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The quality inspection of each precast utility tunnel segment is crucial, especially the cross-sectional dimensions and surface smoothness, since they influence the assembly precision at the construction site. Traditional manual inspection methods are not only time-consuming and costly but also limited in accuracy. In order to achieve a high-precision and high-efficiency geometric quality inspection for multi-type precast utility tunnel segments, this paper proposes an automated inspection method based on the Building Information Model (BIM) and Light Detection and Ranging (LiDAR). Initially, the point cloud data (PCD) of the precast utility tunnel segment are acquired through LiDAR and preprocessed to obtain independent point clouds of the precast utility tunnel segment. Then, the shape of the precast utility tunnel segment is identified using the proposed Cross-Sectional Geometric Ratio Feature Identification (CSGRFI) algorithm. Subsequently, the geometric features of the components are extracted based on preset conditions, and the geometric dimensions are calculated. Finally, the quality inspection results are obtained by comparing with the design information provided by the BIM. The proposed method was validated in a real precast component factory. The results indicate that the method achieved a 100% success rate in identifying the cross-sectional shapes of the segments. Compared with the manual measurement method, the proposed method demonstrated a higher accuracy in the geometric quality assessment and an improved time efficiency by 44%. The proposed method enables the efficient geometric quality inspection of tunnel segments, effectively addressing the construction industry’s need for large-scale, high-quality tunnel projects.

The application of paclitaxel (PTX) for chemotherapy of tongue squamous cell carcinoma shows unavoidable damage to normal tissue, thus need to develop drug delivery and tumor-targeting nanomaterials. Mesoporous silica nanoparticles (MSNs) exhibit advantages including a convenient synthesis process, adjustable structure, high drug loading efficiency and low cytotoxicity. In this study, we synthesized PTX-loaded calcium carbonate-coated degradable disulfide-doped MSNs to construct a pH/redox dual-responsive controlled-release nanosystem. A high PTX loading rate of 9.68 ± 0.21% was measured with significantly accelerated release at low pH and in the presence of GSH. Moreover, surface decoration of the cell membrane was conducted to realize homologous targeted killing of tongue squamous cell carcinoma cells (PTX/ssMSN@CaCO3@TC), as confirmed by dynamic light scattering and gel electrophoresis analyses. Our nanocomposite material could be effectively taken up by Tca8113 cells but not by L929 and HeLa cells. Moreover, excellent tumor killing performance was measured both in vitro and in vivo. A total of 94.00 ± 1.66% and 98.12 ± 0.28% of Tca8113 cells were killed after culturing for 1 day and 3 days, respectively. This study developed a novel nanomaterial with the abilities of homologous targeting and dual-responsive release of PTX in tumor cells, exhibiting great value for the design of nanotargeting tumor killing drugs.

Homologous to E6AP C‐terminus (HECT)‐type E3 ubiquitin ligase SMAD‐specific E3 ubiquitin protein ligase 1 (Smurf1) was originally identified to ubiquitinate Smad protein in the TGF‐β/BMP signaling pathway. Recently, Smurf1 has been reported to promote tumorigenesis by regulating multiple biological processes. High expression of Smurf1 plays a vital role in brain tumor progression by mediating aberrant cell signaling pathways. Previous reports have shown that Smurf1 is degraded mainly through the ubiquitin–proteasome system, but it remains unclear whether Smurf1 is degraded by autophagy in tumor cells. In this study, we show that autophagy activators promote Smurf1 degradation in glioblastoma (GB) cells. The autophagy receptor p62 colocalizes with ubiquitinated substrates to promote sequestration of cytoplasm cargo into the autophagosome. We report that autophagic degradation of Smurf1 is dependent on p62. Moreover, the autophagic degradation of Smurf1 is prevented in the absence of the HECT domain or E3 ubiquitin ligase activity. We further proved that activation of autophagy leads to a decrease of Smurf1 and the inhibition of the phosphoinositide 3‐kinase/protein kinase B signaling pathway in GB cells. Our results suggest that enhancement of autophagic degradation of Smurf1 may be a potential approach to treating GB.

S100 calcium binding protein beta (S100B) is an S-100 low molecular weight binding protein that regulates intracellular processes. This protein is involved in myocardial contractility and calcium handling capacity. In this study, a human embryonic stem cell (hESC) line with homozygous S100B knockout (S100B-KO) was generated using the CRISPR/Cas9 editing system. This S100B-KO hESC line maintained normal cell morphology and karyotype, expressed pluripotency markers, and could differentiate into cells of all three germ layers.

Abstract Background Glioblastoma multiforme (GBM) is the most malignant tumor in human brain. Diagnosis and treatment of GBM may lead to psychological disorders such as depressive and anxiety disorders. There was no research focusing on the correlation between depressive/anxiety disorder and the outcome of GBM. Thus, the aim of this study was to investigate the possibility of depressive/anxiety disorder correlated with the outcome of GBM patients, as well as the overlapped mechanism bridge which could link depressive/anxiety disorders and GBM. Methods Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) were used to investigate the psychological condition of GBM patients in our department. To further explore the potential mechanism, bioinformatic methods were used to screen out genes that could be indicators of outcome in GBM, followed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein–protein interaction (PPI) analysis. Further, cellular experiments were conducted to evaluate the proliferation, migration capacity of primary GBM cells from the patients. Results It was revealed that patients with higher PHQ-9 and GAD-7 scores had significantly worse prognosis than their lower-scored counterparts. Bioinformatic mining revealed that LTBP1 could be a potential genetic mechanism in both depressive/anxiety disorder and GBM. Primary GBM cells with different expression level of LTBP1 should significantly different proliferation and migration capacity. GO, KEGG analysis confirmed that extracellular matrix (ECM) was the most enriched function of LTBP1. PPI network showed the interaction of proteins altered by LTBP1. Hub genes COL1A2, COL5A1 and COL10A1, as well as mesenchymal marker CD44 and Vimentin were statistically higher expressed in LTBP1 high group; while proneural marker E-cadherin was significantly higher expressed in low LTBP1 group. Conclusion There is closely correlation between depressive/anxiety disorders and GBM. LTBP1 could be a potential bridge linking the two diseases through the regulation of ECM.

Summary: Amplification of ubiquitin E3 ligase Smurf1 promotes degradation of PTEN leading to hyperactivation of the Akt/mTORC1 pathway. However, inhibitors of this pathway have not hitherto yielded promising results in clinical studies because of strong drug resistance. Here, we investigated Smurf1 expression in various glioblastoma (GB) cell lines and patient tissues. The therapeutic efficacy of Smurf1 silencing and Torin1 treatment was assessed in GB cells and orthotopic mouse model. We found Smurf1 loss elevates PTEN levels that interrupt the epidermal growth factor receptor pathway activity. Cotreatment with Smurf1 silencing and mTORC1/C2 inhibitor Torin1 remarkably decreased phosphorylation of Akt, and mTORC1 downstream targets 4EBP1 and S6K resulting in synergistic inhibitory effects. Smurf1 knockdown in orthotopic GB mouse model impaired tumor growth and enhanced cytotoxicity of Torin1. Together, these findings suggest a rational combination of Smurf1 inhibition and Torin1 as a promising new avenue to circumvent PI3K/Akt pathway-driven tumor progression and drug resistance.

An amendment to this paper has been published and can be accessed via the original article.

The tumor suppressor PTEN mainly inhibits the PI3K/Akt pathway in the cytoplasm and maintains DNA stability in the nucleus. The status of PTEN remains therapeutic effectiveness for chemoresistance of the DNA alkylating agent temozolomide (TMZ) in glioblastoma (GB). However, the underlying mechanisms of PTEN’s interconnected role in the cytoplasm and nucleus in TMZ resistance are still unclear. In this study, we report that TMZ-induced PTEN nuclear import depends on PTEN ubiquitylation modification by Smurf1. The Smurf1 suppression decreases the TMZ-induced PTEN nuclear translocation and enhances the DNA damage. In addition, Smurf1 degrades cytoplasmic PTEN K289E (the nuclear-import-deficient PTEN mutant) to activate the PI3K/Akt pathway under TMZ treatment. Altogether, Smurf1 interconnectedly promotes PTEN nuclear function (DNA repair) and cytoplasmic function (activation of PI3K/Akt pathway) to resist TMZ. These results provide a proof-of-concept demonstration for a potential strategy to overcome the TMZ resistance in PTEN wild-type GB patients by targeting Smurf1.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

Nanozymes are nanomaterials with intrinsic enzyme-mimic activity, but their large-scale application is generally limited by their low catalytic activity. Herein, we demonstrated that highly exposed Cu active sites on twodimensional (2D) nitrogen-doped carbon (Cux/NC) can serve as efficient peroxidase-like (POD) catalysts with high atomic utilization. Specially, the uniformly distributed Cu active sites could react with H2 O2 to produce singlet oxygen (¹O2) under acidic conditions, which can efficiently oxidizes colorless 3,3 ', 5,5 ' -tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB). Among various Cux/NC nanozymes studied, the Cu0.14 /NC exhibited smaller maximum catalytic velocities (Vmax) and Menten constant (Km) for TMB and H2 O2. Benefiting from the highly active peroxidase-like activity, the Cu0.14 /NC nanozyme could be successfully applied for the hydroquinone (HQ) and ascorbic acid (AA) detection applications through the inhibitory effect of HQ and AA. More interestingly, α-glucosidase (α-Glu) detection sensing platform could be constructed based on HQ as a signal transmitter, with the detection range ranging from 0 to 12 U/L and the minimum detection limit being 0.68 U/L. This work provides not only an idea for the rational design of highly exposed Cu active sites but also fabricate an effective detection sensing platform for HQ, AA, and α-Glu detection. [ABSTRACT FROM AUTHOR]

Background and Objectives: The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. Methods: Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. Results: In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). Conclusions: The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.

To improve the accuracy of short-term multi-energy load prediction models for integrated energy systems, the historical development law of the multi-energy loads must be considered. Moreover, understanding the complex coupling correlation of the different loads in the multi-energy systems, and accounting for other load-influencing factors such as weather, may further improve the forecasting performance of such models. In this study, a two-stage fuzzy optimization method is proposed for the feature selection and identification of the multi-energy loads. To enrich the information content of the prediction input feature, we introduced a copula correlation feature analysis in the proposed framework, which extracts the complex dynamic coupling correlation of multi-energy loads and applies Akaike information criterion (AIC) to evaluate the adaptability of the different copula models presented. Furthermore, we combined a NARX neural network with Bayesian optimization and an extreme learning machine model optimized using a genetic algorithm (GA) to effectively improve the feature fusion performances of the proposed multi-energy load prediction model. The effectiveness of the proposed short-term prediction model was confirmed by the experimental results obtained using the multi-energy load time-series data of an actual integrated energy system.

Background. Gastric low-grade intraepithelial neoplasia (LGIN) is a precancerous lesion of gastric cancer. Endoscopic therapies represented by radiofrequency ablation (RFA) and argon plasma coagulation (APC) have been applied to treat gastric LGIN in recent years. However, no comparative study examining the effectiveness and safety profiles of RFA and APC has been reported. Methods. A single-center, large-scale, retrospective study, including 73 and 50 patients treated with RFA and APC, respectively, was conducted in the First Medical Center of Chinese PLA General Hospital from October 2015 to October 2020, with a two-year follow-up. Effectiveness, complications, operative factors, and other data were assessed. Results. At 2 years of follow-up, cure, relapse, recurrence, and progression rates were 90.4%, 9.6%, 9.6%, and 2.7% in the RFA group, respectively, versus 90%, 10%, 12%, and 4% in the APC group, respectively, with no statistically significant differences between the two groups (all p>0.05). However, the mean lesion size was significantly larger in the RFA group (2.6 ± 1.0 cm) than in the APC group (1.5 ± 0.6 cm) (p

Background. The correct surgical position is very important in the treatment of peroral endoscopic myotomy (POEM) for achalasia, which can make the procedure safer and more efficient. Currently, there are two commonly used positions: the supine position with the right shoulder raised and the left lateral position. This study aims to evaluate the differences in the safety and efficacy of these two positions. Methods. We conducted a retrospective study of 702 patients with achalasia undergoing POEM from December 2010 to December 2020. These patients were divided into the supine position with the right shoulder raised group (n=579) and the left lateral position group (n=123). The efficacy of POEM and adverse events were analyzed. Results. The clinical characteristics were similar in both groups, and there were no significant differences between the two groups in the Eckardt score change, lower esophageal sphincter (LES) basal pressure or residual pressure after POEM (all p>0.05). The mean operative time in the supine position with the right shoulder raised group was significantly shorter than that in the left lateral position group (43.5 min vs. 54.6 min, respectively, p

The penetration of large-diameter tubular piles and their relevant construction effect have significant influences on the bearing capacity of piles and nearby buildings (structures). This study focuses on developing an indoor test model device for the dynamic field monitoring of the construction effect of penetrated large-diameter tubular piles based on monocular visual digital photography. The results show that the relationship between the penetration of the tubular piles and time function (blow counts) changes from a logarithmic function to a linear function when piles penetrate from the loose layer to the sandy layer, and then to the silty soil layer. The penetration rates differ significantly under different formation conditions. There are obvious plugging and squeezing effects as tubular piles penetrate different strata. The plugging effect radiates outward in a rectangular shape. The influence sphere of the squeezing effect is divided into the shear failure zone, radial squeezing zone, and hemispherical expansion zone. According to the measurement data, the squeezing effect increases first and then weakens during the construction of tubular piles. This makes the adjacent pile deviate from the initial position by 17.4 mm, making the next pile deviate from the initial position by 6.4 mm, to the maximum extent. This further verifies the superiority of pile-jumping construction. The research conclusions can provide reasonable suggestions and a reference basis to improve the penetration parameters of tubular piles and optimise their construction techniques.