bluuebunny/crossref_metadata_2025 huggingface dataset:
Portable Device for Multipurpose Research on Dendritic Yanson Point Contacts and Quantum Sensing
Authors: Savytskyi Andriy , Pospelov Alexander , Herus Anna , Vakula Volodymyr , Kalashnyk Nataliya , Faulques Eric , Kamarchuk Gennadii
Published: March 2023

Quantum structures are ideal objects by which to discover and study new sensor mechanisms and implement advanced approaches in sensor analysis to develop innovative sensor devices. Among them, one of the most interesting representatives is the Yanson point contact. It allows the implementation of a simple technological chain to activate the quantum mechanisms of selective detection in gaseous and liquid media. In this work, a portable device for multipurpose research on dendritic Yanson point contacts and quantum sensing was developed and manufactured. The device allows one to create dendritic Yanson point contacts and study their quantum properties, which are clearly manifested in the process of the electrochemical cyclic switchover effect. The device tests demonstrated that it was possible to gather data on the compositions and characteristics of the synthesized substances, and on the electrochemical processes that influence the production of dendritic Yanson point contacts, as well as on the electrophysical processes that provide information on the quantum nature of the electrical conductance of dendritic Yanson point contacts. The small size of the device makes it simple to integrate into a micro-Raman spectrometer setup. The developed device may be used as a prototype for designing a quantum sensor that will serve as the foundation for cutting-edge sensor technologies, as well as be applied to research into atomic-scale junctions, single-atom transistors, and any relative subjects.
Nanotextured CeO2−SnO2 Composite: Efficient Photocatalytic, Antibacterial, and Energy Storage Fibers
Authors: Algethami Jari , Hassan M. , Amna Touseef , Sheikh Faheem , Alhamami Mohsen , Seliem Amal , Faisal M. , Kim H.
Published: March 2023

Bacterial infections remain a serious and pervasive threat to human health. Bacterial antibiotic resistance, in particular, lowers treatment efficacy and increases mortality. The development of nanomaterials has made it possible to address issues in the biomedical, energy storage, and environmental fields. This paper reports the successful synthesis of CeO2−SnO2 composite nanofibers via an electrospinning method using polyacrylonitrile polymer. Scanning and transmission electron microscopy assessments showed that the average diameter of CeO2−SnO2 nanofibers was 170 nm. The result of photocatalytic degradation for methylene blue dye displayed enhanced efficiency of the CeO2−SnO2 composite. The addition of SnO2 to CeO2 resulted in the enhancement of the light absorption property and enriched charge transmission of photoinduced electron–hole duos, which conspicuously contributed to momentous photoactivity augmentation. Composite nanofibers exhibited higher specific capacitance which may be accredited to the synergism between CeO2 and SnO2 particles in nanofibers. Furthermore, antibacterial activity was screened against Escherichia coli and CeO2−SnO2 composite nanofibers depicted excellent activity. The findings of this work point to new possibilities as an electrode material in energy storage systems and as a visible-light-active photocatalyst for the purification of chemical and biological contaminants, which would substantially benefit environmental remediation processes.
Dual-Functional Solar-to-Steam Generation and SERS Detection Substrate Based on Plasmonic Nanostructure
Authors: Trinh Ba Thong , Cho Hanjun , Lee Deunchan , Omelianovych Oleksii , Kim Taehun , Nguyen Sy Khiem , Choi Ho-Suk , Kim Hongki , Yoon Ilsun
Published: March 2023

Solar-to-steam (STS) generation based on plasmonic materials has attracted significant attention as a green method for producing fresh water. Herein, a simple in situ method is introduced to fabricate Au nanoparticles (AuNPs) on cellulose filter papers as dual-functional substrates for STS generation and surface-enhanced Raman spectroscopy (SERS) sensing. The substrates exhibit 90% of broadband solar absorption between 350 and 1800 nm and achieve an evaporation rate of 0.96 kg·m−2·h−1 under 1-sun illumination, room temperature of 20 °C, and relative humidity of 40%. The STS generation of the substrate is stable during 30 h continuous operation. Enriched SERS hotspots between AuNPs endow the substrates with the ability to detect chemical contamination in water with ppb limits of detection for rhodamine 6G dye and melamine. To demonstrate dual-functional properties, the contaminated water was analyzed with SERS and purified by STS. The purified water was then analyzed with SERS to confirm its purity. The developed substrate can be an improved and suitable candidate for fresh water production and qualification.
Hesperetin Ameliorates Inhibition of Neuronal and Oligodendroglial Cell Differentiation Phenotypes Induced by Knockdown of Rab2b, an Autism Spectrum Disorder-Associated Gene Product
Authors: Kato Yukino , Shirai Remina , Ohbuchi Katsuya , Oizumi Hiroaki , Yamamoto Masahiro , Miyata Wakana , Iguchi Tomoki , Mimaki Yoshihiro , Miyamoto Yuki , Yamauchi Junji
Published: March 2023

Autism spectrum disorder (ASD) is a central nervous system (CNS) neurodevelopmental disorder that includes autism, pervasive developmental disorder, and Asperger’s syndrome. ASD is characterized by repetitive behaviors and social communication deficits. ASD is thought to be a multifactorial disorder with a range of genetic and environmental factors/candidates. Among such factors is the rab2b gene, although it remains unclear how Rab2b itself is related to the CNS neuronal and glial developmental disorganization observed in ASD patients. Rab2 subfamily members regulate intracellular vesicle transport between the endoplasmic reticulum and the Golgi body. To the best of our knowledge, we are the first to report that Rab2b positively regulates neuronal and glial cell morphological differentiation. Knockdown of Rab2b inhibited morphological changes in N1E-115 cells, which are often used as the neuronal cell differentiation model. These changes were accomplished with decreased expression levels of marker proteins in neuronal cells. Similar results were obtained for FBD-102b cells, which are used as the model of oligodendroglial cell morphological differentiation. In contrast, knockdown of Rab2a, which is another Rab2 family member not known to be associated with ASD, affected only oligodendroglial and not neuronal morphological changes. In contrast, treatment with hesperetin, a citrus flavonoid with various cellular protective effects, in cells recovered the defective morphological changes induced by Rab2b knockdown. These results suggest that knockdown of Rab2b inhibits differentiation in neuronal and glial cells and may be associated with pathological cellular phenotypes in ASD and that hesperetin can recover their phenotypes at the in vitro level at least.
Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease
Authors: Rodriguez Daphne M. , Hintze Korry J. , Rompato Giovanni , Stewart Eliza C. , Barton Abbey H. , Mortensen-Curtis Emily , Green Porter A. , Van Wettere Arnaud J. , Thomas Aaron J. , Benninghoff Abby D.
Published: March 2023

Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.
Effects of Wild Blueberries on Fat Oxidation Rates in Aerobically Trained Males
Authors: Pilolla Kari D. , Armendariz Jessie , Burrus Boe M. , Baston David S. , McCarthy Karli A. , Bloedon Taylor K.
Published: March 2023

Wild blueberries (WBs) have been documented to decrease oxidative stress in active and sedentary populations as well as influence lipolytic enzymes and increase the rate of fat oxidation (FAT-ox) during rest. To examine the effect of WBs on the rate of FAT-ox and lipid peroxidation during submaximal exercise, 11 healthy, aerobically trained males (26 ± 7.5 years, 74.9 ± 7.54 kg, 10.5 ± 3.2% BF) completed a 2-week washout avoiding foods high in anthocyanins, then completed a control exercise protocol cycling at 65% of VO2peak for 40 min. Participants then consumed 375 g/d of anthocyanins for two weeks before repeating the exercise protocol. WBs increased FAT-ox when cycling at 65% of VO2peak by 19.7% at 20, 43.2% at 30, and 31.1% at 40 min, and carbohydrate oxidation (CHO-ox) decreased by 10.1% at 20, 19.2% at 30, and 14.8% at 40 min of cycling at 65% of VO2peak. Lactate was lower with WBs at 20 (WB: 2.6 ± 1.0, C: 3.0 ± 1.1), 30 (WB: 2.2 ± 0.9, C: 2.9 ± 1.0), and 40 min (WB: 1.9 ± 0.8, C: 2.5 ± 0.9). Results indicate that WBs may increase the rate of FAT-ox during moderate-intensity activity in healthy, active males.
Naringenin Attenuates Isoprenaline-Induced Cardiac Hypertrophy by Suppressing Oxidative Stress through the AMPK/NOX2/MAPK Signaling Pathway
Authors: Li Yu , He Bo , Zhang Chao , He Yanji , Xia Tianyang , Zeng Chunyu
Published: March 2023

Cardiac hypertrophy is accompanied by increased myocardial oxidative stress, and whether naringenin, a natural antioxidant, is effective in the therapy of cardiac hypertrophy remains unknown. In the present study, different dosage regimens (25, 50, and 100 mg/kg/d for three weeks) of naringenin (NAR) were orally gavaged in an isoprenaline (ISO) (7.5mg/kg)-induced cardiac hypertrophic C57BL/6J mouse model. The administration of ISO led to significant cardiac hypertrophy, which was alleviated by pretreatment with naringenin in both in vivo and in vitro experiments. Naringenin inhibited ISO-induced oxidative stress, as demonstrated by the increased SOD activity, decreased MDA level and NOX2 expression, and inhibited MAPK signaling. Meanwhile, after the pretreatment with compound C (a selective AMPK inhibitor), the anti-hypertrophic and anti-oxidative stress effects of naringenin were blocked, suggesting the protective effect of naringenin on cardiac hypertrophy. Our present study indicated that naringenin attenuated ISO-induced cardiac hypertrophy by regulating the AMPK/NOX2/MAPK signaling pathway.
The Association between Plant-Based Diet Indices and Metabolic Syndrome in Chinese Adults: Longitudinal Analyses from the China Health and Nutrition Survey
Authors: Huo Yating , Cao Suixia , Liu Jingchun , Zhang Binyan , Xu Kun , Wang Yutong , Liu Huimeng , Yang Peiying , Zeng Lingxia , Yan Hong , Dang Shaonong , Mi Baibing
Published: March 2023

Objectives: To investigate the association between a plant-based diet and metabolic syndrome (MetS) among Chinese adults. Methods: Based on the data from the 2004–2015 China Health and Nutrition Survey and the corresponding edition of China Food Composition, we calculated the healthy plant-based diet indices (hPDI) and unhealthy plant-based diet indices (uPDI). The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for MetS. Mediation analysis was further conducted to explore the mediator role of Body Mass Index (BMI) in the association between hPDI and MetS. Results: We included 10,013 participants, and over a median follow-up of 5 years, 961 patients (9.60%) developed MetS. Compared to those in the lowest quintile of hPDI score, we found that those in the highest quintile of hPDI score had a 28% lower ([HR]: 0.72, 95% CI 0.56–0.93, Ptrend = 0.021) risk of developing MetS and had a 20% lower (hazard ratio [HR]: 0.80, 95% CI 0.70–0.92, Ptrend = 0.004) risk of developing abdominal obesity. No significant associations were observed between uPDI and the MetS, but those in the highest quintile of uPDI score had a 36% higher (hazard ratio [HR]: 1.36, 95% CI 1.20–1.64, Ptrend < 0.001) risk of developing abdominal obesity, compared to those in the lowest quintile of uPDI score. In exploratory analysis, we observed that BMI at baseline mediated 27.8% of the association between hPDI and incident MetS, and BMI at baseline mediated 29.7% of the association between hPDI and abdominal obesity. Conclusion: The current findings reveal a possible causal relationship between a healthy plant-based diet and a reduced risk of MetS, especially abdominal obesity. It is observed that BMI may mediate the relationship between hPDI score and MetS. Controlling early dietary patterns and BMI may help reduce the risk of MetS.
Estimation of Free Sugars in the Filipino Food Composition Table and Evaluation of Population-Level Intake
Authors: Mainardi Fabio , Campos Vanessa Caroline , Côté Richard Gaston , Silber Nele Kristin , Plestina Roko , Angeles-Agdeppa Imelda
Published: March 2023

Recommendations to reduce intake of free sugars are included in some national dietary guidelines. However, as the content of free sugars is absent from most of the food composition tables, the adherence to such recommendations is hard to monitor. We developed a novel method to estimate the free sugar content in the Philippines food composition table, based on a data-driven algorithm that enabled automated annotation. We then used these estimates to analyze the free sugar intake of 66,016 Filipinos aged 4 years and over. The average free sugar consumption was 19 g/day, accounting for an average of 3% of the total caloric intake. Snacks and breakfast were the meals with the highest content of free sugars. Intake of free sugars, in grams per day and as % of energy, was positively associated with wealth status. The same pattern was observed for the consumption of sugar-sweetened beverages.
Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials
Authors: Lang-Illievich Kordula , Klivinyi Christoph , Lasser Christian , Brenna Connor T. A. , Szilagyi Istvan S. , Bornemann-Cimenti Helmar
Published: March 2023

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.
Isolation of Alginate-Degrading Bacteria from the Human Gut Microbiota and Discovery of Bacteroides xylanisolvens AY11-1 as a Novel Anti-Colitis Probiotic Bacterium
Authors: Fu Tianyu , Wang Yamin , Ma Mingfeng , Dai Wei , Pan Lin , Shang Qingsen , Yu Guangli
Published: March 2023

Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate the anti-colitis effect of alginate has not been fully characterized. We hypothesized that alginate-degrading bacteria might play a role here since these bacteria could utilize alginate as a carbon source. To test this hypothesis, we isolated 296 strains of alginate-degrading bacteria from the human gut. Bacteroides xylanisolvens AY11-1 was observed to have the best capability for alginate degradation. The degradation and fermentation of alginate by B. xylanisolvens AY11-1 produced significant amounts of oligosaccharides and short-chain fatty acids. Further studies indicated that B. xylanisolvens AY11-1 could alleviate body weight loss and contraction of colon length, reduce the incidences of bleeding and attenuate mucosal damage in dextran sulfate sodium (DSS)-fed mice. Mechanistically, B. xylanisolvens AY11-1 improved gut dysbiosis and promoted the growth of probiotic bacteria, including Blautia spp. And Prevotellaceae UCG-001, in diseased mice. Additionally, B. xylanisolvens AY11-1 showed no oral toxicity and was well-tolerated in male and female mice. Altogether, we illustrate for the first time an anti-colitis effect of the alginate-degrading bacterium B. xylanisolvens AY11-1. Our study paves the way for the development of B. xylanisolvens AY11-1 as a next-generation probiotic bacterium.
Factors Affecting the Breastfeeding Duration of Infants and Young Children in China: A Cross-Sectional Study
Authors: Yang Ziming , Ding Yingfang , Song Shuyao , Zhang Yaoyun , Li Aolin , Su Mintao , Xu Yajun
Published: March 2023

Objective: To investigate the factors affecting the duration of continuous breastfeeding of infants within 2 years of age, and to explore intervention strategies that may promote breastfeeding duration in China. Method: A self-made electronic questionnaire was used to investigate the breastfeeding duration of infants, and the influencing factors were collected from three levels of individual, family, and social support. The Kruskal–Wallis rank sum test and the multivariable ordinal logistic regression model were used for data analysis. Subgroup analysis was carried out according to region and parity. Results: A total of 1001 valid samples from 26 provinces across the country were obtained. Among them, 9.9% breastfed for less than 6 months, 38.6% for 6 to 12 months, 31.8% for 12 to 18 months, 6.7% for 18 to 24 months, and 13.1% for more than 24 months. Barriers to sustained breastfeeding included the mother’s age at birth being over 31, education level below junior high, cesarean delivery, and the baby’s first nipple sucking at 2 to 24 h after birth. Factors that promote continued breastfeeding included freelancer or full-time mother, high breastfeeding knowledge score, supporting breastfeeding, baby with low birth weight, first bottle feeding at 4 months and later, first supplementary food at over 6 months old, high family income, the mother’s family and friends supporting breastfeeding, breastfeeding support conditions after returning to work, etc. Conclusion: The breastfeeding duration in China is generally short, and the proportion of mothers breastfeeding until the age of 2 years and above, recommended by WHO, is very low. Multiple factors at the individual, family, and social support levels influence the duration of breastfeeding. It is suggested to improve the current situation by strengthening health education, improving system security, and enhancing social support.
Dual RNA-Seq of Flavobacterium psychrophilum and Its Outer Membrane Vesicles Distinguishes Genes Associated with Susceptibility to Bacterial Cold-Water Disease in Rainbow Trout (Oncorhynchus mykiss)
Authors: Chapagain Pratima , Ali Ali , Salem Mohamed
Published: March 2023

Flavobacterium psychrophilum (Fp), the causative agent of Bacterial Cold-Water disease in salmonids, causes substantial losses in aquaculture. Bacterial outer membrane vesicles (OMVs) contain several virulence factors, enzymes, toxins, and nucleic acids and are expected to play an essential role in host–pathogen interactions. In this study, we used transcriptome sequencing, RNA-seq, to investigate the expression abundance of the protein-coding genes in the Fp OMVs versus the Fp whole cell. RNA-seq identified 2190 transcripts expressed in the whole cell and 2046 transcripts in OMVs. Of them, 168 transcripts were uniquely identified in OMVs, 312 transcripts were expressed only in the whole cell, and 1878 transcripts were shared in the two sets. Functional annotation analysis of the OMV-abundant transcripts showed an association with the bacterial translation machinery and histone-like DNA-binding proteins. RNA-Seq of the pathogen transcriptome on day 5 post-infection of Fp-resistant versus Fp-susceptible rainbow trout genetic lines revealed differential gene expression of OMV-enriched genes, suggesting a role for the OMVs in shaping the host–microbe interaction. Interestingly, a cell wall-associated hydrolase (CWH) gene was the most highly expressed gene in OMVs and among the top upregulated transcripts in susceptible fish. The CWH sequence was conserved in 51 different strains of Fp. The study provides insights into the potential role of OMVs in host–pathogen interactions and explores microbial genes essential for virulence and pathogenesis.
Phytochemical Profile, Antioxidant, Antimicrobial and Cytoprotective Effects of Cornelian Cherry (Cornus mas L.) Fruit Extracts
Authors: Aurori Mara , Niculae Mihaela , Hanganu Daniela , Pall Emoke , Cenariu Mihai , Vodnar Dan Cristian , Bunea Andrea , Fiţ Nicodim , Andrei Sanda
Published: March 2023

Cornus mas L. is characterized by an increased quantity of bioactive compounds, namely polyphenols, monoterpenes, organic acids, vitamin C and lipophilic compounds such as carotenoids, being anciently used in the treatment of various diseases. This paper’s objectives were to characterize the phytochemical profile of Cornus mas L. fruits and to evaluate the in vitro antioxidant, antimicrobial and cytoprotective effects on renal cells exposed to gentamicin. As such, two ethanolic extracts were obtained. The resulting extracts were used to assess the total polyphenols, flavonoids and carotenoids through spectral and chromatographic methods. The antioxidant capacity was assessed using DPPH and FRAP assays. Due to the high content of phenolic compounds analyzed in fruits and the results obtained regarding antioxidant capacity, we decided to further use the ethanolic extract to investigate the in vitro antimicrobial and cytoprotective effects on renal cells stressed with gentamicin. The antimicrobial activity was assessed using agar well diffusion and broth microdilution methods, with great results regarding Pseudomonas aeruginosa. The cytotoxic activity was assessed using MTT and Annexin-V assays. According to the findings, extract-treated cells had a higher cell viability. However, at high concentrations, viability was shown to decline, most likely due to the extract and gentamicin’s additive effects.
Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier
Authors: Spiers Harry V. M. , Stadler Lukas K. J. , Smith Hugo , Kosmoliaptsis Vasilis
Published: March 2023

Extracellular vesicles are lipid bilayer-delimited nanoparticles excreted into the extracellular space by all cells. They carry a cargo rich in proteins, lipids and DNA, as well as a full complement of RNA species, which they deliver to recipient cells to induce downstream signalling, and they play a key role in many physiological and pathological processes. There is evidence that native and hybrid EVs may be used as effective drug delivery systems, with their intrinsic ability to protect and deliver a functional cargo by utilising endogenous cellular mechanisms making them attractive as therapeutics. Organ transplantation is the gold standard for treatment for suitable patients with end-stage organ failure. However, significant challenges still remain in organ transplantation; prevention of graft rejection requires heavy immunosuppression and the lack of donor organs results in a failure to meet demand, as manifested by growing waiting lists. Pre-clinical studies have demonstrated the ability of EVs to prevent rejection in transplantation and mitigate ischemia reperfusion injury in several disease models. The findings of this work have made clinical translation of EVs possible, with several clinical trials actively recruiting patients. However, there is much to be uncovered, and it is essential to understand the mechanisms behind the therapeutic benefits of EVs. Machine perfusion of isolated organs provides an unparalleled platform for the investigation of EV biology and the testing of the pharmacokinetic and pharmacodynamic properties of EVs. This review classifies EVs and their biogenesis routes, and discusses the isolation and characterisation methods adopted by the international EV research community, before delving into what is known about EVs as drug delivery systems and why organ transplantation represents an ideal platform for their development as drug delivery systems.
Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs
Authors: Lootens Orphélie , De Boevre Marthe , Ning Jia , Gasthuys Elke , Van Bocxlaer Jan , De Saeger Sarah , Vermeulen An
Published: March 2023

Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one’s daily exposure, especially in certain regions, e.g., sub-Saharan Africa. AFB1 is mostly metabolised by cytochrome P450 (CYP) enzymes, namely, CYP1A2 and CYP3A4. As a consequence of chronic exposure, it is interesting to check for interactions with drugs taken concomitantly. A physiologically based pharmacokinetic (PBPK) model was developed based on the literature and in-house-generated in vitro data to characterise the pharmacokinetics (PK) of AFB1. The substrate file was used in different populations (Chinese, North European Caucasian and Black South African), provided by SimCYP® software (v21), to evaluate the impact of populations on AFB1 PK. The model’s performance was verified against published human in vivo PK parameters, with AUC ratios and Cmax ratios being within the 0.5–2.0-fold range. Effects on AFB1 PK were observed with commonly prescribed drugs in South Africa, leading to clearance ratios of 0.54 to 4.13. The simulations revealed that CYP3A4/CYP1A2 inducer/inhibitor drugs might have an impact on AFB1 metabolism, altering exposure to carcinogenic metabolites. AFB1 did not have effects on the PK of drugs at representative exposure concentrations. Therefore, chronic AFB1 exposure is unlikely to impact the PK of drugs taken concomitantly.
An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice
Authors: Vijayanand Sharon , Patil Smital , Menon Ipshita , Braz Gomes Keegan , Kale Akanksha , Bagwe Priyal , Uddin Mohammad N. , Zughaier Susu M. , D’Souza Martin J.
Published: March 2023

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is needed. A microneedle (MN) vaccine delivery system is non-invasive, patient-friendly, and can be self-administered. Here, we tested the immune response produced by an adjuvanted inactivated SARS-CoV-2 microparticulate vaccine administered via the transdermal route using a dissolving MN. The inactivated SARS-CoV-2 vaccine antigen and adjuvants (Alhydrogel® and AddaVax™) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer matrices. The resulting MP were approximately 910 nm in size, with a high percentage yield and percent encapsulation efficiency of 90.4%. In vitro, the vaccine MP was non-cytotoxic and increased the immunostimulatory activity measured as nitric oxide release from dendritic cells. The adjuvant MP potentiated the immune response of the vaccine MP in vitro. In vivo, the adjuvanted SARS-CoV-2 MP vaccine induced high levels of IgM, IgG, IgA, IgG1, and IgG2a antibodies and CD4+ and CD8+ T-cell responses in immunized mice. In conclusion, the adjuvanted inactivated SARS-CoV-2 MP vaccine delivered using MN induced a robust immune response in vaccinated mice.
Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug–Drug Interactions in Rats
Authors: Melillo Nicola , Scotcher Daniel , Kenna J. Gerry , Green Claudia , Hines Catherine D. G. , Laitinen Iina , Hockings Paul D. , Ogungbenro Kayode , Gunwhy Ebony R. , Sourbron Steven , Waterton John C. , Schuetz Gunnar , Galetin Aleksandra
Published: March 2023

Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (khe), and biliary excretion (kbh). The observed median fold-decreases in gadoxetate liver AUC were 3.8- and 1.5-fold for ciclosporin and rifampicin, respectively. Ketoconazole unexpectedly decreased systemic and liver gadoxetate AUCs; the remaining drugs investigated (asunaprevir, bosentan, and pioglitazone) caused marginal changes. Ciclosporin decreased gadoxetate khe and kbh by 3.78 and 0.09 mL/min/mL, while decreases for rifampicin were 7.20 and 0.07 mL/min/mL, respectively. The relative decrease in khe (e.g., 96% for ciclosporin) was similar to PBPK-predicted inhibition of uptake (97–98%). PBPK modelling correctly predicted changes in gadoxetate systemic AUCR, whereas underprediction of decreases in liver AUCs was evident. The current study illustrates the modelling framework and integration of liver imaging data, PBPK, and tracer-kinetic models for prospective quantification of hepatic transporter-mediated DDI in humans.
Anti-Inflammatory Chilean Endemic Plants
Authors: Otero Carolina , Klagges Carolina , Morales Bernardo , Sotomayor Paula , Escobar Jorge , Fuentes Juan A. , Moreno Adrian A. , Llancalahuen Felipe M. , Arratia-Perez Ramiro , Gordillo-Fuenzalida Felipe , Herrera Michelle , Martínez Jose L. , Rodríguez-Díaz Maité
Published: March 2023

Medicinal plants have been used since prehistoric times and continue to treat several diseases as a fundamental part of the healing process. Inflammation is a condition characterized by redness, pain, and swelling. This process is a hard response by living tissue to any injury. Furthermore, inflammation is produced by various diseases such as rheumatic and immune-mediated conditions, cancer, cardiovascular diseases, obesity, and diabetes. Hence, anti-inflammatory-based treatments could emerge as a novel and exciting approach to treating these diseases. Medicinal plants and their secondary metabolites are known for their anti-inflammatory properties, and this review introduces various native Chilean plants whose anti-inflammatory effects have been evaluated in experimental studies. Fragaria chiloensis, Ugni molinae, Buddleja globosa, Aristotelia chilensis, Berberis microphylla, and Quillaja saponaria are some native species analyzed in this review. Since inflammation treatment is not a one-dimensional solution, this review seeks a multidimensional therapeutic approach to inflammation with plant extracts based on scientific and ancestral knowledge.
Micro-Injection Moulding of PEO/PCL Blend–Based Matrices for Extended Oral Delivery of Fenbendazole
Authors: Bezerra Gilberto S. N. , De Lima Gabriel G. , Colbert Declan M. , Halligan Elaine , Geever Joseph , Geever Luke
Published: March 2023

Fenbendazole (FBZ) is a broad-spectrum anthelmintic administered orally to ruminants; nevertheless, its poor water solubility has been the main limitation to reaching satisfactory and sustained levels at the site of the target parasites. Hence, the exploitation of hot-melt extrusion (HME) and micro-injection moulding (µIM) for the manufacturing of extended-release tablets of plasticised solid dispersions of poly(ethylene oxide) (PEO)/polycaprolactone (PCL) and FBZ was investigated due to their unique suitability for semi-continuous manufacturing of pharmaceutical oral solid dosage forms. High-performance liquid chromatography (HPLC) analysis demonstrated a consistent and uniform drug content in the tablets. Thermal analysis using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the amorphous state of the active ingredient, which was endorsed by powder X-ray diffraction spectroscopy (pXRD). Fourier transform infrared spectroscopy (FTIR) analysis did not display any new peak indicative of either a chemical interaction or degradation. Scanning electron microscopy (SEM) images showed smoother surfaces and broader pores as we increased the PCL content. Electron-dispersive X-ray spectroscopy (EDX) revealed that the drug was homogeneously distributed within the polymeric matrices. Drug release studies attested that all moulded tablets of amorphous solid dispersions improved the drug solubility, with the PEO/PCL blend–based matrices showing drug release by Korsmeyer–Peppas kinetics. Thus, HME coupled with µIM proved to be a promising approach towards a continuous automated manufacturing process for the production of oral solid dispersions of benzimidazole anthelmintics to grazing cattle.
Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma
Authors: Al Saqr Ahmed , Annaji Manjusha , Poudel Ishwor , Aldawsari Mohammed F. , Alrbyawi Hamad , Mita Nur , Dhanasekaran Muralikrishnan , Boddu Sai H. S. , Neupane Rabin , Tiwari Amit K. , Babu R. Jayachandra
Published: March 2023

This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.
Mode-Modulation Structure Based on 650 nm Ridge Waveguide Edge-Emitting Laser
Authors: Sun Xiao , Liu Peng , Ma Xiangen , Zhang Xiaodong , Su Jian , Chen Kang , Liu Qi , Jiang Kai , Tang Wenjing , Xia Wei , Xu Xiangang
Published: March 2023

Traditional laser diodes operating at 650 nm are more prone to high-order mode excitation, resulting in poorer beam quality. In this paper, we designed GaInP–AlGaInP laser diodes (LD) with a 650 nm range and a trench mode-modulation structure based on the structure of edge-emitting laser (EEL) diodes. The effect of the three-trench structure was investigated theoretically and experimentally. The right trench structure laser chips demonstrated good beam quality while maintaining a high power output. An electro-optical conversion efficiency of 56% was demonstrated with a slope efficiency of 1.32 W/A at a 40 mA current. The maximum optical output power reached 40.8 mW.
All-Monolithically Integrated Self-Scanning Addressable VCSEL Array for 3D Sensing
Authors: Kondo Takashi , Hayakawa Junichiro , Iguchi Daisuke , Sakita Tomoaki , Higuchi Takafumi , Takeyama Kei , Ohno Seiji , Murata Michiaki , Usami Hiroyuki
Published: March 2023

We propose an all-monolithically integrated self-scanning addressable vertical-cavity surface-emitting laser array for time-of-flight measurement. Some advantages of addressable VCSELs for ToF measurement applications include large reductions in power consumption, heat generation, multi-pass noise, and flare noise. In this paper, we discuss the characteristics of the proposed self-scanning addressable VCSEL array. All layers in the epilayer structure of the proposed VCSEL array were formed at once by metal-organic chemical vapor deposition. The device consists of an (Al)GaAs-based thyristor and a conventional top-emitting 940-nm oxide-confined VCSEL on an n-type GaAs substrate. The array contained 12 blocks (4 × 3) that have more than 40 emitters each. The device required only four signals from a field-programmable gate array to select the emitting blocks and one emission signal from a conventional VCSEL driver, even for arrays containing hundreds of blocks. The proposed module is capable of one-block sequential emission, parallel emission from several blocks, and emission from all blocks. The rise and fall times of the fabricated VCSEL array were observed to be 200 and 400 ps, respectively, for each emission mode. The influence of flare noise from an obstacle in front of the camera was dramatically reduced by avoiding emission to the obstacle.
Spin-Orbit Coupling in Quasi-Monochromatic Beams
Authors: Egorov Yuriy , Rubass Alexander
Published: March 2023

We investigate the concept that the value of the spin-orbit coupling is the energy efficiency of energy transfer between orthogonal components. The energy efficiency changes as the beam propagates through the crystal. For a fundamental Gaussian beam, its value cannot exceed 50%, while the energy efficiency for Hermite–Gaussian and Laguerre–Gaussian beams of higher orders of the complex argument can reach a value close to 100%. For Hermite–Gauss and Laguerre–Gauss beams of higher orders of real argument, the maximum energy efficiency can only slightly exceed 50%. It is shown that zero-order Bessel–Gauss beams are able to achieve an energy efficiency close to 100% when generating an axial vortex in the orthogonal component in both monochromatic and polychromatic light, while for a polychromatic Laguerre–Gauss or Hermite–Gauss beam of a complex argument, the energy efficiency reduced to a value not exceeding 50%. The spin angular momentum is compensated by changing the orbital angular momentum of the entire beam, which occurs as a result of the difference in the topological charge of the orthogonally polarized component by 2 units.
Minor Variety of Campania Olive Germplasm (“Racioppella”): Effects of Kaolin on Production and Bioactive Components of Drupes and Oil
Authors: Cirillo Aurora , Graziani Giulia , De Luca Lucia , Cepparulo Marco , Ritieni Alberto , Romano Raffaele , Di Vaio Claudio
Published: March 2023

The effects of climate change have a great impact on the Mediterranean regions which are experiencing an increase in drought periods with extreme temperatures. Among the various solutions reported to reduce the damage caused by extreme environmental conditions on olive plants, the application of anti-transpirant products is widespread. In an increasingly current scenario of climate change, this study was designed to evaluate the effect of kaolin on the quantitative and qualitative parameters of drupes and oil in a little-known olive cultivar known as “Racioppella”, belonging to the autochthonous germplasm of Campania (Southern Italy). To this purpose, the determination of maturation index, olive yield/plant, and bioactive components analysis (anthocyanins, carotenoids, total polyphenols, antioxidant activity, and fatty acids) were carried out. Kaolin applications showed no statistically significant differences in terms of production/plant while a significant increase in the drupe oil content was observed. Kaolin treatments resulted in increased anthocyanins (+24%) and total polyphenols (+60%) content and at the same time a significant increase in the antioxidant activity (+41%) of drupes was recorded. As far as oil is concerned, the results showed an increase in monounsaturated fatty acids, oleic and linoleic acids, and total polyphenols (+11%). On the basis of the results obtained, we can conclude that kaolin treatment can be considered as a sustainable solution to improve qualitative parameters in olive drupes and oil.
Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma
Authors: Wu Kevin Y. , Ashkar Said , Jain Shrieda , Marchand Michael , Tran Simon D.
Published: March 2023

The eye has anatomical structures that function as robust static and dynamic barriers, limiting the penetration, residence time, and bioavailability of medications administered topically. The development of polymeric nano-based drug-delivery systems (DDS) could be the solution to these challenges: it can pass through ocular barriers, offering higher bioavailability of administered drugs to targeted tissues that are otherwise inaccessible; it can stay in ocular tissues for longer periods of time, requiring fewer drug administrations; and it can be made up of polymers that are biodegradable and nano-sized, minimizing the undesirable effects of the administered molecules. Therefore, therapeutic innovations in polymeric nano-based DDS have been widely explored for ophthalmic drug-delivery applications. In this review, we will give a comprehensive overview of polymeric nano-based drug-delivery systems (DDS) used in the treatment of ocular diseases. We will then examine the current therapeutic challenges of various ocular diseases and analyze how different types of biopolymers can potentially enhance our therapeutic options. A literature review of the preclinical and clinical studies published between 2017 and 2022 was conducted. Thanks to the advances in polymer science, the ocular DDS has rapidly evolved, showing great promise to help clinicians better manage patients.
Essential Oil Nanoemulsion Hydrogel with Anti-Biofilm Activity for the Treatment of Infected Wounds
Authors: Cai Kun , Liu Yang , Yue Yan , Liu Yuancheng , Guo Fengbiao
Published: March 2023

The formation of a bacterial biofilm on an infected wound can impede drug penetration and greatly thwart the healing process. Thus, it is essential to develop a wound dressing that can inhibit the growth of and remove biofilms, facilitating the healing of infected wounds. In this study, optimized eucalyptus essential oil nanoemulsions (EEO NEs) were prepared from eucalyptus essential oil, Tween 80, anhydrous ethanol, and water. Afterward, they were combined with a hydrogel matrix physically cross-linked with Carbomer 940 (CBM) and carboxymethyl chitosan (CMC) to prepare eucalyptus essential oil nanoemulsion hydrogels (CBM/CMC/EEO NE). The physical-chemical properties, in vitro bacterial inhibition, and biocompatibility of EEO NE and CBM/CMC/EEO NE were extensively investigated and the infected wound models were proposed to validate the in vivo therapeutic efficacy of CBM/CMC/EEO NE. The results showed that the average particle size of EEO NE was 15.34 ± 3.77 nm with PDI ˂ 0.2, the minimum inhibitory concentration (MIC) of EEO NE was 15 mg/mL, and the minimum bactericidal concentration (MBC) against S. aureus was 25 mg/mL. The inhibition and clearance of EEO NE against S. aureus biofilm at 2×MIC concentrations were 77.530 ± 7.292% and 60.700 ± 3.341%, respectively, demonstrating high anti-biofilm activity in vitro. CBM/CMC/EEO NE exhibited good rheology, water retention, porosity, water vapor permeability, and biocompatibility, meeting the requirements for trauma dressings. In vivo experiments revealed that CBM/CMC/EEO NE effectively promoted wound healing, reduced the bacterial load of wounds, and accelerated the recovery of epidermal and dermal tissue cells. Moreover, CBM/CMC/EEO NE significantly down-regulated the expression of two inflammatory factors, IL-6 and TNF-α, and up-regulated three growth-promoting factors, TGF-β1, VEGF, and EGF. Thus, the CBM/CMC/EEO NE hydrogel effectively treated wounds infected with S. aureus, enhancing the healing process. It is expected to be a new clinical alternative for healing infected wounds in the future.
Repair of Aerospace Composite Structures Using Liquid Thermoplastic Resin
Authors: Khan Tayyab , Hafeez Farrukh , Umer Rehan
Published: March 2023

In this study, two types of carbon-fiber-reinforced plastic (CFRP) composite scarf geometries were created using two scarf angles, i.e., 1.43° and 5.71°. The scarf joints were adhesively bonded using a novel liquid thermoplastic resin at two different temperatures. The performance of the repaired laminates was compared with pristine samples in terms of residual flexural strength using four-point bending tests. The repair quality of the laminates was examined by optical micrographs, and the failure modes after flexural tests were analyzed using a scanning electron microscope. The thermal stability of the resin was evaluated by thermogravimetric analysis (TGA), whereas the stiffness of the pristine samples was determined using dynamic mechanical analysis (DMA). The results showed that the laminates were not fully repaired under ambient conditions, and the highest recovery strength at room temperature was only 57% of the total strength exhibited by pristine laminates. Increasing the bonding temperature to an optimal repair temperature of 210 °C resulted in a significant improvement in the recovery strength. The best results were achieved for laminates with a higher scarf angle (5.71°). The highest residual flexural strength was recorded as 97% that of the pristine sample repaired at 210 °C with a scarf angle of 5.71°. The SEM micrographs showed that all the repaired samples exhibited delamination as the dominant failure mode, whereas the pristine samples exhibited dominant fiber fracture and fiber pullout failure modes. The residual strength recovered using liquid thermoplastic resin was found to be much higher than that reported for conventional epoxy adhesives.