Dual-stage semantic segmentation of endoscopic surgical instruments.

BACKGROUND: Endoscopic instrument segmentation is essential for ensuring the safety of robotic-assisted spinal endoscopic surgeries. However, due to the narrow operative region, intricate surrounding tissues, and limited visibility, achieving instrument segmentation within the endoscopic view remains challenging. PURPOSE: This work aims to devise a method to segment surgical instruments in endoscopic video. By designing an endoscopic image classification model, features of frames before and after the video are extracted to achieve continuous and precise segmentation of instruments in endoscopic videos. METHODS: Deep learning techniques serve as the algorithmic core for constructing the convolutional neural network proposed in this study. The method comprises dual stages: image classification and instrument segmentation. MobileViT is employed for image classification, enabling the extraction of key features of different instruments and generating classification results. DeepLabv3+ is utilized for instrument segmentation. By training on distinct instruments separately, corresponding model parameters are obtained. Lastly, a flag caching mechanism along with a blur detection module is designed to effectively utilize the image features in consecutive frames. By incorporating specific parameters into the segmentation model, better segmentation of surgical instruments can be achieved in endoscopic videos. RESULTS: The classification and segmentation models are evaluated on an endoscopic image dataset. In the dataset used for instrument segmentation, the training set consists of 7456 images, the validation set consists of 829 images, and the test set consists of 921 images. In the dataset used for image classification, the training set consists of 2400 images and the validation set consists of 600 images. The image classification model achieves an accuracy of 70% on the validation set. For the segmentation model, experiments are conducted on two common surgical instruments, and the mean Intersection over Union (mIoU) exceeds 98%. Furthermore, the proposed video segmentation method is tested using videos collected during surgeries, validating the effectiveness of the flag caching mechanism and blur detection module. CONCLUSIONS: Experimental results on the dataset demonstrate that the dual-stage video processing method excels in performing instrument segmentation tasks under endoscopic conditions. This advancement is significant for enhancing the intelligence level of robotic-assisted spinal endoscopic surgeries.

OsCYP706C2 diverts rice strigolactone biosynthesis to a noncanonical pathway branch.

Strigolactones exhibit dual functionality as regulators of plant architecture and signaling molecules in the rhizosphere. The important model crop rice exudes a blend of different strigolactones from its roots. Here, we identify the inaugural noncanonical strigolactone, 4-oxo-methyl carlactonoate (4-oxo-MeCLA), in rice root exudate. Comprehensive, cross-species coexpression analysis allowed us to identify a cytochrome P450, OsCYP706C2, and two methyl transferases as candidate enzymes for this noncanonical rice strigolactone biosynthetic pathway. Heterologous expression in yeast and Nicotiana benthamiana indeed demonstrated the role of these enzymes in the biosynthesis of 4-oxo-MeCLA, which, expectedly, is derived from carlactone as substrate. The oscyp706c2 mutants do not exhibit a tillering phenotype but do have delayed mycorrhizal colonization and altered root phenotype. This work sheds light onto the intricate complexity of strigolactone biosynthesis in rice and delineates its role in symbiosis and development.

Advances of surgical robotics: image-guided classification and application.

Surgical robotics application in the field of minimally invasive surgery has developed rapidly and has been attracting increasingly more research attention in recent years. A common consensus has been reached that surgical procedures are to become less traumatic and with the implementation of more intelligence and higher autonomy, which is a serious challenge faced by the environmental sensing capabilities of robotic systems. One of the main sources of environmental information for robots are images, which are the basis of robot vision. In this review article, we divide clinical image into direct and indirect based on the object of information acquisition, and into continuous, intermittent continuous, and discontinuous according to the target-tracking frequency. The characteristics and applications of the existing surgical robots in each category are introduced based on these two dimensions. Our purpose in conducting this review was to analyze, summarize, and discuss the current evidence on the general rules on the application of image technologies for medical purposes. Our analysis gives insight and provides guidance conducive to the development of more advanced surgical robotics systems in the future.

Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice.

Postoperative pain is a type of pain that occurs in clinical patients after surgery. Among the factors influencing the transition from acute postoperative pain to chronic postoperative pain, chronic stress has received much attention in recent years. Here, we investigated the role of dopamine receptor D1/D2 expressing pyramidal neurons in the prelimbic cortex (PrL) in modulating chronic social defeat stress (CSDS)-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice. Our results showed that preoperative CSDS induced anxiety-like behavior and significantly prolonged postoperative pain caused by plantar incision, but did not affect plantar wound recovery and inflammation. Reduced activation of dopamine receptor D1 or D2 expressing neurons in the PrL is a remarkable feature of male mice after CSDS, and chronic inhibition of dopamine receptor D1 or D2 expressing neurons in the PrL induced anxiety-like behavior and persistent postoperative pain. Further studies found that activation of D1 expressing but not D2 expressing neurons in the PrL ameliorated CSDS-induced anxiety-like behavior and postoperative hyperalgesia. Our results suggest that dopamine receptor D1 expressing neurons in the PrL play a crucial role in CSDS-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

Advantages of robot-assisted resection of large mediastinal tumors: a single-center preliminary study.

Current study aims to assess the safety and efficacy of robot-assisted thoracoscopic surgery (RATS) for sizable mediastinal masses with a minimum diameter ≥6 cm, compared with video-assisted thoracoscopic surgery (VATS) and open surgery. This study enrolled 130 patients with mediastinal tumors with no less than 6 cm diameter in Zhongnan Hospital, Wuhan University, including 33 patients who underwent RATS, 52 patients who underwent VATS and 45 patients who underwent open surgery. After classifying based on mass size and whether it has invaded or not, we compared their clinical characteristics and perioperative outcomes. There was no significant difference in age, gender, mass size, myasthenia gravis, mass location, pathological types (p > 0.05) in three groups. Patients undergoing open surgery typically presenting at a more advanced stage (p < 0.05). No obvious difference was discovered in the average postoperative length of stay, operation duration, chest tube duration and average postoperative day 1 drainage output between RATS group and VATS group (p > 0.05), while intraoperative blood loss in RATS group was significantly lower than VATS group (p = 0.046). Moreover, the postoperative length of stay, operation duration, chest tube duration and intraoperative blood loss in RATS group were significantly lower than open surgery group (p < 0.001). RATS is a secure and efficient approach for removing large mediastinal masses at early postoperative period. In comparison with VATS, RATS is associated with lower intraoperative blood loss. Compared with open surgery, RATS is also associated with shorter postoperative length of stay, operation duration, chest tube duration and intraoperative blood loss.

Discovery of Near-Infrared Heptamethine Cyanine Probes for Imaging-Guided Surgery in Solid Tumors.

Near-infrared (NIR) fluorescence imaging has attracted much attention in image-guided interventions with unique advantages. However, the clinical translation rate of fluorescence probes is extremely low, primarily due to weak lesion signal contrast and poor specificity. To address this dilemma, a series of small-molecule near-infrared fluorescence probes have been designed for tumor imaging. Among them, YQ-04-03 showed notable optical stability and remarkable sensitivity toward tumor targeting. Moreover, within a specific concentration and time range against oxidizing reducing agents and laser, it demonstrated better stability than ICG. The retention time of YQ-04-03 in tumors was significantly longer compared to other nonspecific uptake sites in the subjects, and its tumor-to-normal tissue ratio (TNR) outperformed ICG. Successful resection of in situ hepatocarcinoma and peritoneal carcinoma was achieved using probe imaging guidance, with the smallest visual lesion resected measuring approximately 1 mm3. Ultimately, this probe holds great potential for advancing tumor tracer.

A Respiratory Motion Prediction Method Based on LSTM-AE with Attention Mechanism for Spine Surgery.

Respiratory motion-induced vertebral movements can adversely impact intraoperative spine surgery, resulting in inaccurate positional information of the target region and unexpected damage during the operation. In this paper, we propose a novel deep learning architecture for respiratory motion prediction, which can adapt to different patients. The proposed method utilizes an LSTM-AE with attention mechanism network that can be trained using few-shot datasets during operation. To ensure real-time performance, a dimension reduction method based on the respiration-induced physical movement of spine vertebral bodies is introduced. The experiment collected data from prone-positioned patients under general anaesthesia to validate the prediction accuracy and time efficiency of the LSTM-AE-based motion prediction method. The experimental results demonstrate that the presented method (RMSE: 4.39%) outperforms other methods in terms of accuracy within a learning time of 2 min. The maximum predictive errors under the latency of 333 ms with respect to the x, y, and z axes of the optical camera system were 0.13, 0.07, and 0.10 mm, respectively, within a motion range of 2 mm.

Integrating transcriptomics and network pharmacology to reveal the mechanisms of total Rhizoma Coptidis alkaloids against nonalcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY: This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS: The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS: TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS: TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.

Circulating exosomal microRNA-4497 as a potential biomarker for metastasis and prognosis in non-small-cell lung cancer.

Circulating exosomal microRNAs (miRNAs) have shown great potential for the diagnosis, prognosis, and treatment monitoring of patients with non-small-cell lung cancer (NSCLC). Our main purpose was to determine the clinical value of serum exosomal miR-4497 as a new non-invasive biomarker for NSCLC. The exoRNeasy Kit (QIAGEN, Hilden, Germany) was used to isolate exosomes and exoRNA from the serum of 84 patients with NSCLC (NSCLC group), 30 patients with benign lung lesion (BLL group), and 47 healthy controls. Six serum exosomal miRNAs (Let-7b-5p, miR-122-5p, miR-155-5p, miR-223-3p, miR-320c, and miR-4497) were selected as candidate miRNAs and analyzed using real-time qPCR, among which miR-4497 displayed the most striking differences. Exosomal miR-4497 expressed significantly lower in NSCLC than in BLL patients and healthy controls (P < 0.001). Further investigation showed that miR-4497 was negatively correlated with the malignant characteristics of tumors (tumor size, tumor-node-metastasis [TNM] stage, and distant metastasis) and was an independent tumor suppressor (P < 0.05). According to receiver operating characteristic (ROC) analysis, exosomal miR-4497 independently exhibited excellent diagnostic efficacy, which could be improved by combining it with traditional markers (for identifying tumor size, the area under the curve [AUC] = 0.761; TNM stage, AUC = 0.878; distant metastasis, AUC = 0.895; all P < 0.001). Moreover, longitudinal analysis revealed that exosomal miR-4497 levels increased after chemoradiotherapy (P < 0.001). According to the survival analysis, poor overall survival (OS) and disease-free survival (DFS) were associated with low exosomal miR-4497 levels (P < 0.05). Moreover, exosomal miR-4497 was an independent protective factor affecting DFS (hazard ratio = 0.190, P = 0.009) in the Cox proportional hazards model. Therefore, serum exosomal miR-4497 can be used as a potential biomarker to identify NSCLC and healthy individuals or BLL patients for early screening or as a biomarker for staging and grading, prognosis, and monitoring recurrence, metastasis, and the therapeutic effects in patients with NSCLC.

Fixed-Time Recurrent NN Learning Control of Uncertain Robotic Manipulators with Time-Varying Constraints: Experimental Verification.

This paper proposes a learning control framework for the robotic manipulator's dynamic tracking task demanding fixed-time convergence and constrained output. In contrast with model-dependent methods, the proposed solution deals with unknown manipulator dynamics and external disturbances by virtue of a recurrent neural network (RNN)-based online approximator. First, a time-varying tangent-type barrier Lyapunov function (BLF) is introduced to construct a fixed-time virtual controller. Then, the RNN approximator is embedded in the closed-loop system to compensate for the lumped unknown term in the feedforward loop. Finally, we devise a novel fixed-time, output-constrained neural learning controller by integrating the BLF and RNN approximator into the main framework of the dynamic surface control (DSC). The proposed scheme not only guarantees the tracking errors converge to the small neighborhoods about the origin in a fixed time, but also preserves the actual trajectories always within the prescribed ranges and thus improves the tracking accuracy. Experiment results illustrate the excellent tracking performance and verify the effectiveness of the online RNN estimate for unknown dynamics and external disturbances.

In Vivo Staging the Progression of Colitis and Associated Cancer by Concurrent Microimaging of Key Biomarkers.

Currently colorectal cancer (CRC) staging (colitis, adenoma, and carcinoma) mainly relies on ex vivo pathologic analysis requiring an invasive surgical process with limited sample collection and increased metastatic risk. Thus, in vivo noninvasive pathological diagnosis is extremely demanded. By verifying the samples of clinical patients and CRC mouse models, it was found that vascular endothelial growth factor receptor 2 (VEGFR2) was barely expressed in the colitis stage and only appeared in adenoma and carcinoma stages with obvious elevation, while prostaglandin E receptor 4 (PTGER4) could be observed from colitis to adenoma and carcinoma stages with a gradient increase of expression. VEGFR2 and PTGER4 were further chosen as key biomarkers for molecular pathological diagnosis in vivo and corresponding molecular probes were constructed. The feasibility of in vivo noninvasive CRC staging by concurrent microimaging of dual biomarkers using confocal laser endoscopy (CLE) was verified in CRC mouse models and further confirmed by ex vivo pathological analysis. In vivo CLE imaging exhibited the correlation of severe colonic crypt structural alteration with a higher biomarker expression in adenoma and carcinoma stages. This strategy shows promise in benefiting patients undergoing CRC progression with in-time, noninvasive, and precise pathological staging, thus providing valuable guidance for selecting therapeutic strategies.

Rapid and efficient removal of multiple aqueous pesticides by one-step construction boric acid modified biochar.

Tricyclazole, propiconazole, imidacloprid, and thiamethoxam are commonly used pesticides in paddy fields. It is necessary and practical to remove pesticides from the water environment because the low utilization rate of pesticides will produce residues in the water environment. It is known that there are few studies on the preparation of biochar adsorption pesticides by the walnut shell and few studies on the removal of tricyclazole and propiconazole. Based on this, this paper used the walnut shell as raw material and boric acid as an activator to prepare biochar by the one-step method. The boric acid modified walnut shell biochar (WAB4) with a specific surface area of 640.6 m2 g-1, exhibited the high adsorption capacity of all four pesticides (>70%) at pH 3-9. The adsorption capacities of tricyclazole, propiconazole, imidacloprid, and thiamethoxam were 171.67, 112.27, 156.40, and 137.46 mg g-1, respectively. The adsorption kinetics fitted the pseudo-second-order kinetic model and the adsorption isotherm curves conformed to the Freundlich isotherm model. The adsorption of pesticides by WAB4 was associated with hydrogen bonding, pore filling, hydrophobic effects, and π-π interactions. More significantly, WAB4 has excellent adsorption capacity compared to other adsorbents for real water samples. Finally, walnut shell biochar has no significant acute toxicity to Daphnia magna. This work shows that walnut shell-based biochar has a good effect on the removal of pesticides at a wide range of pH and is economical and safe, providing a new idea for the removal of pesticides in water.

LCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine.

AIMS: Nonalcoholic steatohepatitis (NASH) is becoming one of the most common causes of liver transplantation and hepatocellular carcinoma, but no specific drugs are FDA-approved to treat it. 8-cetylberberine (CBBR), which is a long-chain alkane derivative of berberine, exhibits potent pharmacological activities and improves metabolism performance. The aim of this study is to explore the function and mechanism of CBBR against NASH. MATERIALS AND METHODS: L02 and HepG2 hepatocytes were treated with the medium containing palmitic acids and oleic acids (PO) and incubated with CBBR for 12 h, then the levels of lipid accumulation were tested by kits or western blots. C57BL/6 J mice were fed with a high-fat diet or a high-fat/high-cholesterol diet. CBBR (15 mg/kg or 30 mg/kg) was orally administered for 8 weeks. Liver weight, steatosis, inflammation, and fibrosis were evaluated. Transcriptomic indicated the target of CBBR in NASH. KEY FINDINGS: CBBR significantly reduced lipid accumulation, inflammation, liver injury, and fibrosis in NASH mice. CBBR also decreased lipid accumulation and inflammation in PO-induced L02 and HepG2 cells. RNA sequencing and bioinformatics analysis indicated that CBBR inhibited the pathways and key regulators associated with lipid accumulation, inflammation, and fibrosis in the pathogenesis of NASH. Mechanically, CBBR may prevent NASH via inhibiting LCN2, as proved by the finding that the anti-NASH effect of CBBR was more obvious in PO-stimulated HepG2 cells treated with LCN2 overexpression. SIGNIFICANCE: Our work provides an insight into the effectiveness of CBBR in improving metabolic-stress-caused NASH as well as the mechanism by regulating LCN2.

A Novel Robotic Bronchoscope System for Navigation and Biopsy of Pulmonary Lesions.

Transbronchial biopsy sampling, as a minimally invasive method with relatively low risk, has been proved to be a promising treatment in the field of respiratory surgery. Although several robotic bronchoscopes have been developed, it remains a great challenge to balance size and flexibility, while integrating multisensors to realize navigation during complex airway networks. This paper proposes a novel robotic bronchoscope system composed by end effector with relatively small size, relevant actuation unit, and navigation system with path planning and surgical guidance capability. The main part of the end effector is machined by bidirectional groove on a nickel-titanium tube, which can realize bending, rotation, and translation 3 degrees of freedom. A prototype of the proposed robotic bronchoscope system is designed and fabricated, and its performance is tested through several experiments to verify the stiffness, flexibility, and navigation performance. The results show that the proposed system is with good environment adaptiveness, and it can become a promising biopsy method through natural cavity of the human body.

Deep learning-based classification and segmentation for scalpels.

PURPOSE: Scalpels are typical tools used for cutting in surgery, and the surgical tray is one of the locations where the scalpel is present during surgery. However, there is no known method for the classification and segmentation of multiple types of scalpels. This paper presents a dataset of multiple types of scalpels and a classification and segmentation method that can be applied as a first step for validating segmentation of scalpels and further applications can include identifying scalpels from other tools in different clinical scenarios. METHODS: The proposed scalpel dataset contains 6400 images with labeled information of 10 types of scalpels, and a classification and segmentation model for multiple types of scalpels is obtained by training the dataset based on Mask R-CNN. The article concludes with an analysis and evaluation of the network performance, verifying the feasibility of the work. RESULTS: A multi-type scalpel dataset was established, and the classification and segmentation models of multi-type scalpel were obtained by training the Mask R-CNN. The average accuracy and average recall reached 94.19% and 96.61%, respectively, in the classification task and 93.30% and 95.14%, respectively, in the segmentation task. CONCLUSION: The first scalpel dataset is created covering multiple types of scalpels. And the classification and segmentation of multiple types of scalpels are realized for the first time. This study achieves the classification and segmentation of scalpels in a surgical tray scene, providing a potential solution for scalpel recognition, localization and tracking.

Prediction of lung cancer metastasis by gene expression.

Tumor metastasis is the main cause of death in cancer patients. Early prediction of tumor metastasis can allow for timely intervention. At present, research on tumor metastasis mainly focuses on manual diagnosis by imaging or diagnosis by computational methods. With the deterioration of the tumor, gene expression levels in blood change greatly. It is feasible to measure the transcripts of key genes to predict whether cancer will metastasize. Therefore, in this paper, we obtained gene expression data from 226 patients from TCGA. These data included 239,322 transcripts. Background screening and LASSO analysis were used to select 31 transcripts as features. Finally, a deep neural network (DNN) was used to determine whether or not lung cancer would metastasize. We compared our methods with several other methods and found that our method achieved the best precision. In addition, in a previous study, we identified 7 genes that play a vital role in lung cancer. We added those gene transcripts into the DNN and found that the AUC and AUPR of the model were increased.

Hydrophobic-action-driven removal of six organophosphorus pesticides from tea infusion by modified carbonized bacterial cellulose.

The abuse of organophosphorus pesticides (OPPs) in tea planting makes it easy to transfer from tea into its infusion, bringing potential health risks to consumers. Thus, it is essential to adopt reliable techniques to remove OPPs from tea infusion. In this study, three treatment methods were used to modify carbonized bacterial cellulose (CBC) to improve its adsorption performance. Among them, CBC treated by hydrazine hydrate (N-CBC) had the best adsorption effect, whose removal rate for dicrotophos is 13 times that of CBC. The in-depth study of adsorption mechanism proved that hydrophobic interaction dominated the adsorption of OPPs onto N-CBC. The pseudo-second-order kinetic model and Langmuir isotherm model were more suitable to describe the process. Additionally, there were no significant changes in tea infusion quality after N-CBC treatment. This work clarifies that N-CBC benefitted from simple preparation method, excellent adsorption performance and unique adsorption mechanism has potential applications in tea infusion.

JUND facilitates proliferation and angiogenesis of esophageal squamous cell carcinoma cell via MAPRE2 up-regulation.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a globally aggressive malignant tumor. This study aimed to investigate the mechanism of JUND in ESCC development via MAPRE2. METHODS: ESCC cells (KYSE-450 and ECA109) were transfected with small interfering RNA (si)-JUND, si-MAPRE2, si-JUND, or pcDNA3.1-MAPRE2. JUND and MAPRE2 expression in ESCC cells was detected with quantitative real-time polymerase chain reaction and western blot. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to determine ESCC cell proliferation. Dual-luciferase reporter gene and chromatin immunoprecipitation assays were performed to assess binding between JUND and MAPRE2. Human umbilical vein endothelial cells (HUVECs) were co-cultured with ESCC cell supernatants. Angiogenesis was assessed with an in vitro angiogenesis assay. Western blot was conducted to evaluate the expression of angiogenic proteins [vascular endothelial growth factor A (VEGFA), matrix metallopeptidase 9 (MMP-9), and angiopoietin-2 (ang2)]. RESULTS: The levels of expression of JUND and MAPRE2 were high in ESCC cells. Mechanistically, JUND bound to MAPRE2 promoter and increased MAPRE2 transcription. Downregulation of JUND or MAPRE2 inhibited KYSE-450 and ECA109 cell proliferation and reduced the levels of expression of VEGFA, MMP-9, and ang2 and tube formation in HUVECs co-cultured with ESCC cell supernatants. MAPRE2 upregulation counteracted the inhibitory effects of JUND silencing on cell proliferative and angiogenic capabilities in ESCC. CONCLUSIONS: JUND promoted MAPRE2 transcription, thereby facilitating cell proliferative and angiogenic abilities in ESCC.

In vivo near-infrared fluorescence and SPECT-CT imaging of colorectal Cancer using the bradykinin B2R-specific ligand icatibant.

Cancer molecular imaging using specific probes designed to identify target proteins in cancer is a powerful tool to guide therapeutic selection, patient management, and follow-up. We demonstrated that icatibant may be used as a targeting probe for the significantly upregulated bradykinin B2R in colorectal cancer (CRC). Icatibant-based probes with high affinity towards bradykinin B2R were identified. The near-infrared (NIR) fluorescent dye conjugate MPA-PEG3-k-Icatibant and radioconjugate [99mTc]Tc-HYNIC-PEG4-Icatibant exhibited favourable selective and specific uptake in tumours when the subcutaneous and orthotopic colorectal tumour-bearing mouse models were imaged using NIR fluorescence imaging and Single-Photon Emission Computed Tomography-Computed Tomography (SPECT-CT), respectively. The tracer of [99mTc]Tc-HYNIC-PEG4-Icatibant accumulated in tumours according to biodistribution studies and peaked at 4 h with an uptake value of 3.41 ± 0.27%ID/g in HT29 tumour-bearing nude mice following intravenous injection (i.v.). The tumour-to-colorectal signal ratios were 5.03 ± 0.37, 15.45 ± 0.32, 13.58 ± 1.19 and 11.33 ± 1.73 1, 2, 4 and 6 h after tail-veil injection, respectively. Overall, in the wake of rapid and precise tumour delineation and penetration characteristics, icatibant-based probes represent promising high-contrast molecular imaging probes for the detection of bradykinin B2R.