Search

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.

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.

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.

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.

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]

Objective: This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4) in primary hepatic carcinoma (PHC). Methods: The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC. The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup. Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased, and the expression of NRF2 and GPX4 in the cells was determined. NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2, and changes in cell proliferation and invasion capabilities were observed. Results: The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH (p < 0.05), and the two indicators combined was excellent in diagnosing PHC. Moreover, patients with high expression of NRF2 and GPX4 had a higher risk of death (p < 0.05). In in vitro experiments, both NRF2 and GPX4 expression was elevated in HepG2 (p < 0.05). HepG2 activity was enhanced by increasing the expression of the two, vice versa (p < 0.05). Conclusion: NRF2 and GPX4 combined is excellent in diagnosing PHC, and promotes the malignant development of PHC. [ABSTRACT FROM AUTHOR]