bluuebunny/crossref_metadata_2025 huggingface dataset:
Deformation Analysis of Novel Sorbite Stainless Steel-Aluminum Alloy Attached Lifting Protection Platform
Authors: Xu Jin , Yang Jianjun , Huang Yongqi , Jiang Liqiang , Zeng Jie
Published: May 2023

The all-steel attached lifting protection platform widely employed in recent years has always suffered from self-weight issues and corrosion. Aluminum alloy is the ideal option for steel owing to its low bulk density and resistance to corrosion and rust. However, its elastic modulus is insufficient, causing the deformation of the structure to easily exceed the limitation of the Code for Design of Aluminum Alloy Structures. Therefore, this study recommended using sorbite stainless steel with high strength and a reasonable price as the guide rail of a protection platform having a significant force in conjunction with aluminum alloy to maximize their advantages. Regarding the overall structure, Midas GEN was used to verify whether their deformation adheres to the specifications. For exploring the stiffness of exact nodes, the wall-attached support was modeled by Abaqus, discovering that its maximum composite deformation is 0.725 mm, and its highest stress (490.2 MPa) appears at the intersection of the bottom and the side plate. Additionally, the influence of three key factors (the cantilever height of the protection platform, the horizontal spacing between two wall-attached supports, and the sectional size of the main frame fittings) on the structural deformation was investigated. Finally, the cost per extension meter was compared between the all-steel and the novel sorbite stainless steel-aluminum alloy attached lifting protection platform. The findings of the aforementioned works can effectively guide the design and construction of this novel structure and play a crucial role in its popularization and application.
How Should We Deal with Neoplastic Disease and Serious Infections Caused by Epstein–Barr Virus?
Authors: Yoshiyama Hironori , Nanbo Asuka , Yasuda Tomoharu
Published: May 2023

Epstein–Barr virus (EBV) is a ubiquitous herpesvirus, but also the first discovered human tumor virus [...]
Tackling Insomnia Symptoms through Vestibular Stimulation in Patients with Breast Cancer: A Perspective Paper
Authors: Perrier Joy , Galin Melvin , Denise Pierre , Giffard Bénédicte , Quarck Gaëlle
Published: May 2023

Insomnia symptoms are common among patients with breast cancer (BC; 20–70%) and are predictors of cancer progression and quality of life. Studies have highlighted sleep structure modifications, including increased awakenings and reduced sleep efficiency and total sleep time. Such modifications may result from circadian rhythm alterations consistently reported in this pathology and known as carcinogenic factors, including lower melatonin levels, a flattened diurnal cortisol pattern, and lower rest-activity rhythm amplitude and robustness. Cognitive behavioral therapy and physical activity are the most commonly used non-pharmacological interventions to counter insomnia difficulties in patients with BC. However, their effects on sleep structure remain unclear. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms. Indeed, recent reports have shown that vestibular stimulation could resynchronize circadian rhythms and improve deep sleep in healthy volunteers. Moreover, vestibular dysfunction has been reported following chemotherapy. This perspective paper aims to support the evidence of using galvanic vestibular stimulation to resynchronize circadian rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival.
A Brief Review on the Latest Developments on Pharmaceutical Compound Degradation Using g-C3N4-Based Composite Catalysts
Authors: Biswas Subhadeep , Pal Anjali
Published: May 2023

Pharmaceutical compounds (PCs) are one of the most notable water pollutants of the current age with severe impacts on the ecosystem. Hence, scientists and engineers are continuously working on developing different materials and technologies to eradicate PCs from aqueous media. Among various new-age materials, graphitic carbon nitride (g-C3N4) is one of the wonder substances with excellent catalytic property. The current review article describes the latest trend in the application of g-C3N4-based catalyst materials towards the degradation of various kinds of drugs and pharmaceutical products present in wastewater. The synthesis procedure of different g-C3N4-based catalysts is covered in brief, and this is followed by different PCs degraded as described by different workers. The applicability of these novel catalysts in the real field has been highlighted along with different optimization techniques in practice. Different techniques often explored to characterize the g-C3N4-based materials are also described. Finally, existing challenges in this field along with future perspectives are presented before concluding the article.
Effect of Zirconia on Pd–Pt Supported SBA-15 Catalysts for the Oxidation of Methane
Authors: Caravaggio Gianni , Nossova Lioudmila , Turnbull Matthew
Published: May 2023

A series of methane oxidation catalysts were prepared by doping Santa Barbara Amorphous-15 (SBA-15), a highly mesoporous silica sieve, with varying amounts of Zr (5, 10, and 15 wt%) and loading with 2 wt% Pd and 4 wt% Pt. The catalysts were characterized using various techniques, including BET, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and H2-temperature programmed reduction (H2-TPR). Fresh and aged catalysts were evaluated for methane oxidation. Aging was performed using a simulated lean burn natural gas (NG) engine exhaust containing water vapor (10% vol) and sulfur (10 ppm). It was found that the catalyst with 15 wt% zirconia was the most active and stable of the series, exhibiting the lowest T50 of 481 °C after 40 h of aging. The Pd–Pt catalyst loaded on pure SBA-15 had a T50 of 583 °C after aging, which was 102 °C higher than that of the Pd–Pt catalyst with 15 wt% Zr. The results suggest that the increased performance was due to the higher amount of reducible PtOx species in the proximity of ZrO2 and the sulfur scavenging effect of zirconia, which protected the active metals from forming inactive sulfur complexes. Overall, the Pd–Pt catalyst with 15 wt% Zr loaded on SBA-15 demonstrated excellent methane oxidation activity, hydrothermal stability, and sulfur resistance and can be considered a viable candidate for reducing the methane slip from a lean burn NG engine exhaust.
Phosphate Removal by Ca-Modified Magnetic Sludge Biochar Prepared by a One-Step Hydrothermal Method
Authors: Liu Xu , Li Yushan , Zhou Hao , Guo Jing , Xiao Yonghou , Liu Cong , An Boxing , Liang Zhengqi
Published: May 2023

The problem of phosphorus pollution and its resource utilization has been a source of general concern. The preparation of green, renewable, and non-secondary pollution adsorbents has become a research direction. In this paper, a one-step hydrothermal preparation method of Ca-modified magnetic sludge biochar (Ca-MSBC) is used for enhancing phosphate removal. The results show that the adsorption rate of phosphate by Ca-MSBC is mainly controlled by chemisorption but is also related to physical adsorption and an internal diffusion mechanism. The maximum phosphorus adsorption capacity of Ca-MSBC was 89.25 mg g−1 at 343 K (initial phosphate concentration 500 mg L−1). After nine cycles of adsorption experiments, the adsorption capacity of 70.16 mg g−1 was still high. In addition, coexisting ions Cl−, NO3−, SO42−, and CO32− have no significant effect on the adsorption properties of phosphate. XRD, FT-IR, VSM, XPS, and N2 adsorption/desorption isotherms showed that the mechanism of phosphate removal from water by Ca-MSBC was mainly the chemical precipitation reaction of phosphate and calcium. The results of this study indicate that Ca-MSBC has potential application and environmental value as a solid waste recycling material for environmental remediation.
Influence of Age on Hyperoxia-Induced Cardiac Pathophysiology in Type 1 Diabetes Mellitus (T1DM) Mouse Model
Authors: Saleem Faizan , Mansour Hussein , Vichare Riddhi , Ayalasomayajula Yashwant , Yassine Jenna , Hesaraghatta Anagha , Panguluri Siva Kumar
Published: May 2023

Mechanical ventilation often results in hyperoxia, a condition characterized by excess SpO2 levels (>96%). Hyperoxia results in changes in the physiological parameters, severe cardiac remodeling, arrhythmia development, and alteration of cardiac ion channels, all of which can point toward a gradual increase in the risk of developing cardiovascular disease (CVD). This study extends the analysis of our prior work in young Akita mice, which demonstrated that exposure to hyperoxia worsens cardiac outcomes in a type 1 diabetic murine model as compared to wild-type (WT) mice. Age is an independent risk factor, and when present with a major comorbidity, such as type 1 diabetes (T1D), it can further exacerbate cardiac outcomes. Thus, this research subjected aged T1D Akita mice to clinical hyperoxia and analyzed the cardiac outcomes. Overall, aged Akita mice (60 to 68 weeks) had preexisting cardiac challenges compared to young Akita mice. Aged mice were overweight, had an increased cardiac cross-sectional area, and showed prolonged QTc and JT intervals, which are proposed as major risk factors for CVD like intraventricular arrhythmias. Additionally, exposure to hyperoxia resulted in severe cardiac remodeling and a decrease in Kv 4.2 and KChIP2 cardiac potassium channels in these rodents. Based on sex-specific differences, aged male Akita mice had a higher risk of poor cardiac outcomes than aged females. Aged male Akita mice had prolonged RR, QTc, and JT intervals even at baseline normoxic exposure. Moreover, they were not protected against hyperoxic stress through adaptive cardiac hypertrophy, which, at least to some extent, is due to reduced cardiac androgen receptors. This study in aged Akita mice aims to draw attention to the clinically important yet understudied subject of the effect of hyperoxia on cardiac parameters in the presence of preexisting comorbidities. The findings would help revise the provision of care for older T1D patients admitted to ICUs.
Evaluation of RAS Mutational Status in Liquid Biopsy to Monitor Disease Progression in Metastatic Colorectal Cancer Patients
Authors: Lastraioli Elena , Bettiol Alessandra , Iorio Jessica , Limatola Elvira , Checcacci Daniele , Parisi Erica , Bianchi Cristina , Arcangeli Annarosa , Iannopollo Mauro , Di Costanzo Francesco , Di Lieto Marco
Published: May 2023

In this study we evaluated both~ K- and N-RAS mutations in plasma samples from patients with metastatic colorectal cancer by means of the BEAMing technology, and we assessed their diagnostic performance compared to RAS analyses performed on tissue. The sensitivity of BEAMing in identifying KRAS mutations was of 89.5%, with a fair specificity. The agreement with tissue analysis was moderate. The sensitivity for NRAS was high with a good specificity, and the agreement between tissue analysis and BEAMing was fair. Interestingly, significantly higher mutant allele fraction (MAF) levels were detected in patients with G2 tumors, liver metastases, and in those who did not receive surgery. NRAS MAF level was significantly higher in patients with mucinous adenocarcinoma and for those with lung metastases. A sharp increase in the MAF values was observed in patients who moved towards disease progression. More strikingly, molecular progression always anticipated the radiological one in these patients. These observations pave the way to the possibility of using liquid biopsy to monitor patients during treatment, and to enable oncologists to anticipate interventions compared to radiological analyses. This will allow time to be saved and ensure a better management of metastatic patients in the near future.
Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC Transporter ABCA7 in Breast Cancer
Authors: Zappe Katja , Kopic Antonio , Scheichel Alexandra , Schier Ann-Katrin , Schmidt Lukas Emanuel , Borutzki Yasmin , Miedl Heidi , Schreiber Martin , Mendrina Theresa , Pirker Christine , Pfeiler Georg , Hacker Stefan , Haslik Werner , Pils Dietmar , Bileck Andrea , Gerner Christopher , Meier-Menches Samuel , Heffeter Petra , Cichna-Markl Margit
Published: May 2023

The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5–intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5–intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon–intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.
Tauroursodeoxycholic Acid Enhances Osteogenic Differentiation through EGFR/p-Akt/CREB1 Pathway in Mesenchymal Stem Cells
Authors: Kang Hyojin , Yang Sunsik , Lee Jun
Published: May 2023

Background: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that are among the most appealing candidates for regenerative medicine and may aid in the repair and regeneration of skeletal disorders through multiple mechanisms, including angiogenesis, differentiation, and response to inflammatory conditions. Tauroursodeoxycholic acid (TUDCA) has recently been used in various cell types as one of these drugs. The mechanism of osteogenic differentiation by TUDCA in hMSCs remains unknown. Methods: Cell proliferation was performed by the WST-1 method, and alkaline phosphatase activity and alizarin red-sulfate staining were used to confirm the osteogenic differentiation indicator. Expression of genes related to bone differentiation and specific genes related to signaling pathways was confirmed by quantitative real-time polymerase chain reaction. Results: We found that cell proliferation was higher as the concentration increased, and showed that the induction of osteogenic differentiation was significantly enhanced. We also show that osteogenic differentiation genes were upregulated, with the expression of the epidermal growth factor receptor (EGFR) and cAMP responsive element binding protein 1 (CREB1) being specifically high. To confirm the participation of the EGFR signaling pathway, the osteogenic differentiation index and expression of osteogenic differentiation genes were determined after using an EGFR inhibitor. As a result, EGFR expression was remarkably low, and that of CREB1, cyclin D1, and cyclin E1 was also significantly low. Conclusions: Therefore, we suggest that TUDCA-induced osteogenic differentiation of human MSCs is enhanced through the EGFR/p-Akt/CREB1 pathway.
Epidrugs in the Therapy of Central Nervous System Disorders: A Way to Drive on?
Authors: Gladkova Marina G. , Leidmaa Este , Anderzhanova Elmira A.
Published: May 2023

The polygenic nature of neurological and psychiatric syndromes and the significant impact of environmental factors on the underlying developmental, homeostatic, and neuroplastic mechanisms suggest that an efficient therapy for these disorders should be a complex one. Pharmacological interventions with drugs selectively influencing the epigenetic landscape (epidrugs) allow one to hit multiple targets, therefore, assumably addressing a wide spectrum of genetic and environmental mechanisms of central nervous system (CNS) disorders. The aim of this review is to understand what fundamental pathological mechanisms would be optimal to target with epidrugs in the treatment of neurological or psychiatric complications. To date, the use of histone deacetylases and DNA methyltransferase inhibitors (HDACis and DNMTis) in the clinic is focused on the treatment of neoplasms (mainly of a glial origin) and is based on the cytostatic and cytotoxic actions of these compounds. Preclinical data show that besides this activity, inhibitors of histone deacetylases, DNA methyltransferases, bromodomains, and ten-eleven translocation (TET) proteins impact the expression of neuroimmune inflammation mediators (cytokines and pro-apoptotic factors), neurotrophins (brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF)), ion channels, ionotropic receptors, as well as pathoproteins (β-amyloid, tau protein, and α-synuclein). Based on this profile of activities, epidrugs may be favorable as a treatment for neurodegenerative diseases. For the treatment of neurodevelopmental disorders, drug addiction, as well as anxiety disorders, depression, schizophrenia, and epilepsy, contemporary epidrugs still require further development concerning a tuning of pharmacological effects, reduction in toxicity, and development of efficient treatment protocols. A promising strategy to further clarify the potential targets of epidrugs as therapeutic means to cure neurological and psychiatric syndromes is the profiling of the epigenetic mechanisms, which have evolved upon actions of complex physiological lifestyle factors, such as diet and physical exercise, and which are effective in the management of neurodegenerative diseases and dementia.
Response of Prolyl 4 Hydroxylases, Arabinogalactan Proteins and Homogalacturonans in Four Olive Cultivars under Long-Term Salinity Stress in Relation to Physiological and Morphological Changes
Authors: Azariadis Aristotelis , Vouligeas Filippos , Salame Elige , Kouhen Mohamed , Rizou Myrto , Blazakis Kostantinos , Sotiriou Penelope , Ezzat Lamia , Mekkaoui Khansa , Monzer Aline , Krokida Afroditi , Adamakis Ioannis-Dimosthenis , Dandachi Faten , Shalha Boushra , Kostelenos George , Figgou Eleftheria , Giannoutsou Eleni , Kalaitzis Panagiotis
Published: May 2023

Olive (Olea europeae L.) salinity stress induces responses at morphological, physiological and molecular levels, affecting plant productivity. Four olive cultivars with differential tolerance to salt were grown under saline conditions in long barrels for regular root growth to mimic field conditions. Arvanitolia and Lefkolia were previously reported as tolerant to salinity, and Koroneiki and Gaidourelia were characterized as sensitive, exhibiting a decrease in leaf length and leaf area index after 90 days of salinity. Prolyl 4-hydroxylases (P4Hs) hydroxylate cell wall glycoproteins such as arabinogalactan proteins (AGPs). The expression patterns of P4Hs and AGPs under saline conditions showed cultivar-dependent differences in leaves and roots. In the tolerant cultivars, no changes in OeP4H and OeAGP mRNAs were observed, while in the sensitive cultivars, the majority of OeP4Hs and OeAGPs were upregulated in leaves. Immunodetection showed that the AGP signal intensity and the cortical cell size, shape and intercellular spaces under saline conditions were similar to the control in Arvanitolia, while in Koroneiki, a weak AGP signal was associated with irregular cells and intercellular spaces, leading to aerenchyma formation after 45 days of NaCl treatment. Moreover, the acceleration of endodermal development and the formation of exodermal and cortical cells with thickened cell walls were observed, and an overall decrease in the abundance of cell wall homogalacturonans was detected in salt-treated roots. In conclusion, Arvanitolia and Lefkolia exhibited the highest adaptive capacity to salinity, indicating that their use as rootstocks might provide increased tolerance to irrigation with saline water.
Primary Ciliary Dyskinesia Patient-Specific hiPSC-Derived Airway Epithelium in Air-Liquid Interface Culture Recapitulates Disease Specific Phenotypes In Vitro
Authors: von Schledorn Laura , Puertollano Martín David , Cleve Nicole , Zöllner Janina , Roth Doris , Staar Ben Ole , Hegermann Jan , Ringshausen Felix C. , Nawroth Janna , Martin Ulrich , Olmer Ruth
Published: May 2023

Primary ciliary dyskinesia (PCD) is a rare heterogenic genetic disorder associated with perturbed biogenesis or function of motile cilia. Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage. Current approaches to treat PCD are symptomatic, only, indicating an urgent need for curative therapeutic options. Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures. Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.
Kinetics of Wound Development and Healing Suggests a Skin-Stabilizing Effect of Allogeneic ABCB5+ Mesenchymal Stromal Cell Treatment in Recessive Dystrophic Epidermolysis Bullosa
Authors: Niebergall-Roth Elke , Dieter Kathrin , Daniele Cristina , Fluhr Silvia , Khokhrina Maria , Silva Ines , Ganss Christoph , Frank Markus H. , Kluth Mark A.
Published: May 2023

Recessive dystrophic epidermolysis (RDEB) is a rare, inherited, and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial, three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved the healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs, the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.
Adipose-Derived Mesenchymal Stromal Cell Transplantation for Severe Spinal Cord Injury: Functional Improvement Supported by Angiogenesis and Neuroprotection
Authors: Takahashi Ai , Nakajima Hideaki , Kubota Arisa , Watanabe Shuji , Matsumine Akihiko
Published: May 2023

Mesenchymal stromal cell transplantation alone is insufficient when motor dysfunction is severe; combination therapy with rehabilitation could improve motor function. Here, we aimed to analyze the characteristics of adipose-derived MSCs (AD-MSCs) and determine their effectiveness in severe spinal cord injury (SCI) treatment. A severe SCI model was created and motor function were compared. The rats were divided into AD-MSC-transplanted treadmill exercise-combined (AD-Ex), AD-MSC-transplanted non-exercise (AD-noEx), PBS-injected exercise (PBS-Ex), and no PBS-injected exercise (PBS-noEx) groups. In cultured cell experiments, AD-MSCs were subjected to oxidative stress, and the effects on the extracellular secretion of AD-MSCs were investigated using multiplex flow cytometry. We assessed angiogenesis and macrophage accumulation in the acute phase. Spinal cavity or scar size and axonal preservation were assessed histologically in the subacute phase. Significant motor function improvement was observed in the AD-Ex group. Vascular endothelial growth factor and C-C motif chemokine 2 expression in AD-MSC culture supernatants increased under oxidative stress. Enhanced angiogenesis and decreased macrophage accumulation were observed at 2 weeks post-transplantation, whereas spinal cord cavity or scar size and axonal preservation were observed at 4 weeks. Overall, AD-MSC transplantation combined with treadmill exercise training improved motor function in severe SCI. AD-MSC transplantation promoted angiogenesis and neuroprotection.
Inhibiting WEE1 Augments the Antitumor Efficacy of Cisplatin in Urothelial Carcinoma by Enhancing the DNA Damage Process
Authors: Su Yu-Li , Xiao Ling-Yi , Huang Shih-Yu , Wu Chia-Che , Chang Li-Chung , Chen Yi-Hua , Luo Hao-Lun , Huang Chun-Chieh , Liu Ting-Ting , Peng Jei-Ming
Published: May 2023

Urothelial carcinoma (UC) is characterized by a high incidence of TP53 mutation, and overcoming resistance to cisplatin-based chemotherapy in UC is a major concern. Wee1 is a G2/M phase regulator that controls the DNA damage response to chemotherapy in TP53-mutant cancers. The combination of Wee1 blockade with cisplatin has shown synergistic efficacy in several types of cancers, but little is known regarding UC. The antitumor efficacy of the Wee1 inhibitor (AZD-1775) alone or in combination with cisplatin was evaluated in UC cell lines and a xenograft mouse model. AZD-1775 enhanced the anticancer activity of cisplatin by increasing cellular apoptosis. AZD-1775 inhibited the G2/M checkpoint, improving the sensitivity of mutant TP53 UC cells to cisplatin by enhancing the DNA damage process. We confirmed that AZD-1775 combined with cisplatin reduced tumor volume and proliferation activity and increased the markers of cell apoptosis and DNA damage in the mouse xenograft model. In summary, the Wee1 inhibitor AZD-1775 combined with cisplatin elicited a promising anticancer efficacy in UC, and constitutes an innovative and promising therapeutic strategy.
Emerging Anti-Diabetic Drugs for Beta-Cell Protection in Type 1 Diabetes
Authors: Ajmal Nida , Bogart Maislin C. , Khan Palwasha , Max-Harry Ibiagbani M. , Nunemaker Craig S.
Published: May 2023

Type 1 diabetes (T1D) is a chronic autoimmune disorder that damages beta cells in the pancreatic islets of Langerhans and results in hyperglycemia due to the loss of insulin. Exogenous insulin therapy can save lives but does not halt disease progression. Thus, an effective therapy may require beta-cell restoration and suppression of the autoimmune response. However, currently, there are no treatment options available that can halt T1D. Within the National Clinical Trial (NCT) database, a vast majority of over 3000 trials to treat T1D are devoted to insulin therapy. This review focuses on non-insulin pharmacological therapies. Many investigational new drugs fall under the category of immunomodulators, such as the recently FDA-approved CD-3 monoclonal antibody teplizumab. Four intriguing candidate drugs fall outside the category of immunomodulators, which are the focus of this review. Specifically, we discuss several non-immunomodulators that may have more direct action on beta cells, such as verapamil (a voltage-dependent calcium channel blocker), gamma aminobutyric acid (GABA, a major neurotransmitter with effects on beta cells), tauroursodeoxycholic acid (TUDCA, an endoplasmic reticulum chaperone), and volagidemab (a glucagon receptor antagonist). These emerging anti-diabetic drugs are expected to provide promising results in both beta-cell restoration and in suppressing cytokine-derived inflammation.
Mitochondrial Transfer to Host Cells from Ex Vivo Expanded Donor Hematopoietic Stem Cells
Authors: Kawano Hiroki , Kawano Yuko , Yu Chen , LaMere Mark W. , McArthur Matthew J. , Becker Michael W. , Ballinger Scott W. , Gojo Satoshi , Eliseev Roman A. , Calvi Laura M.
Published: May 2023

Mitochondrial dysfunction is observed in various conditions, from metabolic syndromes to mitochondrial diseases. Moreover, mitochondrial DNA (mtDNA) transfer is an emerging mechanism that enables the restoration of mitochondrial function in damaged cells. Hence, developing a technology that facilitates the transfer of mtDNA can be a promising strategy for the treatment of these conditions. Here, we utilized an ex vivo culture of mouse hematopoietic stem cells (HSCs) and succeeded in expanding the HSCs efficiently. Upon transplantation, sufficient donor HSC engraftment was attained in-host. To assess the mitochondrial transfer via donor HSCs, we used mitochondrial-nuclear exchange (MNX) mice with nuclei from C57BL/6J and mitochondria from the C3H/HeN strain. Cells from MNX mice have C57BL/6J immunophenotype and C3H/HeN mtDNA, which is known to confer a higher stress resistance to mitochondria. Ex vivo expanded MNX HSCs were transplanted into irradiated C57BL/6J mice and the analyses were performed at six weeks post transplantation. We observed high engraftment of the donor cells in the bone marrow. We also found that HSCs from the MNX mice could transfer mtDNA to the host cells. This work highlights the utility of ex vivo expanded HSC to achieve the mitochondrial transfer from donor to host in the transplant setting.
SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents
Authors: Oliveira-Mendes Barbara B. R. , Alameh Malak , Ollivier Béatrice , Montnach Jérôme , Bidère Nicolas , Souazé Frédérique , Escriou Nicolas , Charpentier Flavien , Baró Isabelle , De Waard Michel , Loussouarn Gildas
Published: May 2023

Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly acquired round shapes that detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this by using flow cytometry. In adhering cells expressing E or 3a protein, the whole-cell currents were not different from those of the control, suggesting that E and 3a proteins are not plasma membrane viroporins. In contrast, recording the currents on detached cells uncovered outwardly rectifying currents much larger than those observed in the control. We illustrate for the first time that carbenoxolone and probenecid block these outwardly rectifying currents; thus, these currents are most probably conducted by pannexin channels that are activated by cell morphology changes and also potentially by cell death. The truncation of C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent these outwardly rectifying currents. This suggests distinct pathways for the induction of these cellular events by the two proteins. We conclude that SARS-CoV-2 E and 3a proteins are not viroporins expressed at the plasma membrane.
Near-Infrared Fluorescence Probe for Visualizing Fluctuations of Peroxynitrite in Living Cells and Inflammatory Mouse Models
Authors: Qin Shuchun , Ran Yiming , He Yitian , Lu Xiaoyan , Wang Jiamin , Zhao Weili , Zhang Jian
Published: May 2023

Inflammation is a vital protective response in living systems and closely related to various diseases. As a member of the reactive oxygen species (ROS) family, peroxynitrite (ONOO−) is involved in the organism’s inflammatory process and considered as an important biomarker of inflammation. Therefore, the construction of a simple, rapid, and sensitive tool for detecting ONOO− is of great importance for the diagnosis of inflammation. In this study, we constructed the new near-infrared fluorescence probe BDP-ENE-S-Py+ based on BODIPY dye, which has the advantages of fast response speed (2 min), good selectivity, and a high signal-to-noise ratio. Moreover, the probe had a good linear relationship (LOD = 120 nM) when the ONOO− concentration was 10–35 µM. In addition, BDP-ENE-S-Py+ could detect exogenous ONOO− in liver cancer cells without interference from other reactive oxygen species and visualize the fluctuations in ONOO− concentrations in cells. More importantly, BDP-ENE-S-Py+ was able to track the upregulation of ONOO− content in a mouse model of peritonitis induced by LPS. This work demonstrated that the near-infrared fluorescent probe for visualizing ONOO− level fluctuations could provide a promising tool for inflammation-related studies.
Molecularly Imprinted Plasmonic Sensors for the Determination of Environmental Water Contaminants: A Review
Authors: Rebelo Patrícia , Seguro Isabel , Nouws Henri P. A. , Delerue-Matos Cristina , Pacheco João G.
Published: May 2023

The scarcity of clean water leads to the exploration of the possibility of using treated wastewater. However, monitoring campaigns have proven the presence of emerging contaminants, such as pharmaceuticals, pesticides and personal care products, not only in trace amounts. Various analytical methodologies have been developed over the last years for the quantification of these compounds in environmental waters. Facing the need to achieve a higher sensitivity, fast response and practical use via miniaturization, the potential of plasmonic sensors has been explored. Through the introduction of molecularly imprinted polymers (MIPs) as recognition elements, MIP-based plasmonic sensors seem to be a good alternative for monitoring a wide range of analytes in water samples. This work attempts to provide a general overview of this form of sensor, which has been reported as being able to sense different contaminants in waters using surface plasmon resonance (SPR) and surface-enhanced Raman-scattering (SERS) techniques. Particular emphasis is given to the fabrication/recognition procedure, including the preparation of MIPs and the use of metals and nanomaterials to increase the performance characteristics of the sensors.
Severe Pemphigus Vulgaris Resistant to Conventional Therapies and with Hypersensitivity to Rituximab in a 12-Year-Old Child
Authors: De Felici Del Giudice Maria Beatrice , Calanca Carolina , Sassetti Chiara , Caffarelli Carlo , Feliciani Claudio , Esposito Susanna
Published: May 2023

Pemphigus vulgaris (PV) is a rare, potentially lethal blistering disease typically occurring in adulthood and characterized by autoantibodies directed against mucocutaneous desmosomal proteins. Clinically, flaccid vesicles, bullae and erosions after breakage are the main clinical features. According to the literature, the incidence of PV is rare in the pediatric population, ranging from 1 to 4% of reported cases. We describe an interesting case of a 12-year-old boy with severe PV that was referred to our university hospital for a mucocutaneous disease resistant to anti-infective therapy. Following the appearance of bullous lesions on the skin, antibody screening for autoimmune diseases showed positivity for PV and corticosteroid therapy was started. In view of the numerous adverse effects, we decided to set up biological therapy with rituximab, which was interrupted due to the onset of an urticarial reaction. Further second-line therapies were therefore attempted, with only a partial response. For this reason, a desensitizing therapy with rituximab was decided, thus allowing a clear improvement in the clinical picture and quality of life of the patient. To the best of our knowledge, this is the first report of a child with severe PV resistant to conventional therapies and with an urticarial reaction to rituximab. This case highlights that despite PV being extremely rare in the pediatric population, this diagnosis should not be entirely discounted. In case of severe clinical manifestations, rituximab represents a valid option in children and desensitization tests should be recommended in the presence of hypersensitivity to this drug.
Metabolic Silencing via Methionine-Based Amino Acid Restriction in Head and Neck Cancer
Authors: Wünsch Anna Chiara , Ries Elena , Heinzelmann Sina , Frabschka Andrea , Wagner Peter Christoph , Rauch Theresa , Koderer Corinna , El-Mesery Mohamed , Volland Julian Manuel , Kübler Alexander Christian , Hartmann Stefan , Seher Axel
Published: May 2023

In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines.
A Method to Identify the Critical Seismic Input for Curved Bridges
Authors: Tao Chengcheng , Guan Shanyue
Published: May 2023

To address the rapidly growing demands of traffic congestion, more highway bridges have been constructed, especially curved bridges. With more curved bridges designed and constructed, people have conducted a comprehensive analysis of the structural performance. Due to the nature of the structural complexity of curved bridges, dynamic responses of the curve bridges vary dramatically from the standard linear bridges. Although some work has been conducted to investigate the curved bridge dynamic analysis under seismic inputs, the framework for analyzing the curved bridges’ vulnerability under various angles of inputs is still lacking. In this paper, we conducted a series of curved bridge seismic analyses based on different inputs and conducted a parametric study of the bridge performance using finite element models. We conducted time history analyses by applying seismic inputs to investigate the bridge dynamic responses based on different angle inputs and other different structural parameters. We developed an approach identifying the most vulnerable direction of the seismic inputs and the strongest dynamic responses for curved bridges based on time series analysis. This approach was validated with the dynamic analysis of a simplified bridge model. The method developed in this paper will help improve the curved bridge design code and further provide suggestions about mitigating seismic response for device design.
Climate Change Knowledge and Perception among Farming Households in Nigeria
Authors: Madaki Mustapha Yakubu , Muench Steffen , Kaechele Harald , Bavorova Miroslava
Published: May 2023

Nigeria is committed to achieving a 20% unconditional and 45% conditional reduction of GHG emissions by 2030 through a strong focus on awareness of and preparedness for climate change impacts via the mobilization of local communities for climate change mitigation actions. As land cover changes and forestry contribute 38% and agriculture contributes 13% of the country’s GHGs, farmers are among the stakeholders to be aware of and prepare for climate change mitigations and adaptations. This study assessed the knowledge of agriculturally related practices associated with climate change and its relation to climate change perception. One thousand and eighty (1080) smallholder farmers were interviewed across six agroecological zones (AEZs) of Nigeria using a structured questionnaire. The results revealed that most farmers know that deforestation and land clearance by bush burning contributes to climate change. However, many farmers did not know that methane emissions from livestock (enteric fermentation) can cause climate change. Our results further show that the farmers’ perception of climate change is associated with climate change knowledge. Factors affecting the climate change knowledge of farmers include information received from government extension services, environmental NGOs, and radio, as well as experiencing extreme weather events. Farmers of dry AEZs were more aware and knowledgeable of the agricultural practices contributing to the changing environment. Increased exposure to climate change events thus appears to elevate the knowledge on the topic. Using government services, environmental NGOs, and radio to disseminate climate change information will help further in guiding and shaping farmers’ perceptions towards scientific findings for appropriate actions.
The Efficacy of Regeneration Oil and Almond Oil on Split-Thickness Skin Graft Donor Sites: A Single-Blinded Randomized Controlled Trial
Authors: Riedler Karoline , Hecker Andrzej , Bauer Birgit , Tax Christa , Gmainer Daniel Georg , Pignet Anna-Lisa , Kamolz Lars-Peter , Lumenta David Benjamin
Published: May 2023

Background and Objectives: Essential oils are a complementary treatment and can play an important role in scar care. The aim of this study was to evaluate and compare the efficacy of a new essential oil (regeneration oil) with a control group on scar quality in healed split-thickness skin graft donor sites. Materials and Methods: A single-center blinded randomized controlled study was performed on 30 patients with healed split-thickness skin graft donor site. The patients were randomly allocated into blended regeneration oil (n = 14) and pure almond oil (n = 16) groups. Application of the assigned oil occurred twice a day for 6 months. Scarring (Patient and Observer Scar Assessment Scale), itching (ITCH Assessment Scale) and scar discoloration (colorimetry) of the donor sites were assessed after 1, 3 and 6 months. Results: We found no statistically significant differences between the groups in any applied parameter. We observed comparable outcomes (scar quality, itchiness, colorit) in healed split-thickness skin graft donor sites for both oils. Conclusions: Regeneration oil and control oil presented comparable results regarding scar quality, itchiness and colorit in healed split-thickness skin graft donor sites after 6 months of application. Both oils are suitable for skin/scar care in split-thickness skin graft donor sites.
Principle and Method for Determining the Calendar Safety Life of Aircraft Structural Protection Systems
Authors: Zhang Teng , Zhang Tianyu , He Yuting , Hou Bo , Li Changfan
Published: May 2023

The calendar safety life of the surface protection system in aircraft structures is the time limit for it to be used without functional failure at a certain level of reliability and confidence. The reliability of such protection systems and the operational safety and economy of the structure are closely related. This paper firstly establishes two methods for determining the calendar safety life of aircraft structural protection systems under a single service environment and in multiple service environments. A method for determining the reliability of the calendar safety life of the aircraft structural protection system was proposed, and an expression of the relationship between the maintenance costs for the aircraft fleet and the reliability of the calendar safety life of the aircraft structural protection system based on the relationship between the amount of corrosion damage to the structural substrate and the corrosion time and the expression of the calendar safety life of the protection system was established. Finally, taking a hypothetical aircraft fuselage wall plate connection structure as an example, an alternating corrosion fatigue test with protection system specimens was carried out. The process for determining the calendar safety life of the structural protection system and its reliability are given. This method is important to ensure the safety of aircraft structures, improve the efficiency of use, and reduce maintenance costs. Generally speaking, the reliability of the calendar safety life of the structure is 99.9%, and after the analysis in this paper, the reliability of the structural protection system is about 70%.
Comparative Evaluation of Coated Carbide and CBN Inserts Performance in Dry Hard-Turning of AISI 4140 Steel Using Taguchi-Based Grey Relation Analysis
Authors: Özdemir Mustafa , Rafighi Mohammad , Al Awadh Mohammed
Published: May 2023

Dry hard-turning is a vital manufacturing method for machining hardened steel due to its low cost, high machining efficiency, and green environmental protection. This study aims to analyze the effect of various machining parameters on cutting forces and surface roughness by employing RSM and ANOVA. In addition, multi-objective optimization (Grey Relation Analysis: GRA) is performed to determine the optimum machining parameters. Dry hard-turning tests were carried out on AISI 4140 steel (50 HRC) using coated carbide and CBN inserts with different nose radii. The results show that the cutting force components are greatly affected by the cutting depth and cutting speed for both cutting inserts. As the level of cutting depth and cutting speed rise, the cutting forces also increase. However, the feed rate was the main factor in surface roughness. A low feed rate and high cutting speed lead to good surface quality. According to the results, CBN inserts exhibited better performance compared to carbide inserts in terms of minimum cutting forces and surface roughness. The lowest radial force (Fx = 55.59 N), tangential force (Fy = 15.09 N), cutting force (Fz = 30.49 N), and best surface quality (Ra = 0.28 µm, Rz = 1.8 µm) were obtained using a CBN tool. Finally, based on the GRA, the (V = 120 m/min, f = 0.04 mm/rev, a = 0.06 mm, r = 0.8 mm) have been chosen as optimum machining parameters to minimize all responses simultaneously in the machining of AISI 4140 steel using both carbide and CBN inserts.
Vocational Domain Identification with Machine Learning and Natural Language Processing on Wikipedia Text: Error Analysis and Class Balancing
Authors: Nikiforos Maria Nefeli , Deliveri Konstantina , Kermanidis Katia Lida , Pateli Adamantia
Published: May 2023

Highly-skilled migrants and refugees finding employment in low-skill vocations, despite professional qualifications and educational backgrounds, has become a global tendency, mainly due to the language barrier. Employment prospects for displaced communities are mostly decided by their knowledge of the sublanguage of the vocational domain they are interested in working. Common vocational domains include agriculture, cooking, crafting, construction, and hospitality. The increasing amount of user-generated content in wikis and social networks provides a valuable source of data for data mining, natural language processing, and machine learning applications. This paper extends the contribution of the authors’ previous research on automatic vocational domain identification by further analyzing the results of machine learning experiments with a domain-specific textual data set while considering two research directions: a. prediction analysis and b. data balancing. Wrong prediction analysis and the features that contributed to misclassification, along with correct prediction analysis and the features that were the most dominant, contributed to the identification of a primary set of terms for the vocational domains. Data balancing techniques were applied on the data set to observe their impact on the performance of the classification model. A novel four-step methodology was proposed in this paper for the first time, which consists of successive applications of SMOTE oversampling on imbalanced data. Data oversampling obtained better results than data undersampling in imbalanced data sets, while hybrid approaches performed reasonably well.