bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Evidence of Watermelon (Citrullus lanatus) Ingestion on Vascular Health: A Food Science and Technology Perspective
Authors: Volino-Souza Mônica , Oliveira Gustavo Vieira de , Conte-Junior Carlos Adam , Figueroa Arturo , Alvares Thiago Silveira
Published: July 2022

The amino acid L-arginine is crucial for nitric oxide (NO) synthesis, an important molecule regulating vascular tone. Considering that vascular dysfunction precedes cardiovascular disease, supplementation with precursors of NO synthesis (e.g., L-arginine) is warranted. However, supplementation of L-citrulline is recommended instead of L-arginine since most L-arginine is catabolized during its course to the endothelium. Given that L-citrulline, found mainly in watermelon, can be converted to L-arginine, watermelon supplementation seems to be effective in increasing plasma L-arginine and improving vascular function. Nonetheless, there are divergent findings when investigating the effect of watermelon supplementation on vascular function, which may be explained by the L-citrulline dose in watermelon products. In some instances, offering a sufficient amount of L-citrulline can be impaired by the greater volume (>700 mL) of watermelon needed to reach a proper dose of L-citrulline. Thus, food technology can be applied to reduce the watermelon volume and make supplementation more convenient. Therefore, this narrative review aims to discuss the current evidence showing the effects of watermelon ingestion on vascular health parameters, exploring the critical relevance of food technology for acceptable L-citrulline content in these products. Watermelon-derived L-citrulline appears as a supplementation that can improve vascular function, including arterial stiffness and blood pressure. Applying food technologies to concentrate bioactive compounds in a reduced volume is warranted so that its ingestion can be more convenient, improving the adherence of those who want to ingest watermelon products daily.
Litchi-Derived Polyphenol Alleviates Liver Steatosis and Gut Dysbiosis in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Double-Blinded, Placebo-Controlled Study
Authors: Jinato Thananya , Chayanupatkul Maneerat , Dissayabutra Thasinas , Chutaputti Anuchit , Tangkijvanich Pisit , Chuaypen Natthaya
Published: July 2022

Preclinical data suggest the role of litchi extract in alleviating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. We aimed at investigating whether oligonol, a litchi-derived polyphenol, could improve liver steatosis and gut dysbiosis in patients with NAFLD. Adults with grade ≥2 steatosis, defined by an MRI proton density fat fraction (MRI-PDFF) of ≥11%, were randomly assigned to receive either oligonol or placebo for 24 weeks. The alteration in the MRI-PDFF and gut microbiota composition assessed by 16S ribosomal RNA sequencing were examined. There were 38 patients enrolled (n = 19 in each group). A significant reduction in the MRI-PDFF between week 0 and week 24 was observed in the oligonol group, while there was a non-significant decrease in the placebo group. A significant improvement in alpha-diversity was demonstrated in both of the groups. The oligonol-induced microbiota changes were characterized by reduced abundance of pathogenic bacteria, including Dorea, Romboutsia, Erysipelotrichaceae UCG-003 and Agathobacter, as well as increased abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Akkermansia, Lachnospira, Dialister and Faecalibacterium. In summary, this study is the first to provide evidence that supports that oligonol improves steatosis through the modulation of gut bacterial composition. Our results also support the beneficial and complementary role of oligonol in treating NAFLD.
Status and Dietary Intake of Phytoene and Phytofluene in Spanish Adults and the Effect of a Four-Week Dietary Intervention with Lutein-Rich Fruits or Vegetables
Authors: Rodríguez-Rodríguez Elena , Estévez-Santiago Rocío , Sánchez-Prieto Milagros , Olmedilla-Alonso Begoña
Published: July 2022

Phytoene (PT) and phytofluene (PTF) are colourless carotenoids presents in the human diet and in blood, faeces and tissues and are biologically active. However, there is very little data on these carotenoids. This study aims to assess PT and PTF concentrations in serum from healthy Spanish normolipemic subjects (n = 101, 45–65 years) and the effect of a fruit and vegetable dietary intervention (4 weeks, n = 29) on PT and PTF concentration in serum and faeces and dietary intake. Serum and faecal concentrations were analysed by HPLC and dietary intake by 3 × 24 h recalls. PT showed higher concentrations than PTF in serum, faeces and in the dietary intake. Considering both studies, PT and PTF concentrations in serum were 0.16 ± 0.07 and 0.05 ± 0.04 µmol/L, respectively, in faeces 17.7 ± 20.3 and 6.5 ± 7.9 µg/g, respectively, and in dietary intake the median was 2.4 and 0.6 mg/p/day, respectively. Carrots and tomatoes were the major dietary contributors of these carotenoids. The dietary intervention did not cause significant variations in the PT and PTF intake or serum concentrations, but a lower concentration in faeces was observed for the fruit group (PT: p = 0.024; PTF isomer-3: p = 0.034). These data highlight the need for further research on the activities of these carotenoids in humans.
Body Weight, Weight Self-Perception, Weight Teasing and Their Association with Health Behaviors among Chinese Adolescents—The Shanghai Youth Health Behavior Survey
Authors: Tan Yinliang , Lu Weiyi , Gu Wenxin , Yu Zhiping , Zhu Jingfen
Published: July 2022

Weight-related status has been associated with the physical and psychological health of adolescents. This cross-sectional study evaluated three different kinds of weight-related statuses (Body Mass Index (BMI), weight self-perception and weight teasing from others) among Chinese adolescents and identified their associations with health risk behaviors (lack of healthy dietary behavior, unhealthy dietary behavior, binge eating behavior, lack of physical activity (PA), sedentary behaviors (SB) and sleep disturbance). A stratified random cluster sampling method was used to select 10,070 students aged 11–18 years old from schools in Shanghai. Self-reported questionnaires were collected, weight-related statuses were divided into three categories and six specific health risk behaviors were classified into two groups: positive or negative. Overall, 27.82% of the adolescents were classified as being overweight and obese (35.61% of boys and 18.21% of girls), 43.45% perceived themselves as too heavy and 30.46% experienced weight teasing in the past. Among overweight or obese participants, 50.55% have been teased about their weight, and 77.48% perceived themselves as too heavy. Weight perception and weight teasing were significantly associated with health risk behaviors rather than the actual body weight status based on BMI, especially regarding binge eating behavior (body weight status (BMI): p > 0.05, underweight perception: OR = 1.18, 95%CI 1.03–1.34; weight teasing for more than once a year: OR = 2.00, 95%CI 1.76–2.27). In addition, weight perception and weight teasing were significantly associated with health risk behaviors, mainly in normal and overweight/obese groups but not in underweight groups. Weight teasing and weight self-perception play an independent and stronger role than actual body weight in the health behaviors of adolescents. This calls for more attention and intervention to reduce peer bullying and stigmas on weight among adolescents.
Vitamin K2 Improves Osteogenic Differentiation by Inhibiting STAT1 via the Bcl-6 and IL-6/JAK in C3H10 T1/2 Clone 8 Cells
Authors: Wang Huakai , Li Longxian , Zhang Nan , Ma Yongxi
Published: July 2022

Osteogenic activity of vitamin K2 (VK2), a small molecular nutrient, has been suggested. However, the underlying mechanisms have not been fully elucidated. Therefore, this study aimed to explore the mechanisms by which VK2 promotes osteogenic differentiation. The effects of VK2 on osteogenic differentiation indicators were determined in C3H10 T1/2 clone 8 cells. The RNA-seq analysis was used to explore the hypothesis that VK2 promotes osteogenic differentiation. Small interfering RNA (siRNA) assay and plasmid transfection assay were used to determine the potential role of VK2 in the modulation of Bcl-6/STAT axis and IL-6/JAK/STAT signaling pathway. VK2 significantly increased alkaline phosphatase (ALP) activity, ALP, osteocalcin (OCN), and RUNX2 abundance, and RUNX2 protein expression. RNA-seq analysis showed that there were 314 differentially expressed genes (DEGs) upregulated and 1348 DEGs downregulated by VK2. PPI analysis determined the top 10 hub genes upregulated or downregulated by VK2. Overexpression of Bcl-6 increased osteogenic differentiation and decreased expression of STAT1. Administration with VK2 restored the inhibition by siBcl-6 in osteogenic differentiation. Knockdown of IL-6 decreased the mRNA levels of genes associated with the JAK/STAT signaling pathway, and increased markers of osteoblast differentiation. Furthermore, treatment with VK2 improved inhibition in osteogenic differentiation and decreased enhancement of JAK/STAT signaling pathway related genes by overexpression of IL-6. Our study suggests that VK2 could improve osteogenic differentiation via the Bcl-6/STAT axis and IL-6/JAK/STAT signaling pathway.
Effect of Cheese Intake on Cardiovascular Diseases and Cardiovascular Biomarkers
Authors: Hu Meng-Jin , Tan Jiang-Shan , Gao Xiao-Jin , Yang Jin-Gang , Yang Yue-Jin
Published: July 2022

Background: A growing number of cohort studies revealed an inverse association between cheese intake and cardiovascular diseases, yet the causal relationship is unclear. Objective: To assess the causal relationship between cheese intake, and cardiovascular diseases and cardiovascular biomarkers. Methods: A two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Results: Cheese intake per standard deviation increase causally reduced the risks of type 2 diabetes (odds ratio (OR) = 0.46; 95% confidence interval (CI), 0.34–0.63; p = 1.02 × 10−6), heart failure (OR = 0.62; 95% CI, 0.49–0.79; p = 0.0001), coronary heart disease (OR = 0.65; 95% CI, 0.53–0.79; p = 2.01 × 10−5), hypertension (OR = 0.67; 95% CI, 0.53–0.84; p = 0.001), and ischemic stroke (OR = 0.76; 95% CI, 0.63–0.91; p = 0.003). Suggestive evidence of an inverse association between cheese intake and peripheral artery disease was also observed. No associations were observed for atrial fibrillation, cardiac death, pulmonary embolism, or transient ischemic attack. The better prognosis associated with cheese intake may be explained by lower body mass index (BMI; effect estimate = −0.58; 95% CI, from −0.88 to −0.27; p = 0.0002), waist circumference (effect estimate = −0.49; 95% CI, from −0.76 to −0.23; p = 0.0003), triglycerides (effect estimate = −0.33; 95% CI, from −0.50 to −0.17; p = 4.91 × 10−5), and fasting glucose (effect estimate = −0.20; 95% CI, from −0.33 to −0.07; p = 0.0003). There was suggestive evidence of a positive association between cheese intake and high-density lipoprotein. No influences were observed for blood pressure or inflammation biomarkers. Conclusions: This two-sample MR analysis found causally inverse associations between cheese intake and type 2 diabetes, heart failure, coronary heart disease, hypertension, and ischemic stroke.
Coupled Plasmon Wave Dynamics beyond Anomalous Reflection: A Phase Gradient Copper Metasurface for the Visible to Near-Infrared Spectrum
Authors: Sultana Hosna
Published: July 2022

In nanoscale photonic devices, the demand for multifunctionality from 2D metasurface optics has increased rapidly. To explore the required fine-tuning in the design metrics, we reinvestigated the trapezoid-shape copper metasurface using finite-difference time-domain simulation to efficiently utilize linearly polarized light for two different functionalities. From the plasmonic band structure, we could see how the degree of asymmetry in the geometry affected the efficient resonance coupling of the traveling plasmonic modes, along with the different types of mode hybridization profiles that were related to the nanoantenna’s geometric shape. By tuning the nanoantenna’s length, we could excite the effective plasmon mode that was supported by this configuration and guide surface waves unidirectionally from the normal incidence free-space light within the visible to infrared range. The directed surface plasmon polaritons had both antisymmetric and symmetric modes that oscillated between the top and bottom surfaces of the continuous metal layer, depending on the nanoantenna’s length and wavelength. This proposed copper metasurface was optimized for a far-field application of broadband (600–900 nm) anomalous beam steering for an average of 60% efficiency with a maximum angle of 64°. This work offers more understanding of a metasurface being implemented in small plasmonic devices, waveguide mode controlling and beam steering with wavelength-dependent functionalities.
Establishing a Herpesvirus Quiescent Infection in Differentiated Human Dorsal Root Ganglion Neuronal Cell Line Mediated by Micro-RNA Overexpression
Authors: Chen Yu-Chih , Li Hedong , Martin-Caraballo Miguel , Hsia Shaochung Victor
Published: July 2022

HSV-1 is a neurotropic pathogen associated with severe encephalitis, excruciating orofacial sensation, and other chronic neuropathic complications. After the acute infection, the virus may establish a lifelong latency in the neurons of trigeminal ganglia (TG) and other sensory and autonomic ganglia, including the dorsal root ganglia (DRG), etc. The reactivation occurred periodically by a variety of physical or emotional stressors. We have been developing a human DRG neuronal cell-culture model HD10.6, which mimics the mature neurons for latency and reactivation with robust neuronal physiology. We found that miR124 overexpression without acyclovir (ACV) could maintain the virus in a quiescent infection, with the accumulation of latency-associate transcript (LAT). The immediate-early (IE) gene ICP0, on the other hand, was very low and the latent viruses could be reactivated by trichostatin A (TSA) treatment. Together, these observations suggested a putative role of microRNA in promoting HSV-1 latency in human neurons.
TG/HDL-C Ratio Is a Risk Factor Associated with CKD: Use in Assessing the Risk of Progression of CKD
Authors: Nguyen Ha Hong , Tran Ha Hai , Nguyen Le Thi , Nguyen Thang , Nguyen Nhut Anh , Vi Mai Tuyet , Nguyen Kien Trung
Published: July 2022

Background: Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD), and the relationship between dyslipidemia and renal function in these patients remains controversial. Our objectives were to determine the triglycerides/HDL-cholesterol ratio (TG/HDL-C), evaluate the correlation between TG/HDL-C and the urine albumin/creatinine ratio (ACR), and estimate the glomerular filtration rate (eGFR) according to MDRD in CKD patients. Methods: A descriptive cross-sectional study was conducted on 152 patients with CKD at the Endocrine Clinic, the University of Medicine and Pharmacy Hospital, Ho Chi Minh City, Vietnam. Study subjects were medically examined and recorded information on the data collection form. Subjects were tested for total cholesterol, triglycerides, HDL-C, LDL-C, urea, creatinine and albumin, urine creatinine, and eGFR according to the MDRD formula. Data were analyzed using SPSS Statistics version 20.0. Results: The average age was 58.08 ± 15.69 years, and the overweight and obesity rate was 54%. Most patients had comorbidities, among which the most common diseases were hypertension and diabetes mellitus. Among the subjects, 57.3% were CKD stage 3 patients, and ACR was in the range of 30–300 mg/g. According to the classification of CKD using GFR and ACR categories, 40.8% of patients were at very high risk. The average TG/HDL-C ratio was 5.09 ± 4.26. There was a medium negative correlation between TG/HDL-C and eGFR (R = 0.44, p < 0.01) and a weak positive correlation between TG/HDL-C and ACR (R = 0.34, p < 0.01). Conclusions: The TG/HDL-C ratio was a risk factor associated with CKD and was noticeable in monitoring and assessing the risk of progression of CKD.
Co-Delivery of 5-Fluorouracil and Paclitaxel in Mitochondria-Targeted KLA-Modified Liposomes to Improve Triple-Negative Breast Cancer Treatment
Authors: Chen Tianyu , Chen Hui , Jiang Yichun , Yan Qi , Zheng Shuling , Wu Min
Published: July 2022

In this research, KLA-modified liposomes co-loaded with 5-fluorouracil and paclitaxel (KLA-5-FU/PTX Lps) were developed, and their antitumor activity against triple-negative breast cancer (TNBC) was evaluated. KLA-5-FU/PTX Lps were prepared using the thin-film dispersion method, and their in vitro anticancer efficacy was assessed in human breast cancer cells (MDA-MB-231). An MDA-MB-231 tumor-bearing mouse model was also established to evaluate their antitumor efficacy in vivo. KLA-5-FU/PTX Lps showed enhanced cytotoxicity against MDA-MB-231 cells, improved drug delivery to mitochondria, and induced mitochondria-mediated apoptosis. The modified liposomes also showed favorable antitumor activity in vivo due to their strong ability to target tumors and mitochondria. The liposomes showed no obvious systemic toxicity. Our results suggest that KLA-5-FU/PTX Lps are a promising system with which to target the delivery of antitumor drugs to mitochondria as a treatment for TNBC.
The N-Methyl-D-Aspartate Receptor Blocker REL-1017 (Esmethadone) Reduces Calcium Influx Induced by Glutamate, Quinolinic Acid, and Gentamicin
Authors: Bettini Ezio , De Martin Sara , Mattarei Andrea , Pappagallo Marco , Stahl Stephen M. , Bifari Francesco , Inturrisi Charles E. , Folli Franco , Traversa Sergio , Manfredi Paolo L.
Published: July 2022

REL-1017 (esmethadone) is a novel N-methyl-D-aspartate receptor (NMDAR) antagonist and promising rapid antidepressant candidate. Using fluorometric imaging plate reader (FLIPR) assays, we studied the effects of quinolinic acid (QA) and gentamicin, with or without L-glutamate and REL-1017, on intracellular calcium ([Ca2+]in) in recombinant cell lines expressing human GluN1-GluN2A, GluN1-GluN2B, GluN1-GluN2C, and GluN1-GluN2D NMDAR subtypes. There were no effects of QA on [Ca2+]in in cells expressing GluN1-GluN2C subtypes. QA acted as a low-potency, subtype-selective, NMDAR partial agonist in GluN1-GluN2A, GluN1-GluN2B, and GluN1-GluN2D subtypes. REL-1017 reduced [Ca2+]in induced by QA. In cells expressing the GluN1-GluN2D subtype, QA acted as an agonist in the presence of 0.04 μM L-glutamate and as an antagonist in the presence of 0.2 μM L-glutamate. REL-1017 reduced [Ca2+]in induced by L-glutamate alone and with QA in all cell lines. In the absence of L-glutamate, gentamicin had no effect. Gentamicin was a positive modulator for GluN1-GluN2B subtypes at 10 μM L-glutamate, for GluN1-GluN2A at 0.2 μM L-glutamate, and for GluN1-GluN2A, GluN1-GluN2B, and GluN1-GluN2D at 0.04 μM L-glutamate. No significant changes were observed with GluN1-GluN2C NMDARs. REL-1017 reduced [Ca2+]in induced by the addition of L-glutamate in all NMDAR cell lines in the presence or absence of gentamicin. In conclusion, REL-1017 reduced [Ca2+]in induced by L-glutamate alone and when increased by QA and gentamicin. REL-1017 may protect cells from excessive calcium entry via NMDARs hyperactivated by endogenous and exogenous molecules.
Chronic Pruritus in Atopic Patients Treated with Dupilumab: Real Life Response and Related Parameters in 354 Patients
Authors: Mastorino Luca , Rosset François , Gelato Federica , Ortoncelli Michela , Cavaliere Giovanni , Quaglino Pietro , Ribero Simone
Published: July 2022

Chronic pruritus is a major symptom of atopic dermatitis (AD). Its etiopathogenesis is complex, and an understanding of the driving factors of its pathogenesis allows for the development of new molecule-targeted therapies. Dupilumab, targeting and blocking interleukin-4 (IL-4) and interleukin-13 (IL-13) molecules, has shown great efficacy in treating AD symptoms such chronic itching. We performed a retrospective observational study to evaluate possible chronic-itch-related characteristics and parameters in 356 AD patients who received dupilumab. The objective of the study was to evaluate the factors associated with the level of pruritus reported by patients at each of the 1575 detections in the form of the peak pruritus numerical rating scale (NRSpp) and sleep disturbance numerical rating scale (NRSsd). We focused on: the eczema area and severity index (EASI), dermatology life quality index (DLQI), patient-oriented eczema measure (POEMS), eosinophilia, L-lactate dehydrogenase (LDH), immunoglobulin E (IgE) and the time from the start of dupilumab therapy. NRSpp fell from 8.6 (sd 1.7) at baseline to 1.7 (sd 2.3) at 36 months and NRSsd from 7 (sd 3) to 0. Regarding the parameters that correlate with NRSpp, all the parameters analysed were significantly correlated except for eosinophils (p = 0.136). In the multivariate analysis, both considering and not considering treatment duration, the parameters were correlated (p < 0.001); EASI, DLQI, POEM, and LDH significantly correlated with NRSpp (p < 0.001 for each, except for LDH p = 0.003); while IgE tot lost significance (p = 0.337). Similar results were obtained for the parameters correlating with NRSsd. Our results confirm the efficacy of dupilumab on pruritus. The use of questionnaires such as DLQI and POEM is advisable in clinical practice and is adequate for assessing the impact of itching on AD. The low correlation of IgE and eosinophils, the ambiguity of LDH levels with the level of pruritus, and a poor clinical validity and unclear correlation with disease severity suggest a progressive abandonment of monitoring of these values.
A Physiologically Based Pharmacokinetic and Pharmacodynamic Model of the CYP3A4 Substrate Felodipine for Drug–Drug Interaction Modeling
Authors: Fuhr Laura Maria , Marok Fatima Zahra , Mees Maximilian , Mahfoud Felix , Selzer Dominik , Lehr Thorsten
Published: July 2022

The antihypertensive felodipine is a calcium channel blocker of the dihydropyridine type, and its pharmacodynamic effect directly correlates with its plasma concentration. As a sensitive substrate of cytochrome P450 (CYP) 3A4 with high first-pass metabolism, felodipine shows low oral bioavailability and is susceptible to drug–drug interactions (DDIs) with CYP3A4 perpetrators. This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) parent–metabolite model of felodipine and its metabolite dehydrofelodipine for DDI predictions. The model was developed in PK-Sim® and MoBi® using 49 clinical studies (94 plasma concentration–time profiles in total) that investigated different doses (1–40 mg) of the intravenous and oral administration of felodipine. The final model describes the metabolism of felodipine to dehydrofelodipine by CYP3A4, sufficiently capturing the first-pass metabolism and the subsequent metabolism of dehydrofelodipine by CYP3A4. Diastolic blood pressure and heart rate PD models were included, using an Emax function to describe the felodipine concentration–effect relationship. The model was tested in DDI predictions with itraconazole, erythromycin, carbamazepine, and phenytoin as CYP3A4 perpetrators, with all predicted DDI AUClast and Cmax ratios within two-fold of the observed values. The model will be freely available in the Open Systems Pharmacology model repository and can be applied in DDI predictions as a CYP3A4 victim drug.
Hyaluronic Acid: Its Versatile Use in Ocular Drug Delivery with a Specific Focus on Hyaluronic Acid-Based Polyelectrolyte Complexes
Authors: Casey-Power Saoirse , Ryan Richie , Behl Gautam , McLoughlin Peter , Byrne Mark E. , Fitzhenry Laurence
Published: July 2022

Extensive research is currently being conducted into novel ocular drug delivery systems (ODDS) that are capable of surpassing the limitations associated with conventional intraocular anterior and posterior segment treatments. Nanoformulations, including those synthesised from the natural, hydrophilic glycosaminoglycan, hyaluronic acid (HA), have gained significant traction due to their enhanced intraocular permeation, longer retention times, high physiological stability, inherent biocompatibility, and biodegradability. However, conventional nanoformulation preparation methods often require large volumes of organic solvent, chemical cross-linkers, and surfactants, which can pose significant toxicity risks. We present a comprehensive, critical review of the use of HA in the field of ophthalmology and ocular drug delivery, with a discussion of the physicochemical and biological properties of HA that render it a suitable excipient for drug delivery to both the anterior and posterior segments of the eye. The pivotal focus of this review is a discussion of the formation of HA-based nanoparticles via polyelectrolyte complexation, a mild method of preparation driven primarily by electrostatic interaction between opposing polyelectrolytes. To the best of our knowledge, despite the growing number of publications centred around the development of HA-based polyelectrolyte complexes (HA-PECs) for ocular drug delivery, no review articles have been published in this area. This review aims to bridge the identified gap in the literature by (1) reviewing recent advances in the area of HA-PECs for anterior and posterior ODD, (2) describing the mechanism and thermodynamics of polyelectrolyte complexation, and (3) critically evaluating the intrinsic and extrinsic formulation parameters that must be considered when designing HA-PECs for ocular application.
A Degradable and Osteogenic Mg-Based MAO-MT-PLGA Drug/Ion Delivery System for Treating an Osteoporotic Fracture
Authors: Liu Changxin , Zhang Wen , Gao Ming , Yang Ke , Tan Lili , Zhao Wei
Published: July 2022

Osteoporotic fractures are a very common bone disease that is difficult to completely cure. A large number of people worldwide suffer from pain caused by osteoporotic fractures every year, which can even cause disability and death. The compromised skeletal strength, lower density, trabecular microstructure, and bone-forming ability caused by osteoporotic fractures make them difficult to treat relative to normal fractures. An ideal scheme for osteoporotic fractures is to select internal fixation materials with matched mechanical and biological properties and carry anti-osteoporosis drugs on the plant to achieve bio-fixation and improve the condition of osteoporosis simultaneously. We designed a Mg-based MAO-MT-PLGA drug/ion delivery system (DDS) compatible with bone-like mechanical properties, degradation properties, and drug therapy. In this research, we evaluated the degradation behavior of Mg-based MAO-MT-PLGA DDS using immersion tests and electrochemical tests aided by SEM, EDS, XPS, XRD, and FT-IR. The DDS showed better corrosion resistance over Mg alloy and could release more Mg2+ due to the degradation of PLGA. According to cell viability and cell adhesion, the DDS showed better osteogenic characteristics over control group I (Mg alloy) and control group II (Mg-based MAO alloy), especially in the cells co-cultured with the leaching solution for 72 h, in which the DDS group increased to about 15% cell viability compared with group I (p < 0.05). The mRNA relative expressions, including ALP, collagen I, OCN, OPG, and Runx-2, as well as extracellular matrix calcium deposits of the DDS, are 1.5~2 times over control group I and control group II (p < 0.05), demonstrating a better ability to promote bone formation and inhibit bone resorption. After the DDS was implanted into the castrated rat model for one month, the trabeculae in the treatment group were significantly denser and stronger than those in the control group, with a difference of about 1.5 times in bone volume fraction, bone density, and the number of trabeculae, as well as the magnesium content in the bone tissue (p < 0.05). The above results demonstrated that the Mg-based MAO-MT-PLGA drug/ion delivery system is a potential treatment for osteoporotic fractures.
Characterization of a Mesoporous Silica Nanoparticle Formulation Loaded with Mitomycin C Lipidic Prodrug (MLP) and In Vitro Comparison with a Clinical-Stage Liposomal Formulation of MLP
Authors: Manzano Miguel , Gabizón Alberto , Vallet-Regí María
Published: July 2022

Nanomedicines have revolutionized the treatment of certain types of cancer, as is the case of doxil, liposomal formulation with doxorubicin encapsulated, in the treatment of certain types of ovarian cancer, AIDS-related Kaposi sarcoma, and multiple myeloma. These nanomedicines can improve the performance of conventional chemotherapeutic treatments, with fewer side effects and better efficiency against cancer. Although liposomes have been used in some formulations, different nanocarriers with better features in terms of stability and adsorption capabilities are being explored. Among the available nanoparticles in the field, mesoporous silica nanoparticles (MSNP) have attracted great attention as drug delivery platforms for the treatment of different diseases. Here, a novel formulation based on MSNP loaded with a potent antitumor prodrug that works in vitro as well as in a clinically evaluated liposomal formulation has been developed. This novel formulation shows excellent prodrug encapsulation efficiency and effective release of the anticancer drug only under certain stimuli typical of tumor environments. This behavior is of capital importance for translating this nanocarrier to the clinic in the near future.
Axiological Retributivism and the Desert Neutrality Paradox
Authors: Campbell Tim
Published: July 2022

According to axiological retributivism, people can deserve what is bad for them and an outcome in which someone gets what she deserves, even if it is bad for her, can thereby have intrinsic positive value. A question seldom asked is how axiological retributivism should deal with comparisons of outcomes that differ with respect to the number and identities of deserving agents. Attempting to answer this question exposes a problem for axiological retributivism that parallels a well-known problem in population axiology introduced by John Broome. The problem for axiological retributivism is that it supports the existence of a range of negative wellbeing levels such that if a deserving person comes into existence at any of these levels, the resulting outcome is neither better nor worse with respect to desert. However, the existence of such a range is inconsistent with a set of very plausible axiological claims. I call this the desert neutrality paradox. After introducing the paradox, I consider several possible responses to it. I suggest that one reasonable response, though perhaps not the only one, is to reject axiological retributivism.
Effect of Petal Color, Water Status, and Extraction Method on Qualitative Characteristics of Rosa rugosa Liqueur
Authors: Fascella Giancarlo , D’Angiolillo Francesca , Mammano Michele Massimo , Granata Giuseppe , Napoli Edoardo
Published: July 2022

Flowers of Rosa rugosa Thunb. are a rich source of bioactive compounds with high antioxidant properties and are used for the production of jams, teas, juices, and wines. In the present paper, the petals of R. rugosa cv. Alba (white flowers) and Rubra (purple flowers) were evaluated for their morphological and phytochemical characteristics, and for the preparation of an alcoholic liqueur. In particular, the effect of two extraction procedures (conventional and maceration) of fresh and dry petals on the quality of a rose liqueur was determined. As expected, the concentration of the flower’s bioactive compounds was affected by petal water content and by tested cultivars: dry petals showed higher total carotenoids and anthocyanins contents with respect to the fresh ones; cv. Rubra evidenced higher values compared to cv. Alba. As regards the quality of rose liqueur, the two petal extraction procedures did not affect the polyphenol content and higher values were recorded only on dry petals with respect to the fresh ones and, in particular, on those from cv. Rubra. The liqueur’s flavonoid content was influenced by the petal extraction method, water content, and color as higher values were recorded on rose liqueur prepared after the maceration of cv. Rubra dry petals whereas lower values were observed on alcoholic drinks prepared after the conventional extraction of cv. Alba fresh petals. Our study shows that R. rugosa petals have a fair amount of secondary metabolites with antioxidant activity, making them suitable for use in the beverage industry.
Biodegradable Polymer Composites for Electrophysiological Signal Sensing
Authors: Lee Dong Hyun , Park Taehyun , Yoo Hocheon
Published: July 2022

Electrophysiological signals are collected to characterize human health and applied in various fields, such as medicine, engineering, and pharmaceuticals. Studies of electrophysiological signals have focused on accurate signal acquisition, real-time monitoring, and signal interpretation. Furthermore, the development of electronic devices consisting of biodegradable and biocompatible materials has been attracting attention over the last decade. In this regard, this review presents a timely overview of electrophysiological signals collected with biodegradable polymer electrodes. Candidate polymers that can constitute biodegradable polymer electrodes are systemically classified by their essential properties for collecting electrophysiological signals. Moreover, electrophysiological signals, such as electrocardiograms, electromyograms, and electroencephalograms subdivided with human organs, are discussed. In addition, the evaluation of the biodegradability of various electrodes with an electrophysiology signal collection purpose is comprehensively revisited.
Improvement on Thermostability of Pectate Lyase and Its Potential Application to Ramie Degumming
Authors: Xu Huan , Feng Xiangyuan , Yang Qi , Zheng Ke , Yi Le , Duan Shengwen , Cheng Lifeng
Published: July 2022

In order to obtain a thermostable pectate lyase for ramie degumming, a rational design based on structural analysis was carried out on a novel pectate lyase (Pel419) derived from the Dickeya Dadantii DCE-01 for high-efficiency ramie degumming. A total of five potential amino acid sites were chosen to replace residues. Then, the mutant enzymes were subjected to the heterologous expressions in Escherichia coli and their enzymatic characteristics were determined. The optimal reaction temperature for the five mutants kept consistent with that for the wild type. The enzyme activity and thermal stability of mutant V52A were significantly improved. Meanwhile, the weight loss rate obtained by V52A with the best enzymatic characteristics in the ramie degumming process at 50 °C is comparable with that obtained by commercial cotton-ramie processing pectinases, indicating that V52A was a potential industrial enzyme that could be applied to large-scale ramie degumming. In this study, the biological functions of conservative residues of Pel419 were preliminarily explored. The mutant V52A with both enzymatic activity and improved heat resistance was acquired, providing a superior material for developing enzyme preparations of ramie degumming, and rendering an effective method for the rational design aiming to improve the thermostability of pectate lyase.
The Dependence of the Properties of Recycled PET Electrospun Mats on the Origin of the Material Used for Their Fabrication
Authors: Kijeńska-Gawrońska Ewa , Wiercińska Katarzyna , Bil Monika
Published: July 2022

Plastic materials are one of the significant components of construction materials omnipresent in all areas of the industry and everyday life. One of these plastics is polyethylene terephthalate (PET). Due to its processing properties, with a simultaneous low production cost, PET has been used in many industrial applications, including the production of various types of bottles. Moreover, the high consumption of PET bottles causes the accumulation of large amounts of their waste and necessitates finding an effective way to recycle them. Electrospinning is a well-known non-complicated method for the fabrication of nonwovens from polymers and composites, which can be utilized in many fields due to their outstanding properties. In addition, it might be a promising technique for the recycling of plastic materials. Therefore, in this study, the electrospinning approach for the recycling of two types of PET bottle wastes—bottles made of virgin PET and bottles made of recycled PET (PET bottles) has been utilized, and a comparison of the properties of the obtained materials have been performed. The fibers with diameters of 1.62 ± 0.22, 1.64 ± 0.18, and 1.89 ± 0.19 have been produced from solutions made of virgin PET granulate, PET bottles, and PET bottles made of recycled bottles, respectively. Obtained fibers underwent morphological observation using a scanning electron microscope. Physico-chemical properties using FTIR, gel chromatography, and differential scanning calorimetry have been evaluated, and mechanical properties of obtained mats have been investigated. Cytotoxicity tests using the L929 mouse fibroblast cell line revealed no cytotoxicity for all tested materials.
Non-Dominant Genetic Algorithm for Multi-Objective Optimization Design of Unmanned Aerial Vehicle Shell Process
Authors: Chang Hanjui , Zhang Guangyi , Sun Yue , Lu Shuzhou
Published: July 2022

This paper uses Pareto-optimized frames and injection molding process parameters to optimize the quality of UAV housing parts with multi-objective optimization. Process parameters, such as melt temperature, filling time, pressure, and pressure time, were studied as model variables. The quality of a plastic part is determined by two defect parameters, warpage value and mold index, which require minimal defect parameters. This paper proposes a three-stage optimization system. In the first stage, the main node position of the electronic chip in the module is collected by the unified sampling method, and the chip calculation index of these node positions is analyzed by the mold flow analysis software. In the second stage, the kriging function predicts the mathematical relationship between the mold index and warpage value and the process parameters, such as melt temperature, filling time, packing pressure, and packing time. In the third stage, using LHD sampling and non-dominant rank genetic algorithm II, a convergence curve of warp value is found near the Pareto optimal frontier. In the fourth stage, the fitting degree of Pareto optimal leading edge curve points was verified by analytical experiments. According to experimental verification, it can be seen that the injection molding factors are pressure and pressure time, because the injection molding time and pressure time are completely positively correlated with the mold indicators, the correlation is the strongest, the mold temperature and glue temperature are not the main influencing factors, and the mold temperature shows a certain degree of negative correlation. In this experiment, the die index is mainly improved by injection time and pressure, optimal injection parameter factor combination and minimum injection index, the optimization rate of the die index is up to 96.2% through genetic algorithm optimization nodes and experimental verification, the average optimization rate of the four main optimization nodes is 91.2%, and the error rate with the actual situation is only 8.48%, which is in line with the needs of actual production, and the improvement of the UAV IME membrane is realized.
Lean Optimization Techniques for Improvement of Production Flows and Logistics Management: The Case Study of a Fruits Distribution Center
Authors: Proença Ana P. , Gaspar Pedro Dinis , Lima Tânia M.
Published: July 2022

The organizations of horticultural producers and, particularly, those that deal with extremely perishable endogenous fruits, such as peaches and cherries, have a greater need to optimize production flows and processes. A particularity of the horticultural industry is the short shelf life of raw materials and the seasonality of products. In this paper, optimization techniques are used to improve the production flows and the management of cold storage and distribution in a fruit central. The application of Lean tools allowed reducing the cycle time by 4.37 min and the lead time by 7.10 min of the whole process, i.e., a reduction of 35.5% and 10.6% of the cycle time and lead time, respectively, excluding the cold conservation operation. The study shows that it is possible to reduce, or even eliminate, waste throughout the process, reduce unnecessary movement, adapt the layout, maximize workspace, and level stocks, as well as greater supplier involvement in a continuous improvement approach. This approach can be outlined as a good practice for the optimization of productive flows and management logistics that may benefit productivity, energy efficiency, human resources distribution, food quality, and reduce food waste.
A Novel Back-Stepping Sliding Mode Control Strategy of Direct-Drive Wave Energy Converters
Authors: Weng Shiguang , Wang Jianyong
Published: July 2022

In this paper, a maximum energy extraction and tracking strategy for direct-drive wave energy converters (DDWECs) based on back-stepping and sliding mode control strategies are developed. It is well known that the existence of the chattering phenomenon degrades the control performance of conventional sliding mode control (SMC). To mitigate the effects of flutter and external disturbances, a back-stepping sliding model control (BSMC) scheme is proposed. The main features of the proposed methodology are as follows: (1) By using the proposed BSMC, the maximum wave energy of DDWEC can be captured. Moreover, the speed tracking of the permanent magnet linear generator (PMLG), which is a subsystem of DDWEC, tracked in real-time. (2) By virtue of the proposed BSMC, the closed-loop control system is asymptotically stable in finite time. (3) With the superior controllability of the BSMC, it can handle disturbances that the SMC cannot handle. Comprehensive and comparative studies are proved to be superior to the most advanced method
Numerical Investigation on the Flow Instability of Dispersed Bubbly Flow in a Horizontal Contraction Section
Authors: Chen Jingxiang , Li Wei , Fu Cheng , Zhang Jingzhi , Kukulka David J.
Published: July 2022

Dispersed bubbly flow is important to understand when working in a wide variety of hydrodynamic engineering areas; the main objective of this work is to numerically study bubble-induced instability. Surface tension and bubble-induced turbulence effects are considered with the momentum and k-ω transport equations. Steady dispersed bubbly flow is generated at the inlet surface using time-step and user-defined functions. In order to track the interface between the liquid and gas phases, the volume of fraction method is used. Several calculation conditions are considered in order to determine the effects of bubble diameter, bubble distribution, bubble velocity and bubble density on flow instability and void fraction. The void fraction of the domain is set to no more than 0.5% under different bubbly (micro/small) flow conditions; and the order of magnitude of the Reynolds number is 106. Results from the simulation indicate that velocity fluctuation induced by bubble swarm increases with increasing bubble diameter. Bubble density and bubble distribution seem to have a complex influence on flow instability. Bubble-induced turbulence results indicate that small bubbles produce a significant disturbance near the boundary region of bubble swarm; this indicates that induced bubble swarm has a potential capability of enhancing heat and mass transfer in the velocity boundary layer. Results from this study are useful for two-phase flow, bubble floatation and other hydrodynamic engineering applications.
The Ameliorative Role of Hibiscetin against High-Fat Diets and Streptozotocin-Induced Diabetes in Rodents via Inhibiting Tumor Necrosis Factor-α, Interleukin-1β, and Malondialdehyde Level
Authors: Gilani Sadaf Jamal , Bin-Jumah May Nasser , Al-Abbasi Fahad A. , Albohairy Fatima M. , Nadeem Muhammad Shahid , Ahmed Mohammed Muqtader , Alzarea Sami I. , Kazmi Imran
Published: July 2022

Hibiscetin, as one of the main bioactive constituents of Hibiscus sabdariffa, has many pharmacological activities, but its antihyperglycemic activity has not been fully interpreted yet. The current research was developed from this perspective. The study intended to appraise the antidiabetic capability of hibiscetin in a high-fat diet (HFD) and streptozotocin (STZ; 50 mg/kg, intraperitoneally)-induced diabetes in an experimental animal. The efficiency of hibiscetin at 10 mg/kg in an “HFD/STZ model” remedy in rats with experimentally caused diabetes was explored for 42 days. The efficacy of hibiscetin was observed on several diabetes parameters. The average body weight and an array of biochemical markers were determined, including blood glucose, insulin, total protein (TP), lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-6, IL-1β, tumor necrosis factor-α (TNF-α), adiponectin, leptin, resistin, malondialdehyde (MDA), catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD). The antidiabetic benefits of hibiscetin were proven by a substantial reduction in blood glucose, lipid profile (TC and TG), total protein, IL-6, IL-1β, MDA, TNF-α, leptin, adiponectin, ALT, and AST in the therapy group compared to the diabetic disease standard. Furthermore, hibiscetin therapy also reversed the lowered levels of insulin, resistin, GSH, SOD, and CAT in diabetic rats. It was determined that hibiscetin may be beneficial in terms of reducing diabetes problems due to its effects on both oxidative stress and inflammation and that more research for this design should be conducted.
Monitoring the Distribution and Variations of City Size Based on Night-Time Light Remote Sensing: A Case Study in the Yangtze River Delta of China
Authors: Ding Yuan , Hu Jia , Yang Yingbao , Ma Wenyu , Jiang Songxiu , Pan Xin , Zhang Yong , Zhu Jingjing , Cao Kai
Published: July 2022

Effectively monitoring the size of a city in real time enables the scientific planning of urban development. Models that utilize the distribution and variations in city size generally use population data as inputs, which cannot be obtained in a timely and rapid manner. However, night-time light (NTL) remote sensing may be an alternative method. A case study was carried out on the Yangtze River Delta (YRD) in China, and the rank–size rule, the law of primate cities, and the Gini coefficient were employed to monitor the variation in city size in the study area. The urban areas extracted based on NTL remote sensing were utilized instead of the traditionally used population data to evaluate the variations in city size from 2012 to 2017. Considering the empiricism and subjectivity of the thresholding method, urban areas were extracted from NTL data combined with the normalized differential vegetation index and land-surface temperature data based on the artificial neural network algorithm. Based on the results, the YRD did not fit the distribution of the primate cities from 2012 to 2017. However, this region satisfied the rank–size rule well, which indicated that the development of medium–small cities was more prominent than that of larger cities, and the dispersed force was larger than the concentrated force. Notably, the city size reached a relatively balanced level in the study area. Further, sensitivity analysis revealed that the relatively low extraction accuracy of urban areas of few small cities had little effect on the results of city size variations. Moreover, the validation of city size computed from statistical population data and its comparison with results calculated based on the statistical data of urban areas aligned with the results of this study, which indicates the rationality and applicability of monitoring the variations in city size using the urban areas extracted from NTL remote sensing instead of population data.