•A novel symmetrical parallel-kinematic flexure XYZ micro/nano-positioning stage is designed.•It provides a larger travel range and better motion decoupling property with a more compact physical size ...as compared with existing works.•Analytical models are derived and verified by finite-element analysis simulation studies.•A prototype stage is fabricated for experimental studies.•It can be applied in pertinent micro/nano-positioning applications, such as robotic micro/nano-injection, micro/nano-assembly, and so on.
Limited travel stroke constrains the application of existing XYZ parallel micro/nano-positioning stages. In this paper, a novel parallel-kinematic symmetrical micro/nano-positioning stage is proposed to enlarge the travel range with a compact physical size. For a large-stroke parallel stage, the cross-axis motion increases the difficulty of closed-loop control process. The motions of the parallel stage on different axes are decoupled by employing I-shaped flexure hinges in this work. In order to obtain a large input displacement for actuating the stage, three voice coil motors (VCM) are adopted. In view of the lower output force of the VCM, the guiding flexure mechanism is designed with an optimized cross-sectional dimension. To verify the performance of the stage, analytical modeling and simulation study are carried out. A prototype stage is fabricated for experimental studies. Results show that the designed parallel micro/nano-positioning stage owns a three-degree-of-freedom motion workspace of 2.22 mm × 2.22 mm × 1.81 mm with an overall size of 176 mm × 176 mm × 198 mm, which is more compact than existing symmetrical designs containing the actuators. Moreover, the symmetrical design enables a low crosstalk of 1.7% among the three working axes.
Infrared and visible image fusion technologies are used to characterize the same scene using diverse modalities. However, most existing deep learning-based fusion methods are designed as symmetric ...networks, which ignore the differences between modal images and lead to source image information loss during feature extraction. In this paper, we propose a new fusion framework for the different characteristics of infrared and visible images. Specifically, we design a dual-stream asymmetric network with two different feature extraction networks to extract infrared and visible feature maps, respectively. The transformer architecture is introduced in the infrared feature extraction branch, which can force the network to focus on the local features of infrared images while still obtaining their contextual information. The visible feature extraction branch uses residual dense blocks to fully extract the rich background and texture detail information of visible images. In this way, it can provide better infrared targets and visible details for the fused image. Experimental results on multiple datasets indicate that DSA-Net outperforms state-of-the-art methods in both qualitative and quantitative evaluations. In addition, we also apply the fusion results to the target detection task, which indirectly demonstrates the fusion performances of our method.
More adolescents suffered from depressive disorder, and what was worse, the morbidity increased annually. The situation was getting worse during COVID-19 pandemic. The prevalence of depression among ...adolescents in China has increased a lot due to social and economic development, family-associated reasons, academic stress, interpersonal relationships, and so on.
This study aimed to determine the prevalence, gender differences, risk factors, and abnormal illness behaviors of depression among adolescents in Huangshi, China.
A descriptive analysis was conducted based on the data from clinical interviews and self-reports by the patients. Depression was assessed and diagnosed using the DSM-5 Diagnostic and Statistical Manual of Mental Disorders.
Depression was most frequently seen in 674 patients with mental illnesses (282, 41.84%). The male-to-female ratio was 1:2.44, and their age ranged from 9 to 18. The majority of patients are in high school (261/282, 92.55%), and the highest morbidity occurred at 16 years. More cases were diagnosed in urban than in rural areas. Genetic factors, school violence, academic stress, sleep disorders, and family-related factors were essential factors leading to depression among adolescents. Most patients had sleep disorders (84.75%). In family-related factors, left-behind children and unrecognized/misunderstood by their families were prominently diagnosed with depression. A large portion of individuals with depression felt apathetic, solitary, and sluggish and were unable to study, work, and live normally (212/282, 75.18%); they even committed suicide or attempted suicide (228/282, 80.85%) and inflicted self-harm (146/282, 51.77%).
An increasing trend of depression has been observed since 2018, especially in 2021. This depression has led to suicide or suicidal attempts and self-harm, reflecting the severity of mental health among adolescents in Huangshi. Therefore, this study aimed to draw the attention of society, families, and schools to the importance of mental health among adolescents, providing guidance and references for the prevention, diagnosis, and treatment of young depressive disorders in China.
This paper presents the design and testing of a novel 3-DOF parallel flexure micropositioning stage for micro-scale operations. The proposed modular design can obtain the merit of high ...interchangeability during maintenance process. The output platform of the mechanism offers pure translational motion along X, Y, and Z axes by resorting to the flexure guiding of two parallelogram joints. Meanwhile, the output motion is decoupled by using two leaves with symmetric ellipse-shaped flexure hinges, and the platform provides isolated movement without parasitic motion. By using the bridge-type and lever-type compound amplifier, the micropositioning stage provides a large output displacement, which is over 30 times the input displacement provided by piezoelectric actuator. The enlarged displacement is translated to the orthogonal parallel mechanism by four straight beams, which provide perfect decoupling properties. In addition, the modular design principle makes it possible to adopt multiple materials to balance the performance of the actuator and decoupling flexure hinges. Analytical analysis and finite element analysis simulation are conducted to verify the fine decoupling property and large translational motion of the proposed 3-DOF parallel micropositioning stage. Moreover, a prototype is fabricated using multiple materials for experimental testing. Results demonstrate the promising performance of the developed decoupled micropositioning stage.
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•U11 peptide conjugated, pH sensitive DOX prodrug (U11-DOX) was synthesized.•A CUR and U11-DOX co-encapsulated NPs system was constructed to treat lung cancer.•U11-DOX/CUR NPs have ...promising potential for combination treatment of lung cancer.
Lung cancer is the leading cause of cancer death worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, a urokinase plasminogen activator receptor (uPAR) targeting U11 peptide decorated, pH-sensitive, dual drugs co-encapsulated nanoparticles (NPs) system is employed in this study. A U11 peptide conjugated, pH-sensitive DOX prodrug (U11-DOX) was synthesized and used as materials to produce NPs. A curcumin (CUR) and U11-DOX co-encapsulated NPs system (U11-DOX/CUR NPs) was constructed to treat lung cancer. After the characterization of biophysical properties of this NPs system, synergistic chemotherapeutic efficacy was evaluated in both cultured cancer cells and tumor-bearing animal model. U11-DOX/CUR NPs had a uniformly spherical shape with a core-shell structure. The mean particle size and zeta potential of the U11-DOX/CUR NPs was 121.3 nm and -33.5 mV, with a DOX and CUR EE of 81.7 and 90.5%, respectively. The DOX release from U11-DOX/CUR NPs was 83.5, 55.2, and 32.8% correspondence to the pH of 5.0, 6.0 and 7.4. Cellular uptake efficiency of U11-DOX/CUR NPs was significantly higher than non U11 peptide decorated DOX/CUR NPs. U11-DOX/CUR NPs displayed a pronounced synergy effects in vitro and an obvious tumor tissue accumulation efficiency in vivo. In vivo antitumor experiment showed that U11-DOX/CUR NPs could inhibit the tumor growth to a level of 85%.In vitro and in vivo studies demonstrated that U11-DOX/CUR NPs is a sustained released, pH responsive, synergistic antitumor system. This study suggests that the U11-DOX/CUR NPs have promising potential for combination treatment of lung cancer.
Radioresistance, a poorly understood phenomenon, results in the failure of radiotherapy and subsequent local recurrence, threatening a large proportion of patients with ESCC. To date, lncRNAs have ...been reported to be involved in diverse biological processes, including radioresistance.
FISH and qRT-PCR were adopted to examine the expression and localization of lncRNA-NORAD, pri-miR-199a1 and miR-199a-5p. Electron microscopy and nanoparticle tracking analysis (NTA) were conducted to observe and identify exosomes. High-throughput microRNAs sequencing and TMT mass spectrometry were performed to identify the functional miRNA and proteins. A series of in vitro and in vivo experiments were performed to investigate the biological effect of NORAD. ChIP, RIP-qPCR, co-IP and dual-luciferase reporter assays were conducted to explore the interaction of related RNAs and proteins.
We show here that DNA damage activates the noncoding RNA NORAD, which is critical for ESCC radioresistance. NORAD was expressed at high levels in radioresistant ESCC cells. Radiation treatment promotes NORAD expression by enhancing H3K4me2 enrichment in its sequence. NORAD knockdown cells exhibit significant hypersensitivity to radiation in vivo and in vitro. NORAD is required to initiate the repair and restart of stalled forks, G2 cycle arrest and homologous recombination repair upon radiation treatment. Mechanistically, NORAD inhibits miR-199a-5p expression by competitively binding PUM1 from pri-miR-199a1, inhibiting the processing of pri-miR-199a1. Mature miR-199a-5p in NORAD knockdown cells is packaged into exosomes; miR-199a-5p restores the radiosensitivity of radioresistant cells by targeting EEPD1 and then inhibiting the ATR/Chk1 signalling pathway. Simultaneously, NORAD knockdown inhibits the ubiquitination of PD-L1, leading to a better response to radiation and anti-PD-1 treatment in a mouse model.
Based on the findings of this study, lncRNA-NORAD represents a potential treatment target for improving the efficiency of immunotherapy in combination with radiation in ESCC.
Gastric cancer (GC) is one of the most commonly occuring gastrointestinal tumor types, and early diagnosis and operation have a notable effect on the prognosis of patients. Although certain markers, ...including HER2, VEGER-2, ERCC1 and Bcl-2, have been utilized in clinical practise to screen out new patients with GC, the results of using these markers remains poor. The role of olfactomedin-like 2B (OLFML2B) in GC, as a member of the olfactomedin domain-containing proteins family, is remain unclear.
In the present study, we assessed the expression of OLFML2B, including mRNA and protein level, by using The Cancer Genome Atlas (TCGA) database and 13 pairs of clinical samples between GC and NG tissues. The correlation between expression of OLFML2B and prognosis of GC was evaculated by the Kaplan-Meier plotter and OncoLnc online tools. In addition, mechanism analysis of OLFML2B in GC was explored thought bioinformatic tools, including cBioPortal and FunRich software.
In our study, the mRNA expression of OLFML2B in GC both TCGA database and clinical samples was consistently revealed to be significantly higher compared with that in NG tissues (P < 0.0001 for TCGA database and P = 0.0034 for clinical samples), and high OLFML2B expression was found in 9 (69.23%) of 13 clinical GC by immunohistochemistry and was positively correlated with the depth of tumor invasion and clinical stage (TNM). In addition, the AUC for a ROC of 0.867 indicated a moderate diagnostic ability of OLFML2B for GC. Survival analysis from the Kaplan-Meier plotter (P = 2.6 × 10
) and OncoLnc (P = 0.00276) revealed that the high expression of OLFML2B was associated with a short overall survival. Futhermore, 5% (24/478) alterations of OLFML2B were identified from cBioPortal, and among them, missense mutation (14/478) was the primary type. The results from FunRich revealed that OLFML2B participated in mediating multiple biological processes including cell growth and maintenance, regulation of the cell cycle, apoptosis and cell communication through multiple signaling pathways including the M/G1 transition pathway, post-translational protein modification and DNA replication pre-initiation.
Taken together, it could be deduced that OLFML2B may act as an oncogene in the development of GC and the overexpression of OLFML2B in GC may be used as a novel diagnostic and prognostic target for GC.
Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis because of atypical early symptoms and heterogeneous therapeutic responses. 5-methylcytosine (m5C) modification plays an important ...role in the onset and development of many tumors and is widespread in long non-coding RNA (lncRNA) transcripts. However, the functions of m5C and lncRNAs in ESCC have not been completely elucidated. Herein, this study aimed to explore the role of m5C-related lncRNAs in ESCC. The RNA-seq transcriptome profiles and clinical information were downloaded from the TCGA-ESCC database. Pearson analysis was used to identify m5C-related lncRNAs. Then we established the m5C-related lncRNAs prognostic signature (m5C-LPS) using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, the prognostic value of m5C-LPS was evaluated internally and externally using the TCGA-ESCC and GSE53622 databases through multiple methods. We also detected the expression of these lncRNAs in ESCC cell lines and patient tissues. Fluorescence in situ hybridization (FISH) was used to detect the prognostic value of specific lncRNA. In addition, clinical parameters, immune status, genomic variants, oncogenic pathways, enrichment pathways, and therapeutic response features associated with m5C-LPS were explored using bioinformatics methods. We constructed and validated a prognostic signature based on 9 m5C-related lncRNAs (AC002091.2, AC009275.1, CAHM, LINC02057.1, AC0006329.1, AC037459.3, AC064807.1, ATP2B1-AS1, and UBAC2-AS1). The quantitative real-time polymerase chain reaction (qRT-PCR) revealed that most lncRNAs were upregulated in ESCC cell lines and patient tissues. And AC002091.2 was validated to have significant prognostic value in ESCC patients. A composite nomogram was generated to facilitate clinical practice by integrating this signature with the N stage. Besides, patients in the low-risk group were characterized by good clinical outcomes, favorable immune status, and low oncogenic alteration. Function enrichment analysis indicated that the risk score was associated with mRNA splicing, ncRNA processing, and DNA damage repair response. At the same time, we found significant differences in the responses to chemoradiotherapy between the two groups, proving the value of m5C-LPS in treatment decision-making in ESCC. This study established a novel prognostic signature based on 9 m5C-related lncRNAs, which is a promising biomarker for predicting clinical outcomes and therapeutic response in ESCC.
Background:
Hepatocellular Carcinoma (HCC) is an aggressive tumor with an inferior prognosis. Necroptosis is a new form of programmed death that plays a dual effect on the tumor. However, the role of ...necroptosis-related genes(NRGs) in HCC remains unknown.
Methods:
All datasets were downloaded from publicly available databases. The consensus clustering analysis was used to classify patients into different subtypes based on NRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were used to develop a prognostic signature. Tumor Immune Dysfunction and Exclusion (TIDE) was used to predict immunotherapy response.
Results:
The genetic and transcriptional changes of NRGs were observed in HCC. Patients were classified into three clusters based on differentially expressed NRGs, of which Cluster-3 had the worst prognosis and the highest immune infiltration. The prognostic signature was developed based on 8-NRGs, which have shown excellent prognostic performance. The high-risk group in the signature presented significantly higher immune infiltration, such as aDCs, iDCs, macrophages, and Treg, compared to the low-risk group. TMB and immune checkpoints were also higher in the high-risk group. Moreover, a lower TIDE score was observed in the high-risk group, indicating the patients with high risk-score may be suitable for immunotherapy.
Via
the dataset of IMvigor210, we found a higher risk score in the immunotherapy response group.
Conclusion:
We developed a new necroptosis-related signature for predicting prognosis with the potential to predict immunotherapy for HCC patients.
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