bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside
Authors: Gogola Samantha , Rejzer Michael , Bahmad Hisham F. , Abou-Kheir Wassim , Omarzai Yumna , Poppiti Robert
Published: April 2023

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial (“mesenchymal”) transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies.
Selective Hydrogenation of Acetylene over Pd-Co/C Catalysts: The Modifying Effect of Cobalt
Authors: Yurpalova Daria V. , Afonasenko Tatyana N. , Prosvirin Igor P. , Bukhtiyarov Andrey V. , Panafidin Maxim A. , Vinokurov Zakhar S. , Trenikhin Mikhail V. , Gerasimov Evgeny Yu. , Gulyaeva Tatyana I. , Kovtunova Larisa M. , Shlyapin Dmitry A.
Published: April 2023

Novel bimetallic Pd-Co catalysts supported on the carbon material Sibunit were synthesized by an incipient wetness impregnation method and used for ethylene production by selective acetylene hydrogenation. It has been established that an increase in the Pd:Co molar ratio from 1:0 to 1:2 in 0.5%Pd-Co/C catalysts, treated in hydrogen at 500 °C, leads to an increase in the ethylene selectivity from 60 to 67% (T = 45 °C). The selectivity does not change with a further increase in the modifier concentration. The catalysts were investigated by TPR-H2, XRD, TEM HR, EDS, and XPS methods. It was shown that palladium and cobalt in the 0.5%Pd-Co/C samples form Pd(1−x)Cox phases of solid solutions with different compositions depending on the Pd:Co ratio. The cobalt concentration in the Pd-Co particles increases with an increase in the Pd:Co ratio up to 1:2 and then remains at a constant level. In addition, monometallic Co particles were present in the samples with the Pd:Co ratio higher then 1:2. The optimal combination of catalytic properties (the ethylene yield is 62–63%) is typical for catalysts with a Pd:Co molar ratio of 1:2–1:4. which is mainly due to the presence of bimetallic particles containing ~41–43% by at. of cobalt.
Enabling Catalysts for Biodiesel Production via Transesterification
Authors: Wang Baohua , Wang Bingquan , Shukla Sudheesh K. , Wang Rui
Published: April 2023

With the rapid development of industry and the increasing demand for transportation, traditional sources of energy have been excessively consumed. Biodiesel as an alternative energy source has become a research focus. The most common method for biodiesel production is transesterification, in which lipid and low carbon alcohol are commonly used as raw materials, in the presence of a catalyst. In the process of transesterification, the performance of the catalyst is the key factor of the biodiesel yield. This paper reviews the recent research progress on homogeneous and heterogeneous catalysts in biodiesel production. The advantages and disadvantages of current homogeneous acid catalysts and homogeneous base catalysts are discussed, and heteropolyacid heterogeneous catalysts and biomass-derived base catalysts are described. The applications of the homogeneous and heterogeneous catalyst derivatives ionic liquids/deep eutectic solvents and nanocatalysts/magnetic catalysts in biodiesel production are reviewed. The mechanism and economic cost of current homogeneous acid catalysts and homogeneous base catalysts are also analyzed. The unique advantages of each type of catalyst are compared to better understand the microscopic details behind biodiesel. Finally, some challenges of current biodiesel catalysts are summarized, and future research directions are presented. This review will provide general and in-depth knowledge on the achievements, directions, and research priorities in developing novel homogeneous/heterogeneous catalysts for the green and cost-effective production of biodiesel.
The Effect of Polymer Matrix on the Catalytic Properties of Supported Palladium Catalysts in the Hydrogenation of Alkynols
Authors: Talgatov Eldar , Auyezkhanova Assemgul , Zharmagambetova Alima , Tastanova Lyazzat , Bukharbayeva Farida , Jumekeyeva Aigul , Aubakirov Talgat
Published: April 2023

Palladium catalysts were obtained by the adsorption method involving the sequential deposition of polyvinylpyrrolidone (PVP) and then palladium ions on a modified zinc oxide surface without high-temperature calcination and reduction stages. The immobilized PVP-palladium catalysts were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET), infrared spectroscopy (IRS), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and elemental analysis methods. It was found that the introduction of polymer into the catalyst’s composition promotes the dispersion and uniform distribution of active phase nanoparticles (PdO, Pd0) on the surface of zinc oxide. The catalysts were tested in the hydrogenation of complex acetylene alcohol, 3,7,11-trimethyldodecyn-1-ol-3 (C15-yn) under mild conditions (0.1 MPa, 40 °C). For comparison, studies on stereoselective hydrogenation of the short-chain alcohol 2-hexynol-1 were performed. It was shown that modification of the catalyst with polymer improves its catalytic properties. High C15-alkenol selectivity (98%), activity (W = 70 × 10−6 mol/s), and stability (turnover number (TON) 62,000) were achieved on a Pd-PVP/ZnO catalyst. Varying the active phase made it possible to reduce the metal content without deteriorating the catalytic performance of the catalyst.
Positive Effect of Ce Modification on Low-Temperature NH3-SCR Performance and Hydrothermal Stability over Cu-SSZ-16 Catalysts
Authors: Liang Yuqian , Li Rui , Liang Ruicong , Li Zhanhong , Jiang Xiangqiong , Jiang Jiuxing
Published: April 2023

Cu-exchanged SSZ-16 zeolite catalysts exhibit outstanding NH3-SCR activity, but their catalytic performance after hydrothermal treatments is not ideal. In order to improve the hydrothermal stability of Cu-SSZ-16, CuCex-SSZ-16 series catalysts were prepared via an ion exchange process, and the effect of Ce modification on the hydrothermal stability was investigated. In addition, increasing Ce contents significantly improved the hydrothermal stability, and CuCe0.87-SSZ-16 showed the best hydrothermal stability. The effects of adding Ce to active species and the AFX framework were studied by various characterization measurements. The 27Al MAS NMR results reveal that Ce modification can strengthen the structural stability of the CuCex-SSZ-16 catalysts. Furthermore, the combined results of XPS, H2-TPR, and in situ DRIFTS confirm that the introduction of Ce markedly increases the active Cu2+-2Z species, contributing to the remarkable hydrothermal stability.
Preparing Fuel-Range Chemicals via the Direct and Selective Pyrolysis of Disposable Mask Waste for Sustainable Environment
Authors: Gao Xin , Chang Chun-Ran
Published: April 2023

After stepping into the pandemic, it has been entirely not bizarre to wear facial masks to diminish the spreading of viruses in human daily outings. Due to the low expense and stable protection capability, disposable masks are the most widely used types of medical masks. By functionalities and medical standards, disposable masks mainly consist of surgical masks and N95/KN95 respirators in the market. In the assembling scheme, there are typically three or more polymeric layers (i.e., mainly polypropylene) in disposable masks; in addition, the ear loops in masks are usually made from textile constituents, such as polyamides. Therefore, the vast utilization and rapid accumulation of disposal mask waste can directly bring an emerging crisis of foreseeable environmental pollution. To minimize and prevent such mask-led microplastic pollution, chemical pyrolysis of mask waste is one of the most feasible and promising strategies. Via the direct and selective pyrolysis of disposable masks, it can effectively convert the mask waste into high-value fuel-range chemicals, e.g., liquid hydrocarbon blends, aromatics, C1–5 gas alkanes/alkenes, hydrogen, etc. In this way, it can not only tackle environmental challenges from plastic waste but also afford sustainable fuels with low carbon emission and circular economy.
Electrocatalytic Hydrogen Evolution Reaction from Acetic Acid over Gold Immobilized Glassy Carbon Surface
Authors: Alshammari Basmah H. , Begum Humayra , Ibrahim Fatma A. , Hamdy Mohamed S. , Oyshi Tahamida A. , Khatun Nazia , Hasnat Mohammad A.
Published: April 2023

A hydrogen fuel cell is a highly promising alternative to fossil fuel sources owing to the emission of harmless byproducts. However, the operation of hydrogen fuel cells requires a constant supply of highly pure hydrogen gas. The scarcity of sustainable methods of producing such clean hydrogen hinders its global availability. In this work, a noble Au-atom-decorated glassy carbon electrode (Au/GCE) was prepared via a conventional electrodeposition technique and used to investigate the generation of hydrogen from acetic acid (AA) in a neutral electrolyte using 0.1 M KCl as the supporting electrolyte. Electrochemical impedance spectroscopy (EIS), open circuit potential measurement, cyclic voltammetry (CV), and rotating disk electrode voltammetry (RDE) were performed for the characterization and investigation of the catalytic properties. The constructed catalyst was able to produce hydrogen from acetic acid at a potential of approximately −0.2 V vs. RHE, which is much lower than a bare GCE surface. According to estimates, the Tafel slope and exchange current density are 178 mV dec−1 and 7.90×10−6 A cm−2, respectively. Furthermore, it was revealed that the hydrogen evolution reaction from acetic acid has a turnover frequency (TOF) of approximately 0.11 s−1.
Natural Sun-Screening Compounds and DNA-Repair Enzymes: Photoprotection and Photoaging
Authors: Gupta Amit , Singh Ashish P. , Singh Varsha K. , Singh Prashant R. , Jaiswal Jyoti , Kumari Neha , Upadhye Vijay , Singh Suresh C. , Sinha Rajeshwar P.
Published: April 2023

Ultraviolet radiation (UVR) has been scientifically proven to cause skin disorders such as sunburn, skin cancer and the symptoms of chronic exposure. Natural sun screening compounds have recently gained tremendous attention from the cosmetic and cosmeceutical sectors for treating skin disorders such as hyperpigmentation and aging. A wide range of natural UV-absorbing compounds have been used to replace or reduce the number of synthetic sunscreen molecules. One of the primary causes of photoaging is DNA damage, mainly caused by UVR. Photoprotection provided by traditional sunscreens is purely preventative and has no efficacy after DNA damage has been initiated. As a result, the quest for DNA-repair mechanisms that block, reverse, or postpone pathologic processes in UV-exposed skin has stimulated anti-photoaging research and methods to increase the effectiveness of traditional sunscreens. This review summarizes many natural compounds from microalgae, lichens, and plants that have demonstrated potential photoprotection effects against UV radiation-induced skin damage. Furthermore, it offers an overview of current breakthroughs in DNA-repair enzymes utilized in sunscreens and their influence on photoaging.
The Effect of a Nitrogen-Based Ionic Liquid as a Coating over 1Pd9Ag/Al2O3 for the Selective Hydrogenation of 1,7-Octadiene vs 1-Octene
Authors: Chanerika Revana , Shozi Mzamo L. , Prato Mirko , Friedrich Holger B.
Published: April 2023

The effect of tetrabutylammonium nitrate ([N4444][NO3]) was studied as a surface coating over 1Pd9Ag/Al2O3 and applied in the selective hydrogenation of 1,7-octadiene in a mixture with 1-octene. Weight loadings up to a surface of three monolayers (MLs) were investigated and a further comparison coating with 1-ethylimidazole ([EIM]) was carried out to assess anionic effects in the Solid Catalysts with an Ionic Liquid Layer (SCILLs). Catalysts were characterised by H2-chemisorption, TGA-DSC, BET measurements, XPS, and HR-TEM. Catalytic studies showed that the uncoated and EIM-coated (10 wt%) catalysts gave nearly a 100% conversion of 1,7-octadiene and 1-octene with a selectivity mainly towards octane. Coating with [N4444][NO3] at 1 ML significantly decreased the 1-octene conversion by almost 50%, as well as the selectivity to octane (38%) at close to a 100% diene conversion. However, no net gain in 1-octene in the output stream was noted. At 2 ML IL/EIM coverage, a further decline in 1-octene conversion and octane selectivity was found at a diene conversion of 75%. The selectivity to 1-octene steadily increased from over the bare catalyst (52%) to the EIM-coated (62%) catalyst and SCILL (75%). At 3 ML IL coverage, the diene conversion (35%) was significantly reduced due to mass transfer limitations of hydrogen through the thick IL layer. Characterisation of the used catalysts by TG and BET analyses confirmed a leaching of up to 14% of the ionic liquid in the SCILLs coated at 1 ML and 2 ML, with an increase in surface area noted. Furthermore, smaller particle sizes of the used catalysts showed that the metal–support interaction was re-established. These results confirm a mild ligand coordination between the nitrogen in the IL anion and Pd and Ag where the ionic liquid remained physisorbed over the surface of the catalyst. In addition, component miscibility tests revealed partial solubility of the diene in the ionic liquid, indicating the presence of solvent effects also.
Polyoxometalates Encapsulated into Hollow Periodic Mesoporous Organosilica as Nanoreactors for Extraction Oxidation Desulfurization
Authors: Gao Yan , Chen Yu , Wang Cuiying , Yin Aiping , Li Hailong , Zhao Jianshe
Published: April 2023

In this work, the highly active polyoxometalate (PW2Mo2) with Venturello structure and its corresponding catalyst were applied in catalytic desulfurization for the first time. PW2Mo2 as an active component was effectively encapsulated in hollow periodic mesoporous organosilica (HPMOS) to form the nanoreactor PW2Mo2@HPMOS, where the central cavity and mesoporous shell facilitate mass transfer and both provide a stable place to react with organic sulfides. Desulfurization test results show that the hollow nanoreactor PW2Mo2@HPMOS can almost remove four sulfides simultaneously from diesel in 2 h under mild conditions. Besides, the nanocatalyst PW2Mo2@HPMOS can be reused and recycled for at least seven consecutive tests without any noticeable loss in performance. With the rapid development of the economy, the massive use of sulfur-containing fuel has a huge impact on the global climate. After combustion of sulfur-containing fuel, the realized SOX is an important inducement of the formation of acid rain, and the realized sulfur particle is also a major source of haze. Therefore, removing sulfur compounds from fuel is an important issue that needs to be solved immediately.
Band Gap Engineering in Quadruple-Layered Sillén–Aurivillius Perovskite Oxychlorides Bi7Fe2Ti2O17X (X = Cl, Br, I) for Enhanced Photocatalytic Performance
Authors: Chen Jikun , Gu Yan , Xu Shishi , Zhang Yunxiang , Zhang Zhe , Shi Lin , Mu Zhichao , Zhou Chenliang , Zhang Jiali , Zhang Qinfang
Published: April 2023

Developing efficient photocatalyst for the photoreduction of CO2 and degradation of organic pollutants is an effective alternative to address increasingly serious energy problems and environmental pollution. Herein, the isostructural Sillén–Aurivillius oxyhalides, Bi7Fe2Ti2O17X (X = Cl, Br, and I; BFTOX), are fabricated for CO2 reduction and degradation of organic pollutants for the first time. Density functional theory (DFT) calculations show that the valence band maximum (VBM) of BFTOC and BFTOB is contributed by the dispersive 2p orbitals of O-atoms, providing the narrow band gap (Eg) and possibly the stability against self-decomposition deactivation. The photocatalytic activities of BFTOX are strongly affected by the halogens (Cl, Br, and I), namely, the BFTOCl sample displays outstanding activity improvement (3.74 μmol·g−1·h−1) for photocatalytic performance. This is mainly attributed to the high separation of charge carriers, small optical band gap, and extended optical absorption. This work focuses on affording a reference to develop efficient and stable photocatalysts from Sillén-Aurivillius layered oxyhalide materials.
Improvement of Chemical Stability of Perovskite Nanocrystals as a Photoelectrochemical Catalyst for Hydrogen Evolution Reaction
Authors: Kim Hyunjung , Lee Hanleem
Published: April 2023

Recent advances in the synthesis and processing of perovskite materials have led to significant improvements in their stability under harsh conditions, making them increasingly attractive for use as photo and photoelectrochemical catalysts. In particular, core-shell structured perovskite nanocrystals have greatly enhanced chemical stability, enabling their use in aqueous environments; however, their low conductivity remains a challenge. To address this issue, this study developed two-time cross-linkable core-shell perovskite nanocrystals using two types of silanes, resulting in excellent chemical stability and high conductivity. The first cross-linking reaction was spontaneously initiated in the solution state, forming an ultrathin Si-O-Si amorphous matrix on the surface of the perovskite nanocrystals. The second cross-linking reaction was intentionally induced in the film state by exposing it to UV light. The resulting cross-linked perovskite/SiO2 nanocrystal films exhibited a high packing density, and among four different dopants, the Ag-doped film demonstrated the lowest onset potential for HER in a 0.5 M H2SO4 aqueous solution due to effective band modulation. These findings suggest that the two-time cross-linking approach can significantly enhance the performance of perovskite nanocrystals in photoelectrochemical applications.
Bioelectricity in Developmental Patterning and Size Control: Evidence and Genetically Encoded Tools in the Zebrafish Model
Authors: Silic Martin R. , Zhang GuangJun
Published: April 2023

Developmental patterning is essential for regulating cellular events such as axial patterning, segmentation, tissue formation, and organ size determination during embryogenesis. Understanding the patterning mechanisms remains a central challenge and fundamental interest in developmental biology. Ion-channel-regulated bioelectric signals have emerged as a player of the patterning mechanism, which may interact with morphogens. Evidence from multiple model organisms reveals the roles of bioelectricity in embryonic development, regeneration, and cancers. The Zebrafish model is the second most used vertebrate model, next to the mouse model. The zebrafish model has great potential for elucidating the functions of bioelectricity due to many advantages such as external development, transparent early embryogenesis, and tractable genetics. Here, we review genetic evidence from zebrafish mutants with fin-size and pigment changes related to ion channels and bioelectricity. In addition, we review the cell membrane voltage reporting and chemogenetic tools that have already been used or have great potential to be implemented in zebrafish models. Finally, new perspectives and opportunities for bioelectricity research with zebrafish are discussed.
Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts
Authors: Krošel Monika , Moser Larissa , Houtman Miranda , Friščić Jasna , Tomšič Matija , Distler Oliver , Hoffmann Markus H. , Ospelt Caroline , Klein Kerstin
Published: April 2023

Bromodomain- and extra-terminal domain (BET) proteins are epigenetic reader proteins that regulate transcription of their target genes by binding to acetylated histone side chains. Small molecule inhibitors, such as I-BET151, have anti-inflammatory properties in fibroblast-like synoviocytes (FLS) and in animal models of arthritis. Here, we investigated whether BET inhibition can also affect the levels of histone modifications, a novel mechanism underlying BET protein inhibition. On the one hand, FLSs were treated with I-BET151 (1 µM) for 24 h in absence and presence of TNF. On the other hand, FLSs were washed with PBS after 48 h of I-BET151 treatment, and the effects were measured 5 days after I-BET151 treatment or after an additional 24 h stimulation with TNF (5 d + 24 h). Mass spectrometry analysis indicated that I-BET151 induced profound changes in histone modifications, with a global reduction in acetylation on different histone side chains 5 days after treatment. We confirmed changes on acetylated histone side chains in independent samples by Western blotting. I-BET151 treatment reduced mean TNF-induced levels of total acetylated histone 3 (acH3), H3K18ac, and H3K27ac. In line with these changes, the TNF-induced expression of BET protein target genes was suppressed 5 d after I-BET151 treatment. Our data indicate that BET inhibitors not only prevent the reading of acetylated histones but directly influence overall chromatin organization, in particular after stimulation with TNF.
Serotonin Receptors and Their Involvement in Melanization of Sensory Cells in Ciona intestinalis
Authors: Mercurio Silvia , Bozzo Matteo , Pennati Alessandro , Candiani Simona , Pennati Roberta
Published: April 2023

Serotonin (5-hydroxytryptamine (5-HT)) is a biogenic monoamine with pleiotropic functions. It exerts its roles by binding to specific 5-HT receptors (5HTRs) classified into different families and subtypes. Homologs of 5HTRs are widely present in invertebrates, but their expression and pharmacological characterization have been scarcely investigated. In particular, 5-HT has been localized in many tunicate species but only a few studies have investigated its physiological functions. Tunicates, including ascidians, are the sister group of vertebrates, and data about the role of 5-HTRs in these organisms are thus important for understanding 5-HT evolution among animals. In the present study, we identified and described 5HTRs in the ascidian Ciona intestinalis. During development, they showed broad expression patterns that appeared consistent with those reported in other species. Then, we investigated 5-HT roles in ascidian embryogenesis exposing C. intestinalis embryos to WAY-100635, an antagonist of the 5HT1A receptor, and explored the affected pathways in neural development and melanogenesis. Our results contribute to unraveling the multifaceted functions of 5-HT, revealing its involvement in sensory cell differentiation in ascidians.
Prolonged Primary Rhinovirus Infection of Human Nasal Epithelial Cells Diminishes the Viral Load of Secondary Influenza H3N2 Infection via the Antiviral State Mediated by RIG-I and Interferon-Stimulated Genes
Authors: Ong Hsiao Hui , Liu Jing , Oo Yukei , Thong Mark , Wang De Yun , Chow Vincent T.
Published: April 2023

Our previous study revealed that prolonged human rhinovirus (HRV) infection rapidly induces antiviral interferons (IFNs) and chemokines during the acute stage of infection. It also showed that expression levels of RIG-I and interferon-stimulated genes (ISGs) were sustained in tandem with the persistent expression of HRV RNA and HRV proteins at the late stage of the 14-day infection period. Some studies have explored the protective effects of initial acute HRV infection on secondary influenza A virus (IAV) infection. However, the susceptibility of human nasal epithelial cells (hNECs) to re-infection by the same HRV serotype, and to secondary IAV infection following prolonged primary HRV infection, has not been studied in detail. Therefore, the aim of this study was to investigate the effects and underlying mechanisms of HRV persistence on the susceptibility of hNECs against HRV re-infection and secondary IAV infection. We analyzed the viral replication and innate immune responses of hNECs infected with the same HRV serotype A16 and IAV H3N2 at 14 days after initial HRV-A16 infection. Prolonged primary HRV infection significantly diminished the IAV load of secondary H3N2 infection, but not the HRV load of HRV-A16 re-infection. The reduced IAV load of secondary H3N2 infection may be explained by increased baseline expression levels of RIG-I and ISGs, specifically MX1 and IFITM1, which are induced by prolonged primary HRV infection. As is congruent with this finding, in those cells that received early and multi-dose pre-treatment with Rupintrivir (HRV 3C protease inhibitor) prior to secondary IAV infection, the reduction in IAV load was abolished compared to the group without pre-treatment with Rupintrivir. In conclusion, the antiviral state induced from prolonged primary HRV infection mediated by RIG-I and ISGs (including MX1 and IFITM1) can confer a protective innate immune defense mechanism against secondary influenza infection.
Spatiotemporal Cofilin Signaling, Microglial Activation, Neuroinflammation, and Cognitive Impairment Following Hemorrhagic Brain Injury
Authors: Almarghalani Daniyah A. , Sha Xiaojin , Mrak Robert E. , Shah Zahoor A.
Published: April 2023

Intracerebral hemorrhage (ICH) is a significant health concern associated with high mortality. Cofilin plays a crucial role in stress conditions, but its signaling following ICH in a longitudinal study is yet to be ascertained. In the present study, we examined the cofilin expression in human ICH autopsy brains. Then, the spatiotemporal cofilin signaling, microglia activation, and neurobehavioral outcomes were investigated in a mouse model of ICH. Human autopsy brain sections from ICH patients showed increased intracellular cofilin localization within microglia in the perihematomal area, possibly associated with microglial activation and morphological changes. Various cohorts of mice were subjected to intrastriatal collagenase injection and sacrificed at time points of 1, 3, 7, 14, 21, and 28 days. Mice suffered from severe neurobehavioral deficits after ICH, lasting for 7 days, followed by a gradual improvement. Mice suffered post-stroke cognitive impairment (PSCI) both acutely and in the chronic phase. Hematoma volume increased from day 1 to 3, whereas ventricle size increased from day 21 to 28. Cofilin protein expression increased in the ipsilateral striatum on days 1 and 3 and then decreased from days 7 to 28. An increase in activated microglia was observed around the hematoma on days 1 to 7, followed by a gradual reduction up to day 28. Around the hematoma, activated microglia showed morphological changes from ramified to amoeboid. mRNA levels of inflammatory [tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin-6 (IL-6) and anti-inflammatory markers [interleukin-10 (IL-10), transforming growth factor-β TGF-β, and arginase I (Arg1)] increased during the acute phase and decreased in the chronic phase. Blood cofilin levels increased on day 3 and matched the increase in chemokine levels. slingshot protein phosphatase 1 (SSH1) protein, which activates cofilin, was increased from day 1 to 7. These results suggest that microglial activation might be the sequel of cofilin overactivation following ICH, leading to widespread neuroinflammation and consequent PSCI.
Pathophysiological Impact of the MEK5/ERK5 Pathway in Oxidative Stress
Authors: Tusa Ignazia , Menconi Alessio , Tubita Alessandro , Rovida Elisabetta
Published: April 2023

Oxidative stress regulates many physiological and pathological processes. Indeed, a low increase in the basal level of reactive oxygen species (ROS) is essential for various cellular functions, including signal transduction, gene expression, cell survival or death, as well as antioxidant capacity. However, if the amount of generated ROS overcomes the antioxidant capacity, excessive ROS results in cellular dysfunctions as a consequence of damage to cellular components, including DNA, lipids and proteins, and may eventually lead to cell death or carcinogenesis. Both in vitro and in vivo investigations have shown that activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway is frequently involved in oxidative stress-elicited effects. In particular, accumulating evidence identified a prominent role of this pathway in the anti-oxidative response. In this respect, activation of krüppel-like factor 2/4 and nuclear factor erythroid 2-related factor 2 emerged among the most frequent events in ERK5-mediated response to oxidative stress. This review summarizes what is known about the role of the MEK5/ERK5 pathway in the response to oxidative stress in pathophysiological contexts within the cardiovascular, respiratory, lymphohematopoietic, urinary and central nervous systems. The possible beneficial or detrimental effects exerted by the MEK5/ERK5 pathway in the above systems are also discussed.
The Implication of the Gut Microbiome in Heart Failure
Authors: Lupu Vasile Valeriu , Adam Raileanu Anca , Mihai Cristina Maria , Morariu Ionela Daniela , Lupu Ancuta , Starcea Iuliana Magdalena , Frasinariu Otilia Elena , Mocanu Adriana , Dragan Felicia , Fotea Silvia
Published: April 2023

Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one’s state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship.
PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics
Authors: Eleazer Rebekah , De Silva Kalpani , Andreeva Kalina , Jenkins Zoe , Osmani Nour , Rouchka Eric C. , Fondufe-Mittendorf Yvonne
Published: April 2023

Circular RNAs (circRNAs) are a recently discovered class of RNAs derived from protein-coding genes that have important biological and pathological roles. They are formed through backsplicing during co-transcriptional alternative splicing; however, the unified mechanism that accounts for backsplicing decisions remains unclear. Factors that regulate the transcriptional timing and spatial organization of pre-mRNA, including RNAPII kinetics, the availability of splicing factors, and features of gene architecture, have been shown to influence backsplicing decisions. Poly (ADP-ribose) polymerase I (PARP1) regulates alternative splicing through both its presence on chromatin as well as its PARylation activity. However, no studies have investigated PARP1’s possible role in regulating circRNA biogenesis. Here, we hypothesized that PARP1’s role in splicing extends to circRNA biogenesis. Our results identify many unique circRNAs in PARP1 depletion and PARylation-inhibited conditions compared to the wild type. We found that while all genes producing circRNAs share gene architecture features common to circRNA host genes, genes producing circRNAs in PARP1 knockdown conditions had longer upstream introns than downstream introns, whereas flanking introns in wild type host genes were symmetrical. Interestingly, we found that the behavior of PARP1 in regulating RNAPII pausing is distinct between these two classes of host genes. We conclude that the PARP1 pausing of RNAPII works within the context of gene architecture to regulate transcriptional kinetics, and therefore circRNA biogenesis. Furthermore, this regulation of PARP1 within host genes acts to fine tune their transcriptional output with implications in gene function.
Assessment of Covalently Binding Warhead Compounds in the Validation of the Cytomegalovirus Nuclear Egress Complex as an Antiviral Target
Authors: Tillmanns Julia , Häge Sigrun , Borst Eva Maria , Wardin Julia , Eickhoff Jan , Klebl Bert , Wagner Sabrina , Wangen Christina , Hahn Friedrich , Socher Eileen , Marschall Manfred
Published: April 2023

Herpesviral nuclear egress is a regulated process of viral capsid nucleocytoplasmic release. Due to the large capsid size, a regular transport via the nuclear pores is unfeasible, so that a multistage-regulated export pathway through the nuclear lamina and both leaflets of the nuclear membrane has evolved. This process involves regulatory proteins, which support the local distortion of the nuclear envelope. For human cytomegalovirus (HCMV), the nuclear egress complex (NEC) is determined by the pUL50–pUL53 core that initiates multicomponent assembly with NEC-associated proteins and capsids. The transmembrane NEC protein pUL50 serves as a multi-interacting determinant that recruits regulatory proteins by direct and indirect contacts. The nucleoplasmic core NEC component pUL53 is strictly associated with pUL50 in a structurally defined hook-into-groove complex and is considered as the potential capsid-binding factor. Recently, we validated the concept of blocking the pUL50–pUL53 interaction by small molecules as well as cell-penetrating peptides or an overexpression of hook-like constructs, which can lead to a pronounced degree of antiviral activity. In this study, we extended this strategy by utilizing covalently binding warhead compounds, originally designed as binders of distinct cysteine residues in target proteins, such as regulatory kinases. Here, we addressed the possibility that warheads may likewise target viral NEC proteins, building on our previous crystallization-based structural analyses that revealed distinct cysteine residues in positions exposed from the hook-into-groove binding surface. To this end, the antiviral and NEC-binding properties of a selection of 21 warhead compounds were investigated. The combined findings are as follows: (i) warhead compounds exhibited a pronounced anti-HCMV potential in cell-culture-based infection models; (ii) computational analysis of NEC primary sequences and 3D structures revealed cysteine residues exposed to the hook-into-groove interaction surface; (iii) several of the active hit compounds exhibited NEC-blocking activity, as shown at the single-cell level by confocal imaging; (iv) the clinically approved warhead drug ibrutinib exerted a strong inhibitory impact on the pUL50–pUL53 core NEC interaction, as demonstrated by the NanoBiT assay system; and (v) the generation of recombinant HCMV ∆UL50-ΣUL53, allowing the assessment of viral replication under conditional expression of the viral core NEC proteins, was used for characterizing viral replication and a mechanistic evaluation of ibrutinib antiviral efficacy. Combined, the results point to a rate-limiting importance of the HCMV core NEC for viral replication and to the option of exploiting this determinant by the targeting of covalently NEC-binding warhead compounds.
Functionalized Three–Dimensional Graphene Containing Chitosan and Bovine Serum Albumin for Recognizing Chiral Drug Intermediates
Authors: Li Sha , Yao Wenyan , Xie Licheng , Jiang Yan
Published: April 2023

Chiral enantiomer recognition has important research significance in the field of analytical chemistry research. At present, most prepared chiral sensors are used for recognizing amino acids, while they are rarely used in the identification of drug intermediates. This work found that combining CS and reduced graphene oxide can enhance conductivity, increasing the recognition effect by connecting CS with BSA. Based on the above preparation, a new type of chiral sensor (3D–rGO–CS–BSA) was synthesized for the identification of drug intermediates, including the 1–Boc–3–hydroxypyrrolidine enantiomer. An obvious difference was achieved (IR/IS = 2.82) in the oxidation peak currents between the two enantiomers. The detection limits of the R–enantiomer and S–enantiomer were 4.85 nM and 11.76 nM, respectively. The proposed electrochemical sensing platform also has better potential for detecting the percentage content of mixed chiral enantiomer drugs.
Self-Harm Behaviors, Suicide Attempts, and Suicidal Ideation in a Clinical Sample of Children and Adolescents with Psychiatric Disorders
Authors: Predescu Elena , Sipos Roxana
Published: April 2023

Suicidal ideation and self-harm behaviors have been found to be important risk factors for suicide. The aim of this study was to explore the rates of psychiatric disorders among different groups of patients with suicidal ideation, suicide attempts, and non-suicidal self-harm behaviors and to identify the associated socio-demographic and clinical variables. We conducted a cross-sectional study with emergency-admitted patients presenting with non-suicidal self-harm behaviors, suicide attempts, or suicidal ideation to the emergency room of the Child and Adolescent Psychiatry Clinic in Cluj-Napoca, Romania. Data were collected from the patients’ charts using a questionnaire that contained socio-demographic and clinical variables. A total of 95 patients aged between 6 and 18 years were included in the study. Ingesting medication and cutting were the most frequently used methods to attempt suicide. Depression and mixed affective and conduct disorders were the diagnoses most commonly associated with suicidal behavior. Girls with depressive symptoms were more probable to have suicide attempts than boys, and girls with depressive symptoms and behavioral problems registered more self-harm behaviors. Further research should systematically examine the relationship between self-harm behaviors and suicide attempts and the profile of patients at risk of future suicide attempts.
Effect of Co/TiAl on Mechanical Properties of Laser Melted IN 625 on 304SS Matrix
Authors: Yang Tong , Wu Wenxing , Lei Yuantao , Chen Pinghu , Liu Hao , Zhao Li , Qiu Changjun
Published: April 2023

IN 625 is one of the most widely used nickel-based high-temperature alloys. However, the unstable high-temperature mechanical properties of IN625 and the difficulty of processing complex parts have limited its wider application. This work fabricated IN625 coatings with Co/TiAl (1.25, 1.55, and 1.85) on 304SS using laser melting deposition technology, with excellent high-temperature mechanical properties. The effects of Co/TiAl on the microstructure and properties of the laser-cladded resulting coatings have been carefully investigated. Compared to the IN625 coating, the addition of Co, Ti, and Al to the IN625 laser cladding coating significantly enhances its hardness and strength at room temperature, while reducing the elongation rate sharply. After heat treatment (900 °C × 10 h + 850 °C × 2 h), the hardness of the IN625 coating decreases, while the hardness of the IN625 laser cladding coating with added Co, Ti, and Al significantly increases. At a temperature of 850 °C, the yield strength and elongation rate of the IN625 laser cladding coating with Co, Ti, and Al additives exhibit an increasing-then-decreasing trend as the Co/TiAl ratio rises. The results exhibited that the coating had excellent high-temperature mechanical properties when the Co/TiAl is 1.55, and its hardness, tensile strength, yield strength, and elongation rate are 48.62 HRC, 735 Map, 665 MPa, and 11.3%, respectively.
Thermal Barrier Coatings for High-Temperature Performance of Nickel-Based Superalloys: A Synthetic Review
Authors: Barwinska Izabela , Kopec Mateusz , Kukla Dominik , Senderowski Cezary , Kowalewski Zbigniew
Published: April 2023

With the rising demands of industry to increase the working temperature of gas turbine blades and internal combustion engines, thermal barrier coatings (TBC) were found to be an effective way to further enhance the lifetime of aero components through the improvement of mechanical properties and oxidation-resistance. Thus, this paper aims to review coating technologies with special emphasis on plasma-sprayed thermal barrier coatings (PS), and those produced by physical vapor deposition (PVD) and chemical vapor deposition (CVD) methods. Each technology was assessed in terms of its effectiveness to enhance the mechanical response and oxidation resistance of nickel-based parts working at high temperature. The effect of coating technology on mechanical strength, hardness, fatigue and creep of nickel alloys was discussed to reveal the potential candidates for future applications in aggressive environments.
Computational Issues in Insurance and Finance
Authors: Perna Cira , Sibillo Marilena
Published: April 2023

Comparison and cultural exchange always enrich and produce innovative and interesting results [...]
Survey of Recent Deep Neural Networks with Strong Annotated Supervision in Histopathology
Authors: Petríková Dominika , Cimrák Ivan
Published: April 2023

Deep learning (DL) and convolutional neural networks (CNNs) have achieved state-of-the-art performance in many medical image analysis tasks. Histopathological images contain valuable information that can be used to diagnose diseases and create treatment plans. Therefore, the application of DL for the classification of histological images is a rapidly expanding field of research. The popularity of CNNs has led to a rapid growth in the number of works related to CNNs in histopathology. This paper aims to provide a clear overview for better navigation. In this paper, recent DL-based classification studies in histopathology using strongly annotated data have been reviewed. All the works have been categorized from two points of view. First, the studies have been categorized into three groups according to the training approach and model construction: 1. fine-tuning of pre-trained networks for one-stage classification, 2. training networks from scratch for one-stage classification, and 3. multi-stage classification. Second, the papers summarized in this study cover a wide range of applications (e.g., breast, lung, colon, brain, kidney). To help navigate through the studies, the classification of reviewed works into tissue classification, tissue grading, and biomarker identification was used.
Developing Resilient Cyber-Physical Systems: A Review of State-of-the-Art Malware Detection Approaches, Gaps, and Future Directions
Authors: Malik M. Imran , Ibrahim Ahmed , Hannay Peter , Sikos Leslie F.
Published: April 2023

Cyber-physical systems (CPSes) are rapidly evolving in critical infrastructure (CI) domains such as smart grid, healthcare, the military, and telecommunication. These systems are continually threatened by malicious software (malware) attacks by adversaries due to their improvised tactics and attack methods. A minor configuration change in a CPS through malware has devastating effects, which the world has seen in Stuxnet, BlackEnergy, Industroyer, and Triton. This paper is a comprehensive review of malware analysis practices currently being used and their limitations and efficacy in securing CPSes. Using well-known real-world incidents, we have covered the significant impacts when a CPS is compromised. In particular, we have prepared exhaustive hypothetical scenarios to discuss the implications of false positives on CPSes. To improve the security of critical systems, we believe that nature-inspired metaheuristic algorithms can effectively counter the overwhelming malware threats geared toward CPSes. However, our detailed review shows that these algorithms have not been adapted to their full potential to counter malicious software. Finally, the gaps identified through this research have led us to propose future research directions using nature-inspired algorithms that would help in bringing optimization by reducing false positives, thereby increasing the security of such systems.
Real-Time Self-Adaptive Traffic Management System for Optimal Vehicular Navigation in Modern Cities
Authors: Benmessaoud Youssef , Cherrat Loubna , Ezziyyani Mostafa
Published: April 2023

The increase in private car usage in cities has led to limited knowledge and uncertainty about traffic flow. This results in difficulties in addressing traffic congestion. This study proposes a novel technique for dynamically calculating the shortest route based on the costs of the most optimal roads and nodes using instances of road graphs at different timeslots to help minimize congestion for actual drivers in urban areas. The first phase of the study involved reducing traffic congestion in one city. The data were collected using a mobile application installed on more than 10 taxi drivers’ phones, capturing data at different timeslots. Based on the results, the shortest path was proposed for each timeslot. The proposed technique was effective in reducing traffic congestion in the city. To test the effectiveness of the proposed technique in other cities, the second phase of the study involved extending the proposed technique to another city using a self-adaptive system based on a similarity approach regarding the structures and sub-regions of the two cities. The results showed that the proposed technique can be successfully applied to different cities with similar urban structures and traffic regulations. The proposed technique offers an innovative approach to reducing traffic congestion in urban areas. It leverages dynamic calculation of the shortest route and utilizes instances of road graphs to optimize traffic flow. By successfully implementing this approach, we can improve journey times and reduce fuel consumption, pollution, and other operating costs, which will contribute to a better quality of urban life.
Superconducting Diode Effect in Topological Hybrid Structures
Authors: Karabassov Tairzhan , Amirov Emir S. , Bobkova Irina V. , Golubov Alexander A. , Kazakova Elena A. , Vasenko Andrey S.
Published: April 2023

Currently, the superconducting diode effect (SDE) is being actively discussed, due to its large application potential in superconducting electronics. In particular, superconducting hybrid structures, based on three-dimensional (3D) topological insulators, are among the best candidates, due to their having the strongest spin–orbit coupling (SOC). Most theoretical studies on the SDE focus either on a full numerical calculation, which is often rather complicated, or on the phenomenological approach. In the present paper, we compare the linearized and nonlinear microscopic approaches in the superconductor/ferromagnet/3D topological insulator (S/F/TI) hybrid structure. Employing the quasiclassical Green’s function formalism we solve the problem self-consistently. We show that the results obtained by the linearized approximation are not qualitatively different from the nonlinear solution. The main distinction in the results between the two methods was quantitative, i.e., they yielded different supercurrent amplitudes. However, when calculating the so-called diode quality factor the quantitative difference is eliminated and both approaches result in good agreement.