bluuebunny/crossref_metadata_2025 huggingface dataset:
Microclimate Optimization of School Campus Landscape Based on Comfort Assessment
Authors: Sun Bo , Zhang Hong , Zhao Liang , Qu Kaichen , Liu Wenhui , Zhuang Zhicheng , Ye Hongyu
Published: September 2022

The outdoor wind environment and thermal environment are important factors affecting human comfort in cold winter conditions. The spatial layout of plant communities plays an important role in improving the outdoor microclimate and improving outdoor comfort. In order to explore the positive effect of plant layout on outdoor comfort in cold winter, this study took Xuzhou Tangfang Middle School with typical layout characteristics as the research object. In this study, we simulated the wind environment of these models using computational fluid dynamics (CFD) methods and the outdoor thermal environment using Ecotect (2011), and used linear regression and one-way ANOVA for mathematical statistics. The wind environment and Universal Thermal Climate Index (UTCI) of campus outdoor activities distributed in different spaces were analyzed and evaluated. The research results showed that the superposition of wind and thermal environments identified the key areas of the campus (cross-flow area and corner flow area) and showed a negative correlation. The staggered layout of the three plant combinations increases the wind prevention efficiency by 39.4%. At the same time, this study established the linkage mechanism of campus plant layout, environmental microclimate, and activity area comfort, which effectively improved outdoor human comfort in cold winter. This research can provide a reference for the remediation and improvement of the comfort of the same type of campus, and also provide data support and reference significance for the research on the outdoor pedestrian environment in winter.
Experimental Study on Wind Loading Characteristics of Trains under Stationary Tornado-like Vortices
Authors: Li Peng , Li Bo , Han Xiaoyu , Tian Yuji , Li Ruoqi
Published: September 2022

The risk of trains being hit by tornadoes in China continues to increase due to the increasing density of railway lines and the shortening of the train departure intervals and the increasing probability of extreme weather phenomena caused by global climate change. If a train is hit by a tornado, it will cause huge casualties and economic losses, so it is necessary to investigate the tornado-induced effects on trains. A series of rigid-model wind pressure measurement tests on a train car under tornado wind loading were conducted using a tornado-vortex simulator, in order to determine the effects of the distance between the train car and the tornado’s center, the swirl ratio of a tornado-like vortex, and the ground roughness on the wind pressure distributions and wind load characteristics on trains. Apparent discrepancies were observed between tornado-induced wind loading and lateral wind loading obtained from conventional boundary-layer wind tunnel tests. The wind pressure and wind load on the car surface are mainly affected by the combined effects of the aerodynamic flow-structure interaction and the pressure drop accompanying the tornado within 1.5 times the vortex core’s radius, and the impact of tornado-like vortices on the train car is almost negligible as the distance from the train car to the tornado’s center exceeds three times vortex core’s radius. The variation trend of mean/fluctuating pressure coefficients is generally consistent. Large values of fluctuating pressure exist mainly on the top and side surfaces of the train car, especially the side surface proximal to the tornado’s center. The most unfavorable mean sectional side force coefficients were found when the train car is located in the tornado’s core and the largest lift force coefficients at the tornado’s center. The overall side force coefficients peaked when the train car is located at a distance of 1.5 times the tornado’s core radius, whereas the largest lift force coefficients were found when the train car was located at the tornado’s center. The overall distribution patterns of the wind force coefficients of the car under different swirl ratios and ground roughness levels are basically the same. The peak aerodynamic force value increases with increasing swirl ratio, and it decreases as ground roughness increases.
Numerical Investigations on Axial Compressive Behavior of Opening Cold-Formed Thin-Wall C-Steel Combined Double-Limb Column
Authors: He Chang , Cai Yong , Chen Haijun
Published: September 2022

To investigate the axial compressive behavior of an opening cold-formed thin-wall C-steel combined double-limb column, C-steel combined I-section columns were modeled in this paper, and the models were validated by experiments on axial-compressed combined columns. Parametric analyses were carried out on the combined columns. The effects of slenderness ratio, height to thickness ratio, width to thickness ratio, bolt spacing, and opening in the web on the ultimate compressive bearing capacity of the combined columns were investigated. It was observed that the slenderness ratio had the most significant effects on the combined column. Furthermore, the formulas predicting the compressive bearing capacity in the Chinese and AISI standards were compared, and the accuracy of the formulas was studied. Afterward, the formulas with higher accuracy and applicability for the ultimate compressive bearing capacity for the C-steel combined I-section column were proposed. The compression stability factor and reduction factor were fitted in this paper. The proposed formulas and factors can predict the ultimate compressive bearing capacity of the C-steel combined I-section column.
Axial and Shear Behavior of Prestressed Damping Isolation Units Using a Spring and Rubbers
Authors: Yang Keun-Hyeok , Mun Ju-Hyun , Im Chae-Rim
Published: September 2022

This study investigated the axial and shear behaviors of a seismic damping isolation unit (SDI) developed to improve the seismic resistance of suspended ceiling structures. To enhance the energy dissipation of the SDI, it was composed of a spring, embossed rubbers, and prestressed bolts. Twelve specimens were prepared and tested for failure under axial and shear loading. The main parameters were the presence or absence of a spring, loading type, and magnitude of the prestressed force introduced to the bolts to connect the embossed rubbers. The test results showed that in the relationship of axial or shear load–displacement of the SDI, the post-peak behavior tended to be more ductile for specimens with a spring or higher prestressed force magnitude. Consequently, the ductility ratio and equivalent damping coefficient of the SDI with the spring and 0.1fby were 3.81 and 0.166, which was 1.06 and 1.20 times higher than the specimens without spring and prestressed force. In addition, the ductility ratio was approximately 1.07 times higher for the SDI specimens subjected to monotonic loading than for those subjected to cyclic loading. Meanwhile, the JIS B 2704−1 and AISC specifications estimated the tensile strength of the SDI specimens subjected to monotonic loading well, but overestimated that of the specimens subjected to cyclic loading. Hence, the JIS B 2704−1 and AISC specifications should be underestimated by 15.7% and 81.7%, respectively, when estimating the tensile and shear loads of the SDI subjected to cyclic loading.
Bone Health Management in the Continuum of Prostate Cancer Disease
Authors: Boopathi Ettickan , Birbe Ruth , Shoyele Sunday A. , Den Robert B. , Thangavel Chellappagounder
Published: September 2022

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year survival rate for these patients is 47%. Bone-metastasis-induced early changes in the bone that proceed the osteoblastic response in the bone matrix are monitored and detected via modern magnetic resonance and PET/CT imaging technologies. Various treatment options, such as targeting osteolytic metastasis with bisphosphonates, prednisone, dexamethasone, denosumab, immunotherapy, external beam radiation therapy, radiopharmaceuticals, surgery, and pain medications are employed to treat prostate-cancer-induced bone metastasis and manage bone health. However, these diagnostics and treatment options are not very accurate nor efficient enough to treat bone metastases and manage bone health. In this review, we present the pathogenesis of PCa-induced bone metastasis, its deleterious impacts on vital organs, the impact of metastatic PCa on bone health, treatment interventions for bone metastasis and management of bone- and skeletal-related events, and possible current and future therapeutic options for bone management in the continuum of prostate cancer disease.
Exploratory Circular RNA Profiling in Adrenocortical Tumors
Authors: Turai Péter István , Nyirő Gábor , Borka Katalin , Micsik Tamás , Likó István , Patócs Attila , Igaz Peter
Published: September 2022

Differentiation of adrenocortical adenoma (ACA) and carcinoma (ACC) is often challenging even in the histological analysis. Circular RNAs (circRNAs) belonging to the group of non-coding RNAs have been implicated as relevant factors in tumorigenesis. Our aim was to explore circRNA expression profiles in adrenocortical tumors by next-generation sequencing followed by RT-qPCR validation. Archived FFPE (formalin-fixed, paraffin embedded) including 8 ACC, 8 ACA and 8 normal adrenal cortices (NAC) were used in the discovery cohort. For de novo and known circRNA expression profiling, a next-generation sequencing platform was used. CIRI2, CircExplorer2, AutoCirc bioinformatics tools were used for the discovery of circRNAs. The top five most differentially circRNAs were measured by RT-qPCR in an independent validation cohort (10 ACC, 8 ACA, 8 NAC). In silico predicted, interacting microRNAs potentially sponged by differentially expressed circRNAs were studied by individual RT-qPCR assays. We focused on overexpressed circRNAs here. Significantly differentially expressed circRNAs have been revealed between the cohorts by NGS. Only circPHC3 could be confirmed to be significantly overexpressed in ACC, ACA vs. NAC samples by RT-qPCR. We could not observe microRNA expression changes fully corresponding to our sponging hypothesis. To the best of our knowledge, our study is the first to investigate circRNAs in adrenocortical tumors. Further studies are warranted to explore their biological and diagnostic relevance.
Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade
Authors: Marcus Rebecca , Christopher Wade , Keller Jennifer , Nassoiy Sean , Chang Shu-Ching , Goldfarb Melanie , Wolf Ronald , Jutric Zeljka
Published: September 2022

Limited evidence-based management guidelines for resectable intrahepatic cholangiocarcinoma (ICC) currently exist. Using a large population-based cancer registry; the utilization rates and outcomes for patients with clinical stages I-III ICC treated with neoadjuvant chemotherapy (NAT) in relation to other treatment strategies were investigated, as were the predictors of treatment regimen utilization. Oncologic outcomes were compared between treatment strategies. Amongst 2736 patients, chemotherapy utilization was low; however, NAT use increased from 4.3% to 7.2% (p = 0.011) over the study period. A higher clinical stage was predictive of the use of NAT, while higher pathologic stage and margin-positive resections were predictive of the use of adjuvant therapy (AT). For patients with more advanced disease, the receipt of NAT or AT was associated with significantly improved survival compared to surgery alone (cStage II, p = 0.040; cStage III, p = 0.003). Furthermore, patients receiving NAT were more likely to undergo margin-negative resections compared to those treated with AT (72.5% vs. 62.6%, p = 0.027), despite having higher-risk tumors. This analysis of treatment strategies for resectable ICC suggests a benefit for systemic therapy. Prospective and randomized studies evaluating the sequencing of treatments for patients with high-risk resectable ICC are needed.
The Role of HPV in Determining Treatment, Survival, and Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Sharkey Ochoa Imogen , O’Regan Esther , Toner Mary , Kay Elaine , Faul Peter , O’Keane Connor , O’Connor Roisin , Mullen Dorinda , Nur Mataz , O’Murchu Eamon , Barry-O’Crowley Jacqui , Kernan Niamh , Tewari Prerna , Keegan Helen , O’Toole Sharon , Woods Robbie , Kennedy Susan , Feeley Kenneth , Sharp Linda , Gheit Tarik , Tommasino Massimo , O’Leary John J. , Martin Cara M.
Published: September 2022

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV’s involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV’s impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.
Impact of COVID-19 Pandemic on Thyroid Surgery in a University Hospital in South Korea
Authors: Kim Seong Hoon , Min Euna , Hwang Young Mi , Choi Yun Suk , Yi Jin Wook
Published: September 2022

The COVID-19 pandemic has changed healthcare systems around the world. Medical personnel concentrated on infectious disease management and treatments for non-emergency diseases and scheduled surgeries were delayed. We aimed to investigate the change in the severity of thyroid cancer before and after the outbreak of COVID-19 in Korea. We collected three years of data (2019, 2020, and 2021) on patients who received thyroid surgery in a university hospital in South Korea and grouped them as “Before COVID-19”, “After COVID-19 1-year” and “After COVID-19 2-years”. The total number of annual outpatients declined significantly after the outbreak of COVID-19 in both new (1303, 939, and 1098 patients) and follow-up patients (5584, 4609, and 4739 patients). Clinical characteristics, including age, sex, BMI, preoperative cytology results, surgical extent, and final pathologic diagnosis, were not significantly changed after the outbreak of COVID-19. However, the number of days from the first visit to surgery was significantly increased (38.3 ± 32.2, 58.3 ± 105.2, 47.8 ± 124.7 days, p = 0.027). Papillary thyroid carcinoma (PTC) patients showed increased proportions of extrathyroidal extension, lymphatic invasion, vascular invasion, and cervical lymph node metastasis. Increased tumor size was observed in patients with follicular tumor (3.5 ± 2.2, 4.0 ± 1.9, 4.3 ± 2.3 cm, p = 0.019). After the COVID-19 outbreak, poor prognostic factors for thyroid cancer increased, and an increase in the size of follicular tumors was observed. Due to our study being confined to a single tertiary institution in Incheon city, Korea, nationwide studies that include primary clinics should be required to identify the actual impact of COVID-19 on thyroid disease treatment.
Electrochemotherapy: An Alternative Strategy for Improving Therapy in Drug-Resistant SOLID Tumors
Authors: Condello Maria , D’Avack Gloria , Spugnini Enrico Pierluigi , Meschini Stefania
Published: September 2022

Electrochemotherapy (ECT) is one of the innovative strategies to overcome the multi drug resistance (MDR) that often occurs in cancer. Resistance to anticancer drugs results from a variety of factors, such as genetic or epigenetic changes, an up-regulated outflow of drugs, and various cellular and molecular mechanisms. This technology combines the administration of chemotherapy with the application of electrical pulses, with waveforms capable of increasing drug uptake in a non-toxic and well tolerated mechanical system. ECT is used as a first-line adjuvant therapy in veterinary oncology, where it improves the efficacy of many chemotherapeutic agents by increasing their uptake into cancer cells. The chemotherapeutic agents that have been enhanced by this technique are bleomycin, cisplatin, mitomycin C, and 5-fluorouracil. After their use, a better localized control of the neoplasm has been observed. In humans, the use of ECT was initially limited to local palliative therapy for cutaneous metastases of melanoma, but phase I/II studies are currently ongoing for several histotypes of cancer, with promising results. In this review, we described the preclinical and clinical use of ECT on drug-resistant solid tumors, such as head and neck squamous cell carcinoma, breast cancer, gynecological cancer and, finally, colorectal cancer.
Enzymes and Biocatalysis
Authors: Kuo Chia-Hung , Huang Chun-Yung , Shieh Chwen-Jen , Dong Cheng-Di
Published: September 2022

Enzymes, also known as biocatalysts, are proteins produced by living cells and found in a wide range of species, including animals, plants, and microorganisms [...]
Kinetics and Mechanisms of Cr(VI) Removal by nZVI: Influencing Parameters and Modification
Authors: Gao Yizan , Yang Xiaodan , Lu Xinwei , Li Minrui , Wang Lijun , Wang Yuru
Published: September 2022

In this study, single-spherical nanoscale zero valent iron (nZVI) particles with large specific sur-face area were successfully synthesized by a simple and rapid chemical reduction method. The XRD spectra and SEM–EDS images showed that the synthesized nZVI had excellent crystal struc-ture, but oxidation products, such as γ-Fe2O3 and Fe3O4, were formed on the surface of the parti-cles. The effect of different factors on the removal of Cr(VI) by nZVI were studied, and the opti-mum experimental conditions were found. Kinetic and thermodynamic equations at different temperatures showed that the removal of Cr(VI) by nZVI was a single-layer chemical adsorption, conforming to pseudo-second-order kinetics. By applying the intraparticle diffusion model, the ad-sorption process was composed of three stages, namely rapid diffusion, chemical reduction, and in-ternal saturation. Mechanism analysis demonstrated that the removal of Cr(VI) by nZVI in-volved adsorption, reduction, precipitation and coprecipitation. Meanwhile, Cr(VI) was reduced to Cr(III) by nZVI, while FeCr2O4, CrxFe1−xOOH, and CrxFe1−x(OH)3 were formed as end products. In addition, the study found that ascorbic acid, starch, and Cu modified nZVI can promote the removal efficiency of Cr(VI) in varying degrees due to the enhanced mobility of the particles. These results can provide new insights into the removal mechanisms of Cr(VI) by nZVI.
Effect of Biogenic Silica Behavior in the Incorporation of Mesoporous Anatase TiO2 for Excellent Photocatalytic Mineralization of Sodium Diclofenac
Authors: Dantio Nguela Christian Brice , Manga Ngomo Horace , Marchal Clément , Abega Aimé Victoire , Nsami Ndi Julius , Robert Didier
Published: September 2022

TiO2/SiO2 composites were synthesized via a simple sol gel method by surface reduction of Ti4+ ions to Ti3+ using titanium isopropoxide as a TiO2 precursor and rice husks (RHA) as a SiO2 source. The silica content and calcination temperature of the materials were evaluated. Thermal, crystallographic and physicochemical aspects suggest that biogenic silica (SiO2) can improve the thermal stability of the anatase phase of TiO2, when the SiO2 content reaches 20%. The N2 adsorption-desorption isotherms showed that the SiO2-modified samples have uniform pore diameters and a large specific surface area. The XPS analysis showed the surface reduction of Ti4+ ions to Ti3+ within the TiO2 network via oxygen vacancies after SiO2 introduction, which is beneficial for the photocatalytic reaction. Photocatalytic degradation of sodium diclofenac (SDFC) shows that TiO2/SiO2 composites have better activity compared to commercial P25. Mesoporous TiO2 composite modified with 20 wt% SiO2 showed better photocatalytic mineralization than P25 (83.7% after 2 h instead of 57.3% for P25). The excellent photocatalytic mineralization of the photocatalysts can be attributed to the high anatase crystallinity exhibited by XRD analysis, high specific surface area, surface hydroxyl groups, and the creation of oxygen vacancy, as well as the presence of Ti3+ ions.
Functional Intercellular Transmission of miHTT via Extracellular Vesicles: An In Vitro Proof-of-Mechanism Study
Authors: Morais Roberto D. V. S. , Sogorb-González Marina , Bar Citlali , Timmer Nikki C. , Van der Bent M. Leontien , Wartel Morgane , Vallès Astrid
Published: September 2022

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by GAG expansion in exon 1 of the huntingtin (HTT) gene. AAV5-miHTT is an adeno-associated virus serotype 5-based vector expressing an engineered HTT-targeting microRNA (miHTT). Preclinical studies demonstrate the brain-wide spread of AAV5-miHTT following a single intrastriatal injection, which is partly mediated by neuronal transport. miHTT has been previously associated with extracellular vesicles (EVs), but whether EVs mediate the intercellular transmission of miHTT remains unknown. A contactless culture system was used to evaluate the transport of miHTT, either from a donor cell line overexpressing miHTT or AAV5-miHTT transduced neurons. Transfer of miHTT to recipient (HEK-293T, HeLa, and HD patient-derived neurons) cells was observed, which significantly reduced HTT mRNA levels. miHTT was present in EV-enriched fractions isolated from culture media. Immunocytochemical and in situ hybridization experiments showed that the signal for miHTT and EV markers co-localized, confirming the transport of miHTT within EVs. In summary, we provide evidence that an engineered miRNA—miHTT—is loaded into EVs, transported across extracellular space, and taken up by neighboring cells, and importantly, that miHTT is active in recipient cells downregulating HTT expression. This represents an additional mechanism contributing to the widespread biodistribution of AAV5-miHTT.
Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction
Authors: Chang Wei-Ting , Lin Yu-Wen , Chen Chin-Yu , Chen Zhih-Cherng , Shih Jhih-Yuan , Wu Chia-Ching , Luo Chwan-Yau , Liu Ping-Yen
Published: September 2022

Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function—especially when strained—and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.
Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation
Authors: Petrushanko Irina Yu. , Tverskoi Artem M. , Barykin Evgeny P. , Petrovskaya Aleksandra V. , Strelkova Maria A. , Leonova Olga G. , Anashkina Anastasia A. , Tolstova Anna P. , Adzhubei Alexei A. , Bogdanova Anna Yu. , Makarov Alexander A. , Mitkevich Vladimir A.
Published: September 2022

Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer’s disease and as a regulator in brain physiology. The inhibitory effect of Aβ42 oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the monomeric form of Aβ42 interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ42 monomer, triggering Src kinase activation. The co-localization of Aβ42 with α1- and β1-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM Aβ42 causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ42 with α1β1 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the Aβ-induced Src kinase activation. Stimulatory effect of Aβ42 on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a Aβ42 receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ42 in the nervous system.
Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound
Authors: Tomas-Grau Rodrigo , González-Lizárraga Florencia , Ploper Diego , Avila César L. , Socías Sergio B. , Besnault Pierre , Tourville Aurore , Mella Rosa M. , Villacé Patricia , Salado Clarisa , Rose Clémence , Seon-Méniel Blandine , Brunel Jean-Michel , Ferrié Laurent , Raisman-Vozari Rita , Michel Patrick P. , Figadère Bruno , Chehín Rosana
Published: September 2022

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects. The molecule was obtained by removal the dimethylamino substituent at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF) in biophysical assays and in a SH-SY5Y-α-Syn-tRFP cell model. In addition, DDMC rendered α-SynPFF less inflammogenic. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in Parkinson’s disease and other synucleinopathies.
Pharmacological Inhibition of S100A4 Attenuates Fibroblast Activation and Renal Fibrosis
Authors: Wen Jia , Jiao Baihai , Tran Melanie , Wang Yanlin
Published: September 2022

The TGF-β/Smad3 signaling pathway is an important process in the pathogenesis of kidney fibrosis. However, the molecular mechanisms are not completely elucidated. The current study examined the functional role of S100A4 in regulating TGF-β/Smad3 signaling in fibroblast activation and kidney fibrosis development. S100A4 was upregulated in the kidney in a murine model of renal fibrosis induced by folic acid nephropathy. Further, S100A4 was predominant in the tubulointerstitial cells of the kidney. Pharmacological inhibition of S100A4 with niclosamide significantly attenuated fibroblast activation, decreased collagen content, and reduced extracellular matrix protein expression in folic acid nephropathy. Overexpression of S100A4 in cultured renal fibroblasts significantly facilitated TGF-β1-induced activation of fibroblasts by increasing the expression of α-SMA, collagen-1 and fibronectin. In contrast, S100A4 knockdown prevented TGF-β1-induced activation of fibroblast and transcriptional activity of Smad3. Mechanistically, S100A4 interacts with Smad3 to stabilize the Smad3/Smad4 complex and promotes their translocation to the nucleus. In conclusion, S100A4 facilitates TGF-β signaling via interaction with Smad3 and promotes kidney fibrosis development. Manipulating S100A4 may provide a beneficial therapeutic strategy for chronic kidney disease.
Self-Direction in Physics Graduate Education: Insights for STEM from David J. Rowe’s Career-Long Methods
Authors: Nash Carol
Published: September 2022

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of science, technology, engineering, and mathematics (STEM) graduate programs assumes students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning (SDL) as key. This essay explores SDL for STEM, presenting the work of theoretical nuclear physicist David J. Rowe as a key example of applying a process of SDL in practice. Rowe focused on this challenge of physics graduate education by promoting SDL through the type of research flow that has been found to bring the greatest satisfaction to researchers regarding their insights. Strategies he explored involved his space, time, open mindedness and theoretical contributions with students and in collaboration with colleagues. A self-directed learner himself, Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. These strategies for supporting SDL in this context are examined here, with the use of narrative research to interpret the texts and conversations exchanged with the author. The process of SDL developed by Rowe is presented with recommendations on how Rowe’s methods may be modeled to improve self-direction in STEM graduate education more widely.
Remote Learning Experience and Adolescents’ Well-Being during the COVID-19 Pandemic: What Does the Future Hold?
Authors: Tesler Riki
Published: September 2022

Background. Major shifts within the education system have taken place during the COVID-19 pandemic; frontal teaching was often replaced with remote learning, which has affected students in many ways. We investigated the associations and predictors of perceptions of the remote learning experience on well-being (life satisfaction, self-rated health, psychosomatic, and psychological symptoms). Methods. We conducted a cross-sectional research study consisting of 1019 school students in Israel aged 11–18 (53.5% girls, 46.7% boys). Questionnaires were distributed from May–July 2021 during school time. The percentages of participants with various levels of well-being (WB) and remote learning experience were compared. Multiple regression procedures were used to analyze factors predicting wellbeing. Results. All of the remote learning items had statistically significant positive correlations with life satisfaction and self-rated health (i.e., better overall WB was associated with a more positive perception of the remote learning experience). Male gender, high socioeconomic status, greater involvement in lessons in the past year, and connection to the pedagogical team/school and peers predicted better overall WB (F-ratio = 14.03; p < 0.01; adjusted R2 = 0.08). Conclusions. Our results highlight the need for schools to target youths’ coping skills, which may lead to better remote learning experiences. These findings also provide several implications for the need to support children and adolescents through positive activities, relaxation/mindfulness, and cognitive coping to deal with the psychosomatic symptoms during remote learning periods.
COVID-19 and PIMS—Two Different Entities, but the Same Trigger
Authors: Meliț Lorena Elena , Mărginean Cristina Oana , Fleșeriu Tudor , Văsieșiu Anca Meda , Ghiga Dana Valentina , Koller Ana-Maria Roxana
Published: September 2022

COVID-19 and PIMS represent two novel pathologies that have challenged the medical world during the last two years on account of their being very similar, but yet very different. Our aim was to comparatively assess children with SARS-CoV-2 infection and PIMS in terms of symptoms, clinical findings, laboratory parameters, echocardiography, and evolution. Our retrospective study included 46 children with COVID-19 (group 1), and 20 children with confirmed PIMS (group 2). We found no significant differences in terms of age, gender, and originating area between the two groups. We noticed that fever was significantly more common in the PIMS group as compared to COVID-19 group (p = 0.0217). In terms of laboratory parameters, increased bilirubin and creatinine were significantly more frequent in children with COVID-19 (p = 0.0064/p = 0.0064), while hypoalbuminemia and elevated ESR were significantly more common in those with PIMS (p < 0.0001/p = 0.0127). Moreover, prognosis parameters such as D-dimers, NT-proBNP, and CK-MB were also found to be significantly higher in the PIMS group as compared to COVID-19 group (p = 0.0003/p = 0.0182/p = 0.0007). In terms of complications, most were identified in PIMS group, among which cardiac and liver impairment along with dehydration were significantly more common in children diagnosed with PIMS as compared to those detected with COVID-19. Similarly, children with PIMS had a significantly higher chance to have pathological echocardiography changes. Although difficult, the distinction between COVID-19 and PIMS is crucial for the patient’s long-term outcome.
Perceived Difficulties in Physical Tasks and Physical Fitness in Treatment- and Non-Treatment-Seeking Youths with Obesity
Authors: Ballarin Giada , Licenziati Maria Rosaria , Di Vincenzo Olivia , Scalfi Luca , Valerio Giuliana
Published: September 2022

Youths with obesity are more likely to experience physical and psychosocial distress which strongly limits physical activity, with consequences on the quality of life. Most evidence of lower physical fitness and physical activity levels has been reported in treatment-seeking samples, while few data are available in community samples. Our aim was to assess whether perceived difficulties in physical tasks and physical fitness performance differed between treatment- and non-treatment-seeking youths with obesity, enrolled from a hospital (H) and a school (S). Three hundred fifty-one youths (269 from H and 82 from S) were enrolled. Sports participation, sedentary habits and perceived difficulties in physical tasks were assessed by interview. Six-minute walk test (SMWD) and long jump (LJ) were performed. BMI Z-score, sedentary time and perceived difficulties were higher in H vs. S. In addition, youths from H scored worse in SMWD and LJ. For the same BMI Z-score, the perceived difficulties and physical fitness were poorer in the H compared to the S group. The setting (H) was the stronger predictor of perceived difficulties and lower performance. Our findings underline that physical aspects imposed by obesity are more evident in treatment-seeking youths. Counseling related to perceived difficulties in physical tasks and performance is useful to treat youth with obesity with appropriate and personalized modalities.
Production and Characterization of Biochar from Almond Shells
Authors: El Mashad Hamed M. , Edalati Abdolhossein , Zhang Ruihong , Jenkins Bryan M.
Published: September 2022

Biomass from specialty crops, including almonds, walnuts, and numerous others, serves as an important resource for energy and materials as agricultural systems evolve towards greater sustainability and circularity in management and operations. Biochar was produced from almond shells in a laboratory furnace at temperatures between 300 and 750 °C for residence times of 30 and 90 min with moisture contents of 5% to 15% wet basis. Response surface methodology was used to optimize the biochar yield. Feedstock and product temperatures were continuously monitored throughout the experiments. In addition, larger batches of biochar were also produced in a fixed-bed pilot-scale pyrolyzer. The yield of biochar was determined as a weight fraction of the amount of oven-dry almond shells used in each experiment. Physical and chemical characteristics of biochars were evaluated. Pyrolysis temperature and time were found to be the significant parameters affecting the biochar yield, with second-order regression models derived to fit yield results. As anticipated, highest biochar yields (65%) were obtained at a pyrolysis temperature of 300 °C and a pyrolysis time of 30 min due to the limited volatilization at this short residence at low temperature affecting torrefaction of the feedstock. The average biochar yield from the fixed-bed pilot-scale experiments was 39.5% and more closely aligned with the fixed carbon from standard proximate analyses. Higher pyrolysis temperatures resulted in higher C:N ratio and pH with the highest C:N ratio of 19:1 and pH of 10.0 obtained at a pyrolysis temperature of 750 °C for 90 min. Particle density increased with the increase of pyrolysis temperature. Results of this study can aid in predicting biochar yields from almond shells under different pyrolysis conditions and determining the amount of biochar required for different applications.
Functional Coatings and Surface Modifications in Cement–Matrix Composites
Authors: Sambucci Matteo , Valente Marco
Published: September 2022

The construction sector is one of the most active fields in the experimentation and research into new materials and applications capable of responding to the current needs for efficiency, energy saving, and eco-sustainability [...]
Effect of Urea–Formaldehyde Resin–Coated Colour–Change Powder Microcapsules on Performance of Waterborne Coatings for Wood Surfaces
Authors: Ding Tingting , Yan Xiaoxing , Zhao Wenting
Published: September 2022

Microcapsules have received a great deal of attention from researchers due to their excellent properties, and are commonly prepared by interfacial and in situ polymerisation methods. In situ polymerisation is an important method of microcapsule preparation, which has a number of advantages such as low cost and suitability for industrial production. Microencapsulation is used to modify the state of the material in order to improve its practical usability and mechanical and optical properties. In this paper, urea–formaldehyde resin–coated colour–changing powder microcapsules were prepared and their properties were used to study the colour–changing properties of wood surface coatings, and the mechanical and optical properties of waterborne paint films incorporating colour–changing powder microcapsules were tested. The results show that as the microcapsule content increases, the colour–change effect of the coating gradually becomes obvious and the amount of change in the b–value representing the yellow hue gradually increases. As the microcapsule content increased from 1.0% to 13.0%, the b–value increased from 0.7 to 2.6. The gloss of the film decreased significantly with the increase in the microcapsule content of the colour–change powder, with the highest gloss at 1.0%. The impact resistance of the film was also influenced by the content of microcapsules in the waterborne topcoat, with the best impact resistance at 5.0%, level 2 of adhesion at 1.0%–5.0% and 11.0%–13.0%, and level 1 of adhesion at 7.0% and 9.0%. In terms of mechanical and optical properties, the 5.0% content of colour–changing powder microcapsules is the best for the overall performance of waterborne topcoats. In practical furniture applications, the microcapsules prepared in this paper can change the colour in appearance according to the actual temperature and play a decorative role.
Failure Mechanism of EB-PVD Thermal Barrier Coatings under the Synergistic Effect of Thermal Shock and CMAS Corrosion
Authors: Hu Xiaopeng , Liu Guolin , Liu Qing , Zhu Wang , Liu Sai , Ma Zengsheng
Published: September 2022

Thermal barrier coatings (TBCs) suffer from the thermo-chemo-mechanical coupling action of thermal shock and calcium–magnesium–alumina–silicate (CMAS) corrosion. However, the failure mechanism of TBCs under the synergistic effect of thermal shock and CMAS corrosion is still unclear due to a lack of an environmental simulator. Herein, an 8YSZ ceramic coating is deposited on a PtAl bond coating/DD419 nickel-based single crystal superalloy substrate using the electron beam physical vapor deposition (EB-PVD) method. The thermo-chemo-mechanical coupling effect of TBCs is achieved in a self-developed environmental simulator. The interaction of volume expansion induced by the phase transition of ZrO2, structural degradation and thermal fatigue further increases the out-of-plane tensile stress and in-plane shear stress in the ceramic coating, which accelerates the initiation and propagation of surface vertical cracks and horizontal cracks. As multiple surface vertical cracks propagate to the interface and merge with interfacial cracks, the ceramic coating spalls from the substrate.
Atomic Research on the Diffusion Behavior, Mechanical Properties and Fracture Mechanism of Fe/Cu Solid–Liquid Interface
Authors: Zheng Hongyu , Sun Jingwen , Guo Na , Wang Mingjie
Published: September 2022

A molecular dynamics simulation was applied to investigate the diffusion behavior and mechanical properties of a Fe/Cu solid–liquid interface with different orientations, temperatures, and strain rates. The results show that the displacement distance of Fe atoms’ diffusion into the Cu matrix was obviously larger than that of Cu atoms’ diffusion into the Fe matrix at any diffusion temperature and diffusion time. Moreover, the diffusion coefficient and diffusion distance both increase with temperature and time, and reach the highest value when the temperature and diffusion time are 1523 K and 3 ns, respectively. Additionally, the diffusion coefficients of the Fe atoms are arranged in the following order: Fe (100) < Fe (110) < Fe (111). The diffusion coefficients of the Cu atoms are arranged in the following order: Cu (110) > Cu (111) > Cu (100), when temperature and time are 1523 K and 3 ns, respectively. The yield strength and fracture strain of the bimetallic interface is positively correlated with the strain rate, but negatively correlated with the tensile temperature. Moreover, the yield strength of the three orientations can be arranged as follows: Fe (110)/Cu (110) > Fe (100)/Cu (100) > Fe (111)/Cu (111), and the yield strength and fracture strain of Fe (110)/Cu (110) diffusion interface are 12.1 GPa and 21% when the strain rate was 1 × 109/s and the tensile temperature was 300 K. The number of stacking faults and dislocations of the diffused Fe/Cu interface decreased significantly in comparison to the undiffused Fe/Cu interface, even in the length of Stair-rod dislocation and Shockley dislocation. All these results lead to a decrease in the tensile yield strength after interface diffusion.
Overview of Friction and Wear Performance of Sliding Bearings
Authors: Du Fengming , Li Dawei , Sa Xiaoxia , Li Cong , Yu Yang , Li Chengdi , Wang Jingsi , Wang Weiwei
Published: September 2022

Sliding bearings are critical components of the internal combustion engine. Friction and wear occur in the contact area between the shaft and the bearing. Significant wear can occur in poor working conditions or after a long service time, leading to the failure of the sliding bearing and affecting the reliability of the machinery. It is essential to investigate the wear performance of sliding bearings, understand their wear mechanism, predict their service life, and select wear-resistant materials and surface treatments. This paper reviews the current status and prospects of sliding bearing wear research, focusing on the classification of sliding bearing wear tests, wear testing machines, wear test research, wear prediction models, and future research prospects.
Credit Spreads, Leverage and Volatility: A Cointegration Approach
Authors: Maglione Federico
Published: September 2022

This work documents the existence of a cointegration relationship between credit spreads, leverage and equity volatility for a large set of US companies. It is shown that accounting for the long-run equilibrium dynamic between these variables is essential to correctly explain credit spread changes. Using a novel structural model in which equity is modeled as a compound option on the firm’s assets, a new methodology for estimating the unobservable market value of the firm’s assets and volatility is developed. The proposed model allows to significantly reduce the pricing errors in predicting credit spreads when compared with several structural models. In terms of correlation analysis, it is shown that not accounting for the long-run equilibrium equation embedded in an error correction mechanism (ECM) results into a misspecification problem when regressing a set of explanatory variables onto the spread changes. Once credit spreads, leverage and volatility are correctly modeled, thus allowing for a long-run equilibrium, the fit of the regressions sensibly increases if compared to the results of previous research. It is further shown that most of the cross-sectional variation of the spreads appears to be more driven by firm-specific characteristics rather than systematic factors.