bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advancements in Metal and Non-Metal Mixed-Doped Carbon Quantum Dots: Synthesis and Emerging Potential Applications
Authors: Akram Zubair , Raza Ali , Mehdi Muhammad , Arshad Anam , Deng Xiling , Sun Shiguo
Published: August 2023

In nanotechnology, the synthesis of carbon quantum dots (CQDs) by mixed doping with metals and non-metals has emerged as an appealing path of investigation. This review offers comprehensive insights into the synthesis, properties, and emerging applications of mixed-doped CQDs, underlining their potential for revolutionary advancements in chemical sensing, biosensing, bioimaging, and, thereby, contributing to advancements in diagnostics, therapeutics, and the under standing of complex biological processes. This synergistic combination enhances their sensitivity and selectivity towards specific chemical analytes. The resulting CQDs exhibit remarkable fluorescence properties that can be involved in precise chemical sensing applications. These metal-modified CQDs show their ability in the selective and sensitive detection from Hg to Fe and Mn ions. By influencing their exceptional fluorescence properties, they enable precise detection and monitoring of biomolecules, such as uric acid, cholesterol, and many antibiotics. Moreover, when it comes to bioimaging, these doped CQDs show unique behavior towards detecting cell lines. Their ability to emit light across a wide spectrum enables high-resolution imaging with minimal background noise. We uncover their potential in visualizing different cancer cell lines, offering valuable insights into cancer research and diagnostics. In conclusion, the synthesis of mixed-doped CQDs opens the way for revolutionary advancements in chemical sensing, biosensing, and bioimaging. As we investigate deeper into this field, we unlock new possibilities for diagnostics, therapeutics, and understanding complex biological processes.
Ultrasonography for Eating and Swallowing Assessment: A Narrative Review of Integrated Insights for Noninvasive Clinical Practice
Authors: Maeda Keisuke , Nagasaka Motoomi , Nagano Ayano , Nagami Shinsuke , Hashimoto Kakeru , Kamiya Masaki , Masuda Yuto , Ozaki Kenichi , Kawamura Koki
Published: August 2023

Dysphagia is a syndrome of abnormal eating function resulting from a variety of causative diseases, and is associated with malnutrition. To date, the swallowing function has been difficult to examine without the use of invasive and expensive methods, such as the videofluorographic swallowing study or fiberoptic endoscopic evaluation of swallowing. In recent years, progress has been made in the clinical application of ultrasound equipment for the evaluation of body compositions near the body surface, including the assessment of nutritional status. Ultrasound examination is a noninvasive procedure and relatively inexpensive, and the equipment required is highly portable thanks to innovations such as wireless probes and tablet monitoring devices. The process of using ultrasound to visualize the geniohyoid muscle, digastric muscle, mylohyoid muscle, hyoid bone, tongue, masseter muscle, genioglossus muscle, orbicularis oris muscle, temporalis muscle, pharynx, esophagus, and larynx, and the methods used for evaluating these structures, are provided in this study in detail. This study also aims to propose a protocol for the assessment of swallowing-related muscles that can be applied in real-world clinical practice for the diagnosis of sarcopenic dysphagia, which can occur in elderly patients with sarcopenia, and has received much attention in recent years.
Beverage Consumption Patterns among U.S. Adolescents and Adults from a New 24-h Beverage Recall Survey Compared to the National Health and Nutrition Examination Survey (NHANES) 2017–2018
Authors: Bi Xiaoyu , Davis Benjamin J. K. , Barraj Leila M. , Srinivasan Devanathan , Mahadev Parvati , Mathew Preeti , Mishra Dibyendu , Scrafford Carolyn G. , Tran Nga L. , Jack Maia M.
Published: August 2023

Beverages are major dietary components of the United States (U.S.) population. Understanding the current consumption pattern of beverages is an important element in supporting healthy diets. Our objective was to assess the validity of the 24-h beverage consumption recall data collected in 2021 through a self-administered online questionnaire (referred to as the American Beverage Association-Brandscapes Worldwide survey, ABA-BSW) by comparing it to the 24-h dietary recall data collected in the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Summary statistics on the reported consumption amounts and consumption occasions (COs) of 13 beverage types (e.g., bottled water, carbonated soft drinks (CSD), tea, and others) by participants aged 13–64 years were compared between ABA-BSW (n = 20,553) and NHANES (n = 4437). The average daily consumption amount among consumers of all 13 beverage types combined was higher in ABA-BSW than in NHANES (1903 mL/day vs. 1704 mL/day). Within each beverage type, the average daily consumption amounts among consumers were generally lower in ABA-BSW except for CSD, plant-based drinks, and still juices and fruit-flavored drinks. Compared to NHANES, ABA-BSW participants reported consuming a wider variety of beverage groups, a higher number of COs per day, and lower consumption amounts within a given CO. Overall, beverage consumption patterns observed in ABA-BSW and NHANES were generally similar, supporting the design and implementation of the former survey. Further, the ABA-BSW data provide additional information on the within-day temporal beverage consumption patterns among adolescents and adults in the U.S. Differences in the observed consumption patterns between the surveys may be the result of various factors, including the survey implementation method, a consumption pattern shift between the survey time periods, beverage type availability, and impact of the COVID-19 pandemic on dietary patterns.
Reducing Dietary Sodium Intake among Young Adults in Ghana: A Call to Action
Authors: Peprah Emmanuel , Amegbor Prince , Laar Amos , Akasoe Bismark , Commodore-Mensah Yvonne
Published: August 2023

The positive association between excessive dietary sodium intake, hypertension, and cardiovascular disease (CVD) has been widely investigated in observational studies and clinical trials. Reducing sodium intake is a proven strategy to prevent hypertension and the onset of CVD, a major cause of morbidity and mortality globally. Africa has the youngest population globally, which is key to the continent’s sustainable development. However, in Africa, the epidemics of hypertension and CVD negatively impact life expectancy and economic growth. Ghana, like other African countries, is no exception. The factors contributing to the increasing burden of CVD and excessive sodium consumption are multi-faceted and multi-level, including individual lifestyle, neighborhood and built environments, and socio-economic and health policies. Thus, the implementation of evidence-based interventions such as the World Health Organization Best Buys that target the multi-level determinants of sodium consumption is urgently needed in Ghana and other African countries. The aim of this commentary is to highlight factors that contribute to excessive sodium consumption. Second, the commentary will showcase lessons of successful implementation of sodium reduction interventions in other countries. Such lessons may help avert CVD in young adults in Ghana and Africa.
Trophoblast Differentiation: Mechanisms and Implications for Pregnancy Complications
Authors: Lawless Lauren , Qin Yushu , Xie Linglin , Zhang Ke
Published: August 2023

Placental development is a tightly controlled event, in which cell expansion from the trophectoderm occurs in a spatiotemporal manner. Proper trophoblast differentiation is crucial to the vitality of this gestational organ. Obstructions to its development can lead to pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm birth, posing severe health risks to both the mother and offspring. Currently, the only known treatment strategy for these complications is delivery, making it an important area of research. The aim of this review was to summarize the known information on the development and mechanistic regulation of trophoblast differentiation and highlight the similarities in these processes between the human and mouse placenta. Additionally, the known biomarkers for each cell type were compiled to aid in the analysis of sequencing technologies.
Individual Postprandial Glycemic Responses to Meal Types by Different Carbohydrate Levels and Their Associations with Glycemic Variability Using Continuous Glucose Monitoring
Authors: Song Jiwoo , Oh Tae Jung , Song YoonJu
Published: August 2023

This study aimed to investigate individual postprandial glycemic responses (PPGRs) to meal types with varying carbohydrate levels and examine their associations with 14-day glycemic variability using continuous glucose monitoring (CGM) in young adults. In a two-week intervention study with 34 participants connected to CGM, four meal types and glucose 75 g were tested. PPGRs were recorded for up to 2 h with a 15 min interval after meals. Data-driven cluster analysis was used to group individual PPGRs for each meal type, and correlation analysis was performed of 14-day glycemic variability and control with related factors. Participants had a mean age of 22.5 years, with 22.8% being male. Four meal types were chosen according to carbohydrate levels. The mean glucose excursion for all meal types, except the fruit bowl, exhibited a similar curve with attenuation. Individuals classified as high responders for each meal type exhibited sustained peak glucose levels for a longer duration compared to low responders, especially in meals with carbohydrate contents above 50%. A meal with 45% carbohydrate content showed no correlation with either 14-day glycemic variability or control. Understanding the glycemic response to carbohydrate-rich meals and adopting a meal-based approach when planning diets are crucial to improving glycemic variability and control.
Novel Key Ingredients in Urinary Tract Health—The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®)
Authors: Crocetto Felice , Balsamo Raffaele , Amicuzi Ugo , De Luca Luigi , Falcone Alfonso , Mirto Benito Fabio , Giampaglia Gaetano , Ferretti Gianpiero , Capone Federico , Machiella Fabio , Varriale Domenico , Sicignano Enrico , Pagano Giovanni , Lombardi Alessandro , Lucarelli Giuseppe , Lasorsa Francesco , Busetto Gian Maria , Del Giudice Francesco , Ferro Matteo , Imbimbo Ciro , Barone Biagio
Published: August 2023

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.
Maternal Bonding as a Protective Factor for Orthorexia Nervosa Risk in Dietetics Students
Authors: Athanasaki Dafni , Lakoumentas John , Milani Gregorio Paolo , Agostoni Carlo , Berghea Florian , Ionescu Marcela Daniela , Vassilopoulou Emilia
Published: August 2023

This study aimed to determine the prevalence of the risk of orthorexia nervosa (ON) in dietetics students in Greece, and its relationship with diet, risk of eating disorder (ED), body mass index (BMI), body image flexibility, and parental attachment. The participants were 132 dietetics students, with a mean age of 22.94 ± 3.5 years, who completed a series of questionnaires that recorded sociodemographic, clinical, and anthropometric characteristics; adherence to the Mediterranean diet (MedDiet); ON indicators as determined by the ORTO-15 questionnaire; body image flexibility, with the Body Image-Acceptance and Action Questionnaire (BI-AAQ-5); the risk for ED as assessed using the EAT-26; anxiety level according to the STAIT 6 instrument; and recollection of their parents’ attitudes towards them during the first 16 years of life, with the Parental Bonding Instrument (PBI). ON risk appeared to be significantly associated with BMI (p = 0.002), exercise frequency (p = 0.023), anxiety level (p = 0.002), risk of ED (p < 0.001), body image inflexibility (p < 0.001), and inversely with the affectionate constraint of maternal bonding (p = 0.036). In conclusion, disordered eating behaviors and body shape concerns are prevalent among dietetics students, with parental attachment to the mother influencing their occurrence. Identification of potential ON and development of prevention mechanisms during childhood could help eliminate these concerns and improve the lives of dietetics students.
Natural Phytochemicals as SIRT Activators—Focus on Potential Biochemical Mechanisms
Authors: Wiciński Michał , Erdmann Jakub , Nowacka Agnieszka , Kuźmiński Oskar , Michalak Klaudia , Janowski Kacper , Ohla Jakub , Biernaciak Adrian , Szambelan Monika , Zabrzyński Jan
Published: August 2023

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.
Incorporating Immune Cells into Organoid Models: Essential for Studying Human Disease
Authors: Bogoslowski Ania , An Meilin , Penninger Josef M.
Published: August 2023

Organoid-based research has made significant discoveries and contributions to our understanding of human organ function in both health and disease. To continue making progress, it is crucial to acknowledge the crucial role of the immune system in all organs. Various immune cells, such as macrophages, T cells, and neutrophils, are resident in almost all human tissues and play essential roles in organ homeostasis, function, and disease. Using diverse methods, researchers have begun integrating immune cells into organoid models, leading to more physiologically relevant models that better represent various aspects of human disease. These methods range from immune cell injection to co-culture and tissue expansion with existing immune cells. Immune cells can be sourced from mature patients or generated from stem cells as immature immune cells. The successful incorporation of immune cells into organoids will enhance our understanding of organ function and provide a more accurate approximation of human disease.
Macroelement and Microelement Levels in the Urine in Experimental Acanthamoebiasis
Authors: Łanocha-Arendarczyk Natalia , Kot Karolina , Baranowska-Bosiacka Irena , Kupnicka Patrycja , Przydalska Dagmara , Łanocha Aleksandra , Chlubek Dariusz , Wojciechowska-Koszko Iwona , Kosik-Bogacka Danuta Izabela
Published: August 2023

Free-living amoebas can impact the excretion of macroelements and microelements in urine. The aim of the present study was to examine the concentrations of macroelements, including calcium (Ca), phosphorus (P), sodium (Na), potassium (K), and magnesium (Mg), as well as microelements such as manganese (Mn), zinc (Zn), copper (Cu), iron (Fe), and chromium (Cr), in the urine during acanthamoebiasis while considering the host’s immunological status. This is the first study to show an increase in urinary excretion of Ca, Mn, Cu, Fe, Na, and Cr, along with a decreased excretion of K, in immunocompetent mice 16 days post Acanthamoeba sp. infection. In the final phase of infection (24 dpi), there was a further decrease in urinary K excretion and a lower level of P in Acanthamoeba sp. infected immunocompetent hosts. During acanthamoebiasis in immunosuppressed hosts, increased excretion of Zn, Fe, and Cr was observed at the beginning of the infection, and increased Na excretion only at 16 days post Acanthamoeba sp. infection. Additionally, host immunosuppression affected the concentration of Fe, Cr, Zn, Cu, Mn, and Ca in urine.
Traditional Chinese Medicine for Topical Treatment of Skeletal Muscle Injury
Authors: Siu Wing-Sum , Ma Hui , Cheng Wen , Shum Wai-Ting , Leung Ping-Chung
Published: August 2023

Muscle injuries are common musculoskeletal problems, but the pharmaceutical agent for muscle repair and healing is insufficient. Traditional Chinese Medicine (TCM) frequently uses topical treatments to treat muscle injuries, although scientific evidence supporting their efficacy is scarce. In this study, an in vitro assay was used to test the cytotoxicity of a topical TCM formula containing Carthami Flos, Dipsaci Radix, and Rhei Rhizoma (CDR). Then, a muscle contusion rat model was developed to investigate the in vivo effect and basic mechanisms underlying CDR on muscle regeneration. The in vitro assay illustrated that CDR was non-cytotoxic to immortalized rat myoblast culture and increased cell viability. Histological results demonstrated that the CDR treatment facilitated muscle repair by increasing the number of new muscle fibers and promoting muscle integrity. The CDR treatment also upregulated the expression of Pax7, MyoD and myogenin, as evidenced by an immunohistochemical study. A gene expression analysis indicated that the CDR treatment accelerated the regeneration and remodeling phases during muscle repair. This study demonstrated that topical CDR treatment was effective at facilitating muscle injury repair.
Oxidative Stress and Antioxidant-Based Interventional Medicine in Ophthalmology
Authors: Honisch Claudia , Rodella Umberto , Gatto Claudio , Ruzza Paolo , Tóthová Jana D’Amato
Published: August 2023

The different anatomical compartments of the eye are highly subjected to reactive oxygen species (ROS) generation due to internal factors, such as metabolic high oxygen consumption, as well as environmental factors, including UV light. An antioxidant defense system is endowed in the eye tissues to regulate ROS quantity and activity. When this homeostatic system is overwhelmed, oxidative stress occurs, causing cellular damage, chronic inflammation, and tissue degeneration. It also plays a significant role in the development and progression of various ocular diseases. Understanding the mechanisms underlying oxidative stress in ocular conditions is thus crucial for the development of effective prevention and treatment strategies. To track marketed products based on antioxidant substances as active ingredients, the databases of the European Medicines Agency and the U.S. Food and Drug Administration were consulted. Only a limited number of items were identified, which were either used as therapeutic treatment or during ocular surgery, including antioxidants, synthetical derivatives, or pro-drugs designed to enhance tissue permeation and activity. This review aims to provide an overview of the primary ocular pathologies associated with oxidative stress and of the available pharmacological interventions centered around antioxidant molecules. Such insights are essential for advancing the development of effective prevention and novel treatment approaches.
Discovery of Potential Noncovalent Inhibitors of Dehydroquinate Dehydratase from Methicillin-Resistant Staphylococcus aureus through Computational-Driven Drug Design
Authors: Millán-Pacheco César , Rios-Soto Lluvia , Corral-Rodríguez Noé , Sierra-Campos Erick , Valdez-Solana Mónica , Téllez-Valencia Alfredo , Avitia-Domínguez Claudia
Published: August 2023

Bacteria resistance to antibiotics is a concerning global health problem; in this context, methicillin-resistant Staphylococcus aureus (MRSA) is considered as a high priority by the World Health Organization. Furthermore, patients with a positive result for COVID-19 received early antibiotic treatment, a fact that potentially encourages the increase in antibiotic resistance. Therefore, there is an urgency to develop new drugs with molecular mechanisms different from those of the actual treatments. In this context, enzymes from the shikimate pathway, a route absent in humans, such as dehydroquinate dehydratase (DHQD), are considered good targets. In this work, a computer-aided drug design strategy, which involved exhaustive virtual screening and molecular dynamics simulations with MM-PBSA analysis, as well as an in silico ADMETox characterization, was performed to find potential noncovalent inhibitors of DHQD from MRSA (SaDHQD). After filtering the 997 million compounds from the ZINC database, 6700 compounds were submitted to an exhaustive virtual screening protocol. From these data, four molecules were selected and characterized (ZINC000005753647 (1), ZINC000001720488 (2), ZINC000082049768 (3), and ZINC000644149506 (4)). The results indicate that the four potential inhibitors interacted with residues important for substrate binding and catalysis, with an estimated binding free energy like that of the enzyme’s substrate. Their ADMETox-predicted properties suggest that all of them support the structural characteristics to be considered good candidates. Therefore, the four compounds reported here are excellent option to be considered for future in vitro studies to design new SaDHQD noncovalent inhibitors and contribute to the search for new drugs against MRSA.
Therapeutic Potential of Cannabinoids in Glaucoma
Authors: Lindner Theresa , Schmidl Doreen , Peschorn Laura , Pai Viktoria , Popa-Cherecheanu Alina , Chua Jacqueline , Schmetterer Leopold , Garhöfer Gerhard
Published: August 2023

Glaucoma is a leading cause of irreversible blindness worldwide. To date, intraocular pressure (IOP) is the only modifiable risk factor in glaucoma treatment, but even in treated patients, the disease can progress. Cannabinoids, which have been known to lower IOP since the 1970s, have been shown to have beneficial effects in glaucoma patients beyond their IOP-lowering properties. In addition to the classical cannabinoid receptors CB1 and CB2, knowledge of non-classical cannabinoid receptors and the endocannabinoid system has increased in recent years. In particular, the CB2 receptor has been shown to mediate anti-inflammatory, anti-apoptotic, and neuroprotective properties, which may represent a promising therapeutic target for neuroprotection in glaucoma patients. Due to their vasodilatory effects, cannabinoids improve blood flow to the optic nerve head, which may suggest a vasoprotective potential and counteract the altered blood flow observed in glaucoma patients. The aim of this review was to assess the available evidence on the effects and therapeutic potential of cannabinoids in glaucoma patients. The pharmacological mechanisms underlying the effects of cannabinoids on IOP, neuroprotection, and ocular hemodynamics have been discussed.
Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model
Authors: Jiang Yaqun , Cheng Xiang , Zhao Ming , Zhao Tong , Zhang Mengya , Shi Zibi , Yue Xiangpei , Geng Yanan , Gao Jiayue , Wang Chengbo , Yang Junli , Zhu Lingling
Published: August 2023

Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.
Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats
Authors: Niu Xiaochen , Chen Dan , He Wei , Tang Yu , Zhao Jianchun
Published: August 2023

Plinabulin, a new antitumor drug developed from marine natural products that targets microtubules in cancer cells, is currently being tested in a phase III clinical study. Plinabulin has been clinically proven to be effective on leukopenia. However, to our knowledge, there are no reports investigating the pharmacokinetics of plinabulin in individuals with leukopenia and healthy individuals. In this study, we developed a rapid and sensitive UHPLC-MS/MS method for the detection of plinabulin for the first time. Using a novel cyclophosphamide-induced leukopenia model, we investigated the differences in the pharmacokinetic characteristics of plinabulin between rats with leukopenia and normal rats. Plinabulin and propranolol (IS) peaks were separated by gradient elution for a total run time of 5 min. The methodological validation showed a good accuracy (101.96–109.42%) and precision (RSD ≤ 5.37%) with the lower limit of quantification at 0.5 ng/mL. The recovery of plinabulin was between 91.99% and 109.75% (RSD ≤ 7.92%). The values of the area under the plasma concentration-time curve (AUC0-t) for leukopenia groups and control groups at doses of 0.5 mg/kg, 1 mg/kg, and 3 mg/kg were 148.89 ± 78.74 h·μg/L and 121.75 ± 31.56 h·μg/L; 318.15 ± 40.00 h·μg/L and 272.06 ± 42.85 h·μg/L; and 1432.43 ± 197.47 h·μg/L and 1337.12 ± 193.56 h·μg/L; respectively. The half-lives (t1/2s) of plinabulin were 0.49–0.72 h for leukopenia groups and 0.39–0.70 h for control groups at three doses, and the clearance rates (CLs) of plinabulin were 2.13–3.87 L/h/kg for leukopenia groups and 2.29–4.23 L/h/kg for control groups. Pharmacokinetic results showed that there was no significant pharmacokinetic difference between the normal group and the leukopenia group. Based on the power model, plinabulin exhibits a lack of dose proportionality over the dose range of 0.5–3 mg/kg after intravenous administration. This study provides guidance for the development of plinabulin as a potential candidate for the treatment of chemotherapy-induced leukopenia.
Cinnamyl-Modified Polyglycidol/Poly(ε-Caprolactone) Block Copolymer Nanocarriers for Enhanced Encapsulation and Prolonged Release of Cannabidiol
Authors: Toncheva-Moncheva Natalia , Dimitrov Erik , Grancharov Georgi , Momekova Denitsa , Petrov Petar , Rangelov Stanislav
Published: August 2023

The present study describes the development of novel block copolymer nanocarriers of the phytocannabinoid cannabidiol (CBD), designed to enhance the solubility of the drug in water while achieving high encapsulation efficiency and prolonged drug release. Firstly, a well-defined amphiphilic block copolymer consisting of two outer hydrophilic polyglycidol (PG) blocks and a middle hydrophobic block of poly(ε-caprolactone) bearing pendant cinnamyl moieties (P(CyCL-co-CL)) were synthesized by the click coupling reaction of PG-monoalkyne and P(CyCL-co-CL)-diazide functional macroreagents. A non-modified polyglycidol/poly(ε-caprolactone) amphiphilic block copolymer was obtained as a referent system. Micellar carriers based on the two block copolymers were formed via the solvent evaporation method and loaded with CBD following two different protocols—loading during micelle formation and loading into preformed micelles. The key parameters/characteristics of blank and CBD-loaded micelles such as size, size distribution, zeta potential, molar mass, critical micelle concentration, morphology, and encapsulation efficiency were determined by using dynamic and static multiangle and electrophoretic light scattering, transmission electron microscopy, and atomic force microscopy. Embedding CBD into the micellar carriers affected their hydrodynamic radii to some extent, while the spherical morphology of particles was not changed. The nanoformulation based on the copolymer bearing cinnamyl moieties possessed significantly higher encapsulation efficiency and a slower rate of drug release than the non-modified copolymer. The comparative assessment of the antiproliferative effect of micellar CBD vs. the free drug against the acute myeloid leukemia-derived HL-60 cell line and Sezary Syndrome HUT-78 demonstrated that the newly developed systems have pronounced antitumor activity.
Translation of Monoclonal Antibodies Pharmacokinetics from Animal to Human Using Physiologically Based Modeling in Open Systems Pharmacology (OSP) Suite: A Retrospective Analysis of Bevacizumab
Authors: Pasquiers Blaise , Benamara Salih , Felices Mathieu , Ternant David , Declèves Xavier , Puszkiel Alicja
Published: August 2023

Interspecies translation of monoclonal antibodies (mAbs) pharmacokinetics (PK) in presence of target-mediated drug disposition (TMDD) is particularly challenging. Incorporation of TMDD in physiologically based PK (PBPK) modeling is recent and needs to be consolidated and generalized to provide better prediction of TMDD regarding inter-species translation during preclinical and clinical development steps of mAbs. The objective of this study was to develop a generic PBPK translational approach for mAbs using the open-source software (PK-Sim® and Mobi®). The translation of bevacizumab based on data in non-human primates (NHP), healthy volunteers (HV), and cancer patients was used as a case example for model demonstration purpose. A PBPK model for bevacizumab concentration-time data was developed using data from literature and the Open Systems Pharmacology (OSP) Suite version 10. PK-sim® was used to build the linear part of bevacizumab PK (mainly FcRn-mediated), whereas MoBi® was used to develop the target-mediated part. The model was first developed for NHP and used for a priori PK prediction in HV. Then, the refined model obtained in HV was used for a priori prediction in cancer patients. A priori predictions were within 2-fold prediction error (predicted/observed) for both area under the concentration-time curve (AUC) and maximum concentration (Cmax) and all the predicted concentrations were within 2-fold average fold error (AFE) and average absolute fold error (AAFE). Sensitivity analysis showed that FcRn-mediated distribution and elimination processes must be accounted for at all mAb concentration levels, whereas the lower the mAb concentration, the more significant the target-mediated elimination. This project is the first step to generalize the full PBPK translational approach in Model-Informed Drug Development (MIDD) of mAbs using OSP Suite.
Targeting EGFR/PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma
Authors: Bang Jieun , Jun Mihyeon , Lee Soyun , Moon Hyuk , Ro Simon Weonsang
Published: August 2023

Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is a multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, significant progress has been made in understanding the molecular signaling pathways that play central roles in hepatocarcinogenesis. In particular, the EGFR/PI3K/AKT/mTOR signaling pathway in HCC has garnered renewed attention from both basic and clinical researchers. Preclinical studies in vitro and in vivo have shown the effectiveness of targeting the key components of this signaling pathway in human HCC cells. Thus, targeting these signaling pathways with small molecule inhibitors holds promise as a potential therapeutic option for patients with HCC. In this review, we explore recent advancements in understanding the role of the EGFR/PI3K/AKT/mTOR signaling pathway in HCC and assess the effectiveness of targeting this signaling cascade as a potential strategy for HCC therapy based on preclinical studies.
A Non-Isothermal Pore Network Model of Primary Freeze Drying
Authors: Thomik Maximilian , Faber Felix , Gruber Sebastian , Foerst Petra , Tsotsas Evangelos , Vorhauer-Huget Nicole
Published: August 2023

In this work, a non-isothermal pore network (PN) model with quasi-steady vapor transport and transient heat transfer is presented for the first time for the application of primary freeze drying. The pore-scale resolved model is physically based and allows for the investigation of correlations between spatially distributed structure and transport conditions. The studied examples were regular PN lattices with a significantly different structure, namely a spatially homogeneous PN, also denoted as monomodal PN, and a PN with significant structure variation, referred to as bimodal PN because of its bimodal pore size distribution. The material properties selected for the solid skeleton in this study are equivalent to those of maltodextrin. The temperature ranges applied here were −28 °C to −18 °C in the PN and −42 °C in the surrounding environment. The environmental vapor pressure was 10 Pa. The PNs were dried with constant temperature boundary conditions, and heat was transferred at the top side by the vapor leaving the PN. It is shown how the structural peculiarities affect the local heat and mass transfer conditions and result in a significant widening of the sublimation front in the case of the bimodal PN. The possibility of spatially and temporally resolved front structures is a unique feature of the PN model and allows the study of situations that are not yet described by classical continuum approaches, namely heterogeneous frozen porous materials. As demonstrated by the thin layers studied here, the pore-scale simulations are of particular interest for such situations, such as in lyomicroscopes or collagen scaffolds, where a length-scale separation between dry and ice-saturated regions is not possible.
Development of Nanotechnology-Based Drug Delivery Systems for Controlling Clinical Multidrug-Resistant Staphylococcus aureus and Escherichia coli Associated with Aerobic Vaginitis
Authors: Haddaji Najla , Bahloul Badr , Bahia Wael , Bechambi Olfa , Mahdhi Abdelkarim
Published: August 2023

The growing prevalence of resistance to antibiotics potentially makes Escherichia coli and Staphylococcus aureus serious pathogens, necessitating the development of new antimicrobial agents. We extracted crude biosurfactants from a potential probiotic Bacillus spp. to control pathogenic bacteria associated with aerobic vaginal infection. Using nanotechnology formulations, we developed nanoemulsions based on biosurfactants at different concentrations (1% and 3.33%). The results showed that these nanoemulsions were stable, with a weighted index of 0.3, and demonstrated broad-spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus, with MICs ranging between 1.25 and 4 mg/mL. Additionally, the nanoemulsions exhibited interesting antibiofilm effects. All strains became more sensitive to the antibiotics to which they were resistant because of various biosurfactant formulations combined with antibiotics. Lower concentrations of BNE1% and 3.33% were still more efficient than the crude biosurfactants. Our findings demonstrated that the biosurfactant had a strong antibiofilm effect against all tested pathogens. This antibacterial effect can be explained by their ability to alter cell physiology such as cell hydrophobicity and membrane disintegration. Thus, we can conclude that the use of nanotechnology formulations has improved this effect, and the nanoemulsions developed in this study can be used as a potential anti-infectious therapy against multidrug-resistant bacterial strains of clinical origin.
Experimental Comparison of Carrier Phase Recovery Algorithms for Uniform and Probabilistically Shaped QAM in a 324.1 Gb/S Fiber-mm-Wave Integration System at W-Band
Authors: Zhang Junhao , Zhang Jiao , Wang Qingsong , Chen Jian , Luo Wei , Xiang Shitong , Cai Yuancheng , Hua Bingchang , Lei Mingzheng , Zou Yucong , Tian Liang , Chen Xingyu , Zhu Min
Published: August 2023

We have experimentally implemented a photonics-aided large-capacity fiber-mm-wave wireless communication system employing a simple dual-polarized single-input single-output (SISO) wireless based on polarization multiplexing at the W-band. To compare the performance of different algorithms, 18G-baud, and 35G-baud 16-level quadrature-amplitude-modulation (16QAM), probabilistically shaped 16QAM (PS-16QAM), 64QAM and PS-64QAM signal using different carrier phase recovery (CPR) algorithms are transmitted in the system. Moreover, we compare the Viterbi–Viterbi (VV), improved new algorithm based on VV (NVV), blind phase search (BPS), and two-stage BPS algorithms’ computational complexity to better compare different algorithms. Using the experiment result, we can demonstrate that the BPS algorithm is about half a magnitude better than the NVV algorithm for PS-QAM signals, while the NVV algorithm has the lowest computational complexity. Additionally, we also achieve error-free wireless transmission at a net data rate of 324.1 Gb/s with the bit error ratio (BER) below the forward-error correction (FEC) threshold of 1 × 10−2 assuming soft-decision forward-error correction (SD-FEC) when using the BPS algorithm.
Multi-Parameter Model-Based Polarimetric Calibration for Dual-Coded Spectral Polarization Imaging System
Authors: Wang Jiayu , Shi Haodong , Li Yingchao , Fu Qiang , Zhao Yingjie , Jiang Huilin
Published: August 2023

A polarization analysis method based on a multi-parameter model is proposed to address the polarization effect analysis and calibration requirements of a dual-coded snapshot spectral polarization imaging system. A full-link polarization effect model for a spectral polarization imaging system is established that includes a digital micromirror array (DMD), prism grating prism (PGP), micro-polarizer array detector (MPA), and multi-film. The influence of parameters such as the refractive index, incident angle, grating refractive index, constant, prism refractive index, vertex angle, multi-layer film complex refractive index, and film thickness on the optical transmittance of the system are analyzed. Using a dynamic data exchange mechanism to perform full-link, full-FOV, and full-pupil ray tracing on the optical system, the polarization effect distribution of the system under different degrees of polarization (DOP) and wavelengths is obtained. A calibration experiment for the controllable incident wavelength and DOP using narrowband filters and glass stacks is established. The experimental results show that in the 420 nm, 532 nm, and 635 nm wavelength bands, the MSEs of the calibrated values are 1.3924 × 10−4, 1.6852 × 10−4, and 1.6735 × 10−4, respectively. It is proven that the calibration method based on a multi-parameter model is feasible. Finally, the spectral polarization image at 532 nm is calibrated. The contrast ratio of metallic aluminum is calibrated from 7.13 to 15.33. This study provides a theoretical basis for the analysis and calibration of polarization effects in a dual-coded snapshot spectral polarization imaging system.
Gaussian-Shaped Free-Space Optical Beam Intensity Estimation in Detector Arrays
Authors: Umair Muhammad Ali , Khalid Hira , Sajid Sheikh Muhammad , Nistazakis Hector E.
Published: August 2023

Photon counting detector arrays are commonly used for deep space optical communication receivers operating on the principle of intensity modulation/direct detection (IM/DD). In scenarios where beam parameters can vary at the receiver due to scattering, it is important to estimate beam parameters in order to minimize the probability of error. The use of array of detectors increases the sensitivity of the receiver as compared to single photo-detector of the same size. In this paper, we present the derivation of a maximum likelihood estimator (ML) for peak optical intensity, providing both numerical and closed form expressions for the estimator. Performance of both forms of ML estimator are compared using the mean squared error (MSE) criterion and Cramer–Rao Lower Bound (CRLB) is also derived to assess the proposed estimator’s efficiency. This research contributed to the advancement of estimation techniques and has practical implications for optimizing deep space optical communication systems.
A Comprehensive Insight into Māmaki (Pipturus albidus): Its Ethnomedicinal Heritage, Human Health Research, and Phytochemical Properties
Authors: Koher Grant , Khan Ajmal , Suarez-vega Gabriel , Meesakul Pornphimon , Bacani Ann-Janin , Kohno Tomomi , Zhu Xuewei , Kim Ki Hyun , Cao Shugeng , Jia Zhenquan
Published: August 2023

In Hawaii, the plants P. albidus, P. forbesii, P. kauaiensis, and P. ruber are collectively known as māmaki in ethnomedicine, where P. albidus predominates. Farmed māmaki is becoming increasingly popular in Hawaii and the United States. Māmaki teas (such as bottled Shaka tea) are the dominant product. Historically, māmaki has been utilized for its medicinal properties, promoting well-being and good health through consuming tea made from its leaves, ingesting its fruit, and incorporating it into ointments. Māmaki holds cultural significance among Native Hawaiians and is widely used in ethnic medicine, having been incorporated into traditional practices for centuries. However, the scientific mechanisms behind its effects remain unclear. This review consolidates current knowledge of māmaki, shedding light on its potential therapeutic properties, physical properties, nutritional and mineral composition, and active phytochemicals. We also highlight recent research advances in māmaki’s antibacterial, anti-viral, chemopreventive, anti-inflammatory, and antioxidant activities. Additionally, we discuss future prospects in this field.
Shade Increased Seed Yield and Quality of Incarvillea sinensis var. przewalskii
Authors: Wang Yan , Wang Jingjing , Chen Dali , Hui Zhenning , Hu Xiaowen
Published: August 2023

Incarvillea sinensis var. przewalskii has attracted great attention because of the anticancer value of its alkaloids and the potential use of the species for ecological restoration. However, the scarcity of high-quality seeds has significantly hindered the cultivation and efficient utilization of this species. Understanding how seeds respond to maternal environmental conditions is crucial for developing high-yield and top-notch seed accessions, but the available knowledge in this area is limited. Here, we determined the effect of shading treatments on seed development, seed quality, and yield. Compared to the control, shade significantly increased the seed germination rate and 1000-seed weight by 29.2% and 25.6%, respectively. Regardless of light conditions, the seed germination rate and 1000-seed weight decreased by 7.13% and 37.5%, respectively, as the fruit positioned from base to apical. The seed yield per plant was 27.9% higher under shade than under the control treatment. The structural equation model showed that shade promoted seed yield through increasing flowers per reproductive branch and seed numbers per capsule. These findings suggest that adjusting shading conditions and optimizing inflorescence development can lead to high-yield and high-quality seeds. Additionally, prioritizing the number of flowers per reproductive branch and seeds per capsule in breeding programs can further enhance the seed yield of I. sinensis var. przewalskii.
Resveratrol and Other Natural Oligomeric Stilbenoid Compounds and Their Therapeutic Applications
Authors: Duta-Bratu Cosmina-Gabriela , Nitulescu George Mihai , Mihai Dragos Paul , Olaru Octavian Tudorel
Published: August 2023

The use of natural compounds as an alternative to synthetic molecules has become a significant subject of interest in recent decades. Stilbenoids are a group of phenolic compounds found in many plant species and they have recently gained the focus of a multitude of studies in medicine and chemistry, resveratrol being the most representative molecule. In this review, we focused on the research that illustrates the therapeutic potential of this class of natural molecules considering various diseases with higher incidence rates. PubChem database was searched for bioactivities of natural stilbenoids, while several keywords (i.e., “stilbenoids”, “stilbenoid anticancer”) were used to query PubMed database for relevant studies. The diversity and the simplicity of stilbenes’ chemical structures together with the numerous biological sources are key elements that can simplify both the isolation of these compounds and the drug design of novel bioactive molecules. Resveratrol and other related compounds are heterogeneously distributed in plants and are mainly found in grapes and wine. Natural stilbenes were shown to possess a wide range of biological activities, such as antioxidant, anti-inflammatory, antihyperglycemic, cardioprotective, neuroprotective, and antineoplastic properties. While resveratrol is widely investigated for its benefits in various disorders, further studies are warranted to properly harness the therapeutic potential of less popular stilbenoid compounds.