bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Concentric Magnetic Continuum Robot with Multiple Stiffness Modes for Potential Delivery of Nanomedicine
Authors: Li Na , Lin Daojing , Wu Junfeng , Gan Quan , Hu Xingyue , Jiao Niandong
Published: May 2023

The utilisation of miniature robots has become essential in the domain of minimally invasive surgery and long-distance delivery of nanomedicine. Among these, the miniature magnetic continuum robot (MCR) stands out because of its simple structure and dexterity, which allow it to penetrate small cavities, transport specialised tools such as a laser, and deliver medications to support surgical treatment. Nevertheless, because of their soft bodies with a single stiffness, conventional MCRs have limited controllability when navigating through intricate cavities. To address this limitation, we propose a novel concentric magnetic continuum robot (C-MCR) comprising a concentric magnetic catheter with a guidewire having varying stiffness. The C-MCR allows substantial curvature bending owing to its difference in stiffness, and its detachable nature allows it to have four working modes to adapt to specific application requirements with improved stiffness controllability. Experiments demonstrate the ability of the C-MCR to navigate complex pathways and deliver nanomedicines over long distances to specific areas via its internal channels using a large homemade eight-coil electromagnetic system. The C-MCR offers promising application prospects for the long-distance delivery of tailored nanomedicines because of its simple operation, reduced risks, and larger attainable workspace.
Finite-Time Synchronization of Quantized Markovian-Jump Time-Varying Delayed Neural Networks via an Event-Triggered Control Scheme under Actuator Saturation
Authors: Shanmugam Saravanan , Vadivel Rajarathinam , Gunasekaran Nallappan
Published: May 2023

In this paper, we present a finite-time synchronization (FTS) for quantized Markovian-jump time-varying delayed neural networks (QMJTDNNs) via event-triggered control. The QMJTDNNs take into account the effects of quantization on the system dynamics and utilize a combination of FTS and event-triggered communication to mitigate the effects of communication delays, quantization error, and efficient synchronization. We analyze the FTS and convergence properties of the proposed method and provide simulation results to demonstrate its effectiveness in synchronizing a network of QMJTDNNs. We introduce a new method to achieve the FTS of a system that has input constraints. The method involves the development of the Lyapunov–Krasovskii functional approach (LKF), novel integral inequality techniques, and some sufficient conditions, all of which are expressed as linear matrix inequalities (LMIs). Furthermore, the study presents the design of an event-triggered controller gain for a larger sampling interval. The effectiveness of the proposed method is demonstrated through numerical examples.
A Screening Approach to Assess the Impact of Various Commercial Sources of Crude Marine λ-Carrageenan on the Production of Oligosaccharides with Anti-heparanase and Anti-migratory Activities
Authors: Manseur Chanez , Groult Hugo , Porta Manon , Bodet Pierre-Edouard , Mersni-Achour Rachida , Petit Raphaëlle , Ali-Moussa Samir , Musnier Benjamin , Le Cerf Didier , Varacavoudin Tony , Haddad Oualid , Sutton Angela , Leal Cíntia Emi Yanaguibashi , Alencar-Filho Edilson Beserra , Piot Jean-Marie , Bridiau Nicolas , Maugard Thierry , Fruitier-Arnaudin Ingrid
Published: May 2023

Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CAR) is that they are heterogeneous mixtures of different CAR families, and are named according to the thickening-purpose final-product viscosity which does not reflect the real composition. Consequently, this can limit their use in a clinical applications. To address this issue, six commercial λ-CARs were compared and differences in their physiochemical properties were analyzed and shown. Then, a H2O2-assisted depolymerization was applied to each commercial source, and number- and weight-averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in terms of molar masses and DS, which ranged within previously reported values suitable for antitumor properties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features, such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, and it also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.
Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients
Authors: Yang Kai , Pan Ying , Liu Liwei , Sun Beibei , Shi Wei
Published: May 2023

Background and Objectives: Non-invasive methods for evaluating liver fibrosis have been a crucial focus of clinical research. The aim of the current study is to assess the accuracy of serum alpha-fetoprotein (AFP) in determining the stage of liver fibrosis in patients with chronic hepatitis B (CHB) who are positive for HBeAg. Materials and Methods: The current study included a total of 276 HBeAg-positive CHB patients who underwent liver biopsy. The levels of serum AFP were measured in these patients using electrochemiluminescence immunoassays. The correlations between serum AFP levels and other laboratory parameters were analyzed using Spearman’s correlation analysis. Binary logistic regression analysis was performed to determine the independent associations between serum AFP levels and liver fibrosis. The diagnostic performance of serum AFP and other non-invasive markers was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 59 (21.4%) patients were found to have elevated levels of serum AFP (>7 ng/mL). These patients displayed a significantly higher proportion of both advanced fibrosis and cirrhosis compared to those with normal serum AFP levels (0–7 ng/mL). The level of serum AFP was positively associated with levels of serum globulin (GLB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL), as well as the AST-to-platelet ratio (APRI), fibrosis-4 (FIB-4), and Scheuer’s classification, and negatively correlated with platelet (PLT) counts. Furthermore, serum AFP was found to be independently associated with significant fibrosis, advanced fibrosis, and cirrhosis. The results of the ROC analysis showed that serum AFP was an effective predictor of significant fibrosis, advanced fibrosis, and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% CI: 0.721–0.821), 0.889 (95% CI: 0.847–0.923), and 0.925 (95% CI: 0.887–0.953), respectively. These values are higher than those of the APRI and FIB-4. Conclusions: Serum AFP could serve as a valuable supplemental biomarker for determining the severity of liver fibrosis in HBeAg-positive patients with chronic hepatitis B.
Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer
Authors: Schubert Melanie , Bauerschlag Dirk Olaf , Muallem Mustafa Zelal , Maass Nicolai , Alkatout Ibrahim
Published: May 2023

Cervical cancer is still the fourth most common cancer in women throughout the world; an estimated 604,000 new cases were observed in 2020. Better knowledge of its pathogenesis, gained in recent years, has introduced new preventive and diagnostic approaches. Knowledge of its pathogenesis has made it possible to provide individualized surgical and drug treatment. In industrialized countries, cervical cancer has become a less frequent tumor entity due to the accessibility of the human papilloma virus vaccination, systematic preventive programs/early detection programs, health care infrastructure and the availability of effective therapy options. Nevertheless, globally, neither mortality nor morbidity has been significantly reduced over the past 10 years, and therapy approaches differ widely. The aim of this review is to address recent advances in the prevention, diagnostic investigation and treatment of cervical cancer globally, focusing on advances in Germany, with a view toward providing an updated overview for clinicians. The following aspects are addressed in detail: (a) the prevalence and causes of cervical cancer, (b) diagnostic tools using imaging techniques, cytology and pathology, (c) pathomechanisms and clinical symptoms of cervical cancer and (d) different treatment approaches (pharmacological, surgical and others) and their impact on outcomes.
Impact of Plasma Rich in Growth Factors (PRGF) Eye Drops on Ocular Redness and Symptomatology in Patients with Dry Eye Disease
Authors: Lozano-Sanroma Javier , Barros Alberto , Alcalde Ignacio , Sánchez-Ávila Ronald M. , Queiruga-Piñeiro Juan , Fernández-Vega Cueto Luis , Merayo-Lloves Jesús
Published: May 2023

Background and Objectives: Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). Materials and Methods: Patients were divided into two groups of treatment: standard treatment group (n = 43 eyes) and PRGF group (n = 59). Patients’ symptomatology (inferred from OSDI and SANDE questionnaires), ocular inflammation, tear stability, and ocular surface damage were analyzed at baseline and after 3 months of treatment. Results: OSDI test scores were significantly lower in both groups (p < 0.001). SANDE frequency test scores also improved statistically, with differences between groups (p = 0.0089 SANDE frequency and p < 0.0119 SANDE severity). There was a greater reduction in ocular redness (ocular inflammation) in the PRGF group (p < 0.0001) and fluorescein tear break-up time was significantly improved in the PRGF group (p = 0.0006). No significant changes were found in terms of ocular surface damage. No adverse events were obtained in either group. Conclusions: The addition of PRGF to the standard treatment of DED, according to the results obtained, proved to be safe and produced an improvement in ocular symptomatology and signs of inflammation, particularly in moderate and severe cases, when compared to standard treatment.
Migraine Treatment Using Erenumab: Can Lead to a Cognitive and Psychological Qualitative Improvement?
Authors: Torrisi Michele , Corallo Francesco , Lo Buono Viviana , Di Cara Marcella , Grugno Rosario , Lo Presti Riccardo , Quartarone Angelo , De Cola Maria Cristina
Published: May 2023

Migraine is one of the most disabling disorders in the world, associated with poor quality of life. Migraine prevention strategies have increasingly evolved since monoclonal antibodies against the calcitonin gene-related peptide (CGRP), or its receptor, were identified. CGRP is the ideal target of monoclonal antibodies (mAbs). In particular, erenumab is the mAb that has shown good therapeutic efficacy in reducing pain intensity and having high tolerability. In this study, we aimed to investigate the efficacy of erenumab on both cognitive performance and psychological well-being. This was a pilot study with a retrospective design that included 14 subjects (2 males and 12 females), with a mean age of 52.29 ± 9.62, who attended the Headache and Migraine outpatient clinic of the IRCCS Centro Neurolesi Bonino-Pulejo of Messina. The evaluation consisted of measuring cognitive and psychological functioning. Comparing clinical and psychometric test scores between baseline and follow-up, we found a significant improvement in both cognitive performance and quality of life. We also observed a decrease in migraine disability. Our findings have shown improvements in global cognitive performance and quality of life in migraine patients taking erenumab.
Microscopic Observation of Membrane Fusion between Giant Liposomes and Baculovirus Budded Viruses Activated by the Release of a Caged Proton
Authors: Nishigami Misako , Uno Yuki , Tsumoto Kanta
Published: May 2023

Baculovirus (Autographa californica multiple nucleopolyhedrovirus, AcMNPV) is an envelope virus possessing a fusogenic protein, GP64, which can be activated under weak acidic conditions close to those in endosomes. When the budded viruses (BVs) are bathed at pH 4.0 to 5.5, they can bind to liposome membranes with acidic phospholipids, and this results in membrane fusion. In the present study, using the caged-proton reagent 1-(2-nitrophenyl)ethyl sulfate, sodium salt (NPE-caged-proton), which can be uncaged by irradiation with ultraviolet light, we triggered the activation of GP64 by lowering the pH and observed membrane fusion on giant liposomes (giant unilamellar vesicles, GUVs) by visualizing the lateral diffusion of fluorescence emitted from a lipophilic fluorochrome (octadecyl rhodamine B chloride, R18) that stained viral envelopes of BVs. In this fusion, entrapped calcein did not leak from the target GUVs. The behavior of BVs prior to the triggering of membrane fusion by the uncaging reaction was closely monitored. BVs appeared to accumulate around a GUV with DOPS, implying that BVs preferred phosphatidylserine. The monitoring of viral fusion triggered by the uncaging reaction could be a valuable tool for revealing the delicate behavior of viruses affected by various chemical and biochemical environments.
Wear Resistance Prediction of AlCoCrFeNi-X (Ti, Cu) High-Entropy Alloy Coatings Based on Machine Learning
Authors: Kang Jiajie , Niu Yi , Zhou Yongkuan , Fan Yunxiao , Ma Guozheng
Published: May 2023

In order to save the time and cost of friction and wear experiments, the coating composition (different contents of Al, Ti, and Cu elements), ratio of hardness and elastic modulus (H3/E2), vacuum heat treatment (VHT) temperature, and wear form were used as input variables, and the wear rates of high-entropy alloy (HEA) coatings were used as output variables. The dataset was entirely obtained by experiment. Four machine learning algorithms (classification and regression tree (CART), random forest (RF), gradient boosting decision tree (GBDT), and adaptive boosting (AdaBoost)) were used to predict the wear resistance of HEA coatings based on a small amount of data. The results show that except for the GBDT model, the other three models had good performance. Because of the small amount of data, the CART model demonstrated the best prediction performance and can provide guidance for predicting the wear resistance of AlCoCrFeNi-X (Ti, Cu) HEA coatings for drilling equipment. Furthermore, the contribution of different factors to the wear rate of AlCoCrFeNi-X (Ti, Cu) HEA coatings was obtained. Al content had the greatest influence on wear rate, followed by H3/E2, wear form, and VHT temperature.
Differences Due to Sex and Sweetener on the Bioavailability of (Poly)phenols in Urine Samples: A Machine Learning Approach
Authors: Hernández-Prieto Diego , Garre Alberto , Agulló Vicente , García-Viguera Cristina , Egea Jose A.
Published: May 2023

Metabolic diseases have been related to the overdrinking of high-sugar content beverages. As a result, the demand for alternative formulations based on plant-based ingredients with health-promoting properties has increased during the last few years. Nonetheless, the design and production of effective formulations requires understanding the bioavailability of these compounds. For this purpose, a two-month longitudinal trial with 140 volunteers was conducted to measure the beneficial effects of a maqui–citrus beverage, rich in (poly)phenols. From data obtained by quantifying metabolites present in urine samples, biostatistical and machine learning (data imputation, feature selection, and clustering) methods were applied to assess whether a volunteer’s sex and the sweetener added to the beverage (sucrose, sucralose, or stevia) affected the bioavailability of (poly)phenol metabolites. Several metabolites have been described as being differentially influenced: 3,4-dihydroxyphenylacetic acid and naringenin with its derivatives were positively influenced by stevia and men, while eriodictyol sulfate and homoeridictyol glucunoride concentrations were enhanced with stevia and women. By examining groups of volunteers created by clustering analysis, patterns in metabolites’ bioavailability distribution as a function of sex and/or sweeteners (or even due to an uncontrolled factor) were also discovered. These results underline the potential of stevia as a (poly)phenol bioavailability enhancer. Furthermore, they also evidence sex affects the bioavailability of (poly)phenols, pointing at a sex-dependent metabolic pathway regulation.
Biosensors for the Isolation and Detection of Circulating Tumor Cells (CTCs) in Point-of-Care Settings
Authors: Goldstein Isaac , Alyas Sobia , Asghar Waseem , Ilyas Azhar
Published: May 2023

Circulating tumor cells (CTCs) are cells that have been shed from tumors and circulate in the bloodstream. These cells can also be responsible for further metastases and the spread of cancer. Taking a closer look and analyzing CTCs through what has come to be known as “liquid biopsy” has immense potential to further researchers’ understanding of cancer biology. However, CTCs are very sparse and are therefore difficult to detect and capture. To combat this issue, researchers have attempted to create devices, assays, and further techniques to successfully isolate CTCs for analysis. In this work, new and existing biosensing techniques for CTC isolation, detection, and release/detachment are discussed and compared to evaluate their efficacy, specificity, and cost. Here, we specifically aim to evaluate and identify the potential success of these techniques and devices in point-of-care (POC) settings.
A 28 GHz Phased-Array Transceiver for 5G Applications in 22 nm FD-SOI CMOS
Authors: Cracan Dan , Elsayed Nourhan , Sanduleanu Mihai
Published: May 2023

This paper presents the design and implementation of a 28 GHz phased array transceiver for 5G applications using 22 nm FD-SOI CMOS technology. The transceiver consists of a four-channel phased array receiver and transmitter, which employs phase shifting based on coarse and fine controls. The transceiver employs a zero-IF architecture, which is suitable for small footprints and low power requirements. The receiver achieves a 3.5 dB NF with a 1 dB compression point of −21 dBm and a gain of 13 dB.
Revealing the Mechanism of the Bias Temperature Instability Effect of p-GaN Gate HEMTs by Time-Dependent Gate Breakdown Stress and Fast Sweeping Characterization
Authors: Li Xiangdong , Wang Meng , Zhang Jincheng , Gao Rui , Wang Hongyue , Yang Weitao , Yuan Jiahui , You Shuzhen , Chang Jingjing , Liu Zhihong , Hao Yue
Published: May 2023

The bias temperature instability (BTI) effect of p-GaN gate high-electron-mobility transistors (HEMTs) is a serious problem for reliability. To uncover the essential cause of this effect, in this paper, we precisely monitored the shifting process of the threshold voltage (VTH) of HEMTs under BTI stress by fast sweeping characterizations. The HEMTs without time-dependent gate breakdown (TDGB) stress featured a high VTH shift of 0.62 V. In contrast, the HEMT that underwent 424 s of TDGB stress clearly saw a limited VTH shift of 0.16 V. The mechanism is that the TDGB stress can induce a Schottky barrier lowering effect on the metal/p-GaN junction, thus boosting the hole injection from the gate metal to the p-GaN layer. This hole injection eventually improves the VTH stability by replenishing the holes lost under BTI stress. It is the first time that we experimentally proved that the BTI effect of p-GaN gate HEMTs was directly dominated by the gate Schottky barrier that impeded the hole supply to the p-GaN layer.
Triboelectric Nanogenerators Based on 2D Materials: From Materials and Devices to Applications
Authors: Zhou Yukai , Zhang Jia-Han , Li Songlin , Qiu Hao , Shi Yi , Pan Lijia
Published: May 2023

Recently, there has been an increasing consumption of fossil fuels such as oil and natural gas in both industrial production and daily life. This high demand for non-renewable energy sources has prompted researchers to investigate sustainable and renewable energy alternatives. The development and production of nanogenerators provide a promising solution to address the energy crisis. Triboelectric nanogenerators, in particular, have attracted significant attention due to their portability, stability, high energy conversion efficiency, and compatibility with a wide range of materials. Triboelectric nanogenerators (TENGs) have many potential applications in various fields, such as artificial intelligence (AI) and the Internet of Things (IoT). Additionally, by virtue of their remarkable physical and chemical properties, two-dimensional (2D) materials, such as graphene, transition metal dichalcogenides (TMDs), hexagonal boron nitride (h-BN), MXenes, and layered double hydroxides (LDHs), have played a crucial role in the advancement of TENGs. This review summarizes recent research progress on TENGs based on 2D materials, from materials to their practical applications, and provides suggestions and prospects for future research.
The Covariation of Color and Orange Fluorescence Instabilities in Yellow Sapphires
Authors: Yang Yunqi , Wang Chaowen , Wang Chengsi , Shen Xibing , Yin Ke , Chen Tao , Shen Andy Hsitien , Algeo Thomas J. , Hong Hanlie
Published: May 2023

In recent years, some sapphires were found to fade in sunlight and to increase their color after UV irradiation. This unstable color phenomenon is attributed to the photochromism of corundum. The photochromic effect seriously affects the grading and evaluation of sapphires, although its mechanism is still uncertain. Here, we performed a set of photochromic experiments on sapphire specimens using a 254 nm shortwave UV light source and a D65 light source (which simulates sunlight) to generate different color states exhibiting characteristic absorption, emission, and excitation spectra. We observed that, for different color states, variation in the intensity of the absorption band at ~460 nm was consistent with that of orange fluorescence at 500–800 nm. This observation indicates a relationship between color instability and orange fluorescence. Peaks in excitation spectra at 320, 420, 490, 560, and 637 nm provide insight into the source(s) of excited orange fluorescence, which are related to different types of F-centers and Mg-trapped holes. We propose an explanation for the photochromic phenomenon: the color of photochromic yellow sapphire is the result of a variety of defects that release orange fluorescence simultaneously. Further, we hypothesize that the mechanism of photochromism in yellow sapphires is linked to electron transfer between F-centers and Mg-trapped holes.
Semi-Synthesis of Different Pyranoflavonoid Backbones and the Neurogenic Potential
Authors: Urmann Corinna , Bieler Lara , Hackl Michael , Chia-Leeson Olivia , Couillard-Despres Sebastien , Riepl Herbert
Published: May 2023

Flavonoids and chalcones are known for their manifold biological activities, of which many affect the central nervous system. Pyranochalcones were recently shown to have a great neurogenic potential, which is partly due to a specific structural motif-the pyran ring. Accordingly, we questioned if other flavonoid backbones with a pyran ring as structural moiety would also show neurogenic potential. Different semi-synthetic approaches starting with the prenylated chalcone xanthohumol, isolated from hops, led to pyranoflavanoids with different backbones. We identified the chalcone backbone as the most active backbone with pyran ring using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker. Pyranochalcones therefore appear to be promising compounds for further development as a treatment strategy for neurodegenerative diseases.
Hard-Carbon Negative Electrodes from Biomasses for Sodium-Ion Batteries
Authors: Lu Bin , Lin Chengjun , Xiong Haiji , Zhang Chi , Fang Lin , Sun Jiazhou , Hu Ziheng , Wu Yalong , Fan Xiaohong , Li Guifang , Fu Jile , Deng Dingrong , Wu Qihui
Published: May 2023

With the development of high-performance electrode materials, sodium-ion batteries have been extensively studied and could potentially be applied in various fields to replace the lithium-ion cells, owing to the low cost and natural abundance. As the key anode materials of sodium-ion batteries, hard carbons still face problems, such as poor cycling performance and low initial Coulombic efficiency. Owning to the low synthesis cost and the natural presence of heteroatoms of biomasses, biomasses have positive implications for synthesizing the hard carbons for sodium-ion batteries. This minireview mainly explains the research progress of biomasses used as the precursors to prepare the hard-carbon materials. The storage mechanism of hard carbons, comparisons of the structural properties of hard carbons prepared from different biomasses, and the influence of the preparation conditions on the electrochemical properties of hard carbons are introduced. In addition, the effect of doping atoms is also summarized to provide an in-depth understanding and guidance for the design of high-performance hard carbons for sodium-ion batteries.
Improved Synthesis of Deoxyadenosine Triphosphate by Saccharomyces cerevisiae Using an Efficient ATP Regeneration System: Optimization of Response Surface Analysis
Authors: Xiong Jian , Xu Hanghang , Wang Qi , Sun Wenyuan
Published: May 2023

Deoxyadenosine triphosphate (dATP) is an important biochemical molecule. In this paper, the synthesis of dATP from deoxyadenosine monophosphate (dAMP), catalyzed by Saccharomyces cerevisiae, was studied. By adding chemical effectors, an efficient ATP regeneration and coupling system was constructed to achieve efficient synthesis of dATP. Factorial and response surface designs were used to optimize process conditions. Optimal reaction conditions were as follows: dAMP 1.40 g/L, glucose 40.97 g/L, MgCl2·6H2O 4.00 g/L, KCl 2.00 g/L, NaH2PO4 31.20 g/L, yeast 300.00 g/L, ammonium chloride 0.67 g/L, acetaldehyde 11.64 mL/L, pH 7.0, temperature 29.6 °C. Under these conditions, the substrate conversion was 93.80% and the concentration of dATP in the reaction system was 2.10 g/L, which was 63.10% higher than before optimization, and the concentration of product was 4 times higher than before optimization. The effects of glucose, acetaldehyde, and temperature on the accumulation of dATP were analyzed.
The Photodynamic Anticancer and Antibacterial Activity Properties of a Series of meso-Tetraarylchlorin Dyes and Their Sn(IV) Complexes
Authors: Soy Rodah , Babu Balaji , Mack John , Nyokong Tebello
Published: May 2023

A series of tetraarylchlorins with 3-methoxy-, 4-hydroxy- and 3-methoxy-4-hydroxyphenyl meso-aryl rings (1-3-Chl) and their Sn(IV) complexes (1-3-SnChl) were synthesized and characterized so that their potential utility as photosensitizer dyes for use in photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) can be assessed. The photophysicochemical properties of the dyes were assessed prior to in vitro PDT activity studies against MCF-7 breast cancer cells through irradiation with Thorlabs 625 or 660 nm LED for 20 min (240 or 280 mW·cm−2). PACT activity studies were performed against both planktonic bacteria and biofilms of Gram-(+) S. aureus and Gram-(−) E. coli upon irradiation with Thorlabs 625 and 660 nm LEDs for 75 min. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.69−0.71 for 1-3-SnChl. Relatively low IC50 values between 1.1−4.1 and 3.8−9.4 µM were obtained for the 1-3-SnChl series with the Thorlabs 660 and 625 nm LEDs, respectively, during the PDT activity studies. 1-3-SnChl were also found to exhibit significant PACT activity against planktonic S. aureus and E. coli with Log10 reduction values of 7.65 and >3.0, respectively. The results demonstrate that the Sn(IV) complexes of tetraarylchlorins merit further in depth study as photosensitizers in biomedical applications.
The Potential of Algae in the Nutricosmetic Sector
Authors: Dini Irene
Published: May 2023

Seaweeds or algae are marine autotrophic organisms. They produce nutrients (e.g., proteins, carbohydrates, etc.) essential for the survival of living organisms as they participate in biochemical processes and non-nutritive molecules (such as dietary fibers and secondary metabolites), which can improve their physiological functions. Seaweed polysaccharides, fatty acids, peptides, terpenoids, pigments, and polyphenols have biological properties that can be used to develop food supplements and nutricosmetic products as they can act as antibacterial, antiviral, antioxidant, and anti-inflammatory compounds. This review examines the (primary and secondary) metabolites produced by algae, the most recent evidence of their effect on human health conditions, with particular attention to what concerns the skin and hair’s well-being. It also evaluates the industrial potential of recovering these metabolites from biomass produced by algae used to clean wastewater. The results demonstrate that algae can be considered a natural source of bioactive molecules for well-being formulations. The primary and secondary metabolites’ upcycling can be an exciting opportunity to safeguard the planet (promoting a circular economy) and, at the same time, obtain low-cost bioactive molecules for the food, cosmetic, and pharmaceutical industries from low-cost, raw, and renewable materials. Today’s lack of methodologies for recovering bioactive molecules in large-scale processes limits practical realization.
Rosmarinic Acid-Grafted Dextran/Gelatin Hydrogel as a Wound Dressing with Improved Properties: Strong Tissue Adhesion, Antibacterial, Antioxidant and Anti-Inflammatory
Authors: Yin Yi , Xu Qianqian , Wei Xin , Ma Qianyun , Li Dongsheng , Zhao Juanjuan
Published: May 2023

Designing a strong tissue adhesive and multifunctional hydrogel dressing for various skin injuries is still a significant challenge. Based on the bioactive activities of rosmarinic acid (RA) and its catechol structure being similar to dopamine, RA-grafted dextran/gelatin hydrogel (ODex−AG−RA) was designed and systemically characterized in this study. The ODex−AG−RA hydrogel exhibited excellent physicochemical properties, including fast gelation time (61.6 ± 2.8 s), strong adhesive strength (27.30 ± 2.02 kPa) and enhanced mechanical properties (1.31 × 104 Pa of G′). The examination of hemolysis and co-culturing with L929 cells showed the strong in vitro biocompatibility of ODex−AG−RA hydrogels. The ODex−AG−RA hydrogels exhibited a 100% mortality rate against S. aureus and at least 89.7% against E. coli in vitro. In vivo evaluation for efficacy in skin wound healing was carried out in a rat model of full-thickness skindefect. The amount of collagen deposition and CD31 on wounds in the two ODex−AG−RA−1 groups on day 14 was 4.3 times and 2.3 times of that in the control group, respectively. Furthermore, the mechanism of ODex−AG−RA−1 for promoting wound healing was proved to be related to its anti-inflammatory properties by adjusting the expression of inflammatory cytokines (TNF-α and CD163) and reducing the level of oxidative stress (MDA and H2O2). Overall, this study demonstrated the wound-healing efficacy of RA-grafted hydrogels for the first time. ODex−AG−RA−1 hydrogel, due to its adhesive, anti-inflammatory, antibacterial and antioxidative activities, was a promising candidate as a wound dressing.
Hybrid Nanocomposites of Tenoxicam: Layered Double Hydroxides (LDHs) vs. Hydroxyapatite (HAP) Inorganic Carriers
Authors: Maggi Lauretta , Friuli Valeria , Bruni Giovanna , Rinaldi Alessia , Bini Marcella
Published: May 2023

The search for effective systems to facilitate the release of poorly bioavailable drugs is a forefront topic for the pharmaceutical market. Materials constituted by inorganic matrices and drugs represent one of the latest research strategies in the development of new drug alternatives. Our aim was to obtain hybrid nanocomposites of Tenoxicam, an insoluble nonsteroidal anti-inflammatory drug, with both layered double hydroxides (LDHs) and hydroxyapatite (HAP). The physicochemical characterization on the base of X-ray powder diffraction, SEM/EDS, DSC and FT-IR measurements was useful to verify the possible hybrids formation. In both cases, the hybrids formed, but it seemed that the drug intercalation in LDH was low and, in fact, the hybrid was not effective in improving the pharmacokinetic properties of the drug alone. On the contrary, the HAP–Tenoxicam hybrid, compared to the drug alone and to a simple physical mixture, showed an excellent improvement in wettability and solubility and a very significant increase in the release rate in all the tested biorelevant fluids. It delivers the entire daily dose of 20 mg in about 10 min.
Oligosaccharide Ligands of Galectin-4 and Its Subunits: Multivalency Scores Highly
Authors: Slámová Kristýna , Červený Jakub , Mészáros Zuzana , Friede Tereza , Vrbata David , Křen Vladimír , Bojarová Pavla
Published: May 2023

Galectins are carbohydrate-binding lectins that modulate the proliferation, apoptosis, adhesion, or migration of cells by cross-linking glycans on cell membranes or extracellular matrix components. Galectin-4 (Gal-4) is a tandem-repeat-type galectin expressed mainly in the epithelial cells of the gastrointestinal tract. It consists of an N- and a C-terminal carbohydrate-binding domain (CRD), each with distinct binding affinities, interconnected with a peptide linker. Compared to other more abundant galectins, the knowledge of the pathophysiology of Gal-4 is sparse. Its altered expression in tumor tissue is associated with, for example, colon, colorectal, and liver cancers, and it increases in tumor progression, and metastasis. There is also very limited information on the preferences of Gal-4 for its carbohydrate ligands, particularly with respect to Gal-4 subunits. Similarly, there is virtually no information on the interaction of Gal-4 with multivalent ligands. This work shows the expression and purification of Gal-4 and its subunits and presents a structure–affinity relationship study with a library of oligosaccharide ligands. Furthermore, the influence of multivalency is demonstrated in the interaction with a model lactosyl-decorated synthetic glycoconjugate. The present data may be used in biomedical research for the design of efficient ligands of Gal-4 with diagnostic or therapeutic potential.
HPLC Analysis and Molecular Docking Study of Myoporum serratum Seeds Extract with Its Bioactivity against Pathogenic Microorganisms and Cancer Cell Lines
Authors: Mashraqi Abdullah , Modafer Yosra , Al Abboud Mohamed A. , Salama Hanaa M. , Abada Emad
Published: May 2023

Natural constituents have been utilized to avoid humanity from various diseases, such as microbial infection and cancer, over several decades due to bioactive compounds. Myoporum serratum seeds extract (MSSE) was formulated via HPLC for flavonoid and phenolic analysis. Moreover, antimicrobial via well diffusion method, antioxidant via 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, anticancer activities against HepG-2 cells (human hepatocellular cancer cell line), and MCF-7 cells (human breast cancer cell line), and molecular docking of the main detected flavonoid and phenolic compounds with the cancer cells were performed. The phenolic acids, including cinnamic acid (12.75 µg/mL), salicylic acid (7.14 µg/mL), and ferulic (0.97 µg/mL), while luteolin represents the main detected flavonoid with a concentration of 10.74 µg/mL, followed by apegenin 8.87 µg/mL were identified in MSSE. Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, and Candida albicans were inhibited by MSSE with 24.33, 26.33, 20.67, and 18.33 mm of inhibition zone, respectively. MSSE exhibited a low inhibition zone of 12.67 mm against Escherichia coli while showing no inhibitory activity against Aspergillus fumigatus. The values of MIC ranged from 26.58 to 136.33 µg/mL for all tested microorganisms. MBC/MIC index and cidal properties were attributed to MSSE for all tested microorganisms except E. coli. MSSE demonstrated anti-biofilm 81.25 and 50.45% of S. aureus and E. coli, respectively. IC50 of the antioxidant activity of MSSE was 120.11 µg/mL. HepG-2 and MCF-7 cell proliferation were inhibited with IC50 140.77 ± 3.86 µg/mL and 184.04 µg/mL, respectively. Via Molecular docking study, luteolin and cinnamic acid have inhibitory action against HepG-2 and MCF-7 cells, supporting the tremendous anticancer of MSSE.
Lactiplantibacillus plantarum NKK20 Alleviates High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Regulating Bile Acid Anabolism
Authors: Sun Chang , Qiu Chenguang , Zhang Yanyan , Yan Man , Tan Jiajun , He Jiayuan , Yang Dakai , Wang Dongxu , Wu Liang
Published: May 2023

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.
Pharmacophore-Based Virtual Screening and In-Silico Explorations of Biomolecules (Curcumin Derivatives) of Curcuma longa as Potential Lead Inhibitors of ERBB and VEGFR-2 for the Treatment of Colorectal Cancer
Authors: Ejaz Syeda Abida , Aziz Mubashir , Fawzy Ramadan Mohamed , Fayyaz Ammara , Bilal Muhammad Sajjad
Published: May 2023

The newly FDA-approved drug, Axitinib, is an effective therapy against RTKs, but it possesses severe adverse effects like hypertension, stomatitis, and dose-dependent toxicity. In order to ameliorate Axitinib’s downsides, the current study is expedited to search for energetically stable and optimized pharmacophore features of 14 curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) derivatives. The rationale behind the selection of curcumin derivatives is their reported anti-angiogenic and anti-cancer properties. Furthermore, they possessed a low molecular weight and a low toxicity profile. In the current investigation, the pharmacophore model-based drug design, facilitates the filtering of curcumin derivatives as VEGFR2 interfacial inhibitors. Initially, the Axitinib scaffold was used to build a pharmacophore query model against which curcumin derivatives were screened. Then, top hits from pharmacophore virtual screening were subjected to in-depth computational studies such as molecular docking, density functional theory (DFT) studies, molecular dynamics (MD) simulations, and ADMET property prediction. The findings of the current investigation revealed the substantial chemical reactivity of the compounds. Specifically, compounds S8, S11, and S14 produced potential molecular interactions against all four selected protein kinases. Docking scores of −41.48 and −29.88 kJ/mol for compounds S8 against VEGFR1 and VEGFR3, respectively, were excellent. Whereas compounds S11 and S14 demonstrated the highest inhibitory potential against ERBB and VEGFR2, with docking scores of −37.92 and −38.5 kJ/mol against ERBB and −41.2 and −46.5 kJ/mol against VEGFR-2, respectively. The results of the molecular docking studies were further correlated with the molecular dynamics simulation studies. Moreover, HYDE energy was calculated through SeeSAR analysis, and the safety profile of the compounds was predicted through ADME studies.
Exploitation of Sugarcane Bagasse and Environmentally Sustainable Production, Purification, Characterization, and Application of Lovastatin by Aspergillus terreus AUMC 15760 under Solid-State Conditions
Authors: Ramadan Ahmed M. A. A. , Shehata Reda M. , EL-Sheikh Hussein H. , Ameen Fuad , Stephenson Steven L. , Zidan Sabry A. H. , Al-Bedak Osama A. M.
Published: May 2023

Using the internal transcribed spacer (ITS) region for identification, three strains of Aspergillus terreus were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the Assiut University Mycological Centre culture collection. The ability of the three strains to manufacture lovastatin in solid-state fermentation (SSF) using wheat bran was assessed using gas chromatography-mass spectroscopy (GC-MS). The most potent strain was strain AUMC 15760, which was chosen to ferment nine types of lignocellulosic waste (barley bran, bean hay, date palm leaves, flax seeds, orange peels, rice straw, soy bean, sugarcane bagasse, and wheat bran), with sugarcane bagasse turning out to be the best substrate. After 10 days at pH 6.0 at 25 °C using sodium nitrate as the nitrogen source and a moisture content of 70%, the lovastatin output reached its maximum quantity (18.2 mg/g substrate). The medication was produced in lactone form as a white powder in its purest form using column chromatography. In-depth spectroscopy examination, including 1H, 13C-NMR, HR-ESI-MS, optical density, and LC-MS/MS analysis, as well as a comparison of the physical and spectroscopic data with published data, were used to identify the medication. At an IC50 of 69.536 ± 5.73 µM, the purified lovastatin displayed DPPH activity. Staphylococcus aureus and Staphylococcus epidermidis had MICs of 1.25 mg/mL, whereas Candida albicans and Candida glabrata had MICs of 2.5 mg/mL and 5.0 mg/mL, respectively, against pure lovastatin. As a component of sustainable development, this study offers a green (environmentally friendly) method for using sugarcane bagasse waste to produce valuable chemicals and value-added commodities.
Synthesis and Antiproliferative Insights of Lipophilic Ru(II)-Hydroxy Stearic Acid Hybrid Species
Authors: Drius Giacomo , Bordoni Silvia , Boga Carla , Monari Magda , Fiori Jessica , Esposito Erika , Zalambani Chiara , Pincigher Luca , Farruggia Giovanna , Calonghi Natalia , Micheletti Gabriele
Published: May 2023

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.
Carbene-Catalyzed Atroposelective Annulation for Quick Access to Axially Chiral Thiazine Derivatives
Authors: Yang Xiaoqun , Li Tingting , Chen Jinli , Huang Yixian , Shen Tingwei , Li Shiguang , Jin Zhichao , Ren Shi-Chao
Published: May 2023

An N-heterocyclic carbene (NHC)-catalyzed atroposelective annulation reaction is disclosed for quick and efficient access to thiazine derivatives. A series of axially chiral thiazine derivatives bearing various substituents and substitution patterns were produced in moderate to high yields with moderate to excellent optical purities. Preliminary studies revealed that some of our products exhibit promising antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) that causes rice bacterial blight.
Antihyperglycemic Properties of Extracts and Isolated Compounds from Australian Acacia saligna on 3T3-L1 Adipocytes
Authors: Asmara Anjar P. , Prasansuklab Anchalee , Chiabchalard Anchalee , Chen Hui , Ung Alison T.
Published: May 2023

Our early work indicated that methanolic extracts from the flowers, leaves, bark, and isolated compounds of Acacia saligna exhibited significant antioxidant activities in vitro. The overproduction of reactive oxygen species (ROS) in the mitochondria (mt-ROS) interfered with glucose uptake, metabolism, and its AMPK-dependent pathway, contributing to hyperglycemia and diabetes. This study aimed to screen the ability of these extracts and isolated compounds to attenuate the production of ROS and maintain mitochondrial function via the restoration of mitochondrial membrane potential (MMP) in 3T3-L1 adipocytes. Downstream effects were investigated via an immunoblot analysis of the AMPK signalling pathway and glucose uptake assays. All methanolic extracts effectively reduced cellular ROS and mt-ROS levels, restored the MMP, activated AMPK-α, and enhanced cellular glucose uptake. At 10 µM, (−)-epicatechin-6 (from methanolic leaf and bark extracts) markedly reduced ROS and mt-ROS levels by almost 30% and 50%, respectively, with an MMP potential ratio 2.2-fold higher compared to the vehicle control. (−)-Epicatechin 6 increased the phosphorylation of AMPK-α by 43%, with an 88% higher glucose uptake than the control. Other isolated compounds include naringenin 1, naringenin-7-O-α-L-arabinopyranoside 2, isosalipurposide 3, D-(+)-pinitol 5a, and (−)-pinitol 5b, which also performed relatively well across all assays. Australian A. saligna active extracts and compounds can reduce ROS oxidative stress, improve mitochondrial function, and enhance glucose uptake through AMPK-α activation in adipocytes, supporting its potential antidiabetic application.