bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung Ultrasound Findings in Healthy Children and in Those Who Had Recent, Not Severe COVID-19 Infection
Authors: Cantinotti Massimiliano , Marchese Pietro , Assanta Nadia , Pizzuto Alessandra , Corana Giulia , Santoro Giuseppe , Franchi Eliana , Viacava Cecilia , Van den Eynde Jef , Kutty Shelby , Gargani Luna , Giordano Raffaele
Published: October 2022

Background: Lung ultrasound (LUS) is gaining consensus as a non-invasive diagnostic imaging method for the evaluation of pulmonary disease in children. Aim: To clarify what type of artifacts (e.g., B-lines, pleural irregularity) can be defined normal LUS findings in children and to evaluate the differences in children who did not experience COVID-19 and in those with recent, not severe, previous COVID-19. Methods: LUS was performed according to standardized protocols. Different patterns of normality were defined: pattern 1: no plural irregularity and no B-lines; pattern 2: only mild basal posterior plural irregularity and no B-lines; pattern 3: mild posterior basal/para-spine/apical pleural irregularity and no B-lines; pattern 4: like pattern 3 plus rare B-lines; pattern 5: mild, diffuse short subpleural vertical artifacts and rare B-lines; pattern 6: mild, diffuse short subpleural vertical artifacts and limited B-lines; pattern 7: like pattern 6 plus minimal subpleural atelectasis. Coalescent B-lines, consolidations, or effusion were considered pathological. Results: Overall, 459 healthy children were prospectively recruited (mean age 10.564 ± 3.839 years). Children were divided into two groups: group 1 (n = 336), those who had not had COVID-19 infection, and group 2 (n = 123), those who experienced COVID-19 infection. Children with previous COVID-19 had higher values of LUS score than those who had not (p = 0.0002). Children with asymptomatic COVID-19 had similar LUS score as those who did not have infections (p > 0.05), while those who had symptoms showed higher LUS score than those who had not shown symptoms (p = 0.0228). Conclusions: We report the pattern of normality for LUS examination in children. We also showed that otherwise healthy children who recovered from COVID-19 and even those who were mildly symptomatic had more “physiological” artifacts at LUS examinations.
Cladribine Reduces Trans-Endothelial Migration of Memory T Cells across an In Vitro Blood–Brain Barrier
Authors: Ford Rachel K. , Juillard Pierre , Hawke Simon , Grau Georges E. , Marsh-Wakefield Felix
Published: October 2022

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory effect on lymphocytes at the blood–brain barrier (BBB) in addition to its lymphocyte-depleting and modulating effects, this has not been properly studied. Here, we aimed to determine if cladribine treatment influences trans-endothelial migration of T cell subsets across an inflamed BBB. Human brain endothelial cells stimulated with pro-inflammatory cytokines were used to mimic the BBB. Peripheral blood mononuclear cells were obtained from healthy controls, untreated and cladribine-treated MS patients. The trans-endothelial migration of CD4+ effector memory T (TEM) and CD8+ central memory T (TCM) cells was reduced in cladribine-treated MS patients. CD28 expression was decreased on both CD4+ TEM and CD8+ TCM cells, suggesting lowered peripheral activation of these cells thereby maintaining the integrity of the BBB. In addition, these cells have likely reconstituted following cladribine treatment, revealing a long-term anti-migratory effect. These results highlight new mechanisms by which cladribine acts to control MS pathogenesis.
Vitamin D Levels in Patients with Overlap Syndrome, Is It Associated with Disease Severity?
Authors: Archontogeorgis Kostas , Voulgaris Athanasios , Nena Evangelia , Zissimopoulos Athanasios , Bouloukaki Izolde , Schiza Sophia E. , Steiropoulos Paschalis
Published: October 2022

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in patients with OVS is scarce. The aim of the present study was to evaluate Vit D serum levels and to explore the association of those levels with anthropometric, pulmonary function and sleep parameters in patients with OVS. Methods: Vit D serum levels were measured in patients diagnosed with OVS, as confirmed by overnight polysomnography and pulmonary function testing. Results: A total of 90 patients (79 males and 11 females) were included in the analysis. The patients were divided into three groups matched for age, gender, and BMI: the control group that included 30 patients (27 males and 3 females), the OSA group that included 30 patients (26 males and 4 females), and the OVS group that included 30 patients (26 males and 4 females). Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients and controls (14.5 vs. 18.6 vs. 21.6 ng/mL, p < 0.001). In the OVS group, multiple linear regression analysis identified AHI and FEV1, as predictors of serum 25(OH)D levels (p = 0.041 and p = 0.038, respectively). Conclusions: Lower Vit D levels have been observed in patients with OVS compared with OSA patients and non-apneic controls, indicating an increased risk of hypovitaminosis D in this population which might be associated with disease severity.
Cyclic Change in Right and Left Ventricular Systolic and Diastolic Function in Patients with Neuromuscular Disorders on Permanent Mechanical Ventilation
Authors: Fayssoil Abdallah , Mansencal Nicolas , Bergounioux Jean , Wahbi Karim , Stojkovic Tanya
Published: October 2022

Home mechanical ventilation is classically used to treat neuromuscular patients with chronic respiratory insufficiency. Since the heart and lungs are localized in the thorax, intrathoracic pressure may directly affect heart function. Here, we report the direct cyclic effects of mechanical ventilation on the right and left ventricular systolic and diastolic function in serial cases. These cases highlight the importance of performing Doppler echocardiography in patients with neuromuscular disorders, focusing on the right and left ventricular systolic and diastolic functions in the context of ventilation setting modifications or introduction.
Negative Pressure Wound Therapy for the Treatment of Fournier’s Gangrene: A Rare Case with Rectal Fistula and Systematic Review of the Literature
Authors: Altomare Michele , Benuzzi Laura , Molteni Mattia , Virdis Francesco , Spota Andrea , Cioffi Stefano Piero Bernardo , Reitano Elisa , Renzi Federica , Chiara Osvaldo , Sesana Giovanni , Cimbanassi Stefania
Published: October 2022

Fournier’s gangrene (FG) is a Necrotizing Soft Tissue Infection (NSTI) of the perineal region characterized by high morbidity and mortality even if appropriately treated. The main treatment strategies are surgical debridement, broad-spectrum antibiotics, hyperbaric oxygen therapy, NPWT (Negative Pressure Wound Therapy), and plastic surgery reconstruction. We present the case of a 50-year-old woman with an NSTI of the abdomen, pelvis, and perineal region associated with a rectal fistula referred to our department. After surgical debridement and a diverting blow-out colostomy, an NPWT system composed of two sponges connected by a bridge through a rectal fistula was performed. Our target was to obtain healing in a lateral-to-medial direction instead of depth-to-surface to prevent the enlargement of the rectal fistula, promoting granulation tissue growth towards the rectum. This eso-endo-NPWT technique allowed for the primary suture of the perineal wounds bilaterally, simultaneously treating the rectal fistula and the perineum lesions. A systematic review of the literature underlines the spreading of NPWT and its effects.
Financial Report Readability and Accounting Conservatism
Authors: Yu Zhimin (Jimmy)
Published: October 2022

Accounting conservatism could affect the quantitative information on a financial statement. In this paper, the author focuses on qualitative information on financial statements. The author investigates the association between financial report readability and accounting conservatism and uses the FOG index to measure financial report readability. By using management discussion and analysis (MD&A) from 1996 to 2019, the author finds that financial report readability is positively associated with accounting conservatism. Additionally, the author separates the samples into high-compensation incentive and low-compensation incentive subsamples. The results show that the above association is stronger in the high-compensation incentive samples than in the low-compensation incentive samples. This result implies that accounting conservatism could mitigate managerial opportunism in the qualitative disclosure setting.
Evaluating Capability of Green Stormwater Infrastructure on Large Properties toward Adaptive Flood Mitigation: The HLCA+C Methodology
Authors: Muangsri Suphicha , McWilliam Wendy , Lawson Gillian , Davies Tim
Published: October 2022

Current flood protection capacities will become inadequate to protect many low-lying coastal cities from climate change-induced flooding in the future. Under climate change uncertainty, an adaptive strategy is required to provide supplemental flood mitigation. Green Stormwater Infrastructure (GSI) in developed areas has the potential to provide substantial catchment runoff reduction. However, individual properties vary in their Flood Mitigation Capability (FMC) depending on their land characteristics. An effective methodology is needed to evaluate the FMC of properties to help urban planners determine which to target for GSI and when to implement GSI in light of increased climate change impacts. We advance the Hydrology-based Land Capability Assessment and Classification (HLCA+C) methodology for evaluating the FMC of large properties over the long term (80 to 100-year). It builds on the strengths of existing methodologies and uses a land unit analysis approach for assessing FMC, considering interdependent hydrological and geographical variables. The FMC classification system groups properties with similar flood mitigation characteristics, helping urban planners to understand their potentials and limitations for flood mitigation toward the development of adaptive strategies through time. Step-by-step instructions demonstrate how to apply the methodology to any low-lying coastal city.
On the Normativity of Presumptions: Contrasting Kauffeld’s and Whatelian Accounts
Authors: Godden David
Published: October 2022

On a Whatelian conception, a presumption is a “supposition … [that] must stand good until some sufficient reason is adduced against it.” This view may be understood as operationalizing a distinct quality of warrant for the acceptability of claims. Against this Whatelian conception, Kauffeld offers an account on which “ordinary presumptions are inferences based on suppositions regarding the risk of resentment persons face should they fail to live up to (often openly incurred) commitments.” On Kauffeld’s analysis, presumptions are distinguished according to a special kind of backing, or grounding, upon which presumed claims are based. This article contrasts these views according to the different accounts each provides of the normative mechanisms at work in, and underwriting, warranted presumption. Viable argumentative norms must be both objectively well-founded and effective in regulating the activity of argumentation. Whatelian conceptions seek to explain the effectiveness (specifically, the binding force) of presumptions in terms of an arguer’s recognition of their well-foundedness by providing an account of presumptions as particularly well-adapted to methodological features inherent in the activity of transacting reasons. By contrast, Kauffeld’s analysis reverses this order of explanation, explaining the well-foundedness (specifically, the validity) of presumption and presumptive inference in terms of its effectiveness (specifically its binding force) over agents. By identifying a class of presumptions that are inherently, and extra-argumentatively, binding upon agents in ways that can manifestly influence their behavioral calculations to make it the case that what is presumed is so, Kauffeld’s analysis of presumption normatively generates well-foundedness out of effectiveness. Thus, a distinctive and innovative feature of Kauffeld’s analysis of presumption is that it identifies a hitherto unrecognized dimension of normativity—namely, our extra-argumentative obligations and our reactive attitudes concerning them—as capable of underwriting warranted presumptive inference.
Object Clitic Reduplication in Perugino
Authors: Di Domenico Elisa
Published: October 2022

This work describes a case of object clitic reduplication (OCR) in restructuring sentences, in a Central Italian dialect: Perugino. OCR (not attested in the local variety of Italian spoken in Perugia) is optional and alternates with either enclisis or proclisis. It may concern direct and indirect object clitics, without person restrictions, locatives, partitives and reflexives. Only proclisis is instead possible with middle se. In sentences with more than one restructuring predicate, the clitic can occur only twice, and with some restrictions. The data suggest that middle se does not behave like (other) object clitics, including reflexive uses of se, a distinction also revealed by standard Piedmontese. The data also reveal that the boundaries of the two closely related non-standard varieties (the dialect and the local variety of Italian spoken in Perugia) are not blurred, nor are there intermediate repertoires or dialect continua. OCR is compatible with monoclausal as well as with biclausal analyses of restructuring sentences, but not with models that assume a different structure/derivation for restructuring sentences in the case of proclisis and in the case of enclisis. If a monoclausal structure is to be assumed, OCR suggests that there are (only) two clitic positions/strings in the clause. The lower position/string, however, cannot be made available only by lexical verbs.
Design and Fabrication of an Additively Manufactured Aluminum Mirror with Compound Surfaces
Authors: Zhang Jizhen , Wang Chao , Qu Hemeng , Guan Haijun , Wang Ha , Zhang Xin , Xie Xiaolin , Wang He , Zhang Kai , Li Lijun
Published: October 2022

Microsatellites have a great attraction to researchers due to their high reliability, resource utilization, low cost, and compact size. As the core component of the optical payload, the mirror directly affects the system package size. Therefore, the structural design of mirrors is critical in the compact internal space of microsatellites. This study proposes a closed-back mirror with composite surfaces based on additive manufacturing (AM). Compared with the open-back mirror, it provides excellent optomechanical performance. In addition, AM significantly reduces the intricate mechanical parts’ manufacturing difficulty. Finally, the roughness was better than 2 nm. The surface shape of the AM aluminum mirror reached RMS 1/10λ (λ = 632.8 nm) with the aid of ultra-precision machining technologies such as single-point diamond turning (SPDT), surface modification, and polishing, and the maximum deviation of the surface shape was about RMS 1/42λ (λ = 632.8 nm) after the thermal cycle test, which verified the optical grade application of AM.
Three-Dimensional Finite Element Modeling of Drilling-Induced Damage in S2/FM94 Glass-Fiber-Reinforced Polymers (GFRPs)
Authors: Manzoor Shahryar , Ud Din Israr , Giasin Khaled , Köklü Uğur , Khan Kamran A. , Panier Stéphane
Published: October 2022

Considering that the machining of composites particularly fiber-reinforced polymer composites (FRPCs) has remained a challenge associated with their heterogeneity and anisotropic nature, damage caused by drilling operations can be considerably mitigated by following optimum cutting parameters. In this work, we numerically evaluated the effects of cutting parameters, such as feed rate and spindle speed, on the thrust force and torque during the drilling of glass-fiber-reinforced polymers (GFRPs). A meso-scale, also known as unidirectional ply-level-based finite element modeling, was employed assuming an individual homogenized lamina with transversely isotropic material principal directions. To initiate the meso-scale damage in each lamina, 3D formulations of Hashin’s failure theory were used for fiber damage and Puck’s failure theory was implemented for matrix damage onset via user subroutine VUMAT in ABAQUS. The developed model accounted for the complex kinematics taking place at the drill–workpiece interface and accurately predicted the thrust force and torque profiles as compared with the experimental results. The thrust forces for various drilling parameters were predicted with a maximum of 10% error as compared with the experimental results. It was found that a combination of lower feed rates and higher spindle speeds reduced the thrust force, which in turn minimized the drilling-induced damage, thus providing useful guidelines for drilling operations with higher-quality products. Finally, the effect of coefficient of friction was also investigated. Accordingly, a higher coefficient of friction between the workpiece and drill-bit reduced the thrust force.
Study on the Mechanism of Elastic Instability Caused by Natural Growth in Orthotropic Material
Authors: Wu Diquan , He Liwen
Published: October 2022

Compared to synthetic materials, naturally grown biological materials have more specific behavioral patterns and life connotations in their morphological evolution over millions of years of environmental evolution on Earth. In this paper, we investigate the physical mechanisms and manifestations of out-of-plane deformation instability. Firstly, the origin of the instability phenomenon caused by the growth of the leaf is introduced. Leaf instability problems are modeled using rectangular thin plates. Secondly, the variation in the critical intrinsic strain with the principal shear modulus is obtained by numerical solution. The post-buckling behavior of the growth instability is further analyzed by general static analysis, and we obtain the phase diagram of morphogenesis of thin plant organs as functions of the principal shear modulus and off-axis angle. The research results enhance the understanding of the mechanism of elastic instability caused by natural growth in orthotropic materials.
Degradation of Polylactide and Polycaprolactone as a Result of Biofilm Formation Assessed under Experimental Conditions Simulating the Oral Cavity Environment
Authors: Łysik Dawid , Deptuła Piotr , Chmielewska Sylwia , Bucki Robert , Mystkowska Joanna
Published: October 2022

Polylactide (PLA) and polycaprolactone (PCL) are biodegradable and bioabsorbable thermoplastic polymers considered as promising materials for oral applications. However, any abiotic surface used, especially in areas naturally colonized by microorganisms, provides a favorable interface for microbial growth and biofilm development. In this study, we investigated the biofilm formation of C. krusei and S. mutans on the surface of PLA and PCL immersed in the artificial saliva. Using microscopic (AFM, CLSM) observations and spectrometric measurements, we assessed the mass and topography of biofilm that developed on PLA and PCL surfaces. Incubated up to 56 days in specially prepared saliva and microorganisms medium, solid polymer samples were examined for surface properties (wettability, roughness, elastic modulus of the surface layer), structure (molecular weight, crystallinity), and mechanical properties (hardness, tensile strength). It has been shown that biofilm, especially S. mutans, promotes polymer degradation. Our findings indicate the need for additional antimicrobial strategies for the effective oral applications of PLA and PCL.
Ising-like Magnetism in Quasi-Two-Dimensional Co(NO3)2·2H2O
Authors: Vorobyova Anna A. , Danilovich Igor L. , Morozov Igor V. , Vasiliev Alexander N. , Volkova Olga S. , Iqbal Asif , Rahaman Badiur , Saha-Dasgupta Tanusri
Published: October 2022

The appearance of electrically neutral water molecules in the structure of cobalt dinitrate dihydrate, Co(NO3)2⋅2H2O, drastically changes its magnetic properties as compared to its waterless counterpart, Co(NO3)2. The title compound shows Ising-like behavior reflected in its thermodynamic properties. It experiences long-range antiferromagnetic order at TN = 20.5 K and metamagnetic transition at µ0HC = 0.76 T. First-principles calculations produce the values of leading exchange interactions J1 ~ 10 K and J2 ~ 0.5 K and single-ion anisotropy D ~ 1 K which allows us to consider Co(NO3)2⋅2H2O as a quasi-two-dimensional magnetic system.
Influence of Heat Treatment on Microstructure and Mechanical Properties of AZ61 Magnesium Alloy Prepared by Selective Laser Melting (SLM)
Authors: Liu Shuai , Guo Hanjie
Published: October 2022

From previous studies, it is known that the dissolution of β-Mg17Al12 at high temperature and the increase of densities at high pressure after hot isostatic pressing (HIP) are the two main reasons for significant improvement in the ductility of AZ61 magnesium alloy prepared by SLM. However, the mechanism of dissolution of β-Mg17Al12 in SLMed AZ61 magnesium alloy at high temperature is not clear. To illustrate the mechanism of the effect of β-Mg17Al12 dissolution on the ductility of SLMed AZ61 Mg alloy, the effect of solid solution heat treatment (T4) on the microstructure and mechanical properties of SLMed AZ61 was investigated and the kinetic model of β-Mg17Al12 dissolution of SLMed AZ61 magnesium alloy was established. According to the results, there is no significant change in the dissolution of the β-Mg17Al12 with an increase of temperature and time when the T4 temperature is lower than 410 °C. At the optimum solution heat treatment temperature of 410 °C, the dissolution rate is accelerated and the β-Mg17Al12 is completely dissolved after 2 h. In addition, the dissolution rate of β-Mg17Al12 decreases with the increase of dissolution time. The strength of SLMed AZ61 magnesium alloy decreases and the ductility increases as the T4 temperature increases. The strength of the specimens is reduced by grain coarsening (29.2 ± 3.7 μm), but the elongation is increased by 90% compared to SLMed AZ61, due to the effect of β-Mg17Al12 dissolution.
Low Cycle Fatigue of G20Mn5 Cast Steel Relation between Microstructure and Fatigue Life
Authors: Bermond Antonin , Roume Claire , Stolarz Jacques , Lenci Matthieu , Carton Jean-François , Klocker Helmut
Published: October 2022

Cast steel is commonly used to produce structural and safety parts. Foundry processes allow producing parts from scrap steel directly to the required dimensions without any forming operation. Cast components may, however, exhibit macro- and micro-shrinkage porosities. The combined effect of macro- and micro-shrinkages on the fatigue behavior of cast steel has been characterized in the literature. Macro-shrinkages may nowadays be eliminated by adequate positioning of risers. However, micro-shrinkages will always be present in cast steel components. Present work addresses the influence of micro-shrinkage porosity on a G20Mn5 cast steel. G20Mn5 (normalized) ingots have been cast under industrial conditions, but ensuring the absence of macro-porosities. Solidification leads to two very different microstructures prior to the normalization treatment: columnar dendrites beneath the surface (Skin) and equiaxed microstructures close to the center (Core). First, metallographic observations of the whole ingot revealed the same grain size in both areas. Fatigue samples were extracted, by differentiating two sampling volumes corresponding to columnar (S) and equiaxed solidification (C), respectively. The distribution of micro-porosities was determined on all samples by Micro-CT-scans. Core samples exhibit micro-porosities with volumes 1.7 larger than Skin samples. Low cycle fatigue tests (3 levels of fixed plastic strain) were run on both sample series (C, S). Results follow a Manson–Coffin law. Core specimens exhibit lower fatigue life than Skin specimens. The differences in fatigue life have been related successfully to the differences in micro-porosities sizes.
A Complementary Dual of Single-Valued Neutrosophic Entropy with Application to MAGDM
Authors: Sharma Sonam , Singh Surender
Published: October 2022

A single-valued neutrosophic set (SVNS) is a subcategory of neutrosophic set that is used to represent uncertainty and fuzziness in three tiers, namely truthfulness, indeterminacy, and falsity. The measure of entropy of a SVNS plays an important role to determine the ambiguity in a variety of situations. The knowledge measure is a dual form of entropy and is helpful in certain counterintuitive situations. In this paper, we introduce a knowledge measure for the SVNS and contrast the same with existing measures. The comparative study reveals that the proposed knowledge measure is more effective in modeling the structured linguistic variables. We provide the relations of the proposed knowledge measure with single valued neutrosophic similarity and distance measures. We also investigate the application of the proposed measure in multi-attribute group decision making (MAGDM). The proposed MAGDM model is helpful when the decision makers in the group have varied background and the hiring organization is unable to assign the level of importance or weight to a decision-maker.
Study on the Solidification Mechanism of Cr in Ettringite and Friedel’s Salt
Authors: Wang Ke , Xu Dong , Li Keqing , Ni Wen
Published: October 2022

The solidification of heavy metal Cr has always been a challenge in the treatment of Cr-containing wastes, due to its high mobility in alkaline environments. In addition, the solidification mechanism of Cr has not been fully investigated. In this study, blast furnace slag (BFS)-based cementitious materials were used as binders for the immobilization of heavy metal Cr to investigate the solidification mechanism of Cr in different hydration products. From XRD, FTIR, XPS, and XANES analyses, it could be seen that SO42− in ettringite was replaced by Cr in the form of CrO42−, making SO42− re-dissolve in the liquid phase. The SO42− in the solution would compete with CrO42− ions, leading to the direct influence of SO42− content on the solidification efficiency of Cr. In ettringite, Cr mainly existed in the form of Cr6+, accounting for more than 84% however, Cr was solidified in Friedel’s salt under two coexisting valence states (Cr6+ and Cr3+). This resulted not only from the slow excitation rate of the BFS in the cementitious system that did not contain sulfate, but also from the existence of a certain amount of reducing substances in the BFS, such as Fe2+ and S2−, which could reduce some of Cr6+ to Cr3+. In Friedel’s salt, the residual Cr6+ replaced Cl− in the form of CrO42−, whereas the Cr3+ replaced Al3+. The binding energies of Cr 2p3/1 and Cr 2p3/2 decreased with the addition of Cr, indicating that the coordination numbers of Cr3+ and Cr6+ increased, and that the binding energies of Cr3+ and Cr6+ decreased after entering the structure of Friedel’s salt.
Increasing Performances of 1–3 Piezocomposite Ultrasonic Transducer by Alternating Current Poling Method
Authors: Zhu Ke , Ma Jinpeng , Liu Yang , Shen Bingzhong , Huo Da , Yang Yixiao , Qi Xudong , Sun Enwei , Zhang Rui
Published: October 2022

Ultrasonic transducers are the basic core component of diagnostic imaging devices, wherein the piezoelectric materials are the active element of transducers. Recent studies showed that the alternating current poling (ACP) method could develop the properties of piezocomposites, which had great potential to improve transducer performance. Herein, transducers (fc = 3 MHz) made of DCP and ACP 1–3 piezocomposites (prepared by PZT-5H ceramics and PMN-PT single crystals) were fabricated. The effect of the ACP method on the bandwidth and insertion loss (sensitivity) was explored. The results indicate that the ACP method can significantly enhance the bandwidth and slightly increase the insertion loss of transducers. Particularly, a superhigh bandwidth of 142.8% was achieved in the transducer of ACP 1–3 PMN-PT single crystal combined with suitable matching and backing layers. This bandwidth is higher than that of all reported transducers with similar center frequency. Moreover, the optimization mechanism of transducer performance by the ACP method was discussed. The obtained results suggested that the ACP is an effective and convenient technology to improve transducer performances, especially for the bandwidth.
Microfluidic Gas Sensors: Detection Principle and Applications
Authors: Kaaliveetil Sreerag , Yang Juliana , Alssaidy Saud , Li Zhenglong , Cheng Yu-Hsuan , Menon Niranjan Haridas , Chande Charmi , Basuray Sagnik
Published: October 2022

With the rapid growth of emerging point-of-use (POU)/point-of-care (POC) detection technologies, miniaturized sensors for the real-time detection of gases and airborne pathogens have become essential to fight pollution, emerging contaminants, and pandemics. However, the low-cost development of miniaturized gas sensors without compromising selectivity, sensitivity, and response time remains challenging. Microfluidics is a promising technology that has been exploited for decades to overcome such limitations, making it an excellent candidate for POU/POC. However, microfluidic-based gas sensors remain a nascent field. In this review, the evolution of microfluidic gas sensors from basic electronic techniques to more advanced optical techniques such as surface-enhanced Raman spectroscopy to detect analytes is documented in detail. This paper focuses on the various detection methodologies used in microfluidic-based devices for detecting gases and airborne pathogens. Non-continuous microfluidic devices such as bubble/droplet-based microfluidics technology that have been employed to detect gases and airborne pathogens are also discussed. The selectivity, sensitivity, advantages/disadvantages vis-a-vis response time, and fabrication costs for all the microfluidic sensors are tabulated. The microfluidic sensors are grouped based on the target moiety, such as air pollutants such as carbon monoxide and nitrogen oxides, and airborne pathogens such as E. coli and SARS-CoV-2. The possible application scenarios for the various microfluidic devices are critically examined.
Editorial for the Special Issue on Micro/Nanofluidic and Lab-on-a-Chip Devices for Biomedical Applications
Authors: Carvalho Violeta Meneses , Teixeira Senhorinha , Ribeiro João E.
Published: October 2022

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [...]
Engineering Cell Polarization Improves Protein Production in Saccharomyces cerevisiae
Authors: Yang Shuo , Shen Junfeng , Deng Jiliang , Li Hongxing , Zhao Jianzhi , Tang Hongting , Bao Xiaoming
Published: October 2022

Saccharomyces cerevisiae has been widely used as a microbial cell factory to produce recombinant proteins. Therefore, enhancing the protein production efficiency of yeast cell factories to expand the market demand for protein products is necessary. Recombinant proteins are often retained in the secretory pathway because of the limited protein transport performed by vesicle trafficking. Cell polarization describes the asymmetric organization of the plasma membrane cytoskeleton and organelles and tightly regulates vesicle trafficking for protein transport. Engineering vesicle trafficking has broadly been studied by the overexpression or deletion of key genes involved but not by modifying cell polarization. Here, we used α-amylase as a reporter protein, and its secretion and surface-display were first improved by promoter optimization. To study the effect of engineering cell polarization on protein production, fourteen genes related to cell polarization were overexpressed. BUD1, CDC42, AXL1, and BUD10 overexpression increased the activity of surface-displayed α-amylase, and BUD1, BUD3, BUD4, BUD7, and BUD10 overexpression enhanced secreted α-amylase activity. Furthermore, BUD1 overexpression increased the surface-displayed and secreted α-amylase expression by 56% and 49%, respectively. We also observed that the combinatorial modification and regulation of gene expression improved α-amylase production in a dose-dependent manner. BUD1 and CDC42 co-overexpression increased the α-amylase surface display by 100%, and two genomic copies of BUD1 improved α-amylase secretion by 92%. Furthermore, these modifications were used to improve the surface display and secretion of the recombinant β-glucosidase protein. Our study affords a novel insight for improving the surface display and secretion of recombinant proteins.
Secondary Metabolites Produced by Plant Growth-Promoting Bacterial Endophytes
Authors: Narayanan Zareen , Glick Bernard R.
Published: October 2022

There is an increasing interest in the use of beneficial microorganisms as alternatives to chemically synthesized or plant-derived molecules to produce therapeutic agents. Bacterial endophytes are plant-associated microorganisms that can colonize different parts of living plants without causing any diseases. Diverse endophytic bacteria possess the ability to synthesize a wide range of secondary metabolites with unique chemical structures that have been exploited for their anti-microbial, antiviral, anti-cancer, and anti-inflammatory properties. Additionally, production of these bioactive compounds can also benefit the host plant as they may play a significant role in a plant’s interaction with the environment for adaptation and defense. As a result of their significant impact as curative compounds or as precursors to produce new drugs, the biotechnological possibilities of secondary metabolites derived from endophytic bacteria are immense.
Heterocyclization of Bis(2-chloroprop-2-en-1-yl)sulfide in Hydrazine Hydrate–KOH: Synthesis of Thiophene and Pyrrole Derivatives
Authors: Rozentsveig Igor B. , Nikonova Valentina S. , Manuilov Victor V. , Ushakov Igor A. , Borodina Tatyana N. , Smirnov Vladimir I. , Korchevin Nikolay A.
Published: October 2022

The article is devoted to heterocyclization of bis(2-chloroprop-2-en-1-yl)sulfide which proceeds in hydrazine hydrate–alkali medium and leads to formation of thiophene and pyrrole derivatives: previously described 4,5,9,10-tetrahydrocycloocta[1,2-c;5,8-c’]dithiophene, as well as unknown hydrazone of 5-methylidene-3-methyldihydrothiophen-2-one and 1-amino-2-(propynylsulfanylpropenylsulfanyl)-3,5-dimethylpyrrole. Tentative mechanisms for the formation of the heterocyclic products are discussed. Obtained hydrazone of 5-methylidene-3-methyldihydrothiophen-2-one was used for the synthesis of a range of azine derivatives and in oxidation process with SeO2. The found reactions open up expedient approaches to the formation of various hardly accessible thiophene and pyrrole compounds from 2,3-dichloropropene and elemental sulfur as starting reagents.
Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
Authors: Wu Cheng-Zhu , Gao Mei-Jia , Chen Jie , Sun Xiao-Long , Zhang Ke-Yi , Dai Yi-Qun , Ma Tao , Li Hong-Mei , Zhang Yu-Xin
Published: October 2022

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.
Characteristic Volatile Organic Compound Analysis of Different Cistanches Based on HS-GC-IMS
Authors: Zhou Shiqi , Feng Duo , Zhou Yaxi , Duan Hao , He Yue , Jiang Yongjun , Yan Wenjie
Published: October 2022

Cistanche is a medicinal and food homologous substance with a long history of consumption and medicinal use in China. In order to further understand the volatile organic compound differences between different cistanches, this study selected oil cistanche, blood cistanche and cistanche tubulosa in Xinjiang for HS-GC-IMS volatile organic compounds, and established the characteristic fingerprints of different cistanches for organic content and characteristic organic compound analysis. PCA and cluster analysis were used to study the similarity between different cistanches. After qualitative analysis, a total of 32 volatile organic compounds were identified, covering aldehydes (17), ketones (5), furans (1), alcohols (5), lactones (1) and esters (3), and the volatile organic compounds between samples a, b and c could be significantly distinguished, affecting the flavor of cistanche itself. It provides a basic theoretical basis for the study of cistanche flavor.
Comprehensive Comparison of Two Color Varieties of Perillae Folium by GC-MS-Based Metabolomic Approach
Authors: Chen Jiabao , Zhang Dan , Wang Qian , Yang Aitong , Zheng Yuguang , Wang Lei
Published: October 2022

Perillae Folium (PF), the leaf of Perilla frutescens (L.) Britt, is extensively used as culinary vegetable in many countries. It can be divided into two major varietal forms based on leaf color variation, including purple PF (Perilla frutescens var. arguta) and green PF (P. frutescens var. frutescens). The aroma of purple and green PF is discrepant. To figure out the divergence of chemical composition in purple and green PF, gas chromatography–tandem mass spectrometry (GC-MS) was applied to analyze compounds in purple and green PF. A total of 54 compounds were identified and relatively quantified. Multivariate statistical methods, including principal component analysis (PCA), orthogonal partial least-squares discrimination analysis (OPLS-DA) and clustering analysis (CA), were used to screen the chemical markers for discrimination of purple and green PF. Seven compounds that accumulated discrepantly in green and purple PF were characterized as chemical markers for the discrimination of the purple and green PF. Among these 7 marker compounds, limonene, shisool and perillaldehyde that from the same branch of the terpenoid biosynthetic pathway were with relatively higher contents in purple PF, while perilla ketone, isoegomaketone, tocopheryl and squalene on other branch pathways were higher in green PF. The results of the present study are expected to provide theoretical support for the development and utilization of PF resources.
Optimization of Lipid Extraction from Spirulina spp. by Ultrasound Application and Mechanical Stirring Using the Taguchi Method of Experimental Design
Authors: Neag Emilia , Stupar Zamfira , Varaticeanu Cerasel , Senila Marin , Roman Cecilia
Published: October 2022

The present study uses the Taguchi method of experimental design to optimize lipid extraction from Spirulina spp. by ultrasound application and mechanical stirring. A Taguchi L9 orthogonal array was used to optimize various parameters, such as methanol: chloroform (M:C) ratio, biomass: solvent ratio, and extraction time for lipid extraction. The results were analyzed using the signal-to-noise (S/N) ratio and analysis of variance (ANOVA). The biomass: solvent ratio significantly influenced lipid content (p < 0.05) with 92.1% and 92.3% contributions to the lipid and S/N ratio data, respectively. The extraction time presented a contribution value of 5.0%, while the M:C ratio presented the most negligible contribution of 0.4% for S/N data. The optimum extraction conditions were: M:C ratio of 1:1, biomass: solvent ratio of 1:60, and extraction time of 30 min. The predominant fatty acids were palmitic acid (44.5%), linoleic acid (14.9%), and gamma-linolenic acid (13.4%). The confirmation experiments indicated a lipid content of 8.7%, within a 95% confidence interval, proving the Taguchi method’s effectiveness in optimizing the process parameters for lipid extraction.
Advancement of Phenoxypyridine as an Active Scaffold for Pesticides
Authors: Liu Yanfei , Fu Bin , Xu Yanjun , Ren Bo , Qin Zhaohai
Published: October 2022

Phenoxypyridine, the bioisostere of diaryl ethers, has been widely introduced into bioactive molecules as an active scaffold, which has different properties from diaryl ethers. In this paper, the bioactivities, structure-activity relationships, and mechanism of compounds containing phenoxypyridine were summarized, which may help to explore the lead compounds and discover novel pesticides with potential bioactivities.
Utilizing Nutritional and Polyphenolic Compounds in Underutilized Plant Seeds for Health Application
Authors: Zaini Nur Syamimi , Karim Roselina , Abdull Razis Ahmad Faizal , Zawawi Norhasnida
Published: October 2022

Plants represent a significant part of the human diet. Humans have utilized every part of plants for survival, and seeds are no exception. Seeds offer high protein, unsaturated fats, fibre, essential vitamins, and minerals for various food applications. They are also a promising reservoir of bioactive compounds, where various phytochemicals, such as polyphenolic compounds, capable of maintaining and improving well-being, are present in abundant quantities. Plants from Malvaceae and Cannabaceae families are known for their fibre-rich stems that benefit humankind by serving numerous purposes. For many centuries they have been exploited extensively for various commercial and industrial uses. Their seeds, which are often regarded as a by-product of fibre processing, have been scientifically discovered to have an essential role in combating hypercholesterolemia, diabetes, cancer, and oxidative stress. Maximizing the use of these agricultural wastes can be a promising approach to creating a more sustainable world, in accordance with the concept of Sustainable Development Goals (SDGs).
Elucidation of Binding Features and Dissociation Pathways of Inhibitors and Modulators in SARS-CoV-2 Main Protease by Multiple Molecular Dynamics Simulations
Authors: Xu Lei , Xie Liangxu , Zhang Dawei , Xu Xiaojun
Published: October 2022

COVID-19 can cause different neurological symptoms in some people, including smell, inability to taste, dizziness, confusion, delirium, seizures, stroke, etc. Owing to the issue of vaccine effectiveness, update and coverage, we still need one or more diversified strategies as the backstop to manage illness. Characterizing the structural basis of ligand recognition in the main protease (Mpro) of SARS-CoV-2 will facilitate its rational design and development of potential drug candidates with high affinity and selectivity against COVID-19. Up to date, covalent-, non-covalent inhibitors and allosteric modulators have been reported to bind to different active sites of Mpro. In the present work, we applied the molecular dynamics (MD) simulations to systematically characterize the potential binding features of catalytic active site and allosteric binding sites in Mpro using a dataset of 163 3D structures of Mpro-inhibitor complexes, in which our results are consistent with the current studies. In addition, umbrella sampling (US) simulations were used to explore the dissociation processes of substrate pathway and allosteric pathway. All the information provided new insights into the protein features of Mpro and will facilitate its rational drug design for COVID-19.
A Closed-Loop Autologous Erythrocyte-Mediated Delivery Platform for Diabetic Nephropathy Therapy
Authors: Feng Lingzi , Huang Xinzhong , Li Jia , Chen Chao , Ma Yidan , Gu Haiying , Hu Yong , Xia Donglin
Published: October 2022

Failure to control blood glucose level (BGL) may aggravate oxidative stress and contribute to the development of diabetic nephropathy (DN). Using erythrocytes (ERs) as the carriers, a smart self-regulatory insulin (INS) release system was constructed to release INS according to changes in BGLs to improve patients’ compliance and health. To overcome the limited sources of ERs and decrease the risk of transmitting infections, we developed an in vitro, closed-loop autologous ER-mediated delivery (CAER) platform, based on a commercial hemodialysis instrument modified with a glucose-responsive ER-based INS delivery system (GOx-INS@ER). After the blood was drained via a jugular vein cannula, some of the blood was pumped into the CAER platform. The INS was packed inside the autologous ERs in the INS reactor, and then their surface was modified with glucose oxidase (GOx), which acts as a glucose-activated switch. In vivo, the CAER platform showed that the BGL responsively controlled INS release in order to control hyperglycemia and maintain the BGL in the normal range for up to 3 days; plus, there was good glycemic control without the added burden of hemodialysis in DN rabbits. These results demonstrate that this closed-loop extracorporeal hemodialysis platform provides a practical approach for improving diabetes management in DN patients.
Chemokine-Decorated Nanoparticles Target Specific Subpopulations of Primary Blood Mononuclear Leukocytes
Authors: Pisani Anissa , Donno Roberto , Valenti Giulio , Pompa Pier , Tirelli Nicola , Bardi Giuseppe
Published: October 2022

Specific cell targeting to deliver nanoparticles can be achieved by tailored modifications of the material surface with chemical moieties. The selection of the cell targets can be optimized by covering the nanoparticle with molecules, the receptor expression of which is restricted to particular cell subsets. Chemokines perform their biological action through 7-TM Gi-protein-coupled receptors differently expressed in all tissues. We decorated the surface of biocompatible polymer nanoparticles with full-length CCL5, an inflammatory chemokine that attracts leukocytes by binding CCR5, which is highly expressed in blood-circulating monocytes. Our observations showed that CCL5 functionalization does not affect the nanoparticle biocompatibility. Notably, CCL5 NPs delivered to PBMCs are selectively internalized by CCR5+ monocytes but not by CCR5- lymphocytes. The efficacy of PBMC subpopulation targeting by chemokine-decorated nanoparticles establishes an easy-to-use functionalization for specific leukocyte delivery.