bluuebunny/crossref_metadata_2025 huggingface dataset:
The Preparation of N, P-Doped NiSe Nanorod Electrode Materials on Nickel Foam Using the Microwave Method for High-Performance Supercapacitors
Authors: Lu Zhen , Kang Hongjie , Duan Qianwen , Lv Chao , Liu Rui , Feng Feng , Zhao Haidong
Published: July 2024

Transition metal selenides have the leading position in the field of energy storage and conversion due to their high theoretical capacity, good electrical conductivity, and cycling stability. Nickel is widely used for the construction of positive electrodes in devices due to its good conductivity, variable valence state, and ideal redox activity. NiSe materials have high internal resistance and are prone to volume change during charging and discharging, thus affecting the practical application of this electrode material, and the reported NiSe materials have not achieved a more desirable capacity value. Therefore, in this study, N, P-NiSe nanoelectrode materials were prepared using nickel foam as the nickel source and hexachlorocyclotriphonitrile as the nitrogen and phosphorus dopant using an efficient, energy-saving, and simple microwave method. It was also characterised by XRD and XPS to confirm the successful preparation of N, P-NiSe materials. In addition, the material yielded a high capacitance value (3184 F g−1) and good cycling stability (72% of the initial capacitance value was retained after 4000 cycles) in electrochemical tests. To demonstrate its excellent suitability for practical applications, an asymmetric supercapacitor was assembled using N, P-NiSe as the anode and activated carbon as the cathode. At an operating voltage of 1.6 V, the device achieved an energy density of 289.06 Wh kg−1 and a power density of 799.26 W kg−1 and retained 80% of its initial capacity after 20,000 cycles.
The Recyclability of Fire-Retarded Biobased Polyamide 11 (PA11) Composites Reinforced with Basalt Fibers (BFs): The Influence of Reprocessing on Structure, Properties, and Fire Behavior
Authors: Barczewski Mateusz , Hejna Aleksander , Andrzejewski Jacek , Aniśko Joanna , Piasecki Adam , Mróz Adrian , Ortega Zaida , Rutkowska Daria , Sałasińska Kamila
Published: July 2024

The growing requirements regarding the safety of using polymers and their composites are related to the emergence of more effective, sustainable, and hazardous-limited fire retardants (FRs). Significant amounts of FRs are usually required to effectively affect a polymer’s burning behavior, while the knowledge of their recycling potential is still insufficient. At the same time, concerns are related not only to the reduced effectiveness of flame retardancy but also, above all, to the potential deterioration of mechanical properties caused by the degradation of temperature-affected additives under processing conditions. This study describes the impact of the four-time reprocessing of bio-based polyamide 11 (PA11) modified with an intumescent flame-retardant (IFR) system composed of ammonium polyphosphate (APP), melamine cyanurate (MC), and pentaerythritol (PER) and its composites containing additional short basalt fibers (BFs). Composites manufactured via twin-screw extrusion were subjected to four reprocessing cycles using injection molding. A comprehensive analysis of their structural, mechanical, and fire behavior changes in each cycle was conducted. The obtained results confirmed the safety of using the proposed fire-retarded polyamide and its composites while reprocessing under the recommended process parameters without the risk of significant changes in the structure. The partial increase in flammability of reprocessed PA-based materials caused mainly by polymer degradation has been described.
Bi-Directional Full-Color Generation and Tri-Channel Information Encoding Based on a Plasmonic Metasurface
Authors: Huo Dewang , Li Guoqiang
Published: July 2024

Dynamic optical structural color is always desired in various display applications and usually involves active materials. Full-color generation, especially bi-directional full-color generation in both reflective and transmissive modes, without any active materials included, has rarely been investigated. Herein, we demonstrate a scheme of bi-directional full-color generation based on a plasmonic metasurface modulated by the rotation of the polarization angle of the incident light without varying the geometry and the optical properties of the materials and the environment where the metasurface resides. The metasurface unit cell consists of plasmonic modules aligning in three directions and is patterned in a square array. The metasurface structural color device is numerically confirmed to generate full colors in both reflection and transmission. Based on the proposed polarization-dependent structural color, the information encoding process is demonstrated for three multiplexed animal images and quick-responsive (QR) codes to verify the efficient information encoding and decoding of the proposed scheme. In the simulation, the animals can be seen under different polarization incidences, and the QR codes can be successfully decoded by the polarization rotation in transmission. The proposed bi-directional full-color generation metasurface has great potential in applications such as kaleidoscope generation, anti-counterfeiting, dynamic color display, and optical information encoding.
Association between Uric Acid Levels and the Consumption of Sugar-Sweetened Carbonated Beverages in the Korean Population: The 2016 Korea National Health and Nutrition Examination Survey
Authors: Lee Su Min , Lee Sang Yeoup , Park Eun Ju , Lee Young In , Choi Jung In , Lee Sae Rom , Kwon Ryuk Jun , Son Soo Min , Lee Jeong Gyu , Yi Yu Hyeon , Tak Young Jin , Lee Seung Hun , Kim Gyu Lee , Ra Young Jin , Cho Young Hye
Published: July 2024

Elevated uric acid levels are linked with obesity and diabetes. Existing research mainly examines the relationship between sugar-sweetened carbonated beverage (SSB) consumption and uric acid levels. This study explored the association between the quantity and frequency of SSB consumption and elevated uric acid levels in Korean adults. Data from 2881 participants aged 19–64 years (1066 men and 1815 women) in the 2016 Korea National Health and Nutrition Examination Survey were analyzed. Serum uric acid levels were categorized into quartiles, with the highest defined as high uric acid (men, ≥6.7 mg/dL; women, ≥4.8 mg/dL). SSB consumption was classified into quartiles (almost never, <1 cup (<200 mL), 1–3 cups (200–600 mL), ≥3 cups (≥600 mL)) and frequency into tertiles (almost never, ≤1/week, ≥2/week). Multivariate logistic regression assessed the association, with separate analyses for men and women. Increased daily SSB consumption and frequency were significantly associated with high uric acid levels in men but not in women. After adjusting for sociodemographic and health characteristics, consuming ≥3 cups (≥600 mL) of SSBs per day and SSBs ≥ 2/week were significantly associated with high serum uric acid levels in men, but this association was not observed in women. The study concludes that increased SSB intake is linked to elevated uric acid levels in Korean men, but not in women.
Biochemical and Anthropometric Outcomes in Paediatric Patients with Heterozygous Familial Hypercholesterolemia after COVID-19 Pandemic Lockdowns: An Exploratory Analysis
Authors: Peres Maria , Moreira-Rosário André , Padeira Gonçalo , Gaspar Silva Patrícia , Correia Carla , Nunes Andreia , Garcia Elisabete , Faria Ana , Teixeira Diana , Calhau Conceição , Pereira-da-Silva Luís , Ferreira Ana Cristina , Rocha Júlio César
Published: July 2024

The COVID-19 pandemic lockdowns affected the lifestyles of children and adolescents, leading to an increase in childhood obesity. Paediatric patients with familial hypercholesterolemia (FH) may be more susceptible to lockdown effects due to their increased cardiovascular risk. However, data are lacking. We investigated the effect of lockdowns on the metabolic profile of paediatric patients with FH. Blood lipids and anthropometry measured in September 2021–April 2022 were retrospectively compared with pre-pandemic values. Thirty participants were included (1–16 years; 57% female). From baseline to post-pandemic, median [P25, P75] blood LDL-C concentration was 125 [112, 150] mg/dL vs. 125 [100, 147] mg/dL (p = 0.894); HDL-C was 58 [52, 65] mg/dL vs. 56 [51, 61] mg/dL (p = 0.107); triglycerides were 64 [44, 86] mg/dL vs. 59 [42, 86] mg/dL (p = 0.178). The BMI z-score did not change significantly (0.19 [−0.58, 0.89] vs. 0.30 [−0.48, 1.10], p = 0.524). The lack of deterioration in metabolic profiles during lockdowns is positive, as some deterioration was expected. We speculate that patients and caregivers were successfully educated about healthy lifestyle and dietary habits. Our results should be interpreted with caution since the study sample was small and heterogeneous. Multicentre research is needed to better understand the impact of lockdowns on this population.
Breastfeeding Practices and Postpartum Weight Retention in an Asian Cohort
Authors: Loy See Ling , Chan Hiu Gwan , Teo Joyce Xinyun , Chua Mei Chien , Chay Oh Moh , Ng Kee Chong
Published: July 2024

This study examines relationships between breastfeeding practices and postpartum weight retention (PPWR) at 6 and 12 months postpartum among 379 first-time mothers participating in a clinical trial in Singapore. We categorized feeding modes at 6 months into exclusive breastfeeding, mixed feeding, and exclusive formula feeding. Participants were analyzed in two groups based on their PPWR assessment at 6 and 12 months postpartum, with complete datasets available for each assessment. We calculated PPWR by subtracting pre-pregnancy weight from self-reported weight at 6 and 12 months postpartum, defining substantial PPWR as ≥5 kg retention. Modified Poisson regression models adjusted for potential confounders were performed. At 6 and 12 months, 35% (n = 132/379) and 31% (n = 109/347) of women experienced substantial PPWR, respectively. Compared to exclusive breastfeeding, mixed feeding (risk ratio 1.85; 95% confidence interval 1.15, 2.99) and exclusive formula feeding (2.11; 1.32, 3.28) were associated with a higher risk of substantial PPWR at 6 months. These associations were slightly attenuated at 12 months and appeared stronger in women with pre-pregnancy overweight or obesity. This study suggests that breastfeeding by 6 months postpartum may help mitigate PPWR, particularly with exclusive breastfeeding. It also draws attention to targeted interventions to promote breastfeeding among women with overweight or obesity.
Antioxidant Activity, Antiproliferative Activity, Antiviral Activity, NO Production Inhibition, and Chemical Composition of Essential Oils and Crude Extracts of Leaves, Flower Buds, and Stems of Tetradenia riparia
Authors: Sena Jéssica da Silva , Rodrigues Selma Alves , Sakumoto Karina , Inumaro Rodrigo Sadao , González-Maldonado Pamela , Mendez-Scolari Emilio , Piau Ranulfo , Gonçalves Daniela Dib , Mandim Filipa , Vaz Josiana , Gonçalves José Eduardo , Sotelo Pablo Hernan , Valle Juliana Silveira do , Gazim Zilda Cristiani
Published: July 2024

The chemical composition of extracts (CEs) and essential oils (EOs) from Tetradenia riparia leaves, flower buds, and stems was analyzed. Antiproliferative activity against tumor cell lines, NO production inhibition, and antioxidant and antiviral activities were assessed. The CEs contained flavonoids, phenolic acids, coumarins, and saturated fatty acids. The EOs included monoterpenes, oxygenated sesquiterpenes, and diterpenes. NO production inhibition ranged from 76 to 247 µg mL−1, and antiproliferative activity exhibited GI50 between 20 and >204 µg mL−1, with low cytotoxicity (SI: 1.08 to 4.75). Reactive oxygen species inhibition ranged from 45 to 82%. Antioxidant activity varied when determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (IC50: 0.51 to 8.47 mg mL−1) and ferric reducing antioxidant power (0.35 to 0.81 µM ferrous sulfate per mg). The reduction in β-carotene–linoleic acid co-oxidation varied between 76.13 and 102.25%. The total phenolic content of CEs and EOs was 10.70 to 111.68 µg gallic acid mg−1. Antiviral activity against herpes simplex virus type 1 (HSV-1) showed an EC50 between 9.64 and 24.55 µg mL−1 and an SI between 8.67 and 15.04. Leaf EOs exhibited an EC50 of 9.64 µg mL−1 and an SI of 15.04. Our study unveils the diverse chemical composition and multifaceted pharmacological properties of T. riparia, demonstrating its potential as a valuable source of bioactive compounds for therapeutic applications.
Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia
Authors: Spampinato Mariarita , Zuppelli Tatiana , Dulcamare Ilaria , Longhitano Lucia , Sambataro Domenico , Santisi Annalisa , Alanazi Amer M. , Barbagallo Ignazio A. , Vicario Nunzio , Parenti Rosalba , Romano Alessandra , Musumeci Giuseppe , Li Volti Giovanni , Palumbo Giuseppe A. , Di Raimondo Francesco , Nicolosi Anna , Giallongo Sebastiano , Del Fabro Vittorio
Published: July 2024

Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.
Network Medicine: A Potential Approach for Virtual Drug Screening
Authors: Ma Mingxuan , Huang Mei , He Yinting , Fang Jiansong , Li Jiachao , Li Xiaohan , Liu Mengchen , Zhou Mei , Cui Guozhen , Fan Qing
Published: July 2024

Traditional drug screening methods typically focus on a single protein target and exhibit limited efficiency due to the multifactorial nature of most diseases, which result from disturbances within complex networks of protein–protein interactions rather than single gene abnormalities. Addressing this limitation requires a comprehensive drug screening strategy. Network medicine is rooted in systems biology and provides a comprehensive framework for understanding disease mechanisms, prevention, and therapeutic innovations. This approach not only explores the associations between various diseases but also quantifies the relationships between disease genes and drug targets within interactome networks, thus facilitating the prediction of drug–disease relationships and enabling the screening of therapeutic drugs for specific complex diseases. An increasing body of research supports the efficiency and utility of network-based strategies in drug screening. This review highlights the transformative potential of network medicine in virtual therapeutic screening for complex diseases, offering novel insights and a robust foundation for future drug discovery endeavors.
Monoclonal Antibodies in Smoldering Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance: Current Status and Future Directions
Authors: Ferla Valeria , Farina Francesca , Perini Tommaso , Marcatti Magda , Ciceri Fabio
Published: July 2024

Monoclonal antibodies (MoAbs) targeting several cellular receptors have significantly improved the prognosis of multiple myeloma (MM). Their high effectiveness and safety raise the question of whether earlier therapeutic intervention in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) influences the natural course of the disease. MM is preceded by clinically recognized conditions such as MGUS and SMM. Numerous studies are investigating the disease biology and immune profile of SMM and MGUS to unravel the intricate relationship between immunosurveillance and disease progression. The standard approach to MGUS and SMM remains close observation. Early studies indicate benefits in terms of progression or even survival for promptly treating high-risk SMM patients. Ongoing debates are focused on which patients with SMM and MGUS to treat, as well as on determining the optimal therapeutic approach. The first approach aims to cure by attempting to eliminate the pathological clone, while the second approach is preventive, aiming to manage disease progression to active MM and restore the immune system. In this review, we focus on the available and emerging data on early treatment, particularly with MoAbs alone or in combination with other therapies, in SMM and MGUS patients.
Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model
Authors: Anastasova Ralitsa , Fiorentzis Miltiadis , Liu Hongtao , Dalbah Sami , Bechrakis Nikolaos E. , Seitz Berthold , Berchner-Pfannschmidt Utta , Tsimpaki Theodora
Published: July 2024

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.
Targeting JAK2/STAT3, NLRP3/Caspase-1, and PK2/PKR2 Pathways with Arbutin Ameliorates Lead Acetate-Induced Testicular Injury in Rats
Authors: Arab Hany H. , Alsufyani Shuruq E. , Ashour Ahmed M. , Gad Amany M. , Elhemiely Alzahraa A. , Gadelmawla Mohamed H. A. , Mahmoud Marwa Ahmed , Khames Ali
Published: July 2024

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen’s damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.
The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma
Authors: Esmail Abdullah , Badheeb Mohamed , Alnahar Batool Wael , Almiqlash Bushray , Sakr Yara , Al-Najjar Ebtesam , Awas Ali , Alsayed Mohammad , Khasawneh Bayan , Alkhulaifawi Mohammed , Alsaleh Amneh , Abudayyeh Ala , Rayyan Yaser , Abdelrahim Maen
Published: July 2024

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10–20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation
Authors: Ghaffari Alireza (Allen) , Matter Brock A. , Hartman Rachel R. , Bourne David W. A. , Wang Yan , Choi Stephanie , Kompella Uday B.
Published: July 2024

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.
Physiologically-Based Pharmacokinetic Modeling and In Vitro–In Vivo Correlation of TV-46000 (Risperidone LAI): Prediction from Dog to Human
Authors: Bibi David , Bilgraer Raphael , Steiner Lilach , Hallak Hussein
Published: July 2024

The interest in the development and therapeutic application of long-acting injectable products for chronic or long-term treatments has experienced exponential growth in recent decades. TV-46000 (Uzedy, Teva) is a long-acting subcutaneous (sc) injectable formulation of risperidone, approved for the treatment of schizophrenia in adults. Following sc injection, the copolymers together with risperidone precipitate to form a sc depot under the skin to deliver therapeutic levels of risperidone over a prolonged period of either 1 month or 2 months, depending upon the dose. This work presents the strategy and the results of the physiologically-based pharmacokinetic (PBPK) modeling and establishing of in vitro–in vivo correlation (IVIVC) for the prediction of TV-46000 pharmacokinetic profile in humans, using in vitro release, intravenous (iv), and sc single-dose pharmacokinetic data in beagle dogs. The resulting simulated TV-46000 PK profile in humans showed that the shape of the predicted risperidone and its active metabolite 9-OH-risperidone PK profiles was different from the observed one, thus suggesting that the TV-46000 release profile was species-dependent and cannot be directly extrapolated from dog to human. In conclusion, while level A IVIVC cannot be claimed, this work combining PBPK and IVIVC modeling represents an interesting alternative approach for complex injectable formulations where classical methods are not applicable.
A Novel Inhalable Dry Powder to Trigger Delivery of Voriconazole for Effective Management of Pulmonary Aspergillosis
Authors: Almurshedi Alanood S. , Almarshad Sarah N. , Bukhari Sarah I. , Aldosari Basmah N. , Alhabardi Samiah A. , Alkathiri Fai A. , Saleem Imran , Aldosar Noura S. , Zaki Randa Mohammed
Published: July 2024

Invasive pulmonary aspergillosis (IPA) is a fatal fungal infection with a high mortality rate. Voriconazole (VCZ) is considered a first-line therapy for IPA and shows efficacy in patients for whom other antifungal treatments have been unsuccessful. The objective of this study was to develop a high-potency VCZ-loaded liposomal system in the form of a dry-powder inhaler (DPI) using the spray-drying technique to convert liposomes into a nanocomposite microparticle (NCMP) DPI, formulated using a thin-film hydration technique. The physicochemical properties, including size, morphology, entrapment efficiency, and loading efficiency, of the formulated liposomes were evaluated. The NCMPs were then examined to determine their drug content, production yield, and aerodynamic size. The L3NCMP was formulated using a 1:1 lipid/L-leucine ratio and was selected for in vitro studies of cell viability, antifungal activity, and stability. These formulated inhalable particles offer a promising approach to the effective management of IPA.
Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer
Authors: Ebrahimi Fatemeh , Zargari Nooshin Reisi , Akhlaghi Mehdi , Asghari S. Mohsen , Abdi Khosrou , Balalaie Saeed , Asadi Mahboobeh , Beiki Davood
Published: July 2024

As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient’s chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression.
Enhanced Cytotoxicity against a Pancreatic Cancer Cell Line Combining Radiation and Gold Nanoparticles
Authors: Martins Alexandra , Ferreira Brigida C. , Gaspar Maria Manuela , Vieira Sandra , Lopes Joana , Viana Ana S. , Paulo António , Mendes Filipa , Campello Maria Paula Cabral , Martins Rui , Reis Catarina Pinto
Published: July 2024

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumor cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83 ± 20 nm and 49 ± 12 nm, respectively. For RT alone, a reduction in cell viability of up to 33 ± 12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 μM showed a reduction in cell viability of 20 ± 4% and 35 ± 4%, respectively, while for BBN-AuNPs, at 50 and 200 μM, a reduction in cell viability of 25 ± 3% and 37 ± 3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26 ± 3% and 22 ± 2% between RT + HAOA-AuNPs at 400 μM and RT + BBN-AuNPs at 50 μM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.
Spirothiazolidine-Derivative on Silver Nanoparticles and Carbon Nanotubes: Evaluation of Antibacterial, Anti-Fungal, Anti-Inflammatory, Antioxidant and Gastroprotective Activities
Authors: El-Sofany Walaa I. , Azzam Eid. M. S. , Latif Salman , Hamden Khaled
Published: July 2024

This study aims to develop innovative heterocyclic nanocomposites incorporating silver nanoparticles (SNPs) for potential therapeutic applications targeting infections, gastric ulceration, inflammation, and oxidative damage. By synthesizing new derivatives of spiro-thiazolidine-carbonitrile (Py-ST-X) and incorporating them into Ag nanoparticles (AgNPs) and carbon nanotubes (CNTs), we have prepared Ag@Py-ST-X and Ag@Py-ST-X@CNT nanocomposites, respectively. The physical properties of these materials were studied using XRD, TEM, SEM, and Zeta potential techniques. In our investigation involving rats with gastric ulcers, we observed noteworthy inhibitory effects on gastric acid enzyme activity, specifically H+/K+ATPase, by Ag@Py-ST-NO2 and Ag@Py-ST-Br nanocomposites, demonstrating reductions of 25 and 34%, respectively, compared to untreated ulcers. Nanotubulation of these compounds further improved their inhibitory efficacy to 29 and 45%, respectively. Additionally, these nanoparticles showed the most potent myeloperoxidase (MPO)-inhibitory activity, demonstrating 36 and 49% inhibition, respectively, with nanotubulated versions reaching 44 and 53%. Moreover, Ag@Py-ST-NO2@CNT and Ag@Py-ST-Br@CNT nanotubes showed significant antioxidant activity, reducing thiobarbituric acid reactive substances (TBARS) by 35 and 51%, and hydrogen peroxide (H2O2) levels by 49 and 71%, respectively. These therapeutic effects were confirmed by reductions in gastric surface area (GSA) by 44% and 52%, a decrease in ulcer index (UI) from 80% to 44 and 38%, and an increase in curative index (CI) from 19 to 55 and 62% following administration of Ag@Py-ST-NO2@CNT and Ag@Py-ST-Br@CNT, respectively. Histological studies support these findings, suggesting the potential of these nanocomposites as promising candidates for treating various disorders.
A New Casjensviridae Bacteriophage Isolated from Hospital Sewage for Inactivation of Biofilms of Carbapenem Resistant Klebsiella pneumoniae Clinical Isolates
Authors: Chakraborty Sambuddha , Rohit Anusha , Prasanthi S. Jaya , Chauhan Ashwini
Published: July 2024

Klebsiella pneumoniae, a member of the ESKAPE pathogen group, is a prominent cause of hospital-acquired infections. The WHO has recognized carbapenem-resistant K. pneumoniae as a critical-one priority pathogen. These resilient superbugs have the ability to form biofilms and present a significant global threat. In the present study, we isolated and characterized a bacteriophage SAKp02, from hospital sewage, infectious to carbapenem-resistant K. pneumoniae patient isolates. SAKp02 could infect 43 of 72 clinical isolates, indicating a broad host spectrum. Whole genome analysis classified SAKp02 within the family Casjensviridae, with a 59,343 bp genome encoding 82 ORFs. Comparative genomic analysis revealed significant differences between SAKp02 and its closest viruses, indicating a distinct genetic makeup positioning it as a novel phage strain within the lineage. The SAKp02 genome comprises bacteriolytic enzymes, including holin, endolysin, and phage depolymerase, crucial for bacterial lysis and biofilm disruption. It reduced biofilm biomass by over threefold compared to the control and eradicated 99% of viable cells within a 4 h treatment period. Scanning electron microscopy corroborated the ability of the phage to dismantle biofilm matrices and lyse bacterial cells. Safe and effective treatments are warranted, and hence, the fully characterized lytic phages with therapeutic potential against drug-resistant clinical isolates of bacteria are needed. Our study is the first to report the antibacterial and antibiofilm activity of Casjensviridae phages, and our discovery of a novel K. pneumoniae phage broadens the arsenal against the bacteria.
A Platelet-Powered Drug Delivery System for Enhancing Chemotherapy Efficacy for Liver Cancer Using the Trojan Horse Strategy
Authors: Huang Hao , Wang Xiaoping , Gao Ziqing , Bao Hongyi , Yuan Xiaopeng , Chen Chao , Xia Donglin , Wang Xiangqian
Published: July 2024

Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness of chemotherapy. This system delivers nano-sized dasatinib and atovaquone specifically to liver tumor sites and facilitates intra-tumoral permeation upon release. Through JC-1, immunohistochemistry, and DNA damage analyses, the therapeutic effect of DASA+ATO@PLT was assessed. In vitro simulation and intravital imaging were carried out to determine the accumulation of dasatinib and atovaquone in liver tumor sites. The experiment demonstrated the accumulation of dasatinib and atovaquone in tumor sites, followed by deep permeation in the tumor microenvironment with the assistance of PLTs, while simultaneously revealing the ability of DASA+ATO@PLT to remodel the liver cancer microenvironment (overcoming hypoxia) and enhance chemotherapeutic efficacy. This system utilizes the natural tumor recognition ability of PLTs and enhances the chemo-immunotherapeutic effect through targeted delivery of nano-chemotherapeutic drugs to the tumor, resulting in effective accumulation and infiltration. The PLT-mediated nanodrug delivery system serves as a “Trojan horse” to carry therapeutic drugs as cargo and deliver them to target cells, leading to favorable outcomes.
Quality-by-Design-Driven Nanostructured Lipid Scaffold of Apixaban: Optimization, Characterization, and Pharmacokinetic Evaluation
Authors: Patil Kiran , Gujarathi Nayan , Sharma Charu , Ojha Shreesh , Goyal Sameer , Agrawal Yogeeta
Published: July 2024

Apixaban, an anticoagulant, is limited in its efficacy due to poor solubility, low bioavailability, and extensive metabolism. This study investigates the application of nanostructured lipid carriers (NLCs) to enhance the bioavailability of Apixaban. NLCs were prepared using the high-pressure homogenization method. The influence of independent variables, viz., the amount of Tween 80, HPH pressure, and the number of HPH cycles, were studied using a 23 factorial design. The average particle size, PDI, zeta potential, and entrapment efficiency of the optimized NLCs were found to be 232 ± 23 nm, with 0.514 ± 0.13 PDI and zeta potential of about −21.9 ± 2.1 mV, respectively. Additionally, concerning the thermal and crystallographic properties of the drug, the NLCs showed drug entrapment without altering its potency. The in-vitro drug release studies revealed an immediate release pattern, followed by sustained release for up to 48 h. In-vivo pharmacokinetic experiments demonstrated that Apixaban-loaded NLCs exhibited higher values of t1/2 (27.76 ± 1.18 h), AUC0–∞ (19,568.7 ± 1067.6 ng·h/mL), and Cmax (585.3 ± 87.6 ng/mL) compared to free drugs, indicating improved bioavailability. Moreover, a decrease in the elimination rate constant (Kel) reflected the sustained effect of Apixaban with NLCs. NLCs offer improved oral absorption rates and enhanced therapeutic impact compared to free drugs, potentially reducing dose frequency and improving patient outcomes.
Behavior of Composites Made of Quadriaxial Glass Fiber Fabrics and Epoxy Resin under Three-Point Bending
Authors: Chiracu Ioana Gabriela , Ojoc George Ghiocel , Cristea George Cătălin , Boțan Mihail , Cantaragiu Ceoromila Alina , Pîrvu Cătălin , Vasiliu Alexandru Viorel , Deleanu Lorena
Published: July 2024

This paper presents experimental results from three-point bending tests for a composite made of quadriaxial glass fiber fabrics and an epoxy resin. Two composites were tested, one with 8 layers and the other with 16 layers; both had the same matrix (the epoxy resin). Tests were carried out, using five different test rates from 10 mm/min to 1000 mm/min. The following parameters were recorded and calculated: Young’s modulus, flexural stress, flexural strain, energy, force, and all four for the first peak. The experimental data reveal no sensitivity for these materials based on the test rates, at least for the analyzed range; but, the characteristics for the thicker composite, with 16 layers of fabric, are slightly lower than those for the thinner composite, with 8 layers. The results pointed out that, for the same thickness of composite, certain characteristics, such as stress at the first peak, the flexural modulus, strain at the first peak, and energy at the first peak, are not sensitive to the test rate in the range 10–1000 mm/min. The energy at the first peak is double for the 16-layer composite compared to the 8-layer composite, but the specific energy (as energy on cross-sectional area) has close values: 103.47 kJ/m2 for the 8-layer composite and 106.51 kJ/m2 for the 16-layer composite. The results recommend this composite for applications in components with resistance to bending or for low-velocity impact protection.
Study on the Performance of Asphalt Modified with Bio-Oil, SBS and the Crumb Rubber Particle Size Ratio
Authors: Guo Fengqi , Shen Zhaolong , Jiang Liqiang , Long Qiuliang , Yu Yujie
Published: July 2024

To enhance the properties of SBS and crumb rubber-modified asphalts, four different amounts (5%, 10%, 15%, and 20%) of castor oil were added to crumb rubber-modified asphalts to mitigate the adverse effects of high levels of fine crumb rubber particles on the aging resistance of SBS and crumb rubber-modified asphalt. Initially, a conventional test was conducted to assess the preliminary effects of bio-oil on the high-temperature and anti-aging properties of SBS and crumb rubber-modified asphalt. Subsequently, dynamic shear rheometer and bending beam rheometer tests were employed to evaluate the impact of bio-oil on the high- and low-temperature and anti-fatigue properties of SBS and crumb rubber-modified asphalt. Finally, fluorescence microscopy and Fourier transform infrared spectroscopy were used to examine the micro-dispersion state of the modifier and functional groups in bio-oil, SBS and crumb rubber composite-modified asphalts. The experimental results indicated that bio-oil increased the penetration of SBS and crumb rubber-modified asphalt, decreased the softening point and viscosity, and significantly improved its aging resistance. The addition of bio-oil enhanced the anti-fatigue properties of SBS and crumb rubber-modified asphalt. The optimal amount of added bio-oil was identified. Bio-oil also positively influenced the low-temperature properties of SBS and crumb rubber-modified asphalt. Although the addition of bio-oil had some adverse effects on the asphalt’s high-temperature properties, the asphalt mixture modified with bio-oil, SBS, and crumb rubber still exhibited superior high-temperature properties compared to unmodified asphalt. Furthermore, fluorescence microscopy and Fourier transform infrared spectroscopy results demonstrated that bio-oil can be uniformly dispersed in asphalt, forming a more uniform cross-linked structure and thereby enhancing the aging resistance of SBS and crumb rubber-modified asphalt. The modification process involved the physical blending of bio-oil, SBS, and crumb rubber within the asphalt. Comprehensive research confirmed that the addition of bio-oil has a significant and positive role in enhancing the properties of SBS and crumb rubber-modified asphalt with different composite crumb rubber particle size ratios.
Shaping in the Third Direction: Colloidal Photonic Crystals with Quadratic Surfaces Self-Assembled by Hanging-Drop Method
Authors: Sandu Ion , Antohe Iulia , Fleaca Claudiu Teodor , Dumitrache Florian , Urzica Iuliana , Dumitru Marius
Published: July 2024

High-quality, 3D-shaped, SiO2 colloidal photonic crystals (ellipsoids, hyperboloids, and others) were fabricated by self-assembly. They possess a quadratic surface and are wide-angle-independent, direction-dependent, diffractive reflection crystals. Their size varies between 1 and 5 mm and can be achieved as mechanical-resistant, free-standing, thick (hundreds of ordered layers) objects. High-quality, 3D-shaped, polystyrene inverse-opal photonic superstructures (highly similar to diatom frustules) were synthesized by using an inside infiltration method as wide-angle-independent, reflective diffraction objects. They possess multiple reflection bands given by their special architecture (a torus on the top of an ellipsoid) and by their different sized holes (384 nm and 264 nm). Our hanging-drop self-assembly approach uses setups which deform the shape of an ordinary spherical drop; thus, the colloidal self-assembly takes place on a non-axisymmetric liquid/air interface. The deformed drop surface is a kind of topological interface which changes its shape in time, remaining as a quality template for the self-assembly process. Three-dimensional-shaped colloidal photonic crystals might be used as devices for future spectrophotometers, aspheric or freeform diffracting mirrors, or metasurfaces for experiments regarding space-time curvature analogy.
3D-Bioprinted Gelatin Methacryloyl-Strontium-Doped Hydroxyapatite Composite Hydrogels Scaffolds for Bone Tissue Regeneration
Authors: Codrea Cosmin Iulian , Baykara Dilruba , Mitran Raul-Augustin , Koyuncu Ayşe Ceren Çalıkoğlu , Gunduz Oguzhan , Ficai Anton
Published: July 2024

New gelatin methacryloyl (GelMA)—strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair.
Various Morphologies of Graphitic Carbon Nitride (g-C3N4) and Their Effect on the Thermomechanical Properties of Thermoset Epoxy Resin Composites
Authors: Al Mais Dina , Mustapha Samir , Baghdadi Yasmine N. , Bouhadir Kamal , Tehrani-Bagha Ali R.
Published: July 2024

This research aims to highlight the importance of diverse forms of graphitic carbon nitride (g-C3N4) as strengthening elements in epoxy composites. It explores the influence of three different forms of g-C3N4 and their concentrations on the mechanical properties of the epoxy composites. Various characterization techniques, such as scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR), were utilized to comprehend the effects of g-C3N4 morphology and particle size on the physical and chemical characteristics of epoxy resin. Mechanical properties, such as tensile strength, strain, modulus, and fracture toughness, were determined for the composite samples. SEM analysis was performed to examine crack morphology in samples with different reinforcements. Findings indicate that optimal mechanical properties were achieved with a 0.5 wt% bulk g-C3N4 filler, enhancing tensile strength by 14%. SEM micrographs of fracture surfaces revealed a transition from brittle to rough morphology, suggesting increased toughness in the composites. While the TGA results showed no significant impact on degradation temperature, dynamic mechanical analysis demonstrated a 17% increase in glass transition temperature. Furthermore, the improvement in thermal breakdown up to 600 °C was attributed to reinforced covalent bonds between carbon and nitrogen, supported by FTIR results.