Loss-of-function mutations in the C terminus of TPL2 kinase promote oncogenesis by impeding its proteasomal degradation, leading to sustained protein expression. However, the degradation mechanism for TPL2 has remained elusive. Through proximity-dependent biotin identification (BioID), we uncovered tripartite motif-containing 4 (TRIM4) as the E3 ligase that binds and degrades TPL2 by polyubiquitination of lysines 415 and 439. The naturally occurring TPL2 mutants R442H and E188K exhibit impaired TRIM4 binding, enhancing their stability. We further discovered that TRIM4 itself is stabilized by another E3 ligase, TRIM21, which in turn is regulated by KRAS. Mutant KRAS recruits RNF185 to degrade TRIM21 and subsequently TRIM4, thereby stabilizing TPL2. In the presence of mutant KRAS, TPL2 phosphorylates and degrades GSK3β, resulting in β-catenin stabilization and activation of the Wnt pathway. These findings elucidate the physiological mechanisms regulating TPL2 and its exploitation by mutant KRAS, underscoring the need to develop TPL2 inhibitors for KRAS-mutant cancers.

UNASSIGNED: The precise detection of weeds in the field is the premise of implementing weed management. However, the similar color, morphology, and occlusion between wheat and weeds pose a challenge to the detection of weeds. In this study, a CSCW-YOLOv7 based on an improved YOLOv7 architecture was proposed to identify five types of weeds in complex wheat fields.
UNASSIGNED: First, a dataset was constructed for five weeds that are commonly found, namely, Descurainia sophia, thistle, golden saxifrage, shepherd\'s purse herb, and Artemisia argyi. Second, a wheat weed detection model called CSCW-YOLOv7 was proposed to achieve the accurate identification and classification of wheat weeds. In the CSCW-YOLOv7, the CARAFE operator was introduced as an up-sampling algorithm to improve the recognition of small targets. Then, the Squeeze-and-Excitation (SE) network was added to the Extended Latent Attention Networks (ELAN) module in the backbone network and the concatenation layer in the feature fusion module to enhance important weed features and suppress irrelevant features. In addition, the contextual transformer (CoT) module, a transformer-based architectural design, was used to capture global information and enhance self-attention by mining contextual information between neighboring keys. Finally, the Wise Intersection over Union (WIoU) loss function introducing a dynamic nonmonotonic focusing mechanism was employed to better predict the bounding boxes of the occluded weed.
UNASSIGNED: The ablation experiment results showed that the CSCW-YOLOv7 achieved the best performance among the other models. The accuracy, recall, and mean average precision (mAP) values of the CSCW-YOLOv7 were 97.7%, 98%, and 94.4%, respectively. Compared with the baseline YOLOv7, the improved CSCW-YOLOv7 obtained precision, recall, and mAP increases of 1.8%, 1%, and 2.1%, respectively. Meanwhile, the parameters were compressed by 10.7% with a 3.8-MB reduction, resulting in a 10% decrease in floating-point operations per second (FLOPs). The Gradient-weighted Class Activation Mapping (Grad-CAM) visualization method suggested that the CSCW-YOLOv7 can learn a more representative set of features that can help better locate the weeds of different scales in complex field environments. In addition, the performance of the CSCW-YOLOv7 was compared to the widely used deep learning models, and results indicated that the CSCW-YOLOv7 exhibits a better ability to distinguish the overlapped weeds and small-scale weeds. The overall results suggest that the CSCW-YOLOv7 is a promising tool for the detection of weeds and has great potential for field applications.

UNASSIGNED: The classification of the four tobacco shred varieties, tobacco silk, cut stem, expanded tobacco silk, and reconstituted tobacco shred, and the subsequent determination of tobacco shred components, are the primary tasks involved in calculating the tobacco shred blending ratio. The identification accuracy and subsequent component area calculation error directly affect the composition determination and quality of the tobacco shred. However, tiny tobacco shreds have complex physical and morphological characteristics; in particular, there is substantial similarity between the expanded tobacco silk and tobacco silk varieties, and this complicates their classification. There must be a certain amount of overlap and stacking in the distribution of tobacco shreds on the actual tobacco quality inspection line. There are 24 types of overlap alone, not to mention the stacking phenomenon. Self-winding does not make it easier to distinguish such varieties from the overlapped types, posing significant difficulties for machine vision-based tobacco shred classification and component area calculation tasks.
UNASSIGNED: This study focuses on two significant challenges associated with identifying various types of overlapping tobacco shreds and acquiring overlapping regions to calculate overlapping areas. It develops a new segmentation model for tobacco shred images based on an improved Mask region-based convolutional neural network (RCNN). Mask RCNN is used as the segmentation network\'s mainframe. Convolutional network and feature pyramid network (FPN) in the backbone are replaced with Densenet121 and U-FPN, respectively. The size and aspect ratios of anchors parameters in region proposal network (RPN) are optimized. An algorithm for the area calculation of the overlapped tobacco shred region (COT) is also proposed, which is applied to overlapped tobacco shred mask images to obtain overlapped regions and calculate the overlapped area.
UNASSIGNED: The experimental results showed that the final segmentation accuracy and recall rates are 89.1% and 73.2%, respectively. The average area detection rate of 24 overlapped tobacco shred samples increases from 81.2% to 90%, achieving high segmentation accuracy and overlapped area calculation accuracy.
UNASSIGNED: This study provides a new implementation method for the type identification and component area calculation of overlapped tobacco shreds and a new approach for other similar overlapped image segmentation tasks.

The purpose of this study was to compare the intraoperative outcomes and postoperative complications of patients experiencing transoral thyroidectomy vestibular approach (TOTVA) and conventional open thyroidectomy (COT). PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials in the Cochrane Library, and Web of science expanded between January 2007 and November 2022 comparing TOTVA and COT was exhaustively searched. Fifteen non-randomized controlled studies involving 2955 patients were included. The results of meta-analyses indicated that TOTVA was associated with longer operative time (WMD, 66.86; 95%CI, 47.15-86.56; P < 0.00001), more blood loss (WMD, 2.83; 95%CI, 1.77-3.90; P < 0.00001), higher incidence of wound infection (OR, 5.62; 95%CI, 1.57-20.10, P = 0.008). There was no significant difference in terms of transient recurrent laryngeal nerve (RLN) palsy and other postoperative outcomes. In conclusion, TOTVA appears to be a feasible and safe approach for the treatment of patients with benign thyroid nodules and selected differential thyroid carcinomas just like the COT.

In this article, we propose a soft eel robot design using soft pneumatic actuators that mimic eel muscles. Four pairs of soft actuators are used to construct the eel robot body. Pulse signals with suitable shifting phases are utilized to control delivery of compressed air to the actuators in sequence to create a sinusoidal wave from head to tail of the robot body. A model of hydrodynamic forces acting on an anguilliform swimmer when moving in fluid was built to estimate the thrust force generated by the robot at different tail beat frequencies. Experimental data revealed that the generated thrust force was positively correlated with the beat frequency. Measured data showed that swimming efficiency depended on both generated thrust force and body posture in situ. At the beat frequency of 1.25 Hz, and air pressure at three segments from head to tail of 65, 50, and 30 kPa, respectively, the eel robot body showed the best cost of transport (COT) of 19.21 with velocity of 10.5 cm/s (or 0.198 body length per second [BL/s]), compared to the other\'s values of operation frequency and air pressure. We also found that control shifting phase strongly affects the swimming speed and COT. The robot body reached the highest velocity at around 19 cm/s (0.36 BL/s) with the COT of 10.72. Obtained result in this research would contribute to development of soft elongated swimming robot and enhance the knowledge on swimming performance of both robot and natural eels.

Phospholipids are crucial materials that are not only required for cell membrane construction but also play significant roles as signaling molecules. LPIN1 is an enzyme that displays phosphatidate phosphatase activity in the triglyceride and phospholipid synthesis pathway. Recent studies have shown that overexpression of LPIN1 is involved in breast tumorigenesis, but the underlying mechanism regulating LPIN1 expression has not been elucidated yet. In the present study, we showed that the IL-33-induced COT-JNK1/2 signaling pathway regulates LPIN1 mRNA and protein expression by recruiting c-Jun to the LPIN1 promoter in breast cancer cells. IL-33 dose-dependently and time-dependently increased LPIN1 mRNA and protein expression. Moreover, IL-33 promoted colony formation and mammary tumorigenesis via induction of LPIN1 expression, while inhibition of LPIN1 disturbed IL-33-induced cell proliferation and mammary tumorigenesis. IL-33-driven LPIN1 expression was mediated by the COT-JNK1/2 signaling pathway, and inhibition of COT or JNK1/2 reduced LPIN1 expression. COT-JNK1/2-mediated IL-33 signaling activated c-Jun and promoted its binding to the promoter region of LPIN1 to induce LPIN1 expression. These findings demonstrated the regulatory mechanism of LPIN1 transcription by the IL-33-induced COT/JNK1/2 pathway for the first time, providing a potential mechanism underlying the upregulation of LPIN1 in cancer.

To conduct a meta-analysis to compare the safety and efficacy of transoral endoscopic thyroidectomy vestibular approach (TOETVA) with conventional open thyroidectomy (COT).
MEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library from January 2007 to March 2020 were searched to identify studies comparing TOETVA and COT.
Six eligible nonrandomized studies involving 1151 patients were included. Meta-analysis results revealed that TOETVA group had a significantly longer operative time (weighted mean difference [WMD], 66.09; 95% confidence interval [CI], 35.22-96.96; P < .0001) and larger amount of drainage (WMD, 98; 95% CI, 20.14-175.86; P = .01). There were no significant differences in terms of postoperative outcomes.
TOETVA appears to be as feasible and safe as the COT for the treatment of patients with benign thyroid nodules and selected differential thyroid carcinomas.

暂无摘要。

Tumor progression locus 2 (TPL2, also known as COT or MAP3K8) is a mitogen-activated protein kinase kinase (MAP3K) activated downstream of TNFαR, IL1R, TLR, CD40, IL17R, and some GPCRs. TPL2 regulates the MEK1/2 and ERK1/2 pathways to regulate a cascade of inflammatory responses. In parallel to this, TPL2 also activates p38α and p38δ to drive the production of various inflammatory mediators in neutrophils. We discuss the implications of this finding in the context of various inflammatory diseases.

For paramedics, loading a stretcher into an ambulance is an activity with a high risk of back injury and accidents. The objective of this study was to document strategies paramedics use at work while loading a powered stretcher into an ambulance. A total of 249 stretcher loading operations performed by 58 paramedics, and 51 semistructured post-intervention interviews were analyzed. Almost three quarters of loading operations required additional actions (e.g., raising the shoulders and additional lifting) to insert the stretcher into the cot fastener system in the ambulance. Some strategies that were necessary to complete the stretcher loading operation seemed to have negative impacts on the workers\' health, such as repositioning the stretcher. This action wastes time and requires significant physical efforts, as it is usually done alone. This study suggests some potential solutions, related to equipment, training, workers and work organization, to reduce the risk of injury while loading stretchers.