bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsteady-State Conjugate Heat Transfer Model of Freeze-Sealing Pipe Roof Method and Sensitivity Analysis of Influencing Factors of Freezing Effect
Authors: Deng Shengjun , Lin Huanyu , He Yang , Zhou Feng , She Siyuan , Hong Zequn , Hu Xiangdong
Published: September 2022

The freeze-sealing pipe roof (FSPR) method has been applied to the Gongbei tunnel of the Hongkong–Zhuhai–Macau Bridge, which is the first application of this method in the world. The purpose of the ground-freezing method is soil waterproofing. Temperature is an important indicator for measuring the freezing effect; however, the FSPR method involves unsteady-state conjugate heat transfer between frozen soil, steel pipes, concrete, air, and other media. This paper proposes an unsteady-state conjugate heat transfer model and establishes a global solution algorithm of a strong coupling governing equation based on the virtual density method. Then, a calculation based on COMSOL software is realized and validated. The sensitivity of different factors such as initial formation temperature, different soil layers, and brine temperature on the freezing effect was studied by simulating the FSPR model. It is concluded that the brine temperature had a greater impact on the freezing effect, followed by the soil layer, whereas the formation temperature had the least impact. For muddy silty clay, if the brine temperature is −20 °C, it takes 44 days to meet the design requirements of 2 m. If the brine temperature is −30 °C, 27 days is enough. When the formation temperature is 20 °C, it takes 20 days for medium gravel sand to reach the thickness of the freezing curtain, and 32 days for muddy silty clay. Compared to other soil layers, the freezing effect of the medium gravel sand is relatively better. This research has a certain impetus to similar multimedia freezing heat transfer issues.
Evaluation of Mineral Carbonation of Asbestos-Tex and Analysis of Airborne Asbestos Concentrations
Authors: Lim Yongtaek , Jang Hongseok , So Seungyoung
Published: September 2022

Asbestos is a human carcinogen that causes diseases, such as lung cancer and malignant mesothelioma. In Korea, approximately 1.23 × 109 kg of asbestos raw materials was imported for about 30 years. More than 80% of this were used as building material, such as interior materials and ceiling materials. Among the manufactured asbestos-containing materials, the closest product to the human body is asbestos-tex, used as ceiling material. In this study, asbestos contained in asbestos-tex was transformed into a shape that is physically safe for the human body through mineral carbonation and the results were verified through the analysis of airborne asbestos concentrations. We found that asbestos-tex powder in a buffer solution at 100 °C and at partial CO2 pressures of greater than 10 MPa transformed its constituent chrysotile asbestos moiety ((Mg3Si2O5(OH)4) into magnesite (MgCO3). Consequently, the needle-shaped asbestos fibers (diameters ≤ 3 µm) were converted to an angular rod-shaped mineral (diameters > 5 µm) that is safe for humans.
Degradation Mechanisms of Early Strength for High-Fluidization Cement Mortar under Magnesium Sulfate Corrosion
Authors: Zhang Xiangquan , Wang Siyuan , Zhao Lihong , Tang Gangting , Wang Chunguang , Ren Jiaolong
Published: September 2022

High-fluidization and early strength cement mortar (HECM) has been widely adopted in various fields of civil engineering. Due to the complexity of the engineering environment, sulfate corrosion cannot be ignored for the HECM. Although the effect of sulfate on the properties of the cement-based materials has been addressed, the degradation mechanisms of the HECM in the case of sulfate corrosion are not clear because of the distinct characteristics of the HECM (e.g., early strength and high fluidization) compared with conventional cement-based materials. Hence, considering the more complex corrosion process of magnesium sulfate, the early flexural and compressive strength of the HECM in the case of different magnesium sulfate concentrations and testing ages are investigated in this study. Moreover, the effects of magnesium sulfate concentrations and corrosion times on the microstructure and hydration products of the HECM are analyzed via a Scanning Electron Microscope (SEM) test, an X-ray diffraction (XRD) test, and a Differential Scanning Calorimeter (DSC) test. Finally, the influence mechanisms of the magnesium sulfate on the early strength formation of the HECM are analyzed to reveal the degradation mechanisms of the HECM.
Application of a Modified Differential Quadrature Finite Element Method to Flexural Vibrations of Composite Laminates with Arbitrary Elastic Boundaries
Authors: Xiang Wei , Li Xin , He Lina
Published: September 2022

This paper formulates a modified differential quadrature finite element method (DQFEM) by a combination of the standard DQFEM and the virtual boundary spring technique, which makes it easy to implement arbitrary elastic restraints by assigning reasonable values to the boundary spring stiffnesses. This new formulated method can offer a unified solution for flexural vibrations of composite laminates subjected to general elastic boundary combinations including all the classical cases. The influences of the number of Gauss–Lobatto nodes and the boundary spring stiffnesses on the convergence characteristics of natural frequencies are investigated, and some conclusions are drawn in terms of the minimum number of unilateral nodes required to generate convergent solutions and the optimal values of the boundary spring stiffnesses to simulate classical boundaries. Numerical examples are performed for composite laminates under various classical boundary conditions. Excellent accuracy, numerical stability, and reliability of the present method are demonstrated by comparisons with available exact and numerical solutions in open literatures. Additionally, for elastically constrained composite laminates, which are beyond the scope of most existing approaches, numerous new results obtained by the present method may serve as reference values for other research.
Reality Capture in Construction Project Management: A Review of Opportunities and Challenges
Authors: Fobiri Godfred , Musonda Innocent , Muleya Franco
Published: September 2022

Reality Capture (RC) is a state-of-the-art technology for digital data gathering and visualization of the actual environment through virtual means. In recent years, RC has contributed significantly to the digitalization of the construction industry globally. However, there are no systematic critical analyses of the benefits and challenges of RC technologies in construction project management (CPM) to drive its adoption. This research provides a detailed overview of the potential benefits and constraints of RC to tackle CPM concerns successfully and efficiently. This study uses the PRISMA procedure to conduct a systematic literature review. Based on the inclusion and exclusion criteria set for the study, 96 articles were considered relevant for review. The articles were analyzed using content analysis techniques to synthesize identify emerging themes. A four-step procedure was used to classify the articles into pre-construction planning, designing and construction. The review show that (a) RC is useful during the planning and designing stage, as the success of a construction project depends on accurate data to reduce the risk of cost and time overruns; (b) the benefits of RC adoption are accurate data, reduced time spent on project monitoring, progress tracking, and quality assessment; (c) RC on a construction site aids in the resolution of the industry’s fragmented nature through collaboration; quick and prompt decision making through remote monitoring and control of projects. RC is used as a visualization tool and for digital documentation of as-built models, construction verification, and flaw discovery, thereby improving work processes to achieve project success; (d) the most challenging aspect of incorporating RC on a construction site is the high investment cost. In the digital revolution era, this study could aid in the knowledge and optimal use of Reality Capture in numerous areas of CPM.
Comparative Analysis between Genetic Algorithm and Simulated Annealing-Based Frameworks for Optimal Sensor Placement and Structural Health Monitoring Purposes
Authors: Nasr Dana , Dahr Reina El , Assaad Joseph , Khatib Jamal
Published: September 2022

The arbitrary placement of sensors in concrete structures measures a considerable amount of unnecessary data. Optimal sensor placement methods are used to provide informative data with the least cost and maximum efficiency. In this study, a robust optimal sensor placement framework that combines an optimization-based algorithm, the simulated annealing (SA) algorithm, and the ensemble Kalman filter (EnKF) are presented for structural health monitoring and system identification. The SA algorithm randomly generates an initial population of sensor locations, while the framework undergoes a minimization process. The objective function used is the difference between the actual measured data and their corresponding EnKF predicted values. A comparative analysis between the genetic algorithm–ensemble Kalman filter (GA-EnKF) and the simulated annealing–ensemble Kalman filter (SA-EnKF) approaches is presented. The performance and computational burden of both algorithms, which converge to the best sensor locations for damage detection purposes, are tested on a 10-story building subjected to a seismic excitation. The results are compared to the optimal sensor locations of the brute-force search methodology. The GA-EnKF outperforms the SA-EnKF in terms of accuracy in converging to the optimal results, yet the computational cost of the SA-EnKF is considerably lower.
Dynamic Analysis of a Steel–Concrete Composite Box-Girder Bridge–Train Coupling System Considering Slip, Shear-Lag and Time-Dependent Effects
Authors: Gao Ce , Zhu Li , Han Bing , Tang Qing-Chen , Su Rui
Published: September 2022

A dynamic computational program considering slip, shear-lag and time-dependent effects of composite box-girder bridge–train coupling system is firstly proposed based on the authors’ previous studies. In the program, the long-term vertical displacement of a composite bridge is firstly calculated. The calculated vertical displacement is then superimposed on the existing uneven track as the new excitation of the composite box-girder bridge–train coupling system to obtain the dynamic responses of the bridge–train coupling system. A 3 × 40 m simply supported steel–concrete composite box-girder bridge is selected to investigate the influence of its time-dependent behavior on its dynamic responses. The results showed that the time-dependent effect will amplify the dynamic characteristics of the composite box-girder bridge and the high-speed train. The maximum vertical displacement and acceleration of the composite bridge increase by 8.82% and 13.64%, and the maximum vertical acceleration of the train body increases by 144.78%. Additionally, the slip and shear-lag effects have an impact on the dynamic responses of the composite box-girder bridge–train coupling system at different operation times. The dynamic responses of the coupling system strengthen with the decrease in shear connection stiffness. The dynamic responses of the system may be underestimated when the shear-lag effect is not neglected. Therefore, these conclusions should be given sufficient attention in the design, construction and operation of high-speed railway composite bridges.
Buffer Sizing in Critical Chain Project Management by Brittle Risk Entropy
Authors: Peng Jun-long , Peng Chao
Published: September 2022

In order to solve the problems such as project duration delay caused by unreasonable buffer zone setting, a critical chain buffer zone setting method is proposed based on fragility theory. Firstly, we propose that the construction process is brittle and the brittleness of the construction process was analyzed. Secondly, this paper introduces a risk-integrated impact rate to describe the uncertainty of the construction process and establishes a brittle risk entropy function. Then, it presents entropy models and modification models of project buffers and feeding buffers based on the original Root Square Error Method. Finally, an engineering project was selected as an example, and the simulation was carried out using the Monte Carlo simulation software Crystal Ball, and the resulting method was compared with three buffer zone calculation methods. The results show that the method can effectively reduce the construction period and is effective and practical when compared to the other three buffer calculation methods. The results of the study provide a new way of thinking about buffer settings based on existing critical chain project management methods.
An Ontology-Based Holistic and Probabilistic Framework for Seismic Risk Assessment of Buildings
Authors: Xu Minze , Zhang Peng , Cui Chunyi , Zhao Jingtong
Published: September 2022

To avoid over-reliance on the identification of building damage states post-earthquake in the seismic risk assessment process, an ontology-based holistic and probabilistic framework is proposed here for seismic risk prediction of buildings with various purposes and different damage states. Based on vulnerability analysis, the seismic risk probabilities of buildings are first obtained by considering the on-site seismic hazard. Taking economic losses and casualties as assessment indicators, a system for seismic risk assessment of buildings, OntoBSRA (Ontology for Building Seismic Risk Assessment), is then developed by combining ontology and semantic web rule language. A case study is carried out to demonstrate the application of the proposed framework and further validate the semantic web rules. The results show that the proposed framework can provide a holistic knowledge base that allows risk assessors or asset managers to predict the consequences of earthquakes effectively, thereby improving efficiency in decision-making.
A microRNA Prognostic Signature in Patients with Diffuse Intrinsic Pontine Gliomas through Non-Invasive Liquid Biopsy
Authors: Iannó Maria F. , Biassoni Veronica , Schiavello Elisabetta , Carenzo Andrea , Boschetti Luna , Gandola Lorenza , Diletto Barbara , Marchesi Edoardo , Vegetti Claudia , Molla Alessandra , Kramm Christof M. , van Vuurden Dannis G. , Gasparini Patrizia , Gianno Francesca , Giangaspero Felice , Modena Piergiorgio , Bison Brigitte , Anichini Andrea , Vennarini Sabina , Pignoli Emanuele , Massimino Maura , De Cecco Loris
Published: September 2022

Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set (n = 23) as being able to stratify patients by risk of disease progression (log-rank p = 0.00014; HR = 7.99, 95% CI 2.38–26.87). When challenged in a separate validation set (n = 24), it confirmed its ability to predict progression (log-rank p = 0.00026; HR = 5.51, 95% CI 2.03–14.9). The value of our signature was also confirmed when overall survival was considered (log-rank p = 0.0021, HR = 4.12, 95% CI 1.57–10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient’s risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression.
Application of C-Terminal Clostridium Perfringens Enterotoxin in Treatment of Brain Metastasis from Breast Cancer
Authors: Banga Amita R. , Odiase Peace , Rachakonda Kartik , Garg Amar P. , Adunyah Samuel E. , Rachakonda Girish
Published: September 2022

Claudin-4 is part of the Claudin family of transmembrane tight junction (TJ) proteins found in almost all tissues and, together with adherens junctions and desmosomes, forms epithelial and endothelial junctional complexes. Although the distribution of Claudin-4 occurs in many cell types, the level of expression is cell-specific. Claudin proteins regulate cell proliferation and differentiation by binding cell-signaling ligands, and its expression is upregulated in several cancers. As a result, alterations in Claudin expression patterns or distribution are vital in the pathology of cancer. Profiling the genetic expression of Claudin-4 showed that Claudin-4 is also a receptor for the clostridium perfringens enterotoxin (CPE) and that Claudin-4 has a high sequence similarity with CPE’s high-affinity receptor. CPE is cytolytic due to its ability to form pores in cellular membranes, and CPE treatment in breast cancer cells have shown promising results due to the high expression of Claudin-4. The C-terminal fragment of CPE (c-CPE) provides a less toxic alternative for drug delivery into breast cancer cells, particularly metastatic tumors in the brain, especially as Claudin-4 expression in the central nervous system (CNS) is low. Therefore, c-CPE provides a unique avenue for the treatment of breast–brain metastatic tumors.
Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure
Authors: Capelli Debora , Menotti Diego , Fiorentini Alessandro , Saraceni Francesco , Olivieri Attilio
Published: September 2022

FLT3 ITD and TKD mutations occur in 20% and 10% of Acute Myeloid Leukemia (AML), respectively, and they represent the target of the first approved anti-leukemic therapies in the 2000s. Type I and type II FLT3 inhibitors (FLT3i) are active against FLT3 TKD/ITD and FLT3 ITD mutations alone respectively, but they still fail remissions in 30–40% of patients due to primary and secondary mechanisms of resistance, with variable relapse rate of 30–50%, influenced by NPM status and FLT3 allelic ratio. Mechanisms of resistance to FLT3i have recently been analyzed through NGS and single cell assays that have identified and elucidated the polyclonal nature of relapse in clinical and preclinical studies, summarized here. Knowledge of tumor escape pathways has helped in the identification of new targeted drugs to overcome resistance. Immunotherapy and combination or sequential use of BCL2 inhibitors and experimental drugs including aurora kinases, menin and JAK2 inhibitors will be the goal of present and future clinical trials, especially in patients with FLT3-mutated (FLT3mut) AML who are not eligible for allogeneic transplantation.
Nrf2 Downregulation Contributes to Epithelial-to-Mesenchymal Transition in Helicobacter pylori-Infected Cells
Authors: Bacon Sarah , Seeneevassen Lornella , Fratacci Alison , Rose Faustine , Tiffon Camille , Sifré Elodie , Haykal Maria M. , Moubarak Maya M. , Ducournau Astrid , Bruhl Lucie , Claverol Stéphane , Tokarski Caroline , Gouloumi Alina-Roxani , Pateras Ioannis S. , Daubon Thomas , Lehours Philippe , Varon Christine , Martin Océane C. B.
Published: September 2022

Background: Gastric cancer, the fifth most common cancer worldwide, is mainly linked to Helicobacter pylori infection. H. pylori induces chronic inflammation of the gastric mucosa associated with high oxidative stress. Our study aimed at assessing the implication of Nrf2, a major regulator of cellular redox homeostasis, in H. pylori-induced gastric carcinogenesis. Methods: Using three different gastric epithelial cell lines, a non-cancerous (HFE-145) and two different subtypes of gastric cancer (AGS and MKN74), we analyzed the modulation of Nrf2 expression over time. After invalidation of Nrf2 by CRISPR-cas9, we assessed its role in H. pylori-induced epithelial-to-mesenchymal transition (EMT). Finally, we evaluated the expression of Nrf2 and ZEB1, a central EMT transcription factor, in human gastric tissues. Results: We first demonstrated that the Nrf2 signaling pathway is differentially regulated depending on the infection stage. Rapidly and transiently activated, Nrf2 was downregulated 24 h post-infection in a VacA-dependent manner. We then demonstrated that Nrf2 invalidation leads to increased EMT, which is even exacerbated after H. pylori infection. Finally, Nrf2 expression tended to decrease in human patients’ gastric mucosa infected with H. pylori. Conclusions: Our work supports the hypothesis that Nrf2 downregulation upon H. pylori infection participates in EMT, one of the most important events in gastric carcinogenesis.
Deep View of HCC Gene Expression Signatures and Their Comparison with Other Cancers
Authors: Qian Yuquan , Itzel Timo , Ebert Matthias , Teufel Andreas
Published: September 2022

Background: Gene expression signatures correlate genetic alterations with specific clinical features, providing the potential for clinical usage. A plethora of HCC-dependent gene signatures have been developed in the last two decades. However, none of them has made its way into clinical practice. Thus, we investigated the specificity of public gene signatures to HCC by establishing a comparative transcriptomic analysis, as this may be essential for clinical applications. Methods: We collected 10 public HCC gene signatures and evaluated them by utilizing four different (commercial and non-commercial) gene expression profile comparison tools: Oncomine Premium, SigCom LINCS, ProfileChaser (modified version), and GENEVA, which can assign similar pre-analyzed profiles of patients with tumors or cancer cell lines to our gene signatures of interests. Among the query results of each tool, different cancer entities were screened. In addition, seven breast and colorectal cancer gene signatures were included in order to further challenge tumor specificity of gene expression signatures. Results: Although the specificity of the evaluated HCC gene signatures varied considerably, none of the gene signatures showed strict specificity to HCC. All gene signatures exhibited potential significant specificity to other cancers, particularly for colorectal and breast cancer. Since signature specificity proved challenging, we furthermore investigated common core genes and overlapping enriched pathways among all gene signatures, which, however, showed no or only very little overlap, respectively. Conclusion: Our study demonstrates that specificity, independent validation, and clinical use of HCC genetic signatures solely relying on gene expression remains challenging. Furthermore, our work made clear that standards in signature generation and statistical methods but potentially also in tissue preparation are urgently needed.
The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study
Authors: Xie Mingying , Li Na , Xu Xiaoling , Xu Yanjun , Li Hui , Zhu Liang , Sheng Jiamin , Zhou Zichao , Fan Yun
Published: September 2022

Background: A controversy exists regarding the efficacy of programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors for patients with non-small cell lung cancer (NSCLC) and liver metastases. Our study retrospectively evaluated the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with liver metastases. Methods: This retrospective study included 1627 lung cancer patients who received immunotherapy. Among 648 patients who had advanced NSCLC and received PD-1/PD-L1 inhibitors, 61 had liver metastases and 587 did not have. We analyzed patient characteristics, progression-free survival (PFS) and overall survival (OS). An exploratory analysis of biomarkers including CD4, CD8 and CD68 for efficacy in patients with liver metastases was also performed. Results: In liver metastasis patients receiving PD-1/PD-L1 inhibitors, the objective response rate (ORR) was 29.5%, the disease control rate (DCR) was 72.1%, PFS was 6.4 months and OS was 15.2 months, which were all worse than those of patients without liver metastases (ORR: 35.8%; DCR: 81.8%; PFS: 7.9 months, p = 0.001; OS: 20.6 months, p = 0.008). When compared to non-liver lesions, the ORR (26.2 vs. 39.3%) and DCR (75.4 vs. 88.5%) of liver lesions were lower. During the analysis of PD-L1 expression, 27 PD-L1-positive patients had a longer PFS than 21 patients in the negative group (p = 0.012). Being PD-L1 positive was the independent prognostic indicators for PFS (p = 0.006). Additionally, the PD-L1 and CD8 dual-positive group responded favorably to PD-1/PD-L1 inhibitors. Conclusions: PD-1/PD-L1 inhibitors are effective in liver metastasis–NSCLC patients. However, the efficacy is inferior when compared to those of patients without liver metastases. In NSCLC patients with liver metastases, PD-L1 expression and CD8+ T cell infiltration can predict the response of PD-1/PD-L1-directed immunotherapy.
Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study
Authors: Wagner Michael J. , Hennessy Cassandra , Beeghly Alicia , French Benjamin , Shah Dimpy P. , Croessmann Sarah , Vilar-Compte Diana , Ruiz-Garcia Erika , Ingham Matthew , Schwartz Gary K. , Painter Corrie A. , Chugh Rashmi , Fecher Leslie , Park Cathleen , Zamulko Olga , Trent Jonathan C. , Subbiah Vivek , Khaki Ali Raza , Tachiki Lisa , Nakasone Elizabeth S. , Loggers Elizabeth T. , Labaki Chris , Saliby Renee Maria , McKay Rana R. , Ajmera Archana , Griffiths Elizabeth A. , Puzanov Igor , Tap William D. , Hwang Clara , Tejwani Sheela , Jhawar Sachin R. , Hayes-Lattin Brandon , Wulff-Burchfield Elizabeth , Kasi Anup , Reuben Daniel Y. , Nagaraj Gayathri , Joshi Monika , Polimera Hyma , Kulkarni Amit A. , Esfahani Khashayar , Kwon Daniel H. , Paoluzzi Luca , Bilen Mehmet A. , Durbin Eric B. , Grivas Petros , Warner Jeremy L. , Davis Elizabeth J.
Published: September 2022

Background: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. Methods: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. Results: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. Conclusions: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.
Interleukin 4 Controls the Pro-Tumoral Role of Macrophages in Mammary Cancer Pulmonary Metastasis in Mice
Authors: Rodriguez-Tirado Carolina , Entenberg David , Li Jiufeng , Qian Bin-Zhi , Condeelis John S. , Pollard Jeffrey W.
Published: September 2022

Metastasis is the systemic manifestation of cancer and the main cause of death from breast cancer. In mouse models of lung metastases, recruitment of classical monocytes from blood to the lung and their differentiation to metastasis-associated macrophages (MAMs) facilitate cancer cell extravasation, survival and growth. Ablation of MAMs or their monocytic progenitors inhibits metastasis. We hypothesized that factors controlling macrophage polarization modulate tumor cell extravasation in the lung. We evaluated whether signaling by Th1 or Th2 cytokines in macrophages affected transendothelial migration of tumor cells in vitro. Interferon gamma and LPS inhibited macrophage-dependent tumor cell extravasation while the Th2 cytokine interleukin-4 (IL4) enhanced this process. We demonstrated that IL4 receptor (IL4rα)-null mice developed fewer and smaller lung metastasis in E0771-LG mammary cancer models of this disease. Adoptive transfer of wild-type monocytes to IL4rα-deficient mice partially rescued this phenotype. IL4 signaling in macrophages controlled the expression of the chemokine receptor CXCR2, necessary for IL4-mediated tumor cell extravasation in vitro. Furthermore, IL4 signaling in macrophages regulated the transcript abundance of several other genes already causally associated with mammary cancer lung metastasis including Ccl2, Csf1, Ccr1, Hgf and Flt1. The central role of IL4 signaling in MAMs was confirmed by high-resolution intravital imaging of the lung in mice at the time of metastatic seeding, which showed reduced physical interaction between tumor cells and IL4rα-deficient macrophages. This interaction with wild-type MAMs enhanced tumor cell survival and seeding, which was lost in the IL4rα mice. These data indicate that IL4 signaling in monocytes and macrophages is key during seeding and growth of breast metastasis in the lung, as it regulates pro-tumoral paracrine signaling between cancer cells and macrophages.
Endometrial Cancer Detection Using a Cervical DNA Methylation Assay (MPap) in Women with Abnormal Uterine Bleeding: A Multicenter Hospital-Based Validation Study
Authors: Wen Kuo-Chang , Huang Rui-Lan , Chen Lin-Yu , Wu Tzu-I , Lu Chien-Hsing , Chu Tang-Yuan , Ou Yu-Che , Wu Chen-Hsuan , Hsu Shih-Tien , Ding Dah-Ching , Chu Ling-Hui , Chen Chien-Wen , Chang Heng-Cheng , Liu Yu-Shu , Wang Hui-Chen , Weng Yu-Chun , Su Po-Hsuan , Lin Hao , Lai Hung-Cheng
Published: September 2022

Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. Results: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. Conclusions: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.
Recent Progress of Natural Mineral Materials in Environmental Remediation
Authors: Kang Ningxin , Zhou Weichuang , Qi Zheng , Li Yuhan , Wang Zhi , Li Qin , Lv Kangle
Published: September 2022

Organic contaminants, volatile organic compounds (VOCs), and heavy metals have posed long-term threats to the ecosystem and human health. Natural minerals have aroused widespread interest in the field of environmental remediation due to their unique characteristics such as rich resources, environmentally benign, and excellent photoelectric properties. This review briefly introduced the contributions of natural minerals such as sulfide minerals, oxide minerals, and oxysalt minerals in pollution control, which include organic pollution degradation, sterilization, air purification (NO VOCs oxidation), and heavy metal treatment by means of photocatalysis, Fenton catalysis, persulfate activation, and adsorption process. At last, the future challenges of natural mineral materials in pollution control are also outlooked.
Well-Defined Ultrasmall V-NiP2 Nanoparticles Anchored g-C3N4 Nanosheets as Highly Efficient Visible-Light-Driven Photocatalysts for H2 Evolution
Authors: Niu Mengfan , Cao Liyun , Liu Qianqian , Li Xiaoyi , Chen Qian , Liu Dinghan , Li Wenbin , Huang Jianfeng , Feng Liangliang
Published: September 2022

Exploring low-cost and highly active, cost-effective cocatalysts is of great significance to improve the hydrogen evolution performance of semiconductor photocatalysts. Herein, a novel ultrasmall V-doped NiP2 nanoparticle, as an efficient cocatalyst, is reported to largely upgrade the photocatalytic hydrogen evolution reaction (HER) of g-C3N4 nanosheets under visible-light irradiation. Experimental results demonstrate that V-NiP2 cocatalyst can enhance the visible-light absorption ability, facilitate the separation of photo-generated electron-hole pairs and boost the transfer ability of electrons of g-C3N4. Moreover, the V-NiP2/g-C3N4 hybrid exhibits prominent photocatalytic HER activity 17 times higher than the pristine g-C3N4 counterpart, even outperforming the 1 wt.% platinum-loaded g-C3N4. This work displays that noble-metal-free V-NiP2 cocatalyst can serve as a promising and efficient alternative to Pt for high-efficiency photocatalytic H2 evolution.
Loss of Flocculus Purkinje Cell Firing Precision Leads to Impaired Gaze Stabilization in a Mouse Model of Spinocerebellar Ataxia Type 6 (SCA6)
Authors: Chang Hui Ho Vanessa , Cook Anna A. , Watt Alanna J. , Cullen Kathleen E.
Published: September 2022

Spinocerebellar Ataxia Type 6 (SCA6) is a mid-life onset neurodegenerative disease characterized by progressive ataxia, dysarthria, and eye movement impairment. This autosomal dominant disease is caused by the expansion of a CAG repeat tract in the CACNA1A gene that encodes the α1A subunit of the P/Q type voltage-gated Ca2+ channel. Mouse models of SCA6 demonstrate impaired locomotive function and reduced firing precision of cerebellar Purkinje in the anterior vermis. Here, to further assess deficits in other cerebellar-dependent behaviors, we characterized the oculomotor phenotype of a knock-in mouse model with hyper-expanded polyQ repeats (SCA684Q). We found a reduction in the efficacy of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) in SCA6 mutant mice, without a change in phase, compared to their litter-matched controls. Additionally, VOR motor learning was significantly impaired in SCA684Q mice. Given that the floccular lobe of the cerebellum plays a vital role in the generation of OKR and VOR calibration and motor learning, we investigated the firing behavior and morphology of floccular cerebellar Purkinje cells. Overall, we found a reduction in the firing precision of floccular lobe Purkinje cells but no morphological difference between SCA684Q and wild-type mice. Taken together, our findings establish that gaze stabilization and motor learning are impaired in SCA684Q mice and suggest that altered cerebellar output contributes to these deficits.
Around-the-Clock Noise Induces AD-like Neuropathology by Disrupting Autophagy Flux Homeostasis
Authors: Zheng Pengfang , She Xiaojun , Wang Chunping , Zhu Yingwen , Fu Bo , Ma Kefeng , Yang Honglian , Gao Xiujie , Li Xiaofang , Wu Fangshan , Cui Bo
Published: September 2022

Environmental noise is a common hazard in military operations. Military service members during long operations are often exposed to around-the-clock noise and suffer massive emotional and cognitive dysfunction related to an Alzheimer’s disease (AD)-like neuropathology. It is essential to clarify the mechanisms underlying the effects of around-the-clock noise exposure on the central nervous system. Here, Wistar rats were continuously exposed to white noise (95 dB during the on-duty phase [8:00–16:00] and 75 dB during the off-duty phase (16:00–8:00 the next day)) for 40 days. The levels of phosphorylated tau, amyloid-β (Aβ), and neuroinflammation in the cortex and hippocampus were assessed and autophagosome (AP) aggregation was observed by transmission electron microscopy. Dyshomeostasis of autophagic flux resulting from around-the-clock noise exposure was assessed at different stages to investigate the potential pathological mechanisms. Around-the-clock noise significantly increased Aβ peptide, tau phosphorylation at Ser396 and Ser404, and neuroinflammation. Moreover, the AMPK-mTOR signaling pathway was depressed in the cortex and the hippocampus of rats exposed to around-the-clock noise. Consequently, autophagosome–lysosome fusion was deterred and resulted in AP accumulation. Our results indicate that around-the-clock noise exposure has detrimental influences on autophagic flux homeostasis and may be associated with AD-like neuropathology in the cortex and the hippocampus.
LACTB, a Metabolic Therapeutic Target in Clinical Cancer Application
Authors: Li Xiaohua , Ren Zhongkai , Huang Xiaohong , Yu Tengbo
Published: September 2022

Serine beta-lactamase-like protein (LACTB) is the only mammalian mitochondrial homolog evolved from penicillin-binding proteins and β-lactamases (PBP-βLs) in bacteria. LACTB, an active-site serine protease, polymerizes into stable filaments, which are localized to the intermembrane space (IMS) of mitochondrion and involved in the submitochondrial organization, modulating mitochondrial lipid metabolism. Cancer pathogenesis and progression are relevant to the alterations in mitochondrial metabolism. Metabolic reprogramming contributes to cancer cell behavior. This article (1) evidences the clinical implications of LACTB on neoplastic cell proliferation and migration and tumor growth and metastasis as well as LACTB’s involvement in chemotherapeutic and immunotherapeutic responses; (2) sketches the structural basis for LACTB activity and function; and (3) highlights the relevant regulatory mechanisms to LACTB. The abnormal expression of LACTB has been associated with clinicopathological features of cancer tissues and outcomes of anticancer therapies. With the current pioneer researches on the tumor-suppressed function, structural basis, and regulatory mechanism of LACTB, the perspective hints at a great appeal of enzymic property, polymerization, mutation, and epigenetic and post-translational modifications in investigating LACTB’s role in cancer pathogenesis. This perspective provides novel insights for LACTB as a metabolic regulator with potential to develop targeted cancer therapies or neoadjuvant therapeutic interventions.
Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage
Authors: Cui Qi , Zhang Yingmei , Tian Ning , Yang Jiaxin , Ya Dongshan , Xiang Wenjing , Zhou Zixian , Jiang Yanlin , Deng Jungang , Yang Bin , Lin Xiaohui , Li Qinghua , Liao Rujia
Published: September 2022

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.
Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90
Authors: Wu Hong-Yu , Trevino Jose G. , Fang Bing-Liang , Riner Andrea N. , Vudatha Vignesh , Zhang Guo-Hua , Li Yi-Ping
Published: September 2022

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38β MAPK-mediated catabolic pathways primarily through Toll-like receptor 4 (TLR4). However, whether human PC induces cachexia through releasing Hsp70 and Hsp90 is undetermined. Here, we investigated whether patient-derived PC cells induce muscle cell atrophy directly through this mechanism. We compared cancer cells isolated from patient-derived xenografts (PDX) from three PC patients who had cachexia (PCC) with those of three early-stage lung cancer patients without cachexia (LCC) and two renal cancer patients who were not prone to cachexia (RCC). We observed small increases of Hsp70 and Hsp90 released by LCC and RCC in comparison to non-cancer control cells (NCC). However, PCC released markedly higher levels of Hsp70 and Hsp90 (~ 6-fold on average) than LCC and RCC. In addition, PCC released similarly increased levels of Hsp70/90-containing EVs. In contrast to RCC and LCC, PCC-conditioned media induced a potent catabolic response in C2C12 myotubes including the activation of p38 MAPK and transcription factor C/EBPβ, upregulation of E3 ligases UBR2 and MAFbx, and increase of autophagy marker LC3-II, resulting in the loss of the myosin heavy chain (MHC ~50%) and myotube diameter (~60%). Importantly, the catabolic response was attenuated by Hsp70- and Hsp90-neutralizing antibodies in a dose-dependent manner. These data suggest that human PC cells release high levels of Hsp70 and Hsp90 that induce muscle atrophy through a direct action on muscle cells.
The Dynamic Changes of Alternative Electron Flows upon Transition from Low to High Light in the Fern Cyrtomium fortune and the Gymnosperm Nageia nagi
Authors: Cheng Jun-Bin , Zhang Shi-Bao , Wu Jin-Song , Huang Wei
Published: September 2022

In photosynthetic organisms except angiosperms, an alternative electron sink that is mediated by flavodiiron proteins (FLVs) plays the major role in preventing PSI photoinhibition while cyclic electron flow (CEF) is also essential for normal growth under fluctuating light. However, the dynamic changes of FLVs and CEF has not yet been well clarified. In this study, we measured the P700 signal, chlorophyll fluorescence, and electrochromic shift spectra in the fern Cyrtomium fortune and the gymnosperm Nageia nagi. We found that both species could not build up a sufficient proton gradient (∆pH) within the first 30 s after light abruptly increased. During this period, FLVs-dependent alternative electron flow was functional to avoid PSI over-reduction. This functional time of FLVs was much longer than previously thought. By comparison, CEF was highly activated within the first 10 s after transition from low to high light, which favored energy balancing rather than the regulation of a PSI redox state. When FLVs were inactivated during steady-state photosynthesis, CEF was re-activated to favor photoprotection and to sustain photosynthesis. These results provide new insight into how FLVs and CEF interact to regulate photosynthesis in non-angiosperms.
Differentiation Capacity of Bone Marrow-Derived Rat Mesenchymal Stem Cells from DsRed and Cre Transgenic Cre/loxP Models
Authors: Tseng Hsiang-Ching , Wu Menq-Rong , Lee Chia-Hsun , Hsiao Jong-Kai
Published: September 2022

Cre/loxP recombination is a well-established technique increasingly used for modifying DNA both in vitro and in vivo. Nucleotide alterations can be edited in the genomes of mammalian cells, and genetic switches can be designed to target the expression or excision of a gene in any tissue at any time in animal models. In this study, we propose a system which worked via the Cre/loxP switch gene and DsRed/emGFP dual-color fluorescence imaging. Mesenchymal stem cells (MSCs) can be used to regenerate damaged tissue because of their differentiation capacity. Although previous studies have presented evidence of fusion of transplanted MSCs with recipient cells, the possibility of fusion in such cases remains debated. Moreover, the effects and biological implications of the fusion of MSCs at the tissue and organ level have not yet been elucidated. Thus, the method for determining this issue is significant and the models we proposed can illustrate the question. However, the transgenic rats exhibited growth slower than that of wild-type rats over several weeks. The effects on the stemness, proliferation, cell cycle, and differentiation ability of bone marrow–derived rat MSCs (BM-rMSCs) from the models were examined to ensure our design was appropriate for the in vivo application. We demonstrated that MSC surface markers were maintained in DsRed and Cre transgenic rMSCs (DsRed-rMSCs and Cre-rMSCs, respectively). A WST-8 assay revealed decreased proliferative activity in these DsRed-rMSCs and Cre-rMSCs; this result was validated through cell counting. Furthermore, cell cycle analysis indicated a decrease in the proportion of G1-phase cells and a concomitant increase in the proportion of S-phase cells. The levels of cell cycle–related proteins also decreased in the DsRed-rMSCs and Cre-rMSCs, implying decelerated phase transition. However, the BM-rMSCs collected from the transgenic rats did not exhibit altered adipogenesis, osteogenesis, or chondrogenesis. The specific markers of these types of differentiation were upregulated after induction. Therefore, BM-rMSCs from DsRed and Cre transgenic models can be used to investigate the behavior of MSCs and related mechanisms. Such application may further the development of stem cell therapy for tissue damage and other diseases.