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Objective: Evidence shows that allergic rhinitis (AR) may increase the risk of erectile dysfunction (ED). This study aims to investigate whether there is a causal relationship between AAR and ED by Mendelian randomization (MR) analysis. Methods: We performed a two-sample MR analysis using genome-wide association studies (GWAS) summary data. Single nucleotide polymorphisms (SNPs) associated with AR and ED were obtained from the GWAS database. The MR analysis primarily employed the inverse variance weighted (IVW), MR Egger, and weighted median (WM) methods. We assessed pleiotropy using the MR-PRESSO global test and MR-Egger regression. Cochran's Q test was used to evaluate heterogeneity, and a leave-one-out analysis was performed to verify the robustness and reliability of the results. Results: The IVW analysis demonstrated a positive association between genetic susceptibility to AR and an elevated relative risk of ED (IVW OR = 1.40, p = 0.01, 95% CI 1.08-1.80). The results obtained from MR-Egger regression and WM methods exhibited a consistent trend with the results of the IVW method. Sensitivity analyses showed no evidence of heterogeneity nor horizontal pleiotropy. The leave-one-out analysis showed that the findings remained robust and were unaffected by any instrumental variables. Conclusion: This study presents genetic evidence that indicates a causal association between AR and ED.
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Background: Patients with carotid atherosclerotic stenosis (CAS) often have varying degrees of cognitive decline. However, there is little evidence regarding how brain morphological and functional abnormalities impact the cognitive decline in CAS patients. This study aimed to determine how the brain morphological and functional changes affected the cognitive decline in patients with CAS. Methods: The brain morphological differences were analyzed using surface and voxel-based morphometry, and the seed-based whole-brain functional connectivity (FC) abnormalities were analyzed using resting-state functional magnetic resonance imaging. Further, mediation analyses were performed to determine whether and how morphological and FC changes affect cognition in CAS patients. Results: The CAS-MCI (CAS patients with mild cognitive impairment) group performed worse in working memory, verbal fluency, and executive time. Cortical thickness (CT) of the left postcentral and superiorparietal were significantly reduced in CAS-MCI patients. The gray matter volume (GMV) of the right olfactory, left temporal pole (superior temporal gyrus) (TPOsup.L), left middle temporal gyrus (MTG.L), and left insula (INS.L) were decreased in the CAS-MCI group. Besides, decreased seed-based FC between TPOsup.L and left precuneus, between MTG.L and TPOsup.L, and between INS.L and MTG.L, left middle frontal gyrus, as well as Superior frontal gyrus, were found in CAS-MCI patients. Mediation analyses demonstrated that morphological and functional abnormalities fully mediated the association between the maximum degree of carotid stenosis and cognitive function. Conclusion: Multiple brain regions have decreased GMV and CT in CAS-MCI patients, along with disrupted seed-based FC. These morphological and functional changes play a crucial role in the cognitive impairment in CAS patients.
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Combining the urea oxidation reaction (UOR) with the hydrogen evolution reaction (HER) is an effective technology for energy-saving hydrogen production. Herein, a bifunctional electrocatalyst with CoNiP nanosheet coating on P-doped MoO2 nanorods (P-MoO2@CoNiP) is obtained via a two-step hydrothermal followed a phosphorization process. The catalyst demonstrates exceptional alkaline HER performance due to the formation of MoO2 and the dissolution/absorption of Mo. Meanwhile, the inclusion of Co and P in the P-MoO2@CoNiP catalyst facilitated the formation of NiOOH, enhancing UOR performance. Density functional theory calculations reveal that the hydrogen adsorption Gibbs free energy (ΔGH*) of P-MoO2@CoNiP is closer to 0 eV than CoNiP, favoring the HER. The catalyst only needs -0.08 and 1.38 V to reach 100 mA cm-2 for catalyzing the HER and UOR, respectively. The full urea electrolysis system driven by P-MoO2@CoNiP requires 1.51 V to achieve 100 mA cm-2, 120 mV lower than the traditional water electrolysis.
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Exoristobia philippinensis (Hymenoptera: Encyrtidae) is a worldwide parasitic wasp. This work presents the mitochondrial genome (mitogenome) of E. philippinensis for the first time. The complete mitochondrial genome of E. philippinensis was sequenced and annotated, which was 15,751 bp in length, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). All 13 PCGs were initiated by the ATN (ATG, ATT, and ATA) codon, terminated with the stop codon TAA except for ND1 which ends with TAG. Phylogenetic analysis showed that E. philippinensis has a sister relationship with the genus Lamennaisia.
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Myocardial ischemia-reperfusion injury (MIRI) represents a critical pathology in acute myocardial infarction (AMI), which is characterized by high mortality and morbidity. Cardiac microvascular dysfunction contributes to MIRI, potentially culminating in heart failure (HF). Pigment epithelium-derived factor (PEDF), which belongs to the non-inhibitory serpin family, exhibits several physiological effects, including anti-angiogenesis, anti-inflammatory and antioxidant properties. Our study aims to explore the impact of PEDF and its functional peptide 34-mer on both cardiac microvascular perfusion in MIRI rats and human cardiac microvascular endothelial cells (HCMECs) injury under hypoxia reoxygenation (HR). It has been shown that MIRI is accompanied by ferroptosis in HCMECs. Furthermore, we investigated the effect of PEDF and its 34-mer, particularly regarding the Nrf2/HO-1 signalling pathway. Our results demonstrated that PEDF 34-mer significantly ameliorated cardiac microvascular dysfunction following MIRI. Additionally, they exhibited a notable suppression of ferroptosis in HCMECs, and these effects were mediated through activation of Nrf2/HO-1 signalling. These findings highlight the therapeutic potential of PEDF and 34-mer in alleviating microvascular dysfunction and MIRI. By enhancing cardiac microvascular perfusion and mitigating endothelial ferroptosis, PEDF and its derivative peptide represent promising candidates for the treatment of AMI.
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Células Endoteliales , Proteínas del Ojo , Ferroptosis , Daño por Reperfusión Miocárdica , Factor 2 Relacionado con NF-E2 , Factores de Crecimiento Nervioso , Serpinas , Transducción de Señal , Serpinas/farmacología , Serpinas/metabolismo , Factores de Crecimiento Nervioso/farmacología , Factores de Crecimiento Nervioso/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Ferroptosis/efectos de los fármacos , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Proteínas del Ojo/metabolismo , Proteínas del Ojo/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Hemo-Oxigenasa 1/metabolismo , Masculino , Ratas Sprague-Dawley , Microvasos/efectos de los fármacos , Microvasos/metabolismo , Microvasos/patología , Péptidos/farmacologíaRESUMEN
There is always a doubt that introducing water during oxide growing has a positive or negative effect on the properties of oxide films and devices. Herein, a comparison experiment on the condition of keeping the same oxygen atom flux in the sputtering chamber is designed to examine the influences of H2O on In-Sn-Zn-O (ITZO) films and their transistors. In comparison to no-water films, numerous unstable hydrogen-related defects are induced on with-water films at the as-deposited state. Paradoxically, this induction triggers an ordered enhancement in the microstructure of the films during conventional annealing, characterized by a reduction in H-related and vacancy (Vo) defects as well as an increase in film packing density and the M-O network ordering. Ultimately, the no-water thin-film transistors (TFTs) exhibit nonswitching behavior, whereas 5 sccm-water TFT demonstrates excellent electrical performance with a remarkable saturation field-effect mobility (µFE) of 122.10 ± 5.00 cm2·V-1·s-1, a low threshold (Vth) of -2.30 ± 0.40 V, a steep sub-threshold swing (SS) of 0.18 V·dec-1, a high output current (Ion) of 1420 µA, and a small threshold voltage shift ΔVth of -0.77 V in the negative bias stability test (3600 s).
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Stability of integrated fixed-film indigenous microalgal-bacterial consortium (IF-IMBC) requires further investigation. This study focused on the influence of short-term stagnation (STS), caused by influent variations or equipment maintenance, on IF-IMBC. Results showed that the IF-IMBC system experienced initial inhibition followed by subsequent recovery during STS treatment. Enhanced organics utilization was believed to contribute to system recovery. It is proposed that the attached IMBC possessed greater stress resistance. On the one hand, a higher increase in bacteria potentially participating in organic degradation was observed. Moreover, the dominant eukaryotic species significantly decreased in suspended IMBC while its abundance remained stable in the attached state. On the other hand, increased abundance for most functional enzymes was primarily observed in the attached bacteria. This fundamental research aims to bridge the knowledge gap regarding the response of IMBC to variations in operational conditions.
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Bacterias , Microalgas , Consorcios Microbianos , Bacterias/metabolismo , Consorcios Microbianos/fisiología , Estrés Fisiológico , Reactores BiológicosRESUMEN
Indigenous microalgae-bacteria consortium (IMBC) offers significant advantages for swine wastewater (SW) treatment including enhanced adaptability and resource recovery. In this review, the approaches for enriching IMBC both in situ and ex situ were comprehensively described, followed by symbiotic mechanisms for IMBC which involve metabolic cross-feeding and signal transmission. Strategies for enhancing treatment efficiencies of SW-originated IMBC were then introduced, including improving SW quality, optimizing system operating conditions, and adjusting microbial activities. Recommendations for maximizing treatment efficiencies were particularly proposed using a decision tree approach. Moreover, removal/recovery mechanisms for typical pollutants in SW using IMBC were critically discussed. Ultimately, a technical route termed SW-IMBC-Crop-Pig was proposed, to achieve a closed-loop economy for pig farms by integrating SW treatment with crop cultivation. This review provides a deeper understanding of the mechanism and strategies for IMBC's resource recovery from SW.
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Microalgas , Aguas Residuales , Animales , Aguas Residuales/microbiología , Microalgas/metabolismo , Porcinos , Bacterias/metabolismo , Purificación del Agua/métodos , Eliminación de Residuos Líquidos/métodos , Consorcios Microbianos/fisiología , Biodegradación AmbientalRESUMEN
Multistage flexible heat pipe has been proved to offer advantage of large flexibility as well as low thermal resistance. However, the effects of structural parameters on the comprehensive performances of such multistage thermal control device are still unclear, particularly regarding their mechanical properties. In this paper, effect of structural parameters on the mechanical and thermal performances of bionic multistage heat pipe is investigated. Results show that the stiffness of polymer tubes primarily determines the flexibility of multistage flexible heat pipe. The heat pipe with 4 metal tubes in the adiabatic section can achieve relative large flexibility and maximum bending angle as well as the short start-up time. The bending rigidity of multistage flexible heat pipe increases from 97624.4 N mm2 to 293152.9 N mm2 when its metal ratio raises from 0 % to 80 %. The thermal resistance of multistage flexible heat pipe decreases more than 32.9 % compared to the traditional flexible heat pipe. When the flexible heat pipe remains straight, the heat transfer performance will slightly increase as the shell metal ratio increases. However, its thermal resistance will also have an additional increase when bending. These results can serve as a guide for the design of the multistage flexible thermal control device.
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Leguminous green manure (LGM) has a reputation for improving crop productivity. However, little is known about the beneficial interactions with straw on crop yield and nutrient (N, P, K) use efficiency. Herein, a 9-year field experiment (from 2015 to 2023) containing three treatments-(1) chemical fertilizer as the control (CK), (2) NPK + straw return (Straw) and (3) NPK + straw return with LGM (Straw + LGM)-was conducted to investigate whether the combined application of LGM and straw can increase productivity and nutrient use efficiency in the wheat-maize-sunflower diversified cropping rotation. The results showed that in the third rotation (2021-2023), Straw + LGM significantly increased wheat yield by 10.2% and maize yield by 19.9% compared to CK. The total equivalent yield under Straw + LGM was the highest (26.09 Mg ha-1), exceeding Straw and CK treatments by 2.7% and 12.3%, respectively. For each 2 Mg ha-1 increase in straw returned to the field, sunflower yield increased by 0.2 Mg ha-1, whereas for each 1 Mg ha-1 increase in LGM yield from the previous crop, sunflower yield increased by 0.45 Mg ha-1. Compared to CK, the co-application of LGM and straw increased the N use efficiency of maize in the first and third rotation cycle by 70.6% and 55.8%, respectively, and the P use efficiency by 147.8% in the third rotation cycle. Moreover, Straw treatment led to an increase of net income from wheat and sunflower by 14.5% and 44.6%, while Straw + LGM increased the net income from maize by 15.8% in the third rotation cycle. Combining leguminous green manure with a diversified cropping rotation has greater potential to improve nutrient use efficiency, crop productivity and net income, which can be recommended as a sustainable agronomic practice in the Hetao District, Northwest China.
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Nickel-molybdenum-boron (Ni-Mo-B)-based catalysts with biphasic interfaces are highly advantageous in bifunctional electrocatalytic activity in alkaline water-splitting. However, it remains an ongoing challenge to obtain porous Ni-Mo alloy substrates that provide stable adhesion to catalysts, ensuring the long-term performance of bifunctional self-supporting electrodes at a high current density. Herein, a porous Ni-Mo alloy substrate was effectively obtained by a cost-effective dealloying process on a commercial Ni-Mo alloy with high-energy crystal planes. Subsequently, the Mo2NiB2/Ni3B bifunctional catalyst was in situ synthesized on this substrate via boriding heat treatment, resulting in outstanding catalytic activity and stability. Density functional theory (DFT) calculations reveal that the abundant biphasic interfaces and surface-reconstructed sites of the Mo2NiB2/Ni3B catalyst can decrease the energy barriers for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. Thus, the designed self-supporting electrodes show bifunctional catalytic activity with overpotentials of 151 mV for HER and 260 mV for OER at a current density of 10 mA cm-2. Markedly, the assembled water electrolyzer can be driven up to 10 mA cm-2 at 1.64 V and maintain catalytic activity at a high current density of 1000 mA cm-2 for 100 h. The new strategy is expected to provide a low-cost scheme for designing self-supporting bifunctional electrodes with high activity and excellent stability and contribute to the development of hydrogen energy technology.
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In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.
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Angiotensina II , Células Estrelladas Hepáticas , Hipertensión Portal , Angiotensina II/farmacología , Angiotensina II/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Animales , Hipertensión Portal/metabolismo , Hipertensión Portal/patología , Ratones , Colágeno Tipo I/metabolismo , Actinas/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Masculino , Transducción de Señal , Ratones Endogámicos C57BL , Cadena alfa 1 del Colágeno Tipo I/metabolismo , Citoesqueleto de Actina/metabolismoRESUMEN
BACKGROUND: Lung cancer is the most common malignant tumor. In the present study, we identified a long non-coding RNA (lncRNA) AC100826.1 (simplify to Lnc1), which was highly expressed in non-small cell lung cancer (NSCLC) tissues compared with the paracancerous tissues. We also observed the critical role of Lnc1 in regulating the metastasis ability of NSCLC cells. METHODS: RNA sequencing was performed to detect differential expression levels of lncRNAs in NSCLC tissues and its paracancerous tissues. Effects of Lnc1 on cell proliferation, invasion, and migration were determined by CCK-8, transwell and scratch assays. The xenograft experiment confirmed the effect of Lnc1 on NSCLC cells proliferation and migration abilities in vivo. RT-qPCR and western blots were performed to determine the expression levels of mRNAs and proteins. RESULTS: The expression level of Lnc1 was related to multiple pathological results, knockdown of Lnc1 can inhibit the proliferation and metastasis abilities of NSCLC cells. silencing phospholipase C, ß1(PLCB1) can reverse the promoting effects of overexpression Lnc1 on NSCLC cells proliferation and migration abilities. In addition, the Rap1 signaling pathway was implicated in the regulation of Lnc1 in NSCLC metastasis. CONCLUSION: Our results suggest that Lnc1 regulated the metastatic ability of NSCLC cells through targeting the PLCB1/Rap1 signal pathway.
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Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Neoplasias Pulmonares , Fosfolipasa C beta , ARN Largo no Codificante , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , ARN Largo no Codificante/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones , Animales , Fosfolipasa C beta/metabolismo , Fosfolipasa C beta/genética , Movimiento Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular TumoralRESUMEN
OBJECTIVE: The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). METHODS: Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. CONCLUSIONS: This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.
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Aprendizaje Automático , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Anciano , Gastrectomía , Muñón Gástrico/patología , Curva ROC , Medición de Riesgo/métodos , AlgoritmosRESUMEN
Natural product evodiamine is a multitargeting antitumor lead compound. However, clinical development of evodiamine derivatives was hampered by poor water solubility and limited in vivo antitumor potency. Herein, a series of evodiamine-glucose conjugates were designed by additional targeting glucose transporter-1 (GLUT1). Compared with the lead compound, conjugate 8 exhibited obvious enhancement in water solubility and in vivo antitumor efficacy. Furthermore, the effect of GLUT1 targeting also led to lower cytotoxicity to normal cells. Antitumor mechanism studies manifested that conjugate 8 acted by Top1/Top2 dual inhibition, apoptosis induction, and G2/M cell cycle arrest, which selectively targeted tumor cells with a high expression level of GLUT1. Thus, evodiamine-glucose conjugates showed promising features as potential antitumor agents.
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Antineoplásicos , Apoptosis , Diseño de Fármacos , Glucosa , Quinazolinas , Quinazolinas/farmacología , Quinazolinas/química , Quinazolinas/síntesis química , Humanos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Glucosa/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Transportador de Glucosa de Tipo 1/antagonistas & inhibidores , Transportador de Glucosa de Tipo 1/metabolismo , Relación Estructura-Actividad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ratones Desnudos , Ratones Endogámicos BALB CRESUMEN
The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices. A portable transmitter was used to output the low-frequency magnetic field (<50 Hz), which remotely drives the synchronous rotation of a magnetic core integrated within the pellet-like implantable device, generating an internal rotating magnetic field to induce wireless electricity on the coupled coils of the device. The ULFMEF can achieve energy transfer across thick tissues (up to 20 cm) with excellent transferred power (4-15 mW) and non-heat effects in tissues, which is remarkably superior to existing wireless powering technologies. The ULFMEF is demonstrated to wirelessly power implantable micro-LED devices for optogenetic neuromodulation, and wirelessly charged an implantable battery for programmable electrical stimulation on the sciatic nerve. It also bypassed thick and tough protective shells to power the implanted devices. The ULFMEF thus offers a highly advanced methodology for the generation of wireless powered biodevices.
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Flight parameters are crucial criteria for UAV control, playing a significant role in ensuring the safe and efficient completion of missions. Launch force and airspeed information are key parameters in the early and middle stages of flight, serving as important data for monitoring the UAV's flight status. In response to challenges such as weak launch force, low identification rates, small airspeed, and low recognition accuracy in UAVs, a method for identifying UAV flight parameters based on launch force and airspeed is proposed. From the aspect of launch force identification, a recognition method based on a low-g value accelerometer information source is proposed, utilizing a 'multi-level time window + threshold' approach. For airspeed identification, an optimization method for airspeed measurement under the Kalman filter architecture is introduced. A device for airspeed measurement based on pressure sensors is designed, and the recommended installation position is determined through simulation. Furthermore, the feasibility and robustness of the proposed launch force identification and airspeed measurement optimization methods are validated through simulation. Finally, the effectiveness of the design is verified through centrifuge and wind tunnel experiments. This research provides technical support for the identification of the launch force and airspeed measurement in UAVs.
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Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.
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Emerging evidence suggests a beneficial role of rhizobacteria in ameliorating plant disease resistance in an environment-friendly way. In this study, we characterize a rhizobacterium, Bacillus cereus NJ01, that enhances bacterial pathogen resistance in rice and Arabidopsis. Transcriptome analyses show that root inoculation of NJ01 induces the expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes in Arabidopsis leaves. Genetic evidence showed that EDS1, PAD4, and WRKY18 are required for B. cereus NJ01-induced bacterial resistance. An EDS1-PAD4 complex interacts with WRKY18 and enhances its DNA binding activity. WRKY18 directly binds to the W box in the promoter region of the SA biosynthesis gene ICS1 and ABA biosynthesis genes NCED3 and NCED5 and contributes to the NJ01-induced bacterial resistance. Taken together, our findings indicate a role of the EDS1/PAD4-WRKY18 complex in rhizobacteria-induced disease resistance.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Bacillus cereus , Proteínas de Unión al ADN , Enfermedades de las Plantas , Ácido Salicílico , Bacillus cereus/genética , Ácido Abscísico/metabolismo , Arabidopsis/inmunología , Arabidopsis/microbiología , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Ácido Salicílico/metabolismo , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Oryza/microbiología , Oryza/inmunología , Oryza/genética , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Inmunidad de la PlantaRESUMEN
Extracellular vesicles (EVs) have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins (RNPs), owing to their ability to minimize off-target effects and immune responses. However, enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within EVs. In response, we employed the Fc/Spa interaction system, in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV membrane. Simultaneously, the B domain of the Spa protein was fused to the C domain of cargos such as Cre or spCas9. Due to the robust interaction between Fc and Spa, this method enriched nearly twice the amount of cargo within the EVs. EVs loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in vivo. Moreover, following neuron-targeting peptide RVG modification, the in vivo dosage in neural tissues substantially increased, contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target efficiency. These findings establish a robust platform for efficient EV-based SpCas9 delivery, offering potential therapeutic advantages for HSV1 infections and other neurological disorders.