bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelets and the Role of P2X Receptors in Nociception, Pain, Neuronal Toxicity and Thromboinflammation
Authors: Rawish Elias , Langer Harald F.
Published: June 2022

P2X receptors belong to a family of cation channel proteins, which respond to extracellular adenosine 5′-triphosphate (ATP). These receptors have gained increasing attention in basic and translational research, as they are central to a variety of important pathophysiological processes such as the modulation of cardiovascular physiology, mediation of nociception, platelet and macrophage activation, or neuronal–glial integration. While P2X1 receptor activation is long known to drive platelet aggregation, P2X7 receptor antagonists have recently been reported to inhibit platelet activation. Considering the role of both P2X receptors and platelet-mediated inflammation in neuronal diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and stroke, targeting purinergic receptors may provide a valuable novel therapeutic approach in these diseases. Therefore, the present review illuminates the role of platelets and purinergic signaling in these neurological conditions to evaluate potential translational implications.
The Functional Characterization of GCaMP3.0 Variants Specifically Targeted to Subcellular Domains
Authors: Kempmann Annika , Gensch Thomas , Offenhäusser Andreas , Tihaa Irina , Maybeck Vanessa , Balfanz Sabine , Baumann Arnd
Published: June 2022

Calcium (Ca2+) ions play a pivotal role in physiology and cellular signaling. The intracellular Ca2+ concentration ([Ca2+]i) is about three orders of magnitude lower than the extracellular concentration, resulting in a steep transmembrane concentration gradient. Thus, the spatial and the temporal dynamics of [Ca2+]i are ideally suited to modulate Ca2+-mediated cellular responses to external signals. A variety of highly sophisticated methods have been developed to gain insight into cellular Ca2+ dynamics. In addition to electrophysiological measurements and the application of synthetic dyes that change their fluorescent properties upon interaction with Ca2+, the introduction and the ongoing development of genetically encoded Ca2+ indicators (GECI) opened a new era to study Ca2+-driven processes in living cells and organisms. Here, we have focused on one well-established GECI, i.e., GCaMP3.0. We have systematically modified the protein with sequence motifs, allowing localization of the sensor in the nucleus, in the mitochondrial matrix, at the mitochondrial outer membrane, and at the plasma membrane. The individual variants and a cytosolic version of GCaMP3.0 were overexpressed and purified from E. coli cells to study their biophysical properties in solution. All versions were examined to monitor Ca2+ signaling in stably transfected cell lines and in primary cortical neurons transduced with recombinant Adeno-associated viruses (rAAV). In this comparative study, we provide evidence for a robust approach to reliably trace Ca2+ signals at the (sub)-cellular level with pronounced temporal resolution.
Zinc Coordination Compounds with Benzimidazole Derivatives: Synthesis, Structure, Antimicrobial Activity and Potential Anticancer Application
Authors: Raducka Anita , Świątkowski Marcin , Korona-Głowniak Izabela , Kaproń Barbara , Plech Tomasz , Szczesio Małgorzata , Gobis Katarzyna , Szynkowska-Jóźwik Małgorzata Iwona , Czylkowska Agnieszka
Published: June 2022

Developing new, smart drugs with the anticancer activity is crucial, especially for cancers, which cause the highest mortality in humans. In this paper we describe a series of coordination compounds with the element of health, zinc, and bioactive ligands, benzimidazole derivatives. By way of synthesis we have obtained four compounds named C1, C2, C4 and C4. Analytical analyses (elemental analysis (EA), flame atomic absorption spectrometry (FAAS)), spectroscopic (Fourier transform infrared spectroscopy (FT-IR), mass spectrometry (MS)) and thermogravimetric (TG) methods and the definition of crystal structures were used to explore the nature of bonding and to elucidate the chemical structures. The collected analytical data allowed the determination of the stoichiometry in coordination compounds, thermal stability, crystal structure and way of bonding. The cytotoxicity effect of the new compounds as a potential antitumor agent on the glioblastoma (T98G), neuroblastoma (SK-N-AS) and lung adenocarcinoma (A549) cell lines and human normal skin fibroblasts (CCD-1059Sk) was also determined. Cell viability was determined by the MTT assay. The results obtained confirmed that conversion of ligands into the respective metal complexes significantly improved their anticancer properties. The complexes were screened for antibacterial and antifungal activities. The ADME technique was used to determine the physicochemical and biological properties.
Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility
Authors: Covaceuszach Sonia , Peche Leticia Yamila , Konarev Petr Valeryevich , Grdadolnik Joze , Cattaneo Antonino , Lamba Doriano
Published: June 2022

The human genetic variant BDNF (V66M) represents the first example of neurotrophin family member that has been linked to psychiatric disorders. In order to elucidate structural differences that account for the effects in cognitive function, this hproBDNF polymorph was expressed, refolded, purified, and compared directly to the WT variant for the first time for differences in their 3D structures by DSF, limited proteolysis, FT-IR, and SAXS measurements in solution. Our complementary studies revealed a deep impact of V66M polymorphism on hproBDNF conformations in solution. Although the mean conformation in solution appears to be more compact in the V66M variant, overall, we demonstrated a large increase in flexibility in solution upon V66M mutation. Thus, considering that plasticity in IDR is crucial for protein function, the observed alterations may be related to the functional alterations in hproBDNF binding to its receptors p75NTR, sortilin, HAP1, and SorCS2. These effects can provoke altered intracellular neuronal trafficking and/or affect proBDNF physiological functions, leading to many brain-associated diseases and conditions such as cognitive impairment and anxiety. The structural alterations highlighted in the present study may pave the way to the development of drug discovery strategies to provide greater therapeutic responses and of novel pharmacologic strategy in human populations with this common polymorphism, ultimately guiding personalized medicine for neuropsychiatric disorders.
Editorial to the Special Issue “Molecular Motors: From Single Molecules to Cooperative and Regulatory Mechanisms In Vivo”
Authors: Capitanio Marco , Reconditi Massimo
Published: June 2022

The Molecular motors or motor proteins are able to generate force and do mechanical work that is used to displace a load or produce relative movements between molecules or macromolecular assembles [...]
Multi-Sensor-Based Hierarchical Detection and Tracking Method for Inland Waterway Ship Chimneys
Authors: Wu Fumin , Chen Qianqian , Wen Yuanqiao , Xiao Changshi , Zeng Feier
Published: June 2022

In the field of automatic detection of ship exhaust behavior, a deep learning-based multi-sensor hierarchical detection method for tracking inland river ship chimneys is proposed to locate the ship exhaust behavior detection area quickly and accurately. Firstly, the primary detection uses a target detector based on a convolutional neural network to extract the shipping area in the visible image, and the secondary detection applies the Ostu binarization algorithm and image morphology operation, based on the infrared image and the primary detection results to obtain the chimney target by combining the location and area features; further, the improved DeepSORT algorithm is applied to achieve the ship chimney tracking. The results show that the multi-sensor-based hierarchical detection and tracking method can achieve real-time detection and tracking of ship chimneys, and can provide technical reference for the automatic detection of ship exhaust behavior.
Prevalence and Risk Factors of Zoonotic Dermatophyte Infection in Pet Rabbits in Northern Taiwan
Authors: Chang Che-Cheng , Wechtaisong Wittawat , Chen Shih-Yu , Cheng Ming-Chu , Chung Cheng-Shu , Lin Lee-Shuan , Lien Yi-Yang , Tsai Yi-Lun
Published: June 2022

Dermatophytes are the group of keratinophilic fungi that cause superficial cutaneous infection, which traditionally belong to the genera Trichophyton, Microsporum, and Epidermophyton. Dermatophyte infection is not only a threat to the health of small animals, but also an important zoonotic and public health issue because of the potential transmission from animals to humans. Rabbit dermatophytosis is often clinically identified; however, limited information was found in Asia. The aims of this study are to investigate the prevalence and to evaluate the risk factors of dermatophytosis in pet rabbits in Northern Taiwan. Between March 2016 and October 2018, dander samples of pet rabbits were collected for fungal infection examination by Wood’s lamp, microscopic examination (KOH preparation), fungal culture, and PCR assay (molecular identification). Z test and Fisher’s exact test were performed to evaluate the potential risk factors, and logistic regression analysis was then performed to build the model of risk factors related to dermatophyte infection. Of the collected 250 dander samples of pet rabbits, 29 (11.6%) samples were positive for dermatophytes by molecular identification. In those samples, 28 samples were identified as the T. mentagrophytes complex and 1 sample was identified as M. canis. Based on the results of the Firth’s bias reduction logistic analyses, animal source (rabbits purchased from pet shops) and number of rearing rabbits (three rabbits or more) were shown as the main risks for dermatophyte infection in the pet rabbits in Taiwan. The results of the present study elucidate the prevalence of rabbit dermatophyte infection, pathogens, and risk factors in Taiwan, and provide an important reference for the prevention and control of rabbit dermatophytosis.
Locomotor Activity of Ixodes ricinus Females in 900 MHz Electromagnetic Field
Authors: Vargová Blažena , Majláth Igor , Kurimský Juraj , Cimbala Roman , Zbojovský Ján , Tryjanowski Piotr , Majláthová Viktoria
Published: June 2022

Mobile telecommunications technologies have become an indispensable part of people’s lives of all ages around the world. They affect personal life and social interactions and are a work tool in the work routine. Network availability requirements and the quality of the Internet connection are constantly increasing, to which telecommunications providers are responding. Humans and wildlife live in the permanent presence of electromagnetic radiation with just a minor knowledge of the impact this radiation has. The aim of our study was to investigate the effect of a 900 MHz electromagnetic field (EMF) on the locomotor behavior of female Ixodes ricinus ticks under laboratory conditions. Experiments were performed in the radiation-shielded tube (RST) test and radiation-shielded circular open-field arena placed in an anechoic chamber. Altogether, 480 female I. ricinus ticks were tested. In the RST arena, no differences in preference for irradiated and shielded parts of experimental modules were observed; in the open-field arena, the time spent and the trajectory passed was significantly longer in the part exposed to the EMF.
Experimental Study on Long-Term Mechanical Properties of Prestressed Glulam Continuous Beams
Authors: Guo Nan , Zhou Shouting , Zhao Yan , Mei Lidan , Zhang Yunan
Published: June 2022

To study the effect of wood creep on the long-term performance of prestressed glulam continuous beams, a 180-day test was carried out on beams configured with different numbers of steel wires (2, 4, 6) and with different prestress values (0, 7, 14 kN). By investigating the stress loss of the steel wires in the beam and the change in the mid-span deflection over time, the factors influencing the creep of the continuous beam were analyzed. Three models were selected to fit the creep process of the test beams. Moreover, the creep deformation coefficient θ was introduced to reflect the influence of glulam creep on the deflection change in the test beams and to predict the total deflection of the beam within 50 years. The results showed that with increasing the number of steel wires and the prestress value on the beams, the total stress of the steel wires declined more and faster. Increasing the number of steel wires or decreasing the prestress force value could effectively restrain the change speed of the mid-span long-term deflection of the beam. Three models were compared, and the power-law equation was the most accurate. At familiar steel wire quantities and force levels, the θ value of the test beams within the design service life of 50 years was determined to be 1.28–2.29.
Deposition of Aluminide Coatings onto AISI 304L Steel for High Temperature Applications
Authors: Anwer Zubia , Tufail Muhammad , Chandio Ali Dad
Published: June 2022

The nickel aluminides are commonly employed as a bond coat material in thermal barrier coating systems for the components of aeroengines operated at very high temperatures. However, their lifetime is limited due to several factors, such as outward diffusion of substrate elements, surface roughness at high temperatures, morphological changes of the oxide layer, etc. For this reason, inter-diffusion migrations were studied in the presence and absence of nickel coating. In addition, a hot corrosion study was also carried out. Thus, on one set of substrates, nickel electrodeposition was carried out, followed by a high activity pack aluminizing process, while another set of substrates were directly aluminized. The microstructural, mechanical, and oxidation properties were examined using different characterization techniques, such as SEM-EDS, optical microscopy, XRD, optical emission spectroscopy, surface roughness (Ra), and adhesion tests. In addition, the variable oxidation temperatures were employed to better understand their influence on the roughness, degree of spallation (DoS), and morphology. The results show that AISI 304L substrates do not respond to aluminizing treatment, i.e., no aluminide coating was formed; rather, a nearly pure aluminum (or alloy) was observed on the substrate. On the contrary, successful formation of an aluminide coating was observed on the nickel-electrodeposited substrates. In particular, a minimum amount of migrations were noted, which is attributed to nickel coating. Moreover, the scratch test at 10 N load revealed neither cracking nor peeling off, thereby indicating good adhesion of the aluminide coating before oxidation. The as-aluminized samples were oxidized between 700 °C to 1100 °C in air for 8 h each. The degree of spallation showed an incremental trend as temperatures increased. Likewise, oxide morphologies showed temperature dependence. On the other hand, average surface roughness (from Ra = 2.3 µm to 5.8 µm) was also increased as temperatures rose. Likewise, the mass gain showed linearity as temperatures increased during oxidation. The hot corrosion responses of electrodeposited-aluminized samples were superior among all specimens. An extensive discussion is presented based on the observations noted above.
Effect of Boron Doping on the Interlayer Spacing of Graphite
Authors: Bao Chenguang , Zeng Qing , Li Fujin , Shi Lei , Wu Wei , Yang Li , Chen Yuxi , Liu Hongbo
Published: June 2022

Boron-doped graphite was prepared by the heat treatment of coke using B4C powder as a graphitization catalyst to investigate the effects of the substitutional boron atoms on the interlayer spacing of graphite. Boron atoms can be successfully incorporated into the lattice of graphite by heat treatment, resulting in a reduction in the interlayer spacing of graphite to a value close to that of ideal graphite (0.3354 nm). With an increase in the catalyst mass ratio, the content of substituted boron in the samples increased significantly, causing a decrease in the interlayer spacing of the boron-doped graphite. Density functional theory calculations suggested that the effects of the substitutional boron atoms on the interlayer spacing of the graphite may be attributed to the transfer of Π electrons between layers, the increase in the electrostatic surface potential of the carbon layer due to the electron-deficient nature of boron atoms, and Poisson contraction along the c-axis.
Design of a Morphing Skin with Shape Memory Alloy Based on Equivalent Thermal Stress Approach
Authors: Zhang Wei , Ma Yueyin , Gao Xinyu , Chen Wanhua , Nie Xutao
Published: June 2022

Shape memory alloy (SMA) is one of the potential driving devices for morphing aircraft due to its advantages of pseudoelasticity, superelasticity, and shape memory effect. Precise and fast analysis of SMA has simultaneously become a key requirement for industrial applications. In this study, a user-defined material subroutine (UMAT) was implemented and successfully applied in a three-dimensional numerical simulation in ABAQUS based on the extended Boyd–Lagoudas model. In addition to the conventional detwinned martensite (Md) and austenite (A), twinned martensite (Mt) was also considered to model the practical transformation accurately. Then, the equivalent thermal strain approach was adopted to simplify the simulation complexity with UMAT. By resetting the thermal expansion coefficient, the thermal strain equivalent to the original phase transformation strain was generated. The approach was validated in two cases, showing consistent results with the extended Boyd–Lagoudas model and reduction in time consumption by 89.1%. Lastly, an active morphing skin integrating the single-range SMA and a stainless-steel plate was designed to realize two-way morphing. The calculated arc height variation of the skin was 3.74 mm with a relative error of 1.84% compared to the experimental result of 3.81 mm. The coupled use of UMAT and the equivalent thermal stress approach helped to reduce the challenge in modeling SMA.
Correction: Omar et al. Antifungal Evaluation and Molecular Docking Studies of Olea europaea Leaf Extract, Thymus vulgaris and Boswellia carteri Essential Oil as Prospective Fungal Inhibitor Candidates. Molecules 2021, 26, 6118
Authors: Omar Hanaa S. , Abd El-Rahman Soheir N. , AlGhannam Sheikha M. , Reyad Nour El-Houda A. , Sedeek Mohamed S.
Published: June 2022

The authors of this paper [...]
Accum™ Technology: A Novel Conjugable Primer for Onco-Immunotherapy
Authors: El-Kadiry Abed El-Hakim , Beaudoin Simon , Plouffe Sebastien , Rafei Moutih
Published: June 2022

Compromised activity is a common impediment for biologics requiring endosome trafficking into target cells. In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or subsequently pumped extracellularly, leading to a reduction in intracellular accumulation. In subsets of dendritic cells (DCs), endosome-engulfed antigens face non-specific proteolysis and collateral damage to epitope immunogenicity before proteasomal processing and subsequent surface presentation. To bypass these shortcomings, we devised Accum™, a conjugable biotechnology harboring cholic acid (ChAc) and a nuclear localization signal (NLS) sequence for endosome escape and prompt nuclear targeting. Combined, these mechanisms culminate in enhanced intracellular accumulation and functionalization of coupled biologics. As proof-of-principle, we have biochemically characterized Accum, demonstrating its adaptability to ADCs or antigens in different cancer settings. Additionally, we have validated that endosome escape and nuclear routing are indispensable for effective intracellular accumulation and guaranteed target cell selectivity. Importantly, we have demonstrated that the unique mechanism of action of Accum translates into enhanced tumor cytotoxicity when coupled to ADCs, and durable therapeutic and prophylactic anti-cancer immunogenicity when coupled to tumor antigens. As more pre-clinical evidence accumulates, the adaptability, unique mechanism of action, and high therapeutic potency of Accum signal a promising transition into clinical investigations in the context of onco-immunotherapy.
Stability, Morphology, and Effects of In Vitro Digestion on the Antioxidant Properties of Polyphenol Inclusion Complexes with β-Cyclodextrin
Authors: Ntuli Sunday , Leuschner Machel , Bester Megan J. , Serem June C.
Published: June 2022

Polyphenols are inversely associated with the incidence of chronic diseases, but therapeutic use is limited by poor stability and bioaccessibility. Encapsulation has been shown to overcome some of these limitations. A selection of polyphenols (catechin, gallic acid, and epigallocatechin gallate) and their combinations were encapsulated in beta-cyclodextrin (βCD). Encapsulation was characterized and the thermal and storage stability was evaluated using the 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The samples were then subjected to in vitro digestion using a simple digestion (SD) model (gastric and duodenal phases) and a more complex digestion (CD) model (oral, gastric, and duodenal phases). Thereafter, the chemical (oxygen radical absorbance capacity assay) and cellular (dichlorofluorescein diacetate assay in Caco-2 cells) antioxidant and antiglycation (advanced glycation end-products assay) activities were determined. Inclusion complexes formed at a 1:1 molar ratio with a high encapsulation yield and efficiency. Encapsulation altered the morphology of the samples, increased the thermal stability of some and the storage stability of all samples. Encapsulation maintained the antioxidant activity of all samples and significantly improved the antiglycation and cellular antioxidant activities of some polyphenols following SD. In conclusion, the formed inclusion complexes of βCD with polyphenols had greater storage stability, without altering the beneficial cellular effects of the polyphenols.
Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity
Authors: Habaz Lihi , Bedard Korey , Smith Mitchell , Du Liqin , Kornienko Alexander , Hudlicky Tomas
Published: June 2022

A 15-step chemoenzymatic total synthesis of C-1 methoxycarbonyl narciclasine (10) was accomplished. The synthesis began with the toluene dioxygenase-mediated dihydroxylation of ortho-dibromobenzene to provide the corresponding cis-dihydrodiol (12) as a single enantiomer. Further key steps included a nitroso Diels–Alder reaction and an intramolecular Heck cyclization. The C-1 homolog 10 was tested and evaluated for antiproliferative activity against natural narciclasine (1) as the positive control. Experimental and spectral data are reported for all novel compounds.
Non-Linear Association between Folate/Vitamin B12 Status and Cognitive Function in Older Adults
Authors: Ding Zhe , Luo Lihui , Guo Shaohui , Shen Qing , Zheng Yueying , Zhu Shengmei
Published: June 2022

Although folate and vitamin B12 status have long been implicated in cognitive function, there is no consensus on the threshold of folate and vitamin B12 for assessing their impacts on cognition. The goal of this study was to detail the association between folate and vitamin B12 with cognitive performance. We analyzed cross-sectional data of older adults (≥60 y; n = 2204) from the NHANES (National Health and Nutrition Examination Surveys) cohort from 2011–2014. The restricted cubic spline model was used for describing the associations between serum total folate, RBC folate, 5-methyltetrahydrofolate, and vitamin B12 and the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests, the Animal Fluency (AF) test, and the Digit Symbol Substitution Test (DSST), respectively. Older adults with a different folate and vitamin B12 status were clustered by artificial intelligence unsupervised learning. The statistically significant non-linear relationships between the markers of folate or vitamin B12 status and cognitive function were found after adjustments for potential confounders. Inverse U-shaped associations between folate/vitamin B12 status and cognitive function were observed, and the estimated breakpoint was described. No statistically significant interaction between vitamin B12 and folate status on cognitive function was observed in the current models. In addition, based on the biochemical examination of these four markers, older adults could be assigned into three clusters representing relatively low, medium, and high folate/vitamin B12 status with significantly different scores on the CERAD-DR and DSST. Low or high folate and vitamin B12 status affected selective domains of cognition, and was associated with suboptimal cognitive test outcomes.
High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
Authors: Kim Minju , Kim Yeon-hee , Min Sohyun , Lee Seung-Min
Published: June 2022

Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 weeks of gestation and their offspring until 30 weeks were fed a control (CTRL, FeSO4 0 g/1 kg) or high iron (HFe, FeSO4 9.9 g/1 kg) diets. HFe group showed higher iron accumulation in the liver with increased hepcidin, reduced TfR1/2 mRNAs, and lowered ferritin heavy chain (FTH) proteins in both liver and adipose tissues despite iron loading. HFe decreased body weight, fat weight, adipocyte size, and triglyceride levels in the blood and fat, along with downregulation of lipogenesis genes, including PPARγ, C/EBPα, SREBP1c, FASN, and SCD1, and fatty acid uptake and oxidation genes, such as CD36 and PPARα. UCP2, adiponectin, and mRNA levels of antioxidant genes such as GPX4, HO-1, and NQO1 were increased in the HFe group, while total glutathione was reduced. We conclude that prolonged exposure to high iron from the fetal stage to adulthood may decrease fat accumulation by altering ferritin expression, adipocyte differentiation, and triglyceride metabolism, resulting in an alteration in normal growth.
Tuberculosis and Autoimmunity
Authors: Belyaeva Irina V. , Kosova Anna N. , Vasiliev Andrei G.
Published: June 2022

Tuberculosis remains a common and dangerous chronic bacterial infection worldwide. It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.
Computational Investigations of Traditional Chinese Medicinal Compounds against the Omicron Variant of SARS-CoV-2 to Rescue the Host Immune System
Authors: Naman Ziad Tareq , Kadhim Salim , Al-Isawi Zahraa J. K. , Butch Christopher J. , Muhseen Ziyad Tariq
Published: June 2022

Macrodomain-I of the NSP3 (non-structural protein 3) is responsible for immune response hijacking in the SARS-CoV-2 infection known as COVID-19. In the omicron variant (B.1.1.529), this domain harbors a new mutation, V1069I, which may increase the binding of ADPr and consequently the infection severity. This macrodomain-I, due to its significant role in infection, is deemed to be an important drug target. Hence, using structural bioinformatics and molecular simulation approaches, we performed a virtual screening of the traditional Chinese medicines (TCM) database for potential anti-viral drugs. The screening of 57,000 compounds yielded the 10 best compounds with docking scores better than the control ADPr. Among the top ten, the best three hits—TCM42798, with a docking score of −13.70 kcal/mol, TCM47007 of −13.25 kcal/mol, and TCM30675 of −12.49 kcal/mol—were chosen as the best hits. Structural dynamic features were explored including stability, compactness, flexibility, and hydrogen bonding, further demonstrating the anti-viral potential of these hits. Using the MM/GBSA approach, the total binding free energy for each complex was reported to be −69.78 kcal/mol, −50.11 kcal/mol, and −47.64 kcal/mol, respectively, which consequently reflect the stronger binding and inhibitory potential of these compounds. These agents might suppress NSP3 directly, allowing the host immune system to recuperate. The current study lays the groundwork for the development of new drugs to combat SARS-CoV-2 and its variants.
Longitudinal Effects on Metabolic Biomarkers in Veterans 12 Months Following Discharge from Pharmacist-Provided Diabetes Care: A Retrospective Cohort Study
Authors: Morello Candis M. , Lai Lytia , Chen Claire , Leung Chui Man , Hirsch Jan D. , Bounthavong Mark
Published: June 2022

Clinical pharmacist interventions have resulted in optimized diabetes control in complex patients; however, there are no studies examining the durability of achieved outcomes after patients discontinued being seen by the pharmacist. A pharmacist-led comprehensive medication management (CMM) Diabetes Intensive Medication Management (DIMM) “tune up” clinic provided the opportunity to evaluate long-term glycemic control outcomes following clinical discharge. This study used a retrospective cohort study design with a matched primary care provider (PCP) comparison group. Outcomes were compared between the groups at several post-discharge intervals (6, 9, and 12 months) using independent t tests and chi-square tests, where appropriate. DIMM-managed patients achieved an average HbA1c reduction of 3% upon discharge, and maintained an average HbA1c concentration that was significantly lower than PCP-managed patients at 6 months (p < 0.001) and 9 months (p = 0.009) post-discharge. Although DIMM-managed patients had lower HbA1c than PCP-managed patients at 12 months post-discharge, the difference was not significant (p = 0.105). Similar findings were noted for average FPG and LDL across the study time points. No differences in average HDL levels were reported across the time points. A significantly larger proportion of DIMM-managed patients maintained HbA1c < 8% compared to PCP-managed patients at 6 months (67.5% versus 47.2%, p = 0.001) and 9 months (62.6% versus 40.6%, p = 0.040) post-discharge; DIMM-managed patients had a larger, but non-significant, proportion of goal retention compared to PCP-managed patients at 12 months (56.9% versus 47.2%, p = 0.126) post-discharge. Similarly, a significantly larger proportion of DIMM-managed patients sustained HbA1c < 9% compared to PCP-managed patients at 6 months (87.8% versus 66.7%, p < 0.001) and 9 months (82.1% versus 68.3%, p = 0.012) post-discharge; however, there was no significant difference at 12 months. The attenuation of the DIMM-managed metabolic biomarkers suggests that an additional follow-up visit or touchpoint may be helpful. The personalized care of the DIMM “tune up” approach was successful in achieving sustained glycemic control for up to 9 months. Outcomes can help inform future long-term result durability evaluations.
Physicians’ and Nurses’ Perceptions of Pharmacists’ Competencies, and Their Needs of Pharmacists during COVID-19
Authors: Mamiya Kayoko Takeda , Hirata Kazumasa
Published: June 2022

Objective: To understand how physicians and nurses evaluate Japanese pharmacists’ observed competencies and to explore potential new roles for pharmacists during COVID-19. Methods: A web-based Japanese survey with 25 items assessing physicians’ and nurses’ workplaces and the degree of their relationship with pharmacists in their daily work was conducted (Intage, Inc., Tokyo, Japan) in Japan in June 2021 (for one week beginning on 22 June). The survey asked physicians and nurses whether pharmacists had the required professional competencies and whether the needs of physicians and nurses were met by pharmacists in their workplaces. The scored questionnaire data, which used a Likert scale, were calculated as the mean and standard deviation (S.D.). The perception assessment scale used four levels (1, Agree; 2, Slightly agree; 3, Slightly disagree; and 4, Disagree). Results: This perception study ultimately obtained responses from 304 physicians and 336 nurses. Most pharmacists’ competencies were evaluated as “Agree” or “Slightly agree” by the physicians and nurses. However, the competencies for “Fundamental basic science” and “Prescription analytical skill or case analytical skill” were evaluated significantly lower by physicians than by nurses (Mann–Whitney U test, p < 0.01). Regarding physicians’ and nurses’ needs from pharmacists, nurses hoped that pharmacists could play a greater role as healthcare professionals in response to all items; in contrast, physicians hoped that pharmacists could play a greater role as healthcare professionals in response to five items. The common items were related to the role of healthcare professionals in the community. Conclusion: Our research is necessary for facilitating interprofessional collaboration and reflecting these results in pharmacy education by allowing physicians and nurses to assess the competencies of pharmacists and to understand their needs; however, these data are from only one country.
Anisotropic Tensile Characterisation of Eucalyptus nitens Timber above Its Fibre Saturation Point, and Its Application
Authors: Chen Xudong , Cheng Yingyao , Chan Andrew , Holloway Damien , Nolan Gregory
Published: June 2022

Plantation-grown Eucalyptus nitens (E. nitens) has been grown predominantly for the pulp and paper industry. In this study, the suitability of E. nitens as a structural material is examined using static tensile tests in a universal testing machine. The anisotropic tensile behaviour of 240 Eucalyptus nitens small clear wood samples with a diversity of grain angles was examined in both dry and wet conditions. The samples had a highly anisotropic tensile characterisation in the context of both a low moisture content (MC = 12%) and a high moisture content (MC > its fibre saturation point, FSP). The results showed that, in a high moisture content condition, the wood showed a lower failure strength and more ductility at all grain angles than in a low moisture content condition. The underlying failure mechanism of Eucalyptusnitens timber in tension was determined in detail from the perspective of the microstructure of wood cellulose polymer composites. The mean tensile failure strengths perpendicular and parallel to the fibre direction were, respectively, 5.6 and 91.6 MPa for the low MC and 3.8 and 62.1 MPa for the high MC condition. This research provides a basis for using E. nitens as a potential structural tensile member. The moisture modification factors of Eucalyptus timber at a mean level are higher than those of the traditional construction material, Pinus radiata, implying that E. nitens is promising as a material to be used for tensile members in water saturated conditions.
Blending Modification of Alicyclic Resin and Bisphenol A Epoxy Resin to Enhance Salt Aging Resistance for Composite Core Rods
Authors: Liu Yunpeng , Wang Wanxian , Liu Hechen , Zhang Mingjia , Liu Jie , Qi Junwei
Published: June 2022

In order to promote the application of composite insulators in coastal areas with high temperature, high humidity and high salt, it is of great importance to develop matrix resin with salt corrosion resistance for composite core rods. In this study, bisphenol A epoxy resin was modified by blending with alicyclic epoxy resin (2021P). Three different proportions of 2021P/DGEBA blend resins (0% 2021P/DGEBA, 10% 2021P/DGEBA and 20% 2021P/DGEBA) were prepared, and the high salt medium corrosion test was carried out. The physicochemical (FTIR, DMA, TGA) and electrical properties (dielectric loss, leakage current and breakdown field strength) of the blend resin before and after aging were tested and analyzed, and the optimal blend proportion was determined. The results showed that after salt aging, the Tg of 0% 2021P/DGEBA decreased to 122.99 °C, while the Tg of 10% 2021P/DGEBA reached 134.89 °C; The leakage current of 0% 2021P/DGEBA increased to 48.994 μA, while that of 10% 2021P/DGEBA only increased to 44.549 μA; The breakdown field strength of 0% 2021P/DGEBA dropped to 40.36 kv/mm, while that of 10% 2021P/DGEBA only dropped to 43.63 kv/mm. The introduction of 2021P enhanced the salt corrosion resistance of the blend resin, which could hinder the penetration, diffusion and erosion of external media (such as Na+, Cl−, H2O, etc.) to the matrix resin. The comprehensive properties of 10% 2021P/DGEBA blend system reached the best, which was better than other blending resins, showing great application potential.
Study on Combined Vacuum–Mechanical Defoaming Technology for Flotation Froth and Its Mechanism
Authors: Jiang Haibing , Liu Jiufen , Wang Huaifa , Yang Runquan , Zhao Wenzhi , Yang Duo , Yin Song , Shen Liang
Published: June 2022

Foam is essential in the flotation process. However, the gas–liquid–solid three-phase froth produced in the flotation process has very strong stability and is difficult to burst spontaneously. The existence of these froths will reduce the transport capacity of the pulp and affect the working efficiency of subsequent processes, such as filtration of the flotation concentrate. In this study, a new defoaming device is designed by combining mechanical impact with depressurized defoaming and its defoaming mechanism is analyzed theoretically. In addition, the liquid level height and pulp overflow method are applied to characterize the defoaming efficiency of the new defoaming device. The effects of impeller structure, pressure drop, impeller rotation frequency, and aeration rate on defoaming efficiency were studied. The results show that when increasing the pressure drop, the defoaming increases, but it will also enhance the generation of bubbles. The efficiency of combined mechanical–vacuum defoaming technology is superior under low-pressure drop using an SC impeller. Under −1 kpa vacuum condition, it only takes 168 s to eliminate 20 cm flotation froth height with combined mechanical impact, while it takes 453 s under ambient pressure, indicating that under vacuum conditions, the mechanical-defoaming method can significantly improve the defoaming efficiency, and the two have a certain synergistic effect.
Bridge Crack Inspection Efficiency of an Unmanned Aerial Vehicle System with a Laser Ranging Module
Authors: Kao Szu-Pyng , Wang Feng-Liang , Lin Jhih-Sian , Tsai Jichiang , Chu Yi-De , Hung Pen-Shan
Published: June 2022

In this study, an unmanned aerial vehicle (UAV) with a camera and laser ranging module was developed to inspect bridge cracks. Four laser ranging units were installed adjacent to the camera to measure the distance from the camera to the object to calculate the object’s projection plane and overcome the limitation of vertical photography. The image processing method was adopted to extract crack information and calculate crack sizes. The developed UAV was used in outdoor bridge crack inspection tests; for images taken at a distance of 2.5 m, we measured the crack length, and the error between the result and the real length was less than 0.8%. The developed UAV has a dual-lens design, where one lens is used for bridge inspections and the other lens is used for flight control. The camera of the developed UAV can be rotated from the horizontal level to the zenith according to user requirements; thus, this UAV achieves high safety and efficiency in bridge inspections.
Fault Diagnosis for Power Transformers through Semi-Supervised Transfer Learning
Authors: Mao Weiyun , Wei Bengang , Xu Xiangyi , Chen Lu , Wu Tianyi , Peng Zhengrui , Ren Chen
Published: June 2022

The fault diagnosis of power transformers is a challenging problem. The massive multisource fault is heterogeneous, the type of fault is undetermined sometimes, and one device has only met a few kinds of faults in the past. We propose a fault diagnosis method based on deep neural networks and a semi-supervised transfer learning framework called adaptive reinforcement (AR) to solve the above limitations. The innovation of this framework consists of its enhancement of the consistency regularization algorithm. The experiments were conducted on real-world 110 kV power transformers’ three-phase fault grounding currents of the iron cores from various devices with four types of faults: Phases A, B, C and ABC to ground. We trained the model on the source domain and then transferred the model to the target domain, which included the unbalanced and undefined fault datasets. The results show that our proposed model reaches over 95% accuracy in classifying the type of fault and outperforms other popular networks. Our AR framework fits target devices’ fault data with fewer dozen epochs than other novel semi-supervised techniques. Combining the deep neural network and the AR framework helps diagnose the power transformers, which lack diagnosis knowledge, with much less training time and reliable accuracy.
SafeSoCPS: A Composite Safety Analysis Approach for System of Cyber-Physical Systems
Authors: Ali Nazakat , Hussain Manzoor , Hong Jang-Eui
Published: June 2022

The System of Cyber-Physical Systems (SoCPS) comprises several independent Cyber-Physical Systems (CPSs) that interact with each other to achieve a common mission that the individual systems cannot achieve on their own. SoCPS are rapidly gaining attention in various domains, e.g., manufacturing, automotive, avionics, healthcare, transportation, and more. SoCPS are extremely large, complex, and safety-critical. As these systems are safety-critical in nature, it is necessary to provide an adequate safety analysis mechanism for these collaborative SoCPS so that the whole network of these CPSs work safely. This safety mechanism must include composite safety analysis for a network of collaborative CPS as a whole. However, existing safety analysis techniques are not built for analyzing safety for dynamically forming networks of CPS. This paper introduces a composite safety analysis approach called SafeSoCPS to analyze hazards for a network of SoCPS. In SafeSoCPS, we analyze potential hazards for the whole network of CPS and trace the faults among participating systems through a fault propagation graph. We developed a tool called SoCPSTracer to support the SafeSoCPS approach. Human Rescue Robot System—a collaborative system—is taken as a case study to validate our proposed approach. The result shows that the SafeSoCPS approach enables us to identify 18 percent more general faults and 63 percent more interaction-related faults in a network of a SoCPS.
Multiple-Attention Mechanism Network for Semantic Segmentation
Authors: Wang Dongli , Xiang Shengliang , Zhou Yan , Mu Jinzhen , Zhou Haibin , Irampaye Richard
Published: June 2022

Contextual information and the dependencies between dimensions is vital in image semantic segmentation. In this paper, we propose a multiple-attention mechanism network (MANet) for semantic segmentation in a very effective and efficient way. Concretely, the contributions are as follows: (1) a novel dual-attention mechanism for capturing feature dependencies in spatial and channel dimensions, where the adjacent position attention captures the dependencies between pixels well; (2) a new cross-dimensional interactive attention feature fusion module, which strengthens the fusion of fine location structure information in low-level features and category semantic information in high-level features. We conduct extensive experiments on semantic segmentation benchmarks including PASCAL VOC 2012 and Cityscapes datasets. Our MANet achieves the mIoU scores of 75.5% and 72.8% on PASCAL VOC 2012 and Cityscapes datasets, respectively. The effectiveness of the network is higher than the previous popular semantic segmentation networks under the same conditions.
Ex Vivo and In Vivo Study of Some Isoquinoline Precursors
Authors: Milusheva Miglena , Gledacheva Vera , Batmazyan Margarita , Nikolova Stoyanka , Stefanova Iliyana , Dimitrova Darinka , Saracheva Kremena , Tomov Desislav , Chaova-Gizdakova Veneta
Published: June 2022

This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known as a brain and coronary vasodilator and SM relaxant. Materials and methods: In silico simulation with the PASS online program predicts SM relaxant activity for the compounds. The amides were tested on the isolated gastric SM preparations (SMPs) from rats to determine their effects on spontaneous contractile activity (CA) compared with papaverine. The in vivo effect on the learning and memory processes of rats was also assessed. Results: the data from the isometric measurements showed that one of the compounds caused ex vivo relaxation in circular SM tissues isolated from the stomach (corpus) of male Wistar rats. Conclusion: We found that the compound’s SM relaxation uses the papaverine pathway. It also has an improving effect on the cognitive functions of learning and memory processes in rats.
Modeling and Life Cycle Assessment of a Membrane Bioreactor–Membrane Distillation Wastewater Treatment System for Potable Reuse
Authors: Glover Callan J. , Phillips James A. , Marchand Eric A. , Hiibel Sage R.
Published: June 2022

Wastewater treatment for indirect potable reuse (IPR) is a possible approach to address water scarcity. In this study, a novel membrane bioreactor–membrane distillation (MBR-MD) system was evaluated to determine the environmental impacts of treatment compared to an existing IPR facility (“Baseline”). Physical and empirical models were used to obtain operational data for both systems and inform a life cycle inventory. Life cycle assessment (LCA) was used to compare the environmental impacts of each system. Results showed an average 53.7% reduction in environmental impacts for the MBR-MD system when waste heat is used to operate MD; however, without waste heat, the environmental impacts of MBR-MD are significantly higher, with average impacts ranging from 218% to 1400% greater than the Baseline, depending on the proportion of waste heat used. The results of this study demonstrate the effectiveness of the novel MBR-MD system for IPR and the reduced environmental impacts when waste heat is available to power MD.