bluuebunny/crossref_metadata_2025 huggingface dataset:
IBF-R Regulates IRE1α Post-Translational Modifications and ER Stress in High-Fat Diet-Induced Obese Mice
Authors: Lee Hwa-Young , Lee Geum-Hwa , Yoon Young , Hoang The-Hiep , Chae Han-Jung
Published: January 2022

Obesity is a global health issue linked to the heightened risk of several chronic diseases. Rhus verniciflua (RV) is a traditional food supplement used for a range of pharmacological effects such as antitumor, antioxidant, α-glucosidase inhibitory effects, hepatitis, and arthritis. Despite the traditional medicinal values, scientific evidence for its application in obesity is inadequate and unclear. Thus, this investigation was designed to evaluate the anti-obesity effects of IBF-R, an RV extract, using a high-fat diet (HFD) model. The study has six groups: chow diet group; chow diet with 80 mg/kg IBF-R; HFD group; IBF-R group with 20, 40, and 80 mg/kg. IBF-R supplementation significantly regulated the weight gain than the HFD fed mice. Further, IBF-R supplementation lowered the expressions of adipogenic transcription factors such as SREBP-1c, C/EBPα, FAS, and PPAR-γ in white adipose tissue (WAT) of diet-induced obese mice. In addition, IBF-R supplementation reduced the lipogenic gene expression while enhancing genes was related to fatty acid oxidation. Obesity is linked to redox-based post-translational modifications (PTMs) of IRE1α such as S-nitrosylation, endoplasmic reticulum (ER) stress, and chronic metabolic inflammation. The administration of IBF-R inhibits these PTMs. Notably, IBF-R administration significantly enhanced the expression of AMPK and sirtuin 1 in WAT of HFD-fed mice. Together, these findings reveal the IRE1α S-nitrosylation-inflammation axis as a novel mechanism behind the positive implications of IBF-R on obesity. In addition, it lays a firm foundation for the development of Rhus verniciflua extract as a functional ingredient in the food and pharmaceutical industries.
Labelling Assessment of Greek “Quality Label” Prepacked Cheeses as the Basis for a Branded Food Composition Database
Authors: Katsouri Evangelia , Zampelas Antonios , Drosinos Eleftherios H. , Nychas George-John E.
Published: January 2022

A labelling assessment study of Greek prepacked “quality label” cheeses was conducted with a view to provide an overview of the whole category. In total, 158 prepacked products belonging to 19 “quality label” cheeses were identified in the Greek market. Among them, Feta had the highest share followed by Kasseri, Graviera Kritis, Kefalograviera and Ladotyri Mitilinis with 81, 16, 15, 11 and 9 products found in the market, respectively. For the rest of the 14 cheeses, the share was limited, ranging from 1 to 4. All labelling indications, nutritional information, claims and other labelling data were recorded and analysed in relation to their compliance against European food law requirements. The results of the analysis showed that for only 6 of the 19 cheeses, all products fully complied with EU labelling legislation. Among the 14 mandatory labelling requirements, the lowest overall compliance was observed for allergens declaration (65%). The analysis of the nutritional data showed a remarkable variability between cheeses and products. Differences in the nutritional characteristics were more pronounced among soft, semi-hard, hard and whey cheese. The above data were entered into an archival database. Application of global harmonisation and standardisation guidelines and tools lead to the initialisation of a branded food composition database (BFCD), conceptualising a specialised database for “quality label” foods.
Awareness, Knowledge and Attitude towards ‘Superfood’ Kale and Its Health Benefits among Arab Adults
Authors: Alfawaz Hanan A. , Wani Kaiser , Alrakayan Haya , Alnaami Abdullah M. , Al-Daghri Nasser M.
Published: January 2022

This cross-sectional online survey aimed to determine the awareness of Arab adults on the benefits of consuming nutrient-dense foods, such as kale. A total of 1200 respondents completed the survey. The questionnaire included questions related to socio-economic information, e.g., whether the participants have consumed kale, if they observed any health effects, and 13 other questions to test their knowledge on this superfood. Only 276 (23%) of the participants had previously consumed kale, with 64.5% reporting favorable health outcomes, the most common of which was weight reduction, and only 17.8% reporting side effects, such as constipation and gastrointestinal irritation. From the 13 kale knowledge questions, the average total knowledge score, scaled from 0 to 10, was 3.5 and 3.7 for males and females, respectively. The regression analysis revealed that age, income, and educational status were significant contributors for predicting better knowledge scores, as older individuals with a higher income and higher education scored higher (odds ratio of 2.96, 2.00 and 4.58, respectively). To summarize, there is a dearth of awareness about kale and its health benefits in Saudi Arabia. Kale should be promoted as a super food in all segments, particularly among the younger, lower-income, and less-educated sections of the population.
Design Simulation of Czerny–Turner Configuration-Based Raman Spectrometer Using Physical Optics Propagation Algorithm
Authors: Naeem Muddasir , Fatima Noor-ul-ain , Hussain Mukhtar , Imran Tayyab , Bhatti Arshad Saleem
Published: January 2022

We report the design simulation of the Raman spectrometer using Zemax optical system design software. The design is based on the Czerny–Turner configuration, which includes an optical system consisting of an entrance slit, two concave mirrors, reflecting type diffraction grating and an image detector. The system’s modeling approach is suggested by introducing the corresponding relationship between detector pixels and wavelength, linear CCD receiving surface length and image surface dimension. The simulations were carried out using the POP (physical optics propagation) algorithm. Spot diagram, relative illumination, irradiance plot, modulation transfer function (MTF), geometric and encircled energy were simulated for designing the Raman spectrometer. The simulation results of the Raman spectrometer using a 527 nm wavelength laser as an excitation light source are presented. The present optical system was designed in sequential mode and a Raman spectrum was observed from 530 nm to 630 nm. The analysis shows that the system’s image efficiency was quite good, predicting that it could build an efficient and cost-effective Raman spectrometer for optical diagnostics.
Metabolic Capacity Differentiates Plenodomus lingam from P. biglobosus Subclade ‘brassicae’, the Causal Agents of Phoma Leaf Spotting and Stem Canker of Oilseed Rape (Brassica napus) in Agricultural Ecosystems
Authors: Frąc Magdalena , Kaczmarek Joanna , Jędryczka Małgorzata
Published: January 2022

In contrast to the long-lasting taxonomic classification of Plenodomus lingam and P. biglobosus as one species, formerly termed Leptosphaeria maculans, both species form separate monophyletic groups, comprising sub-classes, differing considerably with epidemiology towards Brassicaceae plants. Considering the great differences between P. lingam and P. biglobosus, we hypothesized their metabolic capacities vary to a great extent. The experiment was done using the FF microplates (Biolog Inc., Hayward, CA, USA) containing 95 carbon sources and tetrazolium dye. The fungi P. lingam and P. biglobosus subclade ‘brassicae’ (3 isolates per group) were cultured on PDA medium for 6 weeks at 20 °C and then fungal spores were used as inoculum of microplates. The test was carried out in triplicate. We have demonstrated that substrate richness, calculated as the number of utilized substrates (measured at λ490 nm), and the number of substrates allowing effective growth of the isolates (λ750 nm), showed significant differences among tested species. The most efficient isolate of P. lingam utilized 36 carbon sources, whereas P. biglobosus utilized 60 substrates. Among them, 25–29 carbon sources for P. lingam and 34–48 substrates for P. biglobosus were efficiently used, allowing their growth. Cluster analysis based on Senath criteria divided P. biglobosus into two groups and P. lingam isolates formed one group (33% similarity). We deduce the similarities between the tested species help them coexist on the same host plant and the differences greatly contribute to their different lifestyles, with P. biglobosus being less specialized and P. lingam coevolving more strictly with the host plant.
Immunization Trials with Recombinant Major Sperm Protein of the Bovine Lungworm Dictyocaulus viviparus
Authors: Springer Andrea , von Holtum Christian , von Samson-Himmelstjerna Georg , Strube Christina
Published: January 2022

The lungworm Dictyocaulus viviparus is one of the most economically important bovine parasites in temperate climate regions. Following infection, D. viviparus induces a temporary protective immunity, and a vaccine based on attenuated, infective larvae is commercially available. However, due to several disadvantages of the live vaccine, the development of a recombinant subunit vaccine is highly desirable. Therefore, the major sperm protein (MSP), which is essential for the parasite’s reproduction, was tested as a recombinantly Escherichia coli-expressed glutathione-S-transferase (GST)-fused vaccine antigen in immunization trials with two different adjuvants, Quil A and Al(OH)3. Calves (N = 4 per group) were immunized on study day (SD) 0, 21 and 42 and given a challenge infection on SD 63–65. The two control groups received only the respective adjuvant. Based on geometric means (GM), a 53.64% reduction in larvae per female worm was observed in the rMSP Quil A group vs. its control group (arithmetic means (AM): 54.43%), but this difference was not statistically significant. In the rMSP Al(OH)3 group, the mean number of larvae per female worm was even higher than in the respective control group (GM: 9.24%, AM: 14.14%). Furthermore, male and female worm burdens and the absolute number of larvae did not differ significantly, while the Al(OH)3 control group harbored significantly longer worms than the vaccinated group. Vaccinated animals showed a rise in rMSP-specific antibodies, particularly IgG and its subclass IgG1, and the native protein was detected by immunoblots. Although rMSP alone did not lead to significantly reduced worm fecundity, it might still prove useful as part of a multi-component vaccine.
News Insights into the Host-Parasite Interactions of Amyloodiniosis in European Sea Bass: A Multi-Modal Approach
Authors: Massimo Michela , Volpatti Donatella , Galeotti Marco , Bron James E. , Beraldo Paola
Published: January 2022

Amyloodiniosis is a disease resulting from infestation by the ectoparasitic dinoflagellate Amyloodinium ocellatum (AO) and is a threat for fish species such as European sea bass (ESB, Dicentrarchus labrax), which are farmed in lagoon and land-based rearing sites. During the summer, when temperatures are highest, mortality rates can reach 100%, with serious impacts for the aquaculture industry. As no effective licensed therapies currently exist, this study was undertaken to improve knowledge of the biology of AO and of the host-parasite relationship between the protozoan and ESB, in order to formulate better prophylactic/therapeutic treatments targeting AO. To achieve this, a multi-modal study was performed involving a broad range of analytical modalities, including conventional histology (HIS), immunohistochemistry (IHC) and confocal laser scanning microscopy (CLSM). Gills and the oro-pharyngeal cavity were the primary sites of amyloodiniosis, with hyperplasia and cell degeneration more evident in severe infestations (HIS). Plasmacells and macrophages were localised by IHC and correlated with the parasite burden in a time-course experimental challenge. CLSM allowed reconstruction of the 3D morphology of infecting trophonts and suggested a protein composition for its anchoring and feeding structures. These findings provide a potential starting point for the development of new prophylactic/therapeutic controls.
Predominance of Acinetobacter spp., Harboring the blaIMP Gene, Contaminating the Hospital Environment in a Tertiary Hospital in Mwanza, Tanzania: A Cross-Sectional Laboratory-Based Study
Authors: Silago Vitus , Mruma Eveline C. , Msemwa Betrand , Mtemisika Conjester I. , Phillip Shukurani , Ndagula Reuben A. , Said Maria M. , Mushi Martha F. , Mshana Stephen E.
Published: January 2022

Data on colonization and hospital contamination of carbapenem-resistant Gram-negative bacteria (CR-GNB) are limited in low- and middle-income countries. We designed this study to determine the prevalence and co-existence of carbapenemase genes among CR-GNB isolated from clinical, colonization, and hospital environmental samples at a tertiary hospital in Mwanza, Tanzania. The modified Hodge test (MHT), the combined disk test (CDT), and the double-disk synergy test (DDST) were used for the phenotypic detection of carbapenemases. A multiplex PCR assay was used to detect blaIMP and blaKPC, and a singleplex PCR assay was used to detect blaOXA-48. Data were analyzed by STATA version 13.0. Overall, 68.8% (44/64) of the CR-GNB had at least one phenotype by phenotypic methods, whereby 60.9% (39/64) were both CDT and DDST positive and 31.3% (20/64) were MHT positive. A total of 23/64 (35.9%) had at least one of the genes tested with the predominance of blaIMP (91.3%; 21/23). In addition, 47.7% (21/44) of the CR-GNB phenotypes had at least one gene. Around 47.8% (11/23) of the CR-GNB carried multiple genes encoding for carbapenem resistance, with the maximum co-existence of blaIMP/blaKPC/blaOXA-48 (45.5%; 5/11). The majority of carbapenem-resistant genes were detected in Acinetobacter spp. (82.6%; 19/23) and isolated from bed swabs (69.6%; 16/23). Acinetobacter spp. carrying the blaIMP gene predominantly contaminated the hospital environment. Therefore, we recommend routine decontamination of inanimate hospital surfaces, including patient beds.
Quantitative Risk Assessment of African Swine Fever Introduction into Spain by Legal Import of Live Pigs
Authors: Muñoz-Pérez Carolina , Bosch Jaime , Ito Satoshi , Martínez-Avilés Marta , Sánchez-Vizcaíno José Manuel
Published: January 2022

African swine fever (ASF) is a devastating infectious disease of pigs that is threatening the global swine industry at present. The current spread of ASF in Europe and its recent incursion into Germany pose a serious risk to Spain, one of the world’s leading pig producers. A quantitative stochastic risk assessment model was developed to estimate the probability of ASF introduction into Spain via the legal import of live pigs. The results suggest a low annual probability of ASF introduction into Spain (1.07 × 10−4), the highest risk being concentrated in Central European countries (Germany, the Netherlands, Belgium, and Luxembourg) during the months of April and February. The methods and results presented herein could contribute to improving prevention and control strategies and, ultimately, would help reduce the risk of ASF introduction into Spain.
Larger Physique as a Risk Factor for Infantile Appendicitis: A Retrospective Study
Authors: Nishimura Katsuhiro , Terui Keita , Mise Naoko , Matsuura Gen , Nakata Mitsuyuki , Komatsu Shugo , Saito Takeshi , Hishiki Tomoro
Published: January 2022

The clinical features and risk factors of acute appendicitis in infants are unclear. Our aim was to evaluate the association between anthropometrics and the occurrence of infantile appendicitis. This was a retrospective study of infants (<6 years of age) and school-age children (6–10 years of age) of Asian ethnicity who required hospitalization for appendicitis at our two participating institutions between 2004 and 2018. The Z-score for height, body weight, and body mass index (BMI) was compared between the two groups, as well as between patients presenting with perforated and non-perforated appendicitis. The analysis included data from 73 infants and 362 school-age children. Z-scores were greater in infants than in school-age children for height (0.37 versus −0.03, p = 0.003) and body weight (0.12 versus −0.36, p = 0.023), with no between-group difference for the Z-score of BMI. There was no difference in Z-scores for height, weight, and BMI between the perforated and non-perforated appendicitis infant groups. Infants presenting with acute appendicitis were characterized by a larger physique but with normal proportion. This trend was not observed in school-age children. Therefore, larger infants presenting with abdominal pain should be screened for appendicitis.
Synthetic Derivatives against Wild-Type and Non-Wild-Type Sporothrix brasiliensis: In Vitro and In Silico Analyses
Authors: de Souza Lais Cavalcanti dos Santos Velasco , Alcântara Lucas Martins , de Macêdo-Sales Pãmella Antunes , Reis Nathália Faria , de Oliveira Débora Sena , Machado Ricardo Luiz Dantas , Geraldo Reinaldo Barros , dos Santos André Luis Souza , Ferreira Vítor Francisco , Gonzaga Daniel Tadeu Gomes , da Silva Fernando de Carvalho , Castro Helena Carla , Baptista Andréa Regina de Souza
Published: January 2022

Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with parameters similar to itraconazole, was obtained. Three hydrazone derivatives were particularly promising candidates as antifungal agents against itraconazole-resistant S. brasiliensis from the Brazilian hyperendemic region. Since sporotrichosis is a neglected zoonosis currently spreading in Latin America, particularly in Brazil, the present data can contribute to its future control by alternative antifungal drug design against S. brasiliensis, the most virulent and prevalent species of the hyperendemic context.
Crystal Structure, Solubility, and Pharmacokinetic Study on a Hesperetin Cocrystal with Piperine as Coformer
Authors: Liu Yanjie , Yang Fan , Zhao Xiuhua , Wang Siying , Yang Qilei , Zhang Xiaoxue
Published: January 2022

Hesperetin (HES) is a key biological active ingredient in citrus peels, and is one of the natural flavonoids that attract the attention of researchers due to its numerous therapeutic bioactivities that have been identified in vitro. As a bioenhancer, piperine (PIP) can effectively improve the absorption of insoluble drugs in vivo. In the present study, a cocrystal of HES and PIP was successfully obtained through solution crystallization. The single-crystal structure was illustrated and comprehensive characterization of the cocrystal was conducted. The cocrystal was formed by two drug molecules at a molar ratio of 1:1, which contained O–H–O hydrogen bonds between the carbonyl and ether oxygen of PIP and the phenolic hydroxyl group of HES. In addition, a solubility experiment was performed on powder cocrystal in simulated gastrointestinal fluid, and the result revealed that the cocrystal improves the dissolution behavior of HES compared with that of the pure substance. Furthermore, HES’s bioavailability in the cocrystal was six times higher than that of pristine drugs. These results may provide an efficient oral formulation for HES.
Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy
Authors: Gomes Eliza Rocha , Franco Marina Santiago
Published: January 2022

Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.
Imination of Microporous Chitosan Fibers—A Route to Biomaterials with “On Demand” Antimicrobial Activity and Biodegradation for Wound Dressings
Authors: Anisiei Alexandru , Rosca Irina , Sandu Andreea-Isabela , Bele Adrian , Cheng Xinjian , Marin Luminita
Published: January 2022

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers’ characterization was undertaken keeping in mind their application to wound healing. Thus, by FTIR and 1H-NMR spectroscopy, it was confirmed the successful imination of the fibers and the conversion degree of the amine groups of chitosan into imine units. The fiber morphology in terms of fiber diameter, crystallinity, inter- and intra-fiber porosity and strength of intermolecular forces was investigated using scanning electron microscopy, polarized light microscopy, water vapor sorption and thermogravimetric analysis. The swelling ability was estimated in water and phosphate buffer by calculating the mass equilibrium swelling. The fiber biodegradation was explored in five media of different pH, corresponding to different stages of wound healing and the antimicrobial activity against the opportunistic pathogens inflicting wound infection was investigated according to standard tests. The biocompatibility and bioadhesivity were studied on normal human dermal fibroblast cells by direct contact procedure. The dynamic character of the imine linkage of the functionalized fibers was monitored by UV-vis spectroscopy. The results showed that the functionalization of the chitosan microporous nanofibers with antimicrobial agents via imine linkage is a great route towards bio-absorbable wound dressings with “on demand” antimicrobial properties and biodegradation rate matching the healing stages.
Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy
Authors: Hao Yang , Chung Chih Kit , Yu Zhenfeng , Huis in ‘t Veld Ruben V. , Ossendorp Ferry A. , ten Dijke Peter , Cruz Luis J.
Published: January 2022

Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT alone is not sufficient to completely ablate tumors in deep tissues, due to its inherent shortcomings. Therefore, depending on the characteristics and type of tumor, PDT can be combined with surgery, radiotherapy, immunomodulators, chemotherapy, and/or targeted therapy, preferably in a patient-tailored manner. Nanoparticles are attractive delivery vehicles that can overcome the shortcomings of traditional photosensitizers, as well as enable the codelivery of multiple therapeutic drugs in a spatiotemporally controlled manner. Nanotechnology-based combination strategies have provided inspiration to improve the anticancer effects of PDT. Here, we briefly introduce the mechanism of PDT and summarize the photosensitizers that have been tested preclinically for various cancer types and clinically approved for cancer treatment. Moreover, we discuss the current challenges facing the combination of PDT and multiple cancer treatment options, and we highlight the opportunities of nanoparticle-based PDT in cancer therapies.
Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate
Authors: Berzosa Melibea , Nemeskalova Alzbeta , Calvo Alba , Quincoces Gemma , Collantes María , Pareja Felix , Gamazo Carlos , Irache Juan Manuel
Published: January 2022

Enterotoxigenic Escherichia coli (ETEC) represents a major cause of morbidity and mortality in the human population. In particular, ETEC infections affect children under the age of five from low-middle income countries. However, there is no licensed vaccine against this pathogen. ETEC vaccine development is challenging since this pathotype expresses a wide variety of antigenically diverse virulence factors whose genes can be modified due to ETEC genetic plasticity. To overcome this challenge, we propose the use of outer membrane vesicles (OMVs) isolated from two ETEC clinical strains. In these OMVs, proteomic studies revealed the presence of important immunogens, such as heat-labile toxin, colonization factors, adhesins and mucinases. Furthermore, these vesicles proved to be immunogenic after subcutaneous administration in BALB/c mice. Since ETEC is an enteropathogen, it is necessary to induce both systemic and mucosal immunity. For this purpose, the vesicles, free or encapsulated in zein nanoparticles coated with a Gantrez®–mannosamine conjugate, were administered orally. Biodistribution studies showed that the encapsulation of OMVs delayed the transit through the gut. These results were confirmed by in vivo study, in which OMV encapsulation resulted in higher levels of specific antibodies IgG2a. Further studies are needed to evaluate the protection efficacy of this vaccine approach.
Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma
Authors: Malfanti Alessio , Catania Giuseppina , Degros Quentin , Wang Mingchao , Bausart Mathilde , Préat Véronique
Published: January 2022

Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood–brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.
NGIWY-Amide: A Bioinspired Ultrashort Self-Assembled Peptide Gelator for Local Drug Delivery Applications
Authors: Theodoroula Nikoleta F. , Karavasili Christina , Vlasiou Manos C. , Primikyri Alexandra , Nicolaou Christia , Chatzikonstantinou Alexandra V. , Chatzitaki Aikaterini-Theodora , Petrou Christos , Bouropoulos Nikolaos , Zacharis Constantinos K. , Galatou Eleftheria , Sarigiannis Yiannis , Fatouros Dimitrios G. , Vizirianakis Ioannis S.
Published: January 2022

Fibrillar structures derived from plant or animal origin have long been a source of inspiration for the design of new biomaterials. The Asn-Gly-Ile-Trp-Tyr-NH2 (NGIWY-amide) pentapeptide, isolated from the sea cucumber Apostichopus japonicus, which spontaneously self-assembles in water to form hydrogel, pertains to this category. In this study, we evaluated this ultra-short cosmetic bioinspired peptide as vector for local drug delivery applications. Combining nuclear magnetic resonance, circular dichroism, infrared spectroscopy, X-ray diffraction, and rheological studies, the synthesized pentapeptide formed a stiff hydrogel with a high β-sheet content. Molecular dynamic simulations aligned well with scanning electron and atomic-force microscopy studies, revealing a highly filamentous structure with the fibers adopting a helical-twisted morphology. Model dye localization within the supramolecular hydrogel provided insights on the preferential distribution of hydrophobic and hydrophilic compounds in the hydrogel network. That was further depicted in the diffusion kinetics of drugs differing in their aqueous solubility and molecular weight, namely, doxorubicin hydrochloride, curcumin, and octreotide acetate, highlighting its versatility as a delivery vector of both hydrophobic and hydrophilic compounds of different molecular weight. Along with the observed cytocompatibility of the hydrogel, the NGIWY-amide pentapeptide may offer new approaches for cell growth, drug delivery, and 3D bioprinting tissue-engineering applications.
Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors
Authors: Lee Woo Tak , Yoon Johyun , Kim Sung Soo , Kim Hanju , Nguyen Nguyen Thi , Le Xuan Thien , Lee Eun Seong , Oh Kyung Taek , Choi Han-Gon , Youn Yu Seok
Published: January 2022

Combined therapy using photothermal and photodynamic treatments together with chemotherapeutic agents is considered one of the most synergistic treatment protocols to ablate hypoxic tumors. Herein, we sought to fabricate an in situ-injectable PEG hydrogel system having such multifunctional effects. This PEG hydrogel was prepared with (i) nabTM-technique-based paclitaxel (PTX)-bound albumin nanoparticles with chlorin-e6 (Ce6)-conjugated bovine serum albumin (BSA-Ce6) and indocyanine green (ICG), named ICG/PTX/BSA-Ce6-NPs (~175 nm), and (ii) an albumin-stabilized perfluorocarbon (PFC) nano-emulsion (BSA-PFC-NEs; ~320 nm). This multifunctional PEG hydrogel induced moderate and severe hyperthermia (41−42 °C and >48 °C, respectively) at the target site under two different 808 nm laser irradiation protocols, and also induced efficient singlet oxygen (1O2) generation under 660 nm laser irradiation supplemented by oxygen produced by ultrasound-triggered PFC. Due to such multifunctionality, our PEG hydrogel formula displayed significantly enhanced killing of three-dimensional 4T1 cell spheroids and also suppressed the growth of xenografted 4T1 cell tumors in mice (tumor volume: 47.7 ± 11.6 and 63.4 ± 13.0 mm3 for photothermal and photodynamic treatment, respectively, vs. PBS group (805.9 ± 138.5 mm3), presumably based on sufficient generation of moderate heat as well as 1O2/O2 even under hypoxic conditions. Our PEG hydrogel formula also showed excellent hyperthermal efficacy (>50 °C), ablating the 4T1 tumors when the irradiation duration was extended and output intensity was increased. We expect that our multifunctional PEG hydrogel formula will become a prototype for ablation of otherwise poorly responsive hypoxic tumors.
Game-Based Learning in Pharmacy Education
Authors: Oestreich Julie H. , Guy Jason W.
Published: January 2022

Game-based learning (GBL) involves adding game elements to non-game activities to encourage engagement. Pharmacy curricula are required to incorporate active learning to meet accreditation standards. The literature supports that well-designed GBL holds the attention of students and improves knowledge in some instances. Furthermore, these adaptable experiences can be leveraged for a variety of content areas in pharmacy education. Some activities utilized by educators require large amounts of technological expertise, while others involve minimal use of technology. The incorporation of technology can create highly immersive experiences for learners; however, there are barriers (e.g., financial and technology prowess) to implementation compared to simpler designs. One area of GBL that is not well defined in the literature is how to adequately assess student learning outcomes. Most current studies describe subjective attitudes and confidence or assess content knowledge through objective pre- and post-tests. In the future, more defined and connected methods for assessment—such as active demonstrations within the game—will be needed to better incorporate GBL into pharmacy curricula. Based on the collective evidence in the literature, some GBL activities may serve as useful tools to improve pharmacy student engagement and learning.
Hobbes and Spinoza on Sovereign Education
Authors: Kabala Boleslaw Z. , Cook Thomas
Published: January 2022

Most comparisons of Thomas Hobbes and Baruch Spinoza focus on the difference in understanding of natural right. We argue that Hobbes also places more weight on a rudimentary and exclusive education of the public by the state. We show that the difference is related to deeper disagreements over the prospect of Enlightenment. Hobbes is more sanguine than Spinoza about using the state to make people rational. Spinoza considers misguided an overemphasis on publicly educating everyone out of superstition—public education is important, but modes of superstition may remain and must be offset by institutions and a civil religion. The differences are confirmed by Spinoza’s interest in the philosopher who stands apart and whose flourishing may be protected, but not simply brought about, by rudimentary public education. Spinoza’s openness to a wisdom-loving elite in a democracy also sets up an interesting parallel with Thomas Jefferson’s own commitment to the natural aristocracy needed to sustain republicanism. In demonstrating the 17th century philosopher’s skepticism toward using the state exclusively to promote rationality, even as he recognizes the importance of a sovereign pedagogical role and the protection of philosophy, we move to suggest that Spinoza is relevant to contemporary debates about public education and may reinvigorate moral and political discourse in a liberal democracy.
Impact of Mode-Area Dispersion on Nonlinear Pulse Propagation in Gas-Filled Anti-Resonant Hollow-Core Fiber
Authors: Wan Ying , Hasan Md Imran , Chang Wonkeun
Published: January 2022

We numerically investigate the effect of mode-area dispersion in a tubular-type anti-resonant hollow-core fiber by using a modified generalized nonlinear Schrödinger equation that takes into account the wavelength-dependent mode area in its nonlinear term. The pulse evolution dynamics with and without the effect of mode-area dispersion are compared and analyzed. We show that strong dispersion of the mode area in the proximity of the cladding wall thickness-induced resonances has a significant impact on the soliton pulse propagation, resulting in considerable changes in the conversion efficiencies in nonlinear frequency mixing processes. The differences become more prominent when the pump has higher energy and is nearer to a resonance. Hence, the mode-area dispersion must be accounted for when modeling such a case.
Effects of Asymmetric Coupling Strength on Nonlinear Dynamics of Two Mutually Long-Delay-Coupled Semiconductor Lasers
Authors: Liao Bin-Kai , Tseng Chin-Hao , Chu Yu-Chen , Hwang Sheng-Kwang
Published: January 2022

This study investigates the effects of asymmetric coupling strength on nonlinear dynamics of two mutually long-delay-coupled semiconductor lasers through both experimental and numerical efforts. Dynamical maps and spectral features of dynamical states are analyzed as a function of the coupling strength and detuning frequency for a fixed coupling delay time. Symmetry in the coupling strength of the two lasers, in general, symmetrizes their dynamical behaviors and the corresponding spectral features. Slight to moderate asymmetry in the coupling strength moderately changes their dynamical behaviors from the ones when the coupling strength is symmetric, but does not break the symmetry of their dynamical behaviors and the corresponding spectral features. High asymmetry in the coupling strength not only strongly changes their dynamical behaviors from the ones when the coupling strength is symmetric, but also breaks the symmetry of their dynamical behaviors and the corresponding spectral features. Evolution of the dynamical behaviors from symmetry to asymmetry between the two lasers is identified. Experimental observations and numerical predictions agree not only qualitatively to a high extent but also quantitatively to a moderate extent.
Patent Portfolio Analysis of the Synergy between Machine Learning and Photonics
Authors: Chang Shu-Hao
Published: January 2022

Machine learning in photonics has potential in many industries. However, research on patent portfolios is still lacking. The purpose of this study was to assess the status of machine learning in photonics technology and patent portfolios and investigate major assignees to generate a better understanding of the developmental trends of machine learning in photonics. This can provide governments and industry with a resource for planning strategic development. I used data-mining methods (correspondence analysis and K-means clustering) to explore competing technological and strategic-group relationships within the field of machine learning in photonics. The data were granted patents in the USPTO database from 2019 to 2020. The results reveal that patents were primarily in image data processing, electronic digital data processing, wireless communication networks, and healthcare informatics and diagnosis. I assessed the relative technological advantages of various assignees and propose policy recommendations for technology development.
Hematological Parameters and Iron Status in Adult Men and Women Using Altitude Adjusted and Unadjusted Hemoglobin Values for Anemia Diagnosis in Cusco, Peru (3400 MASL)
Authors: Alarcón-Yaquetto Dulce E. , Figueroa-Mujica Ramón , Valverde-Bruffau Valeria , Vásquez-Velásquez Cinthya , Sánchez-Huamán Juan José , Jimenez-Troncoso Luis , Rozas-Gamarra Rodrigo , Gonzales Gustavo F.
Published: January 2022

(1) Background: Current diagnosis of anemia in high altitude populations uses an adjustment of observed hemoglobin (Hb) values. Such an approach has been challenged by findings in different populations in Tibet, Ethiopia and the Andes as inappropriate, as it might incorrectly classify an individual with complete iron stores as anemic. We aimed to assess the suitability of this approach in adult men and women from Cusco, Peru (3400 m); (2) Methods: Complete blood count and iron status biomarkers were measured in 345 subjects (189 females and 156 males), iron status biomarkers were quantified with enzyme-linked immunoassays; (3) Results: Anemia prevalence was overestimated when the altitude-adjustment factor was applied. Hematological parameters were better correlated to iron status biomarkers in the non-adjusted anemia category. When stratified by sex, only women showed a significant association between Hb and other hematological parameters with iron storage and availability (Hepcidin and TFR-F); (4) Conclusion: The prevalence of anemia is overestimated with current guidelines. The rate of anemia using non-adjusted Hb values is more closely related to the rates of anemia or iron deficiency when used hematological parameters, markers of iron status, and measurements of hepcidin and erythropoietin. Sex differences related to iron status were observed, suggesting that men are at a higher risk of iron overload than women at high altitudes. It could be highlighted that a personalized approach is important when assessing a subject, taking in to account hematological parameters as well as origin (Southern Andean or other).
Stability of Transgene Inheritance in Progeny of Field-Grown Pear Trees over a 7-Year Period
Authors: Lebedev Vadim
Published: January 2022

Breeding woody plants is a very time-consuming process, and genetic engineering tools have been used to shorten the juvenile phase. In addition, transgenic trees for commercial cultivation can also be used in classical breeding, but the segregation of transgenes in the progeny of perennial plants, as well as the possible appearance of unintended changes, have been poorly investigated. We studied the inheritance of the uidA gene in the progeny of field-grown transgenic pear trees for 7 years and the physical and physiological parameters of transgenic seeds. A total of 13 transgenic lines were analyzed, and the uidA gene segregated 1:1 in the progeny of 9 lines and 3:1 in the progeny of 4 lines, which is consistent with Mendelian inheritance for one and two transgene loci, respectively. Rare and random deviations from the Mendelian ratio were observed only for lines with one locus. Transgenic seeds’ mass, size, and shape varied slightly, despite significant fluctuations in weather conditions during cultivation. Expression of the uidA gene in the progeny was stable. Our study showed that the transgene inheritance in the progeny of pear trees under field conditions occurs according to Mendelian ratio, does not depend on the environment, and the seed vigor of transgenic seeds does not change.
Biobased Terpene Derivatives: Stiff and Biocompatible Compounds to Tune Biodegradability and Properties of Poly(butylene succinate)
Authors: Zeinali Reza , del Valle Luis J. , Franco Lourdes , Yousef Ibraheem , Rintjema Jeroen , Alemán Carlos , Bravo Fernando , Kleij Arjan W. , Puiggalí Jordi
Published: January 2022

Different copolymers incorporating terpene oxide units (e.g., limonene oxide) have been evaluated considering thermal properties, degradability, and biocompatibility. Thus, polycarbonates and polyesters derived from aromatic, monocyclic and bicyclic anhydrides have been considered. Furthermore, ring substitution with myrcene terpene has been evaluated. All polymers were amorphous when evaluated directly from synthesis. However, spherulites could be observed after the slow evaporation of diluted chloroform solutions of polylimonene carbonate, with all isopropene units possessing an R configuration. This feature was surprising considering the reported information that suggested only the racemic polymer was able to crystallize. All polymers were thermally stable and showed a dependence of the maximum degradation rate temperature (from 242 °C to 342 °C) with the type of terpene oxide. The graduation of glass transition temperatures (from 44 °C to 172 °C) was also observed, being higher than those corresponding to the unsubstituted polymers. The chain stiffness of the studied polymers hindered both hydrolytic and enzymatic degradation while a higher rate was detected when an oxidative medium was assayed (e.g., weight losses around 12% after 21 days of exposure). All samples were biocompatible according to the adhesion and proliferation tests performed with fibroblast cells. Hydrophobic and mechanically consistent films (i.e., contact angles between 90° and 110°) were obtained after the evaporation of chloroform from the solutions, having different ratios of the studied biobased polyterpenes and poly(butylene succinate) (PBS). The blend films were comparable in tensile modulus and tensile strength with the pure PBS (e.g., values of 330 MPa and 7 MPa were determined for samples incorporating 30 wt.% of poly(PA-LO), the copolyester derived from limonene oxide and phthalic anhydride. Blends were degradable, biocompatible and appropriate to produce oriented-pore and random-pore scaffolds via a thermally-induced phase separation (TIPS) method and using 1,4-dioxane as solvent. The best results were attained with the blend composed of 70 wt.% PBS and 30 wt.% poly(PA-LO). In summary, the studied biobased terpene derivatives showed promising properties to be used in a blended form for biomedical applications such as scaffolds for tissue engineering.
Non-Woven Sheet Containing Gemcitabine: Controlled Release Complex for Pancreatic Cancer Treatment
Authors: Sakura Kazuma , Sasai Masao , Mino Takayuki , Uyama Hiroshi
Published: January 2022

The 5-year survival rate for pancreatic cancer remains low, and the development of new methods for its treatment is actively underway. After the surgical treatment of pancreatic cancer, recurrence and peritoneal dissemination can be prevented by long-term local exposure to appropriate drug concentrations. We propose a novel treatment method using non-woven sheets to achieve this goal. Poly(L-lactic acid) non-woven sheets containing gemcitabine (GEM) were prepared, and GEM sustained release from this delivery system was investigated. Approximately 35% of the GEM dose was released within 30 d. For in vitro evaluation, we conducted a cell growth inhibition test using transwell assays, and significant inhibition of cell growth was observed. The antitumor effects of subcutaneously implanted GEM-containing non-woven sheets were evaluated in mice bearing subcutaneous Panc02 cells, and it was established that the sheets inhibited tumor growth for approximately 28 d. These results suggest the usefulness of GEM-containing non-woven sheets in pancreatic cancer treatment.
Flexural Behavior of a Novel Textile-Reinforced Polymer Concrete
Authors: Murcia Daniel Heras , Çomak Bekir , Soliman Eslam , Reda Taha Mahmoud M.
Published: January 2022

Textile reinforced concrete (TRC) has gained attention from the construction industry due to its light weight, high tensile strength, design flexibility, corrosion resistance, and remarkably long service life. Some structural applications that utilize TRC components include precast panels, structural repair, waterproofing elements, and façades. TRC is produced by incorporating textile fabrics into thin cementitious concrete panels. Premature debonding between the textile fabric and concrete due to improper cementitious matrix impregnation of the fibers was identified as a failure-governing mechanism. To overcome this performance limitation, in this study, a novel type of TRC is proposed by replacing the cement binder with a polymer resin to produce textile reinforced polymer concrete (TRPC). The new TRPC is created using a fine-graded aggregate, methyl methacrylate polymer resin, and basalt fiber textile fabric. Four different specimen configurations were manufactured by embedding 0, 1, 2, and 3 textile layers in concrete. Flexural performance was analyzed and compared with reference TRC specimens with similar compressive strength and reinforcement configurations. Furthermore, the crack pattern intensity was determined using an image processing technique to quantify the ductility of TRPC compared with conventional TRC. The new TRPC improved the moment capacity compared with TRC by 51%, 58%, 59%, and 158%, the deflection at peak load by 858%, 857%, 3264%, and 3803%, and the toughness by 1909%, 3844%, 2781%, and 4355% for 0, 1, 2, and 3 textile layers, respectively. TRPC showed significantly improved flexural capacity, superior ductility, and substantial plasticity compared with TRC.