bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections
Authors: Pinho Jacinta O. , Ferreira Magda , Coelho Mariana , Pinto Sandra N. , Aguiar Sandra I. , Gaspar Maria Manuela
Published: April 2024

Methicillin-resistant Staphylococcus aureus (M RSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhance the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with similar potency between tested formulations. In MRSA-C1, minimal inhibitory concentrations (MIC) for Free RFB and liposomal RFB were 0.009 and 0.013 μg/mL, respectively. Minimum biofilm inhibitory concentrations able to inhibit 50% biofilm growth (MBIC50) for Free RFB and liposomal RFB against MRSA-C1 were 0.012 and 0.008 μg/mL, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. The in vivo results demonstrated a significant reduction in bacterial burden and growth index in major organs of mice treated with RFB formulations, as compared to Control and VCM (positive control) groups. Furthermore, the VCM therapeutic dose was two fold higher than the one used for RFB formulations, reinforcing the therapeutic potency of the proposed strategy. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.
Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment
Authors: Xu Yaxi , Xin Jianzeng , Sun Yupei , Wang Xuyan , Sun Lili , Zhao Feng , Niu Changshan , Liu Sheng
Published: April 2024

Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.
Improved Chemical and Radiochemical Synthesis of Neuropeptide Y Y2 Receptor Antagonist N-Methyl-JNJ-31020028 and Preclinical Positron Emission Tomography Studies
Authors: Fonseca Inês C. F. , Pais Mariana Lapo , Rodrigues Fábio M. S. , Sereno José , Castelo-Branco Miguel , Cavadas Cláudia , Pereira Mariette M. , Abrunhosa Antero J.
Published: April 2024

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system of mammals and is involved in several physiological processes through NPY Y1, Y2, Y4 and Y5 receptors. Of those, the Y2 receptor has particular relevance for its autoreceptor role in inhibiting the release of NPY and other neurotransmitters and for its involvement in relevant mechanisms such as feeding behaviour, cognitive processes, emotion regulation, circadian rhythms and disorders such as epilepsy and cancer. PET imaging of the Y2 receptor can provide a valuable platform to understand this receptor’s functional role and evaluate its potential as a therapeutic target. In this work, we set out to refine the chemical and radiochemical synthesis of the Y2 receptor antagonist N-[11C]Me-JNJ31020028 for in vivo PET imaging studies. The non-radioactive reference compound, N-Me-JNJ-31020028, was synthesised through batch synthesis and continuous flow methodology, with 43% and 92% yields, respectively. N-[11C]Me-JNJ-31020028 was obtained with a radiochemical purity > 99%, RCY of 31% and molar activity of 156 GBq/μmol. PET imaging clearly showed the tracer’s biodistribution in several areas of the mouse brain and gut where Y2 receptors are known to be expressed.
Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation
Authors: Chen Xiuli , Wu Hao , Li Peibo , Peng Wei , Wang Yonggang , Zhang Xiaoli , Zhang Ao , Li Jinliang , Meng Fenzhao , Wang Weiyue , Su Weiwei
Published: April 2024

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.
Anti-Helicobacter pylori Biofilm Extracts from Rubus idaeus and Rubus occidentalis
Authors: Hałasa Rafał , Turecka Katarzyna , Mizerska Urszula , Krauze-Baranowska Mirosława
Published: April 2024

Helicobacter pylori infections are still an important health problem and are directly related to the development of gastric ulcer, gastric adenocarcinoma, mucosal lymphoid tissue lymphoma, and diabetes. At the same time, the number of substances/drugs effective against these bacteria is limited due to increasing resistance. Raw plant materials from various species of the Rubus genus—fruits and shoots—have shown antimicrobial activity in numerous studies against different bacteria, including H. pylori in a planktonic form. Research carried out on a model using fragments of intravenous infusions and triphenyl tetrazolium chloride (TTC) as a dye showed that the shoot extract of Rubus idaeus ‘Willamette’, the fruit extract of R. idaeus ‘Poranna Rosa’, R. idaeus and R. idaeus ‘Laszka’, and R. occidentalis Litacz’ prevent the formation of biofilm by H. pylori. Active concentrations inhibiting biofilm formation were 6.65 mg/mL for shoots and 16.65 mg/mL for fruits. However, in the resulting biofilm, the extract from the shoots of R. idaeus ‘Willamette’ and the fruit of R. idaeus ‘Poranna Rosa’ at a concentration of 16.65 mg/mL was active against living bacteria, and the remaining extracts showed such activity at a concentration of 33.3 mg/mL. In studies on the interaction of the extract with antibiotics on biofilm, the extract from the shoots of R. idaeus ‘Willamette’ showed synergy with doxycycline and levofloxacin, additivity with amoxicillin and clarithromycin, and neutrality with metronidazole. H. pylori biofilm research was carried out in a newly elaborated research model—culture on fragments of intravenous infusions with the addition of TTC as a marker of living bacterial cells. The research results may constitute the basis for the development of new combination therapies for the treatment of H. pylori infections, including its resistant strains. The proposed new biofilm research model, which is cheap and effective, may allow testing of new substances that are potentially more effective against H. pylori and other biofilm-forming bacterial strains.
Ozonated Sunflower Oil Embedded within Spray-Dried Chitosan Microspheres Cross-Linked with Azelaic Acid as a Multicomponent Solid Form for Broad-Spectrum and Long-Lasting Antimicrobial Activity
Authors: Spogli Roberto , Faffa Caterina , Ambrogi Valeria , D’Alessandro Vincenzo , Pastori Gabriele
Published: April 2024

Multicomponent solid forms for the combined delivery of antimicrobials can improve formulation performance, especially for poorly soluble drugs, by enabling the modified release of the active ingredients to better meet therapeutic needs. Chitosan microspheres incorporating ozonated sunflower oil were prepared by a spray-drying method and using azelaic acid as a biocompatible cross-linker to improve the long time frame. Two methods were used to incorporate ozonated oil into microspheres during the atomization process: one based on the use of a surfactant to emulsify the oil and another using mesoporous silica as an oil absorbent. The encapsulation efficiency of the ozonated oil was evaluated by measuring the peroxide value in the microspheres, which showed an efficiency of 75.5–82.1%. The morphological aspects; particle size distribution; zeta potential; swelling; degradation time; and thermal, crystallographic and spectroscopic properties of the microspheres were analyzed. Azelaic acid release and peroxide formation over time were followed in in vitro analyses, which showed that ozonated oil embedded within chitosan microspheres cross-linked with azelaic acid is a valid system to obtain a sustained release of antimicrobials. In vitro tests showed that the microspheres exhibit synergistic antimicrobial activity against P. aeruginosa, E. coli, S. aureus, C. albicans and A. brasiliensis. This makes them ideal for use in the development of biomedical devices that require broad-spectrum and prolonged antimicrobial activity.
Exploring Microemulsion Systems for the Incorporation of Glucocorticoids into Bacterial Cellulose: A Novel Approach for Anti-Inflammatory Wound Dressings
Authors: Zahel Paul , Bruggink Vera , Hülsmann Juliana , Steiniger Frank , Hofstetter Robert K. , Heinzel Thorsten , Beekmann Uwe , Werz Oliver , Kralisch Dana
Published: April 2024

The effective pharmacological treatment of inflamed wounds such as pyoderma gangraenosum remains challenging, as the systemic application of suitable drugs such as glucocorticoids is compromised by severe side effects and the inherent difficulties of wounds as drug targets. Furthermore, conventional semi-solid formulations are not suitable for direct application to open wounds. Thus, the treatment of inflamed wounds could considerably benefit from the development of active wound dressings for the topical administration of anti-inflammatory drugs. Although bacterial cellulose appears to be an ideal candidate for this purpose due to its known suitability for advanced wound care and as a drug delivery system, the incorporation of poorly water-soluble compounds into the hydrophilic material still poses a problem. The use of microemulsions could solve that open issue. The present study therefore explores their use as a novel approach to incorporate poorly water-soluble glucocorticoids into bacterial cellulose. Five microemulsion formulations were loaded with hydrocortisone or dexamethasone and characterized in detail, demonstrating their regular microstructure, biocompatibility and shelf-life stability. Bacterial cellulose was successfully loaded with the formulations as confirmed by transmission electron microscopy and surprisingly showed homogenous incorporation, even of w/o type microemulsions. High and controllable drug permeation through Strat-M® membranes was observed, and the anti-inflammatory activity for permeated glucocorticoids was confirmed in vitro. This study presents a novel approach for the development of anti-inflammatory wound dressings using bacterial cellulose in combination with microemulsions.
Effect of Micromixer Design on Lipid Nanocarriers Manufacturing for the Delivery of Proteins and Nucleic Acids
Authors: Chiesa Enrica , Caimi Alessandro , Bellotti Marco , Giglio Alessia , Conti Bice , Dorati Rossella , Auricchio Ferdinando , Genta Ida
Published: April 2024

Lipid-based nanocarriers have emerged as helpful tools to deliver sensible biomolecules such as proteins and oligonucleotides. To have a fast and robust microfluidic-based nanoparticle synthesis method, the setup of versatile equipment should allow for the rapid transfer to scale cost-effectively while ensuring tunable, precise and reproducible nanoparticle attributes. The present work aims to assess the effect of different micromixer geometries on the manufacturing of lipid nanocarriers taking into account the influence on the mixing efficiency by changing the fluid–fluid interface and indeed the mass transfer. Since the geometry of the adopted micromixer varies from those already published, a Design of Experiment (DoE) was necessary to identify the operating (total flow, flow rate ratio) and formulation (lipid concentration, lipid molar ratios) parameters affecting the nanocarrier quality. The suitable application of the platform was investigated by producing neutral, stealth and cationic liposomes, using DaunoXome®, Myocet®, Onivyde® and Onpattro® as the benchmark. The effect of condensing lipid (DOTAP, 3–10–20 mol%), coating lipids (DSPE-PEG550 and DSPE-PEG2000), as well as structural lipids (DSPC, eggPC) was pointed out. A very satisfactory encapsulation efficiency, always higher than 70%, was successfully obtained for model biomolecules (myoglobin, short and long nucleic acids).
Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance
Authors: Moutaharrik Saliha , Palugan Luca , Cerea Matteo , Meroni Gabriele , Casagni Eleonora , Roda Gabriella , Martino Piera Anna , Gazzaniga Andrea , Maroni Alessandra , Foppoli Anastasia
Published: April 2024

Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn’s disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery.
Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment
Authors: Silva Raphaela Ariany , Damasio Danielle Soter , Coelho Larissa Dutra , de Morais-Teixeira Eliane , Queiroz-Junior Celso M. , Souza Paulo Eduardo , Azevedo Ricardo Bentes , Tedesco Antônio , Ferreira Lucas Antônio , Oliveira Mônica Cristina , Aguiar Marta Gontijo
Published: April 2024

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.
Machine Learning-Based Analysis Reveals Triterpene Saponins and Their Aglycones in Cimicifuga racemosa as Critical Mediators of AMPK Activation
Authors: Drewe Jürgen , Schöning Verena , Danton Ombeline , Schenk Alexander , Boonen Georg
Published: April 2024

Cimicifuga racemosa (CR) extracts contain diverse constituents such as saponins. These saponins, which act as a defense against herbivores and pathogens also show promise in treating human conditions such as heart failure, pain, hypercholesterolemia, cancer, and inflammation. Some of these effects are mediated by activating AMP-dependent protein kinase (AMPK). Therefore, comprehensive screening for activating constituents in a CR extract is highly desirable. Employing machine learning (ML) techniques such as Deep Neural Networks (DNN), Logistic Regression Classification (LRC), and Random Forest Classification (RFC) with molecular fingerprint MACCS descriptors, 95 CR constituents were classified. Calibration involved 50 randomly chosen positive and negative controls. LRC achieved the highest overall test accuracy (90.2%), but DNN and RFC surpassed it in precision, sensitivity, specificity, and ROC AUC. All CR constituents were predicted as activators, except for three non-triterpene compounds. The validity of these classifications was supported by good calibration, with misclassifications ranging from 3% to 17% across the various models. High sensitivity (84.5–87.2%) and specificity (84.1–91.4%) suggest suitability for screening. The results demonstrate the potential of triterpene saponins and aglycones in activating AMP-dependent protein kinase (AMPK), providing the rationale for further clinical exploration of CR extracts in metabolic pathway-related conditions.
GRPR-Antagonists Carrying DOTAGA-Chelator via Positively Charged Linkers: Perspectives for Prostate Cancer Theranostics
Authors: Obeid Karim , Kanellopoulos Panagiotis , Abouzayed Ayman , Mattsson Adam , Tolmachev Vladimir , Nock Berthold A. , Maina Theodosia , Orlova Anna
Published: April 2024

Gastrin-releasing peptide receptor (GRPR)-antagonists have served as motifs in the development of theranostic radioligands for prostate cancer. Our efforts have been focused on the development of radiolabeled RM26 (H-DPhe6–Gln7–Trp8–Ala9–Val10–Gly11–His12–Sta13–Leu14–NH2) analogs, such as [111In]In-DOTAGA-PEG2-RM26. We recently showed that its Gly11/Sar11-substituted version, [111In]In-AU-RM26-M1, resisted degradation by neprilysin (NEP) while in circulation and achieved higher tumor uptake in mice. We herein introduce the following three new AU-RM26-M1 mimics labeled with In-111, with basic residues in the linker: (i) AU-RM26-M2 (PEG2-Pip), (ii) AU-RM26-M3 (PEG2-Arg), and (iii) AU-RM26-M4 (Arg-Arg-Pip). These analogs were compared in PC-3 cells and animal models vs. AU-RM26-M1 (reference). The new analogs showed high affinity and specificity for the GRPR, exhibiting an uptake and distribution pattern in PC-3 cells typical for a radiolabeled GRPR-antagonist. They showed high stability in peripheral mice blood, except for [111In]In-AU-RM26-M3. AU-RM26-M4 achieved the highest tumor uptake and promising background clearance, followed by [111In]In-RM26-M2, showing lower background levels. These findings were confirmed for [111In]In-AU-RM26-M2 and [111In]In-AU-RM26-M4 by micro-SPECT/CT at 4 and 24 h post-injection. Hence, the type of positively charged residues in the linker of AU-RM26-M1 mimics strongly influenced biological behavior. The analogs with Pip next to DPhe6 demonstrated the best overall characteristics and warrant further investigation.
Assessing the Safety and Therapeutic Efficacy of Cannabidiol Lipid Nanoparticles in Alleviating Metabolic and Memory Impairments and Hippocampal Histopathological Changes in Diabetic Parkinson’s Rats
Authors: Lapmanee Sarawut , Bhubhanil Sakkarin , Wongchitrat Prapimpun , Charoenphon Natthawut , Inchan Anjaree , Ngernsutivorakul Thitaphat , Dechbumroong Piroonrat , Khongkow Mattaka , Namdee Katawut
Published: April 2024

Diabetic Parkinson’s disease (DP) is a progressive neurodegenerative disease with metabolic syndrome that is increasing worldwide. Emerging research suggests that cannabidiol (CBD) is a neuropharmacological compound that acts against this disease, especially CBD in nano-formulation. The safety of cannabidiol lipid nanoparticles (CBD-LNP) was evaluated by assessing in vitro cytotoxicity in neurons and therapeutic outcomes in a DP animal model, including metabolic parameters and histopathology. CBD-LNPs were fabricated by using a microfluidization technique and showed significantly lower cytotoxicity than the natural form of CBD. The DP rats were induced by streptozotocin followed by a 4-week injection of MPTP with a high-fat diet. Rats were treated orally with a vehicle, CBD, CBD-LNP, or levodopa for 4 weeks daily. As a result, vehicle-treated rats exhibited metabolic abnormalities, decreased striatal dopamine levels, and motor and memory deficits. CBD-LNP demonstrated reduced lipid profiles, enhanced insulin secretion, and restored dopamine levels compared to CBD in the natural form. CBD-LNP also had comparable efficacy to levodopa in ameliorating motor deficits and memory impairment in behavior tests. Interestingly, CBD-LNP presented migration of damaged neuronal cells in the hippocampus more than levodopa. These findings suggest that CBD-LNP holds promise as an intervention addressing both metabolic and neurodegenerative aspects of DP, offering a potential therapeutic strategy.
Questionnaire Study to Investigate the Preferences of Children, Parents, and Healthcare Professionals for Different Formulations of Oral Medicinal Products
Authors: Wargenau Manfred , Baase Felicitas , Eckardt Kristin , Spitzhorn Lucas-Sebastian , Reidemeister Sibylle , Klingmann Ingrid , Klingmann Viviane
Published: April 2024

Since the acceptability of a medicine can significantly impact therapeutic outcomes, this study aimed to determine and compare the preferences of children, parents, and healthcare professionals for the most commonly used pediatric oral medicine formulations (syrup, mini-tablets, oblong tablets, round tablets) addressing all pediatric age groups, 0–<18 years (y). This survey study employed sex-, age-, and participant group-adapted questionnaires for eight cohorts of participants, i.e., children 6–<12 y, adolescents 12–<18 y, parents of children in four age groups (0–<2 y, 2–<6 y, 6–<12 y, and 12–<18 y), nurses, and pediatricians. Descriptive statistics were used for data analysis. In the age groups 0–<2 y and 2–<6 y, mini-tablets were preferred over syrup by all participants. In the age group 6–12 y, solid dosage forms were also preferred over syrup by all participants. In the age group 12–<18 y, healthcare professionals preferred solid dosage forms over syrup. Parents preferred higher amounts of mini-tablets and syrup compared to round and oblong tablets, while adolescents’ preferences did not differentiate between these formulations. Based on the study results and in contrast to current practice, it is suggested to consider solid dosage forms for future age-appropriate medicinal products already for younger age groups.
Quantitative Evaluation of the Batwing Effect on Depth Measurement in Coherence Scanning Interferometry for Rectangular Gratings
Authors: Zhang Jiale , Yuan Qun , Fan Xiaoxin , Chen Lu , Lei Lihua , Fu Yunxia , Xu Zhiyi , Ma Jianqiu , Gao Zhishan
Published: April 2024

Coherence scanning interferometry (CSI) is a widely used non-contact method for measuring areal surface topography. The calculation of groove depth typically employs the ‘W/3 rule’ specified in ISO 5436-1. However, the batwing effect causes overshoots near the groove edges, which can introduce noise singularities in the selected W/3 region for depth calculation, thereby affecting the measurement of rectangular grating depth. This paper introduces the definition of batwing height and width and proposes a simulation model that considers various factors, such as the center wavelength, spectrum of the illuminating light, shadow effect, and numerical aperture, to analyze their influence on depth measurement. The simulation results demonstrate that the batwing width is the primary factor influencing depth measurement for small grating periods. Specifically, a decrease in numerical aperture increases the batwing width, leading to larger depth measurement errors, while a decrease in the center wavelength reduces the batwing width, resulting in smaller depth measurement errors. The influence of the illumination spectrum and shadow effect on depth measurement is found to be minor. Experimental validation using a step standard consisting of rectangular gratings with different periods and depths confirms the agreement between the experimental and simulated results. The proposed method provides a quantitative evaluation of depth measurement accuracy in CSI.
Hazelnut and Walnut Nutshell Features as Emerging Added-Value Byproducts of the Nut Industry: A Review
Authors: Manterola-Barroso Carlos , Padilla Contreras Daniela , Ondrasek Gabrijel , Horvatinec Jelena , Gavilán CuiCui Gabriela , Meriño-Gergichevich Cristian
Published: April 2024

The hard-shelled seed industry plays an important role in the global agricultural economy. In fact, only considering hazelnut and walnut, the global nut supply is over 5.6 tons. As a result considerable amounts are produced year by year, burnt or discarded as waste, bypassing a potential source of valuable compounds or features. This review deals with the recent scientific literature on their chemical composition as well as functional applications as an approach to sustain the utilization of the main byproduct derived from industry. Indeed, nutshells have received great interest due to their lignin, antioxidant, physical and mechanical features. It was found that these properties vary among cultivars and localities of plantation, influencing physical and structural features. The inconsistencies regarding the above-mentioned properties of nutshells lead to exploring the status of hazelnut and walnut shell applications in sustainable bio-economy chains. In fact, in terms of potential applications, the state of the art links their use to the construction industry and the manufacture of materials, such as resin or plastic composites, particleboards or construction panels, or vital infrastructure and as a filler in cement pavements. However, their current use continues bypassing their great antioxidant potential and their interesting chemical and mechanical features.
Unveiling the Antioxidant, Cytotoxic, and Anti-Inflammatory Activities and Chemical Compositional Information of an Invasive Plant: Lycium ferocissimum Miers
Authors: Koşar Müberra , Karatoprak Gökçe Şeker , Atlı Beste , İlgün Selen , Köngül Şafak Esra , Öztinen Nesrin , Akçakaya Mutlu Sena , Ak Sakallı Ezgi
Published: April 2024

In this study, the antioxidant (DPPH and ABTS radical-scavenging, ferric-reducing, iron (II)-chelating), anti-inflammatory (LPS-induced Raw 264.7 cell line), and cytotoxic activities (Du145 and A549 cell lines) of raw fruit, ripe fruit and leaves of the Lycium ferocissimum species were examined. By using high-pressure liquid chromatography, p-OH benzoic acid, caffeic acid, and rutin were detected in the ethanol and water extracts. For the most active raw fruit ethanol extract, the IC50 in terms of the DPPH-scavenging activity was 0.57 mg/mL, and the ABTS inhibition percentage was 88.73% at a 3 mg/mL concentration. The raw fruit ethanol extract exhibited significant inhibition of viability in the Du145 cell line in the concentration range of 62.5–1000 µg/mL. Additionally, the extract effectively reduced the LPS-induced inflammation parameters (TNF-α, IFN-γ, PGE 2, and NO) at a concentration of 31.25 µg/mL. The biological activities of L. ferocissimum, which have been elucidated for the first time, have yielded promising results.
Screening of Rice (Oryza sativa L.) Genotypes for Salinity Tolerance and Dissecting Determinants of Tolerance Mechanism
Authors: Chen Tianxiao , Niu Yanan , Yang Changdeng , Liang Yan , Xu Jianlong
Published: April 2024

Soil salinity imposes osmotic, ionic, and oxidative stresses on plants, resulting in growth inhibition, developmental changes, metabolic adaptations, and ion sequestration or exclusion. Identifying salinity-tolerant resources and understanding physiological and molecular mechanisms of salinity tolerance could lay a foundation for the improvement of salinity tolerance in rice. In this study, a series of salinity-tolerance-related morphological and physiological traits were investigated in 46 rice genotypes, including Sea Rice 86, to reveal the main strategies of rice in responding to salinity stress at the seedling stage. No genotypes showed the same tolerance level as the two landraces Pokkali and Nona Bokra, which remain the donors for improving the salinity tolerance of rice. However, due to undesirable agronomic traits of these donors, alternative cultivars such as JC118S and R1 are recommended as novel source of salinity tolerance. Correlation and principal component analyses revealed that the salinity tolerance of rice seedlings is not only controlled by growth vigor but also regulated by ion transport pathways such as long-distance Na+ transport, root Na+ sequestration, and root K+ retention. Therefore, such key traits should be targeted in future breeding programs as the strategy of obtaining better Na+ exclusion is still the bottleneck for improving salinity tolerance in rice.
Decrypting Molecular Mechanisms Involved in Counteracting Copper and Nickel Toxicity in Jack Pine (Pinus banksiana) Based on Transcriptomic Analysis
Authors: Moy Alistar , Nkongolo Kabwe
Published: April 2024

The remediation of copper and nickel-afflicted sites is challenged by the different physiological effects imposed by each metal on a given plant system. Pinus banksiana is resilient against copper and nickel, providing an opportunity to build a valuable resource to investigate the responding gene expression toward each metal. The objectives of this study were to (1) extend the analysis of the Pinus banksiana transcriptome exposed to nickel and copper, (2) assess the differential gene expression in nickel-resistant compared to copper-resistant genotypes, and (3) identify mechanisms specific to each metal. The Illumina platform was used to sequence RNA that was extracted from seedlings treated with each of the metals. There were 449 differentially expressed genes (DEGs) between copper-resistant genotypes (RGs) and nickel-resistant genotypes (RGs) at a high stringency cut-off, indicating a distinct pattern of gene expression toward each metal. For biological processes, 19.8% of DEGs were associated with the DNA metabolic process, followed by the response to stress (13.15%) and the response to chemicals (8.59%). For metabolic function, 27.9% of DEGs were associated with nuclease activity, followed by nucleotide binding (27.64%) and kinase activity (10.16%). Overall, 21.49% of DEGs were localized to the plasma membrane, followed by the cytosol (16.26%) and chloroplast (12.43%). Annotation of the top upregulated genes in copper RG compared to nickel RG identified genes and mechanisms that were specific to copper and not to nickel. NtPDR, AtHIPP10, and YSL1 were identified as genes associated with copper resistance. Various genes related to cell wall metabolism were identified, and they included genes encoding for HCT, CslE6, MPG, and polygalacturonase. Annotation of the top downregulated genes in copper RG compared to nickel RG revealed genes and mechanisms that were specific to nickel and not copper. Various regulatory and signaling-related genes associated with the stress response were identified. They included UGT, TIFY, ACC, dirigent protein, peroxidase, and glyoxyalase I. Additional research is needed to determine the specific functions of signaling and stress response mechanisms in nickel-resistant plants.
Comparative Phytoprofiling of Achillea millefolium Morphotypes: Assessing Antioxidant Activity, Phenolic and Triterpenic Compounds Variation across Different Plant Parts
Authors: Raudone Lina , Vilkickyte Gabriele , Marksa Mindaugas , Radusiene Jolita
Published: April 2024

Achillea millefolium L., commonly known as yarrow, is a versatile and widely distributed plant species with a rich history of ethnopharmacological significance. This study aimed to evaluate the comparative differences of A. millefolium inflorescence morphotypes. The phytochemical profile of white and pink inflorescence morphotypes was characterised by a complex of thirty-four phenolic and triterpene compounds. The species has distinct morphotypes of white and pink inflorescence. Phenolic and triterpenic profiles were determined, and individual compounds were quantified in inflorescence, leaf, and stem samples of two morphotypes tested. The antioxidant activity of plant extracts was evaluated by free radical scavenging (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Caffeoylquinic acids predominated in all parts of the plant tested. Chlorogenic acid and 3,5-dicaffeoylquinic acid were the principal compounds in the phenolic profile. Betulin, betulinic acid, and α-amyrin were the prevailing triterpenic components in the triterpenic profiles of Achillea millefolium morphotypes. The predominant flavonoids in inflorescences were flavones, while in leaves, flavonols were the organ-specific compounds. The quantitative differences were observed between plant parts of morphotypes. Leaves consistently displayed the highest amounts of identified compounds and have been testified as the main source of antioxidant activity. Overall, white inflorescences accumulated a higher total amount of compounds compared to pink ones. The observed differences between morphotypes derived from the same population reflect the differences in specialised metabolites and their chemotypes. This study addresses gaps in knowledge, particularly in phenolic and triterpenic profiling of coloured inflorescence morphotypes, enhancing our understanding of chemotypes and morphotypes within the species.
A Walk on the Wild Side: Genome Editing of Tuber-Bearing Solanum bulbocastanum
Authors: Azariadis Aristotelis , Andrzejczak Olga A. , Carlsen Frida M. , Westberg Ida , Brinch-Pedersen Henrik , Petersen Bent L. , Hebelstrup Kim H.
Published: April 2024

Solanum bulbocastanum is a wild diploid tuber-bearing plant. We here demonstrate transgene-free genome editing of S. bulbocastanum protoplasts and regeneration of gene-edited plants. We use ribonucleoproteins, consisting of Cas9 and sgRNA, assembled in vitro, to target a gene belonging to the nitrate and peptide transporter family. Four different sgRNAs were designed and we observed efficiency in gene-editing in the protoplast pool between 8.5% and 12.4%. Twenty-one plants were re-generated from microcalli developed from individual protoplasts. In three of the plants we found that the target gene had been edited. Two of the edited plants had deletion mutations introduced into both alleles, whereas one only had a mutation in one of the alleles. Our work demonstrates that protocols for the transformation of Solanum tuberosum can be optimized to be applied to a wild Solanum species.
Physio-Biochemical, Anatomical, and Molecular Analysis of Resistant and Susceptible Wheat Cultivars Infected with TTKSK, TTKST, and TTTSK Novel Puccinia graminis Races
Authors: Alafari Hayat Ali , Hafez Yaser , Omara Reda , Murad Rasha , Abdelaal Khaled , Attia Kotb , Khedr Amr
Published: April 2024

Stem rust, caused by Puccinia graminis f.sp. tritici, is one of the most dangerous rust diseases on wheat. Through physiological, biochemical, and molecular analysis, the relationship between the change in resistance of 15 wheat cultivars to stem rust disease and the response of 41 stem rust resistance genes (Sr,s) as well as TTKSK, TTKST, and TTTSK races was explained. Some cultivars and Sr genes, such as Gemmeiza-9, Gemmeiza-11, Sids-13, Sakha-94, Misr-1, Misr-2, Sr31, and Sr38, became susceptible to infection. Other new cultivars include Mir-3 and Sakha-95, and Sr genes 13, 37, 40, GT, and FR*2/SRTT3-SRTT3-SR10 remain resistant. Some resistance genes have been identified in these resistant cultivars: Sr2, Sr13, Sr24, Sr36, and Sr40. Sr31 was not detected in any cultivars. Reactive oxygen species such as hydrogen peroxide and superoxide, enzymes activities (catalase, peroxidase, and polyphenoloxidase), and electrolyte leakage were increased in the highly susceptible cultivars, while they decreased in the resistant ones. Anatomical characteristics such as the thickness of the epidermis, ground tissue, phloem tissue and vascular bundle diameter in the midrib were decreased in susceptible cultivars compared with resistant cultivars. Our results indicated that some races (TTKSK, TTKST, and TTTSK) appeared for the first time in Egypt and many other countries, which broke the resistant cultivars. The wheat rust breeding program must rely on land races and pyramiding genes in order to develop new resistance genes that will survive for a very long time.
A Review with a Focus on Vaccinium-Berries-Derived Bioactive Compounds for the Treatment of Reproductive Cancers
Authors: Alsharairi Naser A.
Published: April 2024

Cancers of the reproductive organs, including prostate, bladder, ovarian, and cervical cancers, are considered the most common causes of death in both sexes worldwide. The genus Vaccinium L. (Ericaceae) comprises fleshy berry crop species, including cranberries, blueberries, lingonberries, bilberries, and bog bilberries, and are widely distributed in many countries. Flavonols, anthocyanins (ACNs), proanthocyanidins (PACs), and phenolic acids are the most bioactive compounds naturally found in Vaccinium berries and have been extensively used as anticancer agents. However, it remains uncertain whether Vaccinium bioactives have a therapeutic role in reproductive cancers (RCs), and how these bioactives could be effective in modulating RC-related signalling pathways/molecular genes. Therefore, this article aims to review existing evidence in the PubMed/MEDLINE database on Vaccinium berries’ major bioactive compounds in RC treatment and unravel the mechanisms underlying this process.
Estimating the Amount of the Wild Artemisia annua in China Based on the MaxEnt Model and Spatio-Temporal Kriging Interpolation
Authors: Wang Juan , Shi Tingting , Wang Hui , Li Meng , Zhang Xiaobo , Huang Luqi
Published: April 2024

In order to determine the distribution area and amount of Artemisia annua Linn. (A. annua) in China, this study estimated the current amount of A. annua specimens based on the field survey sample data obtained from the Fourth National Census of Chinese Medicinal Resources. The amount was calculated using the maximum entropy model (MaxEnt model) and spatio-temporal kriging interpolation. The influencing factors affecting spatial variations in the amount were studied using geographic probes. The results indicated that the amount of A. annua in China was about 700 billion in 2019. A. annua was mainly distributed in the circular coastal belt of Shandong Peninsula, central Hebei, Tianjin, western Liaoning, and along the Yangtze River and in the middle and lower reaches of Jiangsu, Anhui, and the northern Chongqing provinces. The main factors affecting the amount are the precipitation in the wettest and the warmest seasons, the average annual precipitation, and the average temperature in the coldest and the driest seasons. The results show that the amount of A. annua is strongly influenced by precipitation and temperature.
Recent Progress of Carrageenan-Based Composite Films in Active and Intelligent Food Packaging Applications
Authors: Kokkuvayil Ramadas Bharath , Rhim Jong-Whan , Roy Swarup
Published: April 2024

Recently, as concerns about petrochemical-derived polymers increase, interest in biopolymer-based materials is increasing. Undoubtedly, biopolymers are a better alternative to solve the problem of synthetic polymer-based plastics for packaging purposes. There are various types of biopolymers in nature, and mostly polysaccharides are used in this regard. Carrageenan is a hydrophilic polysaccharide extracted from red algae and has recently attracted great interest in the development of food packaging films. Carrageenan is known for its excellent film-forming properties, high compatibility and good carrier properties. Carrageenan is readily available and low cost, making it a good candidate as a polymer matrix base material for active and intelligent food packaging films. The carrageenan-based packaging film lacks mechanical, barrier, and functional properties. Thus, the physical and functional properties of carrageenan-based films can be enhanced by blending this biopolymer with functional compounds and nanofillers. Various types of bioactive ingredients, such as nanoparticles, natural extracts, colorants, and essential oils, have been incorporated into the carrageenan-based film. Carrageenan-based functional packaging film was found to be useful for extending the shelf life of packaged foods and tracking spoilage. Recently, there has been plenty of research work published on the potential of carrageenan-based packaging film. Therefore, this review discusses recent advances in carrageenan-based films for applications in food packaging. The preparation and properties of carrageenan-based packaging films were discussed, as well as their application in real-time food packaging. The latest discussion on the potential of carrageenan as an alternative to traditionally used synthetic plastics may be helpful for further research in this field.
Radio-Absorbing Magnetic Polymer Composites Based on Spinel Ferrites: A Review
Authors: Kostishin Vladimir G. , Isaev Igor M. , Salogub Dmitrij V.
Published: April 2024

Ferrite-containing polymer composites are of great interest for the development of radar-absorbing and -shielding materials (RAMs and RSMs). The main objective of RAM and RSM development is to achieve a combination of efficient electromagnetic wave (EMW) absorption methods with advantageous technological and mechanical properties as well as acceptable weight and dimensions in the final product. This work deals with composite RAMs and RSMs containing spinel-structured ferrites. These materials are chosen since they can act as efficient RAMs in the form of ceramic plates and as fillers for radar-absorbing polymer composites (RAC) for electromagnetic radiation (EMR). Combining ferrites with conducting fillers can broaden the working frequency range of composite RAMs due to the activation of various absorption mechanisms. Ferrite-containing composites are the most efficient materials that can be used as the working media of RAMs and RSMs due to a combination of excellent dielectric and magnetic properties of ferrites. This work contains a brief review of the main theoretical standpoints on EMR interaction with materials, a comparison between the radar absorption properties of ferrites and ferrite–polymer composites and analysis of some phenomenological aspects of the radar absorption mechanisms in those composites.
Investigating How the Properties of Electrospun Poly(lactic acid) Fibres Loaded with the Essential Oil Limonene Evolve over Time under Different Storage Conditions
Authors: Williams Leah , Hatton Fiona L. , Righetti Maria Cristina , Mele Elisa
Published: April 2024

Essential oils have been identified as effective natural compounds to prevent bacterial infections and thus are widely proposed as bioactive agents for biomedical applications. Across the literature, various essential oils have been incorporated into electrospun fibres to produce materials with, among others, antibacterial, anti-inflammatory and antioxidant activity. However, limited research has been conducted so far on the effect of these chemical products on the physical characteristics of the resulting composite fibres for extended periods of time. Within this work, electrospun fibres of poly(lactic acid) (PLA) were loaded with the essential oil limonene, and the impact of storage conditions and duration (up to 12 weeks) on the thermal degradation, glass transition temperature and mechanical response of the fibrous mats were investigated. It was found that the concentration of the encapsulated limonene changed over time and thus the properties of the PLA–limonene fibres evolved, particularly in the first two weeks of storage (independently from storage conditions). The amount of limonene retained within the fibres, even 4 weeks after fibre generation, was effective to successfully inhibit the growth of model microorganisms Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The results of this work demonstrate the importance of evaluating physical properties during the ageing of electrospun fibres encapsulating essential oils, in order to predict performance modification when the composite fibres are used as constituents of medical devices.