bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Role of SlRNC1 in Chloroplast Development and Global Gene Regulation in Tomato Plants
Authors: Nie Yuxin , Zhang Yuhong , Wang Luyou , Wu Jian
Published: June 2024

RNC1, a plant-specific gene, is known for its involvement in splicing group II introns within maize chloroplast. However, its role in chloroplast development and global gene expression remains poorly understood. This study aimed to investigate the role of RNC1 in chloroplast development and identify the genes that mediate its function in the development of entire tomato plants. Consistent with findings in maize, RNC1 silencing induced dwarfism and leaf whitening in tomato plants. Subcellular localization analysis revealed that the RNC1 protein is localized to both the nucleus and cytoplasm, including the stress granule and chloroplasts. Electron microscopic examination of tomato leaf transverse sections exposed significant disruptions in the spatial arrangement of the thylakoid network upon RNC1 silencing, crucial for efficient light energy capture and conversion into chemical energy. Transcriptome analysis suggested that RNC1 silencing potentially impacts tomato plant development through genes associated with all three categories (biological processes, cellular components, and molecular functions). Overall, our findings contribute to a better understanding of the critical role of RNC1 in chloroplast development and its significance in plant physiology.
Yohimbine Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation and Migration via FOXO3a Factor
Authors: Lim Leejin , Kim Hyeonhwa , Jeong Jihye , Han Sung Hee , Yu Young-Bob , Song Heesang
Published: June 2024

Yohimbine (YHB) has been reported to possess anti-inflammatory, anticancer, and cardiac function-enhancing properties. Additionally, it has been reported to inhibit the proliferation, migration, and neointimal formation of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) stimulation by suppressing the phospholipase C-gamma 1 pathway. However, the transcriptional regulatory mechanism of YHB controlling the behavior of VSMCs is not fully understood. In this study, YHB downregulated the expression of cell cycle regulatory proteins, such as proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin E, by modulating the transcription factor FOXO3a in VSMCs induced by PDGF. Furthermore, YHB decreased p-38 and mTOR phosphorylation in a dose-dependent manner. Notably, YHB significantly reduced the phosphorylation at Y397 and Y925 sites of focal adhesion kinase (FAK), and this effect was greater at the Y925 site than Y397. In addition, the expression of paxillin, a FAK-associated protein known to bind to the Y925 site of FAK, was significantly reduced by YHB treatment in a dose-dependent manner. A pronounced reduction in the migration and proliferation of VSMCs was observed following co-treatment of YHB with mTOR or p38 inhibitors. In conclusion, this study shows that YHB inhibits the PDGF-induced proliferation and migration of VSMCs by regulating the transcription factor FOXO3a and the mTOR/p38/FAK signaling pathway. Therefore, YHB may be a potential therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and vascular restenosis.
Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review
Authors: Müller Joachim , Boubaker Ghalia , Müller Norbert , Uldry Anne-Christine , Braga-Lagache Sophie , Heller Manfred , Hemphill Andrew
Published: June 2024

Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical “one drug”—“one target” paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.
Expression of Intracellular Galectin-8 and -9 in Endometrial Cancer
Authors: Beyer Susanne , Wehrmann Maya , Meister Sarah , Trillsch Fabian , Ganster Franziska , Schmoeckel Elisa , Corradini Stefanie , Mahner Sven , Jeschke Udo , Kessler Mirjana , Burges Alexander , Kolben Thomas
Published: June 2024

Endometrial cancer (EC) is a common gynecological cancer worldwide. Treatment has been improved in recent years; however, in advanced stages, therapeutic options are still limited. The expression of galectins is increased in several tumor types and that they are involved in important cell processes. Large studies on endometrial cancer are still pending; Specimens of 225 patients with EC were immunohistochemically stained with antibodies for Gal-8 and Gal-9. Expression was correlated with histopathological variables. The cytosolic expression of both galectins is associated with grading and survival. Cytosolic Galectin-8 expression is a positive prognostic factor for overall survival (OS) and progression-free survival (PFS), while nuclear Gal-8 expression correlates only to OS. The cytosolic presence of Galectin-9 is correlated with a better prognosis regarding OS. Our results suggest that expression of both galectins is associated with OS and PFS in EC. Further studies are needed to understand the underlying molecular mechanisms.
Impact of Global Health Scholarship Programs in the Faculty of Medicine at Mbarara University of Science and Technology
Authors: Tusiimire Jonans , Nakiwala Miriam Josephine , Turigye Brian , Ansiimire Daphine , Kembabazi Annet , Asiimwe Stephen , Ngonzi Joseph
Published: June 2024

In recognition of the critical role of residency programs in narrowing healthcare inequalities, Global Health scholarships were introduced at Mbarara University of Science and Technology (MUST) in 2011. Since then, at least 154 postgraduate students in priority programs have benefited. We conducted an online cross-sectional survey to examine how the scholarships and beneficiaries have impacted MUST and the community. Fifty (50) beneficiaries, representing 32.5%, responded, of whom 36 (72%) were alumni. Most respondents were males (n = 30; 60%) pursing Master of Medicine (n = 29; 58%) or Master of Nursing Science (n = 20; 40%) programs. The scholarship schemes included First Mile (n = 29; 58%), Kayanja (n = 12; 24%), Paiko (n = 5; 10%) and Seed (n = 4; 8%). The majority of the scholarships supported both tuition and research fees (n = 41; 82%), the rest being partial. Career advancement was undertaken by eight (16%) of the scholars in the form of fellowships (n = 3; 6%), other masters (n = 3; 6%) and PhDs (n = 3; 6%), with some students having attained a combination of these. All scholars belonged to at least one health professional association. Over 88% (n = 32) of the alumni and 28% (n = 4) of the students were employed. The majority of those employed were in the public sector (n = 24; 66.7%), mainly the health sector (n = 18; 50%), academia (n = 14; 38.9) or both (n = 4; 11.1%). There was a high impact on health care provision, undergraduate training and research carried out by the scholars both during training and post-graduation. High levels of career satisfaction, scholarship impact and academic program relevance were reported. The findings provide insights on how low-fund specialty scholarships can have a far-reaching impact on local training, health care and research in low- and middle-income countries.
Characterization of Posidonia oceanica Fibers High-Density Polyethylene Composites: Reinforcing Potential and Effect of Coupling Agent
Authors: Haddar Manel , Elloumi Ahmed , Bradai Cheldly , Koubaa Ahmed
Published: June 2024

This study investigated the influence of fiber loading and maleated polyethylene (MAPE) coupling agent on the structural, thermal, mechanical, morphological properties, and torque rheology of high-density polyethylene (HDPE) reinforced with Posidonia oceanica fiber (POF) composites. HDPE/POF composites, both with and without MAPE, were manufactured using a two-step process: composite pellets extrusion, followed by test samples injection molding with various POF loadings (0, 20, 30, and 40 wt%). HDPE/POF composites reinforced with higher loading of POF (40 wt%) exhibit superior stiffness, better crystallinity, and higher stabilized torque and mechanical energy (Em) compared to other composite formulations. Therefore, varying the POF loading leads to extrusion and injection processing variations. Furthermore, the coupling agent significantly enhances the tensile strength, ductility, impact strength, crystallinity, stabilized torque, and Em of the HDPE/POF composite. This improvement is due to the enhanced interfacial adhesion between the POF and the HDPE matrix with the addition of the MAPE, as supported by the Scanning Electron Microscopy (SEM) micrographs.
Designing Dual-Responsive Drug Delivery Systems: The Role of Phase Change Materials and Metal–Organic Frameworks
Authors: Wei Wanying , Lu Ping
Published: June 2024

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal–organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in acidic environments, thus offering pH-sensitive drug release capabilities. The integration of these materials enables the fabrication of complex structures that encapsulate drugs within ZIF-8 or are enveloped by PCM layers, ensuring that drug release is tightly controlled by either temperature or pH levels, or both. This review provides comprehensive insights into the core design principles, material selections, and potential biomedical applications of dual-stimuli responsive DDSs, highlighting the future directions and challenges in this innovative field.
Shear Bond Strength of Orthodontic Brackets Bonded with Thermo-Cured Glass-Based Materials—An In Vitro Study
Authors: Cvitanović Stipo , Zovko Ružica , Mabić Mirela , Jurišić Sanja , Jelić-Knezović Nevenka , Glavina Domagoj , Goršeta Kristina
Published: June 2024

The results of orthodontic therapy largely depend, among other factors, on the preparation of the tooth enamel itself and the choice of material used to bond orthodontic brackets. The aim of this in vitro study was to determine the shear bond strength (SBS) and adhesive remnant index (ARI) score of thermo-cured glass–ionomers on different pretreated enamel, in comparison with the commonly used composite cement. Three commercially available nano-ionomer or highly viscous glass–ionomer cements (EQUIA Forte® Fil, EQUIA Fil, Ketac Universal) and two types of compo-sites (Heliosit Orthodontic, ConTec Go!) were investigated in this study. The research involved two hundred human premolars. The teeth were cleaned and polished, then randomly divided into five groups according to the enamel preparation method and the type of material. The enamel was treated in three different ways: polyacrylic acid, phosphoric acid, 5% NaOCl + etching with phosphoric acid, and a control group without treatment. Glass–ionomer cement was thermo-cured with heat from a polymerization unit during setting. Statistical analysis was performed using a Chi-square test and one-way ANOVA for independent samples. Spearman’s Rho correlation coefficient was used to examine the relationship. Regardless of the material type, the results indicated that the weakest bond between the bracket and tooth enamel was found in samples without enamel pretreatment. The majority of the materials stayed on the brackets in samples without enamel preparation, according to ARI scores. The study’s findings demonstrated that the strength of the adhesion between the bracket and enamel is greatly influenced by enamel etching and glass–ionomer thermo-curing. Clinical investigations would be required to validate the outcomes.
Pecan Shell-Derived Activated Carbon for High-Electrochemical Performance Supercapacitor Electrode
Authors: Zou Sarah J. , Patel Mumukshu D. , Smith Lee M. , Cha Eunho , Shi Sheldon Q. , Choi Wonbong
Published: June 2024

Carbon nanomaterials-based electric double-layer capacitors (EDLCs) are reliable and appealing energy-storage systems offering high power density and long cycling stability. However, these energy storage devices are plagued with critical shortcomings, such as low specific capacitance, inefficient physical/chemical activation process, and self-discharge of electrode materials, hindering their future application. In this work, we use a self-activation process, an environmentally benign and low-cost process, to produce high-performance activated carbon (AC). Novel activated carbon from pecan shells (PS) was successfully synthesized through a single-step self-activation process, which combines the carbonization and activation processes. The as-synthesized pecan shell-derived activated carbon (PSAC) provides a high-porosity, low-resistance, and ordered pore structure with a specific pore volume of 0.744 cm3/g and BET surface area of 1554 m2/g. The supercapacitors fabricated from PSAC demonstrate a specific capacitance of 269 F/g at 2 A/g, excellent cycling stability over 15,000 cycles, and energy and power density of 37.4 Wh/kg and of 2.1 kW/kg, respectively. It is believed that the high-efficiency PSAC synthesized from the novel self-activation method could provide a practical route to environmentally friendly and easily scalable supercapacitors.
Investigation of Materials for Enhanced Vibrational Insulation in Ground Structures Using Concrete Mixtures: A Case Study of Rubber Aggregate Addition
Authors: Gruszczyński Maciej , Kowalska-Koczwara Alicja , Tatara Tadeusz
Published: June 2024

The reduction of vibrations in concrete has been a topic of discussion among scientists. This article presents research on designing concrete mixes for constructing ground barriers with enhanced vibration isolation using waste materials. This study discusses the design of concrete mixes for the construction of concrete partitions with increased vibration isolation, using the polish standards. The experiments were conducted at the Laboratory of Building Materials Engineering at the Cracow University of Technology as part of the project entitled “Innovative construction of vibration-insulating barriers to protect the environment from transport vibrations and similar sources”. The concrete composition utilized blast furnace cement CEM III/A 42.5 N, with mineral and chemical additives. Recycled rubber aggregate from used tires was employed to enhance vibration isolation. Measurement results demonstrated the effectiveness of the concrete in dampening vibrations, confirming its suitability for practical use.
Application of Li6.4La3Zr1.45Ta0.5Mo0.05O12/PEO Composite Solid Electrolyte in High-Performance Lithium Batteries
Authors: Lin Chengjun , Huang Yaoyi , Deng Dingrong , Xiong Haiji , Lu Bin , Weng Jianchun , Fan Xiaohong , Li Guifang , Zeng Ye , Li Yi , Wu Qihui
Published: June 2024

Replacing the flammable liquid electrolytes with solid ones has been considered to be the most effective way to improve the safety of the lithium batteries. However, the solid electrolytes often suffer from low ionic conductivity and poor rate capability due to their relatively stable molecular/atomic architectures. In this study, we report a composite solid electrolyte, in which polyethylene oxide (PEO) is the matrix and Li6.4La3Zr1.45Ta0.5Mo0.05O12 (LLZTMO) and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) are the fillers. Ta/Mo co-doping can further promote the ion transport capacity in the electrolyte. The synthesized composite electrolytes exhibit high thermal stability (up to 413 °C) and good ionic conductivity (LLZTMO–PEO 2.00 × 10−4 S·cm−1, LLZTO–PEO 1.53 × 10−4 S·cm−1) at 35 °C. Compared with a pure PEO electrolyte, whose ionic conductivity is in the range of 10−7~10−6 S·cm−1, the ionic conductivity of composite solid electrolytes is greatly improved. The full cell assembled with LiFePO4 as the positive electrode exhibits excellent rate performance and good cycling stability, indicating that prepared solid electrolytes have great potential applications in lithium batteries.
Genomic Analysis of Novel Sulfitobacter Bacterial Strains Isolated from Marine Biofilms
Authors: Cui Han , Fan Shen , Ding Wei , Zhang Weipeng
Published: June 2024

Bacteria from the genus Sulfitobacter are distributed across various marine habitats and play a significant role in sulfur cycling. However, the metabolic features of Sulfitobacter inhabiting marine biofilms are still not well understood. Here, complete genomes and paired metatranscriptomes of eight Sulfitobacter strains, isolated from biofilms on subtidal stones, have been analyzed to explore their central energy metabolism and potential of secondary metabolite biosynthesis. Based on average nucleotide identity and phylogenetic analysis, the eight strains were classified into six novel species and two novel strains. The reconstruction of the metabolic pathways indicated that all strains had a complete Entner–Doudoroff pathway, pentose phosphate pathway, and diverse pathways for amino acid metabolism, suggesting the presence of an optimized central carbon metabolism. Pangenome analysis further revealed the differences between the gene cluster distribution patterns among the eight strains, suggesting significant functional variation. Moreover, a total of 47 biosynthetic gene clusters were discovered, which were further classified into 37 gene cluster families that showed low similarity with previously documented clusters. Furthermore, metatranscriptomic analysis revealed the expressions of key functional genes involved in the biosynthesis of ribosomal peptides in in situ marine biofilms. Overall, this study sheds new light on the metabolic features, adaptive strategies, and value of genome mining in this group of biofilm-associated Sulfitobacter bacteria.
The Role of Obsessive Compulsive Traits in Fibromyalgia: Is Pain-Related Obsessive Ideation Involved in Pathogenesis?
Authors: Lugassy-Galper Bat-El , Amital Mor , Amital Howard , Buskila Dan , Amital Daniela
Published: June 2024

Background and Objectives: Fibromyalgia syndrome (FMS) is defined as a chronic pain syndrome that is characterized by widespread pain, tenderness, and diffuse stiffness. In addition, neuropsychological symptoms such as fatigue, sleep disorders, poor mood, cognitive impairment, and headaches are often reported. Many reports have addressed the coexistence of affective disorders and anxiety with FMS, yet few have focused on its association with obsessive compulsive disorder (OCD). We investigated the occurrence of classical patterns of OCD in participants with FMS and assessed their effect on pain perception and functional impairment. Material and Methods: The research population included 37 patients diagnosed with FMS, treated at the Rheumatology Clinic in the Sheba Medical Center, Tel-Hashomer, Israel. We used validated questionnaires including a demographic questionnaire, a questionnaire on average and maximal pain intensity, the Eysenck Personality Questionnaire-Revised (EPQ-R), the Perceived Stress Scale, the Pain Catastrophizing Scale, the Pain Obsessive questionnaire, and the Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Results: Patients with FMS were found to have intrusive and obsessive thoughts regarding pain for several hours every day, causing a high degree of anxiety and high levels of pain, catastrophizing, and magnification, leading to helplessness and functional impairment. In total, 27% of the patients reported severe malfunction due to pain and pain ideation, and 49% demonstrated mild obsessive compulsive symptoms that were strongly correlated with pain intensity and functional impairment. Conclusions: Obsessive compulsive thinking patterns contribute to pain magnification and to the cognitive aspects of fibromyalgia syndrome.
Long-Term Outcome of Surgery for Perianal Crohn’s Fistula
Authors: Schaad Marie , Schoepfer Alain , Rossel Jean-Benoît , Barry Mamadou Pathé , Rogler Gerhard , Hahnloser Dieter
Published: June 2024

Background and Objectives: Patients with perianal Crohn’s (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0–12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.
Modeling and Optimization of Concrete Mixtures Using Machine Learning Estimators and Genetic Algorithms
Authors: Oviedo Ana I. , Londoño Jorge M. , Vargas John F. , Zuluaga Carolina , Gómez Ana
Published: June 2024

This study presents a methodology to optimize concrete mixtures by integrating machine learning (ML) and genetic algorithms. ML models are used to predict compressive strength, while genetic algorithms optimize the mixture cost under quality constraints. Using a dataset of over 19,000 samples from a local ready-mix concrete producer, various predictive ML models were trained and evaluated regarding cost-effective solutions. The results show that the optimized mixtures meet the desired compressive strength range and are cost-efficient, thus having 50% of the solutions yielding a cost below 98% of the test cases. CatBoost emerged as the best ML technique, thereby achieving a mean absolute error (MAE) below 5 MPa. This combined approach enhances quality, reduces costs, and improves production efficiency in concrete manufacturing.
A Ratiometric Fluorescent Probe Dye-Functionalized MOFs Integrated with Logic Gate Operation for Efficient Detection of Acetaldehyde
Authors: Li Wenwei , Liu Min , Zhao Yourong , Fan Yangchun , Li Yuting , Gao Hongmei , Li Hongda , Gao Daojiang , Ning Zhanglei
Published: June 2024

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal–organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10−4~10−5 μL/mL, with a low detection limit of 8.12 × 10−4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.
The Influence of Active Compounds of Chips Made from Different Wood Species on the Antioxidant, Oenological and Sensory Properties of Apple Wines
Authors: Tarko Tomasz , Pater Aneta , Januszek Magdalena , Duda Aleksandra , Krankowski Filip
Published: June 2024

Wood chips contain numerous active compounds that can affect the wine’s characteristics. They are commonly used in red grape wines, whisky, cherry and brandy, but in fruit wines, production is not typically utilised. The aim of this study was to compare the impact of an oak barrel ageing with the effect of the addition of chips made from various types of wood (oak, maple, cherry, apple) and with various degrees of toasting to the apple wines on their antioxidant, oenological and sensory properties. The oenological parameters, the polyphenols content, antioxidant activity and content of volatile odour-active compounds were assessed. It was shown that ageing in the presence of wood chips had a less noticeable effect on the oenological and sensory parameters of the wine than barrel ageing. Moreover, wood chips used did not significantly affect the acidity, alcohol and extract content of apple wines. Wines aged in the presence of oak chips (particularly lightly toasted) exhibited the greatest increase in polyphenols, while the polyphenol content of wines aged in the presence of other chips was not dependent on their toasting degree. The ageing of fruit wines with wood chips influences the volatile profile and the olfactory sensations, which can improve their quality.
Scaly MoS2/rGO Composite as an Anode Material for High-Performance Potassium-Ion Battery
Authors: Wang Bin , Deng Tao , Liu Jingjing , Sun Beibei , Su Yun , Ti Ruixia , Shangguan Lihua , Zhang Chaoyang , Tang Yu , Cheng Na , Xu Yan , Guo Junling
Published: June 2024

Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.
PyBox–La(OTf)3-Catalyzed Enantioselective Diels–Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene
Authors: Wei Hao , Zhang Yujie , Jin Sanlin , Yu Ying , Chen Ning , Xu Jiaxi , Yang Zhanhui
Published: June 2024

The PyBox–La(OTf)3-catalyzed enantioselective Diels–Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.
Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells
Authors: Jonić Natalija , Koprivica Ivan , Chatzigiannis Christos M. , Tsiailanis Antonis D. , Kyrkou Stavroula G. , Tzakos Eleftherios Paraskevas , Pavić Aleksandar , Dimitrijević Mirjana , Jovanović Andjelina , Jovanović Milan B. , Marinho Sérgio , Castro-Almeida Inês , Otašević Vesna , Moura-Alves Pedro , Tzakos Andreas G. , Stojanović Ivana
Published: June 2024

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.
Differential Effects of In Vitro Simulated Digestion on Antioxidant Activity and Bioaccessibility of Phenolic Compounds in Purple Rice Bran Extracts
Authors: Wanyo Pitchaporn , Chamsai Tossaporn , Toontom Nitchara , Nghiep Le Ke , Tudpor Kukiat
Published: June 2024

Pigmented rice varieties are abundant in phenolic compounds. Antioxidant activity and bioaccessibility of phenolic compounds are modified in the gastrointestinal tract. After in vitro simulated digestion, changes in antioxidant activity and bioaccessibility of phenolic compounds (phenolic acids, flavonoids, and anthocyanins) in purple rice brans (Hom Nil and Riceberry) were compared with undigested crude extracts. The digestion method was conducted following the INFOGEST protocol. Antioxidant activity was determined using the ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assays. The bioaccessibility index (BI) was calculated from the ratio of digested to undigested soluble phenolic content. Overall results showed that the in vitro simulated digested rice brans had lower antioxidant activity and lower total phenolic, flavonoid, and anthocyanin contents. However, the concentration of sinapic acid was stable, while other phenolic acids (gallic, protocatechuic, vanillic, ρ-coumaric, and ferulic acids) degraded after the oral, gastric, and intestinal phases. The BI of sinapic, gallic, vanillic, and ferulic acids remained stable, and the BI of quercetin was resistant to digestion. Conversely, anthocyanins degraded during the intestinal phase. In conclusion, selective phenolic compounds are lost along the gastrointestinal tract, suggesting that controlled food delivery is of further interest.
Ionic Liquid-Based Immunization Patch for the Transdermal Delivery of Antigens
Authors: Islam Rashedul , Nabila Fahmida Habib , Wakabayashi Rie , Kawaguchi Yoshirou , Kamiya Noriho , Moniruzzaman Muhammad , Goto Masahiro
Published: June 2024

Herein, we report a transdermal patch prepared using an ionic liquid-based solid in oil (IL-S/O) nanodispersion and a pressure-sensitive adhesive (PSA) to deliver the macromolecular antigenic protein, ovalbumin (OVA). The IL-S/O nanodispersion and a PSA were first mixed at an equal weight ratio, then coated onto a release liner, and covered with a support film. To evaluate the effect of the PSA, three types of PSAs, DURO-TAK 87-4098, DURO-TAK 87-4287, and DURO-TAK 87-235A, were used to obtain the corresponding IL-S/O patches SP-4098, SP-4287, and SP-235A, respectively. The prepared IL-S/O patches were characterized for surface morphology, viscoelasticity, and moisture content. In vitro skin penetration and in vivo immunization studies of the IL-S/O patches were performed using Yucatan micropig skin and the C57BL/6NJc1 mice model, respectively. The SP-4098 and SP-4287 delivered 5.49-fold and 5.47-fold higher amounts of drug compared with the aqueous formulation. Although both patches delivered a similar amount of drug, SP-4287 was not detached fully from the release liner after 30 days, indicating low stability. Mice immunized with the OVA-containing SP-4098 produced a 10-fold increase in anti-OVA IgG compared with those treated with an aqueous formulation. These findings suggested that the IL-S/O patch may be a good platform for the transdermal delivery of antigen molecules.
Comprehensive Assessment of Collagen/Sodium Alginate-Based Sponges as Hemostatic Dressings
Authors: Sun Leilei , Shen Yanyan , Li Mingbo , Wang Qiuting , Li Ruimin , Gong Shunmin
Published: June 2024

In our search for a biocompatible composite hemostatic dressing, we focused on the design of a novel biomaterial composed of two natural biological components, collagen and sodium alginate (SA), cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and oxidized sodium alginate (OSA). We conducted a series of tests to evaluate the physicochemical properties, acute systemic toxicity, skin irritation, intradermal reaction, sensitization, cytotoxicity, and in vivo femoral artery hemorrhage model. The results demonstrated the excellent biocompatibility of the collagen/sodium alginate (C/SA)-based dressings before and after crosslinking. Specifically, the femoral artery hemorrhage model revealed a significantly shortened hemostasis time of 132.5 ± 12.82 s for the EDC/NHS cross-linked dressings compared to the gauze in the blank group (hemostasis time of 251.43 ± 10.69 s). These findings indicated that C/SA-based dressings exhibited both good biocompatibility and a significant hemostatic effect, making them suitable for biomedical applications.
Colorimetric Immunoassays with Boronic Acid-Decorated, Peroxidase-like Metal-Organic Frameworks as the Carriers of Antibodies and Enzymes
Authors: Sun Ting , Yi Xinyao , Liu Lin , Zhao Feng
Published: June 2024

The sensitivity of immunoassays is generally limited by the low signal reporter/recognition element ratio. Nanomaterials serving as the carriers can enhance the loading number of signal reporters, thus improving the detection sensitivity. However, the general immobilization strategies, including direct physical adsorption and covalent coupling, may cause the random orientation and conformational change in proteins, partially or completely suppressing the enzymatic activity and the molecular recognition ability. In this work, we proposed a strategy to load recognition elements of antibodies and enzyme labels using boronic acid-modified metal-organic frameworks (MOFs) as the nanocarriers for signal amplification. The conjugation strategy was proposed based on the boronate ester interactions between the carbohydrate moieties in antibodies and enzymes and the boronic acid moieties on MOFs. Both enzymes and MOFs could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2, therefore achieving dual signal amplification. To indicate the feasibility and sensitivity of the strategy, colorimetric immunoassays of prostate specific antigen (PSA) were performed with boronic acid-modified Cu-MOFs as peroxidase mimics to catalyze TMB oxidation and nanocarriers to load antibody and enzyme (horseradish peroxidase, HRP). According to the change in the absorbance intensity of the oxidized TMB (oxTMB), PSA at the concentration range of 1~250 pg/mL could be readily determined. In addition, this work presented a site-specific and oriented conjugation strategy for the modification of nanolabels with recognition elements and signal reporters, which should be valuable for the design of novel biosensors with high sensitivity and selectivity.
Geophysical Surveys to Highlight Buried Ancient Walls of Ugento (Lecce, Italy)
Authors: Barbolla Dora Francesca , Miccoli Ilaria , Ditaranto Immacolata , Scardozzi Giuseppe , Giuri Francesco , Ferrari Ivan , Leucci Giovanni
Published: June 2024

Geophysics is a fundamental tool to detect buried structures of archaeological interest through non-destructive techniques. The Messapian city walls in Ugento (Puglia, southern Italy) are of great archaeological importance, and some sections are still visible. In order to locate a stretch of the city walls, geophysical prospections were performed using the low-frequency electromagnetic method and ground-penetrating radar. The surveys were carried out in a peripheral area of Ugento, near a visible section of the city walls. The analysis and interpretation of the measured data revealed clear anomalies that could be ascribed to the city walls that aligned with an adjacent section of the visible walls. Archaeological excavation campaigns found a part of the walls and some important elements, as identified by the geophysical data interpretation.
Ultra-Processed Food Consumption as a Risk Factor for Gastrointestinal Cancer and Other Causes of Mortality in Southern Italy: A Competing Risk Approach
Authors: Campanella Angelo , Tatoli Rossella , Bonfiglio Caterina , Donghia Rossella , Cuccaro Francesco , Giannelli Gianluigi
Published: June 2024

Background: Ultra-Processed Foods (UPFs) are increasingly consumed worldwide, even in regions with strong dietary traditions like the Mediterranean and can play a crucial role in the development of chronic diseases, including cancer. This population-based prospective cohort study investigates the association between UPF consumption and gastrointestinal cancers and other causes of mortality in Southern Italy. Methods: Data were collected from 4870 participants in the MICOL and NUTRIHEP cohorts. The EPIC questionnaire was used to elicit information on food and drink consumption and UPFs were categorized by degree of processing according to the NOVA classification. Cox proportional hazards regression and competing risk models were employed for statistical analysis. Results: UPF consumption was positively associated with all-cause mortality: participants in the 3rd UFP quartile, as compared to the lowest, had a 27% higher risk of death (SHR 1.27 95% CI, 1.03; 1.57), while in the highest quartile as compared to the lowest, the risk was 34% higher (SHR 1.34 95% CI, 1.00; 1.79). Higher UPFs intake was also correlated with an increased gastrointestinal cancers mortality risk, especially the 2nd (SHR 1.65, 95% CI: 1.01; 2.71) and 4th quartile (SHR 3.14 95% CI: 1.56; 6.32), with a dose-dependent effect. For the other cancers, a SHR 1.61 (95% CI 1.03; 2.54) was observed for the 3rd quartile. Conclusions: Our results reinforce the link between UPF consumption and cancer risk, emphasizing the urgent need for interventions targeting dietary patterns.
The Lipid-Metabolism-Associated Anti-Obesity Properties of Rapeseed Diacylglycerol Oil
Authors: Mao Yilin , Zheng Danhong , He Lin , Chen Jing
Published: June 2024

To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine.
Interplay between Electric Field Strength and Number of Short-Duration Pulses for Efficient Gene Electrotransfer
Authors: Urbanskas Ernestas , Jakštys Baltramiejus , Venckus Justinas , Malakauskaitė Paulina , Šatkauskienė Ingrida , Morkvėnaitė-Vilkončienė Inga , Šatkauskas Saulius
Published: June 2024

Electroporation is a method that shows great promise as a non-viral approach for delivering genes by using high-voltage electric pulses to introduce DNA into cells to induce transient gene expression. This research aimed to evaluate the interplay between electric pulse intensity and 100 µs-duration pulse numbers as an outcome of gene electrotransfer efficacy and cell viability. Our results indicated a close relationship between pulse number and electric field strength regarding gene electrotransfer efficacy; higher electric pulse intensity resulted in fewer pulses needed to achieve the same gene electrotransfer efficacy. Subsequently, an increase in pulse number had a more negative impact on overall gene electrotransfer by significantly reducing cell viability. Based on our data, the best pulse parameters to transfect CHO cells with the pMax-GFP plasmid were using 5 HV square wave pulses of 1000 V/cm and 2 HV of 1600 V/cm, correspondingly resulting in 55 and 71% of transfected cells and maintaining 79 and 54% proliferating cells. This shows ESOPE-like 100 µs-duration pulse protocols can be used simultaneously to deliver cytotoxic drugs as well as immune response regulating genetically encoded cytokines.
Comparative Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity or Overweight: A Systematic Review and Network Meta-Analysis
Authors: Liu Ligang , Shi Hekai , Shi Yufei , Wang Anlin , Guo Nuojin , Tao Heqing , Nahata Milap C.
Published: June 2024

Four glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used in children and adolescents with obesity or overweight. This network meta-analysis was conducted to compare the efficacy and safety of these regimens. Embase, PubMed, and Scopus were searched on March 2023 and updated in June 2024 for eligible randomized controlled trials (RCTs). The primary efficacy outcomes were mean difference in actual body weight, BMI (body mass index), BMI z score, and waist circumference. Safety outcomes included nausea, vomiting, diarrhea, abdominal pain, injection-site reaction, and hypoglycemia. Eleven RCTs with 953 participants were eligible. Semaglutide exhibited greater effects in reducing weight, BMI, and BMI z score versus the placebo. Semaglutide was associated with greater weight loss and BMI z score reduction in comparison with exenatide, liraglutide, and dulaglutide. Semaglutide also significantly decreased BMI than exenatide. None of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, and abdominal pain versus the placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions than the placebo. Liraglutide also had higher odds of causing injection-site reactions than other GLP-1 RAs. Semaglutide appeared to be the most effective and safe option among four GLP-1 RAs in children and adolescents with obesity or overweight.
Conquering the beyond Rule of Five Space with an Optimized High-Throughput Caco-2 Assay to Close Gaps in Absorption Prediction
Authors: Muschong Patricia , Awwad Khader , Price Edward , Mezler Mario , Weinheimer Manuel
Published: June 2024

Current drug development tends towards complex chemical molecules, referred to as “beyond rule of five” (bRo5) compounds, which often exhibit challenging physicochemical properties. Measuring Caco-2 permeability of those compounds is difficult due to technical limitations, including poor recovery and detection sensitivity. We implemented a novel assay, with optimized incubation and analytics, to measure permeability close to equilibrium. In this setup an appropriate characterization of permeability for bRo5 compounds is achievable. This equilibrated Caco-2 assay was verified with respect to data validity, compound recovery, and in vitro to in vivo correlation for human absorption. Compared to a standard assay, it demonstrated comparable performance in predicting the human fraction absorbed (fa) for reference compounds. The equilibrated assay also successfully characterized the permeability of more than 90% of the compounds analyzed, the majority of which were bRo5 (68%). These compounds could not be measured using the standard assay. Permeability and efflux ratio (ER) were highly predictive for in vivo absorption for a large set of internal bRo5 compounds. Reference cut-offs enabled the correct classification of high, moderate, and low absorption. This optimized equilibrated Caco-2 assay closes the gap for a high-throughput cellular permeability method in the bRo5 chemical space.