bluuebunny/crossref_metadata_2025 huggingface dataset:
Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation
Authors: Wang Jiawen , Zhao Yuanyuan , Zhai Bingtao , Cheng Jiangxue , Sun Jing , Zhang Xiaofei , Guo Dongyan
Published: September 2023

Background: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. Methods: Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion–ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. Results: Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 μg/cm2. The data from an in vivo pharmacokinetic study showed that the Cmax and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. Conclusions: Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development.
Water-Floating Hydrogel Polymer Microsphere Composites for Application in Hydrological Mining of Cu(II) Ions
Authors: Honciuc Andrei , Solonaru Ana-Maria , Honciuc Mirela
Published: September 2023

Innovative materials and technologies capable of extraction and recovery of technologically relevant metal ions from various water sources, such as lakes, oceans, ponds, or wastewater reservoirs, are in great demand. Polymer beads are among the most well-known solid-phase adsorbents and ion exchangers employed in metal ion recovery. On the other hand, hydrogels are an emerging platform for producing innovative adsorbents, which are environmentally friendly and biocompatible materials. In this work, we take advantage of both technologies and produce a new type of material by loading nanostructured polymer microsphere adsorbent into a PVA matrix to obtain a hydrogel polymer microsphere (HPM) composite in the form of a block. The main role of the poly(4-vinylpyrridine-co-methacrylic acid) microspheres is to adsorb metal ions, such as Cu(II), from model water samples. The secondary role of these microspheres in the hydrogel is to change the hydrogel morphology by softening it and stabilizing it under a foam-like morphology. The foam-like morphology endows these composites with the capability of floating on water surfaces. In this work, we report, for the first time, an HPM composite capable of floating on water surfaces and extracting Cu(II) ions from model water samples. This could enable more environmentally friendly hydrological mining technologies by simply deploying adsorbents on water surfaces for metal ion extraction and recovery, thus eliminating the need for water pumping and mechanical processing steps.
Pixelated Filter Array for On-Chip Polarized Spectral Detection
Authors: Liu Yuechen , Feng Chao , Dong Siyu , Zhu Jingyuan , Wang Zhanshan , Cheng Xinbin
Published: September 2023

On-chip multi-dimensional detection systems integrating pixelated polarization and spectral filter arrays are the latest trend in optical detection instruments, showing broad application potential for diagnostic medical imaging and remote sensing. However, thin-film or microstructure-based filter arrays typically have a trade-off between the detection dimension, optical efficiency, and spectral resolution. Here, we demonstrate novel on-chip integrated polarization spectral detection filter arrays consisting of metasurfaces and multilayer films. The metasurfaces with two nanopillars in one supercell are designed to modulate the Jones matrix for polarization selection. The angle of diffraction of the metasurfaces and the optical Fabry–Perot (FP) cavities determine the spectrum’s center wavelength. The polarization spectral filter arrays are placed on top of the CMOS sensor; each array corresponds to one pixel, resulting in high spectral resolution and optical efficiency in the selected polarization state. To verify the methodology, we designed nine-channel polarized spectral filter arrays in a wavelength range of 1350 nm to 1550 nm for transverse electric (TE) linear polarization. The array has a 10 nm balanced spectral resolution and average peak transmission efficiency of over 75%, which is maintained by utilizing lossless dielectric material. The proposed array can be fabricated using overlay e-beam lithography, and the process is CMOS-compatible. The proposed array enables broader applications of in situ on-chip polarization spectral detection with high efficiency and spectral resolution, as well as in vivo imaging systems.
Simultaneous 3D Construction and Imaging of Plant Cells Using Plasmonic Nanoprobe-Assisted Multimodal Nonlinear Optical Microscopy
Authors: Liu Kun , Lei Yutian , Li Dawei
Published: September 2023

Nonlinear optical (NLO) imaging has emerged as a promising plant cell imaging technique due to its large optical penetration, inherent 3D spatial resolution, and reduced photodamage; exogenous nanoprobes are usually needed for nonsignal target cell analysis. Here, we report in vivo, simultaneous 3D labeling and imaging of potato cell structures using plasmonic nanoprobe-assisted multimodal NLO microscopy. Experimental results show that the complete cell structure can be imaged via the combination of second-harmonic generation (SHG) and two-photon luminescence (TPL) when noble metal silver or gold ions are added. In contrast, without the noble metal ion solution, no NLO signals from the cell wall were acquired. The mechanism can be attributed to noble metal nanoprobes with strong nonlinear optical responses formed along the cell walls via a femtosecond laser scan. During the SHG-TPL imaging process, noble metal ions that crossed the cell wall were rapidly reduced to plasmonic nanoparticles with the fs laser and selectively anchored onto both sides of the cell wall, thereby leading to simultaneous 3D labeling and imaging of the potato cells. Compared with the traditional labeling technique that needs in vitro nanoprobe fabrication and cell labeling, our approach allows for one-step, in vivo labeling of plant cells, thus providing a rapid, cost-effective method for cellular structure construction and imaging.
Toxic Effects of Copper Fungicides on the Development and Behavior of Zebrafish in Early-Life Stages
Authors: Gao Fei , Yuan Zitong , Zhang Lingling , Peng Yiyuan , Qian Kun , Zheng Mingqi
Published: September 2023

Copper-based fungicides have been used to control various plant diseases for more than one hundred years and play very important roles in agriculture. Accumulation of copper in freshwater and environment pose severe threats to human health and the environment. The current study evaluated the developmental and behavioral toxicity of PEG@Cu NCs (copper nanoclusters), Kocide® 3000 (copper hydroxide), and Cu(CH3COO)2 (copper acetate) to zebrafish in early-life stages. The developmental toxicity was evaluated according to the parameters of mortality, hatching rate, autonomous movement and heartbeat of embryos, and body length of larvae. The 9 dpf (days postfertilization)-LC50 (50% lethal concentration) of embryonic mortality was 0.077, 0.174 or 0.088 mg/L, and the 9 dpf-EC50 (effective concentration of 50% embryos hatching) of hatching rate was 0.079 mg/L, 0.21 mg/L and 0.092 mg/L when the embryos were exposed to PEG@Cu NCs, Kocide® 3000 or Cu(CH3COO)2, respectively. Kocide® 3000 and Cu(CH3COO)2 obviously decreased the spontaneous movements, while PEG@Cu NCs had no adverse effects on that of embryos. The reduced heartbeat can return to normal after exposure to PEG@Cu NCs for 96 h, while it cannot recover from Kocide® 3000. In addition, Kocide® 3000 (≥0.2 mg/L), PEG@Cu NCs and Cu(CH3COO)2 with 0.05 mg/L or higher concentration exhibited obvious behavioral toxicity to zebrafish larvae according to the parameters of movement distance, average velocity, absolute sinuosity, absolute turn angle and absolute angular velocity.
Critical Electrospinning Parameters for Synthesis Control of Stabilized Polyacrylonitrile Nanofibers
Authors: Ruiz Rocha Juan Emmanuel , Moreno Tovar Karla Rebeca , Navarro Mendoza Ricardo , Gutiérrez Granados Silvia , Cavaliere Sara , Giaume Domitille , Barboux Philippe , Jaime Ferrer Jesús Salvador
Published: September 2023

Polyacrylonitrile (PAN) fibers are widely used as precursors in the manufacture of high-conducting and mechanically resistant carbon fibers. The modulation of such fibers is carried out through electrospinning. In this work, we show the production and control of the morphology of nanometric-range PAN fibers for their potential use as precursors for high-electrical-conductivity carbon fibers. PAN samples dissolved in dimethylformamide (DMF) were prepared at 6, 10, and 12% w/w, at 15 and 25 kV. The impact of the rotation of the collector drum at 100, 300, and 500 RPM was also studied. It was found that the percentage of PAN in the solution proportionally affects the diameter of the fibers and that the preparation potential affects the morphology. The rotation speed, when increased, decreases the diameter, and it has a negative impact on the morphology. Fibers prepared with 6% w/w at 15 kV and 500 RPM show 90 nm diameters, the smallest diameter of all the samples.
Tsuchime-like Aluminum Film to Enhance Absorption in Ultra-Thin Photovoltaic Cells
Authors: Marus Mikita , Mukha Yauhen , Wong Him-Ting , Chan Tak-Lam , Smirnov Aliaksandr , Hubarevich Aliaksandr , Hu Haibo
Published: September 2023

Ultra-thin solar cells enable materials to be saved, reduce deposition time, and promote carrier collection from materials with short diffusion lengths. However, light absorption efficiency in ultra-thin solar panels remains a limiting factor. Most methods to increase light absorption in ultra-thin solar cells are either technically challenging or costly, given the thinness of the functional layers involved. We propose a cost-efficient and lithography-free solution to enhance light absorption in ultra-thin solar cells—a Tsuchime-like self-forming nanocrater (T-NC) aluminum (Al) film. T-NC Al film can be produced by the electrochemical anodization of Al, followed by etching the nanoporous alumina. Theoretical studies show that T-NC film can increase the average absorbance by 80.3%, depending on the active layer’s thickness. The wavelength range of increased absorption varies with the active layer thickness, with the peak of absolute absorbance increase moving from 620 nm to 950 nm as the active layer thickness increases from 500 nm to 10 µm. We have also shown that the absorbance increase is retained regardless of the active layer material. Therefore, T-NC Al film significantly boosts absorbance in ultra-thin solar cells without requiring expensive lithography, and regardless of the active layer material.
Discovery and Comprehensive Characterization of Novel Circular RNAs of the Apoptosis-Related BOK Gene in Human Ovarian and Prostate Cancer Cells, Using Nanopore Sequencing
Authors: Kontos Christos K. , Hadjichambi Despina , Papatsirou Maria , Karousi Paraskevi , Christodoulou Spyridon , Sideris Diamantis C. , Scorilas Andreas
Published: September 2023

CircRNAs have become a novel scientific research hotspot, and an increasing number of studies have shed light on their involvement in malignant progression. Prompted by the apparent scientific gap in circRNAs from apoptosis-related genes, such as BOK, we focused on the identification of novel BOK circRNAs in human ovarian and prostate cancer cells. Total RNA was extracted from ovarian and prostate cancer cell lines and reversely transcribed using random hexamer primers. A series of PCR assays utilizing gene-specific divergent primers were carried out. Next, third-generation sequencing based on nanopore technology followed by extensive bioinformatics analysis led to the discovery of 23 novel circRNAs. These novel circRNAs consist of both exonic and intronic regions of the BOK gene. Interestingly, the exons that form the back-splice junction were truncated in most circRNAs, and multiple back-splice sites were found for each BOK exon. Moreover, several BOK circRNAs are predicted to sponge microRNAs with a key role in reproductive cancers, while the presence of putative open reading frames indicates their translational potential. Overall, this study suggests that distinct alternative splicing events lead to the production of novel BOK circRNAs, which could come into play in the molecular landscape and clinical investigation of ovarian and prostate cancer.
Polysaccharide from Smilax glabra Roxb Mitigates Intestinal Mucosal Damage by Therapeutically Restoring the Interactions between Gut Microbiota and Innate Immune Functions
Authors: Abaidullah Muhammad , La Shaokai , Liu Mengqi , Liu Boshuai , Cui Yalei , Wang Zhichang , Sun Hao , Ma Sen , Shi Yinghua
Published: September 2023

Smilax glabra Roxb (S. glabra) is a conventional Chinese medicine that is mainly used for the reliability of inflammation. However, bioactive polysaccharides from S. glabra (SGPs) have not been thoroughly investigated. Here, we demonstrate for the first time that SGPs preserve the integrity of the gut epithelial layer and protect against intestinal mucosal injury induced by dextran sulfate sodium. Mechanistically, SGPs mitigated colonic mucosal injury by restoring the association between the gut flora and innate immune functions. In particular, SGPs increased the number of goblet cells, reduced the proportion of apoptotic cells, improved the differentiation of gut tight junction proteins, and enhanced mucin production in the gut epithelial layer. Moreover, SGPs endorsed the propagation of probiotic bacteria, including Lachnospiraceae bacterium, which strongly correlated with decreased pro-inflammatory cytokines via the blocking of the TLR-4 NF-κB and MyD88 pathways. Overall, our study establishes a novel use of SGPs for the treatment of inflammatory bowel disease (IBD)-associated mucosal injury and provides a basis for understanding the therapeutic effects of natural polysaccharides from the perspective of symbiotic associations between host innate immune mechanisms and the gut microbiome.
Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis
Authors: Chrastina Martin , Dráfi František , Pružinská Katarína , Poništ Silvester , Kamga Kevine Silihe , Khademnematolahi Sasan , Bilka František , Novák Peter , Pašková Ľudmila , Bauerová Katarína
Published: September 2023

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron—SF) is also known for its anti-inflammatory effects. Therefore, we decided to investigate the potential benefit of SF in monotherapy via two doses (SF1—25 mg/kg of b.w.; SF2—50 mg/kg of b.w.) and in combination with MTX (0.3 mg/kg of b.w., twice a week) using adjuvant arthritis in rats. To evaluate these therapeutic settings, we used biometric, immunological, and biochemical parameters, as well as the relative gene expression of the mRNA in the liver. Our results showed a statistically significant increase in the experimental animals’ body weight and the arthritic score (AS) on day 14 for monotherapy with SF1 and SF2. The change of hind paw volume (CHPV) was significant only for SF2 monotherapy on the 14th day of the experiment. A combination of SF1 and SF2 with MTX significantly modulated all the biometric parameters during the experimental period. Additionally, AS and CHPV improved considerably compared to MTX monotherapy on day 21. Furthermore, all monotherapies and combination therapies were significant for the biochemical parameter γ-glutamyl transferase (GGT) in the joint. GGT activity in the spleen was less pronounced; only MTX in combination with SF1 significantly modified this parameter. The higher dose of SF monotherapy (SF2) was similarly significant with respect to immunological parameters, such as plasmatic IL-17A, IL-1β, and MMP-9 on day 21. The combination of both doses of SF with MTX significantly improved these immunological parameters, except for C-reactive protein (CRP), which was influenced only by the higher dose of SF2 in combination with MTX in plasma at the end of the experiment. A different effect was found for the relative expression of CD36 mRNA, where only SF1 significantly decreased gene expression in the liver. However, the relative gene mRNA expression of IL-1β in the liver was significantly reduced by the SF monotherapies and the combination of both SF doses with MTX. Our findings showed SF’s partial antiarthritic and anti-inflammatory potential in monotherapy, but the effect was stronger in combination with MTX.
Pertinence of Salt-Related Knowledge and Reported Behaviour on Salt Intake in Adults: A Cross-Sectional Study
Authors: Marakis Georgios , Marques Domingues Ana , Crispo Anna , Magriplis Emmanuella , Vasara Eleni , Kontopoulou Lamprini , Triantafyllou Christos , Skepastianos Petros , Papadopoulou Sousana K. , Rodopaios Nikolaos E. , Hassapidou Maria , Zampelas Antonis , Cappuccio Francesco P. , Breda João
Published: September 2023

The association between salt-related knowledge, attitude, behaviour (KAB) and actual salt consumption in Greek adults is uncertain. This study investigates the correlation between salt intake, gauged by 24-h urinary sodium excretion, with salt-related KAB. It further explores how socio-demographic factors influence these behaviors. Salt consumption was evaluated using a 24-h urinary sodium test, and compared to self-reported KAB data. Knowledge and behavior scores related to salt were computed. An overall cohort-adjusted model examined the relationship between daily salt consumption, knowledge and behavior scores, and certain covariates. Through the stratification by the cohort random effect, two models were established (Cohort I Adults; Cohort II Students) examining the same relationships of the overall cohort model. 463 Greek adults participated. The average salt intake was 9.54 g/day, nearly double the WHO recommendation. Significant differences in knowledge scores were noted based on sex, age, education, and BMI. A trend suggesting lower discretionary salt use with increased salt intake was observed (p = 0.06). However, comprehensive analysis revealed no direct correlation between salt intake and either knowledge (p = 0.562) or behavior scores (p = 0.210). The results emphasize the need for food product reforms by industry stakeholders and accelerated efforts towards reducing salt intake.
A Translational Approach to Increase Pulse Intake and Promote Public Health through Developing an Extension Bean Toolkit
Authors: Didinger Chelsea , Bunning Marisa , Thompson Henry
Published: September 2023

Practical, affordable solutions need to be implemented to address global challenges confronting human and environmental health. Despite a myriad of benefits for people and the planet, beans and other pulses (e.g., chickpeas, cowpeas, dry peas, lentils) are under-consumed. To better understand consumer concerns and interests, a Food Habits Survey was conducted and the findings were incorporated into the Colorado State University Extension Bean Toolkit. Guided by the Information-Motivation-Behavioral Skills model, the toolkit included informational social media posts, cooking guidance, and an online class. A convenience sample of participants was recruited through Extension and university networks. After class participation, significant gains in knowledge of pulse nutrition, versatility, and cooking were observed, with an average increase of 1.5 points on a 5-point Likert scale (p < 0.001). Moreover, participants (n = 86) perceived a greater importance of motivators (e.g., nutrition, versatility, environmental benefits) and found barriers (e.g., flatulence, long cooking times, unfamiliarity) to be less discouraging. Most participants reported an intention to eat more pulses, and among those who completed the 1-month follow-up survey, pulse intake frequency increased (p = 0.004). Emphasizing motivating factors while simultaneously mitigating barriers to consumption can help reverse insufficient intake and promote healthy behavior change. Leveraging Extension or similar networks is one way to adopt a translational approach to better reach the public with this information.
Association of Mediterranean Diet Adherence with Sociodemographic, Anthropometric, and Lifestyle Factors during the COVID-19 Pandemic: A Cross-Sectional Study in Greece
Authors: Pavlidou Eleni , Papadopoulou Sousana K. , Mentzelou Maria , Dakanalis Antonios , Vorvolakos Theofanis , Antasouras Georgios , Spanoudaki Maria , Pandi Aimilia-Lynn , Serdari Aspasia , Chrysafi Maria , Dimoliani Sofia , Giaginis Constantinos
Published: September 2023

Background: The COVID-19 pandemic has negatively affected several aspects of people’s lifestyle worldwide. Healthy dietary patterns and their bioactive components may improve or even co-treat the negative impacts of the COVID-19 pandemic in several aspects of people’s lifestyle and mental health in daily life. The aim of this survey is to evaluate the potential effect of Mediterranean diet (MD) adherence against COVID-19-induced complications. Methods: This is a cross-sectional survey performed on 3721 adults aged between 18 and 65 years old, which aims to evaluate the potential association of MD adherence with multiple sociodemographic, anthropometric, and lifestyle factors during the COVID-19 pandemic period. Results: This study has supported evidence that elevated MD compliance was independently related to female gender, better economic status, no smoking, increased risk of abdominal obesity, higher physical activity levels, greater prevalence of adequate sleep quality, better quality of life, and reduced probability of anxiety and depression during the COVID-19 pandemic by adjusting for multiple confounders. Conclusions: MD compliance may improve or even co-treat the negative impacts of the COVID-19 pandemic in several aspect of people’s lifestyle in daily life. Further research is strongly recommended exploring the possible beneficial effects of the MD against COVID-19 lifestyle complications in daily life.
Brucella abortus Rough-Type Mutant Induces Ferroptosis and More Oxidative Stress in Infected Macrophages
Authors: Hu Hai , Zhang Guangdong , Tian Mingxing , Guan Xiang , Yin Yi , Ding Chan , Yu Shengqing
Published: September 2023

Brucella is an intracellular parasitic bacterium that uses multiple strategies to evade the host’s defense mechanisms. However, how Brucella manipulates the host-induced oxidative stress and relevant biological processes are still poorly understood. In this study, a comparative transcriptome assay of macrophages infected with Brucella abortus S2308 and its rough mutant RB14 was performed to investigate the differentially expressed genes which might be associated with the pathogenic mechanism of Brucella. Our results showed that numerous host pro-oxidative and antioxidative stress genes were differentially expressed in macrophages infected with B. abortus S2308 and mutant RB14 at 4, 8, 24, and 48 h post-infection. Interestingly, we found that several ferroptosis-associated genes were differentially expressed during B. abortus RB14 infection. Moreover, we found that the rough mutant RB14-induced macrophage death was associated with reduced levels of host glutathione and glutathione peroxidase 4, together with increased free iron, lipid peroxidation, and ROS, all of which are important hallmarks of ferroptosis. The ferroptosis occurring during infection with RB14 was reduced by treatment with the inhibitor ferrostatin-1. However, B. abortus S2308 infection did not induce these hallmarks of ferroptosis. Taken together, our results demonstrate that ferroptosis is involved in rough B. abortus infection. Investigating how Brucella manipulates oxidative stress and ferroptosis in its host will be helpful to clarify the pathogenicity of B. abortus.
LipL41 and LigA/LigB Gene Silencing on a LipL32 Knockout Leptospira interrogans Reveals the Impact of Multiple Mutations on Virulence
Authors: Fernandes Luis Guilherme V. , Foltran Bruno B. , Teixeira Aline F. , Nascimento Ana Lucia Tabet Oller
Published: September 2023

Leptospirosis is a global zoonosis caused by pathogenic bacteria of the genus Leptospira. The application of the CRISPR/Cas9 system has facilitated the generation of mutants and subsequent evaluation of phenotypes. Since DNA breaks induced by RNA-guided Cas9 nuclease are lethal to Leptospira, different methodologies were implemented to overcome this limitation. Initially, CRISPR interference (CRISPRi) was employed to create knockdown mutants, utilizing a catalytically inactive Cas9 (dCas9). Subsequently, the co-expression of CRISPR/Cas9 and a DNA repair system from Mycobacterium smegmatis enabled the generation of scarless knockout mutants. We eliminated plasmids from the lipL32 knockout L. interrogans strain and further achieved multiple gene mutations via gene silencing in this knockout background. Strains lacking both LipL41 and LipL32 and LigA, LigB, and LipL32, were evaluated. The absence of proteins LipL32 and LipL41 had no effect on leptospiral virulence. On the other hand, mutants lacking LigA, LigB, and LipL32 were unable to cause acute disease. The expanded apparatus for genetic manipulation of pathogenic leptospires via the CRISPR/Cas9 system has allowed the evaluation of multiple mutations upon leptospiral virulence. This work shows that LipL32 and LipL41 are not required for acute disease and consolidates LigA and LigB proteins as virulence factors.
Natural History and Hepatitis B Virus Surface Antigen (HBsAg) Spontaneous Seroclearance in Hepatitis B Virus e-Antigen (HBeAg)-Negative Patients with Inactive Chronic Infection: A Multicenter Regional Study from South Italy
Authors: Barone Michele , Iannone Andrea , Mezzapesa Martino , Milella Michele , Di Gennaro Francesco , Niro Grazia , Cotugno Rosa , Cozzolongo Raffaele , Mennea Giuseppe , Rendina Maria , Di Leo Alfredo
Published: September 2023

Spontaneous HBsAg seroclearance has been mainly studied in populations from Asia, Australia, the Pacific Islands, and Polynesia. For the first time, we evaluated the spontaneous HBsAg seroclearance and its possible associated factors and the risk of disease progression in HBeAg-negative patients with inactive infection all coming from the same region in South Italy. In this multicenter retrospective study, 146 patients were selected after 18 months of observation and followed for a median of 82 months (IQR 60–107). For our analyses, they were divided into three groups based on their HBsAg levels: <100 IU/mL, 100–1000 IU/mL, and >1000 IU/mL. Crude and adjusted hazard ratios (HRs) for HBsAg seroclearance were determined. During the follow-up period, three patients (2.0%) showed a disease progression with an increased liver stiffness, whereas 17 (11.6%) cleared the HBsAg. Patients with HBsAg levels <100 IU/mL had the highest probability of HBsAg seroclearance compared to the other two groups (p = 0.009). In the multivariate analysis, the HBsAg level <100 IU/mL was the only parameter independently associated with HBsAg seroclearance (adjusted HR = 3.53; CI 1.29–9.69; p = 0.01). In patients with chronic HBV inactive infection, HBsAg levels <100 IU/mL predicted the highest probability of HBsAg seroclearance.
Special Issue “Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions”
Authors: Nag Okhil K. , Delehanty James B.
Published: September 2023

Over the past several decades, nanoparticles (NPs) have shown promising capabilities in the field of medicine for their applications as vehicles for targeted drug delivery [...]
A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation
Authors: Vichare Riddhi , Crelli Caitlin , Liu Lu , Das Amit Chandra , McCallin Rebecca , Zor Fatih , Kulahci Yalcin , Gorantla Vijay S. , Janjic Jelena M.
Published: September 2023

Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf®) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which leads to erratic bioavailability and toxicity. Local delivery of TAC directly into the graft, instead of systemic delivery, can improve safety, efficacy, and tolerability. Macrophages have emerged as promising therapeutic targets as their increased levels correlate with an increased risk of organ rejection and a poor prognosis post-transplantation. Here, we present a locally injectable drug delivery platform for macrophages, where TAC is incorporated into a colloidally stable nanoemulsion and then formulated as a reversibly thermoresponsive, pluronic-based nanoemulgel (NEG). This novel formulation is designed to undergo a sol-to-gel transition at physiological temperature to sustain TAC release in situ at the site of local application. We also show that TAC-NEG mitigates the release of proinflammatory cytokines and nitric oxide from lipopolysaccharide (LPS)-activated macrophages. To the best of our knowledge, this is the first TAC-loaded nanoemulgel with demonstrated anti-inflammatory effects on macrophages in vitro.
The Neuroprotective Effects of Flavonoid Fisetin against Corticosterone-Induced Cell Death through Modulation of ERK, p38, and PI3K/Akt/FOXO3a-Dependent Pathways in PC12 Cells
Authors: Chang Pei-Rong , Liou Je-Wen , Chen Pei-Yi , Gao Wan-Yun , Wu Chia-Ling , Wu Ming-Jiuan , Yen Jui-Hung
Published: September 2023

The overactive hypothalamic–pituitary–adrenal (HPA) axis is believed to trigger the overproduction of corticosterone, leading to neurotoxicity in the brain. Fisetin is a flavonoid commonly found in fruits and vegetables. It has been suggested to possess various biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study aims to explore the potential neuroprotective properties of fisetin against corticosterone-induced cell death and its underlying molecular mechanism in PC12 cells. Our results indicate that fisetin, at concentrations ranging from 5 to 40 μM, significantly protected PC12 cells against corticosterone-induced cell death. Fisetin effectively reduced the corticosterone-mediated generation of reactive oxygen species (ROS) in PC12 cells. Fisetin treatments also showed potential in inhibiting the corticosterone-induced apoptosis of PC12 cells. Moreover, inhibitors targeting MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K) were found to significantly block the increase in cell viability induced by fisetin in corticosterone-treated cells. Consistently, fisetin enhanced the phosphorylation levels of ERK, p38, Akt, and c-AMP response element-binding protein (CREB) in PC12 cells. Additionally, it was found that the diminished levels of p-CREB and p-ERK by corticosterone can be restored by fisetin treatment. Furthermore, the investigation of crosstalk between ERK and CREB revealed that p-CREB activation by fisetin occurred through the ERK-independent pathway. Moreover, we demonstrated that fisetin effectively counteracted the corticosterone-induced nuclear accumulation of FOXO3a, an apoptosis-triggering transcription factor, and concurrently promoted FOXO3a phosphorylation and its subsequent cytoplasmic localization through the PI3K/Akt pathway. In conclusion, our findings indicate that fisetin exerts its neuroprotective effect against corticosterone-induced cell death by modulating ERK, p38, and the PI3K/Akt/FOXO3a-dependent pathways in PC12 cells. Fisetin emerges as a promising phytochemical for neuroprotection.
The Amorphous Solid Dispersion of Chrysin in Plasdone® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats
Authors: Wang Chenhui , Liu Xiaowei , Zhao Ruihan , Yang Meiqing , Liu Wenqian , Dai Qiuyang , Bao Xiaofeng , Chen Yong , Ma Jun
Published: September 2023

Chrysin is a flavonoid with various biological activities. However, its low water solubility and strong metabolism render its oral bioavailability rather poor. This study aimed to develop a stable solid dispersion formulation of chrysin to improve the dissolution of chrysin, so as to increase its oral bioavailability and improve its antihyperlipidemic activities. A solid dispersion of chrysin was prepared using a solvent evaporation method, with Plasdone® S630 as the hydrophilic carrier. The formulations were characterized via X-ray diffraction, in vitro dissolution studies, and stability studies. An in-situ perfusion model was used to evaluate the absorption rates. Plasma pharmacokinetics and antihyperlipidemic performance after the oral administration of the chrysin formulations were investigated in rats. It was found that the solid dispersion of chrysin prepared using the drug–polymer mass ratio of 1:6 can form the optimized formulation. X-ray diffraction results showed that the chrysin was in an amorphous state in this optimized formulation. The cumulative release percentage of the optimized solid dispersion of chrysin at pH 1.2 and pH 6.8 was elevated to above 90% within 24 h, indicating that the formulation could enhance the dissolution rates of chrysin. Stability studies showed that the optimized formulation presented acceptable long-term storage stability, but it was susceptible to high temperature and humidity. The solid dispersion of chrysin showed higher absorption rates in the in-situ perfusion model. Pharmacokinetic studies revealed that Cmax and AUC after the intragastric administration of solid dispersion of chrysin were appreciably higher than those resulting from chrysin suspension. The oral bioavailability of the solid dispersion of chrysin was 41 times higher than that of chrysin suspension. Pharmacological studies suggested that the solid dispersion of chrysin was more powerful than chrysin raw material in improving biochemical indicators in the hyperlipidemic model in rats. This study reveals the potential use of a novel oral formulation of chrysin to reduce the currently required high dose.
Notifications and Health Consequences of Unauthorized Pharmaceuticals in Food Supplements
Authors: Amidžić Maja , Banović Fuentes Jelena , Banović Jovica , Torović Ljilja
Published: September 2023

Health concerns associated with the consumption of food supplements rise in parallel with the rise in the popularity and market availability of these products. In pursuit of data related to the unauthorized presence of pharmaceuticals in food supplements, the Rapid Alert System for Food and Feed (RASFF) database was searched for the 2011–2022 period. The most “popular” pharmaceuticals for the adulteration of food supplements were phosphodiesterase-5 inhibitors (235 records); anorexics and laxatives (76), including sibutramine and its active metabolite N-didesmethyl sibutramine, phenolphthalein and 2,4-dinitrophenol; stimulants, among which 1,3-dimethylamine (97), and synephrine (53) were the most numerous; nootropic drugs (24); anabolics and prohormones (16); and cannabinoid cannabidiol (14) (pending authorization as a novel food ingredient). Over 65% of notifications of interest were classified as serious risks, and over 80% of these were alert or border rejection notifications, mainly generated as a result of official control on the market. The alarming number of RASFF notifications should be considered a public health issue, demanding clear and targeted recommendation for action for the legislature and authorities. A harmonized nutrivigilance system should be considered as a tool to detect and scrutinize the adverse health effects of food supplements, along with measures to improve their safety, quality, and testing.
Prudence, Rules, and Regulative Epistemology
Authors: García-Valdecasas Miguel , Milburn Joe
Published: September 2023

Following Ballantyne, we can distinguish between descriptive and regulative epistemology. Whereas descriptive epistemology analyzes epistemic categories such as knowledge, justified belief, or evidence, regulative epistemology attempts to guide our thinking. In this paper, we argue that regulative epistemologists should focus their attention on what we call epistemic prudence. Our argument proceeds as follows: First, we lay out an objection to virtue-based regulative epistemology that is analogous to the no-guidance objection to virtue ethics. According to this objection, virtue-based regulative epistemology cannot offer us useful guidance in our deliberations, because an abstract knowledge of virtue does not tell us what we should do here and now, especially in hard cases. We respond to this objection by showing that our making good epistemic decisions cannot simply be a matter of our following the right epistemic rules. In order to reliably inquire and deliberate well, we need epistemic prudence. Thus, while virtue-based regulative epistemology fails to determine how we should inquire and resolve deliberation here and now, this is also true of norm-based regulative epistemology. The upshot of this argument is that regulative epistemologists should focus their attention on understanding the nature of epistemic prudence and on understanding how we can promote its development in ourselves and others.
Measurement-Based Control of Quantum Entanglement and Steering in a Distant Magnomechanical System
Authors: Tan Huatang
Published: September 2023

In this paper, we propose a scheme for measurement-based control of hybrid Einstein–Podolsky–Rosen (EPR) entanglement and steering between distant macroscopic mechanical oscillator and yttrium iron garnet (YIG) sphere in a system of an electromechanical cavity unidirectionally coupled to an electromagnonical cavity. We reveal that when the output of the electromagnonical cavity is continuously monitored by homodyne detection, not only the phonon–magnon entanglement and steering but also the purities of the phononic, magnonic and phonon–magnon states are considerably enhanced. We also find that the measurement can effectively retrieve the magnon-to-phonon steering, which is not yet obtained in the absence of the measurement. We show that unconditional phonon–magnon entanglement and steering can be achieved by introducing indirect feedback to drive the magnon and mechanical subsystems. The long-distance macroscopic hybrid entanglement and steering can be useful for, e.g., fundamental tests for quantum mechanics and quantum networks.
Efficiency Dependence of Radiation-Assisted Ceramic Synthesis Based on Metal Oxides and Fluorides on Initial Powder Particle Sizes
Authors: Lisitsyn Victor , Polisadova Elena , Lisitsyna Liudmila , Tulegenova Aida , Denisov Igor , Golkovski Mikhail
Published: September 2023

The study is devoted to investigating the efficiency dependence of radiation-assisted ceramic synthesis based on metal oxides and fluorides on initial powder particle sizes. The synthesis was performed for 30 series of ceramic samples, including MgO, Al2O3, ZnO, ZrO2, MgF2, and complex compositions: cerium-activated yttrium-aluminum garnet (Y3Al5O12), spinel AlMgO4, and tungstate MgWO4. The synthesis efficiency was evaluated on the mixture weight magnitude losses, morphology, and relative weight of the obtained ceramic samples. Based on the analysis of the synthesis results and measuring the particle distribution spectra of the initial materials, the criteria for selecting the initial materials were established, and possible explanations for the correlation between synthesis efficiency and the initial materials morphology were proposed.
Allelopathic Effect of Aqueous Extracts of Grass Genotypes on Eruca Sativa L.
Authors: Motalebnejad Masoud , Karimmojeni Hassan , Majidi Mohammad Mahdi , Mastinu Andrea
Published: September 2023

The aim of the current research is to evaluate the allelopathic activity of fifty grass genotypes from different species and to identify phenolic compounds in the genotypes that have the highest allelopathic activity and inhibitory effect on Eruca sativa L. (Rocket). Aqueous extract was prepared from the leaves of grass genotypes in different concentrations and its effect on germination and growth of E. sativa L. was measured. According to the results, the type of genotype and the concentration of the extract significantly decreased the percentage of germination, hypocotyl length, radicle length, and dry weight of E. sativa L. seedlings. Increasing the concentration of the extract resulted in a decrease in germination and growth of seedlings. The genotypes of Festulolium (Festulolium) (GR 5009, GR 1692, GR 5004) had the most inhibitory effect on the growth of E. sativa L. Also, among the genotypes studied, two genotypes (DG-M) and (DG-P) of Dactylis glomerata L. (orchardgrass) species showed the least allelopathic activity. The results of HPLC-MS indicated nine phenolic compounds including caffeic acid, syringic acid, vanillic acid, p-coumaric acid, ferulic acid, apigenin acid, chlorogenic acid, 4-hydroxybenzoic acid, and gallic acid. The phenolic compound most present in the aqueous extract was caffeic acid. However, phenolic compounds derived from Festulolium genotypes showed the greatest allelopathic action on the growth parameters of E. sativa L. The aqueous extracts of the Festulolium genotypes can be considered valid systems of sustainable weed control thanks to the phytocomplex rich in phenols.
Alternative Tissue Sampling for Improved Detection of Candidatus Liberibacter asiaticus
Authors: Hajeri Subhas , Olkowski Sandra , Kumagai Lucita , McRoberts Neil , Yokomi Raymond K.
Published: September 2023

Early detection and prompt response are key factors in the eradication of ‘huanglongbing’ (HLB) in California. Currently, qPCR testing of leaf tissue guides the removal of infected trees. However, because of the uneven distribution of ‘Candidatus Liberibacter asiaticus’ (CLas) in an infected tree and asymptomatic infection, selecting the best leaves to sample, from a mature tree with more than 200,000 estimated leaves, is a major hurdle for timely detection. The goal of this study was to address this issue by testing alternative tissues that might improve the CLas detection rate. Using two years of field data, old and young leaves, peduncle bark of fruit, and feeder roots were evaluated for the presence of CLas. Quadrant-peduncle (Q-P) tissue sampling consistently resulted in better CLas detection than any other tissue type. Q-P samples had a 30% higher qPCR positivity rate than quadrant-leaf (Q-L) samples. No significant seasonal patterns were observed. Roots and single peduncles had similar detection rates; both were higher than single leaves or Q-L samples. If symptoms were used to guide sampling, 30% of infected trees would have been missed. Taken together, these results suggest that Q-P tissue sampling is the optimal choice for improved CLas detection under California growing conditions.
Identification and Expression Analysis of EPSPS and BAR Families in Cotton
Authors: Li Zhao , Zhang Zhen , Liu Yinbo , Ma Yuanqi , Lv Xing , Zhang Dongmei , Gu Qishen , Ke Huifeng , Wu Liqiang , Zhang Guiyin , Ma Zhiying , Wang Xingfen , Sun Zhengwen
Published: September 2023

Weeds seriously affect the yield and quality of crops. Because manual weeding is time-consuming and laborious, the use of herbicides becomes an effective way to solve the harm caused by weeds in fields. Both 5-enolpyruvyl shikimate-3-phosphate synthetase (EPSPS) and acetyltransferase genes (bialaphos resistance, BAR) are widely used to improve crop resistance to herbicides. However, cotton, as the most important natural fiber crop, is not tolerant to herbicides in China, and the EPSPS and BAR family genes have not yet been characterized in cotton. Therefore, we explore the genes of these two families to provide candidate genes for the study of herbicide resistance mechanisms. In this study, 8, 8, 4, and 5 EPSPS genes and 6, 6, 5, and 5 BAR genes were identified in allotetraploid Gossypium hirsutum and Gossypium barbadense, diploid Gossypium arboreum and Gossypium raimondii, respectively. Members of the EPSPS and BAR families were classified into three subgroups based on the distribution of phylogenetic trees, conserved motifs, and gene structures. In addition, the promoter sequences of EPSPS and BAR family members included growth and development, stress, and hormone-related cis-elements. Based on the expression analysis, the family members showed tissue-specific expression and differed significantly in response to abiotic stresses. Finally, qRT-PCR analysis revealed that the expression levels of GhEPSPS3, GhEPSPS4, and GhBAR1 were significantly upregulated after exogenous spraying of herbicides. Overall, we characterized the EPSPS and BAR gene families of cotton at the genome-wide level, which will provide a basis for further studying the functions of EPSPS and BAR genes during growth and development and herbicide stress.