An integrated machine learning-based model for joint diagnosis of ovarian cancer with multiple test indicators.

OBJECTIVE: To construct a machine learning diagnostic model integrating feature dimensionality reduction techniques and artificial neural network classifiers to develop the value of clinical routine blood indexes for the auxiliary diagnosis of ovarian cancer. METHODS: Patients with ovarian cancer clearly diagnosed in our hospital were collected as a case group (n = 185), and three groups of patients with other malignant otolaryngology tumors (n = 138), patients with benign otolaryngology diseases (n = 339) and those with normal physical examination (n = 92) were used as an overall control group. In this paper, a fully automated segmentation network for magnetic resonance images of ovarian cancer is proposed to improve the reproducibility of tumor segmentation results while effectively reducing the burden on radiologists. A pre-trained Res Net50 is used to the three edge output modules are fused to obtain the final segmentation results. The segmentation results of the proposed network architecture are compared with the segmentation results of the U-net based network architecture and the effect of different loss functions and region of interest sizes on the segmentation performance of the proposed network is analyzed. RESULTS: The average Dice similarity coefficient, average sensitivity, average specificity (specificity) and average hausdorff distance of the proposed network segmentation results reached 83.62%, 89.11%, 96.37% and 8.50, respectively, which were better than the U-net based segmentation method. For ROIs containing tumor tissue, the smaller the size, the better the segmentation effect. Several loss functions do not differ much. The area under the ROC curve of the machine learning diagnostic model reached 0.948, with a sensitivity of 91.9% and a specificity of 86.9%, and its diagnostic efficacy was significantly better than that of the traditional way of detecting CA125 alone. The model was able to accurately diagnose ovarian cancer of different disease stages and showed certain discriminative ability for ovarian cancer in all three control subgroups. CONCLUSION: Using machine learning to integrate multiple conventional test indicators can effectively improve the diagnostic efficacy of ovarian cancer, which provides a new idea for the intelligent auxiliary diagnosis of ovarian cancer.

Mechanistic modelling of relative biological effectiveness of carbon ion beams and comparison with experiments.

Objective.Relative biological effectiveness (RBE) plays a vital role in carbon ion radiotherapy, which is a promising treatment method for reducing toxic effects on normal tissues and improving treatment efficacy. It is important to have an effective and precise way of obtaining RBE values to support clinical decisions. A method of calculating RBE from a mechanistic perspective is reported.Approach.Ratio of dose to obtain the same number of double strand breaks (DSBs) between different radiation types was used to evaluate RBE. Package gMicroMC was used to simulate DSB yields. The DSB inductions were then analyzed to calculate RBE. The RBE values were compared with experimental results.Main results.Furusawa's experiment yielded RBE values of 1.27, 2.22, 3.00 and 3.37 for carbon ion beam with dose-averaged LET of 30.3 keVµm-1, 54.5 keVµm-1, 88 keVµm-1and 137 keVµm-1, respectively. RBE values computed from gMicroMC simulations were 1.75, 2.22, 2.87 and 2.97. When it came to a more sophisticated carbon ion beam with 6 cm spread-out Bragg peak, RBE values were 1.61, 1.63, 2.19 and 2.36 for proximal, middle, distal and distal end part, respectively. Values simulated by gMicroMC were 1.50, 1.87, 2.19 and 2.34. The simulated results were in reasonable agreement with the experimental data.Significance.As a mechanistic way for the evaluation of RBE for carbon ion radiotherapy by combining the macroscopic simulation of energy spectrum and microscopic simulation of DNA damages, this work provides a promising tool for RBE calculation supporting clinical applications such as treatment planning.

Tumor-selective Blockade of CD47 Signaling with CD47 Antibody for Enhanced Anti-tumor Activity in Malignant Meningioma.

BACKGROUND: Patients with WHO grade III meningioma have a poor prognosis with a median survival of less than two years and a high risk of recurrence. However, traditional treatment options have failed to improve prognosis. Therefore, development of novel immunotherapy targets is urgently needed. CD47 acting as a "don't eat me" signal to macrophages can trigger tumor immune escape. However, the role of CD47 in malignant meningioma is not well understood. METHODS: We collected 190 clinical meningioma samples and detected the expression of CD47 and immune infiltration in WHO grade I-III by immunohistochemistry, western blot, qPCR. We also examined the functional effects of anti-CD47 on cell proliferation, migration and invasion, macrophagemediated phagocytosis and tumorigenicity both in vitro and in vivo. RESULTS: We found that the expression of CD47 was increased in malignant meningioma along with a decreased number of T cells and an increase in CD68+ macrophages. Blocking CD47 with anti-CD47 antibody (B6H12) suppressed tumor cell growth, motility and promoted macrophage-mediated phagocytosis in IOMM-Lee cells in vitro. In vivo experiments showed that anti-CD47 antibody (B6H12 or MIAP301) significantly inhibited the tumor growth and this effect was partly blocked by the depletion of macrophages. Finally, p-ERK and EGFR showed higher expression in malignant meningioma with high expression of CD47, which was verified by western blot. CONCLUSION: Our results demonstrated that CD47 maybe involved in the meningioma progression and prognosis and offered a novel therapeutic option by targeting CD47 in malignant meningioma.

Sequentially modified carbon felt for enhanced p-nitrophenol biodegradation through direct interspecific electron transfer.

The widely applied aromatic nitration in modern industry leads to toxic p-nitrophenol (PNP) in environment. Exploring its efficient degradation routes is of great interests. In this study, a novel four-step sequential modification procedure was developed to increase the specific surface area, functional group, hydrophilicity, and conductivity of carbon felt (CF). The implementation of the modified CF promoted reductive PNP biodegradation, attaining 95.2 ± 0.8% of removal efficiency with less accumulation of highly toxic organic intermediates (e.g., p-aminophenol), compared to carrier-free and CF-packed biosystems. The constructed anaerobic-aerobic process with modified CF in 219-d continuous operation achieved further removal of carbon and nitrogen containing intermediates and partial mineralization of PNP. The modified CF promoted the secretion of extracellular polymeric substances (EPS) and cytochrome c (Cyt c), which were essential components to facilitate direct interspecies electron transfer (DIET). Synergistic relationship was deduced that glucose was converted into volatile fatty acids by fermenters (e.g., Longilinea and Syntrophobacter), which donated electrons to the PNP degraders (e.g., Bacteroidetes_vadinHA17) through DIET channels (CF, Cyt c, EPS) to complete PNP removal. This study proposes a novel strategy using engineered conductive material to enhance the DIET process for efficient and sustainable PNP bioremediation.

Breaking through Barriers: Ultrafast Microbullet Based on Cavitation Bubble.

Micromotors hold great promise for extensive practical applications such as those in biomedical domains and reservoir exploration. However, insufficient propulsion of the micromotor limits its application in crossing biological barriers and breaking reservoir boundaries. In this study, an ultrafast microbullet based on laser cavitation that can utilize the energy of a cavitation bubble and realize its own hurtling motion is reported. The experiments are performed using high-speed photography. A boundary integral method is adopted to reveal the motion mechanism of a polystyrene (PS)/magnetic nanoparticle (MNP) microbullet under the action of laser cavitation. Furthermore, the influence of certain factors (including laser intensity, microbullet size, and ambient temperature) on the motion of the microbullet was explored. For the PS/MNP microbullet driven by laser cavitation, the instantaneous velocity obtained can reach 5.23 m s-1 . This strategy of driving the PS/MNP microbullet provides strong penetration ability and targeted motion. It is believed that the reported propulsion mechanism opens up new possibilities for micromotors in a wide range of engineering applications.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

CD47 promotes the proliferation and migration of adamantinomatous craniopharyngioma cells by activating the MAPK/ERK pathway, and CD47 blockade facilitates microglia-mediated phagocytosis.

AIMS: CD47 is overexpressed in multiple tumours and plays an important role in immune escape and other biological processes of tumours. However, its role in adamantinomatous craniopharyngioma (ACP) remains unclear. Therefore, we explored the functions of CD47 in ACP. METHODS: In this study, the expression of CD47 and the infiltration of immune cells in ACP was determined by immunohistochemistry (IHC) or immunofluorescence. Microglia-mediated phagocytosis was analysed using an in vitro phagocytosis assay. Using lentivirus transfection, CD47 was either silenced or overexpressed in primary ACP cells and the biological effects of CD47 on these cells were evaluated in vitro using cell viability, flow cytometry, wound healing, Transwell migration and 3D hydrogel assays. The protein expression levels were analysed by western blotting. RESULTS: Finger-like protrusions, which may be the key factor in the recurrence of ACP, were primarily found in the region of hypothalamic involvement. The expression of CD47 was higher in palisading epithelium compared with stellate reticulum and epithelial whorls. An in vitro phagocytosis assay showed that CD47 blockade could promote microglia-mediated phagocytosis. Functional assays revealed that CD47 promoted the growth, migration and invasion of ACP cells in vitro. Our mechanistic investigations showed that CD47 activated the MAPK/ERK pathway, thereby facilitating the biological behaviour of ACP cells. CONCLUSIONS: Here, we demonstrated that CD47 plays an important role in ACP cells, suggesting that CD47 could be a new potential therapeutic target for ACP, and adding to the body of literature a role for the inhibition of MAPK/ERK in ACP.

Nature-inspired micro/nanomotors.

Living things in nature have evolved with unique morphologies, structures, materials, behaviors, and functions to survive in complex natural environments. Nature has inspired the design ideas, preparation methods, and applications of versatile micro/nanomotors. This review summarizes diverse nature-inspired micro/nanomotors, which can be divided into five groups: (i) natural morphology-inspired micro/nanomotors, whose shapes are designed to imitate the morphologies of plants, animals, and objects in nature. (ii) Natural structure-inspired micro/nanomotors, which use structures from plants, red blood cells, and platelet cells as components of micro/nanomotors, or directly use sperm cells and microorganisms as the engines of micro/nanomotors. (iii) Natural behavior-inspired micro/nanomotors, which are proposed to mimic natural behaviors such as motion behavior, swarm behavior, and communication behavior between individuals. (iv) Micro/nanomotors inspired by both natural morphology and behavior. Nature makes it possible for synthetic micro/nanomotors to possess interesting morphologies, novel preparation methods, new propulsion modes, innovative functions, and broad applications. The nature-inspired micro/nanomotors could provide a promising platform for various practical fields.

Dual-beam antiphase method to improve the WMS measurement limit in long-distance methane detection.

Wavelength modulation spectroscopy (WMS) with second harmonic detection is an extremely effective technique to detect gases in site applications. However, the significant levels of nonlinear effects in a system give rise to high background signals that either limit detection sensitivity or distort the harmonic signals. This paper outlines the theory of WMS-involved background signals and focuses on the elimination of undesirable effects in the background. A real-time, long-distance methane sensor using a tunable diode laser near 1653.7 nm is developed to continuously monitor methane by using a variable optical attenuator to suppress the background. Trace methane detection experiments verify that the minimum detection limit of the system can be increased by 47.5 times compared to the traditional WMS method.

Two-component gas quartz-enhanced photoacoustic spectroscopy sensor based on time-division multiplexing of distributed-feedback laser driver current.

A two-component gas sensor in quartz-enhanced photoacoustic spectroscopy based on time-division multiplexing (TDM) technology of a distributed-feedback (DFB) laser driver current was proposed and experimentally demonstrated. The quartz tuning-fork-based photoacoustic spectroscopy (PAS) cell configuration with two optical collimators and two acoustic microresonators was designed to detect the second-harmonic (${2}f$2f) PAS signal. The two optical collimators guaranteed that the two laser beams would inject the PAS cell conveniently, providing higher power input than a 3 dB optical fiber coupler. Two-component gas sensing was achieved by the TDM of the DFB laser driver current. We used this two-component gas sensing technique to detect acetylene (${{\rm C}_2}{{\rm H}_2}$C2H2) at 1532.83 nm and methane (${{\rm CH}_4}$CH4) at 1653.722 nm. The ${{\rm C}_2}{{\rm H}_2}$C2H2 and ${{\rm CH}_4}$CH4 detection was achieved at a 2.4 s interval. The minimum detection limits of 1 ppmv for ${{\rm C}_2}{{\rm H}_2}$C2H2 and 13.14 ppmv for ${{\rm CH}_4}$CH4 were obtained, and the linear responses reached were 0.99968 and 0.99652 for ${{\rm C}_2}{{\rm H}_2}$C2H2 and ${{\rm CH}_4}$CH4, respectively. Moreover, the continuous monitoring of ${{\rm CH}_4}$CH4 and ${{\rm C}_2}{{\rm H}_2}$C2H2 for 40 min showed a good stability. The TDM technology of the DFB laser driver current would play an important role on the multi-component detection.

Coexisting Cooperative Cognitive Micro-/Nanorobots.

Interaction behaviors are a crucial, distinctive feature of organisms in ecological systems. Inspired by nature, micro-/nanorobots also show interaction behaviors with a significant number of novel and advanced functionalities. The micro-/nanoscale size and self-driven abilities of micro-/nanorobots have attracted considerable attention for potential applications. The mission of micro-/nanorobots has evolved from basic mechanical transfer or assistance to a diverse range of complex tasks, such as targeted drug delivery, biosensing, and environmental remediation. Herein, we focus on the interaction behavior of coexisting cooperative cognitive (Tri-Co) micro-/nanorobots, summarize recent research, and classify the interactions into three broad types: with the environment, with robot peers, and with human external control.

Identification of exosomal and non­exosomal microRNAs associated with the drug resistance of ovarian cancer.

MicroRNAs (miRNAs) serve important roles in drug­resistance; however, exosomal miRNAs associated with drug­resistance in ovarian cancer (OC) have not been reported to date. The current study aimed to analyze the drug resistance­associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE­miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28 DE­miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR­146b­5p, miR­509­5p, miR­574­3p, miR­574­5p and miR­760). In addition, 16 and 35 DE­miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR­30a­3p, miR­30a­5p, miR­612 and miR­617; SKOV3_TR: miR­193a­5p, miR­423­3p, miR­769­5p and miR­922). It was also reported that miR­183­5p was the only one common miRNA among the three cell lines. Furthermore, miR­574­3p, miR­30a­5p and miR­922 may regulate CUL2 to mediate HIF­1 cancer signaling pathway, while miR­183­5p may modulate MECP2, similar to miR­760, miR­30a­5p and miR­922, to influence cell proliferation. Finally, the downregulated miR­612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC.

Downregulation of miR-145-5p in cancer cells and their derived exosomes may contribute to the development of ovarian cancer by targeting CT.

The present study aimed to identify shared microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE103708) available from the Gene Expression Omnibus database, including exosomal samples from 13 OC cell lines and 3 normal ovarian surface epithelial cell lines, and their original cell samples. Differentially expressed miRNAs (DE­miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE­miRNAs were predicted using the miRWalk2 database. The potential functions of target genes were analyzed using Database for Annotation, Visualization and Integrated Discovery and intersected with known OC­associated pathways downloaded from the Comparative Toxicogenomics Database. The associations between crucial miRNAs and target genes, and their clinical associations, were validated using data from The Cancer Genome Atlas. As a result, 16 upregulated and 6 downregulated DE­miRNAs were shared in OC cell lines and their exosomes compared with normal controls. The target genes of 11 common DE­miRNAs were predicted. Among these DE­miRNAs, a low expression of homo sapiens (hsa)­miR­145­5p was significantly correlated with a poor prognosis and higher stages. Although 91 target genes were predicted for hsa­miR­145­5p, only 4 genes [connective tissue growth factor (CTGF), myotubularin­related protein 14, protein phosphatase 3 catalytic subunit alpha and suppressor of cytokine signaling 7] were suggested as risk factors for prognosis. The subsequent Pearson's correlation analysis validated a significant negative correlation between hsa­miR­145­5p and CTGF (r=­0.1126, P=0.02188). According to the results of the functional analysis, CTGF is involved in the Hippo signaling pathway (hsa04390). In conclusion, decreased expression of hsa­miR­145 in OC and OC­derived exosomes may be a crucial biomarker for the diagnosis and treatment of OC.

Identification of genes associated with the effect of inflammation on the neurotransmission of vascular smooth muscle cell.

Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in vascular disorders, and inflammation has a crucial role in the development of these diseases. To investigate the effect of inflammation on the neurotransmission of VSMC, bioinformatic analysis was performed, following next generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next generation sequencing, and each assay was repeated three times. Differentially expressed genes (DEGs) were obtained using the NOISeq package in R. Subsequently, their potential functions were predicted by functional and pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery online tool. Interaction relationships of the proteins enriched in pathways associated with neurological diseases, the proteins which had interaction relationships with adrenoceptor α 1D (ADRA1D) or calcium voltage-gated channel subunit α1 S (CACNA1S), separately, were obtained from STRING, and protein-protein interaction (PPI) networks were constructed using Cytoscape software. A total of 2,038 DEGs, including 1,094 upregulated and 944 downregulated genes in the LPS treatment group were identified when compared with the control group. Enrichment analyses showed that NADH:Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2) was involved in several neurological diseases, including oxidative phosphorylation, Alzheimer's disease, Parkinson's disease and Huntington's disease. Furthermore, NDUFV2 (degree, 20) had a higher degree in the PPI network for DEGs enriched in pathways associated with neurological diseases. In the PPI network for ADRA1D, CACNA1S and the DEGs interacting with them, prohibitin (PHB), oxytocin receptor (OXTR), collapsin response mediator protein 1 (CRMP1) and dihydropyrimidinase like 2 (DPYSL2) had interaction relationships with both ADRA1D and CACNA1S. To conclude, the present study revealed that NDUFV2, PHB, OXTR, CRMP1 and DPYSL2 may have key roles in the effect of inflammation on neurotransmission of VSMC.

Identification of potential gene targets in systemic vasculitis using DNA microarray analysis.

The present study aimed to identify the involvement of critical genes in systemic vasculitis, to gain an improved understanding of the molecular circuity and to investigate novel potential gene targets for systemic vasculitis treatment. The dual­color cDNA microarray data of GSE16945, consisting of peripheral mononuclear blood cell specimens from 13 patients with systemic vasculitis and 16 healthy controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened in systemic vasculitis compared with controls using BRB ArrayTools, followed by the construction of a protein­protein interaction (PPI) network using the clusterProfiler package, and significant functional interaction (FI) module selection. Furthermore, transcriptional factors (TFs) among the identified DEGs were predicted and a transcriptional regulation network was constructed. A total of 173 up- and 93 downregulated genes were identified, which were mainly associated with immune response pathways. FBJ murine osteosarcoma viral oncogene homolog (FOS), ubiquitin B (UBB), signal transducer and activator of transcription 1 (STAT1) and MX dynamin­like GTPase 1 (MX1) were identified as hub proteins in the PPI network. Furthermore, UBB, FOS, and STAT1 were hub proteins in the three identified FI modules, respectively. In total, nine TFs were predicted among the DEGs. Of the DEGs that were predicted to be TFs, STAT1, v­maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) and tyrosine 3­monooxygenase/tryptophan 5­monooxygenase activation protein Z (YWHAZ), which interacted with each other, were identified to regulate further DEGs as target genes. Various genes, including FOS, UBB, MX1, STAT1, MAFB, and YWHAZ may be potential targets useful for the treatment of systemic vasculitis.

Efficacy of Endovascular Radiofrequency Ablation for Thromboangiitis Obliterans (Buerger's Disease).

BACKGROUND: This study aimed to evaluate the efficacy of endovascular radiofrequency ablation (RFA) for the treatment of thromboangiitis obliterans (TAO). METHODS: Total 30 males (median age: 46.00 years, interquartile range: 42.00-51.25 years) with unilateral TAO in the lower extremity underwent RFA were retrospectively enrolled from January 2013 and October 2013. The pre-operative and post-operative digital subtraction angiographic (DSA) images were recorded. Pain scores preoperatively and postoperatively were assessed according to the World Health Organization Pain Guideline. The values of ankle brachial index (ABI) at pre-operation, post-operation, 2 weeks and 2 years after surgery were all recorded and analyzed. Additionally, a 2-year follow up was performed by a computed tomographic angiography (CTA) image. RESULTS: The DSA images indicated that occlusion of femoral artery was improved after surgery. Moreover, there was no recurrence of TAO at 2 years of follow-up based on the CTA images. The pain score (P < 0.001) was significantly deceased after surgery. The values of ABI at postoperation, 2 weeks after surgery, and 2 years after surgery were all significantly higher than the preoperative ABI (P < 0.001). Furthermore, the values of ABI at 2 weeks after surgery and 2 years after surgery were all significantly higher than the postoperative ABI (P < 0.001). CONCLUSIONS: These results supported the application of endovascular RFA for treating TAO.