bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioleaching of Gold in Mine Tailings by Alcaligenes faecalis
Authors: Pineda Yilman S. , Devries Stephanie L. , Steiner Nicholas C. , Block-Cora Karin A.
Published: March 2023

We conducted a series of column experiments on tailing heap samples from the Picacho mine in California to determine the ability of the native Gram-negative bacteria, Alcaligenes faecalis, to leach gold. To mimic heap leaching using our technique, unprocessed and unsorted tailings of mixed grain sizes were placed into columns and leached for three weeks with four treatments: (1) deionized water, (2) bacteria, (3) NaCN by bacteria and (4) NaCN. In all of the experimental runs, the total Au (mg) recovered from the columns treated with A. faecalis and NaCN followed by A. faecalis yielded gold amounts that were higher than those from the deionized water control, and lower than the columns treated with cyanide. However, the total yields were variable across runs, which we attribute to the inherent heterogeneity of gold distribution in the samples. Statistical tests show that the yields from the treatments employing bacteria and/or cyanide were different from those that employed deionized water alone. Our results support previous studies that showed that exudates of A faecalis promoted reduction of Au3+, catalyzing extracellular Au0 particles under alkaline conditions. We propose that A. faecalis is a possible novel alternative to cyanide treatment for recovering Au from mine tailings, and recommend optimization of the method.
Antibacterial and Antibiofilm Effects of Allelopathic Compounds Identified in Medicago sativa L. Seedling Exudate against Escherichia coli
Authors: Abouzeid Sara , Beutling Ulrike , Elekhnawy Engy , Selmar Dirk
Published: March 2023

In this study, the allelopathic properties of Medicago sativa L. (alfalfa) seedling exudates on the germination of seeds of various species were investigated. The compounds responsible for the allelopathic effects of alfalfa were identified and characterized by employing liquid chromatography ion mobility high-resolution mass spectrometry. Crude exudates inhibited the germination of seeds of all various plant species tested. Overall, nine compounds in alfalfa were identified and quantified. The most predominant compounds were a hyperoside representing a flavonoid glucoside, the non-proteinogenic amino acid canavanine, and two dipeptides, identified as H-Glu-Tyr-OH and H-Phe-Glu-OH. The latter corresponds to the first finding that dipeptides are exuded from alfalfa seedlings. In addition, the antibacterial and antibiofilm activities of alfalfa exudate and its identified compounds were elucidated. Both hyperoside and canavanine revealed the best antibacterial activity with minimum inhibitory concentration (MIC) values that ranged from 8 to 32 and 32 to 256 µg/mL, respectively. Regarding the antibiofilm action, hyperoside and canavanine caused a decline in the percentage of E. coli isolates that possessed a strong and moderate biofilm-forming potential from 68.42% to 21.05% and 31.58%, respectively. Studies on their inhibiting effects exhibit that these major substances are predominantly responsible for the allelopathic and antimicrobial effects of the crude exudates.
Removal of Tetracycline Hydrochloride by Photocatalysis Using Electrospun PAN Nanofibrous Membranes Coated with g-C3N4/Ti3C2/Ag3PO4
Authors: Wang Peng , Han Xu , Zheng Xianhong , Wang Zongqian , Li Changlong , Zhao Zhiqi
Published: March 2023

In order to improve the photocatalytic performance of g-C3N4, the g-C3N4/Ti3C2/Ag3PO4 S-type heterojunction catalyst was prepared by electrostatic assembly method, and then the g-C3N4/Ti3C2/Ag3PO4/PAN composite nanofiber membrane was prepared by electrospinning technology. The morphology and chemical properties of the nanofiber membrane were characterized by SEM, FTIR, and XRD, and the photocatalytic degradation of tetracycline hydrochloride (TC) in water by the nanofiber membrane was investigated. The results showed that g-C3N4/Ti3C2/Ag3PO4 could be successfully loaded on PAN and uniformly distributed on the surface of composite nanofiber membrane by electrospinning technology. Increasing the amount of loading and catalyst, lowering the pH value and TC concentration of the system were conducive to the oxidation and degradation of TC. The nano-fiber catalytic membrane had been recycled five times and found to have excellent photocatalytic stability and reusability. The study of catalytic mechanism showed that h+, •OH and •O2− were produced and participated in the oxidation degradation reaction of TC, and •O2− plays a major role in catalysis. Therefore, this work provides a new insight into the construction of high-performance and high-stability photocatalytic system by electrospinning technology.
Mercury and Organic Pollutants Removal from Aqueous Solutions by Heterogeneous Photocatalysis with ZnO-Based Materials
Authors: Gaggero Elisa , López-Muñoz María José , Paganini Maria Cristina , Arencibia Amaya , Bertinetti Stefano , Fernández de Paz Nieves , Calza Paola
Published: March 2023

The removal of four Contaminants of Emerging Concern, namely bisphenol A, sulfamethoxazole, diclofenac and benzotriazole; two odorous compounds, geosmin and 2-methylisoborneol, frequently detected in recirculating aquaculture systems; and Hg(II) was investigated using ZnO-based materials doped or co-doped with Ce and Cu under simulated solar radiation. Photocatalysts were synthetized via a hydrothermal route and their efficiency was assessed by changing some operational parameters in different water matrices of increasing complexity. The mixture of contaminants was successfully degraded in just 1 h, while the complete mineralization was achieved in a few hours; experiments performed in an actual aquaculture water confirmed the efficiency and broad versatility of the synthesized materials.
Quinoline-Malononitrile-Based Aggregation-Induced Emission Probe for Monoamine Oxidase Detection in Living Cells
Authors: Duangkamol Chuthamat , Wangngae Sirilak , Wet-osot Sirawit , Khaikate Onnicha , Chansaenpak Kantapat , Lai Rung-Yi , Kamkaew Anyanee
Published: March 2023

A quinoline-malononitrile (QM)-based aggregation-induced emission probe was developed to detect MAOs in cells through an enzymatic reaction followed by β-elimination. After being incubated at 37 °C, QM-NH2 responded to the MAO enzymes with great specificity and within just 5 min. This 5 min responsive mechanism was fast, with the limit of detection (LOD) at 5.49 and 4.76 µg mL−1 for MAO-A and MAO-B, respectively. Moreover, QM-NH2 displayed high enzyme specificity even in the presence of high concentrations of biological interferences, such as oxidizing and reducing agents, biothiols, amino acids, and glucose. Furthermore, QM-NH2 demonstrated biocompatibility as the cells retained more than 70% viability when exposed to QM-NH2 at concentrations of up to 20 µM. As a result, QM-NH2 was used to detect MAO-A and MAO-B in SH-SY5Y and HepG2 cells, respectively. After 1h incubation with QM-NH2, the cells exhibited enhanced fluorescence by about 20-fold. Moreover, the signal from cells was reduced when MAO inhibitors were applied prior to incubating with QM-NH2. Therefore, our research recommends using a QM probe as a generic method for producing recognition moieties for fluorogenic enzyme probes.
A Simulation of the Effect of External and Internal Parameters on the Synthesis of a Carbyne with More than 6000 Atoms for Emerging Continuously Tunable Energy Barriers in CNT-Based Transistors
Authors: Wong Chi Ho , Yeung Yan Ming , Zhao Xin , Law Wing Cheung , Tang Chak Yin , Mak Chee Leung , Leung Chi Wah , Shi Lei , Lortz Rolf
Published: March 2023

Transistors made up of carbon nanotube CNT have demonstrated excellent current–voltage characteristics which outperform some high-grade silicon-based transistors. A continuously tunable energy barrier across semiconductor interfaces is desired to make the CNT-based transistors more robust. Despite that the direct band gap of the carbyne inside a CNT can be widely tuned by strain, the size of the carbyne cannot be controlled easily. The production of a monoatomic chain with more than 6000 carbon atoms is an enormous technological challenge. To predict the optimal chain length of a carbyne in different molecular environments, we have developed a Monte Carlo model in which a finite-length carbyne with a size of 4000–15,000 atoms is encapsulated by a CNT at finite temperatures. Our simulation shows that the stability of the carbyne@nanotube is strongly influenced by the nature and porosity of the CNT, the external pressure, the temperature, and the chain length. We have observed an initiation of the chain-breaking process in a compressed carbyne@nanotube. Our work provides much-needed input for optimizing the carbyne length to produce carbon chains much longer than 6000 atoms at ~300 K. Design rules are proposed for synthesizing ~1% strained carbyne@(6,5)CNT as a component in CNT-based transistors to tune the energy barriers continuously.
Nanoparticles in the Environment and Nanotoxicology
Authors: Liao Vivian Hsiu-Chuan
Published: March 2023

Nanomaterials, including engineered nanoparticles and microplastics/nanoplastics, have attracted increasing concern as they might potentially release into the environment, leading to potential risks to ecosystems [...]
Abstracts of the Fifth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Italy, 28–30 September 2022
Authors: Ferrara Giovanni
Published: March 2023

On behalf of the BraYn Association Ets, we are pleased to present the Abstracts of the Fifth Brainstorming Research Assembly for Young Neuroscientists, which was held in Rome, Italy from 28–30 September 2022. We congratulate all the presenters on their research work and contribution.
Sleep and Chronobiology as a Key to Understand Cluster Headache
Authors: Pilati Laura , Torrente Angelo , Alonge Paolo , Vassallo Lavinia , Maccora Simona , Gagliardo Andrea , Pignolo Antonia , Iacono Salvatore , Ferlisi Salvatore , Di Stefano Vincenzo , Camarda Cecilia , Brighina Filippo
Published: March 2023

The cluster headache is a primary headache characterized by attacks of unilateral pain associated with ipsilateral cranial autonomic features. These attacks recur in clusters during the years alternating with periods of complete remission, and their onset is often during the night. This annual and nocturnal periodicity hides a strong and mysterious link among CH, sleep, chronobiology and circadian rhythm. Behind this relationship, there may be the influence of genetic components or of anatomical structures such as the hypothalamus, which are both involved in regulating the biological clock and contributing even to the periodicity of cluster headaches. The bidirectional relationship manifests itself also with the presence of sleep disturbances in patients affected by cluster headaches. What if the key to studying the physiopathology of such disease could rely on the mechanisms of chronobiology? The purpose of this review is to analyze this link in order to interpret the pathophysiology of cluster headaches and the possible therapeutic implications.
Clinical Features of Acute Ischemic Stroke Patients with Hypoesthesia as an Initial Symptom
Authors: Akimoto Takayoshi , Ogawa Katsuhiko , Hara Makoto , Ninomiya Satoko , Ishihara Masaki , Morita Akihiko , Kamei Satoshi , Nakajima Hideto
Published: March 2023

This study aimed to evaluate the clinical characteristics of acute ischemic stroke (AIS) patients who experienced hypoesthesia as the initial symptom. We retrospectively analyzed the medical records of 176 hospitalized AIS patients who met our inclusion and exclusion criteria and evaluated their clinical features and MRI findings. Among this cohort, 20 (11%) patients presented with hypoesthesia as the initial symptom. MRI scans of these 20 patients identified lesions in the thalamus or pontine tegmentum in 14 and brain lesions at other sites in 6. The 20 hypoesthesia patients had higher systolic (p = 0.031) and diastolic blood pressure (p = 0.037) on admission, and a higher rate of small-vessel occlusion (p < 0.001) than patients without hypoesthesia. The patients with hypoesthesia had a significantly shorter average hospital stay (p = 0.007) but did not differ significantly from those without hypoesthesia in National Institutes of Health Stroke Scale scores on admission (p = 0.182) or the modified Rankin Scale scores for neurologic disability on discharge (p = 0.319). In the patients with acute onset hypoesthesia, high blood pressure, and neurological deficits were more likely to be due to AIS than other causes. Since most of the lesions in AIS patients with hypoesthesia as the initial symptom were found to be small, we recommend performing MRI scans with such patients to confirm AIS.
PRO-DEMET Randomized Controlled Trial on Probiotics in Depression—Pilot Study Results
Authors: Gawlik-Kotelnicka Oliwia , Margulska Aleksandra , Skowrońska Anna , Strzelecki Dominik
Published: March 2023

There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.
Diet Quality, Microbial Lignan Metabolites, and Cardiometabolic Health among US Adults
Authors: Koemel Nicholas A. , Senior Alistair M. , Benmarhnia Tarik , Holmes Andrew , Okada Mirei , Oulhote Youssef , Parker Helen M. , Shah Sanam , Simpson Stephen J. , Raubenheimer David , Gill Timothy P. , Laouali Nasser , Skilton Michael R.
Published: March 2023

The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectional data from 4685 US adults (age 43.6 ± 16.5 years; 50.4% female) participating in the National Health and Nutrition Examination Survey for 1999–2010. Dietary data were collected from one to two separate 24-hour dietary recalls and diet quality was characterized using the 2015 Healthy Eating Index. Cardiometabolic health markers included blood lipid profile, glycemic control, adiposity, and blood pressure. Microbial lignan metabolites considered were urinary concentrations of enterolignans, including enterolactone and enterodiol, with higher levels indicating a healthier gut microbial environment. Models were visually examined using a multidimensional approach and statistically analyzed using three-dimensional generalized additive models. There was a significant interactive association between diet quality and microbial lignan metabolites for triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, oral glucose tolerance, adiposity, systolic blood pressure, and diastolic blood pressure (all p < 0.05). Each of these cardiometabolic health markers displayed an association such that optimal cardiometabolic health was only observed in individuals with both high diet quality and elevated urinary enterolignans. When comparing effect sizes on the multidimensional response surfaces and model selection criteria, the strongest support for a potential moderating relationship of the gut microbiome was observed for fasting triglycerides and oral glucose tolerance. In this study, we revealed interactive associations of diet quality and microbial lignan metabolites with cardiometabolic health markers. These findings suggest that the overall association of diet quality on cardiometabolic health may be affected by the gut microbiome.
The Genetic Basis of Childhood Obesity: A Systematic Review
Authors: Vourdoumpa Aikaterini , Paltoglou George , Charmandari Evangelia
Published: March 2023

Overweight and obesity in childhood and adolescence represents one of the most challenging public health problems of our century owing to its epidemic proportions and the associated significant morbidity, mortality, and increase in public health costs. The pathogenesis of polygenic obesity is multifactorial and is due to the interaction among genetic, epigenetic, and environmental factors. More than 1100 independent genetic loci associated with obesity traits have been currently identified, and there is great interest in the decoding of their biological functions and the gene–environment interaction. The present study aimed to systematically review the scientific evidence and to explore the relation of single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with changes in body mass index (BMI) and other measures of body composition in children and adolescents with obesity, as well as their response to lifestyle interventions. Twenty-seven studies were included in the qualitative synthesis, which consisted of 7928 overweight/obese children and adolescents at different stages of pubertal development who underwent multidisciplinary management. The effect of polymorphisms in 92 different genes was assessed and revealed SNPs in 24 genetic loci significantly associated with BMI and/or body composition change, which contribute to the complex metabolic imbalance of obesity, including the regulation of appetite and energy balance, the homeostasis of glucose, lipid, and adipose tissue, as well as their interactions. The decoding of the genetic and molecular/cellular pathophysiology of obesity and the gene–environment interactions, alongside with the individual genotype, will enable us to design targeted and personalized preventive and management interventions for obesity early in life.
The Impact of a Low-Carbohydrate Diet on Micronutrient Intake and Status in Adolescents with Type 1 Diabetes
Authors: Levran Neriya , Levek Noah , Sher Bruria , Gruber Noah , Afek Arnon , Monsonego-Ornan Efrat , Pinhas-Hamiel Orit
Published: March 2023

Objective: The aim of this study was to evaluate the macronutrient and micronutrient intake and status in youth with type 1 diabetes mellitus (T1DM) following the consumption of a low-carbohydrate diet (LCD). Research Methods and Procedures: In a prospective intervention clinical trial, adolescents with T1DM using a continuous glucose monitoring device were enrolled. Following a cooking workshop, each participant received a personalized diet regime based on LCD (50–80 g carbohydrate/day). A Food Frequency Questionnaire was administered, and laboratory tests were taken before and 6 months following the intervention. Twenty participants were enrolled. Results: The median age was 17 years (15; 19), and the median diabetes duration was 10 years (8; 12). During the six-months intervention, carbohydrate intake decreased from 266 g (204; 316) to 87 g (68; 95) (p = 0.004). Energy intake, the energy percent from ultra-processed food, and fiber intake decreased (p = 0.001, p = 0.024, and p < 0.0001, respectively). These changes were accompanied by declines in BMI z-score (p = 0.019) and waist-circumference percentile (p = 0.007). Improvement was observed in the median HbA1c from 8.1% (7.5; 9.4) to 7.7% (6.9; 8.2) (p = 0.021). Significant declines below the DRI were shown in median intake levels of iron, calcium, vitamin B1, and folate. Conclusions: The LCD lowered ultra-processed food consumption, BMI z-scores and the indices of central obesity. However, LCDs require close nutritional monitoring due to the possibility of nutrient deficiencies.
Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases
Authors: Vinh Donald C.
Published: March 2023

In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases.
IFN-Induced PARPs—Sensors of Foreign Nucleic Acids?
Authors: Biaesch Katharina , Knapp Sarah , Korn Patricia
Published: March 2023

Cells have developed different strategies to cope with viral infections. Key to initiating a defense response against viruses is the ability to distinguish foreign molecules from their own. One central mechanism is the perception of foreign nucleic acids by host proteins which, in turn, initiate an efficient immune response. Nucleic acid sensing pattern recognition receptors have evolved, each targeting specific features to discriminate viral from host RNA. These are complemented by several RNA-binding proteins that assist in sensing of foreign RNAs. There is increasing evidence that the interferon-inducible ADP-ribosyltransferases (ARTs; PARP9—PARP15) contribute to immune defense and attenuation of viruses. However, their activation, subsequent targets, and precise mechanisms of interference with viruses and their propagation are still largely unknown. Best known for its antiviral activities and its role as RNA sensor is PARP13. In addition, PARP9 has been recently described as sensor for viral RNA. Here we will discuss recent findings suggesting that some PARPs function in antiviral innate immunity. We expand on these findings and integrate this information into a concept that outlines how the different PARPs might function as sensors of foreign RNA. We speculate about possible consequences of RNA binding with regard to the catalytic activities of PARPs, substrate specificity and signaling, which together result in antiviral activities.
Glycosylation and Lipidation Strategies: Approaches for Improving Antimicrobial Peptide Efficacy
Authors: Bellavita Rosa , Braccia Simone , Galdiero Stefania , Falanga Annarita
Published: March 2023

Antimicrobial peptides (AMPs) have recently gained attention as a viable solution for combatting antibiotic resistance due to their numerous advantages, including their broad-spectrum activity, low propensity for inducing resistance, and low cytotoxicity. Unfortunately, their clinical application is limited due to their short half-life and susceptibility to proteolytic cleavage by serum proteases. Indeed, several chemical strategies, such as peptide cyclization, N-methylation, PEGylation, glycosylation, and lipidation, are widely used for overcoming these issues. This review describes how lipidation and glycosylation are commonly used to increase AMPs’ efficacy and engineer novel AMP-based delivery systems. The glycosylation of AMPs, which involves the conjugation of sugar moieties such as glucose and N-acetyl galactosamine, modulates their pharmacokinetic and pharmacodynamic properties, improves their antimicrobial activity, and reduces their interaction with mammalian cells, thereby increasing selectivity toward bacterial membranes. In the same way, lipidation of AMPs, which involves the covalent addition of fatty acids, has a significant impact on their therapeutic index by influencing their physicochemical properties and interaction with bacterial and mammalian membranes. This review highlights the possibility of using glycosylation and lipidation strategies to increase the efficacy and activity of conventional AMPs.
The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility
Authors: Abdulsamad Haia M. R. , Murtaza Zoha F. , AlMuhairi Hessa M. , Bafleh Wjdan S. , AlMansoori Salma A. , AlQubaisi Shaikha A. , Hamdan Hamdan , Kashir Junaid
Published: March 2023

Oocyte activation, a fundamental event during mammalian fertilisation, is initiated by concerted intracellular patterns of calcium (Ca2+) release, termed Ca2+ oscillations, predominantly driven by testis-specific phospholipase C zeta (PLCζ). Ca2+ exerts a pivotal role in not just regulating oocyte activation and driving fertilisation, but also in influencing the quality of embryogenesis. In humans, a failure of Ca2+ release, or defects in related mechanisms, have been reported to result in infertility. Furthermore, mutations in the PLCζ gene and abnormalities in sperm PLCζ protein and RNA, have been strongly associated with forms of male infertility where oocyte activation is deficient. Concurrently, specific patterns and profiles of PLCζ in human sperm have been linked to parameters of semen quality, suggesting the potential for PLCζ as a powerful target for both therapeutics and diagnostics of human fertility. However, further to PLCζ and given the strong role played by Ca2+ in fertilisation, targets down- and up-stream of this process may also present a significantly similar level of promise. Herein, we systematically summarise recent advancements and controversies in the field to update expanding clinical associations between Ca2+-release, PLCζ, oocyte activation and human fertility. We discuss how such associations may potentially underlie defective embryogenesis and recurrent implantation failure following fertility treatments, alongside potential diagnostic and therapeutic avenues presented by oocyte activation for the diagnosis and treatment of human infertility.
Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer
Authors: Sokolov Pavel , Nifontova Galina , Samokhvalov Pavel , Karaulov Alexander , Sukhanova Alyona , Nabiev Igor
Published: March 2023

Multiplexed fluorescent immunohistochemical analysis of breast cancer (BC) markers and high-resolution 3D immunofluorescence imaging of the tumor and its microenvironment not only facilitate making the disease prognosis and selecting effective anticancer therapy (including photodynamic therapy), but also provides information on signaling and metabolic mechanisms of carcinogenesis and helps in the search for new therapeutic targets and drugs. The characteristics of imaging nanoprobe efficiency, such as sensitivity, target affinity, depth of tissue penetration, and photostability, are determined by the properties of their components, fluorophores and capture molecules, and by the method of their conjugation. Regarding individual nanoprobe components, fluorescent nanocrystals (NCs) are widely used for optical imaging in vitro and in vivo, and single-domain antibodies (sdAbs) are well established as highly specific capture molecules in diagnostic and therapeutic applications. Moreover, the technologies of obtaining functionally active sdAb–NC conjugates with the highest possible avidity, with all sdAb molecules bound to the NC in a strictly oriented manner, provide 3D-imaging nanoprobes with strong comparative advantages. This review is aimed at highlighting the importance of an integrated approach to BC diagnosis, including the detection of biomarkers of the tumor and its microenvironment, as well as the need for their quantitative profiling and imaging of their mutual location, using advanced approaches to 3D detection in thick tissue sections. The existing approaches to 3D imaging of tumors and their microenvironment using fluorescent NCs are described, and the main comparative advantages and disadvantages of nontoxic fluorescent sdAb–NC conjugates as nanoprobes for multiplexed detection and 3D imaging of BC markers are discussed.
The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability
Authors: Jang Dong-Jin , Lee Jun Hak , Kim Da Hun , Kim Jin-Woo , Koo Tae-Sung , Cho Kwan Hyung
Published: March 2023

The present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosity hydroxypropyl methylcellulose (HPMC 4.5cp) was selected and worked efficiently to suppress REB precipitation at 40 °C for 16 days. The additionally optimized eye drops formulation (F18 and F19) using aminocaproic acid and D-sorbitol as a buffering agent and an osmotic agent, respectively, demonstrated long-term physicochemical stability at 25 °C and 40 °C for 6 months. The hypotonicity (<230 mOsm) for F18 and F19 noticeably extended the stable period, since the pressure causing the REB precipitation was relieved compared to the isotonic. In the rat study, the optimized REB eye drops showed significantly long-lasting pharmacokinetic results, suggesting the possibility of reducing daily administration times and increasing patient compliance (0.50- and 0.83-times lower Cmax and 2.60- and 3.64-times higher exposure in the cornea and aqueous humor). In conclusion, the formulations suggested in the present study are promising candidates and offer enhanced solubility, stability, patient compliance, and bioavailability.
Travoprost Liquid Nanocrystals: An Innovative Armamentarium for Effective Glaucoma Therapy
Authors: El-Gendy Mohamed A. , Mansour Mai , El-Assal Mona I. A. , Ishak Rania A. H. , Mortada Nahed D.
Published: March 2023

To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween® 80 as a stabilizer, and either oleic acid or Captex® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% and 322.82%, respectively, relative to the market product TRAVATAN®. They exhibited respective intraocular pressure reductions lasting for 48 and 72 h, compared to 36 h for TRAVATAN®. All LCNs exhibited no evidence of ocular injury in comparison to the control eye. The findings revealed the competence of TRAVO-tailored LCNs in glaucoma treatment and suggested the potential application of a novel platform in ocular delivery.
Development of Dipeptide N–acetyl–L–cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides
Authors: Eulálio Denise , Pires Figueiredo Mariana , Taviot-Gueho Christine , Leroux Fabrice , dos Reis Serra Cristina Helena , Faria Dalva Lúcia Araújo de , Constantino Vera Regina Leopoldo
Published: March 2023

N–acetyl–L–cysteine (NAC), a derivative of the L–cysteine amino acid, presents antioxidant and mucolytic properties of pharmaceutical interest. This work reports the preparation of organic-inorganic nanophases aiming for the development of drug delivery systems based on NAC intercalation into layered double hydroxides (LDH) of zinc–aluminum (Zn2Al–NAC) and magnesium–aluminum (Mg2Al–NAC) compositions. A detailed characterization of the synthesized hybrid materials was performed, including X-ray diffraction (XRD) and pair distribution function (PDF) analysis, infrared and Raman spectroscopies, solid-state 13carbon and 27aluminum nuclear magnetic resonance (NMR), simultaneous thermogravimetric and differential scanning calorimetry coupled to mass spectrometry (TG/DSC–MS), scanning electron microscopy (SEM), and elemental chemical analysis to assess both chemical composition and structure of the samples. The experimental conditions allowed to isolate Zn2Al–NAC nanomaterial with good crystallinity and a loading capacity of 27.3 (m/m)%. On the other hand, NAC intercalation was not successful into Mg2Al–LDH, being oxidized instead. In vitro drug delivery kinetic studies were performed using cylindrical tablets of Zn2Al–NAC in a simulated physiological solution (extracellular matrix) to investigate the release profile. After 96 h, the tablet was analyzed by micro-Raman spectroscopy. NAC was replaced by anions such as hydrogen phosphate by a slow diffusion-controlled ion exchange process. Zn2Al–NAC fulfil basic requirements to be employed as a drug delivery system with a defined microscopic structure, appreciable loading capacity, and allowing a controlled release of NAC.
Comparison of Fracture Identification Using Different Definitions in Healthcare Administrative (Claims) Data
Authors: Konstantelos Natalia , Burden Andrea M. , Cheung Angela M. , Kim Sandra , Grootendorst Paul , Cadarette Suzanne M.
Published: March 2023

We identified inconsistency in fracture definitions in a prior review of studies that utilized claims data. Here, we aimed to compare fracture rates estimated using thirteen hip and seven radius/ulna fracture definitions. Our primary analysis compared results in a cohort of 120,363 older adults treated with oral bisphosphonates for ≥3 years. The most inclusive definition (hip: inpatient or emergency diagnosis; radius/ulna: inpatient, emergency, or outpatient diagnosis) served as a referent to compare the number and proportion of fractures captured. In sensitivity analyses, we considered a 180-day washout, excluded fractures associated with trauma; and hip only, excluded: (1) subtrochanteric fractures, and (2) hip replacement procedures. Hip fractures varied by definition in number (52–8058) and incidence (0.7–111.8/10,000 person-years). The second most inclusive definition required one inpatient diagnosis and identified 8% fewer hip fractures than the referent. Excluding hip replacements missed 33% of hip fractures relative to the primary analysis. Radius/ulna fractures also ranged in number (1589–6797) and incidence (22.0–94.3/10,000 person-years). Outpatient data were important, when restricted to inpatient or emergency data, only 78% of radius/ulna fractures were identified. Other than hip replacement procedures, sensitivity analyses had minimal impact on fracture identification. Analyses were replicated in a cohort of patients treated with long-term glucocorticoids. This study highlights the importance and impact of coding decisions on fracture outcome definitions. Further research is warranted to inform best practice in fracture outcome identification.
In-Person or Online? Exploring Student Pharmacists’ Perceived Change in Interprofessional Skills between Two Delivery Formats
Authors: Van Hooser Jared , Olson Anthony W.
Published: March 2023

The COVID-19 pandemic drastically changed how education is delivered. Many academic programs quickly transformed their curriculum to online distance learning. This rapid transition may have compromised the rigor and fidelity of these activities. The Interprofessional Standardized Patient Experience (ISPE) is an interprofessional education activity (IPE) involving a team of students from six different healthcare professions that switched to an online delivery format. This manuscript compares pharmacy students’ perceived change in interprofessional skills between the two formats. Following the ISPE, second-year pharmacy students completed the revised Interprofessional Collaborative Competencies Attainment Survey (ICCAS-R). The ICCAS-R assesses the change in interprofessional collaboration-related competencies in healthcare students before and after IPE training using a retrospective pre–post approach. For each ICCAS-R item and each delivery format (44 in-person and 51 online), paired Student’s t-test on pre- and post-ISPE scores, and Cohen’s d were calculated. Every item of the ICCAS-R was significant (p < 0.001), regardless of delivery format. Nearly all ICCAS-R items had a large effect size, and the remaining items had a medium effect size. The amount of change pre- and post-ISPE for each ICCAS-R item was calculated. Student’s t-test was used to compare the magnitude of change in interprofessional skills between the two delivery formats. Only one difference was noted between the two delivery formats—ICCAS-R item 16, which measured actively listening to interprofessional team members (p = 0.0321). When switching to an online format, the high-fidelity dimension of the ISPE was retained. The ISPE is an effective IPE activity at increasing pharmacy students’ self-perceived interprofessional collaboration skills regardless of delivery format. Even though students reported the ISPE increased their ability to actively listen to the perspectives of interprofessional team members in both formats, the magnitude of the benefit was more profound in the in-person group.
Overwintering Camelina and Canola/Rapeseed Show Promise for Improving Integrated Weed Management Approaches in the Upper Midwestern U.S.
Authors: Chao Wun S. , Anderson James V. , Li Xuehui , Gesch Russ W. , Berti Marisol T. , Horvath David P.
Published: March 2023

Winter oilseed cash cover crops are gaining popularity in integrated weed management programs for suppressing weeds. A study was conducted at two field sites (Fargo, North Dakota, and Morris, Minnesota) to determine the freezing tolerance and weed-suppressing traits of winter canola/rapeseed (Brassica napus L.) and winter camelina [Camelina sativa (L.) Crantz] in the Upper Midwestern USA. The top 10 freezing tolerant accessions from a phenotyped population of winter canola/rapeseed were bulked and planted at both locations along with winter camelina (cv. Joelle) as a check. To phenotype our entire winter B. napus population (621 accessions) for freezing tolerance, seeds were also bulked and planted at both locations. All B. napus and camelina were no-till seeded at Fargo and Morris at two planting dates, late August (PD1) and mid-September (PD2) 2019. Data for winter survival of oilseed crops (plants m−2) and their corresponding weed suppression (plants m−2 and dry matter m−2) were collected on two sampling dates (SD) in May and June 2020. Crop and SD were significant (p < 0.05) for crop plant density at both locations, and PD in Fargo and crop x PD interaction in Morris were significant for weed dry matter. At Morris and Fargo, PD1 produced greater winter B. napus survival (28% and 5%, respectively) and PD2 produced higher camelina survival (79% and 72%, respectively). Based on coefficient of determination (r2), ~50% of weed density was explained by camelina density, whereas ≤20% was explained by B. napus density at both locations. Camelina from PD2 suppressed weed dry matter by >90% of fallow at both locations, whereas weed dry matter in B. napus was not significantly different from fallow at either PD. Genotyping of overwintering canola/rapeseed under field conditions identified nine accessions that survived at both locations, which also had excellent freezing tolerance under controlled conditions. These accessions are good candidates for improving freezing tolerance in commercial canola cultivars.
Weathering of a Polyurethane-Based Gel Electrolyte
Authors: Johannes Christopher , Hartung Michael , Heim Hans-Peter
Published: March 2023

A recently described flexible polyurethane electrolyte was artificially weathered at 25/50 °C and 50% r.h. in air and at 25 °C in a dry nitrogen atmosphere, each with and without UV irradiation. Different formulations and the polymer matrix, used as a reference, were weathered in order to investigate the influence of the amount of conductive lithium salt and the solvent propylene carbonate. The complete loss of the solvent at a standard climate was already observed after a few days, strongly influencing the conductivity and mechanical properties. The essential degradation mechanism appears to be the photo-oxidative degradation of the polyol’s ether bonds, which leads to chain scission, oxidation products and negative changes in the mechanical and optical properties. A higher salt content has no effect on the degradation; however, the presence of propylene carbonate intensifies the degradation.
Synergistic Flame Retardant Effect between Ionic Liquid Functionalized Imogolite Nanotubes and Ammonium Polyphosphate in Epoxy Resin
Authors: Zhu Taohua , Zhou Xuan , Guo Guozheng , Chai Zhihua , Gao Ming
Published: March 2023

Ionic liquid functionalized imogolite nanotubes (INTs-PF6-ILs) were introduced into the epoxy resin (EP)/ammonium polyphosphate (APP) system to investigate the flame retardant performance and thermal properties using the limiting oxygen index (LOI) test, the UL-94 test, and the cone calorimeter test (CCT). The results suggested that a synergistic effect exists between INTs-PF6-ILs and APP on the char formation and anti-dripping behavior of EP composites. For the EP/APP, an UL-94 V-1 rating was obtained for the loading of 4 wt% APP. However, the composites containing 3.7 wt% APP and 0.3 wt% INTs-PF6-ILs could pass the UL-94 V-0 rating without dripping behavior. In addition, compared with the EP/APP composite, the fire performance index (FPI) value and fire spread index (FSI) value of EP/APP/INTs-PF6-ILs composites were remarkably reduced by 11.4% and 21.1%, respectively. Moreover, the char formed by EP/APP composites was intumescent, but of poor quality. In contrast, the char for EP/APP/INTs-PF6-ILs was strong and compact. Therefore, it can resist the erosion due to heat and gas formation and protect the inside of the matrix. This was the main reason for the good flame retardant property of EP/APP/INTs-PF6-ILs composites.
Fabrication of PbO2/PVDF/CC Composite and Employment for the Removal of Methyl Orange
Authors: Song Laizhou , Liu Cuicui , Liang Lifen , Ma Yalong , Wang Xiuli , Ma Jizhong , Li Zeya , Yang Shuqin
Published: March 2023

The in situ electrochemical oxidation process has received considerable attention for the removal of dye molecules and ammonium from textile dyeing and finishing wastewater. Nevertheless, the cost and durability of the catalytic anode have seriously limited industrial applications of this technique. In this work, the lab-based waste polyvinylidene fluoride membrane was employed to fabricate a novel lead dioxide/polyvinylidene fluoride/carbon cloth composite (PbO2/PVDF/CC) via integrated surface coating and electrodeposition processes. The influences of operating parameters (pH, Cl− concentration, current density, and initial concentration of pollutant) on the oxidation efficiency of PbO2/PVDF/CC were evaluated. Under optimal conditions, this composite achieves a 100% decolorization of methyl orange (MO), 99.48% removal of ammonium, and 94.46% conversion for ammonium-based nitrogen to N2, as well as an 82.55% removal of chemical oxygen demand (COD). At the coexistent condition of ammonium and MO, MO decolorization, ammonium, and COD removals still remain around 100%, 99.43%, and 77.33%, respectively. It can be assigned to the synergistic oxidation effect of hydroxyl radical and chloride species for MO and the chlorine oxidation action for ammonium. Based on the determination of various intermediates, MO is finally mineralized to CO2 and H2O, and ammonium is mainly converted to N2. The PbO2/PVDF/CC composite exhibits excellent stability and safety.
Divine Action and Dramatic Christology: A Rereading of Raymund Schwager’s Jesus in the Drama of Salvation
Authors: Sandler Willibald
Published: March 2023

This article shows that and how Raymund Schwager’s five-act dramatic Christology is at the same time a theology of divine action that takes a Christological, personal, dialogical and dramatic approach. Secondly, this article develops a methodological approach of Jesus in the Drama of Salvation, in which Schwager draws on Anselm of Canterbury and thus understands theology as an unfinishable project of “conversion of thought”. This methodology is developed further in the form of a continuous self-application of theological insights to one’s own theology, so that Schwager’s dramatic five-act theology of divine action opens up to ever new readings. In this way, thirdly, Schwager’s dramatic theology of the Gospels is developed in the direction of a biblically based dramatic-kairological phenomenology of divine action. According to this, God acts through and in Jesus by means of events that make the kingdom of God present to people in an exemplary way, thus pulling them out of previous entanglements of catastrophe and placing them in situations of new beginnings. This liberating action of God towards salvation does not overwhelm the free choice of human beings, but places them in Kairoi, i.e., in extraordinary times of salvation, in which they are released to actively accept this offer of salvation in favour of a salvific self-transformation, or to reject God in an aggravated way. On the methodological path described above, this kairological salvific action of God, mediated by Jesus’ proclamation of the kingdom of God and by the work of the Holy Spirit, is grounded in God’s new creative action of the incarnation of Jesus Christ. In this way there emerges an expanded sphere for God’s personal and dramatic kairological salvific action, which embraces the whole of creation.
The Violent Potential of Unconditional Claims in Conflict: Reflections on the Discourse concerning the Destruction of the Buddhas of Bamiyan
Authors: Staudigl Michael
Published: March 2023

On a general level, the article analyzes how the clash of unconditional claims between secular rationales and religious narratives is prone to engender violence. To provide this discussion with material evidence, the case of the destruction of the Buddhas of Bamiyan and its media coverage is put under scrutiny. The author shows how the marker of “religious violence”, otherness, and irrationality was (re)constructed in this context. In the last analysis, the article demonstrates that a parasitic relationship obtains between an occidentalist brand of reason and its presumed other (epitomized in the gestalt of “religious violence”).