bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson’s Disease
Authors: Mallamaci Rosanna , Musarò Debora , Greco Marco , Caponio Antonello , Castellani Stefano , Munir Anas , Guerra Lorenzo , Damato Marina , Fracchiolla Giuseppe , Coppola Chiara , Cardone Rosa Angela , Rashidi Mehdi , Tardugno Roberta , Sergio Sara , Trapani Adriana , Maffia Michele
Published: April 2024

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood–brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187–297 nm, zeta potential values in the range of −4.1–−9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.
Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease
Authors: Wu Xiuyuan , Ze Xiaotong , Qin Shuai , Zhang Beiyu , Li Xinnan , Gong Qi , Zhang Haiyan , Zhu Zheying , Xu Jinyi
Published: April 2024

Alzheimer’s disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (4, AChE: IC50 = 0.223 μM) with pyrimidone compound 5 (GSK-3β: IC50 = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3β (GSK-3β). The optimal compound 18a possessed potent dual AChE/GSK-3β inhibition (AChE: IC50 = 0.047 ± 0.002 μM, GSK-3β: IC50 = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure–activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs.
A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam
Authors: Nguyen Hung Xuan , Nguyen Xuyen Thi , Mai Hang Thi Hong , Nguyen Huong Thi , Vu Nam Duc , Pham Thao Thi Phuong , Nguyen Trung Quang , Nguyen Dat Tien , Duong Nam Thanh , Hoang Anh Le Tuan , Nguyen Tung Ngoc , Le Nhan Van , Dao Ha Viet , Ngoc Minh Truong , Bui Minh Quang
Published: April 2024

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.
Modeling Studies of the Mechanism of Context-Dependent Bidirectional Movements of Kinesin-14 Motors
Authors: Xie Ping
Published: April 2024

Kinesin-14s, a subfamily of the large superfamily of kinesin motor proteins, function mainly in spindle assembly and maintenance during mitosis and meiosis. KlpA from Aspergillus nidulans and GiKIN14a from Giardia intestinalis are two types of kinesin-14s. Available experimental results puzzlingly showed that while KlpA moves preferentially toward the minus end in microtubule-gliding setups and inside parallel microtubule overlaps, it moves preferentially toward the plus end on single microtubules. More puzzlingly, the insertion of an extra polypeptide linker in the central region of the neck stalk switches the motility direction of KlpA on single microtubules to the minus end. Prior experimental results showed that GiKIN14a moves preferentially toward the minus end on single microtubules in either tailless or full-length forms. The tail not only greatly enhances the processivity but also accelerates the ATPase rate and velocity of GiKIN14a. The insertion of an extra polypeptide linker in the central region of the neck stalk reduces the ATPase rate of GiKIN14a. However, the underlying mechanism of these puzzling dynamical features for KlpA and GiKIN14a is unclear. Here, to understand this mechanism, the dynamics of KlpA and GiKIN14a were studied theoretically on the basis of the proposed model, incorporating potential changes between the kinesin head and microtubule, as well as the potential between the tail and microtubule. The theoretical results quantitatively explain the available experimental results and provide predicted results. It was found that the elasticity of the neck stalk determines the directionality of KlpA on single microtubules and affects the ATPase rate and velocity of GiKIN14a on single microtubules.
An Evaluation of ¡Haz Espacio Para Papi!, a Culturally Tailored Nutrition and Physical Activity Pilot Program for Mexican-Heritage Fathers
Authors: Vahk Annika , Monsivais Pablo , Johnson Cassandra M. , Sharkey Joseph R.
Published: April 2024

Fathers are potential leaders of healthy behavior changes in their families. Culturally tailored programs are needed to support behavior changes within families, including Latino families; however, there have been few father-focused nutrition programs for Latino families. This study evaluated the immediate effects of ¡Haz Espacio Para Papi! (Make Room for Daddy!; HEPP), a six-week, father-focused, family-centered program focused on nutrition and physical activity near the Texas–Mexico border. A modified stepped-wedge study design included a treatment group for the HEPP pilot and a wait-listed control group. Pre/post-tests included instant skin carotenoid scores, the self-reported dietary intake of fruits and vegetables (FV), and healthy dietary behavior scores (HDBSs). A 2 × 2 mixed analysis of variance evaluated changes in outcomes across time and between groups for 42 fathers with pre/post-test measures. There were no statistically significant changes in fathers’ VM scores and FV intake across time or between groups. Fathers’ HDBSs increased across time (p ≤ 0.01, 95% CI [0.23, 1.38]). Age, educational attainment, and the number of children living in the household did not have a significant effect on the program outcomes (p > 0.05). The HEPP program may guide the design of future father-focused nutrition interventions aimed at dietary behavior changes.
Dietary Nitrate Metabolism in Porcine Ocular Tissues Determined Using 15N-Labeled Sodium Nitrate Supplementation
Authors: Park Ji Won , Piknova Barbora , Tunau-Spencer Khalid J. , Thomas Samantha M. , Cai Hongyi , Walter Peter J. , Jenkins Audrey , Hellinga David , Parver Leonard M. , Schechter Alan N.
Published: April 2024

Nitrate (NO3−) obtained from the diet is converted to nitrite (NO2−) and subsequently to nitric oxide (NO) within the body. Previously, we showed that porcine eye components contain substantial amounts of nitrate and nitrite that are similar to those in blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. To gain deeper insights into nitrate metabolism in porcine eyes, our current study involved feeding pigs either NaCl or Na15NO3 and assessing the levels of total and 15N-labeled NO3−/NO2− in various ocular tissues. Three hours after Na15NO3 ingestion, a marked increase in 15NO3− and 15NO2− was observed in all parts of the eye; in particular, the aqueous and vitreous humor showed a high 15NO3− enrichment (77.5 and 74.5%, respectively), similar to that of plasma (77.1%) and showed an even higher 15NO2− enrichment (39.9 and 35.3%, respectively) than that of plasma (19.8%). The total amounts of NO3− and NO2− exhibited patterns consistent with those observed in 15N analysis. Next, to investigate whether nitrate or nitrite accumulate proportionally after multiple nitrate treatments, we measured nitrate and nitrite contents after supplementing pigs with Na15NO3 for five consecutive days. In both 15N-labeled and total nitrate and nitrite analysis, we did not observe further accumulation of these ions after multiple treatments, compared to a single treatment. These findings suggest that dietary nitrate supplementation exerts a significant influence on nitrate and nitrite levels and potentially NO levels in the eye and opens up the possibility for the therapeutic use of dietary nitrate/nitrite to enhance or restore NO levels in ocular tissues.
In Vitro Fermentation Shows Polyphenol and Fiber Blends Have an Additive Beneficial Effect on Gut Microbiota States
Authors: Whitman Jordan A. , Doherty Laurel A. , Pantoja-Feliciano de Goodfellow Ida G. , Racicot Kenneth , Anderson Danielle J. , Kensil Katherine , Karl J. Philip , Gibson Glenn R. , Soares Jason W.
Published: April 2024

Polyphenols and fermentable fibers have shown favorable effects on gut microbiota composition and metabolic function. However, few studies have investigated whether combining multiple fermentable fibers or polyphenols may have additive beneficial effects on gut microbial states. Here, an in vitro fermentation model, seeded with human stool combined from 30 healthy volunteers, was supplemented with blends of polyphenols (PP), dietary fibers (FB), or their combination (PPFB) to determine influence on gut bacteria growth dynamics and select metabolite changes. PP and FB blends independently led to significant increases in the absolute abundance of select beneficial taxa, namely Ruminococcus bromii, Bifidobacterium spp., Lactobacillus spp., and Dorea spp. Total short-chain fatty acid concentrations, relative to non-supplemented control (F), increased significantly with PPFB and FB supplementation but not PP. Indole and ammonia concentrations decreased with FB and PPFB supplementation but not PP alone while increased antioxidant capacity was only evident with both PP and PPFB supplementation. These findings demonstrated that, while the independent blends displayed selective positive impacts on gut states, the combination of both blends provided an additive effect. The work outlines the potential of mixed substrate blends to elicit a broader positive influence on gut microbial composition and function to build resiliency toward dysbiosis.
Resources to Support Decision-Making Regarding End-of-Life Nutrition Care in Long-Term Care: A Scoping Review
Authors: Alford Heather , Anvari Nadia , Lengyel Christina , Wickson-Griffiths Abigail , Hunter Paulette , Yakiwchuk Erin , Cammer Allison
Published: April 2024

Resources are needed to aid healthcare providers and families in making end-of-life nutrition care decisions for residents living in long-term care settings. This scoping review aimed to explore what is reported in the literature about resources to support decision-making at the end of life in long-term care. Four databases were searched for research published from 2003 to June 2023. Articles included peer-reviewed human studies published in the English language that reported resources to support decision-making about end-of-life nutrition in long-term care settings. In total, 15 articles were included. Thematic analysis of the articles generated five themes: conversations about care, evidence-based decision-making, a need for multidisciplinary perspectives, honouring residents’ goals of care, and cultural considerations for adapting resources. Multidisciplinary care teams supporting residents and their families during the end of life can benefit from resources to support discussion and facilitate decision-making.
Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments
Authors: Wei Xin , Wang Dan , Liu Jiajia , Zhu Qizhi , Xu Ziming , Niu Jinzhe , Xu Weiping
Published: April 2024

Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, and in vitro experiments were integrated to verify the antidepressant active ingredients in PR and their mechanisms. A total of seven compounds in PR were found to be associated with 45 targets of depression. Preliminarily, DFV docking with cyclooxygenase 2 (COX2) showed good affinity. In vitro, DFV inhibited lipopolysaccharide (LPS)-induced inflammation of BV-2 cells, reversed amoeba-like morphological changes, and increased mitochondrial membrane potential. DFV reversed the malondialdehyde (MDA) overexpression and superoxide dismutase (SOD) expression inhibition in LPS-induced BV-2 cells and decreased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA expression levels in a dose-dependent manner. DFV inhibited both mRNA and protein expression levels of COX2 induced by LPS, and the activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and caspase1 was suppressed, thus exerting an antidepressant effect. This study proves that DFV may be an important component basis for PR to play an antidepressant role.
The Anxiety Burden in Patients with Chronic Intestinal Failure on Long-Term Parenteral Nutrition and in Their Caregivers
Authors: Santarpia Lidia , Orefice Raffaella , Alfonsi Lucia , Marra Maurizio , Contaldo Franco , Pasanisi Fabrizio
Published: April 2024

Background and aims: Home parenteral nutrition (HPN) is a life-saving treatment for patients affected by chronic intestinal failure (CIF). Both this clinical condition and its therapy require radical lifestyle modifications, affecting life quality and psychological balance in patients as well as family members. Patient psychological burden has rarely been taken into consideration, not to mention that of caregivers. This study aims to evaluate the levels of anxiety in CIF patients on HPN, and their caregivers, consequently determining their impact on the psychological and physical aspects. Methods: After a brief introductory interview, adult patients on HPN for CIF and their caregivers were asked to fill in the HAMA-A questionnaire. Results: Fifty patients and their respective caregivers were enrolled. Mean HAMA-A scores were similar in patients and caregivers and testified the presence of a mild to severe impact of CIF and HPN in both groups, with a significantly higher impact on female patients and caregivers. After adjusting age, education level, duration of CIF and HPN dependence, and degree of kinship, no differences were revealed in the scores. Conclusions: The study confirms that CIF patients on HPN and their caregivers have a significant anxiety burden independently from the duration of the disease, therefore needing appropriate support.
Anorexia-Induced Hypoleptinemia Drives Adaptations in the JAK2/STAT3 Pathway in the Ventral and Dorsal Hippocampus of Female Rats
Authors: Targa Giorgia , Mottarlini Francesca , Rizzi Beatrice , Taddini Sofia , Parolaro Susanna , Fumagalli Fabio , Caffino Lucia
Published: April 2024

Leptin is an appetite-regulating adipokine that is reduced in patients with anorexia nervosa (AN), a psychiatric disorder characterized by self-imposed starvation, and has been linked to hyperactivity, a hallmark of AN. However, it remains unknown how leptin receptor (LepR) and its JAK2-STAT3 downstream pathway in extrahypothalamic brain areas, such as the dorsal (dHip) and ventral (vHip) hippocampus, crucial for spatial memory and emotion regulation, may contribute to the maintenance of AN behaviors. Taking advantage of the activity-based anorexia (ABA) model (i.e., the combination of food restriction and physical activity), we observed reduced leptin plasma levels in adolescent female ABA rats at the acute phase of the disorder [post-natal day (PND) 42], while the levels increased over control levels following a 7-day recovery period (PND49). The analysis of the intracellular leptin pathway revealed that ABA rats showed an overall decrease of the LepR/JAK2/STAT3 signaling in dHip at both time points, while in vHip we observed a transition from hypo- (PND42) to hyperactivation (PND49) of the pathway. These changes might add knowledge on starvation-induced fluctuations in leptin levels and in hippocampal leptin signaling as initial drivers of the transition from adaptative mechanisms to starvation toward the maintenance of aberrant behaviors typical of AN patients, such as perpetuating restraint over eating.
The Effect of an Elevated Dietary Copper Level on the Vascular Contractility and Oxidative Stress in Middle-Aged Rats
Authors: Kitala-Tańska Klaudia , Socha Katarzyna , Juśkiewicz Jerzy , Krajewska-Włodarczyk Magdalena , Majewski Michał
Published: April 2024

Copper (Cu), being an essential mineral, plays a crucial role in maintaining physiological homeostasis across multiple bodily systems, notably the cardiovascular system. However, an increased Cu level in the body may cause blood vessel dysfunction and oxidative stress, which is unfavorable for the cardiovascular system. Middle-aged (7–8 months old) male Wistar rats (n/group = 12) received a diet supplemented with 6.45 mg Cu/kg (100% of the recommended daily dietary quantity of copper) for 8 weeks (Group A). The experimental group received 12.9 mg Cu/kg of diet (200%—Group B). An ex vivo study revealed that supplementation with 200% Cu decreased the contraction of isolated aortic rings to noradrenaline (0.7-fold) through FP receptor modulation. Vasodilation to sodium nitroprusside (1.10-fold) and acetylcholine (1.13-fold) was potentiated due to the increased net effect of prostacyclin derived from cyclooxygenase-1. Nitric oxide (NO, 2.08-fold), superoxide anion (O2•−, 1.5-fold), and hydrogen peroxide (H2O2, 2.33-fold) measured in the aortic rings increased. Blood serum antioxidant status (TAS, 1.6-fold), Cu (1.2-fold), Zn (1.1-fold), and the Cu/Zn ratio (1.4-fold) increased. An increase in Cu (1.12-fold) and the Cu/Zn ratio (1.09-fold) was also seen in the rats’ livers. Meanwhile, cyclooxygenase-1 (0.7-fold), cyclooxygenase-2 (0.4-fold) and glyceraldehyde 3-phosphate dehydrogenase (0.5-fold) decreased. Moreover, a negative correlation between Cu and Zn was found (r = −0.80) in rat serum. Supplementation with 200% Cu did not modify the isolated heart functioning. No significant difference was found in the body weight, fat/lean body ratio, and organ weight for either the heart or liver, spleen, kidney, and brain. Neither Fe nor Se, the Cu/Se ratio, the Se/Zn ratio (in serum and liver), heme oxygenase-1 (HO-1), endothelial nitric oxide synthase (eNOS), or intercellular adhesion molecule-1 (iCAM-1) (in serum) were modified. Supplementation with 200% of Cu potentiated pro-oxidant status and modified vascular contractility in middle-aged rats.
The Power of Vitamin D: Is the Future in Precision Nutrition through Personalized Supplementation Plans?
Authors: Mavar Mladen , Sorić Tamara , Bagarić Ena , Sarić Ana , Matek Sarić Marijana
Published: April 2024

In the last few decades, vitamin D has undeniably been one of the most studied nutrients. Despite our ability to produce vitamin D through sunlight exposure, its presence in several natural food sources and fortified foods, and its widespread availability as a dietary supplement, vitamin D deficiency is a serious public health problem, affecting nearly 50% of the global population. Low serum levels of vitamin D are being associated with increased susceptibility to numerous health conditions, including respiratory infections, mental health, autoimmune diseases, and different cancer types. Although the association between vitamin D status and health is well-established, the exact beneficial effects of vitamin D are still inconclusive and indefinite, especially when considering the prevention and treatment of different health conditions and the determination of an appropriate dosage to exert those beneficial effects in various population groups. Therefore, further research is needed. With constant improvements in our understanding of individual variations in vitamin D metabolism and requirements, in the future, precision nutrition and personalized supplementation plans could prove beneficial.
Vitamin A Status Modulates Epithelial Mesenchymal Transition in the Lung: The Role of Furin
Authors: Cabezuelo M. Teresa , Torres Luis , Ortiz-Zapater Elena , López-Rodas Gerardo , Marín M. Pilar , Timoneda Joaquín , Viña Juan R. , Zaragozá Rosa , Barber Teresa
Published: April 2024

Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial–mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT and furin are induced in VAD rats. Furthermore, furin expression continues to increase much more markedly after treatment of VAD rats with RA. In control rats and cell lines, an acute RA treatment induced a significant increase in furin expression, concomitant with changes in EMT markers. A ChIP assay demonstrated that RA directly regulates furin transcription. These results emphasize the importance of maintaining vitamin A levels within the physiological range since both levels below and above this range can cause adverse effects that, paradoxically, could be similar. The role of furin in EMT is discussed.
Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations
Authors: Hübinger Lisa , Wetzig Kerstin , Runge Roswitha , Hartmann Holger , Tillner Falk , Tietze Katja , Pretze Marc , Kästner David , Freudenberg Robert , Brogsitter Claudia , Kotzerke Jörg
Published: April 2024

This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.
First Generic Teriparatide: Structural and Biological Sameness to Its Reference Medicinal Product
Authors: Fernández-Carneado Jimena , Vallès-Miret Mariona , Arrastia-Casado Sílvia , Almazán-Moga Ana , Macias Maria J. , Martin-Malpartida Pau , Vilaseca Marta , Díaz-Lobo Mireia , Vazquez Mayte , Sanahuja Rosa M. , Gambús Gemma , Ponsati Berta
Published: April 2024

Teriparatide is an anabolic peptide drug indicated for the treatment of osteoporosis. Recombinant teriparatide was first approved in 2002 and has since been followed by patent-free alternatives under biosimilar or hybrid regulatory application. The aim of this study is to demonstrate the essential similarity between synthetic teriparatide BGW and the reference medicinal product (RMP), and thus to ensure the development of the first generic teriparatide drug. Hence, an extensive side-by-side comparative exercise, focusing on structural and biological activity, was performed using a wide range of state-of-the-art orthogonal methods. Nuclear magnetic resonance (NMR), ion mobility–mass spectrometry (IM–MS), UV, circular dichroism (CD) and Fourier transform infrared (FTIR) demonstrated the structural similarity between teriparatide BGW and the RMP. Comparative cell-based bioassays showed that the synthetic and recombinant peptides have identical behaviors. Teriparatide BGW, as a generic drug, provides an available treatment option for patients with osteoporosis and offers clinical benefits identical to those provided by the RMP.
Transcription Factor Binding Site in Promoter Determines the Pattern of Plasmid-Based Transgene Expression In Vivo
Authors: Zhang Chunbo , Liu Dexi
Published: April 2024

Understanding the regulation of transgene expression is critical for the success of plasmid-based gene therapy and vaccine development. In this study, we used two sets of plasmid vectors containing secreted embryonic alkaline phosphatase or the mouse IL-10 gene as a reporter and investigated the role of promoter elements in regulating transgene expression in vivo. We demonstrated in mice that hydrodynamic transfer of plasmids with the CMV promoter resulted in a high level of reporter gene expression that declined rapidly over time. In contrast, when plasmids with albumin promoters were used, a lower but sustained gene expression pattern was observed. We also found that plasmids containing a shorter CMV promoter sequence with fewer transcription factor binding sites showed a decrease in the peak level of gene expression without changing the overall pattern of reporter gene expression. The replacement of regulatory elements in the CMV promoter with a single regulatory element of the albumin promoter changed the pattern of transient gene expression seen in the CMV promoter to a pattern of sustained gene expression identical to that of a full albumin promoter. ChIP analyses demonstrated an elevated binding of acetylated histones and TATA box-binding protein to the promoter carrying regulatory elements of the albumin promoter. These results suggest that the strength of a promoter is determined by the number of appropriate transcription factor binding sites, while gene expression persistence is determined by the presence of regulatory elements capable of recruiting epigenetic modifying complexes that make the promoter accessible for transcription. This study provides important insights into the mechanisms underlying gene expression regulation in vivo, which can be used to improve plasmid-based gene therapy and vaccine development.
Role of Pyramidal Low-Dimensional Semiconductors in Advancing the Field of Optoelectronics
Authors: Jiang Ao , Xing Shibo , Lin Haowei , Chen Qing , Li Mingxuan
Published: April 2024

Numerous optoelectronic devices based on low-dimensional nanostructures have been developed in recent years. Among these, pyramidal low-dimensional semiconductors (zero- and one-dimensional nanomaterials) have been favored in the field of optoelectronics. In this review, we discuss in detail the structures, preparation methods, band structures, electronic properties, and optoelectronic applications (photocatalysis, photoelectric detection, solar cells, light-emitting diodes, lasers, and optical quantum information processing) of pyramidal low-dimensional semiconductors and demonstrate their excellent photoelectric performances. More specifically, pyramidal semiconductor quantum dots (PSQDs) possess higher mobilities and longer lifetimes, which would be more suitable for photovoltaic devices requiring fast carrier transport. In addition, the linear polarization direction of exciton emission is easily controlled via the direction of magnetic field in PSQDs with C3v symmetry, so that all-optical multi-qubit gates based on electron spin as a quantum bit could be realized. Therefore, the use of PSQDs (e.g., InAs, GaN, InGaAs, and InGaN) as effective candidates for constructing optical quantum devices is examined due to the growing interest in optical quantum information processing. Pyramidal semiconductor nanorods (PSNRs) and pyramidal semiconductor nanowires (PSNWRs) also exhibit the more efficient separation of electron-hole pairs and strong light absorption effects, which are expected to be widely utilized in light-receiving devices. Finally, this review concludes with a summary of the current problems and suggestions for potential future research directions in the context of pyramidal low-dimensional semiconductors.
In Vitro Collection for the Safe Storage of Grapevine Hybrids and Identification of the Presence of Plasmopara viticola Resistance Genes
Authors: Romadanova Natalya V. , Aralbayeva Moldir M. , Zemtsova Alina S. , Alexandrova Alyona M. , Kazybayeva Saule Zh. , Mikhailenko Natalya V. , Kushnarenko Svetlana V. , Bettoni Jean Carlos
Published: April 2024

This paper focuses on the creation of an in vitro collection of grapevine hybrids from the breeding program of the Kazakh Scientific Research Institute of Fruit Growing and Viticulture and investigates the presence of Plasmopara viticola resistance mediated by Rpv3 and Rpv12 loci. We looked at the optimization of in vitro establishment using either shoots taken directly from field-grown plants or from budwood cuttings forced indoors. We further screened for the presence of endophyte contamination in the initiated explants and optimized the multiplication stage. Finally, the presence of the resistance loci against P. viticola was studied. The shoots initiated from the field-sourced explants were the more effective method of providing plant sources for in vitro initiation once all plant accessions met the goal of in vitro establishment. The concentration of phytohormones and the acidity of the culture medium have a great effect on the multiplication rate and the quality of in vitro stock cultures. Out of 17 grapevine accessions, 16 showed the presence of single or combined resistance loci against P. viticola. The grapevine accessions identified as carrying Rpv3 and Rpv12 alleles represent important genetic resources for disease resistance breeding programs. These accessions may further contribute to the creation of new elite cultivars of economic interest.
Neuroprotective Effects of Chemical Constituents of Leaves of Euonymus hamiltonianus Wall.
Authors: Tran Huynh Nguyen Khanh , Yu Jae Sik , Huang Tianqi , Lee Gakyung , Choi Hyo Sun , Yang Hyun Ok
Published: April 2024

Euonymus hamiltonianus Wall. is considered a medicinal plant and is used to treat pain, cough, dysuria, and cancer, but a clear phytochemical investigation of its biological activities has yet to be performed. Investigation of chemical constituents of the leaves of Euonymus hamiltonianus Wall. led to the isolation of three new compounds by chromatography techniques, euonymusins A–C (1, 10, and 11), and the acquisition of new spectroscopic data for euonymusin D (2), along with the identification of ten known compounds. The chemical structures of the compounds were established using extensive spectroscopic techniques, including NMR, MS, and hydrolysis, and compared with the published data. These compounds were tested in vitro for their inhibitory effects on beta amyloid production (Aβ42). Compounds 13 and 14 displayed weak inhibition, with IC50 values ranging from 53.15 to 65.43 µM. Moreover, these compounds were also assessed for their inhibitory effects on nitric oxide production. Of these compounds, 3, 4, and 14 displayed inhibitory effects on NO production, with IC50 values ranging from 14.38 to 17.44 µM. Compounds 3, 4, and 14 also suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein.
Investigation of Imidazolinone Herbicide Resistance Gene with KASP Markers for Japonica/Geng Rice Varieties in the Huanghuaihai Region of China
Authors: Liu Peng , Feng Wenjie , Wang Tao , Zhang Huadong , Mao Shuaige , Zhang Hua , Huang Wenchao , Liu Haifeng , Feng Shangzong , Chu Zhaohui
Published: April 2024

Rice is a staple food for more than half of the global population due to its food security and sustainable development. Weeds compete with crops for sunlight and indispensable nutrients, affecting the yield and quality of crops. Breeding herbicide-tolerant rice varieties paired with herbicide application is expected to help with weed control. In this study, 194 Japonica/Geng rice varieties or lines collected from the Huanghuaihai region of China were screened by Kompetitive Allele-Specific PCR (KASP) markers based on four mutation sites within OsALS1 (LOC_Os02g30630), which is the target of imidazolinone (IMI) herbicides. Only the OsALS1627N haplotype was identified in 18 varieties, including the previously reported Jingeng818 (JG818), and its herbicide resistance was validated by treatment with three IMIs. To investigate the origin of the OsALS1627N haplotype in the identified varieties, six codominant PCR-based markers tightly linked with OsALS1 were developed. PCR analysis revealed that the other 17 IMI-tolerant varieties were derived from JG818. We randomly selected three IMI-tolerant varieties for comparative whole-genome resequencing with known receptor parent varieties. Sequence alignment revealed that more loci from JG818 have been introduced into IMI-tolerant varieties. However, all three IMI-tolerant varieties carried clustered third type single nucleotide polymorphism (SNP) sites from unknown parents, indicating that these varieties were not directly derived from JG818, whereas those from different intermediate improved lines were crossed with JG818. Overall, we found that only OsALS1627N from JG818 has been broadly introduced into the Huanghuaihai region of China. Additionally, the 17 identified IMI-tolerant varieties provide alternative opportunities for improving such varieties along with other good traits.
Effects of Short-Term Nitrogen Additions on Biomass and Soil Phytochemical Cycling in Alpine Grasslands of Tianshan, China
Authors: Liu Chao , Liu Junjie , Wang Juan , Ding Xiaoyu
Published: April 2024

The nitrogen deposition process, as an important phenomenon of global climate change and an important link in the nitrogen cycle, has had serious and far-reaching impacts on grassland ecosystems. This study aimed to investigate the survival adaptation strategies of plants of different functional groups under nitrogen deposition, and the study identified the following outcomes of differences in biomass changes by conducting in situ simulated nitrogen deposition experiments while integrating plant nutrient contents and soil physicochemical properties: (1) nitrogen addition enhanced the aboveground biomass of grassland communities, in which Poaceae were significantly affected by nitrogen addition. Additionally, nitrogen addition significantly influenced plant total nitrogen and total phosphorus; (2) nitrogen addition improved the plant growth environment, alleviated plant nitrogen limitation, and promoted plant phosphorus uptake; and (3) there was variability in the biomass responses of different functional groups to nitrogen addition. The level of nitrogen addition was the primary factor affecting differences in biomass changes, while nitrogen addition frequency was an important factor affecting changes in plant community structure.
Cassia Seed Gum Films Incorporated with Partridge Tea Extract as an Edible Antioxidant Food Packaging Film for Preservation of Chicken Jerky
Authors: Wei Na , Pan Zijing , Ning Yuping , Liu Wenhua , Wen Xin , Yang Chen , Wang Lijuan
Published: April 2024

The use of edible packaging films to delay food spoilage has attracted widespread attention. In this study, partridge tea extract (PTE) was added to cassia gum (CG) to prepare CG/PTE films. The microstructure, optical, mechanical, barrier, and antioxidant properties of CG/PTE films were investigated, and the effect of PTE on CG films was shown. The films had high transparency and smooth surface structure. Additionally, PTE significantly improved the elongation at break and antioxidant activity of films. At 2.5% of PTE, the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate of the film was 46.88% after diluting 50 times, indicating excellent antioxidant property, which could be applied to food preservation. After 9 days of storage, the thiobarbituric acid reactive substances values (TBARS) of chicken jerk packaged with films containing 0% and 2.5% PTE increased from 0.12% to 1.04% and 0.11% to 0.40%, respectively. This study suggests that CG/PTE films can be used to preserve cooked meat.
Physicochemical Characterization and In Vitro Activity of Poly(ε-Caprolactone)/Mycophenolic Acid Amorphous Solid Dispersions
Authors: Sánchez-Aguinagalde Oroitz , Sanchez-Rexach Eva , Polo Yurena , Larrañaga Aitor , Lejardi Ainhoa , Meaurio Emilio , Sarasua Jose-Ramon
Published: April 2024

The obtention of amorphous solid dispersions (ASDs) of mycophenolic acid (MPA) in poly(ε-caprolactone) (PCL) is reported in this paper. An improvement in the bioavailability of the drug is possible thanks to the favorable specific interactions occurring in this system. Differential scanning calorimetry (DSC) was used to investigate the miscibility of PCL/MPA blends, measuring glass transition temperature (Tg) and analyzing melting point depression to obtain a negative interaction parameter, which indicates the development of favorable inter-association interactions. Fourier transform infrared spectroscopy (FTIR) was used to analyze the specific interaction occurring in the blends. Drug release measurements showed that at least 70% of the drug was released by the third day in vitro in all compositions. Finally, preliminary in vitro cell culture experiments showed a decreased number of cancerous cells over the scaffolds containing MPA, presumably arising from the anti-cancer activity attributable to MPA.
Investigation of Additive-Manufactured Carbon Fiber-Reinforced Polyethylene Terephthalate Honeycomb for Application as Non-Pneumatic Tire Support Structure
Authors: Wang Siwen , He Pan , Geng Quanqiang , Huang Hui , Sang Lin , Yao Zaiqi
Published: April 2024

A non-pneumatic tire (NPT) overcomes the shortcomings of a traditional pneumatic tire such as wear, punctures and blowouts. In this respect, it shows great potential in improving driving safety, and has received great attention in recent years. In this paper, a carbon fiber-reinforced polyethylene terephthalate (PET/CF) honeycomb is proposed as a support structure for NPTs, which can be easily prepared using 3D printing technology. The experimental results showed that the PET/CF has high strength and modulus and provides excellent mechanical properties. Then, a finite element (FE) model was established to predict the compression performance of auxetic honeycombs. Good agreement was achieved between the experimental data and FE analysis. The influence of the cell parameters on the compressive performance of the support structure were further analyzed. Both the wall thickness and the vertically inclined angle could modulate the mechanical performance of the NPT. Finally, the application of vertical force is used to analyze the static load of the structure. The PET/CF honeycomb as the support structure of the NPT showed outstanding bearing capacity and stiffness in contrast with elastomer counterparts. Consequently, this study broadens the material selection for NPTs and proposes a strategy for manufacturing a prototype, which provides a reference for the design and development of non-pneumatic tires.
Development of Biphasic Injectable Hydrogels for Meniscus Scaffold from Photocrosslinked Glycidyl Methacrylate-Modified Poly(Vinyl Alcohol)/Glycidyl Methacrylate-Modified Silk Fibroin
Authors: Jeencham Rachasit , Sinna Jiraporn , Ruksakulpiwat Chaiwat , Tawonsawatruk Tulyapruek , Numpaisal Piya-on , Ruksakulpiwat Yupaporn
Published: April 2024

The development of a hydrogel material with a modified chemical structure of poly(vinyl alcohol) (PVA) and silk fibroin (SF) using glycidyl methacrylate (GMA) (denoted as PVA-g-GMA and SF-g-GMA) is an innovative approach in the field of biomaterials and meniscus tissue engineering in this study. The PVA-g-GMA/SF-g-GMA hydrogel was fabricated using different ratios of PVA-g-GMA to SF-g-GMA: 100/0, 75/25, 50/50, 25/75, and 0/100 (w/w of dry substances), using lithium phenyl (2,4,6-trimethylbenzoyl)phosphinate (LAP) as a free radical photoinitiator, for 10 min at a low ultraviolet (UV) intensity (365 nm, 6 mW/cm2). The mechanical properties, morphology, pore size, and biodegradability of the PVA-g-GMA/SF-g-GMA hydrogel were investigated. Finally, for clinical application, human chondrocyte cell lines (HCPCs) were mixed into PVA-g-GMA/SF-g-GMA solutions and fabricated into hydrogel to study the viability of live and dead cells and gene expression. The results indicate that as the SF-g-GMA content increased, the compressive modulus of the PVA-g-GMA/SF-g-GMA hydrogel dropped from approximately 173 to 11 kPa. The degradation rates of PVA-g-GMA/SF-g-GMA 100/0, 75/25, and 50/50 reached up to 15.61%, 17.23%, and 18.93% in 4 months, respectively. In all PVA-g-GMA/SF-g-GMA conditions on day 7, chondrocyte cell vitality exceeded 80%. The PVA-g-GMA/SF-g-GMA 75:25 and 50:50 hydrogels hold promise as a biomimetic biphasic injectable hydrogel for encapsulated augmentation, offering advantages in terms of rapid photocurability, tunable mechanical properties, favorable biological responses, and controlled degradation.
“Beyond the Window That Can Never Be Opened”—Roger Scruton on “Moments of Revelation” in Human Life
Authors: Hörcher Ferenc
Published: April 2024

This study addresses Roger Scruton’s understanding of what he called “moments of revelation”. In two short essays, both entitled “Effing the ineffable”, Scruton framed his discussion of moments of revelation with reference to the medieval Christian mystical discourse. Introducing the medieval discussion of this topic, this study provides an analysis of Scruton’s approach to the theme. In tune with the traditional discourse on revelation, his general aim was to demonstrate that there are ways of revealing important truths about the supernatural, of the world “beyond the window”, that do not require words to be pronounced. He calls our experiences of such phenomena moments of revelation and identifies four different transitory sources of revelation. This study deals with them one by one, after considering whether it is right to label such a revelation transcendental. The four sources of Scruton’s moments of revelation are natural beauty, the beauty of painting, the beauty of music, and personal encounters. The first three examples are connected to his thoughts on art and beauty as a substitute of divine revelation. Perhaps the most surprising of these is the last ones, moments of intersubjective human relationships, “our knowledge of each other”. Relying on both Buber and Levinas, Scruton makes the strong claim that it is in the other that we can experience that world “beyond the window”. His phenomenological exploration of human encounters sheds light on concepts like grace, shekhinah, or real presence and gift. He explains the Christian understanding of the human–divine relationship as well along the lines of the nature of interpersonal human relationship, both of them being in a certain sense, he claims, transcendental. From grace, his account moves forward to self-sacrifice and finally arrives at his idiosyncratic understanding of gratefulness for life. His moments of revelation in art and interpersonal exchange turn out to be, indeed, late and secular versions of the Christian understanding of revelation. In its summary, this study claims that revelation, understood by Scruton as a form of general human experience, allows to catch a glimpse of that which is beyond the window, by the direct, sensually based experience of either the existence of another person or of the beauty of nature and art.
How to Worship in the Metaverse: Religious Experience and the Affordances of a New Medium
Authors: Adria Marco
Published: April 2024

The extent to which the metaverse will become a site for religious and spiritual experience depends on how the aims of users align with the new medium’s potentialities for action, or “affordances”. Affordances are formed as the social, technological, and contextual capacities of a medium are recognized and then enacted by users. This exploratory essay argues that the metaverse’s affordances, which overlap with those of already existing virtual reality (VR) environments, can deepen a sense of belonging for users of online religious spaces and mediate new ways of being present in those spaces. The following affordances of the metaverse (and of VR) are discussed analytically in the essay: immersion, presence, embodiment, usability, empathy, and contemplation. The phases of the continuing “buildout” of the metaverse are also assessed to uncover their likely effects on the metaverse’s affordances. These phases are massive scale, system interoperability, robust rendering, and persistent continuity.