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Background: The tumor microenvironment (TME) of colorectal cancer (CRC) mainly comprises immune cells, stromal cells, tumor cells, as well as the extracellular matrix (ECM), which holds a pivotal position. The ECM affects cancer progression, but its regulatory roles and predictive potential in CRC are not fully understood. Methods: We analyzed transcriptomes from CRC tumors and paired normal tissues to study ECM features. Up-regulated ECM components were examined through functional enrichment analysis, and single-cell sequencing identified cell types producing collagen, regulators, and secreted factors. Transcription factor analysis and cell-cell interaction studies were conducted to identify potential regulators of ECM changes. Additionally, a prognostic model was developed using TCGA-CRC cohort data, focusing on up-regulated core ECM components. Results: Bulk RNA-seq analysis revealed a unique ECM pattern in tumors, with ECM abundance and composition significantly related to patient survival. Up-regulated ECM components were linked to various cancer-related pathways. Fibroblasts and non-fibroblasts interactions were crucial in forming the TME. Key potential regulators identified included ZNF469, PRRX2, TWIST1, and AEBP1. A prognostic model based on five ECM genes (THBS3, LAMB3, ESM1, SPRX, COL9A3) demonstrated strong associations with immune suppression and tumor angiogenesis. Conclusions: The ECM components were involved in various cell-cell interactions and correlated with tumor development and poor survival outcomes. The ECM prognostic model components could be potential targets for novel therapeutic interventions in colorectal cancer.

Abstract The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.

Abstract Ubiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/β-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.

Spatio-temporal information is an important basis for the construction of intelligent coal mines. How to build the unified integrated control and decision-making platform of mining area based on multi-dimensional GIS is of significance to improve the practicability and operability of the intelligent system. Aiming at the problems existing in the construction process of intelligent mines and intelligent mining areas, such as the single management and application mode of mining area level GIS, the lack of research and application of full scene business in a multi-level control mode, the lack of spatial dimension fusion analysis in multi-source data applications, and the lack of multi-system spatial collaborative control mechanism in production equipment control, the overall frame-work design of intelligent mining area cloud platform based on 4DGIS was proposed. The three-level application fusion technology of “Cloud Edge Device” hierarchical architecture based on the data base of “4DGIS+ digital twin”, the application technology of cross-database multi-source data fusion based on big data, and the collaborative control technology of autonomous controllable equipment group based on 4DGIS were studied. The spatio-temporal graph reasoning model integrating multiple features, the decision support model application sub-platform based on big data, and the 4DGIS cooperative control sub-platform were developed. The intelligent mining cloud platform for the holographic visual production factors, collaborative control of production systems, and intelligent calculation of production management of “the group + mines” was constructed. The platform implemented the functions of one button intelligent patrol inspection under the coal mine based on the “4DGIS+digital twin” data base, collaborative control of the whole production process from “maintenance mode” to “production mode”, intelligent decision analysis based on big data and so on. The leap from the single system intelligent to the whole mining area intelligent systematization was completed. The related technology has been applied in Huangling Mining Company and its No.1 Coal Mine, No.2 Coal Mine, Shuanglong Coal Mine and Ruineng Coal Mine, which has improved the efficiency of mine safety production management and control and the intelligent decision-making level of the group company.

Abstract Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel–Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.

Abstract Background Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles. Methods All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis. Results 365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy. Conclusions Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.

Abstract Image captioning means generate descriptive sentences from a query image automatically. It has recently received widespread attention from the computer vision and natural language processing communities as an emerging visual task. Currently, both components have evolved considerably by exploiting object regions, attributes, attention mechanism methods, entity recognition with novelties, and training strategies. However, despite the impressive results, the research has not yet come to a conclusive answer. This survey aims to provide a comprehensive overview of image captioning methods, from technical architectures to benchmark datasets, evaluation metrics, and comparison of state‐of‐the‐art methods. In particular, image captioning methods are divided into different categories based on the technique adopted. Representative methods in each class are summarized, and their advantages and limitations are discussed. Moreover, many related state‐of‐the‐art studies were quantitatively compared to determine the recent trends and future directions in image captioning. The ultimate goal of this work is to serve as a tool for understanding the existing literature and highlighting future directions in the area of image captioning for Computer Vision and Natural Language Processing communities may benefit from.

As the explosive growth of the data volume, data center is playing a critical role to store and process huge amount of data. Traditional single data center can no longer to adapt into incredibly fast-growing data. Recently, some researches have extended the tasks such data processing to geographically distributed data centers. However, since the joint consideration of task placement and data transfer, it is complex and difficult to design a proper scheduling approach with the goal of minimizing makespan under the constraint of task dependencies, processing capability and network, etc. Therefore, our work proposes $JHTD$ : an efficient joint scheduling framework based on hypergraph for task placement and data transfer across geographically distributed data centers. Generally, there are two crucial stages in $JHTD$ . Initially, due to the outstanding of hypergraphs in modeling complex problems, we have leveraged a hypergraph-based model to establish the relationship between tasks, data files, and data centers. Thereafter, a hypergraph-based partition method has been developed for task placement within the first stage. In the second stage, a task reallocation scheme has been devised in terms of each task-to-data dependency. Meanwhile, a data dependency aware transferring scheme has been designed to minimize the makespan. Last, the real-world model China-VO project has been used to conduct a variety of simulation experiments. The results have demonstrated that $JHTD$ effectively optimizes the problems of task placement and data transfer across geographically distributed data centers. $JHTD$ has been compared with three other state-of-the-art algorithms. The results have demonstrated that $JHTD$ can reduce the makespan by up to 20.6%. Also, various impacts (data transfer volume and load balancing) have been taken into account to show and discuss the effectiveness of $JHTD$ .

This paper presents an adaptive control scheme via combining with an unknown system dynamics estimator (USDE) for attitude control of quadrotors subject to both parametric uncertainties and external disturbances. The presented controller is designed by effectively merging an adaptive control with an USDE via backstepping, where the extraneous uncertainties are addressed by USDE, and the adaptive law driven by tracking errors accounts for identifying unknown inertial moment constants. The unique characteristic is that a reinforced attitude controlling can be realized benefiting from the separate handling of parametric uncertainties and disturbances via an adaptive updating and a concise disturbance observation, significantly releasing the learning load of USDE and a high gain can be avoided in feedback loops. Meanwhile, Lyapunov analysis demonstrates that all error variables are uniformly ultimately bounded in the closed-loop system. Eventually, simulations substantiate the utility of suggested control strategy.

Integrated electro-absorption-modulated distributed feedback laser diodes (EMLs) are attracting much interest in optical communications for the advantages of a compact structure, low power consumption, and high-speed modulation. In integrated EML, the microwave interaction between the distributed feedback laser diode (DFB-LD) and the electro-absorption modulator (EAM) has a nonnegligible influence on the modulation performance, especially at the high-frequency region. In this paper, integrated EML was investigated as a three-port network with two electrical inputs and a single optical output, where the scattering matrix of the integrated device was theoretically deduced and experimentally measured. Based on the theoretical model and the measured data, the microwave equivalent circuit model of the integrated device was established, from which the microwave interaction between DFB-LD and EAM was successfully extracted. The results reveal that the microwave interaction within integrated EML contains both the electrical isolation and optical coupling. The electrical isolation is bidirectional while the optical coupling is directional, which aggravates the microwave interaction in the direction from DFB-LD to EAM.

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

ObjectiveWe analysed the diagnostic performance of thyroglobulin in fine-needle aspiration (FNA-Tg) in the suspicious lateral cervical lymph nodes (CLNs) in patients with papillary thyroid cancer (PTC), proposed the best cutoff value and discussed the factors that may affect the diagnostic value of FNA-Tg.MethodsIn the present study, a retrospective analysis of 403 patients with PTC with 448 suspected lateral CLNs metastasis from October 2019 to May 2021 was performed. The cutoff value according to the receiver operating characteristic (ROC) curve was determined, and the Wilcoxon rank-sum test was used to evaluate the correlation between FNA-Tg and factors.ResultsAccording to the ROC curve, the cutoff value of FNA-Tg was 3.69 ng/ml (sensitivity, 92.48%; specificity, 75.00%). Patients who underwent total thyroidectomy were excluded. Compared with US and FNAC, the diagnostic performance of FNA-Tg was the greatest, especially for small CLNs (diameter ≤ 1 cm), cystic CLNs, and patients with Hashimoto’s thyroiditis (HT). Moreover, FNA-Tg levels were correlated with the presence of HT (p = 0.003), the anti-thyroglobulin antibody (Tg-Ab) (p < 0.001), the ratio of metastatic lateral CLNs (p = 0.004) and Tg assay kits (p < 0.001).ConclusionsFNA-Tg measurement is sensitive enough for diagnosing lateral CLN metastases from PTC, but its diagnostic value is compromised by a number of factors.

ObjectiveThe right cervical central lymph nodes include lymph nodes anterior to the right recurrent laryngeal nerve (LN-arRLN) and lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN), and are separated by the right recurrent laryngeal nerve (RLN). LN-prRLN is a common site of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the complexity in anatomical structure brings difficulties in determining the surgical scope, so it is necessary to assess the pattern and predictive factors of right cervical central lymph nodes, especially LN-prRLN metastasis in papillary thyroid carcinoma.MethodsA total of 562 diagnosed PTC patients who underwent right or total thyroidectomy were enrolled in this retrospective study. The clinicopathological features were collected, univariate and multivariate analyses were performed to determine predictive factors of the right central lymph node metastasis.ResultsIn this study, the metastatic rates of the right CLN, the LN-arRLN and the LN-prRLN were 59.6% (335/562), 51.8% (291/562) and 30.4% (171/562), respectively. And 22.6% (127/562) of patients had both LN-arRLN and LN-prRLN metastasis. Among patients without LN-arRLN metastasis, the rate of LN-prRLN metastasis was 16.2% (44/271), accounting for 25.7% of the LN-prRLN metastasis group. Factors associated with an increased risk of LN-arRLN metastasis include male, age below 55 years, tumor size > 1cm, extrathyroidal extension (ETE), clinical lymph nodes metastasis(cN1), lateral lymph node metastasis, and left CLN metastasis. In addition, ETE, lateral lymph node metastasis, and LN-arRLN metastasis were independent factors of LN-prRLN metastasis. The predictive factors of LN-prRLN in cN0 PTC were further explored, revealing that tumor size ≥1.5cm, ETE, and LN-arRLN metastasis were independent predictors of LN-prRLN metastasis in cN0 PTC.ConclusionThe LN-prRLN should not be ignored in surgery because of its high rate of metastasis. Our findings indicate that thorough dissection of central lymph nodes, especially LN-prRLN is crucial in clinical work.

In tasks of transmission line defect detection, traditional object detection algorithms are ineffective, with few training samples of defective components. Meta-learning uses multi-task learning as well as fine-tuning to learn common features in different tasks, which has the ability to adapt to new tasks quickly, shows good performance in few-shot object detection, and has good generalization in new tasks. For this reason, we proposed a few-shot defect detection method (Meta PowerNet) with a Meta-attention RPN and Feature Reconstruction Module for transmission lines based on meta-learning. First, in the stage of region proposal, a new region proposal network (Meta-Attention Region Proposal Network, MA-RPN) is designed to fuse the support set features and the query set features to filter the noise in anchor boxes. In addition, it has the ability to focus on the subtle texture features of smaller-sized objects by fusing low-level features from the query set. Second, in the meta-feature construction stage, we designed a meta-learner with the defect feature reconstruction module as the core to capture and focus on the defect-related feature channels. The experimental results show that under the condition, there are only 30 training objects for various types of component defects. The method achieves 72.5% detection accuracy for component defects, which is a significant improvement compared with other mainstream few-shot object detection. Meanwhile, the MA-RPN designed in this paper can be used in other meta-learning object detection models universally.

BackgroundDue to the lack of large-scale clinical trials, the treatment strategies of small bowel adenocarcinoma (SBA) are controversial, especially for stage II patients. According to the National Comprehensive Cancer Network (NCCN) guideline, few lymph nodes (LNs) examined (

A textured structure of Ni–Mn–Sn Heusler alloy with [001] preferred orientation has been grown by the directional solidification method. The crystal exhibits a single austenite phase L21 cubic structure (a = 5.997 Å) at room temperature. Magnetization and electronic transport measurements reveal the phase transformation characteristics. The maximum values of magnetic entropy change determined by Maxwell’s thermodynamic relation during the structural and magnetic phase transformations are 3.5 J/kg·K and −4.1 J/kg·K, and the total effective refrigerant capacity reaches about 314 J/kg (5 T). The evident reduction in hysteresis loss and broad operating temperature window provide a greater prospect for improving the cyclic stability of refrigeration and optimizing the application of such a magnetic refrigeration material. Both magnetoresistance (−18%, 5 T) and exchange bias field (302 Oe, 2 K) have also been investigated to understand the nature of phase transformations and exchange interactions. Furthermore, as the material exhibits excellent mechanical properties (1068 MPa, 9.0%), our experimental results provide a new reference for the application of Ni–Mn–Sn Heusler alloys.

BRAF mutated colon cancer presents with poor survival, and the treatment strategies are controversial. The tumor microenvironment, which plays a key role in tumorigenesis as well as responses to treatments, of this subtype is largely unknown. In the present study, we analyzed the differences of immune microenvironments between BRAF mutated and BRAF wild-type colon cancer utilizing datasets from The Cancer Genome Atlas and Gene Expression Omnibus and confirmed the findings by tissue specimens of patients. We found that BRAF mutated colon cancer had more stromal cells, more immune cell infiltration, and lower tumor purity. Many immunotherapeutic targets, including PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3, were highly expressed in BRAF mutated patients. BRAF mutation was also correlated with higher proportions of neutrophils and macrophages M1, and lower proportions of plasma cells, dendritic cells resting, and T cells CD4 naïve. In conclusion, our study demonstrates a different pattern of the immune microenvironment in BRAF mutated colon cancer and provides insights into the future use of checkpoint inhibitors in this subgroup of patients.

IntroductionTo assess the risk factor for the central lymph node (CLN) metastasis and investigated the surgery extent of lymph node dissection for patients with isthmic PTC (papillary thyroid carcinoma).Materials and MethodsA total of 669 patients with a single nodule of isthmic PTC were retrospectively reviewed. The propensity score matching was performed twice separately. 176 patients respectively from patients who underwent thyroidectomy plus bilateral central lymph node dissection (BCLND) and who underwent thyroidectomy plus unilateral central lymph node dissection (UCLND) were matched. 77 patients were respectively selected from patients who underwent thyroidectomy plus BCLND and who underwent thyroidectomy with no central lymph node dissection (NCLND) were matched.ResultsAmong all the patients who underwent BCLND, 81/177 (45.76%) was confirmed with histologically positive CLN metastasis, and the occult lymph node metastasis is 25.42%. A tumor size of 1.05 cm was calculated as the cutoff point for predicting CLN metastasis by ROC curve analysis with 177 patients who underwent BCLND. The 5-year recurrence-free survival (RFS) rates were 92.9% in the NCLND group and 100% in the BCLND group with P1cm, capsule invasion and lymphovascular invasion were significantly associated with CLN metastasis, while only age and lymphovascular invasion were proved to be independent risk factors related to contralateral CLN metastasis.ConclusionsThe thyroidectomy with NCLND could be insufficient for patients with isthmic PTC especially for those patients with high risk of central lymph node metastasis, considering that the rate of occult lymph node metastasis could not be ignored.

The Delphian lymph node (DLN), also known as the prelaryngeal node, is one component of the central lymph node. The DLN has been well studied in laryngeal cancer, although its significance in papillary thyroid cancer (PTC) remains unclear. We retrospectively analyzed 936 patients with PTC who underwent thyroidectomy by a single surgeon in Tianjin Cancer Hospital from 2017 to 2019. Moreover, 250 PTC patients who underwent thyroidectomy by another surgeon in Tianjin Cancer Hospital from January 2019 to April 2019 were used as a validation cohort. Among the 936 patients with PTC, 581 patients (62.1%) had DLNs, of which 177 samples with metastasis (177/581, 30.5%) were verified. DLN metastasis was significantly correlated with sex, age, tumor size, bilateral cancer, multifocality, extrathyroidal extension, lymphovascular invasion and central and lateral neck lymph node metastasis. Multivariate analysis revealed that independent risk factors for DLN metastasis included age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis, which determined the nomogram. In particular, tumor size was proven to be one of the most predominant single predictors. The diagnostic model had an area under the curve (AUC) of 0.829 (95% confidence interval, 0.804–0.854). The internal and external validations of the nomogram were 0.819 and 0.745, respectively. Our results demonstrate that DLN metastasis appears to be a critical parameter for predicting metastatic disease of the central compartments. Furthermore, this study provides a precise criterion for assessing DLN metastasis and has great clinical significance for treating PTC.

We aimed to explore the effect of a new health education model on continuous nursing care in elderly patients with diabetes mellitus who had undergone an operation for fracture.

Heusler alloys crystallize in a close-packed cubic structure, having a four-atom basis forming a face-centred cubic lattice. By selecting different composite elements, Heusler alloys provide a large family of members for frontier research of spintronics and magnetic materials and devices. In this paper, the structural, electronic and magnetic properties of a novel quaternary Heusler alloy, PdMnTiAl, have been investigated using a first-principles computational materials calculation. It was found that the stable ordered structure is a non-magnetic Y-type1, in good agreement with the Slater–Pauling rule. From the band structure and the density of states, it is predicted that this Y-type1 configuration is a new gapless semi-metal material. Furthermore, it was discovered that the Pd–Mn swap-disordered structure is more stable than the Y-type1 structure. The present work provides a guide for experiments to synthesize and characterize this Heusler alloy.

A new artificial spin ice lattice called vortex lattice is proposed based on the Kagome lattice. Monte Carlo simulations were performed to investigate the magnetization reversal process of the new artificial spin ice lattice at external magnetic field and different lattice parameters. The results demonstrate some interesting phenomena which are different from Kagome lattice. There are four typical sub-structures emerged in the vortex lattice, which are clockwise and counter-clockwise hexagons, and frustrated +3q and -3q vertices. The occurrence frequency of the four sub-structures change dramatically at different lattice parameter. The new lattice can be partially frustrated at different lattice parameter.

Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.

A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO− in living cells, image ONOO− in paw edema mice and evaluate anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]