ABSTRACT
The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.
ABSTRACT
OBJECTIVE: The purpose of this work was to develop an anti-CAT-SYI immunoglobulin Y (IgY) antibody that targeted both GtfB (glucosyltransferase B) and GbpB (glucan-binding protein B) and test its anticaries properties in rats. METHODS: A new CAT-SYI fusion gene was created utilising functional DNA fragments from the GtfB and GbpB genes. The recombinant antigens, comprising the fused CAT-SYI antigen, GtfB, and GbpB, were expressed and purified using a prokaryotic expression and purification system. The purified recombinant antigens were utilised to immunise laying hens against particular IgY production. The biological activities of these particular IgY antibodies were then assessed both in vitro and in vivo, including their capacity to suppress biofilm formation and tooth caries. RESULTS: Results indicated that these produced IgY antibodies demonstrated a high antibody titer (>0.1 µg/mL) and could precisely recognise and bind to their respective antigens. Furthermore, it was discovered that these specific IgY antibodies successfully bind to Streptococcus mutans and significantly reduce biofilm development. After 8 weeks of ingesting antigen-specific IgY meals, comprising anti-GtfB IgY and anti-GbpB IgY, the severity of dental caries was dramatically reduced in S mutans-infected Sprague-Dawley rats (P < .01). Anti-CAT-SYI IgY therapy significantly reduced tooth cavities by 89.0% in vivo (P < .05) compared to other treatment groups. CONCLUSIONS: The anti-CAT-SYI IgY, a multitarget antibody that targets both GtfB and GbpB, displayed excellent inhibitory effects against S mutans, making it a promising targeted method with improved anticaries efficacy and significant application opportunities.
ABSTRACT
The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no anti-proliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.
ABSTRACT
Saline-alkali is an important abiotic stressor influencing tomato production. Exogenous methyl jasmonate (MeJA) is well known to increase tomato resistance to a variety of stresses, although its exact mechanism is yet unknown. In this study we confirmed that 22.5 µmol/l MeJA could significantly improve the saline-alkali stress resistance of tomato. Saline-alkali (300 mM) stress increased the endogenous MeJA and jasmonic acid (JA) contents of tomato by 18.8 and 13.4%, respectively. Exogenous application of 22.5 µmol/l MeJA increased the endogenous MeJA and JA contents in tomato by 15.2 and 15.9%, respectively. Furthermore, we found an important transcription factor, SlWRKY80, which responded to MeJA, and constructed its overexpressing and knockout lines through genetic transformation. It was found that SlWRKY80 actively regulated tomato resistance to saline-alkali stress, and the spraying of exogenous MeJA (22.5 µmol/l) reduced the sensitivity of SlWRKY80 knockout lines to saline-alkali stress. The SlWRKY80 protein directly combines with the promoter of SlSPDS2 and SlNHX4 to positively regulate the transcription of SlSPDS2 and SlNHX4, thereby promoting the synthesis of spermidine and Na+/K+ homeostasis, actively regulating saline-alkali stress. The augmentation of JA content led to a notable reduction of 70.6% in the expression of SlJAZ1, and the release of the SlWRKY80 protein interacting with SlJAZ1. In conclusion, we revealed the mechanism of exogenous MeJA in tomato stress resistance through multiple metabolic pathways, elucidated that exogenous MeJA further promotes spermidine synthesis and Na+/K+ homeostasis by activating the expression of SlWRKY80, which provides a new theoretical basis for the study of the JA stress resistance mechanism and the production of tomato.
ABSTRACT
Saline-alkali stress is an important abiotic stress factor affecting tomato (Solanum lycopersicum L.) plant growth. Although the involvement of the tomato SlWRKY gene family in responses to saline-alkali stress has been well established, the mechanism underlying resistance to saline-alkali stress remains unclear. In this study, we investigated the role of SlWRKY81 in conferring saline-alkali stress resistance by using overexpression and knockout tomato seedlings obtained via genetic modification. We demonstrated that SlWRKY81 improves the ability of tomato to withstand saline-alkali stress by enhancing antioxidant capacity, root activity, and proline content while reducing malondialdehyde levels. Saline-alkali stress induces an increase in jasmonic acid (JA) content in tomato seedlings, and the SlWRKY81 promoter responds to JA signaling, leading to an increase in SlWRKY81 expression. Furthermore, the interaction between SlJAZ1 and SlWRKY81 represses the expression of SlWRKY81. SlWRKY81 binds to W-box motifs in the promoter regions of SlSPDS2 and SlNHX4, thereby positively regulating their expression. This regulation results in increased spermidine (Spd) content and enhanced potassium (K+) absorption and sodium (Na+) efflux, which contribute to the resistance of tomato to saline-alkali stress. However, JA and SlJAZ1 exhibit antagonistic effects. Elevated JA content reduces the inhibitory effect of SlJAZ1 on SlWRKY81, leading to the release of additional SlWRKY81 protein and further augmenting the resistance of tomato to saline-alkali stress. In summary, the modulation of Spd synthesis and Na+/K+ homeostasis mediated by the interaction between SlWRKY81 and SlJAZ1 represents a novel pathway underlying tomato response to saline-alkali stress.
Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Potassium , Sodium , Solanum lycopersicum , Spermidine , Alkalies/metabolism , Cyclopentanes/metabolism , Homeostasis , Oxylipins/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Potassium/metabolism , Seedlings/genetics , Seedlings/metabolism , Seedlings/physiology , Signal Transduction , Sodium/metabolism , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Spermidine/metabolismABSTRACT
Modern tomatoes produce colorful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. Here, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci responsible for fruit development. The colorless peel of LBS fruits was caused by a 603 bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as STAY-GREEN 1 (SlSGR1) and PHYTOENE SYNTHASE 1 (SlPSY1). SGR1 and PSY1 co-suppression by RNAi converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were also identified in several wild tomatoes bearing green or gray ripe fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS, and transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii also failed to convert purple-flesh into red-flesh fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1, and SlSGR1 control fruit color in cultivated and some wild tomato species.
Subject(s)
Alkyl and Aryl Transferases , Fruit , Geranylgeranyl-Diphosphate Geranylgeranyltransferase , Plant Proteins , Solanum lycopersicum , Solanum lycopersicum/genetics , Fruit/genetics , Fruit/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/genetics , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/metabolism , Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Mutation , Plants, Genetically Modified/genetics , Gene Expression Regulation, Plant , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.
Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Alleles , Gain of Function Mutation , Mutation , Flowers/genetics , Flowers/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant/geneticsABSTRACT
While deep learning has found widespread utility in gearbox fault diagnosis, its direct application to wind turbine gearboxes encounters significant hurdles. Disparities in data distribution across a spectrum of operating conditions for wind turbines result in a marked decrease in diagnostic accuracy. In response, this study introduces a tailored dynamic conditional adversarial domain adaptation model for fault diagnosis in wind turbine gearboxes amidst cross-condition scenarios. The model adeptly adjusts the importance of aligning marginal and conditional distributions using distance metric factors. Information entropy parameters are also incorporated to assess individual sample transferability, prioritizing highly transferable samples during domain alignment. The amalgamation of these dynamic factors empowers the approach to maintain stability across varied data distributions. Comprehensive experiments on both gear and bearing data validate the method's efficacy in cross-condition fault diagnosis. Comparative outcomes demonstrate that, when contrasted with four advanced transfer learning techniques, the dynamic conditional adversarial domain adaptation model attains superior accuracy and stability in multi-transfer tasks, making it notably suitable for diagnosing wind turbine gearbox faults.
ABSTRACT
DC1 (Divergent C1) domain proteins are a new class of proteins that have been discovered in recent years, which play an important role in plant growth, development, and stress response. In order to better study the distribution and function of DC1 domain proteins in tomatoes, a genome-wide identification was conducted. It was found that there are twenty-one DC1 domain protein genes distributed on nine chromosomes of tomatoes, named SlCHP1-21. Phylogenetic analysis shows that twenty-one SlCHP genes are divided into six subfamilies. Most of the SlCHP genes in tomatoes have no or very short introns. All SlCHP proteins, with the exception of SlCHP8 and SlCHP17, contain variable amounts of C1 domain. Analysis of the SlCHP gene promoter sequence revealed multiple cis-elements responsive to plant stress. qRT-CR analysis showed that most members of SlCHP gene expressed in the roots. The SlCHP11, 13, 16, 17, and SlCHP20 genes showed specific responses to high temperature, low temperature, salt, and drought stress. In addition, the subcellular localization and interaction proteins of SlCHP were analyzed and predicted. Together, these results provides a theoretical basis for further exploration of the function and mechanism of the SlCHP gene in tomatoes.
Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Phylogeny , Stress, Physiological/genetics , Transcription Factors/metabolism , Gene Expression Regulation, Plant , Multigene FamilyABSTRACT
Fast and low-dose reconstructions of medical images are highly desired in clinical routines. We propose a hybrid deep-learning and iterative reconstruction (hybrid DL-IR) framework and apply it for fast magnetic resonance imaging (MRI), fast positron emission tomography (PET), and low-dose computed tomography (CT) image generation tasks. First, in a retrospective MRI study (6,066 cases), we demonstrate its capability of handling 3- to 10-fold under-sampled MR data, enabling organ-level coverage with only 10- to 100-s scan time; second, a low-dose CT study (142 cases) shows that our framework can successfully alleviate the noise and streak artifacts in scans performed with only 10% radiation dose (0.61 mGy); and last, a fast whole-body PET study (131 cases) allows us to faithfully reconstruct tumor-induced lesions, including small ones (<4 mm), from 2- to 4-fold-accelerated PET acquisition (30-60 s/bp). This study offers a promising avenue for accurate and high-quality image reconstruction with broad clinical value.
Subject(s)
Deep Learning , Retrospective Studies , Tomography, X-Ray Computed/methods , Positron-Emission Tomography/methods , Image Processing, Computer-Assisted/methodsABSTRACT
PURPOSE: To propose an acceleration method for 3D variable flip-angle (VFA) T1 mapping based on a technique called shift undersampling improves parametric mapping efficiency and resolution (SUPER). METHODS: The proposed method incorporates strategies of SUPER, controlled aliasing in volumetric parallel imaging (CAIPIRINHA), and total variation-based regularization to accelerate 3D VFA T1 mapping. The k-space sampling grid of CAIPIRINHA is internally undersampled with SUPER along the contrast dimension. A proximal algorithm was developed to preserve the computational efficiency of SUPER in the presence of regularization. The regularized SUPER-CAIPIRINHA (rSUPER-CAIPIRINHA) was compared with low rank plus sparsity (L + S), reconstruction of principal component coefficient maps (REPCOM), and other SUPER-based methods via simulations and in vivo brain T1 mapping. The results were assessed quantitatively with NRMSE and structural similarity index measure (SSIM), and qualitatively by two experienced reviewers. RESULTS: rSUPER-CAIPIRINHA achieved a lower NRMSE and higher SSIM than L + S (0.11 ± 0.01 vs. 0.19 ± 0.03, p < 0.001; 0.66 ± 0.05 vs. 0.37 ± 0.03, p < 0.001) and REPCOM (0.16 ± 0.02, p < 0.001; 0.46 ± 0.04, p < 0.001). The reconstruction time of rSUPER-CAIPIRINHA was 6% of L + S and 2% of REPCOM. For the qualitative comparison, rSUPER-CAIPIRINHA showed improvement of overall image quality and reductions of artifacts and blurring, although with a lower apparent SNR. Compared with 2D SUPER-SENSE, rSUPER-CAIPIRINHA significantly reduced NRMSE (0.11 ± 0.01 vs. 0.23 ± 0.04, p < 0.001) and generated less noisy reconstructions. CONCLUSION: By incorporating SUPER, CAIPIRINHA, and regularization, rSUPER-CAIPIRINHA mitigated noise amplification, reduced artifacts and blurring, and achieved faster reconstructions compared with L + S and REPCOM. These advantages render 3D rSUPER-CAIPIRINHA VFA T1 mapping potentially useful for clinical applications.
Subject(s)
Imaging, Three-Dimensional , Magnetic Resonance Imaging , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Reproducibility of Results , Brain/diagnostic imaging , Image Enhancement/methods , Algorithms , Image Processing, Computer-Assisted/methodsABSTRACT
Multiple Gretchen Hagen 3 (GH3) genes have been implicated in a range of processes in plant growth and development through their roles in maintaining hormonal homeostasis. However, there has only been limited study on the functions of GH3 genes in tomato (Solanum lycopersicum). In this work, we investigated the important function of SlGH3.15, a member of the GH3 gene family in tomato. Overexpression of SlGH3.15 led to severe dwarfism in both the above- and below-ground sections of the plant, accompanied by a substantial decrease in free IAA content and reduction in the expression of SlGH3.9, a paralog of SlGH3.15. Exogenous supply of IAA negatively affected the elongation of the primary root and partially restored the gravitropism defects in SlGH3.15-overexpression lines. While no phenotypic change was observed in the SlGH3.15 RNAi lines, double knockout lines of SlGH3.15 and SlGH3.9 were less sensitive to treatments with the auxin polar transport inhibitor. Overall, these findings revealed important roles of SlGH3.15 in IAA homeostasis and as a negative regulator of free IAA accumulation and lateral root formation in tomato.
Subject(s)
Indoleacetic Acids , Solanum lycopersicum , Indoleacetic Acids/metabolism , Solanum lycopersicum/genetics , Gravitropism/genetics , Homeostasis , Biological Transport/genetics , Gene Expression Regulation, Plant , Plant Roots/metabolismABSTRACT
Osteoporosis and sarcopenia (termed "Osteosarcopenia"), the twin-aging diseases, are major contributors to reduced bone mass and muscle weakness in the elderly population. Connexin 43 (Cx43) in osteocytes has been previously reported to play vital roles in bone homeostasis and muscle function in mature mice. The Cx43-formed gap junctions (GJs) and hemichannels (HCs) in osteocytes are important portals for the exchange of small molecules in cell-to-cell and cell-to-extracellular matrix, respectively. However, the roles of Cx43-based GJs and HCs in both bone and muscle aging are still unclear. Here, we used two transgenic mouse models with overexpression of the dominant negative Cx43 mutants primarily in osteocytes driven by the 10-kb Dmp1 promoter, R76W mice (inhibited gap junctions but enhanced hemichannels) and Δ130-136 mice (both gap junction and hemichannels are inhibited), to determine the actions of Cx43-based hemichannels (HCs) and gap junctions (GJs) in the regulation of bone and skeletal muscle from aged mice (18 months) as compared with those from adult mice (10 months). We demonstrated that enhancement of Cx43 HCs reduces bone mass due to increased osteoclast surfaces while the impairment of Cx43 HCs increases osteocyte apoptosis in aged mice caused by reduced PGE2 levels. Furthermore, altered mitochondrial homeostasis with reduced expression of Sirt-1, OPA-1, and Drp-1 resulted in excessive ROS level in muscle soleus (SL) of aged transgenic mice. In vitro, the impairment of Cx43 HCs in osteocytes from aged mice also promoted muscle collagen synthesis through activation of TGFß/smad2/3 signaling because of reduced PGE2 levels in the PO CM. These findings indicate that the enhancement of Cx43 HCs while GJs are inhibited reduces bone mass, and the impairment of Cx43 HCs inhibits PGE2 level in osteocytes and this reduction promotes muscle collagen synthesis in skeletal muscle through activation of TGFß/smad2/3 signaling, which together with increased ROS level contributes to reduced muscle force in aged mice.
Subject(s)
Connexin 43 , Osteocytes , Animals , Male , Mice , Collagen/metabolism , Connexin 43/genetics , Connexin 43/metabolism , Dinoprostone/metabolism , Gap Junctions/metabolism , Mice, Transgenic , Muscle, Skeletal/metabolism , Osteocytes/metabolism , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
OBJECTIVE: To identify the relation of microvascular density (MVD) to the early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma, and to determine whether MVD could be a prognostic predictor of esophageal squamous cell carcinoma. METHODS: Patients with T1 esophageal squamous cell carcinoma were enrolled. Immunohistochemistry with primary antibody against CD-34 was performed to count MVD. ROC curve was plotted and appropriate cutoff value was determined to evaluate the potential power of MVD in predicting early recurrence and metastasis of T1 esophageal squamous cell carcinoma. Survival curves were drawn by the Kaplan-Meier method and significance were tested by the Mantel-Cox test. RESULTS: A total of 37 patients with T1 esophageal squamous cell carcinoma were enrolled. The MVD of T1 esophageal squamous cell carcinoma patients with early metastasis was significantly higher than that of T1 esophageal squamous cell carcinoma patients without early metastasis (65.83±4.39 vs. 42.26±2.34, p<0.001). MVD was available in distinguishing whether patients with early esophageal are prone to postoperative recurrence or metastasis (AUC=0.861; 95% CI 0.738-0.984, p<0.001), with 88.89% sensitivity and 68.42% specificity of MVD being obtained when the cut-off is 44.5. Kaplan-Meier survival curves showed that patients with a higher MVD had a lower survival (37.35 months) compared with those with low MVD (40.79 months) (p<0.05). CONCLUSIONS: MVD could be a promising indicator for early postoperative recurrence and metastasis of T1 esophageal squamous cell carcinoma and the prognosis of these patients.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/surgery , Humans , Microvascular Density , Neovascularization, Pathologic , PrognosisABSTRACT
Endogenous spermidine can improve the resistance of plants to saline-alkali stress. SlSPDS1 and SlSPDS2 are the main spermidine synthase (SPDS) genes in tomatoes. In comparison with SlSPDS1, SlSPDS2 plays an important role in wild-type tomato seedling under saline-alkali stress. However, limited research has focused on the role of SlSPDS2 in saline-alkali stress. Wild-type (WT) and SPDS gene (SlSPDS2) transgenic over-expression tomato seedlings were used to explore the function of endogenous spermidine on the saline-alkali resistance of tomato seedlings. The results show that SlSPDS2 overexpression under normal conditions and saline-alkali stress increased the content of endogenous free polyamines and the expression levels of polyamine synthesis-related genes in tomato seedlings. Under saline-alkali stress, SlSPDS2 overexpression significantly reduced Na+/K+ ratio, relative electrical conductivity, O2·-, H2O2, and malondialdehyde content, increased Seedling index, relative water content, antioxidant enzyme activities (peroxidase, superoxide dismutase, and catalase), and the contents of proline and soluble sugar in tomato leaf, and mitigated the adverse effect of saline-alkali stress on tomato seedlings. In summary, the overexpression of SlSPDS2 tomato seedlings regulated the ionic homeostasis, antioxidant enzyme system, and osmotic regulatory substances of tomato seedlings living in saline-alkali environment by increasing endogenous free polyamine content, thereby improving the resistance of tomato seedlings against saline-alkali stress.
ABSTRACT
Path planning for wheeled mobile robots on partially known uneven terrain is an open challenge since robot motions can be strongly influenced by terrain with incomplete environmental information such as locally detected obstacles and impassable terrain areas. This paper proposes a hierarchical path planning approach for a wheeled robot to move in a partially known uneven terrain. We first model the partially known uneven terrain environment respecting the terrain features, including the slope, step, and unevenness. Second, facilitated by the terrain model, we use Aâ algorithm to plan a global path for the robot based on the partially known map. Finally, the Q-learning method is employed for local path planning to avoid locally detected obstacles in close range as well as impassable terrain areas when the robot tracks the global path. The simulation and experimental results show that the designed path planning approach provides satisfying paths that avoid locally detected obstacles and impassable areas in a partially known uneven terrain compared with the classical Aâ algorithm and the artificial potential field method.
Subject(s)
Robotics , Algorithms , Computer Simulation , Motion , Robotics/methodsABSTRACT
OBJECTIVE: Currently, the treatment of spontaneous intracerebral hemorrhage (sICH) is limiting, especially in patients with midline shift and supratentorial hemorrhage. Here, we investigated the clinical value of minimally invasive surgery (MIS) in patients with midline shift and supratentorial sICH by observing the consciousness state, midline shift, and short-term mortality. METHODS: A total of 124 supratentorial sICH patients with midline shift, hematoma volume >30 mL and <150 mL were included in this study. Based on treatment methods, the enrolled patients were divided into minimally invasive surgical (MIS) (group 1, n = 61) and conservative (group 2, n = 63) treatment groups. Measurements of midline shift and state of consciousness using the Glasgow Coma Scale (GCS) score were performed on day 2 following treatment. Additionally, mortality, adverse events, and neurologic recovery (modified Rankin Scale score) in each group were observed after 1 month. RESULTS: On postoperative day 2, the recovery rates of midline shift and consciousness state in group 1 patients were 59.02% and 50.82%, respectively, significantly higher than group 2, 26.98% and 25.40% (P < 0.01). By comparing death, adverse events, and neurologic function recovery of the 2 groups within 1 month postoperative, we observed a significantly lower fatality rate in group 1 (16.39%; 10 cases) than group 2 (33.33%; 21 cases) (P < 0.05). No significant difference of the adverse event rates was observed between groups 1 and 2 (19.67% [12 cases] vs. 19.05% [12 cases]). In addition, neurologic function recovery also had no significant difference between the 2 groups (P > 0.05). CONCLUSIONS: MIS could reduce early-stage midline shift, improve consciousness state and reduce short-term mortality in patients with supratentorial sICH.
Subject(s)
Cerebral Hemorrhage , Minimally Invasive Surgical Procedures , Case-Control Studies , Cerebral Hemorrhage/surgery , Glasgow Coma Scale , Humans , Minimally Invasive Surgical Procedures/methods , Retrospective Studies , Treatment OutcomeABSTRACT
Angiopoietin-like 2 (Angptl2) is reported to be correlated with cardiovascular diseases, but its role in hypertension remains unclear. This study aimed to investigate the role and potential mechanism of Angptl2 in hypertension. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were used to detect the expression of Angptl2. Angiotensin II (Ang II) stimulates vascular smooth muscle cells (VSMCs) to mimic hypertension in vitro. Cell proliferation, migration, and invasion abilities were determined using CCK-8, cell colony formation, wound healing, and transwell assays, respectively. The cell cycle distribution was detected by flow cytometry. The expression of Ki67 was determined by immunofluorescence, and protein expression was measured using western blotting. Angptl2 was found to be elevated in hypertensive rats in vivo and in VSMCs upon Ang II stimulation in vitro. Angptl2 knockdown suppressed cell proliferation, colony formation, cell migration, and invasion as well as the downregulation of Ki67. Additionally, Angptl2 knockdown hindered cell cycle progression and downregulated protein expression of CDK2/4 and cyclin D1, but upregulated p21 expression. Furthermore, Angptl2 knockdown inhibited activation of the NLRP3 inflammasome. Our findings suggest that Angptl2 knockdown suppresses VSMC proliferation, migration, and invasion induced by Ang II. Angptl2 may be a new target for vascular remodeling in hypertension.
Subject(s)
Angiotensin II , Hypertension , Angiopoietin-Like Protein 2 , Angiopoietin-like Proteins/genetics , Angiopoietin-like Proteins/metabolism , Angiotensin II/metabolism , Angiotensin II/pharmacology , Animals , Cell Movement , Cell Proliferation , Cells, Cultured , Gene Knockdown Techniques , Hypertension/metabolism , Ki-67 Antigen/metabolism , Muscle, Smooth, Vascular/metabolism , Rats , Rats, Inbred WKYABSTRACT
Controlled-release pesticide formulations using natural polymers as carriers are highly desirable owing to their good biocompatibility, biodegradability, and improved pesticide utilization. In this study, the application potential of our previously prepared spinosad/chitosan controlled-release suspension (SCCS) was evaluated through both toxicity and dissipation tests. A comparison with the spinosad suspension concentrate and the commercial spinosad emulsion in water showed that the insecticidal activity of SCCS against Plutella xylostella larvae displayed the best quick-acting performance as well as long-term efficacy of more than 20 days. The 48 h LC50 for a 20-day efficacy was calculated to be 29.36 mg/L. The dissipation behavior of spinosad in the spinosad/chitosan microparticles in soil was found to follow the first-order kinetics, with a relatively shorter half-life (2.1 days) than that observed for the unformulated spinosad (3.1 days). This work showed the positive effect of chitosan on spinosad in improving insecticidal activity and reducing environmental risks in soil, which provided useful information on the application potential of pesticide-carrier systems based on natural polymer materials in crop protection and food safety.