bluuebunny/crossref_metadata_2025 huggingface dataset:
A Laterally Excited Bulk Acoustic Wave Resonator Based on LiNbO3 with Arc-Shaped Electrodes
Authors: Liu Jieyu , Liu Wenjuan , Wen Zhiwei , Zeng Min , Sun Chengliang
Published: November 2024

High frequency and large bandwidth are growing trends in communication radio-frequency devices. The LiNbO3 thin film material is expected to become the preferred piezoelectric material for high coupling resonators in the 5G frequency band due to its ultra-high piezoelectric coefficient and low loss characteristics. The main mode of laterally excited bulk acoustic wave resonators (XBAR) have an ultra-high sound velocity, which enables high-frequency applications. However, the interference of spurious modes is one of the main reasons hindering the widespread application of XBAR. In this paper, a Z-cut LiNbO3 thin film-based XBAR with arc-shaped electrodes is presented. We investigate the electric field distribution of the XBAR, while the irregular boundary of the arc-shaped electrodes affects the electric field between the existing interdigital transducers (IDTs). The mode shapes and impedance response of the XBAR with arc-shaped electrodes and the XBARs with traditional IDTs are compared in this work. The fabricated XBAR on a 350 nm Z-cut LiNbO3 thin film with arc-shaped electrodes operating at over 5 GHz achieves a high effective electromechanical coupling coefficient of 29.8% and the spurious modes are well suppressed. This work promotes an XBAR with an optimized electrode design to further achieve the desired performance.
Microbial Contamination and Antibiotic Resistance in Fresh Produce and Agro-Ecosystems in South Asia—A Systematic Review
Authors: Kalpana Pachillu , Yasobant Sandul , Saxena Deepak , Schreiber Christiane
Published: November 2024

Fresh produce prone to microbial contamination is a potential reservoir for antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs), posing challenges to food safety and public health. This systematic review aims to comprehensively assess the prevalence of bacterial pathogens and the incidence of ARB/ARGs in fresh produce and agro-ecosystems across South Asia. Twenty-two relevant studies published between 2012 and 2022 from three major scientific databases and the grey literature were identified. The results revealed a wide occurrence of microbial contamination in various types of fresh produce across South Asia, with a predominance of E. coli (16/22), Salmonella spp. (13/22), Staphylococcus spp. (5/22), and Klebsiella spp. (4/22). The agro-ecosystem serves as a complex interface for microbial interactions; studies have reported the prevalence of E. coli (1/4), Salmonella spp. (1/4) and Listeria monocytogenes (1/4) in farm environment samples. A concerning prevalence of ARB has been reported, with resistance to multiple classes of antibiotics. The presence of ARGs in fresh produce underscores the potential for gene transfer and the emergence of resistant pathogens. To conclude, our review provides insights into the requirements of enhanced surveillance, collaborative efforts, implementation of good agricultural practices, and public awareness for food safety and safeguarding public health in the region.
Characterization of the Blood Bacterial Microbiota in Lowland Tapirs (Tapirus terrestris), a Vulnerable Species in Brazil
Authors: Mongruel Anna Claudia Baumel , Medici Emília Patrícia , Machado Rosangela Zacarias , Clay Keith , André Marcos Rogério
Published: November 2024

Microbiome studies targeting hypervariable regions of the 16S rRNA gene are suitable for understanding interactions between animals and their associated bacteria. While many studies focus on the gut microbiome, assessments of blood microbiota remain scarce despite the prevalence of blood-borne pathogens in vertebrates. This study aimed to investigate the bacterial community in blood samples from 79 living and 7 road-killed lowland tapirs (Tapirus terrestris), a vulnerable species, sampled in two biomes in midwestern Brazil: Pantanal and Cerrado. Animals were categorized by condition (living or road-killed), sex, age, and biome. V3–V4 16S rRNA fragments were obtained from 86 blood samples and 4 negative controls. After filtering contaminants, 13,742,198 sequences representing 2146 ASVs were analyzed. Alpha diversity significantly differed by condition, while beta diversity differed by condition, site, and age (adults vs. sub-adults). For living animals (79/86 samples), alpha diversity showed no significant differences, but beta diversity differed by age. Different vector-borne bacterial pathogens, including Anaplasmataceae, Bartonella, and Borrelia spp., were detected. Additionally, evidence of transient translocation of microbial communities from other body regions to the bloodstream was observed. Amplification of bacterial 16S rRNA from blood samples of wild T. terrestris provided novel information about the diversity of blood-borne microbiota of lowland tapirs, members of a poorly studied mammalian family. Next-generation sequencing proved to be a valuable tool for screening potential vector-borne pathogens in this host.
Oxford Nanopore Technology-Based Identification of an Acanthamoeba castellanii Endosymbiosis in Microbial Keratitis
Authors: Scharf Sebastian Alexander , Friedrichs Lennart , Bock Robert , Borrelli Maria , MacKenzie Colin , Pfeffer Klaus , Henrich Birgit
Published: November 2024

(1) Background: Microbial keratitis is a serious eye infection that carries a significant risk of vision loss. Acanthamoeba spp. are known to cause keratitis and their bacterial endosymbionts can increase virulence and/or treatment resistance and thus significantly worsen the course of the disease. (2) Methods and Results: In a suspected case of Acanthamoeba keratitis, in addition to Acanthamoeba spp., an endosymbiont of acanthamoebae belonging to the taxonomic order of Holosporales was detected by chance in a bacterial 16S rDNA-based pan-PCR and subsequently classified as Candidatus Paracaedibacter symbiosus through an analysis of an enlarged 16S rDNA region. We used Oxford Nanopore Technology to evaluate the usefulness of whole-genome sequencing (WGS) as a one-step diagnostics method. Here, Acanthamoeba castellanii and the endosymbiont Candidatus Paracaedibacter symbiosus could be directly detected at the species level. No other microbes were identified in the specimen. (3) Conclusions: We recommend the introduction of WGS as a diagnostic approach for keratitis to replace the need for multiple species-specific qPCRs in future routine diagnostics and to enable an all-encompassing characterisation of the polymicrobial community in one step.
H9 Consensus Hemagglutinin Subunit Vaccine with Adjuvants Induces Robust Mucosal and Systemic Immune Responses in Mice by Intranasal Administration
Authors: Lin Liming , Zhu Shunfan , Yang Beibei , Zhang Xin , Wu Huimin , Wu Shixiang , Wu Li , Shu Jianhong , He Yulong , Feng Huapeng
Published: November 2024

The H9N2 subtype avian influenza viruses mainly cause respiratory symptoms, reduce the egg production and fertility of poultry, and result in secondary infections, posing a great threat to the poultry industry and human health. Currently, all H9N2 avian influenza commercial vaccines are inactivated vaccines, which provide protection for immunized animals but cannot inhibit the spread of the virus and make it difficult to distinguish between the infected animals and vaccinated animals. In this study, a trimeric consensus H9 hemagglutinin (HA) subunit vaccine for the H9N2 subtype avian influenza virus based on a baculovirus expression system was first generated, and then the effects of three molecular adjuvants on the H9 HA subunit vaccine, Cholera toxin subunit B (CTB), flagellin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) fused with H9 HA, and one synthetic compound, a polyinosinic–polycytidylic acid (PolyI:C) adjuvant, were evaluated in mice by intranasal administration. The results showed that these four adjuvants enhanced the immunogenicity of the H9 HA subunit vaccine for avian influenza viruses, and that GM-CSF and PolyI:C present better mucosal adjuvant activity for the H9 HA subunit vaccine. These results demonstrate that we have developed a potential universal H9 HA mucosal subunit vaccine with adjuvants in a baculovirus system that would be helpful for the prevention and control of H9N2 subtype avian influenza viruses.
Randomized Clinical Trials Demonstrate the Safety Assessment of Alkalihalobacillus clausii AO1125 for Use as a Probiotic in Humans
Authors: García Gissel , Soto Josanne , Díaz Antonio , Barreto Jesús , Soto Carmen , Pérez Ana Beatriz , Boffill Suselys , Cano Raúl De Jesús
Published: November 2024

(1) Background: Alkalihalobacillus clausii AO1125 is a Gram-positive, motile, spore-forming bacterium with potential as a probiotic due to its broad-spectrum antimicrobial activity, inhibiting pathogens like Listeria monocytogenes, Staphylococcus aureus, and Clostridium difficile, as well as anti-rotavirus activity. Its resilience in gastrointestinal conditions suggests benefits for gut health. This study evaluates the safety and probiotic potential of A. clausii AO1125. (2) Methods: Genome annotation identified genes linked to probiotic traits such as stress resistance, gut colonization, immune modulation, and antimicrobial production. The genome was screened for antibiotic resistance genes using CARD, bacteriocin clusters using BAGEL4, and virulence factors via VFDB. Cytotoxicity was assessed on Vero cells and erythrocytes, and a Phase I, double-blind, placebo-controlled clinical trial was conducted with 99 healthy volunteers (50 AO1125, 49 placebo). (3) Results: Genomic analysis confirmed minimal antibiotic resistance genes and the absence of virulence factors, supporting safety. A. clausii AO1125 showed no pathogenicity, cytotoxicity, or hemolytic activity and was well-tolerated in clinical settings, with mild, transient abdominal gas as the most common adverse event. (4) Conclusions: The safety profile and genetic basis for probiotic and antimicrobial properties support A. clausii AO1125 as a promising probiotic candidate for gastrointestinal health, warranting further clinical research.
Parameters of Collision and Adhesion Process Between a Rising Bubble and Quartz in Long-Chain Amine Solution and Their Correlation with Flotation
Authors: Gao Shuling , Li Bochao , Ma Lifeng , Liu Wenbao , Zhao Sikai , Shen Yanbai
Published: November 2024

The successful adhesion of air bubbles to mineral particles is the crucial to flotation technology. This paper systematically investigates the parameters variation in the dynamic interaction process between a rising bubble and a quartz plate in long-chain amine solutions (dodecylamine, tedecylamine, and octadecylamine). The results show that the type and concentration of long-chain amine affected the collision and adhesion process between bubbles and quartz plates remarkably. The maximum rebound distance (rebound distance after the first collision) of bubbles and the stable-state liquid film thickness gradually decreases with the increase of reagent concentration. Additionally, the collision-rebound duration and induction time shorten accordingly, the surface tension of the solution decreases, the surface hydrophobicity of quartz increases, and the deformation degree and average movement velocity of bubbles decrease. With the increase in carbon chain length, the adsorption form of the amine collector and quartz surface becomes closer to vertical, and the density of water molecules decreases. The recovery of quartz particles is highest with octadecylamine systems, corresponding well with the changing trend in steady-state liquid film thickness. This research provides an effective method for in-depth analysis of the microscopic interaction mechanism between bubbles and mineral surfaces and the prediction of flotation results.
Characterization of Bioactive Phenolic Compounds Extracted from Hydro-Distillation By-Products of Spanish Lamiaceae Plants
Authors: Pérez-Magariño Silvia , Bueno-Herrera Marta , Asensio-S.-Manzanera M. Carmen
Published: November 2024

Plants of the Lamiaceae family are widely used for the extraction of essential oils, and this industry generates a large number of solid residues as by-products, which contain non-volatile valuable compounds. The aim of this work was to identify and quantify the phenolic compounds present in these solid residues from different important Spanish species of Lamiaceae to characterize and valorize them. Forty-seven phenolic compounds were identified by HPLC-DAD-MS and quantified by HPLC-DAD. Different concentrations and types of phenolic compounds were found between the solid residues. The Rosmarinus officinalis extracts showed the highest total phenolic content due to their high phenolic terpene concentrations. The Thymus mastichina extracts were characterized by kaempferol and flavanones, and some flavones were derived from luteolin and apigenin. Finally, the sample Lavandula and Salvia lavandulifolia extracts presented the lowest content of most phenolic compounds, with the exception of some phenolic acids, such as danshensu, salvianolic acid A, and glucosides of hydroxycinnamic acids. Therefore, this work provides information on the quantification of a large number of phenolic compounds using a simple, sensitive, reproducible, and accurate methodology. In addition, the results indicate that these solid residues still contain important amounts of different polyphenols, which are antioxidants and can be used in different industries.
Solvent- and Catalyst-Free Environmentally Benign High Hydrostatic Pressure-Assisted Synthesis of Bioactive Hydrazones and the Evaluation of Their Stability Under Various Storage Conditions
Authors: Costa Maximilian , Adhamidhi Frances , Mastyugin Maxim , Fusco Adrianna R. , Lazarev Alexander , Zsengeller Zsuzsanna K. , Török Marianna , Török Béla
Published: November 2024

Our group has seen great promise in using substituted diaryl-hydrazones to alleviate oxidative stress in preeclampsia. Specifically, fluorinated diaryl-hydrazones have shown great efficacy, confirmed via antioxidant assays and animal trials using pregnant mice. In addition to efficient antioxidant properties, these diaryl-hydrazones are also considered non-toxic. While the synthesis of these compounds is relatively simple, it commonly utilizes undesirable solvents and glacial acetic acid as the catalyst; additional solvents are needed for the isolation of the desired products, which negatively affects the green synthesis of the hydrazones. To combat this possible industrial roadblock, we have begun incorporating the use of hydrostatic high pressure (HHP) in the synthesis. The use of HHP allowed us to synthesize substituted diaryl-hydrazones in a 1:1 molar ratio without the need for solvents or acid catalysts. The optimized procedure can produce nearly quantitative yields, leading to an easier isolation of the products. Different HHP methodologies, such as constant high-pressure treatment and cycling (with different number of cycles, holding and decompression times) were applied and cycling was observed to be the most efficient activation for the majority of the reactions. Stability experiments were also conducted with one of the products and observed that although the solid-state storage does not alter the hydrazone, storing it in various solvents may significantly decrease the concentration of the active component which should be considered when performing the biochemical/biological assays.
A Review of Non-Destructive Raman Spectroscopy and Chemometric Techniques in the Analysis of Cultural Heritage
Authors: Yogurtcu Burak , Cebi Nur , Koçer Anıl Tevfik , Erarslan Azime
Published: November 2024

Today, there is an increasing concern and effort for protection, conservation, and restoration of cultural heritage materials. Non-invasive analytical methodologies such as Raman spectroscopy offers various advantages such as high speed, robust identification, low cost, and in-site analysis. Previous contributions highlighted the potential of Raman spectroscopy combined with multivariate statistics for identification and quality evaluation of cultural heritage materials such as paints, fiber, dyes, woods, stones, inks, and textile materials. Especially, application of chemometrics and multivariate statistics algorithms opens new horizons for scientists and inspectors. In conclusion, the paper provided an overview of the state-of-the-art uses of multivariate statistically equipped Raman spectroscopy methods for evaluation of cultural heritage and art materials with illustrations from previous research studies.
Effects of Biguanide-PROTACs in Pancreatic Cancer Cells
Authors: Vatté Julie , Bourdeau Véronique , Ferbeyre Gerardo , Schmitzer Andreea R.
Published: November 2024

This study focuses on the synthesis of Biguanide-PROTACs, formed by conjugating the biguanide motif with a spacer and a ligand for recognition subunits of two E3 ubiquitin ligases. Evaluation of their activity on pancreatic cancer cell (KP4) proliferation established a correlation between membrane permeability and median effective concentration. Mechanistic insights revealed that only two compounds exhibited biguanide-like AMPK activation, while only one hydrophobic compound uniquely altered mitochondrial protein levels. The prospect of developing and expanding the Biguanide-PROTAC library holds several promises, offering potential insights into biguanide mechanisms and the creation of more potent anticancer agents. This study contributes to understanding the intricate interplay between compound structure, permeability, and anticancer activity, paving the way for targeted drug development in pancreatic cancer treatment.
Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures
Authors: Mao Frank Yiyang , Tu Mei-Juan , Traber Gavin McAllister , Yu Ai-Ming
Published: November 2024

Understanding the structures of noncoding RNAs (ncRNAs) is important for the development of RNA-based therapeutics. There are inherent challenges in employing current experimental techniques to determine the tertiary (3D) structures of RNAs with high complexity and flexibility in folding, which makes computational methods indispensable. In this study, we compared the utilities of three advanced computational tools, namely RNAComposer, Rosetta FARFAR2, and the latest AlphaFold 3, to predict the 3D structures of various forms of RNAs, including the small interfering RNA drug, nedosiran, and the novel bioengineered RNA (BioRNA) molecule showing therapeutic potential. Our results showed that, while RNAComposer offered a malachite green aptamer 3D structure closer to its crystal structure, the performances of RNAComposer and Rosetta FARFAR2 largely depend upon the secondary structures inputted, and Rosetta FARFAR2 predictions might not even recapitulate the typical, inverted “L” shape tRNA 3D structure. Overall, AlphaFold 3, integrating molecular dynamics principles into its deep learning framework, directly predicted RNA 3D structures from RNA primary sequence inputs, even accepting several common post-transcriptional modifications, which closely aligned with the experimentally determined structures. However, there were significant discrepancies among three computational tools in predicting the distal loop of human pre-microRNA and larger BioRNA (tRNA fused pre-miRNA) molecules whose 3D structures have not been characterized experimentally. While computational predictions show considerable promise, their notable strengths and limitations emphasize the needs for experimental validation of predictions besides characterization of more RNA 3D structures.
Utilization of Single-Pulse Transcranial-Evoked Potentials in Neurological and Psychiatric Clinical Practice: A Narrative Review
Authors: Fogel Hilla , Zifman Noa , Hallett Mark
Published: November 2024

Background: The utility of single-pulse TMS (transcranial magnetic stimulation)-evoked EEG (electroencephalograph) potentials (TEPs) has been extensively studied in the past three decades. TEPs have been shown to provide insights into features of cortical excitability and connectivity, reflecting mechanisms of excitatory/inhibitory balance, in various neurological and psychiatric conditions. In the present study, we sought to review and summarize the most studied neurological and psychiatric clinical indications utilizing single-pulse TEP and describe its promise as an informative novel tool for the evaluation of brain physiology. Methods: A thorough search of PubMed, Embase, and Google Scholar for original research utilizing single-pulse TMS-EEG and the measurement of TEP was conducted. Our review focused on the indications and outcomes most clinically relevant, commonly studied, and well-supported scientifically. Results: We included a total of 55 publications and summarized them by clinical application. We categorized these publications into seven sub-sections: healthy aging, Alzheimer’s disease (AD), disorders of consciousness (DOCs), stroke rehabilitation and recovery, major depressive disorder (MDD), Parkinson’s disease (PD), as well as prediction and monitoring of treatment response. Conclusions: TEP is a useful measurement of mechanisms underlying neuronal networks. It may be utilized in several clinical applications. Its most prominent uses include monitoring of consciousness levels in DOCs, monitoring and prediction of treatment response in MDD, and diagnosis of AD. Additional applications including the monitoring of stroke rehabilitation and recovery, as well as a diagnostic aid for PD, have also shown encouraging results but require further evidence from randomized controlled trials (RCTs).
Survival After Shunt Therapy in Normal-Pressure Hydrocephalus: A Meta-Analysis of 1614 Patients
Authors: Wach Johannes , Güresir Agi , Güresir Erdem , Vychopen Martin
Published: November 2024

Background: Ventriculoperitoneal (VP) shunt therapy is a crucial intervention for normal-pressure hydrocephalus (NPH). This meta-analysis delves into survival time and the impact of baseline symptom burden on survival after VP shunt therapy for NPH, employing reconstructed pooled survival curves and a one-stage meta-analysis. Methods: IPD regarding overall survival (OS) were acquired from published Kaplan–Meier charts, utilizing the R package IPDfromKM in R (Version 4.3.1, the R Foundation for Statistical Computing). Reconstructed Kaplan–Meier charts were then generated from the pooled IPD data. Both one-stage and two-stage meta-analyses were executed, with hazard ratios (HRs) employed as metrics to evaluate effectiveness. Results: From the initial screening of 216 records, five articles encompassing 1614 patients met the eligibility criteria for inclusion. In two of the five included studies, overall survival was stratified by gait score (1–4 vs. ≥4) in 1043 patients, continence score (1–3 vs. ≥4) in 1022 patients, and mRS (0–2 vs. ≥3) in 956 patients. Patients with good gait demonstrated a mean survival of 8.24 years, while those with poor gait had a mean survival of 6.19 years (log-rank test: p < 0.001). The HR for gait was 2.25 (95% CI: 1.81–2.81, p < 0.001). Continence score stratification revealed a significant difference in survival time (log-rank test: p < 0.001), with an HR of 1.66 (95% CI: 1.33–2.06, p < 0.001). Similarly, mRS stratification demonstrated a significant survival difference (log-rank test: p < 0.001), with an HR of 2.21 (95% CI: 1. 74–2.80, p < 0.001). The reconstructed survival curves for all NPH patients treated with VP shunt therapy, pooling data from five studies, revealed a median survival time of 8.82 years (95% CI: 8.23–9.40). Survival rates at 1, 3, 5, 7, 9, 11, and 13 years were 95.7%, 83.8%, 70.5%, 59.5%, 48.7%, 35.8%, and 25.4%, respectively. Comparison with a general control population showed an HR of 1.79 (95% CI: 1.62–1.98, p < 0.001). Conclusions: This comprehensive meta-analysis underscores the influence of baseline symptom burden on survival after VP shunt therapy in NPH. Therapy in the early stages for those without significant comorbidities may enhance survival.
Differential Effect of TRPV1 Modulators on Neural and Behavioral Responses to Taste Stimuli
Authors: Rhyu Mee-Ra , Ozdener Mehmet Hakan , Lyall Vijay
Published: November 2024

In our diet, we ingest a variety of compounds that are TRPV1 modulators. It is important to understand if these compounds alter neural and behavioral responses to taste stimuli representing all taste qualities. Here, we will summarize the effects of capsaicin, resiniferatoxin, cetylpyridinium chloride, ethanol, nicotine, N-geranyl cyclopropylcarboxamide, Kokumi taste peptides, pH, and temperature on neural and behavioral responses to taste stimuli in rodent models and on human taste perception. The above TRPV1 agonists produced characteristic biphasic effects on chorda tympani taste nerve responses to NaCl in the presence of amiloride, an epithelial Na+ channel blocker, at low concentrations enhancing and at high concentrations inhibiting the response. Biphasic responses were also observed with KCl, NH4Cl, and CaCl2. In the presence of multiple stimuli, the effect is additive. These responses are blocked by TRPV1 antagonists and are not observed in TRPV1 knockout mice. Some TRPV1 modulators also increase neural responses to glutamate but at concentrations much above the concentrations that enhance salt responses. These modulators also alter human salt and glutamate taste perceptions at different concentration ranges. Glutamate responses are TRPV1-independent. Sweet and bitter responses are TRPV1-independent but the off-taste of sweeteners is TRPV1-dependent. Aversive responses to acids and ethanol are absent in animals in which both the taste system and the TRPV1-trigeminal system are eliminated. Thus, TRPV1 modulators differentially alter responses to taste stimuli.
Establishment and Validation of Patient-Derived Non-Small Cell Lung Cancer Organoids as In Vitro Lung Cancer Models
Authors: Werner Raphael S. , Jang Jae-Hwi , Rechsteiner Markus , Kirschner Michaela B. , Opitz Isabelle
Published: November 2024

Background: Recent advances in the personalized treatment of non-small cell lung cancer (NSCLC) require representative in vitro model systems that reflect tumor heterogeneity and maintain the characteristic genetic aberrations. We therefore aimed to establish patient-derived NSCLC organoids that offer a reliable platform for further investigations. Methods: NSCLC organoids were cultured between May 2020 and February 2022 from surgically resected NSCLC tissue specimens. After histological and immunohistochemical validation, genetic validation was performed by targeted next-generation sequencing of tissue and organoid specimens using the Oncomine Focus Assay (ThermoFisher Scientific). Results: From 37 resected NSCLC samples, 18 primary organoid cultures were successfully established and expanded during early passages. Upon histomorphological validation, organoids showed complementary characteristics when compared to the resected parental tumor, including adenocarcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, and lung carcinoid differentiation. Among nine parental tumors, traceable genetic alterations were detected, and three corresponding organoids lines retained this mutational profile, including a KRAS p.Gly12Val mutation, KRAS p.Gly12Cys mutation, and RET-fusion. Conclusions: The establishment of primary NSCLC organoids from surgically resected tissue is feasible. Histological, immunohistochemical, and genetic validation is essential to identify representative NSCLC organoids that maintain the characteristics of the parental tumor. Overall, low establishment rates remain a challenge for broad clinical applications.
Trends in Childhood Behavioral, Mental, and Developmental Problems (2019–2022) Using the National Survey of Children’s Health
Authors: Lent Austin , Dunn Ayden , Eldawy Nada , Jhumkhawala Vama , Rao Meera , Sohmer Joshua , Sacca Lea
Published: November 2024

Background: This study examines nationwide prevalence of US childhood behavioral, mental, and developmental problems in the 6–11 age group category between 2019 and 2022, and several key metrics related to caregiver social determinants of health. Methods: We used NSCH data for 6–11-year-old children for the years 2019–2022. Summary statistics for the selected sample were generated and binary logistic regressions were conducted for each severity level binary variable for each study year with caregiver mental or emotional health as a covariate. Results: Our study found significant associations between severe childhood anxiety and “fair” or “poor” caregiver rankings of mental and emotional health for both the 2020 and 2022 survey years. Our study also found that caregiver mental and emotional health may play a role in childhood ADD and ADHD prevalence rates as caregivers who ranked their mental health as “fair” or “good” had significantly higher odds of having a child with severe ADD or ADHD than caregivers who reported “excellent” mental and emotional health. Conclusion: These findings support prospects of an increase in the need for developmental health services, thus necessitating efforts towards effective allocation and focus of developmental treatment programs tailored to children and pediatric population groups.
Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats
Authors: Guo Mu , Yu Xiangbin , Yang Zesheng , Zheng Hanlu , Zhang Jiahui , Wang Junxiang , Liao Yiqi , Huang Weirui , Lin Zhaolong , Yan Yingxue , Qiu Nengfu , Chen Jianmin , Yu Yue
Published: November 2024

Background/Objectives: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by a protracted course, high rates of morbidity, and disability yet lacks effective therapeutic modalities. Levamisole (LVM), an immunomodulatory drug, has been clinically reported for its potential in RA treatment, while its therapeutic mechanism toward RA remains to be elucidated. Hence, this study provides theoretical support for the application of LVM in the treatment of RA. Methods: This study employed male Sprague–Dawley (SD) rats to construct the adjuvant-induced arthritis (AIA) model, administering LVM orally (5 mg/kg, 15 mg/kg, and 45 mg/kg) for 25 days. An evaluation of LVM’s therapeutic effects on RA was conducted through arthritis index scores, paw pad thickness, paw volume, hematoxylin and eosin (H&E) staining, 3D microcomputed tomography (micro-CT) scans, serum levels of pro-/anti-inflammatory cytokines, and serum biochemical indicators. Western blotting and immunohistochemistry staining were utilized to measure the expression levels of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) proteins in synovial and ankle joint tissues. Results: Treatment with the median dose of LVM (15 mg/kg, M-LVM) significantly reduced the arthritis index (p < 0.01), paw pad thickness (p < 0.001), and paw volume (p < 0.01) without affecting body weight. Additionally, M-LVM alleviated inflammatory lesions in the synovium and ankle joints and also normalized serum levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β). The Model group exhibited significant increases in serum levels of alkaline phosphatase (ALP) (p < 0.01), creatine kinase (CK) (p < 0.05), and glucose (GLU) (p < 0.001) compared with the Control group; however, M-LVM effectively regulated these parameters to normal levels. Western blotting and immunohistochemistry staining revealed that PI3K-/Akt-related proteins were highly expressed in the synovial and ankle joint tissues of rats in the Model group, while treatment with M-LVM significantly reduced the expression of these proteins. Furthermore, histological examination of major organs (heart, liver, lungs, kidneys, and thymus) showed no significant pathological changes, with the exception of the spleen, where M-LVM ameliorated splenic lesions. Conclusions: We demonstrate that LVM at an optimal dose substantially relieves synovitis and bone erosion in AIA rats by inhibiting the PI3K/Akt signaling pathway.
Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update
Authors: Damasceno Renan Oliveira Silva , Pinheiro João Lucas Silva , Rodrigues Lucas Henrique Marques , Gomes Rebeca Carneiro , Duarte Allana Brunna Sucupira , Emídio Jeremias Justo , Diniz Lúcio Ricardo Leite , de Sousa Damião Pergentino
Published: November 2024

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.
Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice
Authors: Emeka Promise M. , Badger-Emeka Lorina I. , Thirugnanasambantham Krishnaraj , Alatawi Abdulaziz S.
Published: November 2024

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions.
Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly
Authors: Kalmouni Mona , Oh Yujeong , Alata Wael , Magzoub Mazin
Published: November 2024

Peptides possess a number of pharmacologically desirable properties, including greater chemical diversity than other biomolecule classes and the ability to selectively bind to specific targets with high potency, as well as biocompatibility, biodegradability, and ease and low cost of production. Consequently, there has been considerable interest in developing peptide-based therapeutics, including amyloid inhibitors. However, a major hindrance to the successful therapeutic application of peptides is their poor delivery to target tissues, cells or subcellular organelles. To overcome these issues, recent efforts have focused on engineering cell-penetrating peptide (CPP) antagonists of amyloidogenesis, which combine the attractive intrinsic properties of peptides with potent therapeutic effects (i.e., inhibition of amyloid formation and the associated cytotoxicity) and highly efficient delivery (to target tissue, cells, and organelles). This review highlights some promising CPP constructs designed to target amyloid aggregation associated with a diverse range of disorders, including Alzheimer’s disease, transmissible spongiform encephalopathies (or prion diseases), Parkinson’s disease, and cancer.
Inhalable Anti-EGFR Antibody-Conjugated Osimertinib Liposomes for Non-Small Cell Lung Cancer
Authors: Daram Apoorva , Sawant Shruti S. , Mehta Dhwani A. , Sanhueza Carlos A. , Kunda Nitesh K.
Published: November 2024

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths globally. The most extensive treatment is Tyrosine Kinase Inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) overexpression. Osimertinib, a third-generation TKI is approved to target EGFR exon 19 deletions or exon 21 L858R mutations. However, resistance is inevitable due to emergence of triple mutations (sensitizing mutations, T790M and C797S). To overcome this challenge, a combinatorial approach was used wherein Osimertinib liposomes were conjugated with cetuximab (CTX), an anti-EGFR monoclonal antibody, to improve drug efficacy and delivery. Additionally, pulmonary administration was employed to minimize systemic toxicity and achieve high lung concentrations. Methods: Osimertinib liposomes (OB-LPs) were prepared using thin film hydration method and immunoliposomes (CTX-OB-LPs) were prepared by conjugating the OB-LPs surface with CTX. Liposomes were characterized for particle size, zeta-potential, drug loading, antibody conjugation efficiency, in vitro drug release, and aerosolization performance. Further, the in vitro efficacy of immunoliposomes was evaluated in H1975 cell line. Results: Immunoliposomes exhibited a particle size of 150 nm, high antibody conjugation efficiency (87%), efficient drug release, and excellent aerosolization properties with an aerodynamic diameter of 3 μm and fine particle fraction of 88%. Furthermore, in vitro studies in H1975 cells showed enhanced cytotoxicity with CTX-OB-LPs displaying 1.7-fold reduction and 1.2-fold reduction in IC50 compared to Osimertinib and OB-LPs, respectively. The CTX-OB-LPs also significantly reduced tumor cell migration and colonization compared to Osimertinib and OB-LPs. Conclusions: These successful results for EGFR-targeting inhalable immunoliposomes exhibited potential for contributing to greater anti-tumor efficacy for the treatment of non-small cell lung cancer.
Night Interruption with Red and Far-Red Light Optimizes the Phytochemical Composition, Enhances Photosynthetic Efficiency, and Increases Biomass Partitioning in Italian Basil
Authors: Fallah Soheil , Aliniaeifard Sasan , Zare Mehrjerdi Mahboobeh , Mirzaei Shima , Gruda Nazim S.
Published: November 2024

Controlled environment agriculture is a promising solution to address climate change and resource limitations. Light, the primary energy source driving photosynthesis and regulating plant growth, is critical in optimizing produce quality. However, the impact of specific light spectra during night interruption on improving phytochemical content and produce quality remains underexplored. This study investigated the effects of red (peak wavelength at 660 nm) and far-red night interruption (peak wavelength at 730 nm) on photosynthetic efficiency, biomass distribution, and phytochemical production in Italian basil (Ocimum basilicum L.). Treatments included red light, far-red light, a combination of both, and a control without night interruption. Red light significantly increased chlorophyll a by 16.8%, chlorophyll b by 20.6%, and carotenoids by 11%, improving photosynthetic efficiency and nutritional quality. Red light also elevated anthocyanin levels by 15.5%, while far-red light promoted flavonoid production by 43.56%. Although red light enhanced biomass, the primary benefit was improved leaf quality, with more biomass directed to leaves over roots. Far-red light reduced transpiration, enhancing post-harvest water retention and shelf life. These findings demonstrate that red and far-red night interruption can optimize phytochemical content, produce quality, and post-harvest durability, offering valuable insights for controlled environment agriculture. Future research should focus on refining night interruption light strategies across a broader range of crops to enhance produce quality and shelf life in controlled environment agriculture.
De Novo Transcriptome Assembly of Rice Bean (Vigna umbellata) and Characterization of WRKY Transcription Factors Response to Aluminum Stress
Authors: Ariharasutharsan Gunasekaran , Akilan Manoharan , Dhasarathan Manickam , Amaravel Manivel , Divya Sankaran , Deivamani Mariyappan , Sudha Manickam , Pandiyan Muthaiyan , Karthikeyan Adhimoolam , Senthil Natesan
Published: November 2024

Rice bean is an underutilized legume crop cultivated in Asia, and it is a good source of protein, minerals, and essential fatty acids for human consumption. Moreover, the leaves left over after harvesting rice bean seeds contain various biological constituents beneficial to humans and animals. In our study, we performed a de-novo transcriptome assembly of rice bean, characterized the WRKY transcription factors, and studied their response to aluminum stress. A total of 46.6 million clean reads, with a GC value of 43%, were generated via transcriptome sequencing. De novo assembly of the clean reads resulted in 90,933 transcripts and 74,926 unigenes, with minimum and maximum lengths of 301 bp and 24,052 bp, and N50 values of 1801 bp and 1710 bp, respectively. A total of 27,095 and 28,378 unigenes were annotated and subjected to GO and KEGG analyses. Among the unigenes, 15,593, 20,770, and 15,385 unigenes were identified in the domains of biological process, molecular function, and cellular component, respectively. A total of 16,132 unigenes were assigned to 188 pathways, including metabolic pathways (5500) and secondary metabolite biosynthesis (2858). Transcription factor analysis revealed 4860 unigenes from 98 different transcription factor families. For WRKY, a total of 95 unigenes were identified. Further analysis revealed the diverse response of WRKY transcription factors to aluminum stress. Collectively, the results of this study boost genomic resources and provide a baseline for further research on the role of WRKY transcription factors in aluminum tolerance in rice bean.
Trends in Plants Phytochemistry and Bioactivity Analysis
Authors: Savickiene Nijole , Raudone Lina
Published: November 2024

Biologically active compounds, derived from various natural sources, have garnered significant attention due to their potential therapeutic applications [...]
Genome-Wide Identification and Expression Profiling Analysis of the Mitochondrial Calcium Uniporter Gene Family Under Abiotic Stresses in Medicago sativa
Authors: Li Wanhong , Jia Bowei , Sheng Jiaxun , Shen Yang , Jin Jun , Sun Xiaoli , Liu Xiangping , Sun Mingzhe
Published: November 2024

The mitochondrial calcium uniporters (MCUs) are a family of calcium unidirectional transporters important for cytoplasmic Ca2+ signals. Though the MCU proteins in several plant species have been investigated, genome-wide analysis of MCUs in alfalfa is lacking. Here, via genome-wide analysis, a total of 5, 20, and 6 MCU genes were identified in three different alfalfa cultivars, namely Medicago truncatula Jemalong A17, Medicago sativa XinJiangDaYe, and M. sativa Zhongmu No. 1, respectively. They were further phylogenetically classified into three subfamilies. Most MCU genes have only one intron, and gene duplication events of MCU genes were observed within each alfalfa accession and between different accessions. All alfalfa MCU proteins contained a highly conserved MCU domain and 10 conserved motifs, featuring two transmembrane domains and a DI/VME motif. According to the tissue expression data of M. sativa Zhongmu No. 1, MsMCU6.2 was the most abundant transcript with the highest expression in the leaf, and MsMCU5 and MsMCU1.2 showed higher expression levels in the stem than other tissues. We analyzed the expression profiles of five MCU genes (MsMCU1.1/1.2/5/6.1/6.2) under salt, drought, and cold stresses via qRT-PCR assays. All five MCU genes were induced by drought stress, except MsMCU5, whose expression was up-regulated by salt stress, while cold stress slightly altered MsMCU expression. Nine potential interacting proteins and three miRNAs targeting MtMCUs were predicted. These results provide detailed knowledge of alfalfa MCU genes and suggest their potential functions in abiotic stress response.
Utilization of Alternative Fibres Manufactured from Recycled PET Bottles in Concrete Technology for the Improvement of Fire Resistance
Authors: Sedlmajer Martin , Zach Jiří , Bubeník Jan , Bydžovský Jiří , Novák Vítězslav
Published: November 2024

This article addresses the potential use of secondary polymer fibres in the field of structural concrete as a replacement for primary polymer fibres (mainly polypropylene/PP/), which are used in concrete to enhance its resistance when exposed to high temperatures (especially in the case of fire). Research has shown that, in addition to PP fibres, polyethylene terephthalate/PET/fibres, produced by recycling packaging materials (mainly PET bottles), can also be used as an alternative. These fibres are industrially produced in similar dimensions as PP fibres and exhibit similar behaviour when added to fresh and hardened concrete. In terms of their effect on increasing resistance to extreme heat loads, it has been found that despite a higher melting point (Tm), concrete with these fibres demonstrates comparable fire resistance. Therefore, it can be concluded that secondary PET fibres represent an interesting alternative to primary PP fibres from the perspective of a circular economy, and their use in construction represents a potentially valuable application for PET obtained through the collection and recycling of PET packaging materials.
In Situ Fluorescent Visualization of the Interfacial Layer of Induced Crystallization in Polyvinyl Chloride
Authors: An Zhihang , Liu Renping , Dai Zhenhao , Liu Jiaping , Du Jiaying , Sheng Zhongyi , Liu Heyang
Published: November 2024

Despite the remarkable progress in the modification and application of polyvinyl chloride (PVC), developing processing aids for the induced crystallization of PVC and characterizing its interfacial layer remain challenges. Herein, we propose a new polymeric nucleating agent, polyamidea12-graft-styrene–maleic anhydride copolymer (PA12-g-SMA), which possesses high compatibility and crystallinity, effectively improving the crystallinity to 15.1%, the impact strength to 61.03 kJ/m2, and the degradation temperature of PVC to 267 °C through a single and straightforward processing step. Additionally, after the introduction of two different fluorescent sensors in PA12-g-SMA and PVC, the interfacial layer of the induced crystallization can be monitored in situ via a confocal laser scanning microscope (CLSM). This study highlights a rare strategy for significantly enhancing the physical properties of rigid PVC through simply adding a polymeric nucleating agent during processing, while also emphasizing the importance of visualizing the interfacial layer to understand various polymer crystallization processes.
Development and Application of High-Internal-Phase Water-in-Oil Emulsions Using Amphiphilic Nanoparticle-Based Emulsifiers
Authors: Zhao Chunhua , Wang Xiujun , Zhang Jian , Liu Yigang , Liu Changlong , Huang Bo , Yang Yang
Published: November 2024

High-internal-phase water-in-oil (W/O) emulsions generated in situ have garnered considerable attention as novel profile control systems. However, conventional emulsifiers are unreactive and poorly dispersed in water, necessitating large dosages and resulting in poor injectivity. In this study, we synthesized amphiphilic nanoparticles (SiO2–NH2–DAC NPs) containing amine and long-chain alkyl groups using a one-pot method and investigated the stabilized emulsion properties. Our results indicated that W/O emulsions with a water-to-oil ratio (WOR) of 7:3 to 8:2 could be prepared with just 0.1 wt% of SiO2–NH2–DAC NPs under neutral and basic conditions, with demulsification occurring under acidic conditions (pH = 2.1), demonstrating the pH-responsiveness of the W/O emulsions. The emulsion viscosity increased from 150 to 2555 mPa·s at different WORs. An additional 18.7% oil recovery was achieved using SiO2–NH2–DAC NPs in a heterogeneous core, highlighting their potential as a promising profile control candidate.