success rate of ureteral access sheath placement, and postoperative complications between the two groups (P>0.05). In subgroups with stone diameters ≥1.5 cm and stone CT values ≥1000 Hounsfield units, Sotn ureteroscopy showed more advantages in terms of the SFR of 1 day after operation. Importantly, complications such as ureteral injury, sepsis, fever, and severe hematuria were not statistically different between the two groups (P>0.05). CONCLUSIONS: For renal and upper ureteral calculi, Sotn ureteroscopy has the advantage of a higher SFR of 1 day after the operation and a shorter operative time, suggesting that the Sotn ureteroscopy may have further potential applications in clinics.
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Cálculos Renales , Litotricia , Cálculos Ureterales , Ureteroscopía , Humanos , Ureteroscopía/métodos , Ureteroscopía/efectos adversos , Cálculos Ureterales/cirugía , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Cálculos Renales/cirugía , Cálculos Renales/diagnóstico por imagen , Resultado del Tratamiento , Adulto , Litotricia/métodos , Litotricia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
C4 NAD-malic enzyme (NAD-ME) species occurs in drier regions and exhibit different drought responses compared to C4 NADP-malic enzyme (NADP-ME) species. However, a physiological mechanism explaining the geographical discrepancies remains uncertain. This study examined gas exchange patterns that might explain different distributions observed between two subtypes of C4 photosynthesis. We measured the response of leaf gas exchange to vapour pressure deficit (VPD) and CO2 in plants from six distinct C4 clades having closely related NAD-ME and NADP-ME species using a Li-Cor 6400 gas exchange system. We found that NAD-ME species exhibited greater relative reductions in stomatal conductance with increases in VPD than NADP-ME species but observed no consistent subtype differences in C4 cycle activity as indicated by the initial slope of the A response to intercellular CO2 concentration. Based on these results, we hypothesise the greater response of gs to increasing VPD may enable NAD-ME plants to outperform NADP-ME plants in hot, dry environments where VPD is normally high.
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Dióxido de Carbono , Malato Deshidrogenasa , Fotosíntesis , Estomas de Plantas , Presión de Vapor , Estomas de Plantas/fisiología , Dióxido de Carbono/metabolismo , Fotosíntesis/fisiología , Malato Deshidrogenasa/metabolismo , Malato-Deshidrogenasa (NADP+)/metabolismo , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismo , Transpiración de Plantas/fisiologíaRESUMEN
Soil salinity is an important limiting factor in agricultural production. Rhizospheric fungi can potentially enhance crop salinity tolerance, but the precise role of signaling substances is still to be systematically elucidated. A rhizospheric fungus identified as Paecilomyces vaniformisi was found to enhance the salinity tolerance of rice seedlings. In this study, a novel polysaccharide (PPL2b) was isolated from P. vaniformisi and identified as consisting of Manp, Glcp, GalpA, and Galp. In a further study, PPL2b showed significant activity in alleviating salinity stress-induced growth inhibition in rice seedlings. The results indicated that under salinity stress, PPL2b enhances seed germination, plant growth (height and biomass), and biochemical parameters (soluble sugar and protein contents). Additionally, PPL2b regulates genes such as SOS1 and SKOR to decrease K+ efflux and increase Na+ efflux. PPL2b increased the expression and activity of genes related to antioxidant enzymes and nonenzyme substances in salinity-induced oxidative stress. Further study indicated that PPL2b plays a crucial role in regulating osmotic substances, such as proline and betaine, in maintaining the osmotic balance. It also modulates plant hormones to promote rice seedling growth and enhance their tolerance to soil salinity. The variables interacted and were divided into two groups (PC1 77.39% and PC2 18.77%) based on their relative values. Therefore, these findings indicate that PPL2b from P. vaniformisi can alleviate the inhibitory effects of salinity stress on root development, osmotic adjustment, ion balance, oxidative stress balance, and growth of rice seedlings. Furthermore, it suggests that polysaccharides produced by rhizospheric fungi could be utilized to enhance crop tolerance to salinity.
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Oryza , Paecilomyces , Plantones , Oryza/metabolismo , Salinidad , Polisacáridos/metabolismo , Suelo/química , Estrés FisiológicoRESUMEN
BACKGROUND: Conflicting results regarding the impact of selenium on reducing prostate cancer have been reported. The current analysis aimed to understand whether there are potential factors affecting the relationship between selenium and prostate cancer. OBJECTIVE: To clarify the relationship between dietary selenium intake and prostate cancer, we evaluated the correlation between dietary selenium intake and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: After screening the NHANES survey data from 2005 to 2010, data for 3,614 of 31,034 participants were considered suitable to include in our study. Dietary selenium intake was the independent variable of our study, while PSA was the dependent variable. We stratified participants into current, former, and never smokers and performed an interaction test on the relationship between selenium intake and PSA using multivariable logistic regression for each smoking-status subgroup. RESULTS: For our subgroup analysis, we grouped participants based on smoking status and investigated the association between dietary selenium intake and PSA levels. Among the 242 participants with a PSA level of 4 or higher, the mean age was 58.5 years (±12.1). After adjusting for covariates, we did not find a significant association between dietary selenium and the odds of having a high PSA level. However, we observed a significant interaction between smoking status and dietary selenium in relation to PSA levels (Pâ¯=â¯.007). Specifically, smokers had lower odds of having high PSA levels, while nonsmokers had higher odds. This suggests that smoking status may modify the effect of dietary selenium on PSA levels. CONCLUSION: Our findings suggest that smoking status affects the relationship between dietary selenium intake and PSA and that smokers are at lower odds of having a high PSA level.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Selenio , Fumar , Humanos , Masculino , Persona de Mediana Edad , Estudios Transversales , Encuestas Nutricionales , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/prevención & control , Fumar/epidemiologíaRESUMEN
OBJECTIVE: To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes. METHODS: From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears). CONCLUSION: Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.
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Lesiones del Manguito de los Rotadores , Masculino , Femenino , Humanos , Recién Nacido , Lactante , Preescolar , Niño , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/diagnóstico por imagen , Sensibilidad y Especificidad , Ultrasonografía , Imagen por Resonancia Magnética/métodos , Rotura , ArtroscopíaRESUMEN
Paratesticular liposarcoma (PLS) causes scrotal mass changes, rarely in the urinary system. Before surgery, PLS causes scrotal mass changes that are difficult to distinguish from other causes. There has been a report of a giant paratestis liposarcoma resection and refusal to undergo orchiectomy. A 65-year-old man presented with finding the left scrotal mass after 2 years. Physical examination showed that the left scrotal mass was obviously difficult to retract. Pelvic CT showed that the left scrotal mass and flaky fat density shadow accompanied with left inguinal hernia. During surgery, laparoscopic exploration was performed to rule out inguinal hernia, and a scrotal exploration was also performed concurrently. The intraoperative frozen pathology considered lipogenic tumor, and the patient's wife refused to undergo simultaneous left radical orchiectomy. Later the mass was completely removed, and postoperative pathology confirmed paratestis liposarcoma. During a 15-month routine follow-up, the tumor did not recur locally or metastasize distantly. PLS should be focused on early diagnosis and treatment, preoperative examinations and postoperative pathology should be combined, and highly personalized treatment will be implemented.
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Background: Depressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery. Methods: In this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality. Main results: A total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = -10.5, 95%CI = -19.6% to -0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = -10.8, 95%CI = -20.2% to -0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001). Conclusion: Perioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).
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Toxic substances in the environment disturb the adsorption of pollutants in plants but little is known about the underlying mechanisms of these processes. This study evaluated the PAH adsorption by Phragmites australis under NAs stress. Results showed that Naphthenic acids (NAs) significantly decreased the adsorption of PAHs and had higher selectivity for type and structure. P. australis root cell growth and mitosis were significantly affected by NAs, which was accompanied by serious disturbances in mitochondrial function. The physiological evaluation showed the NAs could increase Reactive Oxygen Species (ROS) accumulation by around 16-fold and cause damage to the root cell normal redox equilibrium. The levels of three key related antioxidants, PLA, CAT and POD, decreased significantly to 35-50% under NAs stress and were dependent upon NAs concentration. Furthermore, NAs could significantly change the concentration and species of root exudates of P. ausralis. Autotoxic substances, including alcohol and amines, increased by 28.63% and 23.96, respectively. Sixteen compounds were identified and assumed as potential biomarkers. Galactonic, glyceric, and octadecanoic acid had the general effect of activating PAH in soil. The global view of the metabolic pathway suggests that NAs influenced the citric acid cycle, fatty acid synthesis, amino acid metabolism and the phenylpropanoid pathway. Detection data results indicated that the energy products cause hypoxia and oxidative stress, which are the main processes under the NAs. Furthermore, verification of these processes was fulfilled through gene expression and biomarkers quantification. Our results provide novel metabolic insights into the mechanisms of PAHs adsorption by P. australis under NAs disturbance, suggesting that monitoring NAs in phytoremediation applications is necessary.
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Hidrocarburos Policíclicos Aromáticos , Adsorción , Poaceae/metabolismo , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/metabolismoRESUMEN
As one of the best means of obtaining the geometry information of special shaped structures, point cloud data acquisition can be achieved by laser scanning or photogrammetry. However, there are some differences in the quantity, quality, and information type of point clouds obtained by different methods when collecting point clouds of the same structure, due to differences in sensor mechanisms and collection paths. Thus, this study aimed to combine the complementary advantages of multi-source point cloud data and provide the high-quality basic data required for structure measurement and modeling. Specifically, low-altitude photogrammetry technologies such as hand-held laser scanners (HLS), terrestrial laser scanners (TLS), and unmanned aerial systems (UAS) were adopted to collect point cloud data of the same special-shaped structure in different paths. The advantages and disadvantages of different point cloud acquisition methods of special-shaped structures were analyzed from the perspective of the point cloud acquisition mechanism of different sensors, point cloud data integrity, and single-point geometric characteristics of the point cloud. Additionally, a point cloud void repair technology based on the TLS point cloud was proposed according to the analysis results. Under the premise of unifying the spatial position relationship of the three point clouds, the M3C2 distance algorithm was performed to extract the point clouds with significant spatial position differences in the same area of the structure from the three point clouds. Meanwhile, the single-point geometric feature differences of the multi-source point cloud in the area with the same neighborhood radius was calculated. With the kernel density distribution of the feature difference, the feature points filtered from the HLS point cloud and the TLS point cloud were fused to enrich the number of feature points in the TLS point cloud. In addition, the TLS point cloud voids were located by raster projection, and the point clouds within the void range were extracted, or the closest points were retrieved from the other two heterologous point clouds, to repair the top surface and façade voids of the TLS point cloud. Finally, high-quality basic point cloud data of the special-shaped structure were generated.
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BACKGROUND: Sinisan (SNS) consists of four kinds of herbs, which is the core of antidepressant prescription widely used in traditional Chinese medicine clinic treatment for depression induced by early life stress. However, the role and precise mechanism of SNS antidepressant have not yet been elucidated. PURPOSE: This study aimed to investigate the mechanism SNS on antidepressant of regulating mitochondrial function to improve hippocampal synaptic plasticity. METHODS: 90 Sprague-Dawley (SD) rats male pups on Post-Natal Day (PND) 0 were randomly divided into Control group (ddH20), Model group (ddH20), Fluoxetine group (5.0â¯mg/kg fluoxetine), and SNS-L group (2.5â¯g/kg SNS), SNS-M group (5.0â¯g/kg SNS) and SNS-H group (10.0â¯g/kg SNS), 15 animals per group. Maternal separation (MS) from PND1 to PND21, drug intervention from PND60 to PND90, and behavior tests including sucrose preference test, open field test and forced swimming test from PND83 to PND90 were performed. Synaptic structure and mitochondrial structure were observed by TEM. The expression levels of PSD-95 and SYN were detected by immunohistochemistry and western blot test, the adenosine triphosphate (ATP) content in the hippocampus was detected by assay kits, and the expression levels of Mfn2, Drp1 and Fis1 protein were detected by western bolt test. RESULTS: SNS can alleviate depression-like and anxiety-like behaviors in MS rats, improve the damage of synapses and mitochondria, reduce the decrease of ATP in hippocampus, and reverse the expression levels of PSD-95, SYN, Mfn2, Drp1, and Fis1 proteins. CONCLUSION: SNS reduced the risk of early life stress induced depression disorder via regulating mitochondrial function and synaptic plasticity. Targeting mitochondrial may be a novel prospective therapeutic avenue for antidepressant.
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Fluoxetina , Privación Materna , Adenosina Trifosfato/metabolismo , Animales , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos , Fluoxetina/farmacología , Hipocampo , Masculino , Mitocondrias , Plasticidad Neuronal , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Sacarosa/metabolismoRESUMEN
This work aimed to detect the vegetation coverage and evaluate the benefits of afforestation and ecological protection. Unmanned aerial vehicle (UAV) aerial survey was adopted to obtain the images of tailings area at Ma'anshan near the Dianchi Lake estuary, so as to construct a high-resolution Digital Orthophoto Map (DOM) and high-density Dense Image Matching (DIM) point cloud. Firstly, the optimal scale was selected for segmentation by considering the terrain. Secondly, the visible-band difference vegetation index (VDVI) of the classified vegetation information of the tail mining area was determined from the index gray histogram, ground class error analysis, and the qualitative and quantitative analysis of the bimodal index. Then, the vegetation information was extracted by combining the random forest (RF) classification algorithm. Finally, the extracted two-dimensional (2D) vegetation information was mapped to the three-dimensional (3D) point cloud, and the redundant data was eliminated. Fractional vegetation cover (FVC) was counted in the way of surface to point and human-machine combination. The experimental results showed that the vegetation information extracted from the 2D image was mapped to the 3D point cloud in the form of surface to point, and the redundant bare ground information was eliminated. The statistical FVC was 36.06%. The field survey suggested that the vegetation information in the turf dam area adjacent to the open phosphate deposit accumulation area research area was sparse. Relevant measures should be taken in the subsequent mining to avoid ecological damage caused by expanded phosphate mining. In general, applying UAV measurement technology and related 2D and 3D products to detect the vegetation coverage in an open phosphate mine area was of practical significance and unique technical advantages.
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Lagos , Tecnología de Sensores Remotos , Humanos , Minería , FosfatosRESUMEN
Although artesunate has been reported to be a promising candidate for colorectal cancer (CRC) treatment, the underlying mechanisms and molecular targets of artesunate are yet to be explored. Here, we report that artesunate acts as a senescence and autophagy inducer to exert its inhibitory effect on CRC in a reactive oxygen species (ROS)-dependent manner. In SW480 and HCT116 cells, artesunate treatment led to mitochondrial dysfunction, drastically promoted mitochondrial ROS generation, and consequently inhibited cell proliferation by causing cell cycle arrest at G0/G1 phase as well as subsequent p16- and p21-mediated cell senescence. Senescent cells underwent endoplasmic reticulum stress (ERS), and the unfolded protein response (UPR) was activated via IRE1α signaling, with upregulated BIP, IRE1α, phosphorylated IRE1α (p-IRE1α), CHOP, and DR5. Further experiments revealed that autophagy was induced by artesunate treatment due to oxidative stress and ER stress. In contrast, N-Acetylcysteine (NAC, an ROS scavenger) and 3-Methyladenine (3-MA, an autophagy inhibitor) restored cell viability and attenuated autophagy in artesunate-treated cells. Furthermore, cellular free Ca2+ levels were increased and could be repressed by NAC, 3-MA, and GSK2350168 (an IRE1α inhibitor). In vivo, artesunate administration reduced the growth of CT26 cell-derived tumors in BALB/c mice. Ki67 and cyclin D1 expression was downregulated in tumor tissue, while p16, p21, p-IRE1α, and LC3B expression was upregulated. Taken together, artesunate induces senescence and autophagy to inhibit cell proliferation in colorectal cancer by promoting excessive ROS generation.
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Neoplasias Colorrectales , Endorribonucleasas , Animales , Apoptosis , Artesunato/farmacología , Autofagia , Línea Celular Tumoral , Proliferación Celular , Senescencia Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Ratones , Proteínas Serina-Treonina Quinasas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Landslide susceptibility maps (LSM) are often used by government departments to carry out land use management and planning, which supports decision makers in urban and infrastructure planning. The accuracy of conventional landslide susceptibility maps is often affected by classification errors. Consequently, they become less reliable, which makes it difficult to meet the needs of decision-makers. Therefore, it is proposed in this paper to reduce classification errors and improve LSM reliability by integrating the Small Baseline Subsets-Interferometric Synthetic Aperture Radar (SBAS-InSAR) technique and LSM. By using the logistic regression model (LR) and the support vector machine model (SVM), experiments were conducted to generate LSM in the Dongchuan district. It was classified into five classes: very high susceptibility, high susceptibility, medium susceptibility, low susceptibility, and very low susceptibility. Then, the surface deformation rate of the Dongchuan area was obtained through the ascending and descending orbit sentinel-1A data from January 2018 to January 2021. To correct the classification errors, the SBAS-InSAR technique was integrated into LSM under the optimal model by constructing the contingency matrix. Finally, the LSMs obtained before and after correction were compared. Moreover, the correction results were validated and analyzed by combining remote sensing images, InSAR deformation results, and field surveys. According to the research results, the susceptibility class of 66,094 classification error cells (59.48 km2) was significantly improved in the LSM after the integration of the SBAS-InSAR correction. The enhanced susceptibility classes and the spectral characteristics of remote sensing images are highly consistent with the trends of InSAR cumulative deformation and the results of field investigation. It is suggested that integrating SBAS-InSAR and LSM is effective in correcting classification errors and further improving the reliability of LSM for landslide prediction. The LSM obtained by using this method plays an important role in guiding local government departments on disaster prevention and mitigation, which is conducive to eliminating the risk of landslides.
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Deslizamientos de Tierra , China , Deslizamientos de Tierra/prevención & control , Radar , Reproducibilidad de los Resultados , Máquina de Vectores de SoporteRESUMEN
PURPOSE: To investigated the association between serum total testosterone and Gleason score upgrading of low-risk prostate cancer after radical prostatectomy (RP). MATERIALS AND METHODS: Medline, Web of Science, Embase, and Cochrane Library databases were searched to identify eligible studies published before October 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random or fixed effects models. RESULTS: Five studies comprising 1,203 low-risk prostate cancer patients were included. The results showed that low serum total testosterone (<300 ng/dL) is associated with a high rate of Gleason score upgrading after RP (OR, 2.3; 95% CI, 1.38-3.83; p<0.001; I², 92.2%). Notably, sensitivity and meta-regression analyses further strengthen the reliability of our results. CONCLUSIONS: Our results support the idea that low serum total testosterone is associated with a high rate of Gleason score upgrading in prostate cancer patients after RP. It is beneficial for urologist to ensure close monitoring of prostate-specific antigen levels and imaging examination when choosing non-RP treatment for low-risk prostate cancer patients.
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Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Clasificación del Tumor , Próstata , Antígeno Prostático Específico , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Reproducibilidad de los Resultados , Estudios Retrospectivos , TestosteronaRESUMEN
The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 1010 vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased. There was a significant but limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. All the major organs increased in weight except the brain. Our study is the first to use gene therapy to treat GH-receptor deficiency. We propose that gene therapy with AAV-GHR may eventually be useful for the treatment of human LS.
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Hormona del Crecimiento , Síndrome de Laron , Animales , Modelos Animales de Enfermedad , Terapia Genética , Hormona del Crecimiento/genética , Hormona del Crecimiento/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Síndrome de Laron/tratamiento farmacológico , Síndrome de Laron/terapia , Ratones , Receptores de Somatotropina/genética , Receptores de Somatotropina/metabolismo , Receptores de Somatotropina/uso terapéuticoRESUMEN
Unmanned Aerial Vehicles (UAVs) are a novel technology for landform investigations, monitoring, as well as evolution analyses of long-term repeated observation. However, impacted by the sophisticated topographic environment, fluctuating terrain and incomplete field observations, significant differences have been found between 3D measurement accuracy and the Digital Surface Model (DSM). In this study, the DJI Phantom 4 RTK UAV was adopted to capture images of complex pit-rim landforms with significant elevation undulations. A repeated observation data acquisition scheme was proposed for a small amount of oblique-view imaging, while an ortho-view observation was conducted. Subsequently, the 3D scenes and DSMs were formed by employing Structure from Motion (SfM) and Multi-View Stereo (MVS) algorithms. Moreover, a comparison and 3D measurement accuracy analysis were conducted based on the internal and external precision by exploiting checkpoint and DSM of Difference (DoD) error analysis methods. As indicated by the results, the 3D scene plane for two imaging types could reach an accuracy of centimeters, whereas the elevation accuracy of the orthophoto dataset alone could only reach the decimeters (0.3049 m). However, only 6.30% of the total image number of oblique images was required to improve the elevation accuracy by one order of magnitude (0.0942 m). (2) An insignificant variation in internal accuracy was reported in oblique imaging-assisted datasets. In particular, SfM-MVS technology exhibited high reproducibility for repeated observations. By changing the number and position of oblique images, the external precision was able to increase effectively, the elevation error distribution was improved to become more concentrated and stable. Accordingly, a repeated observation method only including a few oblique images has been proposed and demonstrated in this study, which could optimize the elevation and improve the accuracy. The research results could provide practical and effective technology reference strategies for geomorphological surveys and repeated observation analyses in sophisticated mountain environments.