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Abstract Background We aimed to study the prognostic risk factors affecting patients with anaplastic thyroid carcinoma (ATC), develop a clinical prognostic model, and assess patient survival outcomes. Methods Patients with anaplastic thyroid carcinoma from 2000 to 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. The dataset was divided into training (70%) and validation (30%) sets based on a 7:3 ratio. Univariate and LASSO regression analyses were performed on clinical variables from the training set to identify independent prognostic factors. Independent prognostic factors were determined by Univariate and lasso regression according to the clinical variables of the training set, and a nomogram model was established to construct a prognostic model based on the contribution degree of the predictors. The prognostic model was evaluated and internally verified by C-index, ROC curve and calibration curve. Results A total of 713 ATC patients were included in the SEER database. LASSO regression results indicated that age, marital status, race, tumor size, whether the primary lesion was limited to the thyroid gland, surgery, radiotherapy and chemotherapy, were associated with overall survival(OS) prognosis of ATC, and were used to construct nomograms. In the training cohort, the OS nomogram’s C-index was 0.708 (95% CI 0.672–0.745); in the internal validation cohort, the C-index was 0.677 (95% CI 0.620–0.735). ROC curves demonstrated that the OS nomogram exhibits excellent predictive accuracy and discriminative ability. Calibration curves indicated strong consistency between the OS nomogram’s predicted survival rates and actual survival rates. Conclusions We established a survival prediction model for ATC, which can assist clinicians in assessing patient prognosis and making personalized treatment decisions.

Abstract Underground grouting is a concealed project, and it is difficult to test the strength of grouting stones in engineering practice. Aiming at the problems of high confined water pressure and strong water-richness of the roadway floor, a pressure filtration test device was developed, and a PFC2D uniaxial compression model was established to study the variation law of stone strength and crack evolution mechanism of grouting materials under different grouting pressures. The results show that with the increase of pressure filtration value, the amount of slurry dehydration increases, the pore water pressure dissipates, the pores between particles are tightly compressed, the contact force between particle skeletons increases, and the strength of stone body increases. Under the condition of the same cement powder ratio (mass ratio of cement to stone powder) or stone powder particle size, the strength of stone body of stone powder-cement grouting material increases with the increase of pressure filtration value. The stress-strain curves of the stone body with different pressure filtration values all experienced three stages: continuous elasticity, fracture expansion and strength failure. Before the peak, the number of cracks increases slowly; after reaching the peak, the micro-cracks extend rapidly and the number increases rapidly, resulting in the final tensile failure of the specimen. This study can provide a basis for the selection of grouting engineering material ratio and grouting pressure parameters.

Objectives Acute type A aortic dissection is a life-threatening cardiovascular disease commonly seen in emergency department, resulting in substantial mortality and morbidity. We aimed to investigate the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) among this critically ill population.Design The design of this study was a retrospective cohort study.Setting The study population was recruited in the Emergency Department of Fuwai hospital in China from 2018 to 2020.Participants We consecutively enrolled 829 patients with acute type A aortic dissection and measurable baseline NT-proBNP.Primary outcome The primary endpoint was 1-year all-cause death.Results Based on tertiles of NT-proBNP (pg/mL), patients were stratified into low (≤150.3, n=276), intermediate (150.3–667.6, n=277) and high (>667.6, n=276) NT-proBNP groups. Compared with patients with low NT-proBNP, the Kaplan-Meier estimates for primary 1-year mortality were higher in intermediate (32.5% vs 18.1%; HR 1.91, 95% CI 1.35 to 2.69) and high (42.0% vs 18.1%; HR 2.56, 95% CI 1.84 to 3.57) NT-proBNP groups, respectively. After multivariable regression adjusted for confounders, NT-proBNP tertiles were independent predictors for 1-year mortality (adjusted HR for intermediate group 1.52, 95% CI 1.02 to 2.27; adjusted HR for high group 2.17, 95% CI 1.41 to 3.32). Notably, the predictive performance of NT-proBNP for 1-year mortality was greater in patients receiving surgery than conservative treatment (between-cohorts difference in area under the curve 0.13, Delong’s test p=0.04).Conclusion NT-proBNP provides incremental prognostic information for mortality in patients with acute type A aortic dissection who underwent surgical repairment, which could aid in risk stratification as a pragmatic and versatile biomarker in this critically ill population while having limited prognostic value for those receiving conservative treatment.

Recent developments in targeted protein degradation have provided great opportunities to eliminating extracellular protein targets using potential therapies with unique mechanisms of action and pharmacology. Among them, Lysosome-Targeting Chimeras (LYTACs) acting through mannose 6-phosphate receptor (M6PR) have been shown to facilitate degradation of several soluble and membrane-associated proteins in lysosomes with high efficiency. Herein we have developed a novel site-specific antibody conjugation approach to generate antibody mannose 6-phosphate (M6P) conjugates. The method uses a high affinity synthetic M6P glycan, bisM6P, that is coupled to an Fc-engineered antibody NNAS. This mutant without any effector function was generated by switching the native glycosylation site from position 297 to 298 converting non-sialylated structures to highly sialylated N-glycans. The sialic acid of the glycans attached to Asn298 in the engineered antibody was selectively conjugated to bisM6P without chemoenzymatic modification, which is often used for site-specific antibody conjugation through glycans. The conjugate is mainly homogeneous by analysis using mass spectrometry, typically with one or two glycans coupled. The M6P-conjugated antibody against a protein of interest (POI) efficiently internalized targeted soluble proteins, such as human tumor necrosis factor (TNF), in both cancer cell lines and human immune cells, through the endo-lysosomal pathway as demonstrated by confocal microscopy and flow cytometry. TNF in cell culture media was significantly depleted after the cells were incubated with the M6P-conjugated antibody. TNF internalization is mediated through M6PR, and it is correlated well with cell surface expression of cation-independent M6PR (CI-MPR) in immune cells. A significant amount of CI-MPR remains on the cell surface, while internalized TNF is degraded in lysosomes. Thus, the antibody-M6P conjugate is highly efficient in inducing internalization and subsequent lysosome-mediated protein degradation. Our platform provides a unique method for producing biologics-based degraders that may be used to treat diseases through event-driven pharmacology, thereby addressing unmet medical needs.

Abstract Background Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. Case presentation This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and β-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. Conclusions OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

Cemented paste backfill is a suspension composed of solid-liquid-gas three-phase. For a long time, the focus has been mostly on the rheological behavior of solid-liquid two-phase, while the effect of gas phase on slurry with complex rheological behavior remains obscure. The gaseous phase components can significantly reduce the yield stress and viscosity of high-concentration backfilling slurry, which plays a significant role on improving pipeline transportation performance and reducing pipeline wear. In order to reveal the mechanism of bubbles to its rheological properties of slurry, the gas content of slurry was controlled by adjusting the content of air entrainment agent (TTAB), and tests such as surface tension, air content and rheological properties were carried out to find out the influence of bubbles on the rheological behavior of slurry, and capillary force (Fcay) and the bubble evolution model of dimensionless yield stress (\begin{document}$ {\tau }_{{\mathrm{ref}}}/{\tau }_{{\mathrm{y}}} $\end{document}) were introduced to analyze the bubble evolution characteristics in the slurry and reveal the mechanism of bubbles on the rheological properties of slurry. The results showed that under the low gas content ( < 12.5%), the gas phase had little effect on the rheological behavior of the suspended slurry. As the increase of gas content, the effect of bubbles on the rheological behavior of backfilling slurry was immense. Under the action of the air-entraining, the bubble surface had a repulsive force on the fine particles in the slurry, and could reduce the adsorption capacity of cement and solid waste, resulting in a decreasing trend of slurry yield stress and increasing fluidity. Based on capillary force (Fcay) and dimensionless yield stress theory (\begin{document}$ {\tau }_{{\mathrm{ref}}}/{\tau }_{{\mathrm{y}}} $\end{document}), evolutional mechanism of rheological properties of slurry in different gas content was analyzed. It could be seen that as the gas content increased (12.5%−27.7%), the surface tension and yield stress of slurry decreased, and the bubble would be deformed by extrusion. When the gas content (28.6%) was high, the bubbles in the slurry were easy to burst. In addition, bubbles, retained inside the backfilling body, leading to strength degradation, so the effect of bubbles on the mechanical properties of the backfilling body and its solution were explored and three effective measures were proposed. By revealing the effect of bubbles on the rheological properties of suspension slurry and its evolution characteristics, it provides theoretical support for the development of high bubble filling, which can achieve the goal of drag reduction and friction reduction.

A trajectory tracking control scheme is proposed in this paper to achieve unmanned underground construction of a new type of shaft boring machine. The body motion model is constructed, and the control relationship between the driving system and the body motion is deduced. MATLAB and Simulink simulate the joint of the track tracking process in the new shaft boring machine. The actual effect of the track tracking control scheme is validated by the track tracking field test of the new shaft boring machine. The results show that the new shaft boring machine can complete various complex track tracking tasks, with the maximum position error being less than 0.005 m. The running track and excavation areas of the boring machine are observed along with the track tracking field test of the new shaft boring machine, demonstrating that the track tracking control scheme makes the new shaft boring machine realize unmanned construction and verifies the co-simulation accuracy. The PID (proportional–integral–derivative control) algorithm can complete complex trajectory tracking tasks and promote the development of unmanned construction technology.

Abstract Background Natural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index. Methods A semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells. A library of rhIL-2 molecules was constructed with single site-specific, biorthogonal chemistry-compatible non-canonical amino acids installed near the interface where IL-2 engages its cognate receptor βγ (IL-2Rβγ) signaling complex. Biorthogonal site-specific pegylation and functional screening identified variants that retained engagement of the IL-2Rα chain with attenuated potency at the IL-2Rβγ complex. Results Phenotypic screening in mouse identifies SAR444336 (SAR’336; formerly known as THOR-809), rhIL-2 pegylated at H16, as a potential development candidate that specifically expands peripheral CD4+ Tregs with upregulation of markers that correlate with their suppressive function including FoxP3, ICOS and Helios, yet minimally expands CD8 + T or NK cells. In non-human primate, administration of SAR’336 also induces dose-dependent expansion of Tregs and upregulated suppressive markers without significant expansion of CD8 + T or NK cells. SAR’336 administration reduces inflammation in a delayed-type hypersensitivity mouse model, potently suppressing CD4+ and CD8 + T cell proliferation. Conclusion SAR’336 is a specific Treg activator, supporting its further development for the treatment of AI diseases.

Abstract Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a kind of pentacyclic triterpene, which widely distributes in nature. OA possesses a powerful anti-cancer effect; however, its low solubility limits its bioavailability and application. In this study, a new OA derivative, K73-03, was used to determine its effect on liver cancer cells and detailed molecular mechanisms. Here, we show that K73-03 may lead to the disorder of mitochondria in HepG2 cells, leading to excessive ROS production and apoptosis in cells. Meanwhile, K73-03 could induce cell apoptosis by inhibiting JAK2/STAT3 pathway and NF-κB/P65 pathway. Collectively, this study may provide a preliminary basis for further cancer treatment of hepatocellular carcinoma.

This paper proposes a solution based on the particle swarm optimization algorithm to address the issue of Proportional Integral Derivative parameter selection in the motion control of a two-wheel differential car. The mathematical motion model is established based on the driving principle of a two-wheel differential car. The transfer function of the DC motor is derived in detail, based on Kirchhoff’s law and the Laplace transform. The pose renewal equation and error renewal equation of the car are based on the mathematical motion model. Finally, a numerical simulation and experimental analysis were conducted using MATLAB R2022a, Simulink 9.1 (part of R2018a), VOFA 1.3.10 software, an STM32 microcontroller, an L298N driver chip, and other hardware components. The results indicate that the particle swarm optimization algorithm enables the rapid acquisition of optimal Proportional Integral Derivative parameters. The optimized parameter of the motor speed convergence time is set to 10 ms, with an overshoot of 1 r/min and an enhanced anti-interference ability. The optimized parameters effectively regulate the car’s motion, ensuring a maximum error control of approximately 0.003 m.

BackgroundPrimary cardiac tumors are uncommon, with the majority being benign myxomas. Cystic myxoma, a particularly rare type of benign cardiac tumor, demands cautious differential diagnosis from other cardiac tumors.Case summaryA 43-year-old male patient presenting with intermittent dyspnea was referred to our department for surgical evaluation. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) unveiled an intra-left atrial cyst, which was subsequently found to be blood-filled during a video-assisted microinvasive heart surgery. Pathological examination depicted a cyst wall filled with small stellate and fat spindle cells, along with a mucoid matrix, indicating a diagnosis of cystic myxoma.ConclusionsWe herein presented a rare case of an adult patient with cystic myxoma, initially misdiagnosed as an intracardiac blood cyst (CBC) prior to surgery, and ultimately verified via pathological findings.

Abstract Lung cancer, with non‐small cell lung cancer (NSCLC) being the main subtype, is the leading cause of cancer death worldwide, which is mainly due to the cancer metastasis. Glutathione peroxidase 2 (GPX2), an antioxidant enzyme, is involved in tumor progression and metastasis. Nevertheless, the role of GPX2 in NSCLC metastasis has not been clarified. In this study, we found that GPX2 expression was elevated in NSCLC tissues and high GPX2 expression was correlated with poor prognosis in patients with NSCLC. In addtion, GPX2 expression was related to the patient's clinicopathological features, including lymph node metastasis, tumor size, and TNM stage. Overexpression of GPX2 promoted epithelial–mesenchymal transition (EMT), migration, and invasion of NSCLC cells in vitro. Knockdown of GPX2 showed the opposite effects in vitro and inhibited the metastasis of NSCLC cells in nude mice. Furthermore, GPX2 reduced reactive oxygen species (ROS) accumulation and activated the PI3K/AKT/mTOR/Snail signaling axis. Therefore, our results indicate that GPX2 promotes EMT and metastasis of NSCLC cells by activating the PI3K/AKT/mTOR/Snail signaling axis via the removal of ROS. GPX2 may be an effective diagnostic and prognostic biomarker for NSCLC.

Abstract Hepatocellular carcinoma (HCC) has a desmoplastic and hypoxic tumor microenvironment (TME), resulting in poor prognosis and treatment resistance. This study aimed to construct a novel prognostic classifier to investigate the degree of hypoxia and immune profiles in HCC. Patients with HCC from public databases were classified into three HIF-1α clusters according to 16 reported HIF-1α-related genes. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α clusters. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α cluster. Besides, oncologic pathways and immune infiltration profiles were also investigated among HCCs with different HIF-1α scores. The reliable predictive abilities of the HIF-1α score system for patients’ survival were impressively suggested by the significant C-indexes and ROC analysis. All enrolled tumors were divided into high-, medium-, and low-HIF-1α score groups. Compared with the other two groups, the high HIF-1α score group exhibited highest enrichment of multiple oncogenic pathways, such as TNF-α signaling via NF-кB, IL6-JAK-STAT3 signaling, mTORC1 signaling, MYC signaling, Hedgehog signaling. Notably, higher HIF-1α scores correlated with advanced immunosuppressive TME. Besides, tumors with high HIF-1α scores represented high non-response rate to transcatheter arterial chemoembolization (TACE) and immune checkpoint blockade (ICB). In conclusion, we developed a novel HIF-1α score system to distinguish HCC with different degree of hypoxia and immune infiltration profiles.

Introduction: Lenvatinib has recently become available as the first-line therapy for advanced hepatocellular carcinoma (HCC), but its molecular mechanism in HCC remains largely unknown. Objectives: The current study aims to identify the molecular mechanisms of lenvatinib in HCC. Methods: Gene expression microarrays, flow cytometry, western blot, qRT-PCR, immunohistochemistry and immunofluorescence were used to study the response of HCC cells to lenvatinib. Xenograft tumor of Huh7 cells was also established to detect the effect of lenvatinib in vivo. Results: Herein, we found that lenvatinib could induce apoptosis via increasing reactive oxygen species (ROS) levels in HCC cells. Then, microarray analysis and qRT-PCR results confirmed that GPX2 was a vital target for lenvatinib against HCC. Loss and gain function of experiment showed that regulating GPX2 levels markedly affected the lenvatinib-induced ROS levels and apoptosis in HCC cells. In addition, analyses of The Cancer Genome Atlas database and the qRT-PCR results in our cohort both showed that GPX2 markedly overexpressed in tumor tissues and correlated with poor overall survival in HCC. Mechanistically, our findings further demonstrated that GPX2 was a downstream gene regulated by β-catenin, while lenvatinib could prevent nuclear translocation of β-catenin and further inhibit GPX2 expression in HCC cells. More importantly, the correlation of GPX2 expression with lenvatinib response was further analyzed in 22 HCC patients who received lenvatinib therapy, and the results showed that the objective response rate (ORR) in patients with low GPX2 expression was 44.4% (4/9), while the ORR in patients with high GPX2 levels was only 7.7% (1/13). Conclusion: Our findings indicated that GPX2 plays an important role in lenvatinib-induced HCC cell apoptosis, which might serve as a biomarker for instruction of lenvatinib therapy in HCC patients.

Psoriasis (PSO) is a common skin disease affecting approximately 1%–3% of the population, and the incidence rate is increasing yearly. PSO is associated with a dramatically increased risk of cardiovascular disease, the most common of which is atherosclerosis (AS). In the past, inflammation was considered to be the triggering factor of the two comorbidities, but in recent years, studies have found that lipid metabolism disorders increase the probability of atherosclerosis in patients with psoriasis. In this review, we discuss epidemiological studies, clinical treatment methods, risk factors, and lipid metabolism of psoriasis and atherosclerosis comorbidities.

Existing malicious device detection preprocessing ignores the topological similarity of node neighborhood structures in the network. According to the structural equivalence hypothesis, devices with approximately local symmetry in the device-account graph have similar topological embeddings after preprocessing. In order to improve the performance of malicious device detection, we propose the Graph Structural-topic Similar Subgraph Merging, abbreviated GraphSTSGM, to extract topological similarity between nodes. GraphSTSGM extracts approximate local symmetry features by adding local neighborhood structural patterns merge to Graph Structural-topic Neural Network (GraphSTONE). In this algorithm, we build a device-account relationship graph $G$ with devices and accounts as nodes, build an edge between associated devices and accounts, and then calculate the approximate local symmetry of each device via the merge-similar-substructures-based anonymous walk in $G$ . Then, the approximate local symmetry features and device features of the nodes are aggregated through Graph Convolutional Network (GCN). We use the above algorithm as a preprocessing method to enhance the ability of malicious device detection by accurately characterizing the approximate local symmetry features of nodes. Finally, the obtained aggregated features are used as the input of the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) model for malicious device detection. Experiments based on Alibaba Cloud Security data show that the proposal outperforms the state-of-the-art algorithms by 3.6% with respect to the AUC of malicious device detection. In addition, experiments based on the graph dataset Cora show that the proposal outperforms the state-of-the-art algorithms by 2.6% with respect to the AUC of node classification.

Psoriasis is an immune-mediated, persistent inflammatory disease with a genetic predisposition, and the involvement of multiple organs in psoriasis remains indicative of systemic disease. Atherosclerosis (AS) is a common complication of patients with severe or prolonged psoriasis. The specific pathogenesis of psoriasis is still unclear. Current studies suggest that psoriasis is a polygenic genetic disease with the interaction of multiple factors such as heredity and environment. Keratinocytes are proliferated through immune-mediated inflammatory pathway, which leads to cell activation, infiltration of dermis cells and release of inflammatory factors. Activation of inflammatory cells and pro-inflammatory factors play an important role in the progression of psoriasis and atherosclerosis. Studies have found that there is a close relationship between psoriasis and atherosclerosis, and systemic inflammation may be the common feature of psoriasis and AS. This paper attempts to explore the possibility of the relationship between psoriasis and atherosclerotic comorbidities from the aspects of potential epidemiology and immune mechanism, in order to provide some reference for the subsequent scientific research.

Exploring the spatial heterogeneity of urban multi-dimensional networks and influencing factors are of great significance for the integrated development of metropolitan circle. This study took Hangzhou metropolitan circle as an example, using multi-source geospatial big data to obtain urban population, transportation, goods, capital, and information flow information among sub-cities. Then, spatial visualization analysis, social network analysis, and geographical detector were applied to analyze the differences in spatial structure of multiple urban networks and influencing factors in Hangzhou metropolitan circle, respectively. The results showed that (1) the network connections of population, traffic, goods, and capital flows transcended geographical proximity except that of information flow, and population and traffic flow networks were found to be more flattened in Hangzhou metropolitan circle than in other urban networks; (2) the comprehensive urban network of Hangzhou metropolitan circle was imbalanced across sub-cities, presenting hierarchical and unipolar characteristics; and (3) the influence of traffic distance on the network spatial structure of Hangzhou metropolitan was stronger than the geographical distance, and the interactions between traffic distance and socioeconomic factors would further enhance the regional differentiation of the network spatial structure. This study could provide scientific reference for constructing a coordinated and integrated development pattern in a metropolitan circle.

Abstract Nowadays, online gambling has a great negative impact on the society. In order to study the effect of people’s psychological factors, anti-gambling policy, and social network topology on online gambling dynamics, a new SHGD (susceptible–hesitator–gambler–disclaimer) online gambling spreading model is proposed on scale-free networks. The spreading dynamics of online gambling is studied. The basic reproductive number R 0 $R_{0}$ is got and analyzed. The basic reproductive number R 0 $R_{0}$ is related to anti-gambling policy and the network topology. Then, gambling-free equilibrium E 0 $E_{0}$ and gambling-prevailing equilibrium E + $E_{ +} $ are obtained. The global stability of E 0 $E_{0}$ is analyzed. The global attractivity of E + $E_{ +} $ and the persistence of online gambling phenomenon are studied. Finally, the theoretical results are verified by some simulations.

This paper investigates the multi-group formation tracking (MGFT) control problem for second-order nonlinear multi-agent systems (MASs) with unknown dynamics. The objective of the MGFT control is to divide all agents into several subgroups to form different desired sub-formations while following their respective leaders. Firstly, the neural network (NN) approximator is constructed to solve the problem of unknown dynamics. Then, the distributed adaptive control protocol is designed based on the NN approximator. According to the Lyapunov stability theory and algebraic graph theory, sufficient criteria are obtained to realize the MGFT control. The semi-globally uniformly ultimately boundedness of formation errors is proved in detail. Finally, a numerical simulation example is given to confirm the validity of our theoretical results.

Nowadays, pyramid schemes have caused extremely negative effects on people’s lives and seriously damaged the social economy. With the rapid development of network and communication technology, people’s direct or indirect social interaction is more frequent, which makes the phenomenon of pyramid schemes more serious. Therefore, it is necessary to study transmission mechanisms and transmission rules of pyramid schemes. In order to study the influence of government management and social interaction topology on the spreading of pyramid schemes, a novel SHIPR (susceptible-hesitator-involved-punished-resister) pyramid scheme spreading model is proposed on scale-free networks. The spreading dynamics of pyramid schemes are analyzed in detail by mean-field theory. Then, the basic reproduction number $R_{0}$ and equilibria are got. Theoretical analysis shows that the basic reproduction number $R_{0}$ has a great correlation with government crackdown intensity for involved individuals, the coverage rate of government anti-pyramid scheme publicity for susceptible individuals and hesitator, and social interaction topology. Furthermore, the local asymptotic stability of fraud-elimination equilibrium is analyzed based on the Routh-Hurwitz criterion, the global asymptotic stability of the fraud-elimination equilibrium is discussed by the Lyapunov function, the global attractivity of fraud-prevailing equilibrium is proved in detail by comparison principle. Finally, numerical simulations verify the theoretical analysis results.

The frequent fast closing action of the governing valve in a 1000 MW ultra-supercritical unit occurred during the cold running process, which caused the valve body to sway greatly and could not continue to speed up. The problem had not been solved by governing the impulse parameters, checking the solenoid valve oil circuit, retesting the control oil quality and other measures. Therefore, starting from the speed control logic, the conditions of fast closing action and the change of proportional integral (PI) regulating quantity were analyzed. It was concluded that the main factor affecting the total flow instruction (the final valve position opening) in the process of fast closing is the feedforward change of speed regulation, not the change of PI output. Based on this analysis, the boundary value of feedforward quantity of speed control was calculated without changing the impulse parameters and the flow characteristic curve of the valve. Through many attempts to establish the optimal value of feedforward quantity, the fast closing action of the governing valve can be avoided due to the unreasonable parameter setting in the control logic. After optimization, the actual speed rises steadily with the set value, the valve opening is opened linearly, and there is no more frequent swing, which meets the requirements of speed up control.

Abstract Background Human polypyrimidine tract binding protein 3 (PTBP3), which belongs to the PTB family, demonstrate a significant tumorigenic capability in a variety of malignancies. However, the correlation between PTBP3 expression and pathogenesis of non-small cell lung cancer (NSCLC) remains little known. The design of the study attempts to examine the role of PTBP3 in the pathogenesis and prognosis of NSCLC. Methods Our study conducted an investigation on the PTBP3 expression in human NSCLC tissues and a comprehensive analysis of the associations between three factors, involving the PTBP3 expression, clinicopathological features, and patient’s survival. Additionally, we also explored the role of PTBP3 expression in the proliferation and invasion of cancer cells. Results The mining of The Cancer Genome Atlas (TCGA) database, western blotting and immunohistochemistry analyses showed significantly up-regulation of PTBP3 in NSCLC tissues than in normal tissues. Although overexpress or knockdown PTBP3 expression had no significant effect on proliferation of selected cell line, it could promotes migration of NSCLC cells via regulating E-cadherin in epithelial–mesenchymal transition (EMT) signaling pathway. Moreover, in the univariate analysis, the PTBP3-high is markedly related to poor overall survival results where hazard ratio (HR): 1.55; 95% confidence interval (95% CI): 1.87–2.01; p = 0.0001. Also, according to the multivariate analysis, an independent prognostic factor among NSCLC patients is the PTBP3 with an HR of 1.42 (CI: 1.09–1.9; p = 0.011). To explore potential signaling pathways, we used the TCGA dataset and performed Gene Set Enrichment Analysis (GSEA). Moreover, its expression in NSCLC was related to Tumor differentiation, lymph node metastasis, distant metastasis status and poor prognosis. Beside, by changing the expression of PTBP3 in selected cell lines, we found that overexpress or knockdown PTBP3 expression had no significant effect on proliferation, however it regulated migration possibly by EMT signaling. Conclusions Collectively, our findings suggested that PTBP3 contributed to the progression of NSCLC and might serve as a potential target for anti-cancer therapy.

BackgroundSmith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC.MethodsThe clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm.ResultsLSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells.ConclusionThis study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.

BackgroundTransient Receptor Potential (TRP) channel is a kind of channel protein widely distributed in peripheral and central nervous system. They can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role and function of the TRP family genes in tumours remain unclear.MethodsGene alterations (mutation, copy number, methylation), expression, clinical features, and prognostic value of the TRP family genes were evaluated in pan-cancer using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. TRP score was calculated by the ssGSEA function of the R package “GSVA”. The association of TRP score and the tumour microenvironment (TME), especially the tumour immune microenvironment (TIME), along with immunotherapy response were explored in-depth.ResultsTRP family genes were involved in tumour progression and highly associated with poor prognosis in a variety of cancers. TRP score was positively associated with malignant pathways in pan-cancer, such as IL6–JAK–STAT3 signalling, interferon-gamma response, and inflammatory response. All pathways were closely associated with TIME. Elevated TRP score also correlated with multiple immune-related characteristics of the TIME in pan-cancer. Moreover, the TRP score was a predictive biomarker for immune checkpoint inhibitor (ICI) treatments in patients with tumours.ConclusionsTRP family genes play a key role in pan-cancer and are closely associated with TME. Patients with high TRP scores have excellent immune-activated TIME and immunotherapy sensitivity. Therefore, the TRP score could be a potential biomarker for patients with tumours treated with ICI.

ObjectivesTo investigate the role of hepatocyte growth factor (HGF)/c-Met signaling in oral malignant transformation.MethodsWe used immunohistochemistry to investigate HGF and c-Met expression in 53 oral squamous cell carcinoma (OSCC) specimens and 21 adjacent nontumor specimens and evaluated the associations between HGF and c-Met expression and clinicopathological parameters. Additionally, HGF-overexpression transgenic (HGF-Tg) and wild-type (Wt) mice were treated with 4-nitroquinoline-1-oxide (4NQO) to induce oral carcinogenesis for 16 weeks. At 16, 20, and 24 weeks, tongue lesions were collected for clinical observation; estimation of HGF, c-Met, and PCNA expression; apoptosis (TUNEL) assays; and RNA sequencing (RNA-seq).ResultsHGF and c-Met were positively expressed in 92.5% and 64% of OSCC samples, respectively. High HGF expression was significantly associated with smaller tumor size (p = 0.006) and inferior TNM stage (p = 0.032). No correlation between HGF and c-Met levels and other clinical parameters or prognosis was noted. In addition, HGF and c-Met expression was elevated in 4NQO-induced lesions of Wt mice. Compared with Wt mice, HGF-Tg mice have lower tumor incidence, number, volume, and lesion grade. In addition, the percentage of PCNA-positive cells in Wt mice was significantly higher than that in HGF-Tg mice at different time points. At 16 weeks, HGF-Tg mice exhibited less apoptotic cells compared with Wt mice (p < 0.000), and these levels gradually increased until the levels were greater than that of Wt mice at 24 weeks (p < 0.000). RNA-seq data revealed that 140 genes were upregulated and 137 genes were downregulated in HGF-Tg mice. KEGG enrichment analysis showed that upregulated differentially expressed genes (DEGs) are highly correlated with oxidative and metabolic signaling and that downregulated DEGs are related to MAPK and PI3K-AKT signaling.ConclusionsHGF and c-Met expression is upregulated in OSCC tissues and is associated with the occurrence and development of OSCC. HGF overexpression in normal oral epithelial tissue can inhibit 4NQO-induced tumorigenesis potentially through inhibiting proliferation and accelerating apoptosis via MAPK and PI3K-AKT signaling.

BackgroundFerroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis.MethodsFerroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs.ResultsA carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients.ConclusionsThe ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.

Abstract Considering the influence of the preferential degree, the hesitation psychology of customers and the heterogeneity of underlying networks in preferential information spreading, we propose a novel model called AHFB (adherent–hesitator–forwarder–beneficiary) model to illustrate the dynamic behaviors of preferential information spreading on scale-free networks. The mean-field theory is adopted to describe the formulas of AHFB model. To begin with, we analyze the spreading dynamics of preferential information. Then we determine the basic reproductive number and equilibria by the next generation matrix method. The relationship among the basic reproductive number, preferential degree, and hesitation parameter is also analyzed. In addition, the globally asymptotical stability of information-eliminate equilibrium and the permanence of the preferential information spreading are proved in detail. Furthermore, a preferential information competition model is proposed, and the corresponding dynamic behaviors are studied. We have found that under certain conditions, a greater competitive advantage can be achieved by improving a certain range of preferential strengths. Numerical simulations are also presented to verify and extend theoretical results.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a poor prognosis. We previously found that protein disulfide isomerase family 6 (PDIA6) is upregulated in lung squamous cell carcinoma (LSCC). This study aimed to elucidate the clinical relevance, biological functions, and molecular mechanisms of PDIA6 in NSCLC. Methods: The expression of PDIA6 in NSCLC was assessed using the TCGA database, western blotting, and immunohistochemistry. Correlations of PDIA6 expression with clinicopathological and survival features were evaluated. The functions of PDIA6 in regulating NSCLC cell growth, apoptosis, and autophagy were investigated using gain-and loss-of-function strategies in vitro or in vivo. The underlying molecular mechanisms of PDIA6 function were examined by human phospho-kinase array and co-immunoprecipitation. Findings: PDIA6 expression was upregulated in NSCLC compared with adjacent normal tissues, and the higher PDIA6 expression was correlated with poor prognosis. PDIA6 knockdown decreased NSCLC cell proliferation and increased cisplatin-induced intrinsic apoptosis, while PDIA6 overexpression had the opposite effects. In addition, PDIA6 regulated cisplatin-induced autophagy, and this contributed to PDIA6-mediated apoptosis in NSCLC cells. Mechanistically, PDIA6 reduced the phosphorylation levels of JNK and c-Jun. Moreover, PDIA6 interacted with MAP4K1 and inhibited its phosphorylation, ultimately inhibiting the JNK/c-Jun signaling pathway. Interpretation: PDIA6 is overexpressed in NSCLC and inhibits cisplatin-induced NSCLC cell apoptosis and autophagy via the MAP4K1/JNK/c-Jun signaling pathway, suggesting that PDIA6 may serve as a biomarker and therapeutic target for NSCLC patients. Fund: National Natural Science Foundation of China and Institutions of higher learning of innovation team from Liaoning province. Keywords: PDIA6, Apoptosis, Autophagy, MAP4K1, NSCLC

Clay cement grout is frequently employed in geotechnical reinforcement projects. However, laboratory test revealed that clay cement slurry does not consolidate in a closed environment for an extended period of time, with cracks forming during the consolidation process under natural conditions, indicating that the geotechnical reinforcement poses dangers. Stone powder is a powdery solid waste similar to clay materials. Stone powder particle surfaces provide an attachment point for cement reaction, which can speed up cement hydration, with the ability to substitute clay cement slurry. According to our findings, the bleeding rate of clay cement slurry is 14.80% at 290 mm fluidity, and that of the same mass ratio (1:3) as stone powder cement slurry is 11.09%. The bleeding rate is minimal, which promotes the creation of an integral structure after setting between the slurry and lose rock and soil. Mechanical test results show that the strength of the stone powder cement slurry hardened body is 1458 kPa, whereas the strength of the clay cement slurry hardened body is 436 kPa. Microstructural analysis shows that the stone powder cement hardened body has more hydration products and is porous than the clay cement hardened body. The hardened body of stone powder cement slurry has high strength and resistance to external loads, which can increase the bearing capacity and improve the geotechnical reinforcement effect.

The metropolitan circle is the basic unit of regional competition. Enhancing the connection between cities in the metropolitan circle and optimizing the spatial layout of the metropolitan circle is one of the goals of regional high-quality development in the new era. Therefore, it is of great significance to analyze the spatial network structure of the metropolitan circle. Taking Hangzhou metropolitan circle as an example, this study used web crawler technology to obtain data in multiple Internet big data platforms; used centrality analysis, flow data model, and social network analysis to construct the network connection matrix of human flow, goods flow, capital flow, information flow, and traffic flow; and explored the spatial network structure of the metropolitan circle. The results showed that the node intensity of the metropolitan circle presented a distribution pattern of strong in the east and weak in the west. The network connections of each county under the action of different element flows were different, and the skeleton of the integrated flow network connections showed a starfish-shaped feature. Hangzhou, Jiaxing, Huzhou, and Shaoxing cities had strong group effects in goods flow and traffic flow, while Quzhou and Huangshan cities had relatively independent cohesive subgroups in human flow and information flow. This study can provide useful references for regional development and spatial planning implementation.

Identifying urban production–living–ecological spaces and their interactive relationships is conducive to better understanding and optimizing urban space development. This paper took the main urban area of Hangzhou city as an example, and a two-level scoring evaluation model was constructed to accurately identify urban production–living–ecological spaces using point of interest (POI) data. Then, kernel density analysis, a spatial transfer matrix, and a bivariate spatial autocorrelation model were used to reveal the spatial patterns of urban production–living–ecological spaces and their interactive relationships during 2010 and 2019. The results showed that the proposed two-level scoring evaluation model combining both the physical area and density of POIs was effective in accurately identifying urban production–living–ecological spaces using POI data, with an identification accuracy of 88.9%. Urban production space was concentrated on the south bank of the Qiantang River and around the north of Hangzhou. Urban living space had the highest proportion, mainly distributed within the ring highway of Hangzhou in a contiguous distribution pattern, and urban ecological space was concentrated around West Lake and Xiang Lake. During 2010 and 2019, the expansion of urban production–living–ecological spaces had obvious spatial differences. Additionally, the mutual transformation between production and living spaces was more frequent during the study period and was mainly distributed within the ring highway of Hangzhou. There were significant positive spatial correlations between production and living and between living and ecological spaces, while a significant negative spatial correlation occurred between production and ecological spaces. The spatial correlations of urban production–living–ecological spaces revealed obvious spatial heterogeneity. This study proposed a two-level scoring evaluation model to accurately identify the spatial patterns of urban production–living–ecological spaces and their interactive relationships using POI data, which can provide detailed information and scientific references for urban spatial planning and management in rapidly urbanizing cities.

Pasteurized Akkermansia muciniphila (p-AKK) is related to lipid metabolism and helps control obesity. The main goal of this study was to investigate the role and mechanism of p-AKK in lipid metabolism using Caenorhabditis elegans. The results showed that p-AKK increased the healthy lifespan of nematodes and helped maintain exercise ability in aging, suggesting a potential increase in energy expenditure. The overall fat deposition and triglyceride level were significantly decreased and the p-AKK anti-oxidative stress helped to regulate fatty acid composition. Additionally, the transcriptome results showed that p-AKK increased the expression of lipo-hydrolase and fatty acid β-oxidation-related genes, including lipl-4, nhr-49, acs-2 and acdh-8, while it decreased the expression of fat synthesis-related genes, including fat-7, elo-2 and men-1. These results partially explain the mechanisms underlying the fact that p-AKK decreases fat accumulation of C. elegans via nhr-49/acs-2-mediated signaling involved in fatty acid β-oxidation and synthesis.

The grouting method is often used to strengthen the bearing capacity of building foundations. In the process of grouting, the stress structure of slurry and rock and the soil mass under the condition of high permeability and high stress (“double height”) is complex, and the strength mechanism of slurry stone under different double-height conditions is not clear. Therefore, stone samples of grout under the curing pressures of 2 MPa, 4 MPa, 6 MPa, 8 MPa and 10 MPa were prepared for the uniaxial compression test to analyze the influence of curing pressure on compressive strength. The microstructure of the slurry stone was observed by scanning electron microscope, and the development law of microcracks was further studied using the particle flow program. The research shows that the strength of the slurry stone body increases with the increase of curing pressure. When the curing pressure increases from 2 MPa to 10 MPa, the compressive strength of the stone powder-cement slurry stone body increases from 8.3 MPa to 22.7 MPa, an increase of nearly 2.7 times, and the compressive strength of the clay-cement slurry stone body increases from 5.7 MPa to 16.8 MPa, an increase of 2.9 times. According to the axial compressive stress-strain curve of the specimen, the failure process goes through three continuous stages: continuous elasticity, crack propagation, and strength failure. When the stress peak is reached, the number of cracks increases slowly; when the stress peak is reached, the cracks expand rapidly, the number increases exponentially, and a penetrating main crack is finally formed, which destroys the specimen. This study provides a reliable basis for the selection of grouting parameters and grouting materials in stratum-grouting engineering.

Chronic kidney disease (CKD) is the end result of a plethora of renal insults, including repeated episodes of acute or toxic kidney injury, glomerular, or diabetic kidney disease. It affects a large number of the population worldwide, resulting in significant personal morbidity and mortality and economic cost to the community. Hence it is appropriate to focus on treatment strategies that interrupt the development of kidney fibrosis, the end result of all forms of CKD, in addition to upstream factors that may be specific to certain diseases. However, the current clinical approach to prevent or manage renal fibrosis remains unsatisfactory. The rising importance of receptor-interacting serine/threonine-protein kinase (RIPK) 3 in the inflammatory response and TGF-β1 signaling is increasingly recognized. We discuss here the biological functions of RIPK3 and its role in the development of renal fibrosis.

Capsule network (CapsNet) can recognize the objects by encoding the part-whole relationships in a way similar to our human perceptual system and has already shown its great potential in image classification tasks. However, it is limited to the real domain while the complex numbers having much richer representational capacity and facilitating the noise-robust memory retrieval mechanisms. Therefore, we propose two architectures: Complex-valued Dense CapsNet (Cv-CapsNet) and Complex-valued Diverse CapsNet (Cv-CapsNet++), each of them consists of three stages. In the first stage, multi-scale complex-valued features are obtained by the restricted dense complex-valued subnetwork. Particularly, Cv-CapsNet++ utilizes a three-level Cv-CapsNet hierarchical model to extract the multi-scale high-level complex-valued features in order to adapt to the complicated datasets. In the second stage, these complex-valued features are encoded into the complex-valued primary capsules, Particularly, Cv-CapsNet++ encodes the complex-valued features from different hierarchies into the multi-dimensional complex-valued primary capsules. In the third stage, we generalize the dynamic routing algorithm to the complex-valued domain and employ it to fuse the real- and imaginary-valued information of complex-valued primary capsules. The experimental results show that the proposed architectures lead to fewer trainable parameters, better performance, and fewer iterations during training than Real-valued CapsNets (Rv-CapsNets) with similar structure and original CapsNet on FashionMNIST and CIFAR10 datasets.

A larger mining height leads to easy caving of the coal wall in the working face. The flexible reinforcement method during the mining period of the working face affects the normal mining of the working face, and the high strength of the traditional bolt/cable material affects the operation of the shearer drum, so it is necessary to seek a reinforcement material which does not affect the production and the drum coal cutting. This paper proposed a technical scheme of coal wall reinforcement by pre-grouting with a cuttable aluminum–plastic composite pipe which is easy to cut during mining in the working face, tested the mechanical properties of the “grouting + flexible pipe” specimen, and obtained the optimal support spacing by numerical simulation and carrying out an industrial test. The results show that the tensile strength of aluminum–plastic composite pipe is much higher than that of coal spalling and the elongation is much higher than that of the anchor rod. When double-row composite grouting holes are arranged 1.5 and 3.0 m away from the roof, the supporting effect is better. Underground grouting shows that pre-grouting before mining according to the advancing speed of the working face 10–14 days in advance can effectively fill the coal cracks and significantly improve the integrity of the coal wall.

Abstract Background Tumor suppressor epigenetic silencing plays an important role in non-small cell lung cancer (NSCLC) development and progression. Previously, the expression of speckle-type POZ protein (SPOP) has been found to be significantly inhibited in NSCLC. Our research aimed to investigate the molecular mechanisms, clinical significance and epigenetic alteration of SPOP in NSCLC. Materials and methods Bisulfite sequencing PCR and methylation-specific PCR were performed to test gene methylation. Chromatin immunoprecipitation (ChIP) was performed to detect transcription factor C/EBPα combinations and the promoter of the SPOP gene. Furthermore, we evaluated the effects of C/EBPα siRNA on SPOP expression, tumor cell migration and proliferation via MTT and Transwell assays in vitro and tumor growth in vivo. The relationship between the methylation status of the SPOP gene and clinicopathologic characteristics was investigated. Results Hypermethylation was found in the CpG island of the SPOP gene promoter in NSCLC tissues, and this methylation was found to be correlated with SPOP expression. SPOP promoter methylation was associated with the pathology grade. The transcriptional activities were significantly inhibited by the hypermethylation of specific CpG sites within the SPOP gene promoter, while 5-aza-2′-deoxycytidine significantly increased SPOP gene expression. C/EBPα also played a key role in SPOP regulation. Five C/EBPα binding sites in the CpG island of the SPOP gene promoter were identified by ChIP. Inhibition of C/EBPα significantly reduced SPOP expression. SPOP mediated the C/EBPα-regulated suppression of invasion, migration and proliferation in vitro and tumor growth in vivo. Conclusions SPOP function and expression in NSCLS were regulated by DNA methylation and C/EBPα transcriptional regulation combination effects, indicating that the SPOP promoter methylation status could be utilized as an epigenetic biomarker and that the C/EBPα-SPOP signaling pathway could be a potential therapeutic target in NSCLC.

The macroscopic aspects of adding basalt fiber (BF) to concrete has been the subject of studies that document great increases in compression strength. Research into the microscopic aspects of the reinforcement mechanism is still in an exploratory stage, and the quantitative analysis and visual observation of fibers in the concrete matrix are difficult. In this paper, the reinforcement effect of fiber on concrete is studied by means of computed tomography (CT) scanning technology and digital image processing (DIP) technology, combined with the macro-mechanical properties obtained from the unconfined compression strength test, and quantitative analysis from the micro point of view. At the same time, the fiber visualization is realized with the help of Avizo. The results show that with the increase in fiber dosage, the peak stress of concrete first increases and then decreases. When the fiber dosage is 3 kg/m3, the peak stress is 44.4 MPa, which is 41.85% higher than that of ordinary concrete. Additionally, the proportion of macropores is the least, which is the best fiber dosage. It is found that when the fiber dosage is 3 kg/m3, the angular distribution of φ is relatively uniform, and the uniform distribution of fibers forms a dense network structure, which significantly increases the peak stress of concrete. However, when the fiber dosage is too high, it will lead to the accumulation of fibers and produce macropores, and these excess fibers mainly appear in the horizontal direction and do not contribute to the compression strength.

Huaneng Rudong 300 MW offshore wind farm project is located in eastern China. The wake effect is one of the major concerns for wind farm operators, as all 70 units are plotted in ranks, and the sea surface roughness is low. This paper investigated the wake intensity by combining a field test and a numerical simulation. To carry out further yaw optimization, a Gaussian wake model was adopted. Firstly, a 3D Light Detection and Ranging device (LiDAR) was used to capture the features in both horizontal and vertical directions of the wake. It indicated that Gaussian wake model can precisely predict the characteristics under time average and steady state in the wind farm. The predicted annual energy production (AEP) of the whole wind farm by the Gaussian model is compared with the calculation result of the actuator line (AL)-based LES method, and the difference between the two methods is mostly under 10%.

Medical research has shown that overeating betel nut can be addictive and can damage health. More serious cases may cause mouth cancer and other diseases. Even worse, people’s behavior habit of chewing betel nut may influence each other through social interaction with direct or indirect ways, such as face-to-face communication, Facebook, Twitter, microblog, and WeChat, which leads to the spreading phenomenon of betel nut addiction. In order to investigate the dynamic spreading characteristics of betel nut addiction, a PMSR (Potential-Mild-Severe-Recovered) betel nut addiction spreading model is presented on scale-free networks. The basic reproductive number R0 and equilibria are derived. Theoretical results indicate that the basic reproductive number R0 is significantly dependent on the topology of the underlying networks, and some influence parameters. The existence of equilibria is determined by the basic reproductive number R0. Furthermore, we prove that if R01, the betel nut addiction spreading is permanent, and the addiction-prevailing equilibrium is globally attractive. Finally, numerical simulations confirm the theoretical analysis results.

Background: Although immunosenescence-induced difference on overall immune function and immune cell subsets between younger and older populations has been well characterized, the potential effect of patients’ age on the efficacy of immune checkpoint inhibitors (ICIs) remains little known. We performed a meta-analysis to investigate whether age differences play a role in cancer immunotherapy efficacy based on a large amount of clinical data. Methods: We conducted a systematic search of PubMed, Embase and MEDLINE for relevant randomized controlled trials. The primary outcome was overall survival (OS) and progression-free survival (PFS) was secondary outcome. The interaction test was used to assess the heterogeneity of HR between younger and older groups. Results: In total, 19 clinical randomized trials involving 11157 patients were included. The pooled HR for OS was 0.73 (95% CI 0.69–0.78) and 0.63 (95% CI 0.52–0.73) for PFS in younger patients receiving ICIs treatments, when compared with younger patients treated with controls. For older patients treated with ICIs, the pooled HR for OS compared with controls was 0.64 (95% CI 0.59–0.69) and 0.66 (95% CI 0.58–0.74) for PFS. The difference on OS efficacy between younger and older patients treated with ICIs was significant (Pheterogeneity = 0.025). Conclusions: Immune checkpoint inhibitors significantly improved OS and PFS in both younger and older patients compared with controls, but the magnitude of benefit was clinically age-dependent. Patients ≥65 y can benefit more from immunotherapy than younger patients. Future research should take age difference into consideration in trials and focus on tolerance and toxicity of ICIs in older patients.

The wind characteristics of the mountainous environment in Western China are extremely complex. Many advances have occurred in the study of wind characteristics in plains or hilly areas. However, some limitations remain in the study of mountain passes and riverbanks. We selected a mountain pass and river beach in a certain area as the research objects, then set up observation instruments at different locations to establish temporary observation stations to collect more than one year of measured data. By processing the measurement data during the observation period, the mean wind characteristics and fluctuating wind characteristics of the area were obtained. Through comparison with the standard, we found strong nonstationary characteristics of the wind, such as large deviations between the wind field characteristics values in the standard and measured values, proving the need for wind field observations of mountain passes and riverbanks.

Adding basalt fiber into concrete can significantly improve its mechanical properties. In order to explore the influence of basalt fiber content on the uniaxial compressive strength and splitting tensile strength of concrete and the mechanism of fiber action, this paper conducts compressive and splitting tensile tests on three kinds of basalt fiber concrete specimens with different fiber content and obtains the relationship between the macro mechanical properties and the fiber content. At the same time, with the help of CT scanning equipment and digital image processing technology, the microstructure of basalt fiber concrete with three groups of fiber content is reconstructed, and the pore, crack, and fiber distribution are quantitatively described using the calculation and processing function of the Avizo reconstruction software. The results show that when the optimal fiber content is 3 kg/m3, the improvement rates of uniaxial compressive strength and splitting tensile strength are 31.9% and 23.7%, respectively. The network structure formed by fiber in concrete has the best compactness and the least number of pores, with an average sphericity of 0.89 and an average pore volume of 20.26 μm3. Through analysis, it was found that the initial defects of basalt fiber concrete exist in the form of pores, and the addition of basalt fiber will destroy the large pore size of concrete, change the pore size distribution, and increase the average sphericity; The distribution of the fiber in the concrete is a three-dimensional network, and the distribution of the fiber in the initial defect distribution area is parallel to the direction of pore arrangement.

This study focuses on toughness enhancement of basalt fibre-reinforced shotcrete (BFRS). Four-point bending experiments of underground shooting and curing beams combined with a roadway-supporting deformation monitoring test were conducted. The flexural performance was analysed based on the toughness standards, namely, DBV-1998, JSCE SF-4, and nuclear magnetic resonance (NMR) pore testing. The results demonstrate that, given a basalt fibre (BF) dosage of 0–7.5 kg/m3, 18 mm BF can significantly increase the residual stress under the same deformation, rather than the peak values of the flexural strength. Meanwhile, the trend in the flexural toughness increases to a peak at a dosage of 3–4.5 kg/m3, followed by a declining curve. The pores from an NMR test can be divided into three types based on size: (1) closed pores, R 5 μm. The connected pores are detrimental, playing a crucial role in the shotcrete performance. Furthermore, the deformations of the roadway walls are significantly restrained by the BFRS, and the 80-day convergences are approximately 2 mm, which is only 25% of the control. Finally, the comprehensive results indicate that a dosage range of 3–4.5 kg/m3 can demonstrate reasonable beneficial effects for the BFRS performance.

2,4,6-trinitrotoluene (TNT) is a commonly used explosive. It is not only a threat to public safety but also causes environmental pollution, affecting human health. However, at this stage of TNT detection, technology cannot meet the demands of the current situation. To acquire a new method devoted to the study of fast and quantitative detection of TNT. It combines the molecular imprinting technique (MIT) with surface plasmon resonance (SPR) technology for high sensitivity. In this study, a molecularly imprinted polymer (MIP) film for the detection of TNT was synthesized by heat in acetonitrile at 60°C, using the TNT imprinting molecule and azobisisobutyronitrile (AIBN) as initiators. In the present work, there are many factors that can influence the elution efficiency, such as raw material ratios,fore-reaction time, reaction time, etc. The polymers have the highest elution efficiency when raw material mole ratios [n(TNT):n methacrylic acid (MAA):n ethylene glycol dimethylacrylate (EGDMA)] were 1:4:8; the MIP sensor could detect a TNT concentration as low as 1×10-10 M. Compared to the blank polymer with the same chemical composition, the imprinted polymer had higher binding efficiency and higher selectivity.

Basal cell adenocarcinomas (BCACs) of salivary glands are rare malignant neoplasms that mostly affect the major salivary glands. They are generally considered low-grade carcinomas that are locally destructive and tend to recur, but only occasionally metastasize. Currently there are only a few reported cases of distant metastases from BCAC, and metastasis to the liver is not previously described. We report the first case of BCAC with histologically confirmed liver metastases. A 40-year-old man presented with a 2-month history of a painless swelling in the left buccal region. The lesion was completely resected, and the patient underwent postoperative radiotherapy. Permanent histology and immunohistochemical studies revealed a BCAC of the buccal minor salivary gland. After 14 months, two hepatic metastatic nodules were detected. The patient underwent a partial hepatectomy with adjuvant chemotherapy. No evidence of progressive disease or further recurrence was observed for 20 months after the hepatic metastasectomy. BCACs grow indolently and long-term survival can be expected. Surgery should be considered in selected patients as a therapeutic option in metastatic disease.

Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.