bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivations and Specialization of Birders Are Differently Related to Engagement in Citizen Science Projects of Different Complexity
Authors: Randler Christoph
Published: October 2022

Citizen Science (CS) projects are an important aspect of scientific data collection and biodiversity conservation. In ornithology, various CS projects exist, and even laypersons can contribute, but advanced birdwatchers also spend considerable time and effort in data collection. Here, different CS projects for birders were analyzed and compared with respect to recreation specialization and motivations for birdwatching. Established, psychometrically valid, and reliable scales were applied in this study. N = 2856 respondents from Austria, Germany, and Switzerland were grouped into no, low, and sustained engagement clusters. Sustained engagement was related to more complex programs, such as the breeding bird census and waterfowl counting. When comparing the engagement clusters, effect sizes were considerable, ranging from 0.098 (attraction) to 0.306 (skill/knowledge). Thus, birders of the three engagement clusters differed significantly in birding specialization, especially skill/knowledge, psychological commitment, social motivations, and the psychological construct centrality to lifestyle. No differences were found in enjoyment and achievement motivations. In conclusion, low-threshold projects are needed to attract participants, but keeping people within programs or moving them to a higher level of engagement might be easier when social dimensions are addressed.
Categorization of Factors Affecting the Resistance and Parameters Optimization of Ultra-Fine Cemented Paste Backfill Pipeline Transport
Authors: Sun Haikuan , Gan Deqing , Xue Zhenlin , Zhang Yajie
Published: October 2022

Ultra-fine cemented paste backfill (UCPB) is prepared using tailings, binder and water. The factors affecting the resistance of UCPB pipe transport are numerous and complex, and the factor interactions restrict the rational development of the filling pipe transport design, which is not conducive to reducing the resistance. This paper categorizes and integrates the factors of pipe transport resistance by theoretical analysis and uses response surface methodology (RSM) to study the influence of different types of factors on the UCPB pipe transport resistance. The results show that the pipe transport resistance factors are classified into endogenous and exogenous factors. According to the classification, the reduction rate of the optimized pipe transport resistance is as high as 25.31% and 15.81%. This shows that the categorization of factors affecting the pipe transport resistance is important for investigating UCPB pipe flow. The single-factor terms with the highest significance under the effect of endogenous and exogenous factors are mass concentration and pipe diameter, respectively. The two interaction terms with highest significance are mass concentration and slurry temperature, pipe diameter and flow velocity, respectively. The results provide new ideas to reduce the resistance of mine pipeline and improve the filling benefit and convenience of pipeline design.
Analysis and Evaluation of the Progressive Collapse Behaviour of a Cable Dome Structure
Authors: Chen Lianmeng , Li Zebin , Liu Yijie , Huang Kaiyu , Zeng Yihong , Zhou Yiyi , Dong Shilin
Published: October 2022

In this study, the progressive collapse behaviour of a cable dome structure was analysed and evaluated according to the importance of element. First, the dynamic response and collapse mode caused by the removal of different types of cables and struts from a cable dome structure were studied using the instantaneous unloading method of full dynamic equivalent load. Second, a method was developed for element importance classification based on collapse modes, and the importance coefficient was introduced after comparing the node displacements before and after the removal of different elements. On this basis, the correlations of the importance coefficient of an element with its importance classification and the collapse mode caused by its removal were examined. Third, the influences of some design parameters on the resistance of cable dome structures to progressive collapses and on the importance coefficients of components were analysed and evaluated. Finally, a method was proposed to determine the critical value of the element importance category. The results of this study indicated that Cable-Strut elements differed in their antiprogressive collapse effects and importance coefficients, and thus produced different dynamic responses and collapse modes when they were removed. Cable domes differed in their critical importance coefficients for Cable-Strut elements, and design parameters differed in their influence on the antiprogressive collapse resistance of cable domes.
Variable Factors Affecting Progressive Destruction of Composite Steel Tall Building
Authors: Lotfy Sameh , Mortagi Mohamed , El Madawy Mohamed E.
Published: October 2022

In recent years, the presence of progressive collapse in tall buildings induced a catastrophic event which attracted the majority of the community’s attention. The purpose of this paper is to develop a 3D numerical analysis of tall building under column loss. A composite steel frame building with 25 stories with five spans in both directions is proposed. The building has 3 m story height and 8 m span in both directions. The building is designed through the commercial software SAP2000 software against wind loads based on Eurocode 1-2005. The focus here is to investigate various parametric studies under abrupt column loss of multi-story composite building. The effect of composite slab is considered with full composite action between beam and slab. The findings of a parametric formulation incorporating important parameters for the progressive collapse design technique are given and confirmed using nonlinear dynamic time history analyses. The assessment of results has been introduced based on deformation, axial force in columns, equivalent plastic strain, major moment and axial force in the considered beams above the column loss. Next, a probabilistic analysis has been performed to assess the behavior of composite steel buildings against column loss. The study investigates the critical column loss and pinpoints the location of the next critical column. The results show that the concrete grade, position of the removed column, beams cross-section, and place of bracings have a significant effect in the response of the building rather than the steel grade and bottom reinforcement density. The removal of exterior column has the significant increase of the axial force percentage by 111.4% for the corner column. The corner column removal gives the maximum equivalent plastic strain with a value of 0.00449. Furthermore, the results reveal the potential impact of uncertainty on the structural elements of the considered buildings through the progressive collapse analysis. The vertical displacement above the column is fitted with mean value of 0.0251387 m and with a coefficient of variation 0.01664.
Thermal Effects of Vertical Greening in Summer: An Investigation on Evapotranspiration and Shading of Façade Greening in Vienna
Authors: Salonen Tarja , Hollands Jutta , Sesto Eldira , Korjenic Azra
Published: October 2022

Global urbanization is advancing, and with it, the densification of cities. Due to increased sealing of open spaces and the re-densification of existing urban settings, green spaces in the city are becoming scarcer. At the same time, greening within the urban fabric is known for its positive effects on the environment and decisively counteracts the urban heat effect. This study deals with the benefits of green façades for the environment as a cooling measure. Two façade greening systems, one trough and one cassette system, consisting of curtain wall elements with a basic metal structure, installed at a south-facing outdoor wall of a school building in Vienna, Austria, were taken under metrological examination. In order to evaluate the cooling effect caused by evapotranspiration, the amount of water evaporated was calculated using the difference of inflow and outflow. Furthermore, the surface temperatures of the greened and non-greened walls were measured to display the influence of the interaction of shading and evapotranspiration on the surrounding microclimate. The investigated vertical greening system with an area of 58 m2 has an average evaporation capacity of 101.38 L per day in the summer. The maximum surface temperature difference was measured to be 11.6 °C.
Predicting Recurrence of Non-Muscle-Invasive Bladder Cancer: Current Techniques and Future Trends
Authors: Shalata Aya T. , Shehata Mohamed , Van Bogaert Eric , Ali Khadiga M. , Alksas Ahmed , Mahmoud Ali , El-Gendy Eman M. , Mohamed Mohamed A. , Giridharan Guruprasad A. , Contractor Sohail , El-Baz Ayman
Published: October 2022

Bladder cancer (BC) is the 10th most common cancer globally and has a high mortality rate if not detected early and treated promptly. Non-muscle-invasive BC (NMIBC) is a subclassification of BC associated with high rates of recurrence and progression. Current tools for predicting recurrence and progression on NMIBC use scoring systems based on clinical and histopathological markers. These exclude other potentially useful biomarkers which could provide a more accurate personalized risk assessment. Future trends are likely to use artificial intelligence (AI) to enhance the prediction of recurrence in patients with NMIBC and decrease the use of standard clinical protocols such as cystoscopy and cytology. Here, we provide a comprehensive survey of the most recent studies from the last decade (N = 70 studies), focused on the prediction of patient outcomes in NMIBC, particularly recurrence, using biomarkers such as radiomics, histopathology, clinical, and genomics. The value of individual and combined biomarkers is discussed in detail with the goal of identifying future trends that will lead to the personalized management of NMIBC.
Effects of Weight Status and Related Metabolic Disorders on Fertility-Sparing Treatment Outcomes in Endometrial Atypical Hyperplasia and Endometrial Cancer: A Retrospective Study
Authors: Liu Sijia , Wang Lulu , Wu Pengfei , Luo Shuhan , Shan Weiwei , Chen Xiaojun , Luo Xuezhen
Published: October 2022

Background: Although obesity was an independent risk factor for fertility-sparing treatment in endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the roles of other weight statuses and related metabolism were unclear. This study aimed to investigate the body mass index (BMI) interval that produced optimal treatment efficacy and the effects of related metabolic disorders in EAH/EEC patients. Methods: A total of 286 patients (including 209 EAH and 77 well-differentiated EEC) under progestin therapy were retrospectively analyzed. The cumulative complete response (CR) rate, relapse rate, and fertility outcomes were compared among different weight or metabolic statuses. Results: Underweight and overweight/obese status significantly decreased the cumulative 16-week and 32-week CR rate (p = 0.004, p = 0.022, respectively). The highest 16-week CR rate was observed at a BMI of 21–22 kg/m2 in the overall population (p = 0.033). Obesity (HR 0.37, 95%CI 0.15–0.90, p = 0.029) and PCOS (HR 0.55, 95%CI 0.31–0.99, p = 0.047) were associated with lower 16-week CR rate. Hyperuricemia (HR 0.66, 95%CI 0.45–0.99, p = 0.043) was associated with lower 32-week CR rate. The 16-week and 32-week CR rate (p = 0.036, p = 0.008, respectively) were significantly lower in patients exhibiting both obesity and hyperuricemia. Conclusions: The optimal fertility-sparing treatment efficacy was observed at a BMI of 21–22 kg/m2 in EAH/EEC. Hyperuricemia was an independent risk factor for long-term treatment outcomes.
Selective Intra-Arterial Doxorubicin Eluting Microsphere Embolization for Desmoid Fibromatosis: A Combined Prospective and Retrospective Study
Authors: Elnekave Eldad , Ben Ami Eytan , Shamai Sivan , Peretz Idit , Tamir Shlomit , Bruckheimer Elchanan , Stemmer Amos , Erinjeri Joseph , Abu Quider Abed , Seidensticker Max , Wildgruber Moritz , Ricke Jens , Anazodo Antoinette , Fung Kin Fen , Zer Alona , Ash Shifra
Published: October 2022

Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16–34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1–4), with a median of 49 mg (range, 8–75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3–13), median tumor volumes decreased by 59% (interquartile range, 40–71%) and T2 signal intensity decreased by 36% (interquartile range, 19–55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3–4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.
An Expanded Interplay Network between NF-κB p65 (RelA) and E2F1 Transcription Factors: Roles in Physiology and Pathology
Authors: Foutadakis Spyros , Roupakia Eugenia , Liakopoulos Panagiotis , Kolovos Petros , Kolettas Evangelos
Published: October 2022

Transcription Factors (TFs) are the main regulators of gene expression, controlling among others cell homeostasis, identity, and fate. TFs may either act synergistically or antagonistically on nearby regulatory elements and their interplay may activate or repress gene expression. The family of NF-κB TFs is among the most important TFs in the regulation of inflammation, immunity, and stress-like responses, while they also control cell growth and survival, and are involved in inflammatory diseases and cancer. The family of E2F TFs are major regulators of cell cycle progression in most cell types. Several studies have suggested the interplay between these two TFs in the regulation of numerous genes controlling several biological processes. In the present study, we compared the genomic binding landscape of NF-κB RelA/p65 subunit and E2F1 TFs, based on high throughput ChIP-seq and RNA-seq data in different cell types. We confirmed that RelA/p65 has a binding profile with a high preference for distal enhancers bearing active chromatin marks which is distinct to that of E2F1, which mostly generates promoter-specific binding. Moreover, the RelA/p65 subunit and E2F1 cistromes have limited overlap and tend to bind chromatin that is in an active state even prior to immunogenic stimulation. Finally, we found that a fraction of the E2F1 cistrome is recruited by NF-κΒ near pro-inflammatory genes following LPS stimulation in immune cell types.
Quantum Dot-Based Screening Identifies F3 Peptide and Reveals Cell Surface Nucleolin as a Therapeutic Target for Rhabdomyosarcoma
Authors: Dzhumashev Dzhangar , Timpanaro Andrea , Ali Safa , De Micheli Andrea J. , Mamchaoui Kamel , Cascone Ilaria , Rössler Jochen , Bernasconi Michele
Published: October 2022

Active drug delivery by tumor-targeting peptides is a promising approach to improve existing therapies for rhabdomyosarcoma (RMS), by increasing the therapeutic effect and decreasing the systemic toxicity, e.g., by drug-loaded peptide-targeted nanoparticles. Here, we tested 20 different tumor-targeting peptides for their ability to bind to two RMS cell lines, Rh30 and RD, using quantum dots Streptavidin and biotin-peptides conjugates as a model for nanoparticles. Four peptides revealed a very strong binding to RMS cells: NCAM-1-targeting NTP peptide, nucleolin-targeting F3 peptide, and two Furin-targeting peptides, TmR and shTmR. F3 peptide showed the strongest binding to all RMS cell lines tested, low binding to normal control myoblasts and fibroblasts, and efficient internalization into RMS cells demonstrated by the cytoplasmic delivery of the Saporin toxin. The expression of the nucleophosphoprotein nucleolin, the target of F3, on the surface of RMS cell lines was validated by competition with the natural ligand lactoferrin, by colocalization with the nucleolin-binding aptamer AS1411, and by the marked sensitivity of RMS cell lines to the growth inhibitory nucleolin-binding N6L pseudopeptide. Taken together, our results indicate that nucleolin-targeting by F3 peptide represents a potential therapeutic approach for RMS.
Polyethylenimine, an Autophagy-Inducing Platinum-Carbene-Based Drug Carrier with Potent Toxicity towards Glioblastoma Cancer Stem Cells
Authors: McCartin Conor , Dussouillez Candice , Bernhard Chloé , Mathieu Eric , Blumberger Juliette , Dontenwill Monique , Herold-Mende Christel , Idbaih Ahmed , Lavalle Philippe , Bellemin-Laponnaz Stéphane , Kichler Antoine , Fournel Sylvie
Published: October 2022

The difficulty involved in the treatment of many tumours due to their recurrence and resistance to chemotherapy is tightly linked to the presence of cancer stem cells (CSCs). This CSC sub-population is distinct from the majority of cancer cells of the tumour bulk. Indeed, CSCs have increased mitochondrial mass that has been linked to increased sensitivity to mitochondrial targeting compounds. Thus, a platinum-based polyethylenimine (PEI) polymer–drug conjugate (PDC) was assessed as a potential anti-CSC therapeutic since it has previously displayed mitochondrial accumulation. Our results show that CSCs have increased specific sensitivity to the PEI carrier and to the PDC. The mechanism of cell death seems to be necrotic in nature, with an absence of apoptotic markers. Cell death is accompanied by the induction of a protective autophagy. The interference in the balance of this pathway, which is highly important for CSCs, may be responsible for a partial reversion of the stem-like phenotype observed with prolonged PEI and PDC treatment. Several markers also indicate the cell death mode to be capable of inducing an anti-cancer immune response. This study thus indicates the potential therapeutic perspectives of polycations against CSCs.
Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools
Authors: Papale Massimo , Netti Giuseppe Stefano , Stallone Giovanni , Ranieri Elena
Published: October 2022

One of the most dangerous aspects of cancer cell biology is their ability to grow, spread and form metastases in the main vital organs. The identification of dysregulated markers that drive intracellular signalling involved in the malignant transformation of neoplastic cells and the understanding of the mechanisms that regulate these processes is undoubtedly a key objective for the development of new and more targeted therapies. RAF-kinase inhibitor protein (RKIP) is an endogenous tumour suppressor protein that affects tumour cell survival, proliferation, and metastasis. RKIP might serve as an early tumour biomarker since it exhibits significantly different expression levels in various cancer histologies and it is often lost during metastatic progression. In this review, we discuss the specific impact of transcriptional, post-transcriptional and post-translational regulation of expression and activation/inhibition of RKIP and focus on those tumours for which experimental data on all these factors are available. In this way, we could select how these processes cooperate with RKIP expression in (1) Lung cancer; (2) Colon cancer, (3) Breast cancer; (4) myeloid neoplasm and Multiple Myeloma, (5) Melanoma and (6) clear cell Renal Cell Carcinoma. Furthermore, since RKIP seems to be a key marker of the development of several tumours and it may be assessed easily in various biological fluids, here we discuss the potential role of RKIP dosing in more accessible biological matrices other than tissues. Moreover, this objective may intercept the still unmet need to identify new and more accurate markers for the early diagnosis and prognosis of many tumours.
Hall Current and Soret Effects on Unsteady MHD Rotating Flow of Second-Grade Fluid through Porous Media under the Influences of Thermal Radiation and Chemical Reactions
Authors: Bafakeeh Omar T , Raghunath Kodi , Ali Farhan , Khalid Muhammad , Tag-ElDin El Sayed Mohamed , Oreijah Mowffaq , Guedri Kamel , Khedher Nidhal Ben , Khan Muhammad Ijaz
Published: October 2022

The unsteady MHD free convection heat and mass transfer flow of a viscous, incompressible, and electrically conducting fluid passing through a vertical plate embedded in a porous medium in the presence of chemical reactions and thermal radiation is investigated. The effects of the Hall current, rotation and Soret are studied. Using the perturbation approach, one can obtain an accurate analytical solution to the governing equations for the fluid velocity, fluid temperature, and species concentration, provided that the initial and boundary conditions are acceptable. It is possible to obtain expressions for the shear stress, rate of heat transfer, and rate of mass transfer for both plates with the ramping temperature and isothermal conditions. On the one hand, the numerical values of the primary and secondary fluid velocities, fluid temperature, and species concentration are presented graphically. On the other hand, the numerical values of the shear stress and rate of mass transfer for the plate are presented in tabular form for various values of the relevant flow parameters. These values are given for a range of pertinent flow parameters. It was determined that an increase in the Hall and Soret parameters over the whole fluid area leads to a corresponding increase in the resulting velocity. The resultant velocity continually climbs to a high level due to the contributions of the thermal and solute buoyancy forces. Lowering the heat source parameter reduces the temperature distribution, resulting in a lower overall temperature. When there is a rise in the chemical reaction parameter over the whole fluid area, there is a corresponding decrease in the concentration. The concentration buoyancy force, Hall current, and Prandtl number reduce the skin friction. On the other hand, the permeability of the porous medium, rotation, chemical reaction, the Soret number, thermal buoyancy force, and mass diffusion all have the opposite effects on the skin friction.
A Review on Photocatalytic Glass Ceramics: Fundamentals, Preparation, Performance Enhancement and Future Development
Authors: Wang Jun , Wang Mitang , Tian Yingliang , Deng Wei
Published: October 2022

Photocatalytic technology is considered as one of the most attractive and promising technologies to directly harvest, convert and store renewable solar energy for generating sustainable and green energy and a broad range of environmental applications. However, the use of a photocatalyst in powder or coating forms restricts its applications due to its disadvantages, such as difficulty in recovery of nano-powder, secondary pollution, low adhesion between photocatalytic coating and substrate material, short service life of photocatalytic film and so on. The investigation and application of photocatalytic glass-ceramics (PGCs) in water purification, bacterial disinfection, self-cleaning and hydrogen evolution have received extensive attention due to their inherent advantages of low cost, easy fabrication, transparency, chemical and mechanical stability. Real-time solutions to energy shortage and environmental pollution faced by the development of human society can be provided by rationally designing the chemical composition and preparation methods of glass ceramics (GCs). This review introduces the concept and crystallization mechanism of PGCs and expounds on the basic mechanism of photocatalysis. Then, the key point difficulties of GCs’ design are discussed, mainly including the methods of obtaining transparency and controlling crystallization technologies. Different modification strategies to achieve better photocatalytic activity are highlighted. Finally, we look forward to further in-depth exploration and research on more efficient PGCs suitable for various applications.
In Situ Formation of Z-Scheme Bi2WO6/WO3 Heterojunctions for Gas-Phase CO2 Photoreduction with H2O by Photohydrothermal Treatment
Authors: Zhang Zekai , Zhang Ding , Lyu Lin , Cui Guokai , Lu Hanfeng
Published: October 2022

We report a new photohydrothermal method to prepare a Bi2WO6/WO3 catalytic material for CO2 photoreduction by solar concentrators. The photohydrothermal treatment improves the physico-chemical properties of the Bi2WO6/WO3 material and forms well contact Bi2WO6/WO3 heterojunctions, which increase the maximum reaction rate of CO2 photoreduction to 8.2 times under the simulated light, and the hydrocarbon yield under the real concentrating solar light achieves thousands of μmol·gcata−1. The reason for the high activity is attributed to the direct Z-scheme effect of Bi2WO6/WO3 heterojunctions and the photothermal effect during the course. These findings highlight the utilization of solar energy in CO2 photoreduction and open avenues for the rational design of highly efficient photocatalysts.
Improving Photocatalytic Stille Coupling Reaction by CuPd Alloy-Doped Ordered Mesoporous TiO2
Authors: Tang Ting , Jin Lehong , Chai Wei , Shen Jing , Xu Zhenmin , Mao Haifang
Published: October 2022

Rational surface engineering of noble metal-doped photocatalysts is essential for the efficient conversion of solar energy into chemical energy, but it is still challenging to perform. Herein, we reported an effective strategy for structuring alloyed CuPd (CP) nanoclusters on the ordered mesoporous TiO2 (CPT) by a pore confinement effect. The resultant CPT exhibited an extraordinary photocatalytic activity during Stille reaction under visible light. The X-ray photoelectron spectroscopy spectra, the field emission scanning electron microscope (FESEM) images, and the aberration-corrected high-angle annular dark scanning transmission electron microscopy (HAADF-STEM) images demonstrated that CP nanoclusters were anchored in the mesoporous pore wall of TiO2, and the atomic ratio as well as densities of CP could be precisely modulated via the coordination configuration. As the atomic ratio of CP to TiO2 increased to a certain extent, their photocatalytic activity during Stille reaction increased. A mechanistic investigation suggested that the CP alloy could absorb visible light and its conduction electrons gained energy, which were available at the surface Pd sites. This allowed the Pd sites to become electron-rich and to accelerate the rate-determining step of the Stille reaction. As a result, the efficiency of the photocatalytic Stille coupling reaction was extraordinary enhanced.
Copper-on-Magnetically Activated Carbon-Catalyzed Azide-Alkyne Click Cycloaddition in Water
Authors: Aflak Noura , El Mouchtari El Mountassir , Ben El Ayouchia Hicham , Anane Hafid , Rafqah Salah , Julve Miguel , Stiriba Salah-Eddine
Published: October 2022

The copper-catalyzed cycloaddition of alkynes and azides (CuAAC) to give the corresponding 1,4-disubstituted-1,2,3-triazoles is the most successful and leading reaction within the click chemistry regime. Its heterogenization stands out as the innovative strategy to solve its environmental concerns and toxicity issue. In this report, magnetically retrievable activated carbon produced from biomass Persea Americana Nuts was loaded with a catalytically active copper(I) catalyst, resulting into a heterogeneous nanocatalyst, namely Cu-Fe3O4-PAC. This new compound was fully characterized using several techniques such as Powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray diffraction (EDX), Brunauer–Emmett–Teller (BET) analysis, and Raman spectroscopy. Cu-Fe3O4-PAC catalyzed the cycloaddition of a variety of substituted terminal alkynes and organic azides in water at room temperature with excellent yields and in a regioselective manner. The hot filtration test demonstrated that no significant leaching of catalytically active copper particles took place during the CuAAC process, a feature that supports the stability of Cu-Fe3O4-PAC and its heterogeneous action way. Cu-Fe3O4-PAC was magnetically separable by applying an external magnetic field and was recyclable up to five runs, with only an 8% decline in its activity after the 5th catalytic test. The hot filtration experiment heavily suggested that the present catalytic system would proceed in a heterogeneous manner in CuAAC. The electronic characteristics, nature of the intermediate complexes, and type of ligand-to-copper bonding interactions were studied by using quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) calculations, which enabled the confirmation of the proposed binuclear mechanism.
Targeted Inhibition of Matrix Metalloproteinase-8 Prevents Aortic Dissection in a Murine Model
Authors: Zhang Chengxin , Niu Kaiyuan , Ren Meixia , Zhou Xinmiao , Yang Zhisheng , Yang Mei , Wang Xinxin , Luo Jun , Shao Yue , Zhang Cheng , Chen Dan , Gao Shan , Ge Shenglin , Wu Qingchen , Xiao Qingzhong
Published: October 2022

Aortic dissection (AD) is a lethal aortic pathology without effective medical treatments since the underlying pathological mechanisms responsible for AD remain elusive. Matrix metalloproteinase-8 (MMP8) has been previously identified as a key player in atherosclerosis and arterial remodeling. However, the functional role of MMP8 in AD remains largely unknown. Here, we report that an increased level of MMP8 was observed in 3-aminopropionitrile fumarate (BAPN)-induced murine AD. AD incidence and aortic elastin fragmentation were markedly reduced in MMP8-knockout mice. Importantly, pharmacologic inhibition of MMP8 significantly reduced the AD incidence and aortic elastin fragmentation. We observed less inflammatory cell accumulation, a lower level of aortic inflammation, and decreased smooth muscle cell (SMC) apoptosis in MMP8-knockout mice. In line with our previous observation that MMP8 cleaves Ang I to generate Ang II, BAPN-treated MMP8-knockout mice had increased levels of Ang I, but decreased levels of Ang II and lower blood pressure. Additionally, we observed a decreased expression level of vascular cell adhesion molecule-1 (VCAM1) and a reduced level of reactive oxygen species (ROS) in MMP8-knockout aortas. Mechanistically, our data show that the Ang II/VCAM1 signal axis is responsible for MMP8-mediated inflammatory cell invasion and transendothelial migration, while MMP8-mediated SMC inflammation and apoptosis are attributed to Ang II/ROS signaling. Finally, we observed higher levels of aortic and serum MMP8 in patients with AD. We therefore provide new insights into the molecular mechanisms underlying AD and identify MMP8 as a potential therapeutic target for this life-threatening aortic disease.
Activity and Stability of Panx1 Channels in Astrocytes and Neuroblastoma Cells Are Enhanced by Cholesterol Depletion
Authors: Cibelli Antonio , Scemes Eliana , Spray David C.
Published: October 2022

Pannexin1 (Panx1) is expressed in both neurons and glia where it forms ATP-permeable channels that are activated under pathological conditions such as epilepsy, migraine, inflammation, and ischemia. Membrane lipid composition affects proper distribution and function of receptors and ion channels, and defects in cholesterol metabolism are associated with neurological diseases. In order to understand the impact of membrane cholesterol on the distribution and function of Panx1 in neural cells, we used fluorescence recovery after photobleaching (FRAP) to evaluate its mobility and electrophysiology and dye uptake to assess channel function. We observed that cholesterol extraction (using methyl-β-cyclodextrin) and inhibition of its synthesis (lovastatin) decreased the lateral diffusion of Panx1 in the plasma membrane. Panx1 channel activity (dye uptake, ATP release and ionic current) was enhanced in cholesterol-depleted Panx1 transfected cells and in wild-type astrocytes compared to non-depleted or Panx1 null cells. Manipulation of cholesterol levels may, therefore, offer a novel strategy by which Panx1 channel activation might modulate various pathological conditions.
Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer
Authors: Mariniello Annapaola , Tabbò Fabrizio , Indellicati Davide , Tesauro Martina , Rezmives Nicole Alessia , Reale Maria Lucia , Listì Angela , Capelletto Enrica , Carnio Simona , Bertaglia Valentina , Mecca Caterina , Consito Lorena , De Filippis Marco , Bungaro Maristella , Paratore Chiara , Di Maio Massimo , Passiglia Francesco , Righi Luisella , Sangiolo Dario , Novello Silvia , Geuna Massimo , Bironzo Paolo
Published: October 2022

Background: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB). Methods: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion. Results: Of 33 patients undergoing BAL and PB sampling, 21 had histologically-confirmed LC. Most cases were locally-advanced or metastatic non-small cell LC. T cell characteristics were not significantly different in t-BAL vs. cl-BAL. Compared to PB, CD8 T cells in BAL presented features of immune activation and exhaustion (high PD-1, low IFN-g production). Accordingly, regulatory CD4 T cells were also higher in BAL vs. PB. When dichotomizing T cell density in t-BAL in high and low, we found that PD-L1 expression in LC was associated with T cell density in t-BAL. T-BAL with high T cell density had higher %IFN-g+CD8 T cells and lower %T-regs. Conclusion: In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome.
Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis
Authors: Ren Sen , Chen Jing , Guo Jiahe , Liu Yutian , Xiong Hewei , Jing Boping , Yang Xiaofan , Li Gongchi , Kang Yu , Wang Cheng , Xu Xiang , Liu Zhenyu , Zhang Maojie , Xiang Kaituo , Li Chengcheng , Li Qianyun , Machens Hans-Günther , Chen Zhenbing
Published: October 2022

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.
Glutathione S-Transferases S1, Z1 and A1 Serve as Prognostic Factors in Glioblastoma and Promote Drug Resistance through Antioxidant Pathways
Authors: Cheng Bo , Wang Yu , Ayanlaja Abiola Abdulrahman , Zhu Jing , Kambey Piniel Alphayo , Qiu Ziqiang , Zhang Caiyi , Hu Wei
Published: October 2022

The glutathione S-transferase (GST) family of detoxification enzymes can regulate the malignant progression and drug resistance of various tumors. Hematopoietic prostaglandin D synthase (HPGDS, also referred to as GSTS1), GSTZ1, and GSTA1 are abnormally expressed in multiple cancers, but their roles in tumorigenesis and development remain unclear. In this study, we used bioinformatics tools to analyze the connections of HPGDS, GSTZ1, and GSTA1 to a variety of tumors in genetic databases. Then, we performed biochemical assays in GBM cell lines to investigate the involvement of HPGDS in proliferation and drug resistance. We found that HPGDS, GSTZ1, and GSTA1 are abnormally expressed in a variety of tumors and are associated with prognoses. The expression level of HPGDS was significantly positively correlated with the grade of glioma, and high levels of HPGDS predicted a poor prognosis. Inhibiting HPGDS significantly downregulated GBM proliferation and reduced resistance to temozolomide by disrupting the cellular redox balance and inhibiting the activation of JNK signaling. In conclusion, this study suggested that HPGDS, GSTZ1, and GSTA1 are related to the progression of multiple tumors, and HPGDS is expected to be a prognostic factor in GBM.
The Power of Gene Technologies: 1001 Ways to Create a Cell Model
Authors: Karagyaur Maxim , Primak Alexandra , Efimenko Anastasia , Skryabina Mariya , Tkachuk Vsevolod
Published: October 2022

Modern society faces many biomedical challenges that require urgent solutions. Two of the most important include the elucidation of mechanisms of socially significant diseases and the development of prospective drug treatments for these diseases. Experimental cell models are a convenient tool for addressing many of these problems. The power of cell models is further enhanced when combined with gene technologies, which allows the examination of even more subtle changes within the structure of the genome and permits testing of proteins in a native environment. The list and possibilities of these recently emerging technologies are truly colossal, which requires a rethink of a number of approaches for obtaining experimental cell models. In this review, we analyze the possibilities and limitations of promising gene technologies for obtaining cell models, and also give recommendations on the development and creation of relevant models. In our opinion, this review will be useful for novice cell biologists, as it provides some reference points in the rapidly growing universe of gene and cell technologies.
Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study
Authors: Schmitt Andrea , Tatsch Laura , Vollhardt Alisa , Schneider-Axmann Thomas , Raabe Florian J. , Roell Lukas , Heinsen Helmut , Hof Patrick R. , Falkai Peter , Schmitz Christoph
Published: October 2022

Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia.
Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis
Authors: Qian Benheng , Li Kexin , Lou Xiaoying , Guo Ye , Wang Yidong , Wu Lianpin , Zhang Donghong
Published: October 2022

Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE−/− mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS.
Melatonin and Indole-3-Acetic Acid Synergistically Regulate Plant Growth and Stress Resistance
Authors: Zhang Min , Gao Chunxue , Xu Ling , Niu Hui , Liu Qian , Huang Yixiao , Lv Guoshuai , Yang Hengshan , Li Minhui
Published: October 2022

Plant growth and development exhibit plasticity, and plants can adapt to environmental changes and stress. Various phytohormones interact synergistically or antagonistically to regulate these responses. Melatonin and indole-3-acetic acid (IAA) are widespread across plant kingdom. Melatonin, an important member of the neuroendocrine immune regulatory network, can confer autoimmunity and protect against viral invasion. Melatonin functions as a plant growth regulator and biostimulant, with an important role in enhancing plant stress tolerance. IAA has a highly complex stress response mechanism, which participates in a series of stress induced physiological changes. This article reviews studies on the signaling pathways of melatonin and IAA, focusing on specific regulatory mechanisms. We discuss how these hormones coordinate plant growth and development and stress responses. Furthermore, the interactions between melatonin and IAA and their upstream and downstream transcriptional regulation are discussed from the perspective of modulating plant development and stress adaptation. The reviewed studies suggest that, at low concentrations, melatonin promotes IAA synthesis, whereas at high levels it reduces IAA levels. Similarly to IAA, melatonin promotes plant growth and development. IAA suppresses the melatonin induced inhibition of germination. IAA signaling plays an important role in plant growth and development, whereas melatonin signaling plays an important role in stress responses.
Naturally Occurring Bicoumarin Compound Daphnoretin Inhibits Growth and Induces Megakaryocytic Differentiation in Human Chronic Myeloid Leukemia Cells
Authors: Huang Yu-Chuen , Huang Chun-Ping , Lin Chin-Ping , Yang Kai-Chien , Lei Yu-Jie , Wang Hao-Pei , Kuo Yueh-Hsiung , Chen Yu-Jen
Published: October 2022

Daphnoretin extracted from the stem and roots of Wikstroemia indica (L.) C.A. Mey has been shown to possess antiviral and antitumor activities. Herein, we hypothesized that daphnoretin might induce megakaryocytic differentiation, thereby inhibiting the proliferation of cells and serving as a differentiation therapy agent for chronic myeloid leukemia (CML). Daphnoretin-treated K562 and HEL cells were examined for growth inhibition, cell morphology, and megakaryocyte-specific markers. Potential mechanisms of megakaryocytic differentiation of daphnoretin-treated K562 cells were evaluated. The results showed that daphnoretin inhibited the growth of K562 and HEL cells in a dose- and time-dependent manner. Flow cytometry analyses revealed that daphnoretin treatment slightly increased the proportion of sub-G1 and polyploid cells compared to that of dimethyl sulfoxide (DMSO)-treated control cells. Morphological examination showed that daphnoretin-treated K562 and HEL cells exhibited enlarged contours and multinucleation as megakaryocytic characteristics compared to DMSO-treated control cells. Daphnoretin treatment also dramatically enhanced the expression of megakaryocytic markers CD61 and CD41. Under optimal megakaryocytic differentiation conditions, daphnoretin increased the phosphorylation of STAT3 but not STAT5. In summary, daphnoretin inhibited cell growth and induced megakaryocytic differentiation in K562 and HEL cells. The efficacy of daphnoretin in vivo and in patients with CML may need further investigations for validation.
Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience
Authors: Li Zengyan , Wu Zhiming , Dong Youhong , Zhang Dongdong
Published: October 2022

Objective: Embryonal tumors with multilayered rosettes (ETMRs) are highly aggressive pediatric brain tumors with poor prognosis. No standard treatment strategy for them exists because of their rarity. This study aimed to share experiences on the clinical diagnosis and treatment of ETMRs at China Children’s Medical Center (CCMC). Methods: Patients who received a diagnosis of an ETMR between January 2017 and June 2020 were included. Clinical characteristics, such as age of onset, tumor size, stage, tumor site, treatment strategy, and clinical outcome, were retrospectively analyzed. Results: There were four boys and one girl within 4 years who received a diagnosis during this 4-year timeframe, and were thus included. The average age of morbidity was 29 months (range 16–66 months). The common clinical presentation was headaches and nausea caused by intracranial hypertension. All four patients were chromosome 19 microRNA cluster (C19MC) amplification positive. Two patients achieved complete remission, and one patient attained partial remission after multimodal treatment. Of the two deaths, one died from the rapid progression of the disease and another from tumor-related complications. Conclusion: ETMRs are extremely rare brain tumors with a high, early mortality in children. Surgery is the mainstream treatment for ETMRs. Some patients may also benefit from postoperative adjuvant chemotherapy and radiotherapy.