bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Canker Processing and Viability Droplet Digital PCR Allow Detection of Erwinia amylovora Viable Nonculturable Cells in Apple Bark
Authors: Dhar Bidhan Chandra , Delgado Santander Ricardo , Aćimović Srđan G.
Published: February 2024

The bacterium Erwinia amylovora causes fire blight and continues to threaten global commercial apple and pear production. Conventional microbiology techniques cannot accurately determine the presence of live pathogen cells in fire blight cankers. Several factors may prevent E. amylovora from growing on solid culture media, including competing microbiota and the release of bacterial-growth-inhibitory compounds by plant material during sample processing. We previously developed a canker processing methodology and a chip-based viability digital PCR (v-dPCR) assay using propidium monoazide (PMA) to bypass these obstacles. However, sample analysis was still time-consuming and physically demanding. In this work, we improved the previous protocol using an automatic tissue homogenizer and transferred the chip-based v-dPCR to the BioRad QX200 droplet dPCR (ddPCR) platform. The improved sample processing method allowed the simultaneous, fast, and effortless processing of up to six samples. Moreover, the transferred v-ddPCR protocol was compatible with the same PMA treatment and showed a similar dynamic range, from 7.2 × 102 to 7.6 × 107 cells mL−1, as the previous v-dPCR. Finally, the improved protocol allowed, for the first time, the detection of E. amylovora viable but nonculturable (VBNC) cells in cankers and bark tissues surrounding cankers. Our v-ddPCR assay will enable new ways to evaluate resistant pome fruit tree germplasm, further dissect the E. amylovora life cycle, and elucidate E. amylovora physiology, epidemiology, and new options for canker management.
Predominantly Orphan Secretome in the Lung Pathogen Mycobacterium abscessus Revealed by a Multipronged Growth-Phase-Driven Strategy
Authors: Chandra Harish , Gupta Manish K. , Lam Ying-Wai , Yadav Jagjit S.
Published: February 2024

The emerging lung pathogen Mycobacterium abscessus is understudied for its virulence determinants and molecular targets for diagnosis and therapeutics. Here, we report a comprehensive secretome (600 proteins) of this species, which was identified using a multipronged strategy based on genetic/genomic, proteomic, and bioinformatic approaches. In-solution digested bottom-up proteomics from various growth phases identified a total of 517 proteins, while 2D-GE proteomics identified 33 proteins. A reporter-gene-fusion-based genomic library that was custom-generated in this study enabled the detection of 23 secretory proteins. A genome-wide survey for N-terminal signal sequences using bioinformatic tools (Psortb 2.0 and SignalP 3.0) combined with a strategy of the subtraction of lipoproteins and proteins containing multiple transmembrane domains yielded 116 secretory proteins. A homology search against the M. tuberculosis database identified nine additional secretory protein homologs that lacked a secretory signal sequence. Considering the little overlap (80 proteins) among the different approaches used, this study emphasized the importance of using a multipronged strategy for a comprehensive understanding of the secretome. Notably, the majority of the secreted proteins identified (over 50%) turned out to be “orphans” (those with no known functional homologs). The revelation of these species-specific orphan proteins offers a hitherto unexplored repertoire of potential targets for diagnostic, therapeutic, and vaccine research in this emerging lung pathogen.
A Response Surface Methodology Study for Chlorella vulgaris Mixotrophic Culture Optimization
Authors: Rincon Sandra Milena , Beyenal Haluk , Romero Hernán Mauricio
Published: February 2024

Glycerol is a carbon source that produces good biomass under mixotrophic conditions. Enhancing the composition of culture media in algae biomass production improves growth rates, biomass yield, nutrient utilization efficiency, and overall cost-effectiveness. Among the key nutrients in the medium, nitrogen plays a pivotal role. Urea can be effectively used as a nitrogen source and is considered a low-cost form of nitrogen compared to other sources. Urea metabolism releases some CO2 in photosynthesis, and magnesium plays a major role in urea uptake. Magnesium is another key nutrient that is key in photosynthesis and other metabolic reactions. To maximize glycerol consumption in the mixotrophic system and to obtain high biomass and lipid productions, the variations in MgSO4·7H2O and urea concentrations were evaluated in the growth medium of the microalgae. A response surface methodology (RSM) using a central composite design (CCD) was designed to maximize glycerol consumption at the initial cellular growth rates (up to four days). The magnesium and urea supply varied from 0.3 to 1.7 g L−1. Response surface methodology was utilized to analyze the results, and the highest glycerol consumption rate, 770.2 mg L−1 d−1, was observed when C. vulgaris was grown at 1.7 g L−1 urea, 1.0 g L−1 MgSO4·7H2O. Using the optimal urea and magnesium concentrations with acetate, glucose, and glycerol as carbon sources, the same lipid content (10% average) was achieved on day 4 of mixotrophic C. vulgaris culture. Overall, the results show that mixotrophic growth of C. vulgaris using urea with an optimum magnesium concentration yields large amounts of fatty acids and that the carbon source greatly influences the profile of the fatty acids.
Preparation of Silicon Carbide Powder from Amorphous Silica and Investigation of Synthesis Mechanism
Authors: Duan Xuqin , Lu Shuaiyu , Jiang Xiaocui , Liu Tong , Yang Huifen
Published: February 2024

An innovative process for preparing silicon carbide (SiC) from acid leaching residue of ferronickel slag through a carbon–thermal reduction process was proposed in this study. The results indicate that the acid leaching residue is an ideal silicon source for SiC preparation according to its high amorphous silica content of 84.20% and fine particle size of d50 = 29.16 μm. Compared with carbon black, activated carbon, and graphite, coke is the more appropriate carbon source for SiC preparation. A micron-size SiC powder with grade of 88.90% and an average particle size (d50) of 44.68 μm can be obtained under the following conditions: the mass ratio of coke to leaching residue as 1.2:1, in an air atmosphere, reducing at 1600 °C for 3 h, following by decarbonizing at 700 °C for 4 h. The XRD, SEM and FTIR analyses show that the prepared powder is 3C-SiC and belongs to the β-SiC crystal type. Based on thermodynamic analysis and micromorphology observation, it can be concluded that with amorphous silica as the silicon source, the carbon–thermal synthesis of SiC powder follows both the solid–solid reaction mechanism and the gas–solid mechanism. The SiC created through solid–solid reaction is primarily nucleated in situ on amorphous SiO2, with a size close to that of the original acid-leaching slag, while the SiC generated according to the gas–solid mechanism mainly nucleates heterogeneously on the surface of carbon particles, resulting in a smaller particle size and mostly adhering to the surface of solid–solid nucleated SiC particles. This study provides a feasible method for the effective utilization of amorphous silica, which is also significant for the efficient consumption of the vast acid leaching residue.
5-Dodecylsalicylaldoxime as a Novel Collector in Cassiterite Flotation: Performance and Mechanism
Authors: Sun Lei , Qiao Yi , Cao Yang , Wang Qingqing , Wang Xin , Sun Wei , Liu Guobin
Published: February 2024

Hydroxamic acid and fatty acid collectors are commonly used in cassiterite flotation but face issues like poor selectivity, high dosage, and strict requirements on ore composition and grinding fineness. This study investigates the collecting performance of a novel flotation reagent, 5-dodecylsalicylaldoxime (DSA), in cassiterite flotation. DSA exhibits remarkable selectivity, achieving an impressive 82.5% recovery of Sn at a concentration of only 9 × 10−5 mol/L in single mineral flotation tests. Moreover, DSA significantly outperforms benzohydroxamic acid (BHA), enhancing Sn recovery by 33.55% in artificially mixed ore flotation experiments. In the flotation test of a copper–tin polymetallic ore, compared with the BHA flotation effect, the recovery rate of DSA increased by 12.29% when the Sn grade remained basically unchanged. Analyses such as zeta potential, FT-IR, and XPS indicate that DSA’s superior collecting performance stems from its stable adsorption onto cassiterite surfaces through a chelating ring formation, resembling the adsorption mechanism of hydroxamic acid collectors. Furthermore, DSA’s larger cluster size in the solution compared to BHA contributes to its enhanced selectivity and collectability. Overall, DSA emerges as a promising alternative to traditional cassiterite flotation collectors, offering a combination of enhanced selectivity, lower dosage requirements, and robustness in complex ore systems.
Interactions between Clays and Carbonates in the Aptian Pre-Salt Reservoirs of Santos Basin, Eastern Brazilian Margin
Authors: Schrank Argos Belmonte Silveira , Dos Santos Thisiane , Altenhofen Sabrina Danni , Freitas William , Cembrani Elias , Haubert Thiago , Dalla Vecchia Felipe , Barili Rosalia , Rodrigues Amanda Goulart , Maraschin Anderson , De Ros Luiz Fernando
Published: February 2024

The giant Pre-salt reservoirs represent most of the oil production in Brazil. The main Aptian sag reservoirs were deposited in a unique and highly complex hyper-alkaline lacustrine setting. These deposits are essentially constituted by fascicular and spherulitic calcite precipitated in a magnesian clay matrix (stevensite, kerolite, and saponite/hectorite). Although vital for understanding the origin and main reservoir quality control, the genesis and interactions of clays and carbonates are still poorly constrained. The detailed petrographic description was focused on 812 thin sections from five wells drilled in the Santos Basin Aptian Barra Velha Formation, combined with cathodoluminescence, UV epifluorescence, and X-ray diffraction analyses. The main syngenetic processes were the deposition of finely laminated peloidal and ooidal Mg-clays, the formation of fascicular calcite crusts on the sediment–water interface, and the redeposition of these materials as intraclasts. Abundant clay peloids engulfed in syngenetic shrubs indicate that calcite and clay precipitation was concomitant, though with highly variable rates. Eodiagenetic phases include matrix-replacive and -displacive spherulites and fascicular shrubs; matrix-replacive blocky calcite and dolomite; lamellar carbonates filling matrix shrinkage pores; and microcrystalline calcite, dolomite, and silica replacing the Mg-clay matrix. The preferential dolomitization and calcitization of peloidal layers were most likely due to their higher permeability and larger specific surface. Matrix-replacive saddle dolomite, macrocrystalline calcite, and dawsonite are interpreted as mesodiagenetic or hydrothermal phases after significant matrix dissolution. Unraveling the processes of the formation and alteration of the carbonates and clays and their interactions in the Pre-salt deposits is essential for constraining the depositional and diagenetic conditions in their unique environments and their diagenetic overprinting and for decreasing the exploration risks and increasing the production of those extraordinary reservoirs.
The Effect of Substrate Properties on Cellular Behavior and Nanoparticle Uptake in Human Fibroblasts and Epithelial Cells
Authors: Sousa de Almeida Mauro , Lee Aaron , Itel Fabian , Maniura-Weber Katharina , Petri-Fink Alke , Rothen-Rutishauser Barbara
Published: February 2024

The delivery of nanomedicines into cells holds enormous therapeutic potential; however little is known regarding how the extracellular matrix (ECM) can influence cell–nanoparticle (NP) interactions. Changes in ECM organization and composition occur in several pathophysiological states, including fibrosis and tumorigenesis, and may contribute to disease progression. We show that the physical characteristics of cellular substrates, that more closely resemble the ECM in vivo, can influence cell behavior and the subsequent uptake of NPs. Electrospinning was used to create two different substrates made of soft polyurethane (PU) with aligned and non-aligned nanofibers to recapitulate the ECM in two different states. To investigate the impact of cell–substrate interaction, A549 lung epithelial cells and MRC-5 lung fibroblasts were cultured on soft PU membranes with different alignments and compared against stiff tissue culture plastic (TCP)/glass. Both cell types could attach and grow on both PU membranes with no signs of cytotoxicity but with increased cytokine release compared with cells on the TCP. The uptake of silica NPs increased more than three-fold in fibroblasts but not in epithelial cells cultured on both membranes. This study demonstrates that cell–matrix interaction is substrate and cell-type dependent and highlights the importance of considering the ECM and tissue mechanical properties when designing NPs for effective cell targeting and treatment.
Fully Printed Cellulose Nanofiber–Ag Nanoparticle Composite for High-Performance Humidity Sensor
Authors: Won Mijin , Jung Minhun , Kim Jaehwan , Kim Dong-Soo
Published: February 2024

This paper reports a high-performance humidity sensor made using a novel cellulose nanofiber (CNF)–silver nanoparticle (AgNP) sensing material. The interdigital electrode pattern was printed via reverse-offset printing using Ag nano-ink, and the sensing layer on the printed interdigitated electrode (IDE) was formed by depositing the CNF-AgNP composite via inkjet printing. The structure and morphology of the CNF-AgNP layer are characterized using ultraviolet–visible spectroscopy, an X-ray diffractometer, field emission scanning electron microscopy, energy-dispersive X-ray analysis, and transmission electron microscopy. The humidity-sensing performance of the prepared sensors is evaluated by measuring the impedance changes under the relative humidity variation between 10 and 90% relative humidity. The CNF-AgNP sensor exhibited very sensitive and fast humidity-sensing responses compared to the CNF sensor. The electrode distance effect and the response and recovery times are investigated. The enhanced humidity-sensing performance is reflected in the increased conductivity of the Ag nanoparticles and the adsorption of free water molecules associated with the porous characteristics of the CNF layer. The CNF-AgNP composite enables the development of highly sensitive, fast-responding, reproducible, flexible, and inexpensive humidity sensors.
Sustainable Synthesis of Zeolitic Imidazolate Frameworks at Room Temperature in Water with Exact Zn/Linker Stoichiometry
Authors: Molina María Asunción , Rodríguez-Campa Jorge , Flores-Borrell Rosa , Blanco Rosa M. , Sánchez-Sánchez Manuel
Published: February 2024

Zeolitic imidazolate frameworks (ZIFs) are widely used MOFs because of certain characteristics, but also because they can be prepared at room temperature using water as the unique solvent. However, these a priori sustainable conditions inevitably entail a huge and somehow unusable excess of linker. Here, we present the formation of ZIFs at room temperature in water, starting from mixtures with a linker/metal ratio of two, that is, coinciding with the stoichiometry found in the final MOFs, in the presence of amines. ZIF-8 can be prepared with triethylamine (TEA), giving a yield of Zn of 96.6%. Other bases, like NaOH, tetraethylammonium hydroxide or ammonium hydroxide, do not lead to ZIF-8 under the same conditions. The so-obtained ZIF-8 contains TEA inside its cavities, making it less porous than its conventionally prepared counterparts. Amine can be removed by mild thermal treatments (200–250 °C). Such thermal treatments induce the generation of g-C3N4-like species which could give added value to these materials as potential photocatalysts, increasing their affinity to CO2, as proved in this work. This methodology can be successfully extended to other amines, like N,N-dicyclohexylmethylamine, as well as to other prepared ZIFs, like Co-based ZIF-67, isostructural to ZIF-8.
Improvement of Near-Infrared Light-Emitting Diodes’ Optical Efficiency Using a Broadband Distributed Bragg Reflector with an AlAs Buffer
Authors: Lee Hyung-Joo , Park Jin-Young , Kwac Lee-Ku , Lee Jongsu
Published: February 2024

This study developed an advanced 850 nm centered distributed Bragg reflector (DBR) (broadband DBR) composed of nanomaterial-based multiple structures to improve the optical efficiency of an 850 nm near-infrared light-emitting diode (NIR-LED). A combined 850 nm centered broadband DBR was fabricated by growing an 800 nm centered ten-pair DBR on a 900 nm centered ten-pair DBR (denoted as a combined DBR). The combined DBR exhibited a slightly wider peak band than conventional DBRs. Furthermore, the peak band width of the combined DBR significantly increased upon using a reflective AlAs buffer layer that reduced the overlapped reflection. The output power (20.5 mW) of NIR-LED chips using the combined DBR with an AlAs buffer layer exceeded that of a conventional 850 nm centered DBR (14.5 mW) by more than 40%. Results indicated that combining the optical conditions of wavelengths and the AlAs buffer layer effectively strengthened the broadband effect of the DBR and increased the optical efficiency of the 850 nm NIR-LED.
Application of Surface Stress-Driven Model for Higher Vibration Modes of Functionally Graded Nanobeams
Authors: Lovisi Giuseppe , Feo Luciano , Lambiase Annavirginia , Penna Rosa
Published: February 2024

This paper employs a surface stress-driven nonlocal theory to investigate the synergistic impact of long-range interaction and surface energy on higher vibration modes of Bernoulli–Euler nanobeams made of functionally graded material. It takes into account surface effects such as the surface modulus of elasticity, residual surface stresses, surface density, and rotary inertia. The governing equation is derived through the application of Hamilton’s principle. The novelty of this work lies in its pioneering approach to studying higher-order vibrations, carefully considering the combination of long-range interactions and surface energy in nanobeams of functionally graded materials through a well-posed mathematical model of nonlocal elasticity. This study conducts a parametric investigation, examining the effects of the nonlocal parameter and the material gradient index for four static schemes: Cantilever, Simply-Supported, Clamped-Pinned and Clamped-Clamped nanobeams. The outcomes are presented and discussed, highlighting the normalized nonlocal natural frequencies for the second through fifth modes of vibration in each case under study. In particular, this study illustrates the central role of surface effects in the dynamic response of nanobeams, emphasizing the importance of considering them. Furthermore, the parametric analysis reveals that the dynamic response is influenced by the combined effects of the nonlocal parameter, the material gradient index, the shapes of the cross-sections considered, as well as the static scheme analyzed.
Design of a Remote Time-Restricted Eating and Mindfulness Intervention to Reduce Risk Factors Associated with Early-Onset Colorectal Cancer Development among Young Adults
Authors: Lima Oliveira Manoela , Biggers Alana , Oddo Vanessa M. , Naylor Keith B. , Chen Zhengjia , Hamm Alyshia , Pezley Lacey , Peñalver Bernabé Beatriz , Gabel Kelsey , Sharp Lisa K. , Tussing-Humphreys Lisa Marie
Published: February 2024

Early-onset colorectal cancer (EOCRC) is defined as a diagnosis of colorectal cancer (CRC) in individuals younger than 50 years of age. While overall CRC rates in the United States (US) decreased between 2001 and 2018, EOCRC rates have increased. This research project aims to evaluate the feasibility and acceptability of Time-Restricted Eating (TRE), Mindfulness, or TRE combined with Mindfulness among young to middle-aged adults at risk of EOCRC. Forty-eight participants will be randomly assigned to one of four groups: TRE, Mindfulness, TRE and Mindfulness, or Control. Data on feasibility, adherence, and acceptability will be collected. Measures assessed at baseline and post-intervention will include body weight, body composition, dietary intake, physical activity, sleep behavior, circulating biomarkers, hair cortisol, and the gut microbiome. The effects of the intervention on the following will be examined: (1) acceptability and feasibility; (2) body weight, body composition, and adherence to TRE; (3) circulating metabolic, inflammation, and oxidative stress biomarkers; (4) intestinal inflammation; and (5) the gut microbiome. TRE, combined with Mindfulness, holds promise for stress reduction and weight management among individuals at risk of EOCRC. The results of this pilot study will inform the design and development of larger trials aimed at preventing risk factors associated with EOCRC.
Impacts of Habit Formation Effect on Food Consumption and Nutrient Intake in Rural China
Authors: Wen Jinshang , Zhu Wenbo , Han Xinru , Wang Xiudong
Published: February 2024

This study employs panel data and a dynamic Almost Ideal Demand System (AIDS) model to investigate the habit formation effect of food consumption among Chinese rural residents and its consequential impact on nutritional intake. The dataset, spanning from 2012 to 2018, encompasses nine provinces in China and involves 5390 rural households. The findings reveal that, excluding beef, mutton, and poultry, there are significant habit formation effect on the consumption of food categories, notably grains, vegetables, and edible oils. Lower-income and younger demographics demonstrate a more pronounced reliance on established dietary habits. Influenced by the habit formation effect, there is a substantial reduction in the income elasticity differences across various food types. Overlooking the habit formation effect in food consumption would lead to an underestimation of the income elasticity of energy, fat, and carbohydrates. This suggests that, over the long term, food consumption habit formation is a pivotal factor in enabling the enhancement of residents’ dietary structures, amplifying the incremental energy intake associated with income increases, and accelerating the transition towards nutritional surplus. The conclusions drawn from this study offer valuable insights for ensuring food security and nutritional balance. Policy-makers of food and nutrition strategies should duly consider the habit formation effect on residents’ food consumption, and seek to optimize dietary patterns and promote nutritional transformation by food consumption habit intervention.
Improved Cardiovascular Effects of a Novel Pomegranate Byproduct Extract Obtained through Hydrodynamic Cavitation
Authors: Benedetti Giada , Flori Lorenzo , Spezzini Jacopo , Miragliotta Vincenzo , Lazzarini Giulia , Pirone Andrea , Meneguzzo Cosimo , Tagliavento Luca , Martelli Alma , Antonelli Michele , Donelli Davide , Faraloni Cecilia , Calderone Vincenzo , Meneguzzo Francesco , Testai Lara
Published: February 2024

The healthy properties of pomegranate fruit, a highly consumed food, have been known for a long time. However, the pomegranate supply chain is still rather inefficient, with the non-edible fraction, whose weight is roughly half the total and is endowed with plenty of valuable bioactive compounds, either disposed of or underutilized. A novel extract obtained from non-edible byproducts (called PPE), using hydrodynamic cavitation, a green, efficient, and scalable technique, was investigated for its cardiovascular effects in vivo. PPE showed efficacy in an acute phenylephrine (PE)-induced hypertensive rat model, similar to the extract of whole fruit (PFE) obtained using the same extractive technique, along with good intestinal bioaccessibility after oral administration. Finally, when chronically administered for 6 weeks to spontaneously hypertensive rats, PPE was shown to significantly contain the increase in systolic blood pressure, comparable to the reference drug Captopril, and at a dose remarkably lower than the reported effective dose of ellagic acid. The extract from the non-edible fraction of the pomegranate fruit also showed good anti-inflammation and anti-fibrotic effects. The findings of this study, along with the extraction technique, could contribute to enhancing the value of the pomegranate supply chain, relieve the related environmental burden, and potentially improve public health.
Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice
Authors: Nessim Kostandy Erini , Suh Ji Ho , Tian Xiangjun , Okeugo Beanna , Rubin Erin , Shirai Sara , Luo Meng , Taylor Christopher M. , Kim Kang Ho , Rhoads J. Marc , Liu Yuying
Published: February 2024

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids associated with autoimmune disease in SF mice, many of which were downregulated by DSM 17938. The upregulated lipids in SF mice demonstrated a significant correlation with gut bacteria known to be implicated in the pathogenesis of various autoimmune diseases. Chronic hepatitis in SF livers responded to DSM 17938 treatment with a reduction in hepatic inflammation. Altered gene expression associated with lipid metabolism and the positive correlation between lipids and inflammatory cytokines together suggest that autoimmunity leads to dyslipidemia with impaired fatty acid oxidation in SF mice. Probiotics are presumed to contribute to the reduction of lipids by reducing inflammatory pathways.
Pharmacokinetic Analysis of Levodropropizine and Its Potential Therapeutic Advantages Considering Eosinophil Levels and Clinical Indications
Authors: Jang Ji-Hun , Cho Young-Jin , Jeong Seung-Hyun
Published: February 2024

Levodropropizine is a non-narcotic, non-centrally acting antitussive that inhibits the cough reflex triggered by neuropeptides. Despite the active clinical application of levodropropizine, the exploration of its inter-individual pharmacokinetic diversity and of factors that can interpret it is lacking. The purpose of this study was to explore effective covariates associated with variation in the pharmacokinetics of levodropropizine within the population and to perform an interpretation of covariate correlations from a therapeutic perspective. The results of a levodropropizine clinical trial conducted on 40 healthy Korean men were used in this pharmacokinetic analysis, and the calculated pharmacokinetic and physiochemical parameters were screened for effective correlations between factors through heatmap and linear regression analysis. Along with basic compartmental modeling, a correlation analysis was performed between the model-estimated parameter values and the discovered effective candidate covariates for levodropropizine, and the degree of toxicity and safety during the clinical trial of levodropropizine was quantitatively monitored, targeting the hepatotoxicity screening panel. As a result, eosinophil level and body surface area (BSA) were explored as significant (p-value < 0.05) physiochemical parameters associated with the pharmacokinetic diversity of levodropropizine. Specifically, it was confirmed that as eosinophil level and BSA increased, levodropropizine plasma exposure increased and decreased, respectively. Interestingly, changes in an individual’s plasma exposure to levodropropizine depending on eosinophil levels could be interpreted as a therapeutic advantage based on pharmacokinetic benefits linked to the clinical indications for levodropropizine. This study presents effective candidate covariates that can explain the inter-individual pharmacokinetic variability of levodropropizine and provides a useful perspective on the first-line choice of levodropropizine in the treatment of inflammatory respiratory diseases.
An Overview of Biosimilars—Development, Quality, Regulatory Issues, and Management in Healthcare
Authors: Mascarenhas-Melo Filipa , Diaz Mariana , Gonçalves Maria Beatriz S. , Vieira Pedro , Bell Victoria , Viana Sofia , Nunes Sara , Paiva-Santos Ana Cláudia , Veiga Francisco
Published: February 2024

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products. Biosimilars, although similar to reference products, are not identical copies and should not be considered generic substitutes for the original. Their development and evaluation involve a rigorous step-by-step process that includes analytical, functional, and nonclinical evaluations and clinical trials. Clinical studies conducted for biosimilars aim to establish similar efficacy, safety, and immunogenicity, rather than demonstrating a clinical benefit, as with the reference product. However, although the current knowledge regarding biosimilars has significantly increased, several controversies and misconceptions still exist regarding their immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The development of biosimilars stimulates market competition, contributes toward healthcare sustainability, and allows for greater patient access. However, maximizing the benefits of biosimilars requires cooperation between regulators and developers to ensure that patients can benefit quickly from access to these new therapeutic alternatives while maintaining high standards of quality, safety, and efficacy. Recognizing the inherent complexities of comprehending biosimilars fully, it is essential to focus on realistic approaches, such as fostering open communication between healthcare providers and patients, encouraging informed decision-making, and minimizing risks. This review addresses the regulatory and manufacturing requirements for biosimilars and provides clinicians with relevant insights for informed prescribing.
Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?
Authors: Laudani Samuele , Godos Justyna , Romano Giovanni , Gozzo Lucia , Di Domenico Federica , Dominguez Azpíroz Irma , Martínez Diaz Raquel , Giampieri Francesca , Quiles José , Battino Maurizio , Drago Filippo , Galvano Fabio , Grosso Giuseppe
Published: February 2024

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol—a microbiota-derived metabolite—seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.
Integrated UPLC/Q-TOF-MS/MS Analysis and Network Pharmacology to Reveal the Neuroprotective Mechanisms and Potential Pharmacological Ingredients of Aurantii Fructus Immaturus and Aurantii Fructus
Authors: Qiu Mingyang , Zhang Jianqing , Wei Wenlong , Zhang Yan , Li Mengmeng , Bai Yuxin , Wang Hanze , Meng Qian , Guo De-an
Published: February 2024

Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) have been used for thousands of years as traditional Chinese medicine (TCM) with sedative effects. Modern studies have shown that Citrus plants also have protective effects on the nervous system. However, the effective substances and mechanisms of action in Citrus TCMs still remain unclear. In order to explore the pharmacodynamic profiles of identified substances and the action mechanism of these herbs, a comprehensive approach combining ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) analysis and network pharmacology was employed. Firstly, UNIFI 2.1.1 software was used to identify the chemical characteristics of AF and AFI. Secondly, the SwissTargetPrediction database was used to predict the targets of chemical components in AF and AFI. Targets for neuroprotection were also collected from GeneCards: The Human Gene Database (GeneCards-Human Genes|Gene Database|Gene Search). The networks between targets and compounds or diseases were then constructed using Cytoscape 3.9.1. Finally, the Annotation, Visualization and Integrated Discovery Database (DAVID) (DAVID Functional Annotation Bioinformatics Microarray Analysis) was used for GO and pathway enrichment analysis. The results showed that 50 of 188 compounds in AF and AFI may have neuroprotective biological activities. These activities are associated with the regulatory effects of related components on 146 important signaling pathways, derived from the KEGG (KEGG: Kyoto Encyclopedia of Genes and Genomes), such as neurodegeneration (hsa05022), the Alzheimer’s disease pathway (hsa05010), the NF-kappa B signaling pathway (hsa04064), the hypoxia-inducible factor (HIF)-1 signaling pathway (hsa04066), apoptosis (hsa04210), the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance signaling pathway (hsa01521), and others, by targeting 108 proteins, including xanthine dehydrogenase (XDH), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), and glucose-6-phosphate dehydrogenase (G6PD), among others. These targets are thought to be related to inflammation, neural function and cell growth.
Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery
Authors: Lucaciu Constantin Mihai
Published: February 2024

In recent years, nanomedicine has experienced remarkable advancements, due to the development of new nanomaterials with outstanding properties that have demonstrated significant advantages over traditional medicines [...]
Y-Site Compatibility Studies of Parenteral Nutrition and Other Intravenous Medications in Neonatal and Pediatric Patients: A Review of the Literature Evidence
Authors: Gostyńska Aleksandra , Przybylski Tomasz , Ogrodowczyk Magdalena
Published: February 2024

Background: Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. Aim: This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. Methods: A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. Results: A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an “A” grade (very high quality), and the grades “B”, “C”, and “D” were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. Conclusions: This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients.
Planar Bilayer PT-Symmetric Systems and Resonance Energy Transfer
Authors: Arlouski Aliaksandr , Novitsky Andrey
Published: February 2024

Parity-time (PT) symmetry provides an outstanding improvement of photonic devices’ performance due to the remarkable physics behind it. Resonance energy transfer (RET) as an important characteristic mediating the molecules that can be tailored in the PT-symmetric environment, too. We study how planar bilayer PT-symmetric systems affect the process of resonance energy transfer occurring in the vicinity thereof. First, we investigate the reflectance and transmittance spectra of such systems by calculating reflection and transmission coefficients as well as total radiation amplification as functions of medium parameters. We obtain that reflectance and total amplification are greatest near the exceptional points of the PT-symmetric system. Then, we perform numerical calculations of the RET rate and investigate its dependence on the complex permittivity of the PT-symmetric medium, dipole orientation, frequency of radiation and layer thickness. Optically thick PT-symmetric systems may operate at lower gain at the expense of the appearance of chaotic-like behaviors. These appear owing to the dense oscillations in the reflectance and transmittance spectra and vividly manifest themselves as stochastic-like positions of the exceptional points for PT-symmetric bilayers. The RET rate, being a result of the field interference, can be significantly amplified and suppressed near exceptional points exhibiting a Fano-like lineshape.
Stray Light Analysis and Suppression for an Infrared Fourier Imaging Spectrometer
Authors: Ben Chenzhao , Shen Honghai , Yu Xiao , Meng Lingtong , Cheng Huishi , Jia Ping
Published: February 2024

To improve the accuracy of infrared radiation characteristics measurement in the aviation field, an infrared Fourier transform imaging spectrometer based on a double-swing solid angle reflector was designed. This imaging spectrometer operates in the 3–5 μm wavelength range and has a field of view of 1.7° × 1.7°. This article presents a comprehensive analysis of the system’s stray light and also studies the impact of external stray light on the imaging quality, along with the influence of internal stray light on the interference effects and the spectral resolution. It also present the design of a hood that suppresses the point source transmittance of the external stray light down to the order of 10−4. Based on this, we propose a method that incorporates the introduction of wedge and inclination angles. Additionally, a numerical range is provided for the addition of these angles on the beam splitter mirror and compensation plate. This ensures the effective suppression of any internal stray light. This study fills the gap in the knowledge about Fourier transform imaging spectrometers operating in the mid-infrared band for aviation applications, and proposes a suppression method suitable for interference systems, which is also suitable for Fourier transform imaging spectrometers based on other types of interferometers. This study broadens the application field of Fourier transform imaging spectrometers in stray light, and has great significance to promote the development of Fourier transform imaging spectrometer.
Single-Pixel Infrared Hyperspectral Imaging via Physics-Guided Generative Adversarial Networks
Authors: Wang Dong-Yin , Bie Shu-Hang , Chen Xi-Hao , Yu Wen-Kai
Published: February 2024

A physics-driven generative adversarial network (GAN) was utilized to demonstrate a single-pixel hyperspectral imaging (HSI) experiment in the infrared spectrum, eliminating the need for extensive dataset training in most data-driven deep neural networks. Within the GAN framework, the physical process of single-pixel imaging (SPI) was integrated into the generator, and its estimated one-dimensional (1D) bucket signals and the actual 1D bucket signals were employed as constraints in the objective function to update the network’s parameters and optimize the generator with the assistance of the discriminator. In comparison to single-pixel infrared HSI methods based on compressive sensing and physics-driven convolution neural networks, our physics-driven GAN-based single-pixel infrared HSI exhibits superior imaging performance. It requires fewer samples and achieves higher image quality. We believe that our physics-driven network will drive practical applications in computational imaging, including various SPI-based techniques.
Correlation between Antimicrobial Activity Values and Total Phenolic Content/Antioxidant Activity in Rubus idaeus L.
Authors: Ispiryan Audrone , Atkociuniene Vilma , Makstutiene Natalija , Sarkinas Antanas , Salaseviciene Alvija , Urbonaviciene Dalia , Viskelis Jonas , Pakeltiene Rasa , Raudone Lina
Published: February 2024

Plant by-products, which are discarded into the environment, are rich in valuable compounds. The aim of this research was to determine the antibacterial activity of Rubus idaeus L. morphological parts and its correlation with total phenolic content and antioxidant activity. The authors also aimed to evaluate the plant’s potential as added-value products. New aspects were revealed for further use and for making novel and natural products. The study’s results indicated that raspberry leaves, inflorescences, and fruits could effectively combat three Gram-positive bacteria. According to the findings, among the various plant parts, root and seed extracts had the lowest antibacterial activity. Data revealed moderate, weak, or very weak correlation between the antimicrobial activity and phenolic content parameters. These findings underscore the viability of substituting synthetic antimicrobials with natural alternatives. The present study is significant for preparing novel products as antibacterials by appropriate and optimized processing using all raspberry morphological parts, and the research results show promising prospects for future purposeful utilisation of nature-based products. Raspberry plant parts can find applications in emerging fields that generate economic and environmental value.
Two Growing-Season Warming Partly Promoted Growth but Decreased Reproduction and Ornamental Value of Impatiens oxyanthera
Authors: Tao Jiayu , Yang Youqin , Wang Qiong
Published: February 2024

Climate warming profoundly affects the vegetative growth, flowering phenology and sexual reproduction of plants; therefore, it affects the ornamental value of wild flowers. Despite this, the extent and mechanism of the impact remain unclear. Here, we conducted a warming experiment for two growing seasons (increases of 1.89 °C in 2017 and 2.37 °C in 2018) with infrared heaters to examine the effects of warming on the ornamental value of the wild flower Impatiens oxyanthera, endemic to China, in Mount Emei. We evaluated the comprehensive ornamental value based on plant morphology and flowering characteristics using the analytic hierarchy process (AHP) and disentangled the impact of the two traits on ornamental value using principal component analysis (PCA) and the partial least squares structural equation model (PLS-SEM) under ambient and warming treatments. We hypothesized that warming would reduce the ornamental value of I. oxyanthera in terms of plant morphology and flowering traits. Our results showed that warming significantly decreased plant height and crown width and increased branch number and single-leaf area. Warming also decreased vexillum length, corolla tube length, nectar spur length and pedicel length. In addition, warming shortened flowering duration per plant and reduced flower number, while there was no significant effect on flower longevity and flower color at full-bloom stage between the control and warming treatment. Therefore, the comprehensive ornamental value under warming was lower than that under the control. Pedicel length, flower color, flower longevity and flowering duration per plant were the main factors affecting the comprehensive ornamental value. The PLS-SEM showed that warming had an indirect negative effect on ornamental value via direct negative effects on flowering traits. Collectively, these results indicate that, although promoting vegetative growth, short-term warming significantly decreased the ornamental value of I. oxyanthera due to warming-caused smaller flowers and shorter flowering duration.
Atomic Force Microscopy and Molecular Dynamic Simulation of Adsorption of Polyacrylamide with Different Chemistries onto Calcium Carbonate
Authors: Lew Jin Hau , Hue Keat Yung , Matar Omar K. , Müller Erich A. , Luckham Paul F. , Santos Adrielle Sousa , Myo Thant Maung Maung
Published: February 2024

This study investigates the interaction of polyacrylamide (PAM) of different functional groups (sulfonate vs. carboxylate) and charge density (30% hydrolysed vs. 10% hydrolysed) with calcium carbonate (CaCO3) via atomic force microscopy (AFM) and partly via molecular dynamic (MD) simulations. The PAM used were F3330 (30% hydrolysed), AN125 (25% sulfonated), and AN910 (% hydrolysed). A total of 100 ppm of PAMs was prepared in 0.1% NaCl, 3% NaCl, and 4.36% NaNO3 to be employed in AFM experiments, while oligomeric models (30 repeating units) of hydrolysed polyacrylamide (HPAM), sulfonated polyacrylamide (SPAM), and neutral PAM (NPAM) were studied on a model calcite surface on MD simulations. AFM analysis indicated that F3330 has a higher average adhesion and interaction energy with CaCO3 than AN125 due to the bulky sulfonate side group of AN125 interfering with SPAM adsorption. Steric repulsion of both PAMs was similar due to their comparable molecular weights and densities of the charged group. In contrast, AN910 showed lower average adhesion and interaction energy, along with slightly longer steric repulsion with calcite than F3330, suggesting AN910 adopts more loops and tails than the slightly flatter F3330 configuration. An increase in salt concentration from 0.1% to 3% NaCl saw a reduction in adhesion and interaction energy for F3330 and AN125 due to charge screening, while AN910 saw an increase, and these values increased further at 4.36% NaNO3. MD simulations revealed that the salt ions in the system formed salt bridges between PAM and calcite, indicating that the adhesion and interaction energy observed from AFM are likely to be the net balance between PAM charged group screening and salt bridging by the salt ions present. Salt ions with larger bare radii and smaller hydrated radii were shown to form stronger salt bridges.