BACKGROUNDThe development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate ...with the prothrombotic state in some diseases, but are rarely reported in GC patients. AIMTo investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients. METHODSThe levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity (PCA) was determined by fibrin formation and thrombin-antithrombin complex (TAT) assays. Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava (IVC). RESULTSNETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and P-selectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumor-bearing mice compared with control mice. Notably, the combination of deoxyribonuclease I, activated protein C, and sivelestat markedly abolished the PCA of NETs. CONCLUSIONGC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.
Brassinosteroids (BRs) are a group of steroidal phytohormones, playing critical roles in almost all physiological aspects during the life span of a plant. In Arabidopsis, BRs are perceived at the ...cell surface, triggering a reversible phosphorylation‐based signaling cascade that leads to the activation and nuclear accumulation of a family of transcription factors, represented by BES1 and BZR1. Protein farnesylation is a type of post‐translational modification, functioning in many important cellular processes. Previous studies demonstrated a role of farnesylation in BR biosynthesis via regulating the endoplasmic reticulum localization of a key bassinolide (BL) biosynthetic enzyme BR6ox2. Whether such a process is also involved in BR signaling is not understood. Here, we demonstrate that protein farnesylation is involved in mediating BR signaling in Arabidopsis. A loss‐of‐function mutant of ENHANCED RESPONSE TO ABA 1 (ERA1), encoding a β subunit of the protein farnesyl transferase holoenzyme, can alter the BL sensitivity of bak1‐4 from a reduced to a hypersensitive level. era1 can partially rescue the BR defective phenotype of a heterozygous mutant of bin2‐1, a gain‐of‐function mutant of BIN2 which encodes a negative regulator in the BR signaling. Our genetic and biochemical analyses revealed that ERA1 plays a significant role in regulating the protein stability of BES1.
Farnesylation, a type of protein modification critical to the functions of certain proteins, negatively regulates the stability of BES1, one of the main transcription factors controlling brassinosteroid signal output.
•The improvements made to the YOLOv5 algorithm include the addition of a small object detection layer in the neck layer.•The modifications were made to the original loss function to enhance training ...stability and increase training speed.•The precision rate of the enhanced YOLOv5 surpasses that of SSD, Faster RCNN, and the original YOLOv5 by 9.42%, 20.41% and 3.62%, respectively.•The averages for the row recognition rate, navigation line extraction accuracy rate and angle error were recorded at 89.29%, 85.74% and 3.54°, respectively. Moreover, the row recognition rate and navigation line extraction accuracy rate of the proposed algorithm surpassed those of the least squares algorithm and random sample consensus algorithm by 7.69% and 6.8%, as well as 17.56% and 14.94%, respectively.
The unmanned pineapple harvester is required to operate efficiently along crop rows. This study presents a novel approach for extracting visual navigation line in pineapple fields using an enhanced YOLOv5 algorithm. The objective is to overcome challenges related to positioning accuracy rate and stability encountered by unmanned pineapple harvesters. The improvements made to the YOLOv5 algorithm include the addition of a small object detection layer in the neck layer. Furthermore, modifications were made to the original loss function to enhance training stability and increase training speed. Experimental results demonstrate that the enhanced YOLOv5 model achieved a 3.62 % increase in training precision rate and a 2.15 % increase in recall rate compared to the original model. With an image resolution of 960 × 1080 pixels, the average detection speed reached 17.35 frames per second (fps). The enhanced YOLOv5 algorithm was utilized to recognize and extract feature points representing pineapple rows. A clustering algorithm was employed to classify these feature points by row, while a modified shortest distance algorithm was applied to fit the pineapple crop row centerline and calculate the optimal navigation line. Field experiments revealed an average extraction accuracy rate of 89.13 % and 85.32 % for sunny and cloudy weather in high-density crops, respectively, with an average accuracy rate of 85.74 %, row recognition accuracy rate of 89.29 % and angle error of 3.54° in different density crops, respectively. This algorithm offers a method for obtaining navigation paths for unmanned pineapple harvesters.
•1D metallosupramolecular polymer constructed by diazananographene and porphyrin cobalt(II).•Solution-soluble metallosupramolecular polymer•Energy transfer from porphyrin units to diazananographene ...units.
A one-dimensional (1D) metallosupramolecular polymer, consisting of diazananographene (C76N2) and porphyrin cobalt(II) (CoTPP), was synthesized through coordination between pyridinic nitrogen and cobalt (II). Its structure was unambiguously characterized by single crystal X-ray diffraction. Revealed by NMR spectroscopy, this complex in solution still adopted a polymeric structure. The steady and transient absorption spectroscopic measurements of metallosupramolecular polymer indicated fast vibrational relaxation of CoTPP and energy transfer from CoTPP to C76N2.
An aggregation-enhanced emission mitochondrial probe,
LIQ-3
, was developed for ultrafast labeling within one minute and for distinguishing cancer cells from normal cells. Furthermore, the probe ...revealed high-fidelity tracking of mitochondria in a three-dimensional localization with advantages that include a specific targeting capacity and a high signal-to-noise ratio.
An aggregation-enhanced emission probe was developed for ultrafast labeling and high-fidelity imaging of mitochondria in cancer cells with a high signal-to-noise ratio.
In this study, the degree of conversion (DC) of an acrylic-based resin (IP-L 780) in two-photon polymerization (TPP) is systematically investigated via Raman microspectroscopy. A quantitative ...relationship between TPP laser parameters and the DC of the resin is established. Nonlinear increase in DC with increased laser average power is observed. The resin DC is more sensitive to the laser average power than the laser writing speed. Nanoindentation was employed to correlate the results obtained from Raman microspectroscopy with the mechanical properties of microstructures fabricated by TPP. At constant writing speeds, microstructures fabricated with high laser average powers possess high hardness and high reduced Young's modulus (RYM), indicating high DCs. The results are in line with high DCs measured under the same TPP parameters in Raman microspectroscopy. Raman microspectroscopy is proved to be an effective, rapid, and nondestructive method characterizing microstructures fabrication by TPP.
Background
High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive‐like behaviors induced by chronic unpredictable mild stress ...(CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive‐like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive‐like behaviors and its relationship with HMGB1.
Methods
After 4‐week chronic stress, behavioral tests were conducted to evaluate depressive‐like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme‐linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole‐cell patch clamping.
Results
The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down‐regulate Cx36 and alleviate depressive‐like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF‐α), and interleukin‐1β (IL‐1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine.
Conclusions
Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1‐mediated depressive‐like behaviors induced by CUMS through down‐regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.
Inhibition of Cx36 in hippocampal neurons might attenuate HMGB1‐mediated depressive‐like behaviors induced by CUMS through down‐regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.
Depression is partially caused by inflammation in central nervous system. This study investigated the ameliorative effects of phenol glycosides (PG) from Ligustrum lucidum Ait. (Oleaceae) on ...neuroinflammation and depressive‐like behavior in mice hypothalamus as well as the molecular mechanism. Mice were administered with PG extract for 2 weeks prior to treatment with LPS. The mice treated with PG extract showed resistance to LPS‐induced reduction in body weight and LPS‐induced depressive‐like behaviors shown by sucrose preference, tail suspension test, forced swimming test and open field test. LPS‐induced activation of microglial cells and elevation in protein expression of inflammatory cytokines including IL‐1β, RANTES and MCP‐1 in hypothalamus of mice were abrogated by pre‐treatment with PG extract. This extract down‐regulated expression of TLR4, MyD88, NLRP3, renin and angiotensin II and decreased proportional area of Iba‐1+ microglias in hypothalamus. Pre‐treatment with PG extract inhibited LPS‐triggered activation of CaSR/Gα11 signaling, stimulated 1‐OHase expression in hypothalamus, and enhanced circulating 1,25(OH)2D3 level. Overall, pre‐treatment with PG extract ameliorated LPS‐induced depressive‐like behaviors by repressing neuroinflammation in mice hypothalamus which was attributed to its suppression on activation of microglia and production of inflammatory cytokines via acting on TLR4 pathway, CaSR and RAS cascade associated with improving vitamin D metabolism.
A poly-amidosulfonic acid and multi-wall carbon nanotubes composite (PASA/MWNTs) modified electrode has been constructed by electropolymerization on glassy carbon electrode (GCE). The electrochemical ...behaviors of hydroquinone (HQ) and catechol (CC) were investigated using cyclic and differential pulse voltammetries (DPVs) at the prepared electrode. Separation of the reductive peak potentials for HQ and CC was about 120
mV in pH 6.0 phosphate buffer solution (PBS), which makes it suitable for simultaneous determination of these compounds. In the presence of 1.0
×
10
−4
mol
L
−1 isomer, the reductive peak currents of DPV are proportional to the concentration of HQ in the range of 6.0
×
10
−6 to 4.0
×
10
−4
mol
L
−1, and to that of CC in the range of 6.0
×
10
−6 to 7.0
×
10
−4
mol
L
−1. When simultaneously changing the concentration of both HQ and CC, the linear concentration range of HQ (or CC) is 6.0
×
10
−6 to 1.0
×
10
−4
mol
L
−1 (or 6.0
×
10
−6 to 1.8
×
10
−4
mol
L
−1), and the corresponding detection limits are 1.0
×
10
−6
mol
L
−1. The proposed method has been applied to simultaneous determination of HQ and catechol in water sample, and the results are satisfactory.
Aim This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer. Methods Based on TCGA and GTEx databases, the differentially expressed genes ...(DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve. Results We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable. Conclusions This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored. Keywords: Cervical cancer, DEGs, WGCNA, LASSO, Prognosis
PDF
