bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Malnutrition in the Medicine and Neurology Departments: A Complex Challenge
Authors: Starace Erica , De Pasquale Giulia , Morenghi Emanuela , Crippa Camilla , Matteucci Sofia , Pieri Gabriella , Soekeland Fanny , Gibbi Stefano Maria , Lo Cricchio Giuliana , Reggiani Francesco , Calatroni Marta , Pastore Manuela , Mazzoleni Beatrice , Mancin Stefano
Published: December 2023

Hospital malnutrition is especially common among elderly patients with neurological deficits or dementia. These conditions can be exacerbated by unpalatable diets and issues such as dysphagia and presbyphagia. Our study aimed to investigate the prevalence of malnutrition in patients on a homogenized diet and to identify potential correlations with specific clinical variables. We conducted a retrospective observational study in compliance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. The study encompassed 82 patients, mainly elderly and diagnosed with neurodegenerative diseases. Upon initial assessment, 46.34% of the sample displayed a risk of malnutrition based on the Malnutrition Universal Screening Tool (MUST), and 62.20% were classified as malnourished based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Only 45.12% retained autonomy in food intake. Weight loss identified prior to the study was closely tied to malnutrition and influenced BMI. Moreover, autonomy in food intake was strongly associated with a prolonged hospital stay (LOS), and a similar trend was observed for water intake. Our findings emphasize the importance of promptly recognizing patients at risk of malnutrition, especially within such a vulnerable population. Autonomy in food intake and hydration emerge as critical indicators in the clinical management of hospitalized patients.
Women’s Satisfaction with Breastfeeding and Risk of Exclusive Breastfeeding Interruption
Authors: Bizon Agnes Meire Branco Leria , Giugliani Camila , Giugliani Elsa Regina Justo
Published: December 2023

This prospective cohort study was conducted to evaluate the association between women’s satisfaction with breastfeeding at 1 month post-partum and the risk of exclusive breastfeeding (EBF) interruption before 6 months. 287 mother–infant dyads randomly selected from two maternity hospitals were followed from birth to 24 months of infant’s age. Women’s satisfaction with breastfeeding was assessed using the Maternal Breastfeeding Evaluation Scale (MBFES) at 1 month. The association between women’s satisfaction with breastfeeding and risk of EBF interruption before 6 months was estimated using Cox proportional hazards model. Kaplan–Meier survival curves for EBF were compared between women with lower satisfaction with breastfeeding (MBFES score < median 124) and those with higher satisfaction (MBFES score ≥ 124). Median EBF duration in women with higher satisfaction was 120 days (95%CI 109–131), vs. 26 days (95%CI 19–33) in less satisfied women. Each additional point on MBFES promoted a reduction of 2.0% in the risk of EBF interruption. Among women with satisfaction scores < 124, the risk of EBF interruption was 86% higher when compared with those ≥ 124 (adjusted hazard ratio 1.86; 95%CI 1.41–2.46). Lower maternal satisfaction with breastfeeding in the first month post-partum is associated with a higher risk of EBF interruption before 6 months.
How Foods and Beverages Are Promoted Online: A Content Analysis of the Digital Food Environment in China
Authors: Chen Juan , Du Yuetong , Rui Jian Raymond
Published: December 2023

Digital platforms such as social media and e-commerce platforms have become a major space where foods and beverages (F&B) are promoted. Prior research has found that online, unhealthy F&B receive more presence than healthy F&B. This obesogenic food environment may increase the obesity rate. Therefore, it is critical to understand how healthy and unhealthy F&B are promoted online. A content analysis of 2906 posts related to F&B via five digital platforms was conducted in China, where the obesity rate has increased in recent years. Firstly, the results show that unhealthy F&B received more presence on digital platforms than healthy F&B. Secondly, healthy F&B posts tended to highlight the healthiness of the products, whereas unhealthy F&B posts leveraged a wide range of promotional strategies, specifically use cues, food cues, chewing sounds, sensory descriptions, friend cues, local cultural appeal, nostalgia appeal, price information, discount information, and trending hashtags or topics. Next, use cues, chewing sounds, sensory descriptions, family cues, and friend cues increased the quantity of audience feedback, whereas price information and using trending hashtags or topics lowered the quantity of audience feedback. Moreover, local cultural appeal and social proof exhibited the opposite impact on audience feedback. Finally, health benefit statements lowered audience feedback for healthy F&B posts, whereas brand visibility and purchase links inhibited audience feedback for unhealthy F&B posts. In addition to describing the digital food environment in China, the present research provides implications on how to promote healthy F&B. Particularly, we suggest that healthy F&B businesses and healthy eating campaigns should leverage the strategies unhealthy F&B use to receive more consumer attention, in order to increase their own products’ public visibility and attractiveness.
Nutritional Management of Oncological Symptoms: A Comprehensive Review
Authors: Garutti Mattia , Noto Claudia , Pastò Brenno , Cucciniello Linda , Alajmo Massimiliano , Casirati Amanda , Pedrazzoli Paolo , Caccialanza Riccardo , Puglisi Fabio
Published: December 2023

Throughout their experience of illness and during the course of treatment, a substantial proportion of cancer patients are prone to develop nutritional and/or metabolic disturbances. Additionally, cancer patients often encounter long-term side effects from therapies, which may lead to impaired digestion, nutrient absorption or bowel motility. Therefore, the preservation and maintenance of an optimal and balanced nutritional status are pivotal to achieving a better prognosis, increasing the tolerance and adherence to cancer therapies and improving the overall quality of life. In this context, personalized nutritional programs are essential for addressing conditions predisposing to weight loss, feeding difficulties, digestion problems and intestinal irregularity, with the goal of promoting adequate nutrient absorption and minimizing the detrimental effects of treatment regimens. The focus of this research is to examine the most common clinical conditions and metabolic changes that cancer patients may experience, including stomatitis, xerostomia, diarrhea, nausea, vomiting, dysphagia, sub-occlusion, dysgeusia, dysosmia, anorexia, and cachexia. Furthermore, we present a pragmatic example of a multidisciplinary workflow that incorporates customized recipes tailored to individual clinical scenarios, all while maintaining the hedonic value of the meals.
Idiopathic Mandibular Osteosclerosis: A Case of Complex Diagnosis
Authors: Perez Alexandre , Mamane Avigaïl , Lombardi Tommaso
Published: December 2023

The purpose of this study is to report a case of idiopathic osteosclerosis of the mandible and to discuss the differential diagnosis of this lesion. A 17-year-old female was referred to the University Hospital of Geneva by her orthodontist following the fortuitous finding of a radio-opaque lesion in the right posterior mandible at the apex of tooth 44. Intraoral clinical examination revealed no abnormalities of the oral mucosa. Tooth 44 was asymptomatic and reacted positively to the sensitivity test. The orthopantomogram revealed a well-defined unilocular radiodense lesion, surrounded by a thin radiolucent border, measuring 10 × 33 mm, located in the IV quadrant, related to the apex of tooth 44. Differential diagnoses mainly included cementoblastoma, focal cemento-osseous dysplasia, ossifying fibroma, condensing osteitis and idiopathic osteosclerosis. The biopsy material allowed a diagnosis of idiopathic osteosclerosis. The proposed treatment was therefore a “wait and see” approach. After 2 years of follow-up, the patient was asymptomatic, and healing was complete without any neurosensory complications. Our case underlines the differential diagnosis complexity of radio-opaque lesions associated with teeth.
Impact of MgtC on the Fitness of Yersinia pseudotuberculosis
Authors: Li Peng , Wang Hengtai , Sun Wei , Ding Jiabo
Published: December 2023

Yersinia pseudotuberculosis is an extracellular foodborne pathogen and usually causes self-limiting diarrhea in healthy humans. MgtC is known as a key subversion factor that contributes to intramacrophage adaptation and intracellular survival in certain important pathogens. Whether MgtC influences the fitness of Y. pseudotuberculosis is unclear. According to in silico analysis, MgtC in Y. pseudotuberculosis might share similar functions with other bacterial pathogens, such as Salmonella. Studies indicated that MgtC was clearly required for Y. pseudotuberculosis growth in vitro and bacterial survival in macrophages under Mg2+ starvation. Transcriptome analysis by RNA-seq indicated that 127 differentially expressed genes (DEGs) (fold change > 2 and p < 0.001) were discovered between wild-type PB1+ and mgtC mutant inside macrophages. However, a lack of MgtC only moderately, albeit significantly, reduced the virulence of Y. pseudotuberculosis in mice. Overall, this study provides additional insights for the role of MgtC in Y. pseudotuberculosis.
Anti-Toxoplasma gondii Antibodies in European Residents: A Systematic Review and Meta-Analysis of Studies Published between 2000 and 2020
Authors: Calero-Bernal Rafael , Gennari Solange María , Cano Santiago , Salas-Fajardo Martha Ynés , Ríos Arantxa , Álvarez-García Gema , Ortega-Mora Luis Miguel
Published: December 2023

Toxoplasmosis has a major impact on animal and public health. Information regarding the seroprevalence of human Toxoplasma gondii infections from a European perspective has not yet been compiled to date. Thus, the present review summarized available resident data from the period 2000–2020. The overall seroprevalence of anti-T. gondii IgG was 32.1%, with great variability between countries (n = 30). The subgroup analysis identified different pooled prevalence data depending on the geographic area (p < 0.0001), target population (p = 0.0147), and serological diagnosis assays used (p = 0.0059). A high heterogeneity (I2 = 100%, p < 0.001; Q = 3.5e+05, d.f. = 135, p < 0.001) and degree of publication bias (Egger’s test = 6.14, p < 0.001) were observed among the 134 studies considered. The occurrence of anti-T. gondii IgM, which was reported in 64.7% of studies, reached a pooled seroprevalence of 0.6%. In addition, among the eight main risk factors identified, “contact with soil”, “consumption of undercooked beef”, and “intake of unwashed vegetables” were the most significantly associated with infections. The fact that one-third of the European population has been exposed to T. gondii justifies extra efforts to harmonize surveillance systems and develop additional risk-factor analyses based on detailed source attribution assessment.
Innovative Elastomers with Antimicrobial Activity May Decrease Infection Risks during Milking
Authors: Meroni Gabriele , Sora Valerio , Zaghen Francesca , Laterza Giulia , Martino Piera Anna , Zecconi Alfonso
Published: December 2023

Contagious pathogens are very costly to dairy herds, and they may have zoonotic and reverse-zoonotic potentials and may contribute to the spread of antimicrobial resistance. One of the most important risk factors for spreading these infections is milking, when liner contamination may transfer the pathogens from infected to healthy cows. There is no effective protocol to prevent the transmission of infection without the segregation of infected cows. Recently, the availability of elastomers with patented antimicrobial components in their formulations has allowed the exploration of alternative methods to reduce the risk of infection. Two different types of elastomers (rubber and silicone) and nine different formulations were challenged with three major mastitis pathogens (S. aureus, S. agalactiae, and E. coli). The results that were obtained in this study were interesting and unexpected. Indeed, to our knowledge, this is the first study to show that basic rubber materials have intrinsic antimicrobial activity. Silicone elastomers did not exhibit the same levels of bactericidal activity, although they did exhibit some antibacterial capacity. A significant decrease in bacterial survival curves was observed for all the formulations tested when antimicrobial components were added. The different results observed for the various products are likely due to the different formulations and diverse manufacturing processes. The availability of these new materials that significantly reduce the bacterial load on the liner surface may reduce the risk of spreading intramammary infections during milking. This would be an important step forward in achieving global sustainability of dairy herds, consistent with the objectives of One Health, by reducing the risks of zoonotic diseases and antimicrobial treatments.
In Silico Drug Repurposing Studies for the Discovery of Novel Salicyl-AMP Ligase (MbtA)Inhibitors
Authors: Rakshit Gourav , Biswas Abanish , Jayaprakash Venkatesan
Published: December 2023

Tuberculosis (TB) continues to pose a global health challenge, exacerbated by the rise of drug-resistant strains. The development of new TB therapies is an arduous and time-consuming process. To expedite the discovery of effective treatments, computational structure-based drug repurposing has emerged as a promising strategy. From this perspective, conditionally essential targets present a valuable opportunity, and the mycobactin biosynthesis pathway stands out as a prime example highlighting the intricate response of Mycobacterium tuberculosis (Mtb) to changes in iron availability. This study focuses on the repurposing and revival of FDA-approved drugs (library) as potential inhibitors of MbtA, a crucial enzyme in mycobactin biosynthesis in Mtb conserved among all species of mycobacteria. The literature suggests this pathway to be associated with drug efflux pumps, which potentially contribute to drug resistance. This makes it a potential target for antitubercular drug discovery. Herein, we utilized cheminformatics and structure-based drug repurposing approaches, viz., molecular docking, dynamics, and PCA analysis, to decode the intermolecular interactions and binding affinity of the FDA-reported molecules against MbtA. Virtual screening revealed ten molecules with significant binding affinities and interactions with MbtA. These drugs, originally designed for different therapeutic indications (four antiviral, three anticancer, one CYP450 inhibitor, one ACE inhibitor, and one leukotriene antagonist), were repurposed as potential MbtA inhibitors. Furthermore, our study explores the binding modes and interactions between these drugs and MbtA, shedding light on the structural basis of their inhibitory potential. Principal component analysis highlighted significant motions in MbtA-bound ligands, emphasizing the stability of the top protein–ligand complexes (PLCs). This computational approach provides a swift and cost-effective method for identifying new MbtA inhibitors, which can subsequently undergo validation through experimental assays. This streamlined process is facilitated by the fact that these compounds are already FDA-approved and have established safety and efficacy profiles. This study has the potential to lay the groundwork for addressing the urgent global health challenge at hand, specifically in the context of combating antimicrobial resistance (AMR) and tuberculosis (TB).
First Report of Colletotrichum fructicola, C. rhizophorae sp. nov. and C. thailandica sp. nov. on Mangrove in Thailand
Authors: Norphanphoun Chada , Hyde Kevin D.
Published: December 2023

Colletotrichum, a genus within the phylum Ascomycota (Fungi) and family Glomerellaceae are important plant pathogens globally. In this paper, we detail four Colletotrichum species found in mangrove ecosystems. Two new species, Colletotrichum rhizophorae and C. thailandica, and a new host record for Colletotrichum fructicola were identified in Thailand. Colletotrichum tropicale was collected from Taiwan’s mangroves and is a new record for Rhizophora mucronata. These identifications were established through a combination of molecular analysis and morphological characteristics. This expanded dataset for Colletotrichum enhances our understanding of the genetic diversity within this genus and its associations with mangrove ecosystems. The findings outlined herein provide data on our exploration of mangrove pathogens in Asia.
Targeting Transient Receptor Potential (TRP) Channels, Mas-Related G-Protein-Coupled Receptors (Mrgprs), and Protease-Activated Receptors (PARs) to Relieve Itch
Authors: Tsagareli Merab G. , Follansbee Taylor , Iodi Carstens Mirela , Carstens Earl
Published: December 2023

Itch (pruritus) is a sensation in the skin that provokes the desire to scratch. The sensation of itch is mediated through a subclass of primary afferent sensory neurons, termed pruriceptors, which express molecular receptors that are activated by itch-evoking ligands. Also expressed in pruriceptors are several types of Transient Receptor Potential (TRP) channels. TRP channels are a diverse class of cation channels that are responsive to various somatosensory stimuli like touch, pain, itch, and temperature. In pruriceptors, TRP channels can be activated through intracellular signaling cascades initiated by pruritogen receptors and underly neuronal activation. In this review, we discuss the role of TRP channels TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPC3/4 in acute and chronic pruritus. Since these channels often mediate itch in association with pruritogen receptors, we also discuss Mas-related G-protein-coupled receptors (Mrgprs) and protease-activated receptors (PARs). Additionally, we cover the exciting therapeutic targets amongst the TRP family, as well as Mrgprs and PARs for the treatment of pruritus.
Advantages of Long-Wavelength Photosensitizer meso-Tetra(3-pyridyl) Bacteriochlorin in the Therapy of Bulky Tumors
Authors: Plotnikova Ekaterina , Nemtsova Elena , Abakumov Maxim , Suvorov Nikita , Pankratov Andrey , Shegai Peter , Kaprin Andrey
Published: December 2023

This research presents a novel synthetic photosensitizer for the photodynamic therapy (PDT) of malignant tumors: meso-tetra(3-pyridyl) bacteriochlorin, which absorbs at 747 nm (in the long-wavelength region of the spectrum) and is stable when stored in the dark. H2Py4BC demonstrates pronounced photoinduced activity in vitro against tumor cells of various geneses (IC50 varies from 21 to 68 nM for HEp2, EJ, S37, CT26, and LLC cultured cells) and in vivo provides pronounced antitumor efficacy in the treatment of mice bearing small or large S37, Colo26, or LLC metastatic tumors, as well as in the treatment of rats bearing RS-1 liver cholangioma. As a result, total regression of primary tumor nodules and cure of 40 to 100% of the animals was proven by the experiment criteria, MRI, and histological analysis. Meso-tetra(3-pyridyl) bacteriochlorin quickly penetrates and accumulates in the tumor tissue and internal organs of mice, and after 24 h, 80% of the dye is excreted from the skin in addition to 87–92% from the liver, kidneys, and spleen.
Compensative Resistance to Erastin-Induced Ferroptosis in GPX4 Knock-Out Mutants in HCT116 Cell Lines
Authors: Adamiec-Organisciok Malgorzata , Wegrzyn Magdalena , Cienciala Lukasz , Sojka Damian , Nackiewicz Joanna , Skonieczna Magdalena
Published: December 2023

Ferroptosis results from the accumulation of oxidized and damaged lipids which then leads to programmed cell death. This programmed process is iron-dependent, and as a fundamental biological process, plays a crucial role in tissue homeostasis. The ferroptosis molecular pathway depends on self-regulatory genes: GPX4; TFRC; ACSL4; FSP1; SLC7A11, and PROM2. Some of them were considered here as ferro-sensitive or ferro-resistance markers. We examined the impact of GPX4 gene knock-out, using the CRISPR/Cas-9 technique, on ferroptosis induction in the HCT116 colorectal cancer cell line. The results confirmed that cells lacking the GPX4 gene (GPX4 KO) should be more susceptible to ferroptosis after erastin treatment. However, the decrease in cell viability was not as significant as we initially assumed. Based on the lipid peroxidation markers profile and RT-qPCR gene expression analysis, we revealed the activation of an alternative antioxidant system supporting GPX4 KO cells, mostly for cellular ferroptotic death avoidance. Increased expression of FSP1 and PRDX1 genes in knock-out mutants was associated with their function—recognized here as ferroptosis suppressors. For such reasons, studies on the role of GPX4 and other crucial genes from the ferroptotic pathway should be explored. Despite promising prospects, the utilization of ferroptosis mechanisms in cancer therapy remains at the stage of experimental and in vitro preclinical studies.
New Insights for Polyphenolic Compounds as Naturally Inspired Proteasome Inhibitors
Authors: Marchese Emanuela , Gallo Cantafio Maria Eugenia , Ambrosio Francesca Alessandra , Torcasio Roberta , Valentino Ilenia , Trapasso Francesco , Viglietto Giuseppe , Alcaro Stefano , Costa Giosuè , Amodio Nicola
Published: December 2023

Polyphenols, an important class of natural products, are widely distributed in plant-based foods. These compounds are endowed with several biological activities and exert protective effects in various physiopathological contexts, including cancer. We herein investigated novel potential mechanisms of action of polyphenols, focusing on the proteasome, which has emerged as an attractive therapeutic target in cancers such as multiple myeloma. We carried out a structure-based virtual screening study using the DrugBank database as a repository of FDA-approved polyphenolic molecules. Starting from 86 polyphenolic compounds, based on the theoretical binding affinity and the interactions established with key residues of the chymotrypsin binding site, we selected 2 promising candidates, namely Hesperidin and Diosmin. The further assessment of the biologic activity highlighted, for the first time, the capability of these two molecules to inhibit the β5-proteasome activity and to exert anti-tumor activity against proteasome inhibitor-sensitive or resistant multiple myeloma cell lines.
Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine
Authors: Wolska Eliza , Sznitowska Małgorzata , Chorążewicz Juliusz , Krzemińska Katarzyna , Szerkus Oliwia , Radwańska Aleksandra , Markuszewski Michał J. , Kaliszan Roman , Raczyńska Krystyna
Published: December 2023

Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.5% of Cs, proposed for use in eye drops, and the comparison of both. SEO eye drops with Cs or any other drug substance are currently not available as marketed products, and the highest concentration of Cs in the ocular emulsion is only 0.1%. The microscopic evaluation of the emulsion and the SEO after emulsification with water was carried out using a high-resolution digital microscopy. The properties of both preparations were compared using the high dynamic range function or optical shadow effect mode. Images in the 3D composition mode were also recorded. The in vivo study of the Cs formulations was performed on male albino rabbits. The eye tolerance of the preparations was assessed using the ocular irritation test, which is a modified Draize test. Placebo carriers (without the drug substance) were also subjected to irritation testing. The concentration of Cs in the tissues (cornea and conjunctiva) and fluids (tear fluid and aqueous humor) of the rabbit eye was determined after multiple instillations of Cs–EM or Cs–SEO. The tested preparations were compared using the digital microscopy technique, which highlights the features of the formulations and eliminates the risk of unnoticeable properties that are difficult to observe in classical optical microscopy. Both tested Cs-loaded formulations are classified as practically non-irritating. There were also no significant differences when testing the placebo carriers. After a topical administration, Cs was widely distributed in all tissues (e.g., in cornea 1.3 ng/mg and 1.0 ng/mg) and fluids of the eye (e.g., in tear fluid 11.6 µg/mL and 4.3 µg/mL), after the administration of Cs–SEO and Cs–EM, respectively. The obtained results allow us to recognize both tested formulations, the emulsion and the self-emulsifying oil with 0.5% Cs content, as carriers safe for ophthalmic use and effective in delivering the drug substance to the structures of the eye.
Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders
Authors: Isop Laura Mihaela , Neculau Andrea Elena , Necula Radu Dan , Kakucs Cristian , Moga Marius Alexandru , Dima Lorena
Published: December 2023

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer’s, Parkinson’s, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin’s mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as “metformin”, “neuroprotection”, and “neurodegenerative diseases”, with data up to September 2023. Recent research on metformin’s glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1–AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.
Cardiac PET Imaging of ATP Binding Cassette (ABC) Transporters: Opportunities and Challenges
Authors: Liu Wanling , Mossel Pascalle , Schwach Verena , Slart Riemer H. J. A. , Luurtsema Gert
Published: December 2023

Adenosine triphosphate binding cassette (ABC) transporters are a broad family of membrane protein complexes that use energy to transport molecules across cells and/or intracellular organelle lipid membranes. Many drugs used to treat cardiac diseases have an affinity for these transporters. Among others, P-glycoprotein (P-gp) plays an essential role in regulating drug concentrations that reach cardiac tissue and therefore contribute to cardiotoxicity. As a molecular imaging modality, positron emission tomography (PET) has emerged as a viable technique to investigate the function of P-gp in organs and tissues. Using PET imaging to evaluate cardiac P-gp function provides new insights for drug development and improves the precise use of medications. Nevertheless, information in this field is limited. In this review, we aim to examine the current applications of ABC transporter PET imaging and its tracers in the heart, with a specific emphasis on P-gp. Furthermore, the opportunities and challenges in this novel field will be discussed.
Lipidomics Profiling of Metformin-Induced Changes in Obesity and Type 2 Diabetes Mellitus: Insights and Biomarker Potential
Authors: Mujammami Muhammad , Aleidi Shereen M. , Buzatto Adriana Zardini , Alshahrani Awad , AlMalki Reem H. , Benabdelkamel Hicham , Al Dubayee Mohammed , Li Liang , Aljada Ahmad , Abdel Rahman Anas M.
Published: December 2023

Metformin is the first-line oral medication for treating type 2 diabetes mellitus (T2DM). In the current study, an untargeted lipidomic analytical approach was used to investigate the alterations in the serum lipidome of a cohort of 89 participants, including healthy lean controls and obese diabetic patients, and to examine the alterations associated with metformin administration. A total of 115 lipid molecules were significantly dysregulated (64 up-regulated and 51 down-regulated) in the obese compared to lean controls. However, the levels of 224 lipid molecules were significantly dysregulated (125 up-regulated and 99 down-regulated) in obese diabetic patients compared to the obese group. Metformin administration in obese diabetic patients was associated with significant dysregulation of 54 lipid molecule levels (20 up-regulated and 34 down-regulated). Levels of six molecules belonging to five lipid subclasses were simultaneously dysregulated by the effects of obesity, T2DM, and metformin. These include two putatively annotated triacylglycerols (TGs), one plasmenyl phosphatidylcholine (PC), one phosphatidylglycerol (PGs), one sterol lipid (ST), and one Mannosyl-phosphoinositol ceramide (MIPC). This study provides new insights into our understanding of the lipidomics alterations associated with obesity, T2DM, and metformin and offers a new platform for potential biomarkers for the progression of diabetes and treatment response in obese patients.
Orodispersible Films: Current Innovations and Emerging Trends
Authors: Jacob Shery , Boddu Sai H. S. , Bhandare Richie , Ahmad Samiullah Shabbir , Nair Anroop B.
Published: December 2023

Orodispersible films (ODFs) are thin, mechanically strong, and flexible polymeric films that are designed to dissolve or disintegrate rapidly in the oral cavity for local and/or systemic drug delivery. This review examines various aspects of ODFs and their potential as a drug delivery system. Recent advancements, including the detailed exploration of formulation components, such as polymers and plasticizers, are briefed. The review highlights the versatility of preparation methods, particularly the solvent-casting production process, and novel 3D printing techniques that bring inherent flexibility. Three-dimensional printing technology not only diversifies active compounds but also enables a multilayer approach, effectively segregating incompatible drugs. The integration of nanoparticles into ODF formulations marks a significant breakthrough, thus enhancing the efficiency of oral drug delivery and broadening the scope of the drugs amenable to this route. This review also sheds light on the diverse in vitro evaluation methods utilized to characterize ODFs, ongoing clinical trials, approved marketed products, and recent patents, providing a comprehensive outlook of the evolving landscape of orodispersible drug delivery. Current patient-centric approaches involve developing ODFs with patient-friendly attributes, such as improved taste masking, ease of administration, and enhanced patient compliance, along with the personalization of ODF formulations to meet individual patient needs. Investigating novel functional excipients with the potential to enhance the permeation of high-molecular-weight polar drugs, fragile proteins, and oligonucleotides is crucial for rapid progress in the advancing domain of orodispersible drug delivery.
HPLC- and NMR-Based Chemical Profiling, Wound-Healing Potential, Anti-Inflammatory and Antibacterial Activities of Satureja pilosa (Lamiaceae), a Neglected Medicinal–Aromatic Herb
Authors: Panagiotidou Christina , Burgers Luisa D. , Tsadila Christina , Almpani Chara , Krigas Nikos , Mossialos Dimitris , Rallis Michail Christou , Fürst Robert , Karioti Anastasia
Published: December 2023

Satureja pilosa Velen. (Lamiaceae) is a perennial and melliferous aromatic–medicinal subshrub which is range-restricted in adjacent parts of Greece and Bulgaria and locally in Italy, known in Northern Greece as wild oregano (“agriorigani”) and traditionally collected from the wild for culinary purposes. Since the ethnopharmacological data and modern biological activities of Satureja spp. suggest promising applications in skin conditions, the present study aimed to investigate the hitherto unknown phenolic content of cultivated S. pilosa and its potential biological activities, focusing mainly on wound-healing and anti-inflammatory effects. An HPLC-PDA-MS-targeted phytochemical investigation, along with NMR, allowed for the isolation and characterization of the main constituents, resulting in 18 compounds. Representative extracts and purified compounds were tested for wound-healing activity on NIH/3T3 fibroblasts. The butanol extract exhibited a significantly higher cell migration rate (73.4%) compared to aqueous (50.6%) and methanolic (49.6%) ones, enhancing the cell migration more rapidly at both concentration levels, whilst rosmarinic acid was the most potent among the isolated compounds, with a migration rate of 64.0% at the concentration level of 10−5 mg/mL, followed by 3,4-dihydrophenyllactic acid (54.7%). Moreover, potential effects on endothelial activation processes were explored, including the leukocyte–endothelial cell interaction during inflammatory processes and the migratory capacity during angiogenic actions, since these processes are commonly associated with skin diseases. Finally, extracts and purified compounds demonstrated weak antibacterial potential against two important pathogens (Staphylococcus aureus and Pseudomonas aeruginosa), suggesting that further investigation is warrented.
No Pairwise Interactions of GmSNAP18, GmSHMT08 and AtPR1 with Suppressed AtPR1 Expression Enhance the Susceptibility of Arabidopsis to Beet Cyst Nematode
Authors: Zhang Liuping , Zhao Jie , Kong Lingan , Huang Wenkun , Peng Huan , Peng Deliang , Meksem Khalid , Liu Shiming
Published: December 2023

GmSNAP18 and GmSHMT08 are two major genes conferring soybean cyst nematode (SCN) resistance in soybean. Overexpression of either of these two soybean genes would enhance the susceptibility of Arabidopsis to beet cyst nematode (BCN), while overexpression of either of their corresponding orthologs in Arabidopsis, AtSNAP2 and AtSHMT4, would suppress it. However, the mechanism by which these two pairs of orthologous genes boost or inhibit BCN susceptibility of Arabidopsis still remains elusive. In this study, Arabidopsis with simultaneously overexpressed GmSNAP18 and GmSHMT0 suppressed the growth of underground as well as above-ground parts of plants. Furthermore, Arabidopsis that simultaneously overexpressed GmSNAP18 and GmSHMT08 substantially stimulated BCN susceptibility and remarkably suppressed expression of AtPR1 in the salicylic acid signaling pathway. However, simultaneous overexpression of GmSNAP18 and GmSHMT08 did not impact the expression of AtJAR1 and AtHEL1 in the jasmonic acid and ethylene signaling pathways. GmSNAP18, GmSHMT08, and a pathogenesis-related (PR) protein, GmPR08-Bet VI, in soybean, and AtSNAP2, AtSHMT4, and AtPR1 in Arabidopsis could interact pair-wisely for mediating SCN and BCN resistance in soybean and Arabidopsis, respectively. Both AtSNAP2 and AtPR1 were localized on the plasma membrane, and AtSHMT4 was localized both on the plasma membrane and in the nucleus of cells. Nevertheless, after interactions, AtSNAP2 and AtPR1 could partially translocate into the cell nucleus. GmSNAP18 interacted with AtSHMT4, and GmSHMT4 interacted with AtSNAP2. However, neither GmSNAP18 nor GmSHMT08 interacted with AtPR1. Thus, no pairwise interactions among α-SNAPs, SHMTs, and AtPR1 occurred in Arabidopsis overexpressing either GmSNAP18 or GmSHMT08, or both of them. Transgenic Arabidopsis overexpressing either GmSNAP18 or GmSHMT08 substantially suppressed AtPR1 expression, while transgenic Arabidopsis overexpressing either AtSNAP2 or AtSHMT4 remarkably enhanced it. Taken together, no pairwise interactions of GmSNAP18, GmSHMT08, and AtPR1 with suppressed expression of AtPR1 enhanced BCN susceptibility in Arabidopsis. This study may provide a clue that nematode-resistant or -susceptible functions of plant genes likely depend on both hosts and nematode species.
Seed Germination and Growth Improvement for Early Maturing Pear Breeding
Authors: Kan Jialiang , Yuan Na , Lin Jing , Li Hui , Yang Qingsong , Wang Zhonghua , Shen Zhijun , Ying Yeqing , Li Xiaogang , Cao Fuliang
Published: December 2023

Breeding early maturing cultivars is one of the most important objectives in pear breeding. Very early maturing pears provide an excellent parental material for crossing, but the immature embryo and low seed germination of their hybrid progenies often limit the selection and breeding of new early maturing pear cultivars. In this study, we choose a very early maturing pear cultivar ‘Pearl Pear’ as the study object and investigate the effects of cold stratification, the culture medium, and the seed coat on the germination and growth of early maturing pear seeds. Our results show that cold stratification (4 °C) treatment could significantly improve the germination rates of early maturing pear seeds. A total of 100 days of cold-temperature treatment in 4 °C and in vitro germination on White medium increased the germination rate to 84.54%. We also observed that seed coat removal improved the germination of early maturing pear seeds, with middle seed coat removal representing the optimal method, with a high germination rate and low contamination. The results of our study led to the establishment of an improved protocol for the germination of early maturing pear, which will greatly facilitate the breeding of new very early maturing pear cultivars.
Light and Ethephon Overcoming Seed Dormancy in Friar’s Crown (Melocactus zehntneri, Cactaceae), a Brazilian Cactus
Authors: Magnani Mariana Freitas Campos , Cardoso Jean Carlos
Published: December 2023

Seed germination in Melocactus and other cactus species is hampered by dormancy. However, most studies failed to achieve high seed-germination rates, suggesting a complex mechanism of dormancy in Cactaceae. Thus, the objective of this study was to evaluate whether factors such as light and phytoregulators overcome the dormancy in the seeds of the friar’s crown cactus (Melocactus zehntneri). Two consecutive experimental sets were designed: one with seed germination under filter paper conditions and different wavelengths and Photosynthetically Photon Flux Densities (PPFDs); and one in vitro experiment using a culture medium to evaluate the influence of different phytoregulators, such as gibberellic acid (GA3), benzylaminopurine (BAP) and ethephon (ET), both in the germination of seeds of M. zehntneri. Seeds of M. zehntneri are positive photoblastic. Red light and gradual increases in PPFD resulted in the highest germination rates (60.8–61.7%) and germination speed index (4.4–4.5). In vitro seeding in culture media increased the germination percentage to 76% in control without phytoregulators. Ethephon showed a major effect in releasing the germination of dormant seeds of M. zehntneri, totaling 98% of seeds germinated under in vitro conditions, while GA3 and BAP showed minor or no effect on germination. The present study resulted in an efficient in vitro technique for germination and a better understanding of cacti seed dormancy.
Effects of Biochar Applied in Either Rice or Wheat Seasons on the Production and Quality of Wheat and Nutrient Status in Paddy Profiles
Authors: Chen Zirui , Liu Jiale , Sun Haijun , Xing Jincheng , Zhang Zhenhua , Jiang Jiang
Published: December 2023

In a rice–wheat rotation system, biochar (BC) applied in different crop seasons undergoes contrast property changes in the soil. However, it is unclear how aged BC affects the production and quality of wheat and the nutrent status in a soil profile. In the present soil column experiment, the effects of no nitrogen (N) fertilizer and BC addition (control), N fertilizer (N420) and BC (5 t ha−1) applied at rice [N420 + BC(R)], or wheat [N420 + BC(W)] seasons at a same rate of N fertilizer (420 kg ha−1 yr−1) on yield and quality of wheat as well as the nutrient contents of soil profiles (0–5, 5–10, 10–20, 20–30, 30–40, and 40–50 cm) were observed. The results showed that N420 + BC(W) significantly reduced NH4+-N content in 5–10 and 10–20 cm soils by 62.1% and 36.2%, respectively, compared with N420. In addition, N420 + BC(W) significantly reduced NO3−-N contents by 17.8% and 40.4% in 0–5 and 20–30 cm profiles, respectively, but N420 + BC(R) slightly increased them. The BC applied in wheat season significantly increased the 0–5 and 40–50 cm soil total N contents (24.0% and 48.1%), and enhanced the 30–40 and 40–50 cm soil-available phosphorus contents (48.2 and 35.75%) as well as improved the 10–20 and 20–30 cm soil-available potassium content (38.1% and 57.5%). Overall, our results suggest that N420 + BC(W) had stronger improving effects on soil fertility than N420 + BC(R). Compared to N420, there was a significant 5.9% increase in wheat grain yield, but no change in total amino acids in wheat kernels in N420 + BC(W). Considering the responses of soil profile nutrient contents as well as wheat yield and quality to BC application in different crop seasons, it is more appropriate to apply BC in wheat season. Our results could provide a scientific basis for the ideal time to amend BC into the rice–wheat rotation system, in order to achieve more benefits of BC on crop production and soil fertility.
Exploring the Molecular Origin for the Long-Range Propagation of the Substrate Effect in Unentangled Poly(methyl methacrylate) Films
Authors: Xu Jianquan , Guo Xiaojin , Guo Hongkai , Zhang Yizhi , Wang Xinping
Published: December 2023

The polymer/substrate interface plays a significant role in the dynamics of nanoconfined polymers because of its suppression on polymer mobility and its long-range propagation feature, while the molecular origin of the long-range substrate effect in unentangled polymer material is still ambiguous. Herein, we investigated the propagation distances of the substrate effect (h*) by a fluorinated tracer-labeled method of two unentangled polymer films supported on silicon substrates: linear and ring poly(methyl methacrylate) films with relatively low molecular weights. The results indicate that the value of h* has a molecular weight dependence of h*∝N (N is the degree of polymerization) in the unentangled polymer films, while h*∝N1/2 was presented as previously reported in the entangled films. A theoretical model, depending on the polymer/polymer intermolecular interaction, was proposed to describe the above long-range propagation behavior of the substrate effect and agrees with our experiment results very well. From the model, it revealed that the intermolecular friction determines the long-range propagation of the substrate effect in the unentangled system, but the intermolecular entanglement is the dominant role in entangled system. These results give us a deeper understanding of the long-range substrate effect.
Electrically Tunable Two-Color Cholesteric Laser
Authors: Saadaoui Lotfi , Yang Donghao , Wang Yu , Hassan Faheem , Drevensek-Olenik Irena , Zhang Xinzheng , Gan Zenghua , Li Yigang , Xu Jingjun
Published: December 2023

Two-color lasing emission from an asymmetric structure, consisting of two dye-doped cholesteric liquid crystal (DD-CLC) layers separated by a transparent interlayer, is demonstrated. The DD-CLC mixtures have different reflection bands with long-wavelength band edges located at the green and red wavelengths of the visible spectrum, respectively. For the laser action, the CLC hosts provide the feedback, and the fluorescent laser dyes represent the active medium. When the stacked structure is optically pumped above the threshold, two simultaneous laser lines separated by 123 nm are observed at the long-wavelength band edges of the DD-CLC mixtures. The influence of an electric field on lasing behavior is also analyzed and discussed in terms of the reflection spectrum and laser action. The results show a reversible tuning of the reflection band, accompanied by a modification of the lasing characteristics under the application of an external field. Above a specific threshold voltage, one of the emission lines is suppressed and the other is conserved. With a further increase in the voltage, both laser emissions are entirely inhibited. The investigated structure demonstrates a simple technique to obtain an electrically tunable multi-wavelength laser, which might pave the way for a new generation of organic laser sources.
Modifying Effect and Mechanism of Polymer Powder on the Properties of Asphalt Binder for Engineering Application
Authors: Zhao Wensheng , Sun Xiaolong , Ou Zhixin , Li Zhijian , Liu Zhisheng , Qin Xiao
Published: December 2023

For achieving the better modifying effect of polyurethane on asphalt pavement materials, the PUA powder modifier was prepared with fine grinding at the glass transition temperature, and polyurethane-modified asphalt (PUA-MA) with different dosages of modifier was prepared. The impact of the PUA on the physical properties of asphalt binder was studied. The modifying mechanism of PUA on asphalt was explored by investigating the thermal performance and chemical composition of asphalt (thermogravimetric analysis, differential scanning calorimetry test, and Fourier transform infrared spectroscopy). The micrograph of the interactive interface was characterized by scanning an electron microscope. Furthermore, the rheological properties of PUA-MA were also investigated and analyzed. The results indicated that the PUA had a dense structure with few pores on the surface. After mixing with asphalt, it altered the asphalt’s internal structure via physical fusion and chemical reaction (carbamate formation). PUA improved the thermal stability of asphalt, enhanced the asphalt’s thermal decomposition temperature, and further reduced the thermal mass loss while decreasing the glass transition temperature. The addition and dosage increase in the PUA modifier significantly improved the softening point, viscosity, complex shear modulus, and rutting factor of asphalt. Also, the PUA could improve the elastic recovery ability of asphalt and enhance the rutting resistance of asphalt at high temperatures. However, the crack resistance at low temperatures was not effectively improved (ductility and penetration decreased). When the dosage was 6–9%, PUA-MA had the best high-temperature performance, but asphalt showed poor low-temperature performance at this dosage. This study provides a theoretical reference for popularizing and applying polyurethane as an asphalt modifier in road engineering.