bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Correlation of Surface Tension and Surface Composition of Ionic Liquid Mixtures—A Combined Vacuum Pendant Drop and Angle-Resolved X-ray Photoelectron Spectroscopy Study
Authors: Paap Ulrike , Seidl Vera , Meyer Karsten , Maier Florian , Steinrück Hans-Peter
Published: December 2022

We investigated the surface tension and surface composition of various mixtures of the two ionic liquids (ILs) 1-methyl-3-octyl-imidazolium hexafluorophosphate [C8C1Im][PF6] and 1,3-bis(polyethylene glycol)imidazolium iodide [(mPEG2)2Im]I in the temperature range from 230 to 370 K under ultraclean vacuum conditions. The surface tension was measured using a newly developed apparatus, and the surface composition was determined by angle-resolved X-ray photoelectron spectroscopy (ARXPS). In the pure ILs, the alkyl chains of [C8C1Im][PF6] and the PEG chains of [(mPEG2)2Im]I are enriched at the IL/vacuum interface. In the mixtures, a strong selective surface enrichment of the alkyl chains occurs, which is most pronounced at low [C8C1Im][PF6] contents. For the surface tension, strong deviations from an ideal mixing behaviour take place. By applying a simple approach based on the surface composition of the mixtures as deduced from ARXPS, we are able to predict and reproduce the experimentally measured temperature-dependent surface tension values with astonishingly high accuracy.
Pathfinder-Driven Chemical Space Exploration and Multiparameter Optimization in Tandem with Glide/IFD and QSAR-Based Active Learning Approach to Prioritize Design Ideas for FEP+ Calculations of SARS-CoV-2 PLpro Inhibitors
Authors: Gumede Njabulo Joyfull
Published: December 2022

A global pandemic caused by the SARS-CoV-2 virus that started in 2020 and has wreaked havoc on humanity still ravages up until now. As a result, the negative impact of travel restrictions and lockdowns has underscored the importance of our preparedness for future pandemics. The main thrust of this work was based on addressing this need by traversing chemical space to design inhibitors that target the SARS-CoV-2 papain-like protease (PLpro). Pathfinder-based retrosynthesis analysis was used to generate analogs of GRL-0617 using commercially available building blocks by replacing the naphthalene moiety. A total of 10 models were built using active learning QSAR, which achieved good statistical results such as an R2 > 0.70, Q2 > 0.64, STD Dev < 0.30, and RMSE < 0.31, on average for all models. A total of 35 ideas were further prioritized for FEP+ calculations. The FEP+ results revealed that compound 45 was the most active compound in this series with a ΔG of −7.28 ± 0.96 kcal/mol. Compound 5 exhibited a ΔG of −6.78 ± 1.30 kcal/mol. The inactive compounds in this series were compound 91 and compound 23 with a ΔG of −5.74 ± 1.06 and −3.11 ± 1.45 kcal/mol. The combined strategy employed here is envisaged to be of great utility in multiparameter lead optimization efforts, to traverse chemical space, maintaining and/or improving the potency as well as the property space of synthetically aware design ideas.
Three-Dimensional Printed Polyamide 12 (PA12) and Polylactic Acid (PLA) Alumina (Al2O3) Nanocomposites with Significantly Enhanced Tensile, Flexural, and Impact Properties
Authors: Petousis Markos , Vidakis Nectarios , Mountakis Nikolaos , Papadakis Vassilis , Tzounis Lazaros
Published: December 2022

The effect of aluminum oxide (Al2O3) nanoparticles (NPs) as a reinforcing agent of Polyamide 12 (PA12) and Polylactic acid (PLA) in fused filament fabrication (FFF) three-dimensional printing (3DP) is reported herein for the first time. Alumina NPs are incorporated via a melt–mixing compounding process, at four different filler loadings. Neat as well as nanocomposite 3DP filaments are prepared as feedstock for the 3DP manufacturing of specimens which are thoroughly investigated for their mechanical properties. Thermogravimetric analyses (TGA) and Raman spectroscopy (RS) proved the nature of the materials. Their morphological characteristics were thoroughly investigated with scanning electron and atomic force microscopy. Al2O3 NPs exhibited a positive reinforcement mechanism at all filler loadings, while the mechanical percolation threshold with the maximum increase of performance was found between 1.0–2.0 wt.% filler loading (1.0 wt.% for PA12, 41.1%, and 56.4% increase in strength and modulus, respectively; 2.0 wt.% for PLA, 40.2%, and 27.1% increase in strength and modulus, respectively). The combination of 3DP and polymer engineering using nanocomposite PA12 and PLA filaments with low-cost filler additives, e.g., Al2O3 NPs, could open new avenues towards a series of potential applications using thermoplastic engineering polymers in FFF 3DP manufacturing.
Hierarchical Multi-Scale Coupled Periodical Photonic and Plasmonic Nanopatterns Inscribed by Femtosecond Laser Pulses in Lithium Niobate
Authors: Kudryashov Sergey , Rupasov Alexey , Kosobokov Mikhail , Akhmatkhanov Andrey , Krasin George , Danilov Pavel , Lisjikh Boris , Abramov Alexander , Greshnyakov Evgeny , Kuzmin Evgeny , Kovalev Michael , Shur Vladimir
Published: December 2022

The ultrafast interaction of tightly focused femtosecond laser pulses with bulk dielectric media in direct laser writing (inscription) regimes is known to proceed via complex multi-scale light, plasma and material modification nanopatterns, which are challenging for exploration owing to their mesoscopic, transient and buried character. In this study, we report on the first experimental demonstration, analysis and modeling of hierarchical multi-period coupled longitudinal and transverse nanogratings in bulk lithium niobate inscribed in the focal region by 1030 nm, 300 fs laser pulses in the recently proposed sub-filamentary laser inscription regime. The longitudinal Bragg-like topography nanogratings, possessing the laser-intensity-dependent periods ≈ 400 nm, consist of transverse birefringent nanogratings, which are perpendicular to the laser polarization and exhibit much smaller periods ≈ 160 nm. Our analysis and modeling support the photonic origin of the longitudinal nanogratings, appearing as prompt electromagnetic and corresponding ionization standing waves in the pre-focal region due to interference of the incident and plasma-reflected laser pulse parts. The transverse nanogratings could be assigned to the nanoscale material modification by interfacial plasmons, excited and interfered in the resulting longitudinal array of the plasma sheets in the bulk dielectric material. Our experimental findings provide strong support for our previously proposed mechanism of such hierarchical laser nanopatterning in bulk dielectrics, giving important insights into its crucial parameters and opening the way for directional harnessing of this technology.
Monovalent Copper Cation Doping Enables High-Performance CsPbIBr2-Based All-Inorganic Perovskite Solar Cells
Authors: Du Zhaonan , Xiang Huimin , Xie Amin , Ran Ran , Zhou Wei , Wang Wei , Shao Zongping
Published: December 2022

Organic–inorganic perovskite solar cells (PSCs) have delivered the highest power conversion efficiency (PCE) of 25.7% currently, but they are unfortunately limited by several key issues, such as inferior humid and thermal stability, significantly retarding their widespread application. To tackle the instability issue, all-inorganic PSCs have attracted increasing interest due to superior structural, humid and high-temperature stability to their organic–inorganic counterparts. Nevertheless, all-inorganic PSCs with typical CsPbIBr2 perovskite as light absorbers suffer from much inferior PCEs to those of organic–inorganic PSCs. Functional doping is regarded as a simple and useful strategy to improve the PCEs of CsPbIBr2-based all-inorganic PSCs. Herein, we report a monovalent copper cation (Cu+)-doping strategy to boost the performance of CsPbIBr2-based PSCs by increasing the grain sizes and improving the CsPbIBr2 film quality, reducing the defect density, inhibiting the carrier recombination and constructing proper energy level alignment. Consequently, the device with optimized Cu+-doping concentration generates a much better PCE of 9.11% than the pristine cell (7.24%). Moreover, the Cu+ doping also remarkably enhances the humid and thermal durability of CsPbIBr2-based PSCs with suppressed hysteresis. The current study provides a simple and useful strategy to enhance the PCE and the durability of CsPbIBr2-based PSCs, which can promote the practical application of perovskite photovoltaics.
The Use of Pyrolytic Char Derived from Waste Tires in the Removal of Malachite Green from Dyeing Wastewater
Authors: Ji Dongliang , Gai Didi , Xu Yikun , Huang Zhaoqin , Zhao Peitao
Published: December 2022

The organic dye malachite green (MG) poses a potential risk of cancer and fertility loss in humans and aquatic organisms. This study focused on a modified pyrolytic char (PC) derived from waste tires to efficiently remove MG from wastewater. Modified PC has rich -OH functional groups, higher BET (Brunauer-Emmett-Teller) surfaces of 74.4, 64.95, and 67.31 m2/g, and larger pore volumes of 0.52, 0.47, and 0.62 cm3/g for NaOH, Na2CO3, and CaO modification, respectively. The pseudo-second-order model fit the adsorption well, and the maximum equilibrium adsorption capacity was 937.8 mg/g for PC after CaO activation (CaO-PC). NaOH-modified PC (NaOH-PC) showed the best fit with the Langmuir model (R2 = 0.918). It is suggested that alkali-modified waste tire pyrolytic char could be a potential adsorbent for removing MG from dye-containing wastewater.
Modification of SnO2 Electron Transport Layer in Perovskite Solar Cells
Authors: Park Helen Hejin
Published: December 2022

Rapid development of the device performance of organic-inorganic lead halide perovskite solar cells (PSCs) are emerging as a promising photovoltaic technology. Current world-record efficiency of PSCs is based on tin oxide (SnO2) electron transport layers (ETLs), which are capable of being processed at low temperatures and possess high carrier mobilities with appropriate energy- band alignment and high optical transmittance. Modification of SnO2 has been intensely investigated by various approaches to tailor its conductivity, band alignment, defects, morphology, and interface properties. This review article organizes recent developments of modifying SnO2 ETLs to PSC advancement using surface and bulk modifications, while concentrating on photovoltaic (PV) device performance and long-term stability. Future outlooks for SnO2 ETLs in PSC research and obstacles remaining for commercialization are also discussed.
ACE-Vitamin Index and Risk of Glaucoma: The SUN Project
Authors: Moreno-Montañés Javier , Gándara Elsa , Moreno-Galarraga Laura , Hershey Maria S. , López-Gil José Francisco , Kales Stefanos , Bes-Rastrollo Maira , Martínez-González Miguel Ángel , Fernandez-Montero Alejandro
Published: December 2022

Background: Previous studies regarding antioxidant consumption and glaucoma have shown contradictory results. The aim of this study was to analyze the combined effect of the consumption of three vitamins (A, C and E) on the incidence of glaucoma in the SUN Project. Methods: For this study, 18,669 participants were included. The mean follow-up was 11.5 years. An index including vitamins A, C and E (ACE-Vitamin Index) was calculated. Vitamin intake was extracted from participants’ dietary data and vitamin supplements, if taken. Information on glaucoma incidence was collected by previously validated self-reported questionnaires. The association between glaucoma and vitamin intake was assessed by repeated-measures Cox regression using multi-adjusted hazard ratios. Results: A total of 251 (1.3%) cases of glaucoma were detected. Participants with a higher ACE-Vitamin Index presented a reduced risk of glaucoma compared to participants with lower consumption (adjusted HR = 0.73; 95% CI, (0.55–0.98)). When each vitamin was analyzed individually, none of them had a significant protective effect. The protective effect of the ACE-Vitamin Index was higher in men and older participants (≥55 year). Conclusions: The consumption of vitamins A, C and E considered separately do not seem to exert a protective effect against glaucoma, but when these vitamins are considered together, they are associated with a lower risk of glaucoma.
Maternal Supplementation with a Cocoa Extract during Lactation Deeply Modulates Dams’ Metabolism, Increases Adiponectin Circulating Levels and Improves the Inflammatory Profile in Obese Rat Offspring
Authors: Mariné-Casadó Roger , Domenech-Coca Cristina , Crescenti Anna , Rodríguez Gómez Miguel Ángel , Del Bas Josep Maria , Arola Lluís , Boqué Noemí , Caimari Antoni
Published: December 2022

High-flavonoid cocoa consumption has been associated with beneficial properties. However, there are scarce data concerning the effects of maternal cocoa intake on dams and in their progeny. Here, we evaluated in rats whether maternal supplementation with a high-flavan-3-ol cocoa extract (CCX) during lactation (200 mg.kg−1.day−1) produced beneficial effects on dams and in their normoweight (STD-CCX group) and cafeteria-fed obese (CAF-CCX group) adult male offspring. Maternal intake of CCX significantly increased the circulating levels of adiponectin and decreased the mammary gland lipid content of dams. These effects were accompanied by increased energy expenditure and circulating free fatty acids, as well as by a higher expression of lipogenic and adiponectin-related genes in their mammary glands, which could be related to a compensatory mechanism to ensure enough lipid supply to the pups. CCX consumption programmed both offspring groups towards increased plasma total adiponectin levels, and decreased liver weight and lean/fat ratio. Furthermore, CAF-CCX progeny showed an improvement of the inflammatory profile, evidenced by the significant decrease of the monocyte chemoattractant protein-1 (MCP-1) circulating levels and the mRNA levels of the gene encoding the major histocompatibility complex, class II invariant chain (Cd74), a marker of M1 macrophage phenotype, in the epididymal white adipose tissue. Although further studies are needed, these findings can pave the way for using CCX as a nutraceutical supplement during lactation.
Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health
Authors: Rodriguez Daniel , Lavie Carl J. , Elagizi Andrew , Milani Richard V.
Published: December 2022

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a “risk-enhancing factor” for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.
Human Milk Microbiome and Microbiome-Related Products: Potential Modulators of Infant Growth
Authors: Ma Jie , Palmer Debra J. , Geddes Donna , Lai Ching Tat , Stinson Lisa
Published: December 2022

Infant growth trajectory may influence later-life obesity. Human milk provides a wide range of nutritional and bioactive components that are vital for infant growth. Compared to formula-fed infants, breastfed infants are less likely to develop later-onset obesity, highlighting the potential role of bioactive components present in human milk. Components of particular interest are the human milk microbiota, human milk oligosaccharides (HMOs), short-chain fatty acids (SCFAs), and antimicrobial proteins, each of which influence the infant gut microbiome, which in turn has been associated with infant body composition. SCFAs and antimicrobial proteins from human milk may also systemically influence infant metabolism. Although inconsistent, multiple studies have reported associations between HMOs and infant growth, while studies on other bioactive components in relation to infant growth are sparse. Moreover, these microbiome-related components may interact with each other within the mammary gland. Here, we review the evidence around the impact of human milk microbes, HMOs, SCFAs, and antimicrobial proteins on infant growth. Breastfeeding is a unique window of opportunity to promote optimal infant growth, with aberrant growth trajectories potentially creating short- and long-term public health burdens. Therefore, it is important to understand how bioactive components of human milk influence infant growth.
The Potential Impact of Different Taxation Scenarios towards Sugar-Sweetened Beverages on Overweight and Obesity in Brazil: A Modeling Study
Authors: Enes Carla Cristina , Rinaldi Ana Elisa M. , Nucci Luciana Bertoldi , Itria Alexander
Published: December 2022

The adoption of fiscal policies based on the specific taxation of sugar-sweetened beverages (SSBs) has been recommended by international health agencies, as they are measures that potentially reduce consumption. This study is an ex ante risk comparison that estimates the impact of three tax scenarios (20, 25, and 30%) with a 100% pass-on rate to SSBs on the prevalence of high weight and obesity in the Brazilian population. Data on the consumption habits, weight, and height of 46,164 adults aged 20 years or over from Brazilian recent national surveys were used. The shift in consumption after taxation was estimated based on the price elasticity of the demand. The percentage changes in overweight for 20, 25, and 30% taxation were 1.84% (95%CI: 1.82; 1.86), 1.89% (95%CI: 1.87; 1.90), and 2.25% (95%CI: 2.24; 2.27), respectively. The change in the prevalence of obesity was 1.93% (95%CI: 1.87; 2.00), 2.90% (95%CI: 2.80; 3.02), and 4.16% (95%CI: 4.01; 4.32), respectively. Taxes on SSBs may have a more favorable result among the heaviest consumers, who are young adults (20–29 years), especially men, thereby promoting a greater reduction in the prevalence of high weight and obesity.
Associations between Hunger and Psychological Outcomes: A Large-Scale Ecological Momentary Assessment Study
Authors: de Rivaz Romain , Swendsen Joel , Berthoz Sylvie , Husky Mathilde , Merikangas Kathleen , Marques-Vidal Pedro
Published: December 2022

Studies assessing the association between hunger and psychological states have been conducted in laboratory settings, or limited to persons with eating disorders. In this study, 748 community-dwelling adults (56.4% women, 60.0 ± 9.3 years) completed the Ecological Momentary Assessment four times a day (08:00, 12:00, 16:00 and 20:00) for seven days. At each assessment, respondents indicated their current hunger level, food intake, and psychological states (sad, anxious, active, lively, distracted, anhedonic, angry, slow thinking and restless). Time-lagged associations assessing the effect of hunger on subsequent psychological states 4 h later and vice-versa were assessed. Hunger intensity increased subsequent active feeling (coefficient and 95% confidence interval: 0.029 (0.007; 0.051)) and lively feeling (0.019 (0.004; 0.034)) and decreased later slow thinking (−0.016 (−0.029; −0.003)). Previous eating increased later activity (0.116 (0.025; 0.208)). Feeling active (0.050 (0.036; 0.064)), lively (0.045 (0.023; 0.067)) and restless (0.040 (0.018; 0.063)) increased later hunger intensity, while distraction (−0.039 (−0.058; −0.019)) and slow thinking (−0.057 (−0.080; −0.034)) decreased it. No association was found between hunger, food intake and negative psychological states (sadness, anxiety and anger). Conclusions: Positive psychological states and hunger influence each other, while no association was found between hunger and negative psychological states.
Interaction of Depression and Unhealthy Diets on the Risk of Cardiovascular Diseases and All-Cause Mortality in the Chinese Population: A PURE Cohort Substudy
Authors: Lang Xinyue , Liu Zhiguang , Islam Shofiqul , Han Guoliang , Rangarajan Sumathy , Tse Lap Ah , Mushtaha Maha , Wang Junying , Hu Lihua , Qiang Deren , Zhu Yingxuan , Yusuf Salim , Lin Yang , Hu Bo ,   on behalf of the PURE-China Investigators
Published: December 2022

This study aimed to identify the interaction of depression and diets on cardiovascular diseases (CVD) incident and death in China and key subpopulations. We included 40,925 participants from the Prospective Urban Rural Epidemiology (PURE)-China cohort which recruited participants aged 35–70 years from 45 urban and 70 rural communities. Depression was measured by the adapted Short-Form (CIDI-SF). The unhealthy diet was considered when the score of Alternative Healthy Eating Index was below the lowest tertile. The primary outcome was a composite outcome of incident CVD and all-cause mortality. Cox frailty models were used to examine the associations. During a median follow-up of 11.9 years (IQR: 9.6–12.6 years), depression significantly increased the risk of the composite outcome (HR = 2.00; 95% CI, 1.16–3.27), major CVD (HR = 1.82; 95% CI, 1.48–2.23), and all-cause mortality (HR = 2.21; 95% CI, 1.51–3.24) for the unhealthy diet group, but not for the healthy diet group. The interaction between depression and diet for the composite outcome was statistically significant (RERI = 1.19; 95% CI, 0.66–1.72; AP = 0.42, 95% CI, 0.27–0.61; SI = 3.30, 95% CI, 1.42–7.66; multiplicative-scale = 1.74 95% CI, 1.27–2.39), even in the subgroup and sensitivity analyses. In addition, the intake of vegetable and polyunsaturated fatty acids contributed most to the interaction of diets and depression. Depressive participants should focus on healthy diets, especially vegetables and polyunsaturated fatty acids, to avoid premature death and CVD.
3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy
Authors: Zhu Yichen , Kang Elliot , Wilson Matthew , Basso Taylor , Chen Evelynn , Yu Yanqi , Li Yan-Ruide
Published: December 2022

The intricate microenvironment in which malignant cells reside is essential for the progression of tumor growth. Both the physical and biochemical features of the tumor microenvironment (TME) play a critical role in promoting the differentiation, proliferation, invasion, and metastasis of cancer cells. It is therefore essential to understand how malignant cells interact and communicate with an assortment of supportive tumor-associated cells including macrophages, fibroblasts, endothelial cells, and other immune cells. To study the complex mechanisms behind cancer progression, 3D spheroid and organoid models are widely in favor because they replicate the stromal environment and multicellular structure present within an in vivo tumor. It provides more precise data about the cell–cell interactions, tumor characteristics, drug discovery, and metabolic profile of cancer cells compared to oversimplified 2D systems and unrepresentative animal models. This review provides a description of the key elements of the tumor microenvironment as well as early research using cell-line derived, 3D spheroid tumor models that paved the way for the adoption of patient-derived spheroid and organoid models. In particular, 3D spheroid and organoid models provide a method for drug screening with a particular emphasis on influence of the TME in cancer immunotherapy.
Pathogenicity of Asymptomatically Residing Fusarium Species in Non-Gramineous Plants and Weeds to Spring Wheat under Greenhouse Conditions
Authors: Zavtrikovienė Evelina , Gorash Andrii , Kadžienė Gražina , Matelionienė Neringa , Supronienė Skaidrė
Published: December 2022

Despite significant efforts in recent decades to combat Fusarium head blight (FHB), this disease remains one of the most important and widely studied diseases of wheat and other cereal plants. To date, studies have focused on small grain cereals as hostplants for these pathogens, but it was recently discovered that asymptomatic non-gramineous plants and weeds can serve as alternative sources of fungi associated with FHB. The aim of this study was to evaluate the pathogenicity of Fusarium avenaceum, F. culmorum, F. graminearum and F. sporotrichioides isolated from non-gramineous plants and weed species to spring wheat under greenhouse conditions. A total of 91 Fusarium isolates, including 45 from weeds and 46 from non-gramineous plants were floret inoculated at mid anthesis. The FHB incidence and severity (%) of inoculated heads and the area under the disease progress curve (AUDPC) were calculated. To determine yield losses, the weight of 1000 grains (TGW) was evaluated. Results of the research showed that FHB severity (%) values in Fusarium spp.-inoculated heads from non-gramineous plants varied from 9.3% to 69.6% and AUDPC values ranged from 161.5% to 1044.6%. TGW was most significantly reduced by the F. culmorum isolates BN26r and BN39fl from Brassica napus and isolates BV15.1l and BV142.1pe from Beta vulgaris (37%, 30%, 28.8% and 31.8% respectively, compared to the water control). In Fusarium-inoculated heads from weeds, FHB severity values ranged from 6.2% to 81.0% and AUDPC values varied from 134.2% to 1206.6%. TGW was most significantly decreased by CBP1401r isolate from Capsella bursa-pastoris (52%). The study results suggest that the pathogenicity of Fusarium species isolated from different hosts to wheat more strongly depends on the Fusarium species and strain than the hostplant. Under greenhouse conditions, F. culmorum strain groups obtained from weeds, non-gramineous plants and Triticum were more pathogenic to wheat than the water control and other Fusarium species.
Epididymo-Orchitis Caused by POM-1 Metallo-β-Lactamase-Producing Pseudomonas otitidis in an Immunocompetent Patient: Case Report and Molecular Characterization
Authors: Alqurashi Moayad , Alsaedy Abdulrahman , Alalwan Bassam , Alzayer Maha , Alswaji Abdulrahman , Okdah Liliane , Doumith Michel , Zowawi Hosam , Aljohani Sameera , Alghoribi Majed
Published: December 2022

Pseudomonas otitidis is a rare and unique species among the Pseudomonas genus that has not been previously reported as a cause of male genitourinary tract infection. In this report, we describe a case of a 20-year-old immunocompetent male who presented with recurrent epididymo-orchitis, which was initially misidentified as Vibrio vulnificus and treated successfully. The causative agent could not be identified appropriately using the available routine methods, but a final identification was established using 16S rRNA targeted sequencing followed by whole-genome sequencing.
The Essential Oil from the Resurrection Plant Myrothamnus moschatus Is Effective against Arthropods of Agricultural and Medical Interest
Authors: Pavela Roman , Ferrati Marta , Spinozzi Eleonora , Maggi Filippo , Petrelli Riccardo , Rakotosaona Rianasoambolanoro , Ricciardi Renato , Benelli Giovanni
Published: December 2022

This work aimed to evaluate the chemical composition, insecticidal and acaricidal potential of the essential oil (EO) obtained from the resurrection plant Myrothamnus moschatus (Baill.) Baill. (Myrothamnaceae) from Madagascar. The EO bioactivity was evaluated against selected arthropod pests and vectors of agricultural and public health relevance. The most abundant volatile compounds were trans-pinocarveol (37.7 ± 4.2%) and pinocarvone (20.8 ± 3.1%), similar to the EO of the chemotype collected from the same region. Lethal concentrations (LC50) or doses (LD50) from acute toxicity tests were estimated for Musca domestica (L.) adults at 22.7 µg adult−1, for Spodoptera littoralis (Boisduval) larvae at 35.6 µg larva−1, for Culex quinquefasciatus (Say) at 43.6 µg mL−1, for adults of Metopolophium dirhodum (Walker) at 2.4 mL L−1, and for adults of Tetranychus urticae (Koch) at 1.2 mL L−1. The good insecticidal and acaricidal activities determined in this work may open a new perspective on the use of this plant as a source of botanical insecticide ingredients. The exploitation of this species could also be important for the African economy, helping local farmers cultivating this plant.
Update on COVID-19 Therapy in Pediatric Age
Authors: Esposito Susanna , Autore Giovanni , Argentiero Alberto , Ramundo Greta , Perrone Serafina , Principi Nicola
Published: December 2022

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient’s characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.
Vulvodynia: Pain Management Strategies
Authors: Merlino Lucia , Titi Luca , Pugliese Francesco , D’Ovidio Giulia , Senatori Roberto , Rocca Carlo Della , Piccioni Maria Grazia
Published: December 2022

Background: Vulvodynia is defined in this international consensus as persistent vulvar pain that occurs for >3 months without an identifiable cause and with several potential associated factors. At present there is no univocal consensus in the therapeutic treatment of vulvodynia. The methods of intervention are based on various aspects including, above all, the management of painful symptoms. Methods: a research on scientific database such as “Pubmed”, “Medline Plus”, “Medscape” was conducted, using the words “women’s genital pain” and “vulvodynia” for the review of the scientific evidence on the assessment and treatment of women’s genital pain. Results: Among the drugs with pain-relieving action, the most effective in the treatment of vulvodynia would seem to be those with antidepressant and anticonvulsant action, even if their mechanisms of action are not known and there are still insufficient studies able to demonstrate their real validity. Among the least effective are non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. However, the ideal would seem to use a combined treatment with multiple types of drugs. Conclusions: Future studies are needed to draw up a unique therapeutic action plan that considers the stratification of patients with vulvodynia and the variability of the symptom.
Cell-Derived Vesicles for mRNA Delivery
Authors: Li Zhenghua , Liu Zhen , Wu Jiacai , Li Bin
Published: December 2022

The clinical translation of messenger mRNA (mRNA)-based therapeutics requires safe and effective delivery systems. Although considerable progress has been made on the development of mRNA delivery systems, many challenges, such as the dose-limiting toxicity and specific delivery to extrahepatic tissues, still remain. Cell-derived vesicles, a type of endogenous membranous particle secreted from living cells, can be leveraged to load mRNA during or after their biogenesis. Currently, they have received increasing interest for mRNA delivery due to their natural origin, good biocompatibility, cell-specific tropism, and unique ability to cross physiological barriers. In this review, we provide an overview of recent advances in the naturally occurring mRNA delivery platforms and their biomedical applications. Furthermore, the future perspectives on clinical translation of cell-derived vesicles have been discussed.
Tailoring Lipid-Based Drug Delivery Nanosystems by Synchrotron Small Angle X-ray Scattering
Authors: Sartori Barbara , Marmiroli Benedetta
Published: December 2022

Thanks to specific physico-chemical properties, drug delivery systems based on nanoparticles have proven to effectively transport delicate molecules for therapeutic purposes, protecting them from degradation, increasing their stability in the blood circulation and allowing to convey and release the transported substances in specific areas of the body. Nanoparticles obtained from biopolymers for applications in medicine and pharmaceutics have become particularly popular in recent years due to the enormous research effort in the field of vaccines to respond to the pandemic emergency. Among the various types of biopolymers used to produce nanoparticles for therapeutics, lipids have characteristics that make them biocompatible, with low toxicity and ease of clearance. They can be synthesized by designing their characteristics according to the foreseen administration path, or to the target of the transported drug. The analytical methods mostly used to evaluate the characteristics of lipid nanosytems for drug delivery involve studying their effects on cells, in vitro and in vivo. Although it is often considered a “niche technique“ for research in the bio-related sciences, Small Angle X-ray Scattering (SAXS) is a versatile tool to study the structure of nanosystems based on lipids, both ex situ and in situ. Therefore, it allows to evaluate both the effect of the different synthesis parameters and of the exposure of lipid nanoparticles to physiological conditions, which is of fundamental importance to design efficient drug delivery systems. In this mini-review, we will report some recent examples of characterization and design of nanoparticles based on lipids, where SAXS has been a fundamental step both to guide the synthesis of nanomaterials with tailored characteristics, and to understand the interaction between nanomaterials and cells.
Astatine-211-Labeled Gold Nanoparticles for Targeted Alpha-Particle Therapy via Intravenous Injection
Authors: Huang Xuhao , Kaneda-Nakashima Kazuko , Kadonaga Yuichiro , Kabayama Kazuya , Shimoyama Atsushi , Ooe Kazuhiro , Kato Hiroki , Toyoshima Atsushi , Shinohara Atsushi , Haba Hiromitsu , Wang Yang , Fukase Koichi
Published: December 2022

Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. 211At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. In this study, we investigated the intravenous injection of 211At-labeled gold nanoparticles (AuNPs) for targeted alpha-particle therapy (TAT). Different kinds of surface-modified gold nanoparticles can be labeled with 211At in high radiochemical yield in 5 min, and no purification is necessary. The in vivo biodistribution results showed the accumulation of 5 nm 211At-AuNPs@mPEG at 2.25% injection dose per gram (% ID/g) in tumors within 3 h via the enhanced permeability and retention (EPR) effect. Additionally, we observed a long retention time in tumor tissues within 24 h. This is the first study to demonstrate the anti-tumor efficacy of 5 nm 211At-AuNPs@mPEG that can significantly suppress tumor growth in a pancreatic cancer model via intravenous administration. AuNPs are satisfactory carriers for 211At delivery, due to simple and efficient synthesis processes and high stability. The intravenous administration of 5 nm 211At-AuNPs@mPEG has a significant anti-tumor effect. This study provides a new framework for designing nanoparticles suitable for targeted alpha-particle therapy via intravenous injection.
Silk-Elastin-like Polymers for Acute Intraparenchymal Treatment of the Traumatically Injured Spinal Cord: A First Systematic Experimental Approach
Authors: González Pau , González-Fernández Carlos , Maqueda Alfredo , Pérez Virginia , Escalera-Anzola Sara , Rodríguez de Lope Ángel , Arias Francisco Javier , Girotti Alessandra , Rodríguez Francisco Javier
Published: December 2022

Despite the promising potential of hydrogel-based therapeutic approaches for spinal cord injury (SCI), the need for new biomaterials to design effective strategies for SCI treatment and the outstanding properties of silk-elastin-like polymers (SELP), the potential use of SELPs in SCI is currently unknown. In this context, we assessed the effects elicited by the in vivo acute intraparenchymal injection of an SELP named (EIS)2-RGD6 in a clinically relevant model of SCI. After optimization of the injection system, the distribution, structure, biodegradability, and cell infiltration capacity of (EIS)2-RGD6 were assessed. Finally, the effects exerted by the (EIS)2-RGD6 injection—in terms of motor function, myelin preservation, astroglial and microglia/macrophage reactivity, and fibrosis—were evaluated. We found that (EIS)2-RGD6 can be acutely injected in the lesioned spinal cord without inducing further damage, showing a widespread distribution covering all lesioned areas with a single injection and facilitating the formation of a slow-degrading porous scaffold at the lesion site that allows for the infiltration and/or proliferation of endogenous cells with no signs of collapse and without inducing further microglial and astroglial reactivity, as well as even reducing SCI-associated fibrosis. Altogether, these observations suggest that (EIS)2-RGD6—and, by extension, SELPs—could be promising polymers for the design of therapeutic strategies for SCI treatment.
Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization
Authors: Elbardisy Bassant , Boraie Nabila , Galal Sally
Published: December 2022

Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (w/w) as oil, Labrasol:Poloxamer-407 (2:1) (w/w) as surfactant mixture (Smix) and water. The optimum formulation P2TD resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2TD demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2TD promising for the treatment of pediatric PAH.
Current Update on Transcellular Brain Drug Delivery
Authors: Pawar Bhakti , Vasdev Nupur , Gupta Tanisha , Mhatre Mahi , More Anand , Anup Neelima , Tekade Rakesh Kumar
Published: December 2022

It is well known that the presence of a blood–brain barrier (BBB) makes drug delivery to the brain more challenging. There are various mechanistic routes through which therapeutic molecules travel and deliver the drug across the BBB. Among all the routes, the transcellular route is widely explored to deliver therapeutics. Advances in nanotechnology have encouraged scientists to develop novel formulations for brain drug delivery. In this article, we have broadly discussed the BBB as a limitation for brain drug delivery and ways to solve it using novel techniques such as nanomedicine, nose-to-brain drug delivery, and peptide as a drug delivery carrier. In addition, the article will help to understand the different factors governing the permeability of the BBB, as well as various formulation-related factors and the body clearance of the drug delivered into the brain.
Torsemide Pharmacometrics in Healthy Adult Populations Including CYP2C9 Genetic Polymorphisms and Various Patient Groups through Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling
Authors: Jeong Seung-Hyun , Jang Ji-Hun , Lee Yong-Bok
Published: December 2022

Torsemide is a widely used diuretic in clinical practice. In this study, pharmacokinetic (PK) and pharmacodynamic (PD) simulations of torsemide for various population groups and exposure scenarios were performed through human-scale physiologically-based PK-PD (PBPK-PD) modeling of torsemide. For PBPK-PD modeling of torsemide, invitro and clinical data of torsemide reported previously were used. After exposure to clinical doses of torsemide, observed plasma (or serum) concentration and urine torsemide excretion profiles were used as PK-data, and observed urinary sodium excretion rate was used as PD-data. The model was then extended to take into account physiological and biochemical factors according to different CYP2C9 phenotypes or patient populations. The established model captured various torsemide clinical results well. Differences in torsemide PKs and PDs between patient groups or CYP2C9 genetic polymorphisms were modelologically identified. It was confirmed that degrees of differences in torsemide PKs and PDs by disease groups were greater than those according to different CYP2C9 phenotypes. According to torsemide administration frequency or dose change, it was confirmed that although the difference in plasma PKs between groups (healthy adult and patient groups) could increase to 14.80 times, the difference in PDs was reduced to 1.01 times. Results of this study suggested that it is very important to consider disease groups in the setting of torsemide clinical therapy and that it is difficult to predict PD proportionally with only differences in PKs of torsemide between population groups. The PBPK-PD model established in this study is expected to be utilized for various clinical cases involving torsemide application in the future, enabling optimal drug therapy.
Biosimilars in Oncology: Latest Trends and Regulatory Status
Authors: Joshi Deeksha , Khursheed Rubiya , Gupta Saurabh , Wadhwa Diksha , Singh Thakur Gurjeet , Sharma Sumit , Porwal Sejal , Gauniyal Swati , Vishwas Sukriti , Goyal Sanjay , Gupta Gaurav , Eri Rajaraman D. , Williams Kylie A. , Dua Kamal , Singh Sachin Kumar
Published: December 2022

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe’s worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.
Structural Quasi-Isomerism in Au/Ag Nanoclusters
Authors: Zhang Yifei , Busari Kehinde , Cao Changhai , Li Gao
Published: December 2022

Atomically precise metal nanoclusters are a new kind of nanomaterials that appeared in recent years; a pair of isomer nanoclusters have the same metal types, numbers of metal atoms, and surface-protected organic ligands but different metal atom arrangements. This article summarizes the structure features of isomer nanoclusters and concentrates on synthesis methods that could lead to isomer structure. The pairs of isomer inorganic nanoclusters’ conversion to each other and their applications in catalyst and photoluminescence are also discussed. We found that the structure conversions are relevant to their stability. However, with the same molecule formulas, different atom arrangements significantly influence their performance in applications. Finally, the existing challenges and some personal perspectives for this novel field in the nano-science investigation are proposed. We hope this minireview can offer a reference for researchers interested in inorganic isomer nanoclusters.
Modelling and Design of Holographic Optical Elements for Beam-Coupling Applications for a Range of Incident Beam Angles
Authors: Chakraborty Dipanjan , Georgiev Rosen , Aspell Sinead , Toal Vincent , Naydenova Izabela , Cody Dervil , Martin Suzanne
Published: December 2022

Theoretical modelling has been used to calculate the holographic recording beam angles required in air (at any recording wavelength) to produce a Volume Holographic Optical Element (VHOE) for any defined input and output beam angles. The approach is used to facilitate the design and fabrication of diffractive coupling elements through a holographic process that avoids the use of coupling prisms during recording and will help in the design of recording arrangements that better suit the mass production of low-cost elements, especially those designed for non-normal incidence. In this study, the recording angles needed for a range of recording wavelengths were explored for VHOE couplers designed for input angles (in air) ranging from 0° to −55°. Then, in order to validate the model, holographic recording in Bayfol HX 200 photopolymer at 532 nm was used to fabricate photopolymer VHOE couplers for 633 nm light (−45° input angle in air). Bragg curves obtained experimentally for different probe wavelengths (403 nm, 532 nm and 633 nm) confirm the recording of the desired grating structures to a precision of ±1°, and coupling is demonstrated at 633 nm with a diffraction efficiency of up to 72%. Furthermore, the model is used to identify the origins of some weaker spurious gratings observed alongside the expected ones.