bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurobehavioral and Ultrastructural Changes Induced by Phytosynthesized Silver-Nanoparticle Toxicity in an In Vivo Rat Model
Authors: Opris Razvan Vlad , Toma Vlad , Baciu Alina Mihaela , Moldovan Remus , Dume Bogdan , Berghian-Sevastre Alexandra , Moldovan Bianca , Clichici Simona , David Luminita , Filip Gabriela Adriana , Florea Adrian
Published: December 2021

(1) Background: The study aimed to assess neurobehavioral, ultrastructural, and biochemical changes induced by silver nanoparticles synthesized with Cornus mas L. extract (AgNPs-CM) in rat brains. (2) Methods: The study included 36 male adult rats divided into three groups. Over a period of 45 days, AgNPs-CM (0.8 and 1.5 mg/kg b.w.) were administered daily by gavage to two of the groups, while the control group received the vehicle used for AgNP. After treatment, OFT and EPM tests were conducted in order to assess neurobehavioral changes. Six of the animals from each group were sacrificed immediately after completion of treatment, while the remaining six were allowed to recuperate for an additional 15 days. Transmission electron microscopy (TEM), GFAP immunohistochemistry, and evaluation of TNFα, IL-6, MDA, and CAT activity were performed on the frontal cortex and hippocampus. (3) Results: Treated animals displayed a dose- and time-dependent increase in anxiety-like behavior and severe ultrastructural changes in neurons, astrocytes, and capillaries in both brain regions. Immunohistochemistry displayed astrogliosis with altered cell morphology. TNFα, IL-6, MDA, and CAT activity were significantly altered, depending on brain region and time post exposure. (4) Conclusions: AgNPs-CM induced neurobehavioral changes and severe cell lesions that continued to escalate after cessation of exposure.
Sialic Acid Ameliorates Cognitive Deficits by Reducing Amyloid Deposition, Nerve Fiber Production, and Neuronal Apoptosis in a Mice Model of Alzheimer’s Disease
Authors: Xiao Min , Yao Chuangyu , Liu Fang , Xiang Wei , Zuo Yao , Feng Kejue , Lu Shuhuan , Xiang Li , Li Muzi , Li Xiangyu , Du Xiubo
Published: December 2021

(1) Background: As a natural carbohydrate, sialic acid (SA) is helpful for brain development, cognitive ability, and the nervous system, but there are few reports about the effect of SA on Alzheimer’s disease (AD). (2) Method: The present study evaluated the effect of SA on cognitive ability, neuronal activity, Aβ formation, and tau hyperphosphorylation in a double transgenic AD (2×Tg-AD) mice model. The 2×Tg-AD mice were randomly divided into four groups: the AD control group, 17 mg/kg SA-treated AD group, 84 mg/kg SA-treated AD group, and 420 mg/kg SA-treated AD group. Mice from all four groups were fed to 7 months of age for the behavioral test and to 9 months of age for the pathological factors investigation. (3) Results: In the Morris water maze, the escape latency significantly decreased on the fifth day in the SA-treated groups. The number of rearing and crossing times in the open field test also increased significantly, compared with the control group. SA treatment significantly reduced amyloid β-peptide (Aβ) and nerve fibers and increased the number of Nissl bodies in the brain of AD mice. (4) Conclusions: SA reduced the neuron damage by reducing Aβ and inhibited tau protein hyperphosphorylation, which improved the cognitive ability and mobility of AD mice.
Methods for Assessing Willingness to Try and Vegetable Consumption among Children in Indigenous Early Childcare Settings: The FRESH Study
Authors: Wetherill Marianna S. , Williams Mary B. , Reese Jessica , Taniguchi Tori , Sisson Susan B. , Malek-Lasater Adrien D. , Love Charlotte V. , Jernigan Valarie Blue Bird
Published: December 2021

Food preferences begin in early childhood, and a child’s willingness to try (WTT) new vegetables is an important determinant of vegetable intake. Young children living in rural communities are at increased risk for food insecurity, which may limit exposure to and consumption opportunities for vegetables. This manuscript describes the validation of the Farfan-Ramirez WTT (FR-WTT) measure using baseline data from the FRESH study, a gardening intervention for Native American families with preschool-aged children in Osage Nation, Oklahoma. Individually weighed vegetable containers were prepared with six types of vegetables and ranch dip. Researchers presented children (n = 164; M = 4.3 years, SD = 0.8) with these vegetables preceding a snack- or lunch time and recorded the child’s FR-WTT for each vegetable using a 5-point scale, ranging from “did not remove food (0)” to “put food in mouth and swallowed (4)”. After the presentation period, contents were re-weighed to calculate vegetable consumption. Household parents/guardians completed the Child Food Neophobia Scale (CFNS) for their child. FR-WTT scores were positively correlated with consumption weights of all vegetables (r = 0.7613, p < 0.0001) and each vegetable individually (r = 0.2016–0.7664). The total FR-WTT score was inversely correlated with the CFNS score (r = 0.3268, p < 0.0001). Sensitivity analyses demonstrated similar relationships by BMI, food security, and age. In conclusion, the FR-WTT is a valid method for assessing young children’s vegetable eating behavior and intake.
‘Food for Thought’—The Relationship between Diet and Cognition in Breast and Colorectal Cancer Survivors: A Feasibility Study
Authors: Coro Daniel G. , Hutchinson Amanda D. , Dyer Kathryn A. , Banks Siobhan , Koczwara Bogda , Corsini Nadia , Vitry Agnes , Coates Alison M.
Published: December 2021

Survivors of cancer frequently experience persistent and troublesome cognitive changes. Little is known about the role diet and nutrition plays in survivors’ cognition. We explored the feasibility of collecting cross-sectional online data from Australian survivors of breast and colorectal cancer to enable preliminary investigations of the relationships between cognition with fruit and vegetable intake, and the Omega-3 Index (a biomarker of long chain omega 3 fatty acid intake). A total of 76 participants completed online (and postal Omega-3 Index biomarker) data collection (62 breast and 14 colorectal cancer survivors): mean age 57.5 (±10.2) years, mean time since diagnosis 32.6 (±15.6) months. Almost all of the feasibility outcomes were met; however, technical difficulties were reported for online cognitive testing. In hierarchical linear regression models, none of the dietary variables of interest were significant predictors of self-reported or objective cognition. Age, BMI, and length of treatment predicted some of the cognitive outcomes. We demonstrated a viable online/postal data collection method, with participants reporting positive levels of engagement and satisfaction. Fruit, vegetable, and omega-3 intake were not significant predictors of cognition in this sample, however the role of BMI in survivors′ cognitive functioning should be further investigated. Future research could adapt this protocol to longitudinally monitor diet and cognition to assess the impact of diet on subsequent cognitive function, and whether cognitive changes impact dietary habits in survivors of cancer.
Sulforaphane Attenuates Nonalcoholic Fatty Liver Disease by Inhibiting Hepatic Steatosis and Apoptosis
Authors: Li Jinwang , Xie Siyu , Teng Wendi
Published: December 2021

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipotoxicity and ectopic lipid deposition within hepatocytes. Sulforaphane (SFA), an active compound used for inhibiting tumors, was found to have the potency to improve lipid metabolism. However, its molecular mechanisms on ameliorating NAFLD are still incompletely understood. This research evaluated if SFA could inhibit hepatic steatosis and apoptosis. The effects of SFA on cell viability, lipid accumulation, triglyceride (TG) contents, apoptosis, ceramide contents, and reactive oxygen species (ROS) levels were analyzed in palmitic acid (PA)-treated HepG2 cells and high-fat diet (HFD)-fed mice. The related molecular mechanisms were further explored in hepatocytes. The results showed SFA alleviated lipid accumulation and regulated AMPK/SREBP1c/FAS signaling pathway in PA-stressed HepG2 cells. In addition, SFA alleviated PA-mediated apoptosis, downregulated the expressions of cleaved caspase 3, as well as reduced ceramide contents and ROS levels. Moreover, SFA treatment reduced HFD-induced body weight gain, alleviated insulin resistance, decreased serum TG, total cholesterol (TC), and alanine aminotransferase (ALT) levels, and prevented lipid deposition and apoptosis in the liver. This study showed SFA suppressed lipid deposition and apoptosis both in vitro and in vivo, indicating that SFA may be a potential candidate for preventing and treating NAFLD.
American Ginseng Attenuates Eccentric Exercise-Induced Muscle Damage via the Modulation of Lipid Peroxidation and Inflammatory Adaptation in Males
Authors: Lin Ching-Hung , Lin Yi-An , Chen Shu-Li , Hsu Mei-Chich , Hsu Cheng-Chen
Published: December 2021

Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear. Twelve physically active males (age: 22.4 ± 1.7 years; height: 175.1 ± 5.7 cm; weight: 70.8 ± 8.0 kg; peak oxygen consumption [V˙O2peak] 54.1 ± 4.3 mL/kg/min) were administrated by AG extract (1.6 g/day) or placebo (P) for 28 days and subsequently challenged by downhill (DH) running (−10% gradient and 60% V˙O2peak). The levels of circulating 8-iso-prostaglandin F 2α (PGF2α), creatine kinase (CK), interleukin (IL)-1β, IL-4, IL-10, and TNF-α, and the graphic pain rating scale (GPRS) were measured before and after supplementation and DH running. The results showed that the increases in plasma CK activity induced by DH running were eliminated by AG supplementation at 48 and 72 h after DH running. The level of plasma 8-iso-PGF2α was attenuated by AG supplementation immediately (p = 0.01 and r = 0.53), 2 h (p = 0.01 and r = 0.53) and 24 h (p = 0.028 and r = 0.45) after DH running compared with that by P supplementation. Moreover, our results showed an attenuation in the plasma IL-4 levels between AG and P supplementation before (p = 0.011 and r = 0.52) and 72 h (p = 0.028 and r = 0.45) following DH running. Our findings suggest that short-term supplementation with AG alleviates eccentric EIMD by decreasing lipid peroxidation and promoting inflammatory adaptation.
Relationship between Regular Green Tea Intake and Osteoporosis in Korean Postmenopausal Women: A Nationwide Study
Authors: Lee Dan Bi , Song Hong Ji , Paek Yu-Jin , Park Kyung Hee , Seo Young-Gyun , Noh Hye-Mi
Published: December 2021

Mixed results have been reported regarding whether habitual tea intake affects bone health. This study investigated the relationship between green tea intake and bone mineral density (BMD) in postmenopausal Korean women. We used data from the Korean National Health and Nutrition Examination Surveys from 2008 to 2011 and divided the participants into three groups according to their frequency of green tea intake over the past 12 months. BMD of the lumbar spine, total femur, and femur neck was measured using dual-energy X-ray absorptiometry. The odds ratios (ORs) and 95% confidence intervals (CIs) of osteoporosis and osteopenia according to green tea consumption were analyzed. Participants who did not consume green tea or consumed less than one cup per day were more likely to have osteopenia of the lumbar spine or femur than those who consumed it once to three times a day (OR 1.81 and 1.85, 95% CI, 1.20–2.71; and 1.23–2.77). Moreover, ORs for osteoporosis were 1.91 (95% CI 1.13–3.23) and 1.82 (95% CI 1.09–3.05) in non-consumers and consumers who drank less than one cup per day, respectively, compared with the reference group. These results support that green tea consumption may have benefits on bone health.
Endothelium-Independent Relaxation of Vascular Smooth Muscle Induced by Persimmon-Derived Polyphenol Phytocomplex in Rats
Authors: Kudo Risa , Yuui Katsuya , Kasuda Shogo
Published: December 2021

The vasorelaxant effect of polyphenols is well known, and the mortality rate due to coronary artery disease is low in people who consume polyphenol-containing foods. We aimed to elucidate the mechanism by which polyphenols derived from persimmon juice (PJ) and persimmon leaves (PLs) induce vasorelaxation and suppress vasocontraction in the superior mesenteric arteries isolated from male Sprague Dawley rats. Vasocontraction was induced with 1 µM phenylephrine, and polyphenol-induced vasorelaxation was expressed as a percentage of the previous tone induced by phenylephrine. PJ powder (100 mg/L) induced higher levels of vasorelaxation (mean ± standard error of the mean, 88.6% ± 4.4%) than PLs powder (1 g/L; 72.0% ± 10.8%). Nitric oxide pathway inhibitors (NG-nitro-L-arginine methyl ester + carboxy-PTIO) did not affect persimmon-derived polyphenol-induced vasorelaxation, whereas potassium chloride, tetraethylammonium, and potassium-channel inhibitors did. Vasorelaxation was endothelium independent with both extracts. Phenylephrine-induced vasocontraction was suppressed by pretreatment with PJ and PLs powder, even when inositol triphosphate-mediated Ca2+ release and extracellular Ca2+ influx were inhibited. These results suggest that persimmon-derived polyphenol phytocomplex cause vasorelaxation and inhibit vasocontraction through hyperpolarization of smooth muscle cells. Persimmon-derived polyphenols may be able to prevent cardiovascular diseases caused by abnormal contraction of blood vessels.
Relationship between Motor and Nonmotor Symptoms and Quality of Life in Patients with Parkinson’s Disease
Authors: Candel-Parra Eduardo , Córcoles-Jiménez María Pilar , Delicado-Useros Victoria , Hernández-Martínez Antonio , Molina-Alarcón Milagros
Published: December 2021

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disease that implies a progressive and invalidating functional organic disorder, which continues to evolve till the end of life and causes different mental and physical alterations that influence the quality of life of those affected. Objective: To determine the relationship between motor and nonmotor symptoms and the quality of life of persons with PD. Methods: An analytic, descriptive, cross-sectional study was conducted with patients with different degrees of PD in the Albacete Health district. The estimated sample size required was 155 patients. The instruments used for data collection included a purpose-designed questionnaire and “Parkinson’s Disease Questionnaire” (PDQ-39), which measures eight dimensions and has a global index where a higher score indicates a worse quality of life. A descriptive and bivariate analysis was conducted (SPSS® IBM 24.0). Ethical aspects: informed consent and anonymized data. Results: A strong correlation was found between the number of motor and nonmotor symptoms and global health-related quality of life and the domains mobility, activities of daily living, emotional well-being, cognitive status, and pain (p < 0.05). Receiving pharmacological treatment and taking more than four medicines per day was significantly associated with a worse quality of life (p < 0.05). Patients who had undergone surgical treatment did not show better global quality of life (p = 0.076). Conclusions: All nonmotor symptoms and polypharmacy were significantly associated with a worse global quality of life.
Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?
Authors: Lukashenko Mariia V. , Gavrilova Natalia Y. , Bregovskaya Anna V. , Soprun Lidiia A. , Churilov Leonid P. , Petropoulos Ioannis N. , Malik Rayaz A , Shoenfeld Yehuda
Published: December 2021

Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.
Inclusion Complexes of Rifampicin with Native and Derivatized Cyclodextrins: In Silico Modeling, Formulation, and Characterization
Authors: Anjani Qonita Kurnia , Domínguez-Robles Juan , Utomo Emilia , Font María , Martínez-Ohárriz María Cristina , Permana Andi Dian , Cárcamo-Martínez Álvaro , Larrañeta Eneko , Donnelly Ryan F.
Published: December 2021

Inclusion complexation of rifampicin (RIF) with several types of cyclodextrins (βCD, hydroxypropyl-βCD, γCD, hydroxypropyl-γCD) in aqueous solutions at different pH values was investigated to assess the interactions between RIF and cyclodextrins (CDs). Molecular modeling was performed to determine the possible interactions between RIF and CDs at several pH values. The inclusion complexes were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, and scanning electron microscopy. Moreover, this study evaluated the dissolution profile and antibacterial activity of the formed complexes. Phase solubility analysis suggested the formation of RIF-CD affirmed 1:1 stoichiometry at all pH values (except RIF-βCD at pH 4.0 and both βCD and γCD at pH 9.0). The inclusion complexation of RIF with CD successfully increased the percentage of RIF released in in vitro studies. The inclusion complexes of RIF exhibited more than 60% of RIF released in 2 h which was significantly higher (p < 0.05) than release of pure RIF, which was only less than 10%. Antibacterial activity of RIF-CD complexes (measured by the minimum inhibitory concentration of RIF against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) was lower for both RIF-βCD and RIF-HPγCD at pH 7.0 to pure RIF suspension. In conclusion, this work reports that both βCD and γCD can be used to enhance the solubility of RIF and thus, improve the effectivity of RIF by decreasing the required daily dose of RIF for the treatment of bacterial infections.
Baloxavir Marboxil: An Original New Drug against Influenza
Authors: Dufrasne François
Published: December 2021

Baloxavir marboxil is a new drug developed in Japan by Shionogi to treat seasonal flu infection. This cap-dependent endonuclease inhibitor is a prodrug that releases the biologically active baloxavir acid. This new medicine has been marketed in Japan, the USA and Europe. It is well tolerated (more than 1% of the patients experienced diarrhea, bronchitis, nausea, nasopharyngitis, and headache), and both influenza A and B viruses are sensitive, although the B strain is more resistant due to variations in the amino acid residues in the binding site. The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks. It has been also introduced in a recent clinical trial against COVID-19 with favipiravir.
Optical Properties of Crystalline Lactose Fluidized with Dilutions of Various Substances in the Terahertz Frequency Range
Authors: Baranova Anna , Lykina Anastasiya , Antonova Daria , Smolyanskaya Olga
Published: December 2021

Lactose is a commonly used component of pharmaceutical medications in tablet form. It was previously shown that lactose changes conformationally after saturation in fluidized beds with active pharmaceutical ingredients obtained by repeated dilution of antibodies to interferon-gamma in combination with an external intensive vibration treatment. Moreover, it was revealed that these solutions are self-organized dispersed systems in which nano-objects are formed. Their biological activity and mechanism of action were previously established as well. The current work was dedicated to investigating the optical properties of fluidized lactose powders in the terahertz frequency range. Spectral analyses of powders of crystalline lactose saturated in fluidized beds with a diluted solution of either glycine buffer, antibodies to interferon-gamma, or water were carried out, intact lactose served as a control. All powders were tableted before testing. In the course of the study, the macroscopic parameters of the tablets were established, at which they had a stable shape and their THz optical properties had no parasitic diffraction losses. These tablets were analyzed using terahertz time-domain spectroscopy in the frequency range of 0.2–2.6 THz. The differentiation between the spectra was conducted using a principal component analysis. The differences between intact lactose and the lactose saturated with any of studied solutions were demonstrated. Additionally, lactose saturated with solutions of multiple dilutions of a substance (antibodies or glycine buffer) differed not only from intact lactose, but also from lactose saturated with a diluted solution of water. Moreover, discrimination of lactose formulations saturated with different substances (antibodies or glycine buffer) was also possible. Additionally, intact lactose differed from lactose saturated with diluted water. The methods reported could be useful for the quality control of the medications based on the technology of repeated dilution of an original substance.
“Smart” Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy
Authors: Mordovina Ekaterina A. , Plastun Valentina O. , Abdurashitov Arkady S. , Proshin Pavel I. , Raikova Svetlana V. , Bratashov Daniil N. , Inozemtseva Olga A. , Goryacheva Irina Yu. , Sukhorukov Gleb B. , Sindeeva Olga A.
Published: December 2021

Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved. Here, we demonstrate the fabrication of polylactic acid (PLA) “smart” films with microchamber arrays. These microchambers contain ceftriaxone as a payload in concentrations ranging from 12 ± 1 μg/cm2 to 38 ± 8 μg/cm2, depending on the patterned film thickness formed by the different PLA concentrations in chloroform. In addition, the release profile of the antibiotic can be prolonged up to 72 h in saline. At the same time, on the surface of agar plates, the antibiotic release time increases up to 96 h, which has been confirmed by the growth suppression of the Staphylococcus aureus bacteria. The efficient loading and optimal release rate are obtained for patterned films formed by the 1.5 wt % PLA in chloroform. The films produced from 1.5 and 2 wt % PLA solutions (thickness—0.42 ± 0.12 and 0.68 ± 0.16 µm, respectively) show an accelerated ceftriaxone release upon the trigger of the therapeutic ultrasound, which impacted as an expansion of the bacterial growth inhibition zone around the samples. Combining prolonged drug elution with the on-demand release ability of large cargo amount opens up new approaches for personalized and custom-tunable antibacterial therapy.
Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers’ Performance In Vitro and In Vivo
Authors: Shipunova Victoria O. , Kovalenko Vera L. , Kotelnikova Polina A. , Sogomonyan Anna S. , Shilova Olga N. , Komedchikova Elena N. , Zvyagin Andrei V. , Nikitin Maxim P. , Deyev Sergey M.
Published: December 2021

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial–mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.
Single-Molecule Clustering for Super-Resolution Optical Fluorescence Microscopy
Authors: Joshi Prakash , Mondal Partha Pratim
Published: December 2021

Molecular assembly in a complex cellular environment is vital for understanding underlying biological mechanisms. Biophysical parameters (such as single-molecule cluster density, cluster-area, pairwise distance, and number of molecules per cluster) related to molecular clusters directly associate with the physiological state (healthy/diseased) of a cell. Using super-resolution imaging along with powerful clustering methods (K-means, Gaussian mixture, and point clustering), we estimated these critical biophysical parameters associated with dense and sparse molecular clusters. We investigated Hemaglutinin (HA) molecules in an Influenza type A disease model. Subsequently, clustering parameters were estimated for transfected NIH3T3 cells. Investigations on test sample (randomly generated clusters) and NIH3T3 cells (expressing Dendra2-Hemaglutinin (Dendra2-HA) photoactivable molecules) show a significant disparity among the existing clustering techniques. It is observed that a single method is inadequate for estimating all relevant biophysical parameters accurately. Thus, a multimodel approach is necessary in order to characterize molecular clusters and determine critical parameters. The proposed study involving optical system development, photoactivable sample synthesis, and advanced clustering methods may facilitate a better understanding of single molecular clusters. Potential applications are in the emerging field of cell biology, biophysics, and fluorescence imaging.
Anti-Melanogenic Activity of Calocedrus formosana Wood Essential Oil and Its Chemical Composition Analysis
Authors: Hsiao Wen-Wei , Kumar K. J. Senthil , Lee Hui-Ju , Tsao Nai-Wen , Wang Sheng-Yang
Published: December 2021

Calocedrus formosana (Cupressaceae) is one of the five precious woods of Taiwan. In this study, we investigated the anti-melanogenic activity of C. formosana wood essential oil (CFEO) and its bioactive components in vitro. Initially, CFEO exhibited strong mushroom tyrosinase activity in the cell-free mushroom tyrosinase assay system with an IC50 value of 2.72 µg/mL. Next, treatment with CFEO significantly as well as dose-dependently reduced a combination of α-melanocyte-stimulating hormone and forskolin (α-MSH-FSK)-induced melanin synthesis in B16-F10 cells. Indeed, 80 μg/mL CFEO completely inhibited melanin production, which is similar to that of control cells. Further studies revealed that treatment with CFEO significantly inhibited melanogenesis regulatory proteins, including TRP-1, TRP-2, and MITF, whereas tyrosinase was unaffected by either α-MSH-FSK or CFEO. In addition, the composition of the CFEO was characterized. The major components of CFEO were α-terpineol (23.47%), shonanic acid (10.45%), terpinen-4-ol (12.23%), thymol (5.3%), piperitone (3.44%), berbenone (2.81%), thujic acid (1.65%), and chaminic acid (0.13%). Among them, shonanic acid (1), thujic acid (2), and chaminic acid (3) were uncommon constitutes in essential oils, which could be the index compounds of CFEO, and the structure of these compounds were confirmed by spectral analysis. Furthermore, we found that thymol is an active ingredient responsible for CFEO’s anti-melanogenic activity. Based on these results, we suggest that CFEO or thymol could be a potential candidate for the development of skin whitening products for cosmetic purposes.
Mechanism of Thermochromic and Self-Repairing of Waterborne Wood Coatings by Synergistic Action of Waterborne Acrylic Microcapsules and Fluorane Microcapsules
Authors: Yan Xiaoxing , Zhao Wenting , Wang Lin
Published: December 2021

The fluorane thermochromic microcapsules and waterborne acrylic resin microcapsules were added into waterborne coatings at the same time to prepare intelligent waterborne coating film with dual functions of color change and self-repairing. The coating film prepared by adding 15.0% fluorane microcapsules and 5.0% waterborne acrylic resin microcapsules to the primer at the same time had better comprehensive properties. At this time, the coating film changed from yellow to colorless. The repair rate of the coating film was 58.4%. When the temperature was lower than 32 °C, waterborne acrylic resin microcapsules can improve the thermochromic performance of the coating film with fluorane microcapsules. Waterborne acrylic resin microcapsules can alleviate the color change of coating film with fluorane microcapsules. The fluorane microcapsules can improve the self-repairing performance of coating film with waterborne acrylic resin microcapsules. The results lay a theoretical and technical foundation for multifunctional coating film.
Arithmetic Relationship between Fracture Load and Material Thickness of Resin-Based CAD-CAM Restorative Materials
Authors: Graf Tobias , Schweiger Josef , Güth Jan-Frederik , Sciuk Thomas , Schubert Oliver , Erdelt Kurt-Jürgen
Published: December 2021

Data on the long-term behavior of computer-aided designed/computer-aided manufactured (CAD-CAM) resin-based composites are sparse. To achieve higher predictability on the mechanical behavior of these materials, the aim of the study was to establish a mathematical relationship between the material thickness of resin-based materials and their fracture load. The tested materials were Lava Ultimate (LU), Cerasmart (GC), Enamic (EN), and Telio CAD (TC). For this purpose, 60 specimens were prepared, each with five different material thicknesses between 0.4 mm and 1.6 mm (N = 60, n = 12). The fracture load of all specimens was determined using the biaxial flexural strength test (DIN EN ISO 6872). Regression curves were fitted to the results and their coefficient of determination (R2) was computed. Cubic regression curves showed the best R2 approximation (LU R2 = 0.947, GC R2 = 0.971, VE R2 = 0.981, TC R2 = 0.971) to the fracture load values. These findings imply that the fracture load of all tested resin-based materials has a cubic relationship to material thickness. By means of a cubic equation and material-specific fracture load coefficients, the fracture load can be calculated when material thickness is given. The approach enables a better predictability for resin-based restorations for the individual patient. Hence, the methodology might be reasonably applied to other restorative materials.
Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
Authors: Lecot Nicole , Dávila Belén , Sánchez Carina , Fernández Marcelo , González Mercedes , Cabral Pablo , Cerecetto Hugo , Glisoni Romina
Published: December 2021

2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to 14 times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).
Preparation of Melamine/Rice Husk Powder Coated Shellac Microcapsules and Effect of Different Rice Husk Powder Content in Wall Material on Properties of Wood Waterborne Primer
Authors: Yan Xiaoxing , Li Wenbo , Han Yan , Yin Taiyu
Published: December 2021

The melamine/rice husk powder-coated shellac microcapsules were prepared by in-situ polymerization with melamine resin mixed with rice husk powder as microcapsule wall material and shellac as microcapsule core material. The effect of the addition amount of microcapsules with different wall material ratios on the performance of wood waterborne primer coating was investigated. The results show that the most important factor affecting the performance of microcapsules is the content of rice husk powder. Through the preparation and analysis of shellac microcapsule primer coating coated with melamine/rice husk powder, when the content of microcapsule powder is 0–6%, it has little effect on the optical properties of wood waterborne primer coating, and the microcapsule with 5.5% rice husk powder has little effect on the color difference of primer coating. The coating hardness increases with the increase of rice husk powder content in wall material. When the rice husk powder content in wall material is more than 5.5%, the coating hardness reaches the best. When the content of microcapsule powder is 3.0–9.0%, the adhesion of the coating is better, and the coating with rice husk powder content of 5.5% in microcapsule wall material has better impact resistance. When the content of rice husk powder was 5.5% and the content of microcapsule powder was 6%, the elongation at break of the primer coating was the highest and the tensile resistance was the best. The composition of wood waterborne primer did not change after adding microcapsule. The water-based primer with microcapsule has better aging resistance. The water-based primer coating with rice husk powder content of 5.5% and the addition amount of 6% had the best comprehensive performance, which lays the technical reference for the toughness and self-repairing of the waterborne wood coatings.
Transparent PC/PMMA Blends with Enhanced Mechanical Properties via Reactive Compounding of Functionalized Polymers
Authors: Bubmann Tobias , Seidel Andreas , Ruckdäschel Holger , Altstädt Volker
Published: December 2021

Reactive compounding of terminally phenolic OH-functionalized polycarbonate (PC) with epoxy-functionalized polymethylmethacrylate (PMMA) prepared by copolymerization with glycidyl methacrylate was investigated. It was spectroscopically demonstrated that a PC/PMMA copolymer was formed during the melt reaction of the functional groups. Zirconium acetylacetonate could catalytically accelerate this reaction. Correlations of the phenomenological (optical and mechanical) properties with the molecular level and mesoscopic (morphological) structure were discussed. By the investigated reactive compounding process, transparent PC/PMMA blends with two-phase morphologies were obtained in a continuous twin-screw extruder, which, for the first time, combined the high transmission of visible light with excellent mechanical performance (e.g., synergistically improved tensile and flexural strength and high scratch resistance). The transparency strongly depended on (a) the degree of functionalization in both PC and PMMA, (b) the presence of the catalyst, and (c) the residence time of the compounding process. The in-situ-formed PC/PMMA copolymer influenced the observed macroscopic properties by (a) a decrease in the interphase tension, leading to improved and stabilized phase dispersion, (b) the formation of a continuous gradient of the polymer composition and thus of the optical refractive indices in a diffuse mesoscopic interphase layer separating the PC and PMMA phases, and (c) an increase in the phase adhesion between PC and PMMA due to mechanical polymer chain entanglement in this interphase.
Strengthening Cellulose Nanopaper via Deep Eutectic Solvent and Ultrasound-Induced Surface Disordering of Nanofibers
Authors: Batishcheva Elizaveta V. , Sokolova Darya N. , Fedotova Veronika S. , Sokolova Maria P. , Nikolaeva Alexandra L. , Vakulyuk Alexey Y. , Shakhbazova Christina Y. , Ribeiro Mauro Carlos Costa , Karttunen Mikko , Smirnov Michael A.
Published: December 2021

The route for the preparation of cellulose nanofiber dispersions from bacterial cellulose using ethylene glycol- or glycerol-based deep eutectic solvents (DES) is demonstrated. Choline chloride was used as a hydrogen bond acceptor and the effect of the combined influence of DES treatment and ultrasound on the thermal and mechanical properties of bacterial cellulose nanofibers (BC-NFs) is demonstrated. It was found that the maximal Young’s modulus (9.2 GPa) is achieved for samples prepared using a combination of ethylene glycol-based DES and ultrasound treatment. Samples prepared with glycerol-based DES combined with ultrasound exhibit the maximal strength (132 MPa). Results on the mechanical properties are discussed based on the structural investigations that were performed using FTIR, Raman, WAXD, SEM and AFM measurements, as well as the determination of the degree of polymerization and the density of BC-NF packing during drying with the formation of paper. We propose that the disordering of the BC-NF surface structure along with the preservation of high crystallinity bulk are the key factors leading to the improved mechanical and thermal characteristics of prepared BC-NF-based papers.
Sliding Dynamics of Ring Chains on Two Asymmetric/Symmetric Chains in a Simple Slide-Ring Gel
Authors: Wu Jiaxin , Guo Fuchen , Li Ke , Zhang Linxi
Published: December 2021

The sliding dynamics along two asymmetric/symmetric axial chains of ring chains linked by a linear chainis investigated using molecular dynamics (MD) simulations. A novel sub-diffusion behavior is observed for ring chains sliding along eithera fixed rod-like chain or fluctuating axial chain on asymmetric/symmetric axial chainsat the intermediate time range due to their strongly interplay between two ring chains. However, two ring chains slide in the normal diffusion at along time range because their sliding dynamics can be regarded as an overall motion of two ring chains. For ring chains sliding on two symmetric/asymmetricaxial chains, the diffusion coefficient D of ring chains relies on the bending energy of axial chains (Kb) as well as the distance of two axial chains (d). There exists a maximum diffusion coefficient Dmax at d = d* in which ring chains slide at the fastest velocity due to the maximum conformational entropy for the linking chain between two ring chainsat d = d*. Ring chain slide on fixed rod-like axial chainsfaster in the symmetric axial chain case than that in the asymmetric axial chain case. However, ring chains slide on fluctuatingaxial chainsslower in the symmetric axial chain case than that in the asymmetric axial chain case. This investigation can provide insights into the effects of the linked chain conformation on the sliding dynamics of ring chains in a slide-ring gel.
Many-Objective Optimization and Decision-Making Method for Selective Assembly of Complex Mechanical Products Based on Improved NSGA-III and VIKOR
Authors: Pan Rongshun , Yu Jiahao , Zhao Yongman
Published: December 2021

In Industry 4.0, data are sensed and merged to drive intelligent systems. This research focuses on the optimization of selective assembly of complex mechanical products (CMPs) under intelligent system environment conditions. For the batch assembly of CMPs, it is difficult to obtain the best combinations of components from combinations for simultaneous optimization of success rate and multiple assembly quality. Hence, the Taguchi quality loss function was used to quantitatively evaluate each assembly quality and the assembly success rate is combined to establish a many-objective optimization model. The crossover and mutation operators were improved to enhance the ability of NSGA-III to obtain high-quality solution set and jump out of a local optimal solution, and the Pareto optimal solution set was obtained accordingly. Finally, considering the production mode of Human–Machine Intelligent System interaction, the optimal compromise solution is obtained by using fuzzy theory, entropy theory and the VIKOR method. The results show that this work has obvious advantages in improving the quality of batch selective assembly of CMPs and assembly success rate and gives a sorting selection strategy for non-dominated selective assembly schemes while taking into account the group benefit and individual regret.
Kinetic Studies of Esterification of Rosin and Pentaerythritol
Authors: Hardhianti Meiga Putri Wahyu , Rochmadi  , Azis Muhammad Mufti
Published: December 2021

Esterification of rosin with pentaerythritol produces rosin pentaerythritol ester (RPE) which is widely used in paint, coating, and pressure-sensitive and hot-melt adhesive industries. Although RPE has excellent valuable applications and has been industrially produced, studies on the reaction kinetics have not been widely reported in the present literature. This work proposed a kinetic study of RPE synthesis by including a series of consecutive reactions forming mono-, di-, tri-, and tetra-ester with decarboxylation of rosin as a side reaction in the kinetics model. For esterification, the reaction rates were determined by the second-order kinetic model. The first-order kinetic order was proposed for decarboxylation. Kinetic experiments were performed at a temperature range of 260 °C to 290 °C. The initial molar ratio of pentaerythritol to rosin (in the mole of OH/COOH) used was between 0.8 and 1.2. A small amount of samples were withdrawn in certain time interval. The sample was analyzed to evaluate their acid and saponification number. Afterward, those experimental data were used to simulate and validate the proposed kinetic model. In general, the proposed model could capture the experimental data well. The resulting activation energies ranged from 65.81 to 129.13 kJ mol−1 for esterification and 233.00 kJ mol−1 for decarboxylation. This model also offers a new insight that correlates well with tetra-ester formation and the softening point.
mSHAP: SHAP Values for Two-Part Models
Authors: Matthews Spencer , Hartman Brian
Published: December 2021

Two-part models are important to and used throughout insurance and actuarial science. Since insurance is required for registering a car, obtaining a mortgage, and participating in certain businesses, it is especially important that the models that price insurance policies are fair and non-discriminatory. Black box models can make it very difficult to know which covariates are influencing the results, resulting in model risk and bias. SHAP (SHapley Additive exPlanations) values enable interpretation of various black box models, but little progress has been made in two-part models. In this paper, we propose mSHAP (or multiplicative SHAP), a method for computing SHAP values of two-part models using the SHAP values of the individual models. This method will allow for the predictions of two-part models to be explained at an individual observation level. After developing mSHAP, we perform an in-depth simulation study. Although the kernelSHAP algorithm is also capable of computing approximate SHAP values for a two-part model, a comparison with our method demonstrates that mSHAP is exponentially faster. Ultimately, we apply mSHAP to a two-part ratemaking model for personal auto property damage insurance coverage. Additionally, an R package (mshap) is available to easily implement the method in a wide variety of applications.
Using Remote Sensing and Machine Learning to Locate Groundwater Discharge to Salmon-Bearing Streams
Authors: Gerlach Mary E. , Rains Kai C. , Guerrón-Orejuela Edgar J. , Kleindl William J. , Downs Joni , Landry Shawn M. , Rains Mark C.
Published: December 2021

We hypothesized topographic features alone could be used to locate groundwater discharge, but only where diagnostic topographic signatures could first be identified through the use of limited field observations and geologic data. We built a geodatabase from geologic and topographic data, with the geologic data only covering ~40% of the study area and topographic data derived from airborne LiDAR covering the entire study area. We identified two types of groundwater discharge: shallow hillslope groundwater discharge, commonly manifested as diffuse seeps, and aquifer-outcrop groundwater discharge, commonly manifested as springs. We developed multistep manual procedures that allowed us to accurately predict the locations of both types of groundwater discharge in 93% of cases, though only where geologic data were available. However, field verification suggested that both types of groundwater discharge could be identified by specific combinations of topographic variables alone. We then applied maximum entropy modeling, a machine learning technique, to predict the prevalence of both types of groundwater discharge using six topographic variables: profile curvature range, with a permutation importance of 43.2%, followed by distance to flowlines, elevation, topographic roughness index, flow-weighted slope, and planform curvature, with permutation importance of 20.8%, 18.5%, 15.2%, 1.8%, and 0.5%, respectively. The AUC values for the model were 0.95 for training data and 0.91 for testing data, indicating outstanding model performance.