Autonomous Landing of Quadrotor Unmanned Aerial Vehicles Based on Multi-Level Marker and Linear Active Disturbance Reject Control.

Landing on unmanned surface vehicles (USV) autonomously is a critical task for unmanned aerial vehicles (UAV) due to complex environments. To solve this problem, an autonomous landing method is proposed based on a multi-level marker and linear active disturbance rejection control (LADRC) in this study. A specially designed landing board is placed on the USV, and ArUco codes with different scales are employed. Then, the landing marker is captured and processed by a camera mounted below the UAV body. Using the efficient perspective-n-point method, the position and attitude of the UAV are estimated and further fused by the Kalman filter, which improves the estimation accuracy and stability. On this basis, LADRC is used for UAV landing control, in which an extended state observer with adjustable bandwidth is employed to evaluate disturbance and proportional-derivative control is adopted to eliminate control error. The results of simulations and experiments demonstrate the feasibility and effectiveness of the proposed method, which provides an effective solution for the autonomous recovery of unmanned systems.

Surgical anatomy of the lingual lymph nodes: systematic literature analysis and proposition for topographic classification.

PURPOSE: Metastatic involvement of the lingual lymph nodes (LLNs) in oral cavity squamous cell cancer (SCC) has recently been proven to significantly reduce locoregional control and survival. Despite recent refinements in the detection of these lesions, the understanding of the LLN topographic anatomy among clinicians is limited. A proposition of a topographic division on LLN based on a comprehensive literature search and synthesis may be helpful in this condition. METHODS: A literature search and election based on contemporary PRISMA guidelines was performed for sources on LLN anatomy with special attention on their subdivision. RESULTS: Four topographic LLN subgroups were defined: median-between genioglossal and geniohyoid muscles; intermediate parahyoid-medial to the hyoglossal muscle, at the greater cornu of the hyoid bone; lateral sublingual (paraglandular) LLNs-at the sublingual salivary gland; lateral submandibular (paraglandular) LLNs -lateral to the hyoglossal muscle, at the deep surface of the submandibular salivary gland. CONCLUSION: The development and implementation of a unified anatomical topographic classification of LLN subgroups may be among the important conditions for improving the detection and treatment of LLN lesions.

Single-Cell Quantitative Phenotyping via the Aptamer-Mounted Nest-PCR (Apt-nPCR).

Analyzing single-cell phenotypes is increasingly required in biomedical studies, for non-genetic understanding of cellular activities and the biological significance of rare cell subpopulations. However, as compared to the genotypic analysis, single-cell phenotype analysis is technically more challenging. Herein, a tractable method that allows quantitative phenotyping of single cell is developed in this work, termed as the aptamer-mounted nest-PCR (Apt-nPCR). In specific, only two rounds of PCR reactions are required to complete the analysis, where aptamers (short oligonucleotides that bind to specific target molecules) are used as the recognition elements to bind antigens and also as the templates of nPCR for multiplexed and quantitative detection. So, quantitative information of these target antigens can be revealed by quantitative PCR analysis of these aptamers, which can thus be used to interpret cell phenotypes in a quantitative-to-qualitative way. By addressing two technical issues that are involved in single-cell phenotype analysis─multiplexed detection plus high sensitivity, we have shown the availability of this method for single-cell phenotyping. Therefore, the Apt-nPCR method may represent a tractable method to facilitate the single-cell phenotype analysis, which can be used as a complementary method against these single-cell genotyping methods in our daily research.

Long noncoding RNA ZEB1-AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer cells.

PURPOSE: The long noncoding RNA (lncRNA) ZEB1-AS1 is reported overexpressed in sensitive ovarian cancer cells A2780 compared with paclitaxel (PTX)-and cisplatin (DDP)- resistant. However, the function and mechanism of ZEB1-AS1 in EOC cells still unknown. METHODS: We used quantitative real-time PCR (qPCR) to detect ZEB1-AS1 expression in A2780 and A2780/R cells. A combination of siRNA, plasmids, CCK8 and flow cytometry was used to detect the effect of ZEB1-AS1 on ovarian cancer cell A2780 PTX and DDP resistance. Transcriptome sequencing, qPCR, and western blot were used for further mechanistic studies. RESULTS: ZEB1-AS1 depletion using siRNA in chemosensitive A2780 cells significantly increased PTX and DDP resistance. In contrast, ZEB1-AS1 overexpression in PTX- and DDP-resistant A2780/resistant (A2780/R) cells reversed the observed drug resistance. Thus, ZEB1-AS1 plays an important role in PTX and DDP resistance in EOC cells. However, quantitative real-time PCR (qPCR) and western blot results suggested that ZEB1-AS1 did not regulate chemoresistance through regulation of ZEB1 protein. We used sequencing to detect mRNA expression changes in A2780 cells after ZEB1-AS1 silencing. The results indicated that MMP19 was the likely downstream factor of ZEB1-AS1. We further examined whether ZEB1-AS1 played an important role in chemoresistance by silencing MMP19 in ZEB1-AS1-overexpressing cells. CCK8 assay results suggested that MMP19 knockdown promoted ZEB1-AS1-induced chemoresistance to PTX and DDP in A2780 cells. CONCLUSION: This study is the first to reveal that ZEB1-AS1 plays a pivotal role in cancer chemoresistance.

Repeated fed-batch strategy and metabolomic analysis to achieve high docosahexaenoic acid productivity in Crypthecodinium cohnii.

BACKGROUND: Docosahexaenoic acid (DHA) is essential for human diet. However, high production cost of DHA using C. cohnii makes it currently less competitive commercially, which is mainly caused by low DHA productivity. In recent years, repeated fed-batch strategies have been evaluated for increasing the production of many fermentation products. The reduction in terms of stability of culture system was one of the major challenges for repeated fed-batch fermentation. However, the possible mechanisms responsible for the decreased stability of the culture system in the repeated fed-batch fermentation are so far less investigated, restricting the efforts to further improve the productivity. In this study, a repeated fed-batch strategy for DHA production using C. cohnii M-1-2 was evaluated to improve DHA productivity and reduce production cost, and then the underlying mechanisms related to the gradually decreased stability of the culture system in repeated fed-batch culture were explored through LC- and GC-MS metabolomic analyses. RESULTS: It was discovered that glucose concentration at 15-27 g/L and 80% medium replacement ratio were suitable for the growth of C. cohnii M-1-2 during the repeated fed-batch culture. A four-cycle repeated fed-batch culture was successfully developed and assessed at the optimum cultivation parameters, resulting in increasing the total DHA productivity by 26.28% compared with the highest DHA productivity of 57.08 mg/L/h reported using C. cohnii, including the time required for preparing seed culture and fermentor. In addition, LC- and GC-MS metabolomics analyses showed that the gradually decreased nitrogen utilization capacity, and down-regulated glycolysis and TCA cycle were correlated with the decreased stability of the culture system during the long-time repeated fed-batch culture. At last, some biomarkers, such as Pyr, Cit, OXA, FUM, L-tryptophan, L-threonine, L-leucine, serotonin, and 4-guanidinobutyric acid, correlated with the stability of culture system of C. cohnii M-1-2 were identified. CONCLUSIONS: The study proved that repeated fed-batch cultivation was an efficient and energy-saving strategy for industrial production of DHA using C. cohnii, which could also be useful for cultivation of other microbes to improve productivity and reduce production cost. In addition, the mechanisms study at metabolite level can also be useful to further optimize production processes for C. cohnii and other microbes.

Roles of microRNAs in preeclampsia.

Preeclampsia (PE) is a complex disorder that is characterized by hypertension and proteinuria after the 20th week of pregnancy, and it causes most neonatal morbidity and perinatal mortality. Most studies suggest that placental dysfunction is the main cause of PE. However, genetic factors, immune factors, and systemic inflammation are also related to the pathophysiology of this syndrome. Thus far, the exact pathogenesis of PE is not yet fully understood, and intense research efforts are focused on PE to elucidate the pathophysiological mechanisms. MicroRNAs (miRNAs) refer to small single-stranded and noncoding molecules that can negatively regulate gene expression, and miRNA regulatory networks play an important role in diverse pathological processes. Many studies have confirmed deregulated miRNA in pregnant patients with PE, and the function and mechanism of these differentially expressed miRNA are gradually being revealed. In this review, we summarize the current research about miRNA involved in PE, including placenta-specific miRNA, their predictive value, and their function in the development of PE. This review will provide fundamental evidence of miRNA in PE, and further studies are necessary to explore the roles of miRNA in the early diagnosis and treatment of PE.

Identification of a novel ANO5 missense mutation in a Chinese family with familial florid osseous dysplasia.

Familial florid osseous dysplasia (FFOD) is an autosomal dominant disorder of connective tissue, characterized by lobulated cementum-like masses scattered throughout the jaws and the alveolar process. This study aimed to identify the genetic etiology of a three-generation Chinese family affected with FFOD. A novel missense mutation p.C356W in anoctamin 5 (ANO5) gene was successfully identified as the pathogenic mutation by whole-exome sequencing (WES). The p.C356W mutation is located in the first loop between the first and second transmembrane domain of ANO5 protein. Sequence alignment of ANO5 protein among many different species revealed that this position is highly conserved. The p.C356W mutation may damage the predicted protein stability of ANO5 by altering the structure of several extracellular loops of ANO5 and affecting the formation of the disulfide bond, thereby disrupting the correct folding of ANO5 protein. Thus, the amino acid at position 356 appears to play a key role in the protein structural stability and function of ANO5 protein. Our results may also provide new insights into the cause and diagnosis of FFOD and may have implications for genetic counseling and clinical management.

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells.

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study. 2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity. 3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.

WITHDRAWN: Expanded Transoral Microvascular Mandibular Reconstruction: A Scar-Free Approach.

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Comparative pharmacokinetics study of anastrozole after single administration and combination with celecoxib.

1. There are numerous investigations demonstrating that the cyclooxygenase-2 (COX-2) inhibitors might enhance the efficiency of anastrozole in breast cancer. Hence, this study was conducted to investigate the comparative pharmacokinetics of anastrozole after single administration and combination with celecoxib. 2. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recovery for both anastrozole and the internal standard, and then anastrozole was separated and analysed on an ACQUITY BEH UPLC C18 column (50 × 2.0 mm, 1.7 µm, Waters) within 2 min. The calibration curves showed good linarites (r = 0.994). Intra- and inter-day precision were within 4.93 and 13.83%, respectively. The mean extraction recoveries across QC levels were within 91.4%, and the matrix effects were within 94.5%. 3. Results showed that the method was reliable to determine anastrozole in rat plasma. Compared with rats in single administration group, no significant difference was found in the combination group. It is workable to use celecoxib combined with anastrozole in clinical therapy.

Long noncoding RNAs (lncRNAs) in triple negative breast cancer.

Long noncoding RNAs (lncRNAs) are dysregulated in many cancer types, which are believed to play crucial roles in regulating several hallmarks of cancer biology. Triple Negative Breast Cancer (TNBC) is a very aggressive subtype of normal breast cancer, which has features of negativity for ER, PR, and HER2. Great efforts have been made to identify an association between lncRNAs expression profiles and TNBC, and to understand the functional role and molecular mechanism on aberrant-expressed lncRNAs. In this review, we summarized the existed knowledge on the systematics, biology, and function of lncRNAs. The advances from the most recent studies of lncRNAs in the predicament of breast cancer, TNBC, are highlighted, especially the functions of specifically selected lncRNAs. We also discussed the potential value of these lncRNAs in TNBC, providing clues for the diagnosis and treatments of TNBC.

The "Drawer-Like" Resection and Reconstruction With Titanium Mesh: A Novel Surgical Technique for Treatment of Giant Ossifying Fibroma in the Maxilla.

PURPOSE: The aim of this article is to introduce a new surgical method for the treatment of ossifying fibroma (OF) in the maxilla with dislocation of the eyeball and to evaluate the postoperative outcomes and prognosis. PATIENTS AND METHODS: Cases of maxillary OF treated with "drawer-like" resection from 2014 to 2015 were reviewed. The surgical procedure consisted of total removal of the orbital floor and most of the maxilla with preservation of the alveolar ridge immediately followed by reconstruction with titanium mesh. Postoperative appearance and function were assessed. In addition, the recurrence rate was statistically observed. RESULTS: The study included 6 patients with maxillary OF who were treated with drawer-like resection. Good esthetics and decrease of the globe were successfully achieved in all patients. Long-term follow-up showed a low recurrence rate. The original occlusal relation and masticatory function were preserved. CONCLUSIONS: With this new method, the original occlusal relation can be well preserved and bulging of the maxilla and eyeball displacement can be corrected.

Comprehensive profiling of biological processes reveals two major prognostic subtypes in breast cancer.

Heterogeneity is the major obstacle to breast cancer target therapy. Classification of breast cancer with significant biological process may reduce the influence of heterogeneity of intrinsic tumor. We used survival analysis to filter 95 gene sets and classify 638 breast cancer samples into two subtypes based on those gene sets associated with prognosis. Clinical outcome of two subtypes were evaluated with disease-free survival, distant metastasis-free survival, and overall survival levels in three databases and ER+, PR+ HER2+, and TNBC groups. We established a novel classification with 95 prognostic gene sets. In the training and validation cohorts, the subtype 1 was characterized by significant gene sets associated with regulation of metabolic process and enzyme activity and predicted obviously improved clinical outcome than subtype 2, which was enriched by tumor cell division, mitosis, and cell cycle-related gene sets (P < 0.05). When evaluated prognostic impact of subtypes in ER+, PR+ HER2+, and TNBC groups, we found that patients in subtype 1 showed better prognosis in ER+ and PR+ groups (P < 0.05) but had no difference from prognosis of subtype 2 in HER2+ and TNBC groups. These findings may have implications in understanding of breast cancer and filtering effective therapeutic strategies for targeted therapy.

Which Patients With Ossifying Fibroma of the Jaws Would Be Suitable for Radical Ablative Surgery?

OBJECTIVE: The aim of authors' study was to present their 10-year experience in the treatment of giant ossifying fibroma (GOF), and to prove if GOF can be totally excised preventing recurrence. The authors' secondary goal was to study the aesthetic and functional outcomes after radical resection of GOF followed by immediate reconstruction. METHODS: Eighteen patients who underwent radical ablative surgery of GOF of the jaw followed by immediate reconstruction with vascularized fibula flap or ilium flap between May 2003 and May 2013 were taken. Recurrence rate was statistically observed and 2-year postoperative aesthetic and functional outcomes were evaluated. RESULTS: The average length of follow-up was 4.5 years. There was no residual tumor or tumor recurrence observed in any patient during the mean follow-up of 4.5 years, and good cosmesis and functional outcome was noted after ablative surgery of GOF followed by computer-assisted reconstruction. CONCLUSIONS: For giant OF, if it is mainly located in the jaws without invasion of the skull base and/or pterygoid process, radical surgical treatment should be performed for prevention of tumor recurrence. And good aesthetic and functional results can be achieved by immediate computer-assisted reconstruction and dental rehabilitation.

Clinical significance of high expression of circulating serum lncRNA RP11-445H22.4 in breast cancer patients: a Chinese population-based study.

Long noncoding RNAs (lncRNAs) have been gradually confirmed to be tumor-associated biological molecules and became interesting new diagnostic targets of cancer. However, the clinical significances of most cancer-related lncRNAs are largely unknown. Here, we evaluated, for the first time, the feasibility and clinical significances of circulating serum lncRNA RP11-445H22.4 as biomarker for the detection of breast cancer (BC). In this study, the relative concentrations of breast cancer-associated lncRNA RP11-445H22.4 were investigated in a total of 136 serum samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlations between the levels of serum lncRNA RP11-445H22.4 in breast cancer patients and the clinicopathological factors of these patients were further analyzed. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. In breast cancer patients, the expression level of lncRNA RP11-445H22.4 is significantly increased (p < 0.001). The sensitivity and specificity of RP11-445H22.4 for BC were 92 and 74 %, respectively. Its expression levels were correlated with estrogen receptor (ER), progesterone receptor (PR), and menopausal status of the breast cancer patients (p < 0.05). For the detection of breast cancer, the use of RP11-445H22.4 showed a remarkable improvement compared with the clinical serum carcinoembryonic antigen. In conclusions, lncRNA RP11-445H22.4 may be a new potential biomarker of breast cancer.

Gene delivery with IFN-γ-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis.

OBJECTIVE: Interferon-γ (IFN-γ) is known to enhance the immunosuppressive properties of mesenchymal stem cells (MSCs). The aim of this study was to determine whether gene modification with IFN-γ-expression plasmids could boost the therapeutic effects of MSCs on DSS-induced colitis. METHODS: We first reconstructed pcDNA3.1-IFNγ plasmids, transfected them to human umbilical cord derived MSCs, and detected the basic characters of MSCs including immune phenotype, cell vitality, proliferation, apoptosis and cell cycle progression after transfection. Subsequently, we analyzed the inhibition effect of IFN-γ-MSCs on T cell proliferation in vitro. Finally, we induced colitis in female C57BL/6 mice by 3 % DSS treatment and evaluated the therapeutic efficacy of IFN-γ-MSCs on colitis. RESULTS: Transfection with pcDNA3.1-IFNγ did not change the basic characters of MSCs. Interestingly, IFN-γ-MSCs showed more potent immunosuppressive effects on the proliferation of T cells compared to normal MSCs. Furthermore, systemic infusion with IFN-γ-MSCs more efficiently ameliorated DSS-induced mouse colitis including colitis-related ease of body weight, increase of colon length, decrease of disease activity index, and improvement of small intestine tissues structure. In addition, IFN-γ-MSCs increased the populations of Foxp3(+) Tregs and Th2 cells both in mesenteric lymph node and spleen, upregulated indoleamine 2, 3-dioxygenase expression, and suppressed inflammatory cytokine production in mouse colon. CONCLUSIONS: Gene delivery with IFN-γ-expression plasmids enhanced the therapeutic effects of MSCs on DSS-induced mouse colitis. This study provides an effective therapeutic strategy of MSCs for inflammatory diseases.

The effect of plastic rearrangements on the flow of two-dimensional wet foam.

The effect of the elementary plastic events on the flow behavior of the two-dimensional wet foam is investigated by quasistatic simulation on the bubble scale. The position where the plastic event occurs is traced by recording the coordinate at which two bubbles separate in the simulation. A localized shear band is found, and the width of this band increases with the increase of foam quality. From the displacement fields of these bubbles, it shows that the T1 plastic events can give rise to an increase in local bubble displacements due to the separation between these bubbles. The average relative pressure as well as normal stress difference of bubbles increases with the flow of foam in the initial elastic domain and then decreases as the elastic domain turns into the plastic domain. In the plastic domain, the plastic events rearrange the local structure of foam, which leads to decreasing both the average pressure and the normal stress difference. Additionally, the wall slip of foam is discussed in the simulation as well. The width of the localized shear band is narrower under the slip boundary condition. Meanwhile, the plastic events occurring between the first and second layers of bubbles change the pulling force of the films near the wall and cause an instantaneous increase in the slip velocity.

Immediate reconstruction of soft palate defects after ablative surgery and evaluation of postoperative function: an analysis of 45 consecutive patients.

PURPOSE: The aim of the present study was to estimate the effect of different defect sizes and flaps used on the postoperative soft palate functional outcomes. PATIENTS AND METHODS: The study included 45 consecutive patients who were treated by 3 different reconstructive flaps for their soft palate defect. Postoperative speech and swallowing functions were assessed to measure the relationships between the defect size and postoperative function of the soft palate, the different flap reconstructions, and postoperative function. The 1-way analysis of variance test was computed. P < .05 was considered significant. RESULTS: The postoperative evaluation revealed that both speech and swallowing functions were normal or near normal in patients with type II defects, but they were poor in the patients with type III and IV defects. No significant changes in postoperative soft palate function using different flap sizes for the same defect type were found. CONCLUSIONS: The study results have confirmed that the size of the defect, rather than the type of the flap, will have the most critical influence on soft palate postoperative function. A defect size of 50% or less will have a better outcome than defect sizes greater than 50%.

Commensal microbiome and gastrointestinal mucosal immunity: Harmony and conflict with our closest neighbor.

BACKGROUND: The gastrointestinal tract contains a wide range of microorganisms that have evolved alongside the immune system of the host. The intestinal mucosa maintains balance within the intestines by utilizing the mucosal immune system, which is controlled by the complex gut mucosal immune network. OBJECTIVE: This review aims to comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with commensal bacteria. RESULTS: The gut mucosal immune network includes gut-associated lymphoid tissue, mucosal immune cells, cytokines, and chemokines. The connection between microbiota and the immune system occurs through the engagement of bacterial components with pattern recognition receptors found in the intestinal epithelium and antigen-presenting cells. This interaction leads to the activation of both innate and adaptive immune responses. The interaction between the microbial community and the host is vital for maintaining the balance and health of the host's mucosal system. CONCLUSION: The gut mucosal immune network maintains a delicate equilibrium between active immunity, which defends against infections and damaging non-self antigens, and immunological tolerance, which allows for the presence of commensal microbiota and dietary antigens. This balance is crucial for the maintenance of intestinal health and homeostasis. Disturbance of gut homeostasis leads to enduring or severe gastrointestinal ailments, such as colorectal cancer and inflammatory bowel disease. Utilizing these factors can aid in the development of cutting-edge mucosal vaccines that have the ability to elicit strong protective immune responses at the primary sites of pathogen invasion.

Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.

Defects in the prelamin A processing enzyme caused by loss-of-function mutations in the ZMPSTE24 gene are responsible for a spectrum of progeroid disorders characterized by the accumulation of farnesylated prelamin A. Here we report that defective prelamin A processing triggers nuclear RIPK1-dependent signalling that leads to necroptosis and inflammation. We show that accumulated prelamin A recruits RIPK1 to the nucleus to facilitate its activation upon tumour necrosis factor stimulation in ZMPSTE24-deficient cells. Kinase-activated RIPK1 then promotes RIPK3-mediated MLKL activation in the nucleus, leading to nuclear envelope disruption and necroptosis. This signalling relies on prelamin A farnesylation, which anchors prelamin A to nuclear envelope to serve as a nucleation platform for necroptosis. Genetic inactivation of necroptosis ameliorates the progeroid phenotypes in Zmpste24-/- mice. Our findings identify an unconventional nuclear necroptosis pathway resulting from ZMPSTE24 deficiency with pathogenic consequences in progeroid disorder and suggest RIPK1 as a feasible target for prelamin A-associated progeroid disorders.