Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling.

Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11-FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11-FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11-FIP2 in NPC biopsies. Instead of regulating the epithelial-mesenchymal transition or Akt signaling pathway, knockdown of Rab11-FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11-FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.

Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention.

BACKGROUND: 3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC). METHODS: The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay. RESULTS: The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial-mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level. CONCLUSIONS: Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.

Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.

Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20-74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded.

An Integrated Wireless Wearable Sensor System for Posture Recognition and Indoor Localization.

In order to provide better monitoring for the elderly or patients, we developed an integrated wireless wearable sensor system that can realize posture recognition and indoor localization in real time. Five designed sensor nodes which are respectively fixed on lower limbs and a standard Kalman filter are used to acquire basic attitude data. After the attitude angles of five body segments (two thighs, two shanks and the waist) are obtained, the pitch angles of the left thigh and waist are used to realize posture recognition. Based on all these attitude angles of body segments, we can also calculate the coordinates of six lower limb joints (two hip joints, two knee joints and two ankle joints). Then, a novel relative localization algorithm based on step length is proposed to realize the indoor localization of the user. Several sparsely distributed active Radio Frequency Identification (RFID) tags are used to correct the accumulative error in the relative localization algorithm and a set-membership filter is applied to realize the data fusion. The experimental results verify the effectiveness of the proposed algorithms.

Online Monitoring for Human Sit-to-Stand Movement Based on Karush-Kuhn-Tucker Optimized Zonotope Set-Membership Filter.

As the global aging population continues to grow, there has been a significant increase in the number of fall-related injuries among the elderly, primarily due to reduced muscle strength and balance control, especially during sit-to-stand (STS) movements. Intelligent wearable robots have the potential to provide fall prevention assistance to individuals at risk, but an accurate and timely assessment of human movement stability is essential. This article presents a fall prediction algorithm for STS movements based on the Karush-Kuhn-Tucker (KKT) optimized zonotope set-membership filter (KKT-ZSMF), enabling real-time assessment of human stability. To quantify the feasible stability region of human STS movement, a mathematical model is proposed based on dynamic stability theory. Additionally, an online fall-prediction approach is developed, utilizing the zonotope set-membership filter to iteratively update the set that represents the instantaneous stability region. The approach incorporates a KKT optimization algorithm to compute the optimal convex hull, thereby enhancing the accuracy and efficiency of the set-membership filter. Experimental validation is conducted with the participation of 13 subjects including 5 elderly subjects, comparing the performance of the proposed KKT-ZSMF algorithm with other relevant methods. The results confirm the accuracy and real-time performance of the KKT-ZSMF algorithm for predicting human STS movement stability, achieving an overall prediction accuracy of 93.49% and a runtime of no more than 7.91 ms. These findings demonstrate the suitability of the algorithm for fall prevention assistance in daily activities.

Development of a knowledge, attitude and practice questionnaire on urine leakage with an indwelling urethral catheter for nurses in China.

AIM: A knowledge, attitude and practice questionnaire on urine leakage (UL) with an indwelling urethral catheter (IUC) was developed for nurses in China and validated. DESIGN: Observational study. METHODS: A systematic literature review, the Delphi method and focus group evaluation were used to develop the questionnaire, which was administered to 304 registered nurses at two hospitals in Guangdong, China. The validity and reliability of the questionnaire were assessed. RESULTS: The 27-item questionnaire had four dimensions: knowledge I (aetiology), knowledge II (prevention and treatment), attitude and practice. The questionnaire showed excellent content validity and reliability. Four factors accounted for 70.526% of the variance. The data were well-fitted to the four-factor construct model. The questionnaire can be used to measure the knowledge of UL with an IUC among nurses in China, along with related attitudes and practices. This can improve nursing care of patients with IUCs. No patient or public contribution.

Gaze and Environmental Context-Guided Deep Neural Network and Sequential Decision Fusion for Grasp Intention Recognition.

Grasp intention recognition plays a crucial role in controlling assistive robots to aid older people and individuals with limited mobility in restoring arm and hand function. Among the various modalities used for intention recognition, the eye-gaze movement has emerged as a promising approach due to its simplicity, intuitiveness, and effectiveness. Existing gaze-based approaches insufficiently integrate gaze data with environmental context and underuse temporal information, leading to inadequate intention recognition performance. The objective of this study is to eliminate the proposed deficiency and establish a gaze-based framework for object detection and its associated intention recognition. A novel gaze-based grasp intention recognition and sequential decision fusion framework (GIRSDF) is proposed. The GIRSDF comprises three main components: gaze attention map generation, the Gaze-YOLO grasp intention recognition model, and sequential decision fusion models (HMM, LSTM, and GRU). To evaluate the performance of GIRSDF, a dataset named Invisible containing data from healthy individuals and hemiplegic patients is established. GIRSDF is validated by trial-based and subject-based experiments on Invisible and outperforms the previous gaze-based grasp intention recognition methods. In terms of running efficiency, the proposed framework can run at a frequency of about 22 Hz, which ensures real-time grasp intention recognition. This study is expected to inspire additional gaze-related grasp intention recognition works.

A Flexible Wearable Supernumerary Robotic Limb for Chronic Stroke Patients.

In this study, we present a flexible wearable supernumerary robotic limb that helps chronic stroke patients with finger rehabilitation and grasping movements. The design of this innovative limb draws inspiration from bending pneumatic muscles and the unique characteristics of an elephant's trunk tip. It places a strong emphasis on crucial factors such as lightweight construction, safety, compliance, waterproofing, and achieving a high output-to-weight/pressure ratio. The proposed structure enables the robotic limb to perform both envelope and fingertip grasping. Human-robot interaction is facilitated through a flexible bending sensor, detecting the wearer's finger movements and connecting them to motion control via a threshold segmentation method. Additionally, the system is portable for versatile daily use. To validate the effectiveness of this innovation, real-world experiments involving six chronic stroke patients and three healthy volunteers were conducted. The feedback received through questionnaires indicates that the designed mechanism holds immense promise in assisting chronic stroke patients with their daily grasping activities, potentially improving their quality of life and rehabilitation outcomes.

Construction and analysis of a lncRNA-miRNA-mRNA competing endogenous RNA network from inflamed and normal synovial tissues after anterior cruciate ligament and/or meniscus injuries.

Background: Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with posttraumatic osteoarthritis (PTOA) development, the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to PTOA. Methods: Twelve patients with ACL tears and/or meniscus injuries were recruited. During surgery, synovial tissues were obtained from the injured knees. The inflammation status of the synovium was characterized according to macroscopic criteria and histological synovitis grades. Then the synovial tissues were classified as control group or inflamed group. High-throughput RNA sequencing of the synovial samples (3 vs. 3) was conducted to identify differentially expressed (DE) RNAs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate DE mRNAs. Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses. Associations of the identified DE genes (DEGs) with infiltrating immune cells were explored using Pearson correlation analysis. Results: The results showed that 2793 mRNAs, 3392 lncRNAs and 211 miRNAs were significantly DE between two groups. The top 3 significantly upregulated GO terms and KEGG pathways were immune response, adaptive immune response and immune system process, systemic lupus erythematosus, haematopoietic cell lineage and cytokine-cytokine receptor interaction, respectively. In PPI networks, the top 10 hub genes were IL6, CCR7, C3, CCR5, CXCR3, CXCL8, IL2, CCR3, CCR2 and CXCL1. Seven mRNAs (EPHA5, GSN, ORC1, TLN2, SOX6, NKD2 and ADAMTS19), 4 lncRNAs (MIR4435-2HG, TNXA, CEROX1 and TMEM92-AS1) and 3 miRNAs (miR-486-5p, miR-199a-3p and miR-21-3p) were validated by quantitative real-time polymerase chain reaction and sub-networks were constructed. In correlation analysis, MMP9 correlated positively with M0 macrophages and plasma cells, NKD2 positively with CD8 T cells, and CCR7 and IL2RB positively with naive B cells. Conclusion: Our study provides foundational synovial inflammation profiles following knee trauma. The ceRNA and PPI networks provide new insight into the biological processes and underlying mechanisms of PTOA. The differential infiltration profiles of immune cells in synovium may contribute to PTOA development. This study also highlights immune-related DEGs as potential PTOA treatment biomarkers.

Radiation Therapy-Induced Changes of the Nasopharyngeal Commensal Microbiome in Nasopharyngeal Carcinoma Patients.

PURPOSE: The human commensal microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes in commensal microbes in patients with cancer during radiation therapy. We conducted a prospective, longitudinal proof-of-concept cohort study with patients with newly diagnosed nasopharyngeal carcinoma (NPC) who underwent radiation therapy-based treatment. METHODS AND MATERIALS: Nasopharyngeal swabs were collected before radiation therapy, twice per week during radiation therapy, and after radiation therapy. The nasopharyngeal microbiome was assessed using 16S rRNA amplicon sequencing. A patient's response to treatment was measured 3 months after the completion of radiation therapy as a short-term clinical outcome. In total, 39 NPC patients with 445 nasopharyngeal samples were analyzed. RESULTS: There was stable temporal change in the community structure of the nasopharyngeal microbiome among patients with NPC during treatment (P = .0005). Among 73 abundant amplicon sequence variants (ASVs), 7 ASVs assigned to genus Corynebacterium decreased significantly during the treatment (W-statistic >80%); 23 ASVs showed statistically significant changes in the ratio of abundance between early and late responders during treatment (false discovery rate <0.05). CONCLUSIONS: This study addressed stable temporal change in the nasopharyngeal microbiome among patients with NPC during radiation therapy-based treatment and provided preliminary evidence of an association with a short-term clinical outcome.

Inactivation of HMGCL promotes proliferation and metastasis of nasopharyngeal carcinoma by suppressing oxidative stress.

Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular ß-hydroxybutyrate (ß-HB) production, thereby reducing reactive oxygen species (ROS) generation. Ectopic expression of HMGCL restored ß-HB level, associated with suppressed proliferation and colony formation of NPC cells in vitro and decreased tumorigenicity in vivo. HMGCL suppressed the migration and invasion of NPC cells in vitro via mesenchymal-epithelial transition. Furthermore, extracellular ß-HB supply suppressed the proliferation and migration of NPC cells. Both intra- and extracellular ß-HB exerting a suppressive role in NPC depends on ROS generation. Ketogenesis may be impaired in NPC cells due to lack of HMGCL expression, suggesting that it may be a promising target in NPC therapy.