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Abstract Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre‐metastatic “niches” in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high‐resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue‐derived EVs to identify a novel subset of tumour‐derived EVs that contain integrin α6 (ITGA6+EVs) and revealed the positive correlation of ITGA6+EVs with the formation of pre‐metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820‐case BCa patients. BCa‐derived ITGA6+EVs induced E‐selectin (SELE)‐marked lymphatic remodelling pre‐metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA‐LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP‐bound activated state, thus maintaining the production of ITGA6+EVs loaded with LIPAR through endosomal trafficking. ITGA6+EVs targeted lymphatic vessels through ITGA6‐CD151 interplay and released LIPAR to induce SELE overexpression‐marked lymphatic remodelling pre‐metastatic niche. Importantly, we constructed engineered‐ITGA6 EVs to inhibit lymphatic pre‐metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa‐derived ITGA6+EVs mediating pre‐metastatic niche and provides an engineered‐EV‐based strategy against BCa lymphatic metastasis.

Abstract Background Cancer‐associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor‐derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor‐derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor‐derived EV‐mediated CAFs phenotype in regulating BCa LN metastasis. Methods The high‐throughput sequencing was utilized to identify the crucial long non‐coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665‐mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient‐derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. Results We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF‐associated long non‐coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B‐induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B‐HGF‐c‐Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV‐transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. Conclusion Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B‐HGF‐c‐Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.

Robust localization and mapping are crucial for autonomous systems, but traditional handcrafted feature-based visual SLAM often struggles in challenging, textureless environments. Additionally, monocular SLAM lacks scale-aware depth perception, making accurate scene scale estimation difficult. To address these issues, we propose D3L-SLAM, a novel monocular SLAM system that integrates deep keypoints, deep depth estimates, deep pose priors, and a line detector. By leveraging deep keypoints, which are more resilient to lighting variations, our system improves the robustness of visual SLAM. We further enhance perception in low-texture areas by incorporating line features in the front-end and mitigate scale degradation with learned depth estimates. Additionally, point-line feature constraints optimize pose estimation and mapping through a tightly coupled point-line bundle adjustment (BA). The learned pose estimates refine the feature matching process during tracking, leading to more accurate localization and mapping. Experimental results on public and self-collected datasets show that D3L-SLAM significantly outperforms both traditional and learning-based visual SLAM methods in localization accuracy.

Embedded fiber Bragg gratings are increasingly applied for in-situ strain measurement in fiber-reinforced plastics, integral to high-end aerospace equipment. Existing research primarily focuses on in-plane strain measurement, limited by the fact that fiber Bragg gratings are mainly sensitive to axial strain. However, out-of-plane strain measurement is equally important for comprehending structural deformation. The birefringence of fiber Bragg gratings shows promise for addressing this problem; yet, the strain transfer relationship between composites and optical fibers, along with the decoupling method for multi-directional strains, remains inadequately explored. This study introduces an innovative method for multi-directional strain measurement in fiber-reinforced plastics using the birefringence of a single-fiber Bragg grating. The strain transfer relationship between composites and embedded optical fibers was derived based on Kollar’s analytical model, leading to the development of a multi-directional strain decoupling methodology. This method was experimentally validated on carbon fiber/polyetherimide laminates under thermo-mechanical loading. Its reliability was confirmed by comparing experimental results and finite element simulations. These findings significantly broaden the application scenarios of fiber Bragg gratings, advancing the in-situ measurement technology crucial for the next generation of high-end aerospace equipment.

Abstract Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

BackgroundWith the increasing exposure to hazardous chemicals in the workplace and frequency of occupational injuries and occupational safety accidents, the acquisition of occupational exposure limits of hazardous chemicals is imminent.ObjectiveTo obtain more unknown immediately dangerous to life or health (IDLH) concentrations of hazardous chemicals in the workplace by exploring the application of quantitative structure-activity relationship (QSAR) prediction method to IDLH concentrations, and to provide a theoretical basis and technical support for the assessment and prevention of occupational injuries.MethodsQSAR was used to correlate the IDLH values of 50 benzene and its derivatives with the molecular structures of target compounds. Firstly, affinity propagation algorithm was applied to cluster sample sets. Secondly, Dragon 2.1 software was used to calculate and pre-screen 537 molecular descriptors. Thirdly, the genetic algorithm was used to select six characteristic molecular descriptors as dependent variables and to construct a multiple linear regression model (MLR) and two nonlinear models using support vector machine (SVM) and artificial neural network (ANN) respectively. Finally, model performance was evaluated by internal and external validation and Williams diagram was drawn to determine the scopes of selected models.ResultsThe ANN model results showed that \begin{document}$ {R}_{\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}}^{2} $\end{document}=0.8526 and \begin{document}$ {R}_{\mathrm{t}\mathrm{e}\mathrm{s}\mathrm{t}}^{2} $\end{document}=0.8505 respectively, root mean square (RMSE) error=0.5243, mean absolute error (MAE)=0.4610, internal and external validation coefficients \begin{document}$ {Q}_{\mathrm{l}00}^{2} $\end{document}=0.8476 and \begin{document}$ {Q}_{\mathrm{e}\mathrm{x}\mathrm{t}}^{2} $\end{document}=0.8905 respectively. By comparison, the performance verification parameters of the ANN model were superior to the MLR and SVM models, and all substances were in the applicable domain.ConclusionAt present, the ANN model has the best performance in fitting ability, stability, and prediction, and is suitable for predicting IDLH concentrations of benzene and its derivatives. Predicting the IDLH concentraitons of benzene and its derivatives by QSAR method is an effective method, and provides a theoretical basis and technical support for the development of occupational health and safety.

Abstract Background Circular RNAs (circRNAs) circularized by back-splicing of pre-mRNA are widely expressed and affected the proliferation, invasion and metastasis of bladder cancer (BCa). However, the mechanism underlying circRNA biogenesis in mediating the distant metastasis of BCa still unexplored. Methods RNA sequencing data between BCa and normal adjacent tissues was applied to identify the differentially expressed circRNAs. The functions of circNIPBL in BCa were investigated via a series of biochemical experiments. The Clinical significance of circNIPBL was examined in a cohort of larger BCa tissues. Results In the present study, we identified a novel circRNA (hsa_circ_0001472), circNIPBL, which was significantly upregulated and had great influence on the poor prognosis of patients with BCa. Functionally, circNIPBL promotes BCa metastasis in vitro and in vivo. Mechanistically, circNIPBL upregulate the expression of Wnt5a and activated the Wnt/β-catenin signaling pathway via directly sponged miR-16-2-3p, leading to the upregulation of ZEB1, which triggers the EMT of BCa. Moreover, we revealed that ZEB1 interacted with the flanking introns of exons 2–9 on NIPBL pre-mRNA to trigger circNIPBL biogenesis, thus forming a positive feedback loop. Importantly, circNIPBL overexpression significantly facilitated the distant metastasis of BCa in the orthotopic bladder cancer model, while silencing ZEB1 remarkably blocked the effects of metastasis induced by circNIPBL overexpression. Conclusions Our study highlights that circNIPBL-induced Wnt signaling pathway activation triggers ZEB1-mediated circNIPBL biogenesis, which forms a positive feedback loop via the circNIPBL/miR-16-2-3p/Wnt5a/ZEB1 axis, supporting circNIPBL as a novel therapeutic target and potential biomarker for BCa patients. Graphical Abstract

Abstract Objective Bladder cancer is the 13th most common cancer in China with the predominant histologic type being urothelial carcinoma (UC). Locally advanced and metastatic (la/m) UC accounts for 12% of UC and the five‐year survival rate is only 39.4%, imposing a significant disease and economic burden on the patients. The aim of this scoping review is to synthesize existing evidence of epidemiology, the landscape of treatment options and associated efficacy and safety profiles, as well as treatment‐related biomarkers among Chinese la/mUC patients. Methods A systematic search was conducted on five databases (PubMed, Web of Science, Embase, Wanfang, and CNKI) from January 2011 to March 2022 based on the scoping review criteria in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. Results A total of 6211 records were identified, and further review resulted in 41 relevant studies that met all criteria. Additional searches were conducted on epidemiology and treatment‐related biomarkers of bladder cancer to supplement the evidence. Among 41 studies, 24 reported on platinum‐based chemotherapy, eight on non‐platinum‐based chemotherapy, six on immunotherapy, two on targeted therapy, and one on surgery. Efficacy outcomes were summarized by line of therapy. Treatment‐related biomarkers including PD‐L1, HER2, and FGFR3 alterations were identified, and the alteration rate of FGFR3 of Chinese UC patients was lower than that of the western patients. Conclusions Despite chemotherapy has been the main treatment choice for decades, appealing new therapeutic strategies including ICIs, targeted therapies and ADCs were applied in clinical practice. Further research on epidemiology and treatment‐related biomarkers of la/mUC patients is needed given only a limited number of studies have been identified thus far. High genomic heterogeneity and complexity of molecular features were observed among la/mUC patients; thus, further studies are required to identify critical drivers and promote potential precise therapies.

Abstract Since the limitation on the onboard equipment, the sparse stereo vision is becoming a suitable choice for the deployment of micro air vehicles (MAV) and small robots. However, for the point feature‐based sparse stereo, most of the current stereo algorithms ignore the similarity between feature points, so it is hard to achieve high accuracy. In addition, the problem of clustered feature distribution will still affect the performance of point feature‐based algorithms in the application. To make up for these deficiencies, the authors propose an improved features from accelerated segment test (FAST) feature detector to suppress the point detection in complex texture regions. Most importantly, the authors present a novel census transform (CT)‐based algorithm that contains two encoders ‘texture orientation’ and ‘texture gradient’ to get a more efficient census bit string for the feature point. Instead of randomly selecting pixels to calculate the bit string, we combine the texture characteristics of the census windows where feature points are located. Compared with the original CT, the processing speed of our method is improved, and the average error of our method is reduced by 18.05%. The evaluation results show the presented improved point feature‐based sparse stereo algorithm has a great value in engineering applications.

(1) Purpose: The purpose of this study was to evaluate the prognostic capacity of the pathological N status (pN), lymph node ratio (LNR), and the log odds of positive lymph nodes (LODDS), and to build a prognostic nomogram to predict overall survival (OS) for bladder cancer patients treated by radical cystectomy. (2) Methods: The clinical and pathological characteristics of 10,938 patients with bladder cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017. The predictive capacity was assessed by univariate and multivariate Cox regression analyses, the area under the receiver operating characteristic curve (AUC), and C-index. Calibration curves, decision curve analysis (DCA), and risk-grouping were utilized to evaluate the predictive accuracy and discriminative ability of the nomogram. (3) Results: LODDS was an independent risk factor for bladder cancer (all p < 0.001) and demonstrated the highest values of C-index and AUC. The values of AUCs in the training cohort were 0.747, 0.743, and 0.735 for predicting 1-, 3-, and 5-year OS, respectively. Calibration curves and DCA curves suggested the excellent clinical application value of our nomogram. (4) Conclusions: LODDS is a better predictive indicator for bladder cancer patients compared to pN and LNR. The LODDS-incorporated nomogram has excellent accuracy and promising clinical application value for non-metastatic bladder cancer after radical cystectomy.

Abstract Background The purpose of this study was to explore the impact of extreme precipitation on the risk of outpatient visits for depression and to further explore its associated disease burden and vulnerable population. Methods A quasi-Poisson generalized linear regression model combined with distributed lag non-linear model (DLNM) was used to investigate the exposure-lag-response relationship between extreme precipitation (≥95th percentile) and depression outpatient visits from 2017 to 2019 in Suzhou city, Anhui Province, China. Results Extreme precipitation was positively associated with the outpatient visits for depression. The effects of extreme precipitation on depression firstly appeared at lag4 [relative risk (RR): 1.047, 95% confidence interval (CI): 1.005–1.091] and lasted until lag7 (RR = 1.047, 95% CI: 1.009–1.087). Females, patients aged ≥65 years and patients with multiple outpatient visits appeared to be more sensitive to extreme precipitation. The attributable fraction (AF) and numbers (AN) of extreme precipitation on outpatient visits for depression were 5.00% (95% CI: 1.02–8.82%) and 1318.25, respectively. Conclusions Our findings suggested that extreme precipitation may increase the risk of outpatient visits for depression. Further studies on the burden of depression found that females, aged ≥65 years, and patients with multiple visits were priority targets for future warnings. Active intervention measures against extreme precipitation events should be taken to reduce the risk of depression outpatient visits.

PbSn solders are used in semiconductor devices for aerospace or military purposes with high levels of reliability requirements. Microalloying has been widely adopted to improve the reliability for Pb-free solders, but its application in PbSn solders is scarce. In this article, the optimization of PbSn solder reliability with Ge microalloying was investigated using both experimental and calculation methods. Intermetallic compounds (IMC) growth and morphologies evolution during reliability tests were considered to be the main factors of device failure. Through first-principle calculation, the growth mechanism of interfacial Ni3Sn4 was discussed, including the formation of vacancies, the Ni-vacancies exchange diffusion and the dominant Ni diffusion along the [1 0 0] direction. The doping of Ge in the cell increased the exchange energy barrier and thus inhibited the IMC development and coarsening trend. In three reliability tests, only 0.013 wt% Ge microalloying in Pb60Sn40 was able to reduce IMC thickness by an increment of 22.6~38.7%. The proposed Ge microalloying method in traditional PbSn solder could yield a prospective candidate for highly reliable applications.

We analyze 347 galaxies at redshift 4 < z < 9.5 using JWST observations from the Cosmic Evolution Early Release Science (CEERS) program by simultaneously fitting a two-dimensional parametric model to the seven-filter Near Infrared Camera images to measure the overall structural parameters and quantify the global properties of the galaxies in the rest-frame optical band. Particular attention is devoted to deriving robust uncertainties that include, among other factors, the influence of cosmological surface brightness dimming and resolution effects. Using the global Sérsic index ( n < 1.5) and observed axial ratio ( q < 0.6) as a guide, we place a conservative lower limit of ∼45% on the incidence of galactic disks. Galaxies follow a relation between the rest-frame optical luminosity and effective radius in the redshift range 4 < z < 9.5, as well as separately over the intervals 4 < z < 5 and 5 ≤ z < 9.5, with a very similar slope but a marginally lower zero-point in the higher-redshift bin ( R _e = 0.69 ± 0.05 kpc) compared to the lower-redshift bin ( R _e = 0.91 ± 0.04 kpc). Within the limitations of the current sample size, we find no significant redshift evolution of n or R _e at these early epochs.

End-to-end deep neural network (DNN)-based motion planners have shown great potential in high-speed autonomous UAV flight. Yet, most existing methods only employ a single high-capacity DNN, which typically lacks generalization ability and suffers from high sample complexity. We propose a novel event-triggered hierarchical planner (ETHP), which exploits the bi-level optimization nature of the navigation task to achieve both efficient training and improved optimality. Specifically, we learn a depth-image-based end-to-end motion planner in a hierarchical reinforcement learning framework, where the high-level DNN is a reactive collision avoidance rerouter triggered by the clearance distance, and the low-level DNN is a goal-chaser that generates the heading and velocity references in real time. Our training considers the field-of-view constraint and explores the bi-level structural flexibility to promote the spatio–temporal optimality of planning. Moreover, we design simple yet effective rules to collect hindsight experience replay buffers, yielding more high-quality samples and faster convergence. The experiments show that, compared with a single-DNN baseline planner, ETHP significantly improves the success rate and generalizes better to the unseen environment.

Despite promising for anti-icing applications, structured superhydrophobic surfaces usually lose their hydrophobicity after a few icing/melting cycles. Here, authors investigate specific structured surfaces and air bubbles on frozen ice droplets to propose three criteria to enable dewetting transitions.

BackgroundChildhood trauma is closely related to the onset of depression and more severe depressive symptoms; however, the specific mechanisms are unclear. We aimed to examine the relationship between childhood trauma and sleep disorders in children and adolescents with depression and to explore further the role of sleep disorders in the relationship between childhood trauma and depression severity.MethodsA total of 285 children and adolescents with depression completed all scale assessments, including the Childhood Trauma Questionnaire, Self-Reported Insomnia Severity Index and Epworth Sleepiness Scale, and the Center for Epidemiologic Studies Depression Scale. A simple mediation model was used as a theoretical model to examine whether sleep disorders could mediate the relationship between childhood trauma and depression severity.ResultsAmong children and adolescents with depression, childhood trauma is about 78.9%. Compared with patients without childhood trauma, patients with childhood trauma had a higher incidence of sleep disorders (Z = 17.59, P < 0.001), which were characterized by insomnia (Z = 14.45, P < 0.001), not hypersomnia (Z = 2.77, P = 0.096). Different childhood trauma subtypes significantly affected sleep disorders and insomnia (all P < 0.05). Insomnia partially mediated the relationship between childhood trauma and depression severity, and the mediating effect accounted for 35.90%.ConclusionThis study found a high rate of concurrent childhood trauma and insomnia among children and adolescents with depression. Insomnia, as a mediator between childhood trauma and depression severity, partially mediates the relationship.

Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC) and predicts poor prognosis for patients. The KRASG12D mutation confers an aggressive PDAC phenotype that is susceptible to lymphatic dissemination. However, the regulatory mechanism underlying KRASG12D mutation–driven LN metastasis in PDAC remains unclear. Herein, we found that PDAC with the KRASG12D mutation (KRASG12D PDAC) sustained extracellular vesicle–mediated (EV-mediated) transmission of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in a SUMOylation-dependent manner and promoted lymphangiogenesis and LN metastasis in vitro and in vivo. Mechanistically, hnRNPA1 bound with SUMO2 at the lysine 113 residue via KRASG12D-induced hyperactivation of SUMOylation, which enabled its interaction with TSG101 to enhance hnRNPA1 packaging and transmission via EVs. Subsequently, SUMOylation induced EV-packaged-hnRNPA1 anchoring to the adenylate- and uridylate-rich elements of PROX1 in lymphatic endothelial cells, thus stabilizing PROX1 mRNA. Importantly, impeding SUMOylation of EV-packaged hnRNPA1 dramatically inhibited LN metastasis of KRASG12D PDAC in a genetically engineered KrasG12D/+ Trp53R172H/+ Pdx-1-Cre (KPC) mouse model. Our findings highlight the mechanism by which KRAS mutant–driven SUMOylation triggers EV-packaged hnRNPA1 transmission to promote lymphangiogenesis and LN metastasis, shedding light on the potential application of hnRNPA1 as a therapeutic target in patients with KRASG12D PDAC.

Asymptotic homogenization (AH) is a rigorous method used for modeling multiscale mechanical behavior in periodic composites. Unlike conventional AH methods, which predict the effective viscoelasticity using the elastic–viscoelastic correspondence principle, an AH method was proposed to directly calculate the effective material properties in the time domain, thereby enabling the complex transform to be omitted between the time and Laplace domains. This time-domain AH method is reformulated based on the integral form rather than the differential form of the Kelvin–Voigt viscoelastic model. Thus, multiple time-domain-based characteristic elasticity and viscosity displacement tensors are replaced by one integral form characteristic displacement tensor in the polymer matrix composite. Using mathematical formulae, a numerical implementation method was then developed by establishing location- and time-related stress loads. An in-house Python subroutine was also programmed to compute the effective viscoelastic properties from the finite element implementation results. Unidirectional and woven fabric composite homogenization results were comparable to those obtained using the conventional representative volume element method, indicating high effectiveness and accuracy. The results suggest that the proposed time-domain AH method is a powerful tool for modeling the two-scale mechanical behavior of viscoelastic composites and is compatible with the existing commercial software.

BackgroundInternet addiction (IA) symptoms are common among adolescents and negatively impact their academic performance and development. These symptoms are also associated with lower quality of life (QOL) and increased suicidality. This study aimed to examine the prevalence and the sociodemographic and clinical correlates of IA symptoms in adolescents with major depressive disorder (MDD) and their association with QOL.MethodsThis cross-sectional study was conducted in three general and four psychiatric hospitals in Anhui Province, China, from January to July 2021. Sociodemographic and clinical data were collected. The Internet Addiction Test (IAT), Center for Epidemiologic Studies of Depression Symptom Scale (CES-D), and World Health Organization Quality of Life Brief version (WHOQOL-BREF) were utilized to examine IA, depressive symptoms, and QOL, respectively.ResultsIn a multicenter sample of 278 adolescents with MDD, the prevalence of IA symptoms in adolescents with MDD was 46.8% (95% CI: 40.9–52.7%). Logistic regression analysis showed that patients with more severe depressive symptoms (odds ratio [OR] = 1.05, 95% CI: 1.03–1.08), those living in a rural area (OR = 1.94, 95% CI: 1.15–3.27), and those with poor academic performance (OR = 2.90, 95% CI: 1.42–5.95) were more likely to have IA symptoms. After controlling for confounding factors, patients with IA symptoms had significantly poorer QOL in the physical, psychological, and environmental domains than those without IA symptoms.ConclusionIA symptoms are common in adolescents with MDD and appear to be associated with clinical symptoms. We could not infer a causal relationship between IA and depression because this was a cross-sectional study. Considering the positive association between IA symptoms and lower QOL, screening for IA symptoms should be conducted, and effective measures should be implemented for adolescents with MDD.

Abstract Background Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown. Methods Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p. Results In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC. Conclusions Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC. Graphical abstract

Abstract Background Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. Method CircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2′-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p. Results In the present study, we identified a novel circRNA (termed as circBFAR, hsa_circ_0009065) that was upregulated in a 208-case cohort of patients with PDAC. The ectopic expression of circBFAR correlated positively with the tumor-node-metastasis (TNM) stage and was related to poorer prognosis of patients with PDAC. Moreover, circBFAR knockdown dramatically inhibited the proliferation and motility of PDAC cells in vitro and their tumor-promoting and metastasis properties in in vivo models. Mechanistically, circBFAR upregulated mesenchymal-epithelial transition factor (MET) expression via sponging miR-34b-5p. Additionally, circBFAR overexpression increased the expression of MET and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which ultimately promoted the progression of PDAC cells. Importantly, application of MET inhibitors could significantly attenuate circBFAR-mediated tumorigenesis in vivo. Conclusions Our findings showed that circBFAR plays an important role in the proliferation and metastasis of PDAC, which might be explored as a potential prognostic marker and therapeutic target for PDAC.

Abstract Background The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not yet been elucidated. Methods The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays were utilized to examine the interaction of PLACT1 with IκBα promoter. Results We identified a novel lncRNA-PLACT1, which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo. Conclusions Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC.

Radiative cooling is an effective technology with zero energy consumption to alleviate climate warming and combat the urban heat island effect. At present, researchers often use foam boxes to isolate non-radiant heat exchange between the cooler and the environment through experiments, so as to achieve maximum cooling power. In practice, however, there are challenges in setting up foam boxes on a large scale, resulting in coolers that can be cooled below ambient only under low convection conditions. Based on polymer materials and nano-zinc oxide (nano-ZnO, refractive index > 2, the peak equivalent spherical diameter 500 nm), the manufacturing process of heat pump film (HPF) was proposed. The HPF (4.1 mm thick) consists of polyethylene (PE) bubble film (heat transfer coefficient 0.04 W/m/K, 4 mm thick) and Ethylene-1-octene copolymer (POE) cured nano-ZnO (solar reflectance ≈94% at 0.075 mm thick). Covering with HPF, the object achieves 7.15 °C decreasing in normal natural environment and 3.68 °C even under certain circumstances with high surface convective heat transfer (56.9 W/m2/K). HPF has advantages of cooling the covered object, certain strength (1.45 Mpa), scalable manufacturing with low cost, hydrophobic characteristics (the water contact angle, 150.6°), and meeting the basic requirements of various application scenarios.

Objectives: The incidence of psychological and behavioral problems and depression among adolescents is increasing year by year, which has become an important public health problem. Alexithymia, as an important susceptible factor of adolescent depression, may continue to develop and strengthen under the stimulation of COVID-19-related stressors. However, no studies have focused on alexithymia in adolescent depression during the pandemic in China. This study aims to investigate the incidence and related factors of alexithymia in adolescent depression during the pandemic.Methods: Three hundred adolescent patients were enrolled from October 2020 to May 2021. The general demographic information of all participants was collected, and the clinical characteristics were assessed by the 20-item Toronto Alexithymia Scale (TAS-20), the Adolescent Self-Rating Life Events Check (ASLEC) List, the Childhood Trauma Questionnaire (CTQ), and the Positive and Negative Suicide Ideation (PANSI) Inventory.Results: The incidence of alexithymia was significantly higher among adolescents with depression (76.45%) during the pandemic. There were significant differences in school bullying, disease severity, ASLEC score, CTQ score and PANSI score between adolescents with and without alexithymia. In addition, learning stress, health and adaptation problems during the pandemic may be influential factors in alexithymia of adolescent depression (P < 0.05).Conclusions: According to the results, we found a high incidence of alexithymia in adolescent depression during the pandemic. More support and attention from families, schools and society is needed to develop preventive and targeted psychological interventions as early as possible.

Optrodes, which are single shaft neural probes integrated with microelectrodes and optical light sources, offer a remarkable opportunity to simultaneously record and modulate neural activities using light within an animal’s brain; however, a common problem with optrodes is that stimulation artifacts can be observed in the neural recordings of microelectrodes when the light source on the optrode is activated. These stimulation artifacts are undesirable contaminants, and they cause interpretation complexity when analyzing the recorded neural activities. In this paper, we tried to mitigate the effects of the stimulation artifacts by developing a low-noise, double-sided optrode integrated with multiple Electromagnetic Shielding (EMS) layers. The LED and microelectrodes were constructed separately on the top epitaxial and bottom substrate layers, and EMS layers were used to separate the microelectrodes and LED to reduce signal cross-talks. Compared with conventional single-sided designs, in which the LED and microelectrodes are constructed on the same side, our results indicate that double-sided optrodes can significantly reduce the presence of stimulation artifacts. In addition, the presence of stimulation artifacts can further be reduced by decreasing the voltage difference and increasing the rise/fall time of the driving LED pulsed voltage. With all these strategies, the presence of stimulation artifacts was significantly reduced by ~76%. As well as stimulation suppression, the sapphire substrate also provided strong mechanical stiffness and support to the optrodes, as well as improved electronic stability, thus making the double-sided sapphire optrodes highly suitable for optogenetic neuroscience research on animal models.

Abstract Background Patients with lymph node (LN) metastatic bladder cancer (BCa) present with extremely poor prognosis. BCa‐derived exosomes function as crucial bioactive cargo carriers to mediate the signal transduction in tumor microenvironment triggering tumor metastasis. However, the mechanisms underlying exosome‐mediated LN metastasis in BCa are unclear. Methods We conducted the high‐throughput sequencing to explore the expression profile of long noncoding RNA (lncRNA) in urinary exosomes (urinary‐EXO) from patients with BCa and further evaluated the clinical relevance of exosomal lncRNA BCYRN1 in a larger 210‐case cohort. The functional role of exosomal BCYRN1 was evaluated through the migration and tube formation assays in vitro and the footpad‐popliteal LN metastasis model in vivo. RNA pull‐down assays, luciferase assays, and actinomycin assays were conducted to detect the regulatory mechanism of exosomal BCYRN1. Results LncRNA BCYRN1 was substantially upregulated in urinary‐EXO from patients with BCa, and associated with the LN metastasis of BCa. We demonstrated that exosomal BCYRN1 markedly promoted tube formation and migration of human lymphatic endothelial cells (HLECs) in vitro and lymphangiogenesis and LN metastasis of BCa in vivo. Mechanistically, BCYRN1 epigenetically upregulated WNT5A expression by inducing hnRNPA1‐associated H3K4 trimethylation in WNT5A promoter, which activated Wnt/β‐catenin signaling to facilitate the secretion of VEGF‐C in BCa. Moreover, exosomal BCYRN1 was transmitted to HLECs to stabilize the VEGFR3 mRNA and thus formed an hnRNPA1/WNT5A/VEGFR3 feedforward regulatory loop, ultimately promoting the lymphatic metastasis of BCa. Importantly, blocking VEGFR3 with specific inhibitor, SAR131675 significantly impaired exosomal BCYRN1‐induced the LN metastasis in vivo. Clinically, exosomal BCYRN1 was positively associated with the shorter survival of BCa patients and identified as a poor prognostic factor of patients. Conclusion Our results uncover a novel mechanism by which exosomal BCYRN1 synergistically enhances VEGF‐C/VEGFR3 signaling‐induced lymphatic metastasis of BCa, indicating that BCYRN1 may serve as an encouraging therapeutic target for patients with BCa.

The peripheral surface of the grinding wheel can grind the rail according to the envelope of the contour of the rail surface, thus a fuller and smoother rail surface can be obtained. Specifically, a better grinding effect can be obtained in that the end face of the grinding wheel deviates from the longitudinal section of the rail at a certain angle. Based on the traditional grinding technology theory, the mathematical models of the peripheral grinding parameters (kinematic contact arc length, wheel-rail grinding contact area, and maximum undeformed chip thickness) and the grinding force are established, in which the angle exists between the grinding wheel end face and the rail longitudinal section. The main influence of grinding wheel circumferential speed, grinding wheel kinematic speed, and the deflection angle of the grinding wheel end face on the grinding parameters and the force are analyzed. The result shows that: when there is angle θ in the models, the ratios of peripheral grinding parameters between up-grinding and down-grinding varies monotonically with the increase in vm, and their maximum variation range is about 12%, vs has the greatest influence on the peripheral grinding parameters, and the maximum variation range of the ratios is about 20% when the vs is 10 m/s. With the increase in the grinding width, Fa’ cannot be ignored and will increase gradually with the increase in angle θ. The analysis and conclusion have guiding significance for the structural design, grinding control strategy, and experimental research regarding rail curved surface grinding equipment.

Objectives: Healthcare workers (HWs) experienced high levels of work stress during the COVID-19 pandemic, leading to a high risk of sleep disturbances. This meta-analysis aimed to explore the prevalence of sleep disturbances and sleep quality in Chinese HWs during the COVID-19 pandemic.Methods: English (PubMed, EMBASE, PsycINFO, Web of Science, and the Cochrane Library) and Chinese databases (WanFang, Chinese National Knowledge Infrastructure, and SinoMed) were systematically and independently searched for relevant studies published from December 1, 2019, to May 20, 2020. The pooled prevalence of sleep disturbances and sleep quality were calculated using a random-effects model.Results: A total of 17 studies involving 12,682 Chinese HWs were included in the meta-analysis. The pooled prevalence of sleep disturbances in Chinese HWs was 45.1% (95% CI: 37.2–53.1%). We found that the prevalence of sleep disturbances varied among frontline, infected, and non-frontline HWs (Q = 96.96, p < 0.001); females and males (Q = 9.10, p = 0.003); studies using different assessment instruments (Q = 96.05, p < 0.001); and studies with different sample sizes (Q = 5.77, p = 0.016) and cut-off values (Q = 62.28, p < 0.001). The pooled mean total score of the Pittsburgh Sleep Quality Index (PSQI) was 9.83 (95% CI: 8.61–11.04). HWs in Wuhan had a higher total PSQI score than those in other regions (Q = 9.21, p = 0.002).Conclusion: Sleep disturbances were common in Chinese HWs during the COVID-19 pandemic, particularly in frontline and infected HWs. Our results indicate the heavy mental health burden on HWs during the COVID-19 pandemic in China and can provide other countries with valuable information to assist HWs during the crisis.

Mechanism of lymph node (LN) metastasis induced by tumor associated macrophages (TAMs) remains unclear. Here they demonstrate that a long noncoding RNA LNMAT1 promotes LN metastasis of bladder cancer via recruitment of TAMs through epigenetic regulation of CCL2 expression.

Integrated optrodes for optogenetics have been becoming a significant tool in neuroscience through the combination of offering accurate stimulation to target cells and recording biological signals simultaneously. This makes it not just be widely used in neuroscience researches, but also have a great potential to be employed in future treatments in clinical neurological diseases. To optimize the integrated optrodes, this paper aimed to investigate the influence of surface material and illumination upon the performance of the microelectrode/electrolyte interface and build a corresponding evaluation system. In this work, an integrated planar optrode with a blue LED and microelectrodes was designed and fabricated. The charge transfer mechanism on the interface was theoretically modeled and experimentally verified. An evaluation system for assessing microelectrodes was also built up. Using this system, the proposed model of various biocompatible surface materials on microelectrodes was further investigated under different illumination conditions. The influence of illumination on the microelectrode/electrolyte interface was the cause of optical artifacts, which interfere the biological signal recording. It was found that surface materials had a great effect on the charge transfer capacity, electrical stability and recoverability, photostability, and especially optical artifacts. The metal with better charge transfer capacity and electrical stability is highly possible to have a better performance on the optical artifacts, regardless of its electrical recoverability and photostability under the illumination conditions of optogenetics. Among the five metals used in our investigation, iridium served as the best surface material for the proposed integrated optrodes. Thus, optimizing the surface material for optrodes could reduce optical interference, enhance the quality of the neural signal recording for optogenetics, and thus help to advance the research in neuroscience.

Aiming at how to specify the fundamental trade-off between robust stability and nominal performance of mixed H 2 /H ∞ control as well as lack of experimental studies on vibration control for the maglev actuator in microgravity vibration isolation system, a mixed H 2 /H ∞ output feedback controller based on the linear matrix inequality method is designed and analyzed. This article establishes a state–space realization for a one-dimensional vibration isolation system and the H-norm performance indices are identified and calculated. Furthermore, the curves of threshold values and true values of H ∞ and H 2 norms are plotted to specify the relationship between the system’s robust stability and nominal performance. Therefore, the threshold value of system’s H ∞ norm is identified through repeated simulations, and the state–space realization of optimal controller with minimum H 2 norm under the constraints of H ∞ norm threshold value is obtained. The vibration control experimental apparatus of one-dimensional control system is designed and manufactured to test the actual application of mixed H 2 /H ∞ controller for the maglev actuator. The result presents that the designed mixed H 2 /H ∞ control has a better performance in suppressing acceleration vibration and has a higher attenuation amplitude than cascade proportional–integral–derivative control at each corresponding frequency, which proves the practicability and effectiveness of the design method.

Process monitoring of woven fabric thermoplastic composite is crucial to enhance the quality of composite products. In this work, a new fiber Bragg grating based technique was proposed to achieve hybrid temperature and stress monitoring according to the changes of wavelength and reflectivity, respectively. The sensor head consisting of a pre-annealed fiber Bragg grating and a steel capillary was properly designed to overcome the challenge of high forming temperatures up to 332 °C, complex woven structure, and high forming pressure of 2 MPa, which hinder the use of the conventional fiber Bragg grating sensor during the forming process. The forming temperature changes of thermoplastic composite in the heating, dwelling, and cooling phases can be precisely measured by the proposed sensor head after using a curve-reconstruction algorithm based on cubic polynomial fitting. The measured difference from the reference thermocouple is 2.92 °C, averaged from three sets of repeated experiments. Meanwhile, the change of the residual stresses of the composite can be illustrated by using the micro-bending-caused optical power loss of the fiber pigtail commencing at the glass-transition temperature in the cooling phase. The decrease of grating reflectivity that was equivalent to the optical loss was discussed by comparing to strain change detected by strain gauges and a calculated theoretical curve. These results are beneficial for developing an advanced in situ monitoring technique and understanding the forming process of the woven fabric thermoplastic composite.

WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription (Wysocka et al., 2005 [1]; Sandstrom et al., 2014[2]; Ang et al., 2011[3]). Recently, our study found that WDR5 was upregulated in bladder cancer tissues, promoted bladder cancer cell proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro, and tumor growth in vivo (Chen et al., 2015). To gain a molecular understanding of the role of WDR5 in promoting bladder cancer, we performed a genome-wide analysis on WDR5 knockdown by microarray gene expression profiling. Here we provide detailed experimental methods and analysis for the microarray data, which have been deposited into Gene Expression Omnibus (GEO): GSE59132.

In men with adverse prognostic factors (APFs) after radical prostatectomy (RP), the most appropriate timing to administer radiotherapy remains a subject for debate. We conducted a systemic review and meta-analysis to evaluate the therapeutic strategies: adjuvant radiotherapy (ART) and salvage radiotherapy (SRT).We comprehensively searched PubMed, EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis of all randomized controlled trials (RCTs) and retrospective comparative studies assessing the prognostic factors of ART and SRT.Between May 1998 and July 2012, 2 matched control studies and 16 retrospective studies including a total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT). 5-year biochemical failure free survival (BFFS) for ART was longer than that for SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; p

We obtain new estimates – both upper and lower bounds – on the mean values of the Weyl sums over a small box inside of the unit torus. In particular, we refine recent conjectures of C. Demeter and B. Langowski (2022), and improve some of their results [ABSTRACT FROM AUTHOR]