bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric Analysis and Review of Deep Learning-Based Crack Detection Literature Published between 2010 and 2022
Authors: Ali Luqman , Alnajjar Fady , Khan Wasif , Serhani Mohamed Adel , Al Jassmi Hamad
Published: April 2022

The use of deep learning (DL) in civil inspection, especially in crack detection, has increased over the past years to ensure long-term structural safety and integrity. To achieve a better understanding of the research work on crack detection using DL approaches, this paper aims to provide a bibliometric analysis and review of the current literature on DL-based crack detection published between 2010 and 2022. The search from Web of Science (WoS) and Scopus, two widely accepted bibliographic databases, resulted in 165 articles published in top journals and conferences, showing the rapid increase in publications in this area since 2018. The evolution and state-of-the-art approaches to crack detection using deep learning are reviewed and analyzed based on datasets, network architecture, domain, and performance of each study. Overall, this review article stands as a reference for researchers working in the field of crack detection using deep learning techniques to achieve optimal precision and computational efficiency performance in light of electing the most effective combination of dataset characteristics and network architecture for each domain. Finally, the challenges, gaps, and future directions are provided to researchers to explore various solutions pertaining to (a) automatic recognition of crack type and severity, (b) dataset availability and suitability, (c) efficient data preprocessing techniques, (d) automatic labeling approaches for crack detection, (e) parameter tuning and optimization, (f) using 3D images and data fusion, (g) real-time crack detection, and (h) increasing segmentation accuracy at the pixel level.
Dynamic Response Parameter Analysis of Steel Frame Joints under Blast Loading
Authors: Kou Suxia , Zhang Xiuhua , Li Wancheng , Song Chunlei
Published: April 2022

A finite element model of steel frame joints is established using finite element analysis software ANSYS/LS-DYNA. The ideal triangular impact load is used to numerically analyze the dynamic response of steel frame welded joints under blast loading, the main factors affecting this response, and the failure modes of three types of joints, so as to provide reference for the antiexplosive design of steel frame joints. The results show that steel frame joints vibrate violently in the explosive blast direction. Due to the strain rate effect, the strength of steel increases, the material enters the plastic strengthening stage, and there is a certain residual displacement. In addition, displacement and stress caused by blast action in the joint area are large, and the flange shear failure of the beam and column is prone to occur in the joint. Increasing the flange width of the beam and the column cannot improve the antiexplosive performance of the joints, while increasing their thickness can. Furthermore, bolted and welded joints have the highest stiffness and best antiexplosion performance, followed by welded joints, while the antiexplosion performance of bolted joints was the worst.
Tuned-Mass-Damper-Inerter Performance Evaluation and Optimal Design for Transmission Line under Harmonic Excitation
Authors: Liu Xinpeng , Yang Yingwen , Sun Yi , Zhong Yongli , Zhou Lei , Li Siyuan , Wu Chaoyue
Published: April 2022

To investigate vibration control and optimal design of transmission lines with tuned-mass-damper-inerter (TMDI), the motion equation of transmission lines with TMDI is established in the paper, and the closed-form solutions of the response spectrum of transmission line displacement are derived by the frequency domain analysis method. The design parameters of TMDI are optimized by fixed-point theory, and the vibration control performance of TMDI is discussed. The results show that the increase in apparent mass ratio has a positive effect on the vibration control performance of TMDI; the vibration control performance is greatly affected by frequency ratio and limited by damping ratio; the increase in both mass ratio and apparent mass ratio reduces the peak values of the displacement response spectra of transmission line with TMDI; however, blindly increasing the apparent mass and mass ratio (β > 0.2 or μ > 0.4) has a limited effect on improving the vibration control performance of TMDI; compared with conventional TMD, the peak values of the controlled displacement response spectrum of the transmission line with TMDI can be reduced by about 12%, and TMDI has a better vibration suppression effect on the transmission lines.
Optimal Design of Mix Proportion of Hot-Mix Epoxy Asphalt Mixture for Steel Bridge Decks and Its Anti-Slip Performance
Authors: Nie Wen , Wang Duanyi , Yan Junjian , Zhang Xiaoning
Published: April 2022

To solve the problem of the insufficient anti-slip performance of steel bridge deck wear layers, a kind of new epoxy asphalt mixture FAC-10 (Full Epoxy Asphalt Content is shortened to FAC) is proposed in this paper based on the design method of an asphalt-rich mix proportion. The FAC-10 pavement layer was tracked and tested using a pavement texture tester to study the change in its skid resistance under traffic load from a macroscopic and microscopic perspective. The influence of traffic load on the deformation of the FAC-10 wearing layer was also simulated and analyzed via lab tests. The results show that the new FAC-10 epoxy asphalt mixture is superior to the traditional EA-10 epoxy asphalt mixture in terms of skid resistance. During the monitoring and testing period, the three-dimensional (3D) structure depth of the pavement surface showed a decreasing trend followed by an increasing trend, while the density of microtexture distribution showed the opposite trend. After a wheel pressure rutting test, the rutted slab showed slight deformation and a certain degree of reduction in 3D structure depth; the deformation of the rutted slab mainly occured in the surface layer, and the internal deformation was negligible.
Flexural Behavior of Reinforced Concrete Beams under Instantaneous Loading: Effects of Recycled Ceramic as Cement and Aggregates Replacement
Authors: Samadi Mostafa , Baghban Mohammad Hajmohammadian , Kubba Ziyad , Faridmehr Iman , Abdul Shukor Lim Nor Hasanah , Benjeddou Omrane , Ariffin Nur Farhayu Binti , Huseien Ghasan Fahim
Published: April 2022

The flexural behavior of five reinforced concrete beams containing recycled ceramic as cement and aggregate replacement subjected to a monotonic static load up to failure was studied. A full-scale, four-point load test was conducted on these beams for 28 days. The experimental results were compared with the conventional concrete as a control specimen. The cross-section and effective span of these beams were (160 × 200 mm) and 2200 mm, respectively. The data recorded during the tests were the ultimate load at failure, steel-reinforcement bar strain, the strain of concrete, cracking history, and mode of failure. The beam containing 100% recycled aggregates displayed an ultimate load of up to 99% of the control beam specimen. In addition, the first crack load was almost similar for both specimens (about 14 kN). The deflection of the beam composed of 100% of the recycled aggregates was reduced by 43% compared to the control specimen. Regardless of the recycled ceramic aggregates ratio, quantities such as service, yield, and ultimate load of the proposed beams exhibited a comparable trend. It was asserted that the ceramic wastes might be of potential use in producing high-performance concrete needed by the structural industry. It might be an effective strategy to decrease the pressure on the environment, thus reducing the amount of natural resources usage.
Diabetes and Second Neoplasia Impact on Prognosis in Pre-Fibrotic Primary Myelofibrosis
Authors: Cattaneo Daniele , Vener Claudia , Elli Elena Maria , Bucelli Cristina , Galli Nicole , Cavalca Fabrizio , Auteri Giuseppe , Vincelli Donatella , Martino Bruno , Gianelli Umberto , Palandri Francesca , Iurlo Alessandra
Published: April 2022

The 2016 WHO classification recognized pre-fibrotic primary myelofibrosis (pre-PMF) as a distinct entity. Nevertheless, a prognostic model specific for pre-PMF is still lacking. Our aim was to identify the most relevant clinical, histological, and driver mutation information at diagnosis to evaluate outcomes in pre-PMF patients in the real-world setting. We firstly assessed the association between IPSS or DIPSS at diagnosis and response variables in 378 pre-PMF patients. A strict association was observed between IPSS and DIPSS and occurrence of death. Other analyzed endpoints were not associated with IPSS or DIPSS as thrombo-hemorrhagic events at diagnosis or during follow-up, or did not show a clinical plausibility, as transformation into acute leukemia or overt PMF. The only covariates which were significantly associated with death were diabetes and second neoplasia, and were therefore included in two different prognostic settings: the first based on IPSS at diagnosis [class 1 vs. 0, OR (95%CIs): 3.34 (1.85–6.04); class 2 vs. 0, OR (95%CIs): 12.55 (5.04–31.24)], diabetes [OR (95%CIs): 2.95 (1.41–6.18)], and second neoplasia [OR (95%CIs): 2.88 (1.63–5.07)]; the second with DIPSS at diagnosis [class 1 vs. 0, OR (95%CIs): 3.40 (1.89–6.10); class 2 vs. 0, OR (95%CIs): 25.65 (7.62–86.42)], diabetes [OR (95%CIs): 2.89 (1.37–6.09)], and second neoplasia [OR (95%CIs): 2.97 (1.69–5.24)]. In conclusion, our study underlines the importance of other additional risk factors, such as diabetes and second neoplasia, to be evaluated, together with IPSS and DIPSS, to better define prognosis in pre-PMF patients.
Advanced Bile Duct Cancers: A Focused Review on Current and Emerging Systemic Treatments
Authors: Cowzer Darren , Harding James J.
Published: April 2022

Cancers arising in the biliary tract are rare, with varied incidence depending on geographical location. As clinical presentation is typically vague with non-specific symptoms, a large proportion of patients present with unresectable or metastatic disease at diagnosis. When unresectable, the mainstay of treatment is cytotoxic chemotherapy; however, despite this, 5-year overall survival remains incredibly poor. Diagnostic molecular pathology, using next-generation sequencing, has identified a high prevalence of targetable alterations in bile duct cancers, which is transforming care. Substantial genomic heterogeneity has been identified depending on both the anatomical location and etiology of disease, with certain alterations enriched for subtypes. In addition, immune checkpoint inhibitors with anti-PD-1/PD-L1 antibodies in combination with chemotherapy are now poised to become the standard first-line treatment option in this disease. Here, we describe the established role of cytotoxic chemotherapy, targeted precision treatments and immunotherapy in what is a rapidly evolving treatment paradigm for advanced biliary tract cancer.
Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors
Authors: Principi Elisa , Sondo Elvira , Bianchi Giovanna , Ravera Silvia , Morini Martina , Tomati Valeria , Pastorino Cristina , Zara Federico , Bruno Claudio , Eva Alessandra , Pedemonte Nicoletta , Raffaghello Lizzia
Published: April 2022

RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro- or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma- and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients.
Androgen Deprivation Therapy in High-Risk Localized and Locally Advanced Prostate Cancer
Authors: Iwamoto Hiroaki , Izumi Kouji , Makino Tomoyuki , Mizokami Atsushi
Published: April 2022

The recommended treatment for high-risk localized or locally advanced prostate cancer is radical prostatectomy plus extended pelvic lymph node dissection or radiation therapy plus long-term androgen deprivation therapy. However, some patients are treated with androgen deprivation therapy alone for various reasons. In this review, we will discuss the position, indications, complications, and future prospects of androgen deprivation therapy for high-risk localized and locally advanced prostate cancer.
Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany
Authors: Mohr Peter , Scherrer Emilie , Assaf Chalid , Bender Marc , Berking Carola , Chandwani Sheenu , Eigentler Thomas , Grimmelmann Imke , Gutzmer Ralf , Haferkamp Sebastian , Hassel Jessica , Hauschild Axel , Herbst Rudolf , Jiang Ruixuan , Kähler Katharina , Krepler Clemens , Kreuter Alexander , Leiter Ulrike , Loquai Carmen , Meier Friedegund , Pföhler Claudia , Rudolph Anja , Schadendorf Dirk , Schiavone Maximo , Schley Gaston , Terheyden Patrick , Ugurel Selma , Ulrich Jens , Utikal Jochen , Weishaupt Carsten , Welzel Julia , Weichenthal Michael
Published: April 2022

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman’s rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints.
Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults
Authors: Saleh Khalil , Fernandez Alexis , Pasquier Florence
Published: April 2022

Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is the most common subtype of B-ALL in adults and its incidence increases with age. It is characterized by the presence of BCR-ABL oncoprotein that plays a central role in the leukemogenesis of Ph+ ALL. Ph+ ALL patients traditionally had dismal prognosis and long-term survivors were only observed among patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). However, feasibility of allo-HSCT is limited in this elderly population. Fortunately, development of increasingly powerful tyrosine kinase inhibitors (TKIs) from the beginning of the 2000′s dramatically improved the prognosis of Ph+ ALL patients with complete response rates above 90%, deep molecular responses and prolonged survival, altogether with good tolerance. TKIs became the keystone of Ph+ ALL management and their great efficacy led to develop reduced-intensity chemotherapy backbones. Subsequent introduction of blinatumomab allowed going further with development of chemo free strategies. This review will focus on these amazing recent advances as well as novel therapeutic strategies in adult Ph+ ALL.
Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice
Authors: Re Cecconi Andrea David , Barone Mara , Forti Mara , Lunardi Martina , Cagnotto Alfredo , Salmona Mario , Olivari Davide , Zentilin Lorena , Resovi Andrea , Persichitti Perla , Belotti Dorina , Palo Federica , Takakura Nobuyuki , Kidoya Hiroyasu , Piccirillo Rosanna
Published: April 2022

Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ultimately extending plasma stability. Notably, apelin D-peptides alter cAMP-based signaling in vitro as the L-peptides, supporting receptor binding. In vitro apelin 13 protects myotube diameter from dexamethasone-induced atrophy, restrains rates of degradation of long-lived proteins and MuRF1 expression, but fails to protect mice from atrophy. D-apelin 13 given intraperitoneally for 13 days in colon adenocarcinoma C26-bearing mice does not reduce catabolic pathways in muscles, as it does in vitro. Puzzlingly, the levels of circulating apelin seemingly deriving from cachexia-inducing tumors, increase in murine plasma during cachexia. Muscle electroporation of a plasmid expressing its receptor APJ, unlike apelin, preserves myofiber area from C26-induced atrophy, supporting apelin resistance in vivo. Altogether, we believe that during cachexia apelin resistance occurs, contributing to muscle wasting and nullifying any possible peptide-based treatment.
Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT)
Authors: Renzulli Matteo , Mottola Margherita , Coppola Francesca , Cocozza Maria Adriana , Malavasi Silvia , Cattabriga Arrigo , Vara Giulio , Ravaioli Matteo , Cescon Matteo , Vasuri Francesco , Golfieri Rita , Bevilacqua Alessandro
Published: April 2022

Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10−5), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.
Left Ventricular Non-Compaction Spectrum in Adults and Children: From a Morphological Trait to a Structural Muscular Disease
Authors: Fusco Flavia , Borrelli Nunzia , Barracano Rosaria , Ciriello Giovanni Domenico , Verrillo Federica , Scognamiglio Giancarlo , Sarubbi Berardo
Published: April 2022

Left ventricular non-compaction (LVNC) is an extremely heterogeneous disorder with a highly variable clinical presentation, morphologic appearance at imaging testing, and prognosis. It is still unclear whether LVNC should be classified as a separate cardiomyopathy or if it is a mere morphological trait shared by many phenotypically distinct cardiomyopathies. Moreover, the hypertrabeculated phenotype may be reversible in some cases, possibly reflecting the left ventricular physiological response of the cardiac muscle to chronic overload. The current diagnostic criteria have several limitations, leaving many patients in a grey area. Here, we review the available literature on LVNC in order to provide an overview of the current knowledge on this complex disorder.
A Review on Modification Methods of Adsorbents for Naphthalene in Environment
Authors: Xu Qingnan , Yuan Hao , Wang Hongli , Xu Yong , Yang Dezheng
Published: April 2022

Naphthalene is one of the most hazardous polycyclic aromatic hydrocarbons to public health. This paper comprehensively summarized the recent development of modification methods of adsorbents for naphthalene removal in the environment. Various modification methods used in the adsorbent were summarized, mainly including acid oxidation modification, salt modification, doping modification, amino modification, microwave modification, and plasma modification. These methods enhance the adsorption performance of naphthalene mainly by changing the pore size and the oxygen content on the surface of the adsorbent. The modification parameters and their effects on naphthalene removal as well as the advantages and disadvantages of each method are described in detail. This review provides the necessary inspiration and guidance for the researchers who develop polycyclic aromatic hydrocarbons adsorption materials in the environment.
Promotion of Carbon Dioxide Biofixation through Metabolic and Enzyme Engineering
Authors: Pu Xin , Han Yejun
Published: April 2022

Carbon dioxide is a major greenhouse gas, and its fixation and transformation are receiving increasing attention. Biofixation of CO2 is an eco–friendly and efficient way to reduce CO2, and six natural CO2 fixation pathways have been identified in microorganisms and plants. In this review, the six pathways along with the most recent identified variant pathway were firstly comparatively characterized. The key metabolic process and enzymes of the CO2 fixation pathways were also summarized. Next, the enzymes of Rubiscos, biotin-dependent carboxylases, CO dehydrogenase/acetyl-CoA synthase, and 2-oxoacid:ferredoxin oxidoreductases, for transforming inorganic carbon (CO2, CO, and bicarbonate) to organic chemicals, were specially analyzed. Then, the factors including enzyme properties, CO2 concentrating, energy, and reducing power requirements that affect the efficiency of CO2 fixation were discussed. Recent progress in improving CO2 fixation through enzyme and metabolic engineering was then summarized. The artificial CO2 fixation pathways with thermodynamical and/or energetical advantages or benefits and their applications in biosynthesis were included as well. The challenges and prospects of CO2 biofixation and conversion are discussed.
GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation
Authors: Biagioli Michele , Marchianò Silvia , Roselli Rosalinda , Di Giorgio Cristina , Bellini Rachele , Bordoni Martina , Distrutti Eleonora , Catalanotti Bruno , Zampella Angela , Graziosi Luigina , Donini Annibale , Fiorucci Stefano
Published: April 2022

Background & Aims: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. Methods: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn’s disease (CD) patients and three mouse models of colitis and Gpbar1−/− mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. Results: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. Conclusions: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α- and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2.
Specific NLRP3 Inflammasome Assembling and Regulation in Neutrophils: Relevance in Inflammatory and Infectious Diseases
Authors: Paget Christophe , Doz-Deblauwe Emilie , Winter Nathalie , Briard Benoit
Published: April 2022

The NLRP3 inflammasome is a cytosolic multimeric protein platform that leads to the activation of the protease zymogen, caspase-1 (CASP1). Inflammasome activation mediates the proteolytic activation of pro-inflammatory cytokines (IL-1β and IL-18) and program cell death called pyroptosis. The pyroptosis is mediated by the protein executioner Gasdermin D (GSDMD), which forms pores at the plasma membrane to facilitate IL-1β/IL-18 secretion and causes pyroptosis. The NLRP3 inflammasome is activated in response to a large number of pathogenic and sterile insults. However, an uncontrolled inflammasome activation may drive inflammation-associated diseases. Initially, inflammasome-competent cells were believed to be limited to macrophages, dendritic cells (DC), and monocytes. However, emerging evidence indicates that neutrophils can assemble inflammasomes in response to various stimuli with functional relevance. Interestingly, the regulation of inflammasome in neutrophils appears to be unconventional. This review provides a broad overview of the role and regulation of inflammasomes—and more specifically NLRP3—in neutrophils.
On the Connections between TRPM Channels and SOCE
Authors: Souza Bomfim Guilherme H. , Niemeyer Barbara A. , Lacruz Rodrigo S. , Lis Annette
Published: April 2022

Plasma membrane protein channels provide a passageway for ions to access the intracellular milieu. Rapid entry of calcium ions into cells is controlled mostly by ion channels, while Ca2+-ATPases and Ca2+ exchangers ensure that cytosolic Ca2+ levels ([Ca2+]cyt) are maintained at low (~100 nM) concentrations. Some channels, such as the Ca2+-release-activated Ca2+ (CRAC) channels and voltage-dependent Ca2+ channels (CACNAs), are highly Ca2+-selective, while others, including the Transient Receptor Potential Melastatin (TRPM) family, have broader selectivity and are mostly permeable to monovalent and divalent cations. Activation of CRAC channels involves the coupling between ORAI1-3 channels with the endoplasmic reticulum (ER) located Ca2+ store sensor, Stromal Interaction Molecules 1-2 (STIM1/2), a pathway also termed store-operated Ca2+ entry (SOCE). The TRPM family is formed by 8 members (TRPM1-8) permeable to Mg2+, Ca2+, Zn2+ and Na+ cations, and is activated by multiple stimuli. Recent studies indicated that SOCE and TRPM structure-function are interlinked in some instances, although the molecular details of this interaction are only emerging. Here we review the role of TRPM and SOCE in Ca2+ handling and highlight the available evidence for this interaction.
Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia–Ischemia
Authors: Nair Syam , Leverin Anna-Lena , Rocha-Ferreira Eridan , Sobotka Kristina S. , Thornton Claire , Mallard Carina , Hagberg Henrik
Published: April 2022

Hypoxia–ischemia (HI) leads to immature brain injury mediated by mitochondrial stress. If damaged mitochondria cannot be repaired, mitochondrial permeabilization ensues, leading to cell death. Non-optimal turnover of mitochondria is critical as it affects short and long term structural and functional recovery and brain development. Therefore, disposal of deficient mitochondria via mitophagy and their replacement through biogenesis is needed. We utilized mt-Keima reporter mice to quantify mitochondrial morphology (fission, fusion) and mitophagy and their mechanisms in primary neurons after Oxygen Glucose Deprivation (OGD) and in brain sections after neonatal HI. Molecular mechanisms of PARK2-dependent and -independent pathways of mitophagy were investigated in vivo by PCR and Western blotting. Mitochondrial morphology and mitophagy were investigated using live cell microscopy. In primary neurons, we found a primary fission wave immediately after OGD with a significant increase in mitophagy followed by a secondary phase of fission at 24 h following recovery. Following HI, mitophagy was upregulated immediately after HI followed by a second wave at 7 days. Western blotting suggests that both PINK1/Parkin-dependent and -independent mechanisms, including NIX and FUNDC1, were upregulated immediately after HI, whereas a PINK1/Parkin mechanism predominated 7 days after HI. We hypothesize that excessive mitophagy in the early phase is a pathologic response which may contribute to secondary energy depletion, whereas secondary mitophagy may be involved in post-HI regeneration and repair.
HepG2-Based Designer Cells with Heat-Inducible Enhanced Liver Functions
Authors: Kitano Hiroyuki , Kawabe Yoshinori , Kamihira Masamichi
Published: April 2022

Functional human hepatocytes have been a pivotal tool in pharmacological studies such as those investigating drug metabolism and hepatotoxicity. However, primary human hepatocytes are difficult to obtain in large quantities and may cause ethical problems, necessitating the development of a new cell source to replace human primary hepatocytes. We previously developed genetically modified murine hepatoma cell lines with inducible enhanced liver functions, in which eight liver-enriched transcription factor (LETF) genes were introduced into hepatoma cells as inducible transgene expression cassettes. Here, we establish a human hepatoma cell line with heat-inducible liver functions using HepG2 cells. The genetically modified hepatoma cells, designated HepG2/8F_HS, actively proliferated under normal culture conditions and, therefore, can be easily prepared in large quantities. When the expression of LETFs was induced by heat treatment at 43 °C for 30 min, cells ceased proliferation and demonstrated enhanced liver functions. Furthermore, three-dimensional spheroid cultures of HepG2/8F_HS cells showed a further increase in liver functions upon heat treatment. Comprehensive transcriptome analysis using DNA microarrays revealed that HepG2/8F_HS cells had enhanced overall expression of many liver function-related genes following heat treatment. HepG2/8F_HS cells could be useful as a new cell source for pharmacological studies and for constructing bioartificial liver systems.
Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice
Authors: Bartoli Fiona , Evans Elizabeth L. , Blythe Nicola M. , Stewart Leander , Chuntharpursat-Bon Eulashini , Debant Marjolaine , Musialowski Katie E. , Lichtenstein Laeticia , Parsonage Gregory , Futers T. Simon , Turner Neil A. , Beech David J.
Published: April 2022

PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function PIEZO1 mutations are associated with dehydrated hereditary stomatocytosis (DHS), a type of anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent with this hypothesis, mice engineered to contain the M2241R mutation in PIEZO1 to mimic a DHS mutation had increased cardiac mass and interventricular septum thickness at 8–12 weeks of age, without altered cardiac contractility. Myocyte size was greater and there was increased expression of genes associated with cardiac hypertrophy (Anp, Acta1 and β-MHC). There was also cardiac fibrosis, increased expression of Col3a1 (a gene associated with fibrosis) and increased responses of isolated cardiac fibroblasts to PIEZO1 agonism. The data suggest detrimental effects of excess PIEZO1 activity on the heart, mediated in part by amplified PIEZO1 function in cardiac fibroblasts.
Patient-Derived Xenotransplant of CNS Neoplasms in Zebrafish: A Systematic Review
Authors: Sarmiento Beatriz E. , Callegari Santiago , Ghotme Kemel A. , Akle Veronica
Published: April 2022

Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor’s molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.
Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect
Authors: Suzdaltseva Yulia , Goryunov Kirill , Silina Ekaterina , Manturova Natalia , Stupin Victor , Kiselev Sergey L.
Published: April 2022

Mesenchymal stem cells (MSCs) are thought to be a promising therapeutic agent due to their multiple paracrine and immunomodulatory properties, providing protection from chronic inflammation and promoting tissue repair. MSCs can regulate the balance of pro-inflammatory and anti-inflammatory factors in inflamed tissues, creating a microenvironment necessary for successful healing; however, their interactions with immune cells are still poorly studied. We examined the temporal and spatial changes in gene regulation and the paracrine milieu accompanying the MSC-mediated immunosuppression effect in mixed cultures with activated peripheral blood mononuclear cells (PBMCs). Our data reveal that the peak of suppression of PBMC proliferation was achieved within 48 h following co-culture with MSCs and subsequently did not undergo a significant change. This effect was accompanied by an increase in COX-2 expression and an induction of IDO synthesis in MSCs. At this point, the expression of IL-1, IL-6, IL-8, IFN-γ, MCP-1, and G-CSF was upregulated in co-cultured cells. On the contrary, we observed a decrease in the concentrations of IL-10, IL-13, IL-5, and MIP-1b in co-culture supernatants compared to intact cultures of activated PBMCs. The regulation of IDO, IL-1, IL-6, and G-CSF production was accomplished with the involvement of direct cell–cell contact between MSCs and PBMCs. These findings provide new insights into the use of potential precondition inducers or their combinations to obtain functionally qualified MSCs for more effective treatment of inflammatory diseases.
Minimal Important Difference of the Psychosocial Impact of Dental Aesthetics Questionnaire Following Orthodontic Treatment: A Cohort Study
Authors: Wan Hassan Wan Nurazreena , Makhbul Mohd Zambri Mohamed , Yusof Zamros Yuzadi Mohd , Othman Siti Adibah
Published: April 2022

(1) This study aimed to do a longitudinal validation of the psychosocial impact of dental aesthetics questionnaire (PIDAQ) and determine its minimal important difference (MID) following orthodontic treatment; (2) 42 adolescents (11 to 18 years old) were recruited for treatment with fixed appliances and the participants answered the Malaysian PIDAQ prior to treatment (T0), mid-treatment (T1), and post-treatment (T2), plus a global health transition scale at T1 and T2. Data analyses included repeated measures ANOVA and paired sample t-tests. Test–retest was administered 2 to 6 weeks from T0; (3) The final sample comprised 37 subjects (response rate = 88.1%). The 95% limits of agreement were −10.3 to 8.5 points. In the anchor-based approach, those who experienced the smallest changes by reporting their dental aesthetics as “a little improved” had an insignificant PIDAQ score change of −5.3 at T1. At T2, the PIDAQ scores of those in this category were reduced significantly (mean change = −26.2; effect size (ES) = 1.0; p = 0.34). In the distribution-based approach, standardized PIDAQ scores were significantly reduced, with medium (0.7) to large (1.5) ES at T1 and T2, respectively; (4) The PIDAQ can detect orthodontic-related changes in patients’ psychosocial well-being. The post-treatment MID is 26 scale points with large ES.
Effect of Ti Atoms on Néel Relaxation Mechanism at Magnetic Heating Performance of Iron Oxide Nanoparticles
Authors: Can Musa Mutlu , Bairam Chasan , Aksoy Seda , Kuruca Dürdane Serap , Kaneko Satoru , Aktaş Zerrin , Öncül Mustafa Oral
Published: April 2022

The study was based on understanding the relationship between titanium (Ti) doping amount and magnetic heating performance of magnetite (Fe3O4). Superparamagnetic nanosized Ti-doped magnetite ((Fe1−x,Tix)3O4; x = 0.02, 0.03 and 0.05) particles were synthesized by sol-gel technique. In addition to (Fe1−x,Tix)3O4 nanoparticles, SiO2 coated (Fe1−x,Tix)3O4 nanoparticles were produced as core-shell structures to understand the effects of silica coating on the magnetic properties of nanoparticles. Moreover, the magnetic properties were associated with the Néel relaxation mechanism due to the magnetic heating ability of single-domain state nanoparticles. In terms of results, it was observed that the induced RF magnetic field for SiO2 coated (Fe0.97,Ti0.03)3O4 nanoparticles caused an increase in temperature difference (ΔT), which reached up to 22 °C in 10 min. The ΔT values of SiO2 coated (Fe0.97,Ti0.03)3O4 nanoparticles were very close to the values of uncoated Fe3O4 nanoparticles.
An Experimental Analysis of Microcrack Generation during Hydraulic Fracturing of Shale
Authors: Qu Xiaolei , Zhang Yunkai , Liu Fanyue , He Jianming , Dyskin Arcady V. , Qi Chengzhi
Published: April 2022

Hydraulic fracturing is commonly applied in the shale gas exploitation industry. However, the mechanical mechanism of permeability under fracturing has so far been unclear. In this study, an analysis of laboratory experiments on hydraulic fracture propagation and bedding plane reactivation in shale is presented. To investigate microcrack occurrence under fracturing, several small slices were collected from the fracture surface and scanned with a scanning electron microscope (SEM). It was found that observed microscopic microcracks could not be produced by fluid pressure as the latter generated compressive stresses at the site of microcracks. Rather, the microcracks were produced by tensile stress concentration in front of the propagating fracture. This implies that bedding plane reactivation was caused by fracture propagation along the plane. An analysis of microcrack lengths showed that shale exhibited anisotropy in fracture toughness with resistance to fracture propagation parallel to bedding planes being twice as small compared to resistance to fracture propagation in the direction normal to bedding planes.
Layered Double Hydroxides (LDHs) as New Consolidants for Cultural Heritage Masonry
Authors: Ion Rodica-Mariana , Rizescu Claudiu Eduard , Vasile Dan Adrian , Vasilievici Gabriel , Atkinson Irina , Rusu Adriana , Predoana Luminita , Miculescu Florin
Published: April 2022

(1) Background: In time, stone monuments suffer a process of aging and loss of aesthetic and mechanical properties. In order to restore and stop the loss of their properties, various treatments are used, and in this context, a new class of discovered materials with interesting properties are layered double hydroxides, or LDHs. (2) Methods: The LDHs, prepared by a coprecipitation method, were characterized by the structure by X-ray diffraction, composition by FT-IR spectroscopy and X-ray fluorescence spectroscopy, size by diffuse light scattering, and porosity by N2 adsorption/desorption. Additionally, some microscopy techniques such as optical microscopy and SEM/EDAX were used for surface aspects and morphology, and finally, all these were checked with ImageJ software for representative roughness parameters of the treated surfaces by brushing or incorporation. (3) Results: The prepared materials show different degrees of crystallinity and textural properties, and the dispersion of the material presents good stability in time in water/ethanol mixtures. Treatment with the LDH dispersion applied by brushing led to improvements in the mechanical properties (about a 5% increase in compressive strength), to an increased surface stability (about 30%), and to an improvement in the resistance to freeze–thaw cycles. The textural properties of the specimens’ materials were not altered by these treatments. (4) Conclusions: The order of the consolidation efficacity was CaMgAl-LDH > MgAl-LDH > CaAl-LDH, better for application by brushing than by incorporation.
Bismuth Oxychloride Nanomaterials Fighting for Human Health: From Photodegradation to Biomedical Applications
Authors: Wang Lili , Liu Yang , Chen Guoli , Zhang Mengyuan , Yang Xiaodong , Chen Rui , Cheng Yan
Published: April 2022

Environmental pollution and various diseases seriously affect the health of human beings. Photocatalytic nanomaterials (NMs) have been used for degrading pollution for a long time. However, the biomedical applications of photocatalytic NMs have only recently been investigated. As a typical photocatalytic NM, bismuth oxychloride (BiOCl) exhibits excellent photocatalytic performance due to its unique layered structure, electronic properties, optical properties, good photocatalytic activity, and stability. Some environmental pollutants, such as volatile organic compounds, antibiotics and their derivatives, heavy metal ions, pesticides, and microorganisms, could not only be detected but also be degraded by BiOCl-based NMs due to their excellent photocatalytic and photoelectrochemical properties. In particular, BiOCl-based NMs have been used as theranostic platforms because of their CT and photoacoustic imaging abilities, as well as photodynamic and photothermal performances. However, some reviews have only profiled the applications of dye degradation, hydrogen or oxygen production, carbon dioxide reduction, or nitrogen fixation of BiOCl NMs. There is a notable knowledge gap regarding the systematic study of the relationship between BiOCl NMs and human health, especially the biomedical applications of BiOCl-based NMs. As a result, in this review, the recent progress of BiOCl-based photocatalytic degradation and biomedical applications are summarized, and the improvement of BiOCl-based NMs in environmental and healthcare fields are also discussed. Finally, a few insights into the current status and future perspectives of BiOCl-based NMs are given.
New Co-Crystals/Salts of Gallic Acid and Substituted Pyridines: An Effect of Ortho-Substituents on the Formation of an Acid–Pyridine Heterosynthon
Authors: Denisov Gleb L. , Nelyubina Yulia V.
Published: April 2022

Co-crystallization of gallic acid with pyridines and their polyaromatic analogue, quinoline, ortho-substituted by various proton-donating groups able to form hydrogen bonds, produced the only reported co-crystal of gallic acid with an ortho-substituted pyridine, 2-hydroxypyridine, as its preferred pyridone-2 tautomer, and four new crystalline products of gallic acid. These co-crystals, or gallate salts depending on the choice of the pyridine-containing compound, as predicted by the pKa rule, were identified by X-ray diffraction to feature the popular acid–pyridine heterosynthon found in most of the two-component systems of gallic acid that lack ortho-substituents in the pyridine-containing compound. This single-point heterosynthon is, however, modified by one or two proton-donating ortho-substituents, which sometimes may transform into the proton acceptors in an adopted tautomer or zwitterion, to produce its two- or other multi-point variants, including a very rare four-point heterosynthon. The hydrogen bonds they form with the gallic acid species in the appropriate co-crystals/salts strongly favors the formation of the acid–pyridine heterosynthon over the acid–acid homosynthon. In the competitive conditions of multi-component systems, such a modification might be used to reduce supramolecular-synthon-based polymorphism to produce new pharmaceuticals and other crystalline materials with designed properties.
Surface Plasmon Resonance and Increased Interfacial Electron Transfer of 3D AgNWS@TiO2NS Structure for Enhanced Photocatalytic and DSSC Properties
Authors: Zhao Fengyang , Jiang Yongjian
Published: April 2022

Ag nanowires coated with TiO2 nanosheets (AgNWS@TiO2NS, AWT) have been successfully synthesized via a one-pot hydrothermal synthesis. Importantly, the prepared AWT shows enhanced photocatalytic activity compared with Degussa P25, which is attributed to its continuous hierarchical structures, special conductive channel and localized surface plasmon resonance (SPR). Additionally, these prepared AWT were exploited as an electron conductor and scattering material in the TiO2 composite photoanodes of dye-sensitized solar cells (DSSCs). The highest energy conversion efficiency of 6.98% was achieved when the AWT doping rate in the photoanode slurry was 5 wt%. Both enhanced Isc and Voc are attributed to the increased photo-absorption efficiency from the localized SPR. The potential enhanced light-scattering effect and faster photoelectric transmission efficiency of the AWT in the photoanode.