bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafast Deep-Ultraviolet Laser-Induced Voltage Response of Pyrite
Authors: Liu Xuecong , Li Yudong , Wu Haoqiang , Yu Yawen , Zhan Honglei , Miao Xinyang , Zhao Kun
Published: December 2021

Ultrafast, high-sensitivity deep-ultraviolet (UV) photodetectors are crucial for practical applications, including optical communication, ozone layer monitoring, flame detection, etc. However, fast-response UV photodetectors based on traditional materials suffer from issues of expensive production processes. Here, we focused on pyrite with simultaneously cheap production processes and ultrafast response speed. Nanoseconds photovoltaic response was observed under UV pulsed laser irradiation without an applied bias at room temperature. In addition, the response time of the laser-induced voltage (LIV) signals was ~20 ns, which was the same as the UV laser pulse width. The maximum value of the responsivity is 0.52 V/mJ and the minimum value of detectivity was about to ~1.4 × 1013 Jones. When there exists nonuniform illumination, a process of diffusion occurs by which the carriers migrate from the region of high concentration toward the region of low concentration. The response speed is limited by a factor of the diffusion of the carriers. With an increment in laser energy, the response speed of LIV is greatly improved. The high response speed combined with low-cost fabrication makes these UV photodetectors highly attractive for applications in ultrafast detection.
Paleoproterozoic Pt-Pd Fedorovo-Pansky and Cu-Ni-Cr Monchegorsk Ore Complexes: Age, Metamorphism, and Crustal Contamination According to Sm-Nd Data
Authors: Serov Pavel A.
Published: December 2021

This paper continues the Sm-Nd isotope geochronological research carried out at the two largest Paleoproterozoic ore complexes of the northeastern Baltic Shield, i.e., the Cu-Ni-Cr Monchegorsk and the Pt-Pd Fedorovo-Pansky intrusions. These economically significant deposits are examples of layered complexes in the northeastern part of the Fennoscandian Shield. Understanding the stages of their formation and transformation helps in the reconstruction of the long-term evolution of ore-forming systems. This knowledge is necessary for subsequent critical metallogenic and geodynamic conclusions. We applied the Sm-Nd method of comprehensive age determination to define the main age ranges of intrusion. Syngenetic ore genesis occurred 2.53–2.85 Ga; hydrothermal metasomatic ore formation took place 2.70 Ga; and the injection of additional magma batches occurred 2.44–2.50 Ga. The rock transformation and redeposited ore formation at 2.0–1.9 Ga corresponded to the beginning of the Svecofennian events, widely presented on the Fennoscandian Shield. According to geochronological and Nd-Sr isotope data, rocks of the Monchegorsk and the Fedorovo-Pansky complexes seemed to have an anomalous mantle source in common with Paleoproterozoic layered intrusions of the Fennoscandian Shield (enriched with lithophile elements, εNd values vary from −3.0 to +2.5 and ISr 0.702–0.705). The data obtained comply with the known isotope-geochemical and geochronological characteristics of ore-bearing layered intrusions in the northeastern Baltic Shield. An interaction model of parental melts of the Fennoscandian layered intrusions and crustal matter shows a small level of contamination within the usual range of 5–10%. However, the margins of the Monchetundra massif indicate a much higher level of crustal contamination caused by active interaction of parental magmas and host rock.
Sampling CASE Application for the Quality Control of Published Natural Product Structures
Authors: Moreira Lorena Martins Guimarães , Junker Jochen
Published: December 2021

Structure elucidation with NMR correlation data is dicey, as there is no way to tell how ambiguous the data set is and how reliably it will define a constitution. Many different software tools for computer assisted structure elucidation (CASE) have become available over the past decades, all of which could ensure a better quality of the elucidation process, but their use is still not common. Since 2011, WebCocon has integrated the possibility to generate theoretical NMR correlation data, starting from an existing structural proposal, allowing this theoretical data then to be used for CASE. Now, WebCocon can also read the recently presented NMReDATA format, allowing for uncomplicated access to CASE with experimental data. With these capabilities, WebCocon presents itself as an easily accessible Web-Tool for the quality control of proposed new natural products. Results of this application to several molecules from literature are shown and demonstrate how CASE can contribute to improve the reliability of Structure elucidation with NMR correlation data.
Insights on the Inhibitory Power of Flavonoids on Tyrosinase Activity: A Survey from 2016 to 2021
Authors: El-Nashar Heba A. S. , El-Din Mariam I. Gamal , Hritcu Lucian , Eldahshan Omayma A.
Published: December 2021

Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the overexpression of tyrosinase may result in skin-related disorders such as aging spots, wrinkles, melasma, freckles, lentigo, ephelides, nevus, browning and melanoma. Nature expresses itself through the plants as a source of phytochemicals with diverse biological properties. Among these bioactive compounds, flavonoids represent a huge natural class with different categories such as flavones, flavonols, isoflavones, flavan-3-ols, flavanones and chalcones that display antioxidant and tyrosinase inhibitor activities with a diversity of mechanistic approaches. In this review, we explore the role of novel or known flavonoids isolated from different plant species and their participation as tyrosinase inhibitors reported in the last five years from 2016 to 2021. We also discuss the mechanistic approaches through the different studies carried out on these compounds, including in vitro, in vivo and in silico computational research. Information was obtained from Google Scholar, PubMed, and Science Direct. We hope that the updated comprehensive data presented in this review will help researchers to develop new safe, efficacious, and effective drug or skin care products for the prevention of and/or protection against skin-aging disorders.
The Overexpression of YALI0B07117g Results in Enhanced Erythritol Synthesis from Glycerol by the Yeast Yarrowia lipolytica
Authors: Szczepańczyk Mateusz , Rzechonek Dorota A. , Dobrowolski Adam , Mirończuk Aleksandra M.
Published: December 2021

The unconventional yeast Yarrowia lipolytica is used to produce erythritol from glycerol. In this study, the role of the erythrose reductase (ER) homolog YALI0B07117g in erythritol synthesis was analyzed. The deletion of the gene resulted in an increased production of mannitol (308%) and arabitol (204%) before the utilization of these polyols began. The strain overexpressing the YALI0B07117g gene was used to increase the erythritol yield from glycerol as a sole carbon source in batch cultures, resulting in a yield of 0.4 g/g. The specific consumption rate (qs) increased from 5.83 g/g/L for the WT strain to 8.49 g/g/L for the modified strain and the productivity of erythritol increased from 0.28 g/(L h) for the A101 strain to 0.41 g/(L h) for the modified strain. The application of the research may prove positive for shortening the cultivation time due to the increased rate of consumption of the substrate combined with the increased parameters of erythritol synthesis.
Evaluation and Prediction on the Effect of Ionic Properties of Solvent Extraction Performance of Oily Sludge Using Machine Learning
Authors: Hu Changchao , Fu Shuhan , Zhu Lingfu , Dang Wei , Zhang Tingting
Published: December 2021

Oily sludge produced in the process of petroleum exploitation and utilization is a kind of hazardous waste that needs to be urgently dealt with in the petrochemical industry. The oil content of oily sludge is generally between 15–50% and has a great potential for oil resource utilization. However, its composition is complex, in which asphaltene is of high viscosity and difficult to separate. In this study, The oily sludge was extracted with toluene as solvent, supplemented by three kinds of ionic liquids (1-ethyl-3-methylimidazole tetrafluoroborate ([EMIM] [BF4]), 1-ethyl-3-methylimidazole trifluoro-acetate ([EMIM] [TA]), 1-ethyl-3-methylimidazole Dicyandiamide ([EMIM] [N(CN)2])) and three kinds of deep eutectic solutions (choline chloride/urea (ChCl/U), choline chloride / ethylene glycol (ChCl/EG), and choline chloride/malonic acid (ChCl/MA)). This experiment investigates the effect of physicochemical properties of the solvents on oil recovery and three machine learning methods (ridge regression, multilayer perceptron, and support vector regression) are used to predict the association between them. Depending on the linear correlation of variables, it is found that the conductivity of ionic liquid is the key characteristic affecting the extraction treatment in this system.
Hydrolytic Degradation of Polylactic Acid Fibers as a Function of pH and Exposure Time
Authors: Vaid Radhika , Yildirim Erol , Pasquinelli Melissa A. , King Martin W.
Published: December 2021

Polylactic acid (PLA) is a widely used bioresorbable polymer in medical devices owing to its biocompatibility, bioresorbability, and biodegradability. It is also considered a sustainable solution for a wide variety of other applications, including packaging. Because of its widespread use, there have been many studies evaluating this polymer. However, gaps still exist in our understanding of the hydrolytic degradation in extreme pH environments and its impact on physical and mechanical properties, especially in fibrous materials. The goal of this work is to explore the hydrolytic degradation of PLA fibers as a function of a wide range of pH values and exposure times. To complement the experimental measurements, molecular-level details were obtained using both molecular dynamics (MD) simulations with ReaxFF and density functional theory (DFT) calculations. The hydrolytic degradation of PLA fibers from both experiments and simulations was observed to have a faster rate of degradation in alkaline conditions, with 40% of strength loss of the fibers in just 25 days together with an increase in the percent crystallinity of the degraded samples. Additionally, surface erosion was observed in these PLA fibers, especially in extreme alkaline environments, in contrast to bulk erosion observed in molded PLA grafts and other materials, which is attributed to the increased crystallinity induced during the fiber spinning process. These results indicate that spun PLA fibers function in a predictable manner as a bioresorbable medical device when totally degraded at end-of-life in more alkaline conditions.
Highly Efficient Candlelight Organic Light-Emitting Diode with a Very Low Color Temperature
Authors: Shahnawaz Shahnawaz , Siddiqui Iram , Nagar Mangey Ram , Choudhury Abhijeet , Lin Jin-Tin , Blazevicius Dovydas , Krucaite Gintare , Grigalevicius Saulius , Jou Jwo-Huei
Published: December 2021

Low color temperature candlelight organic light-emitting diodes (LEDs) are human and environmentally friendly because of the absence of blue emission that might suppress at night the secretion of melatonin and damage retina upon long exposure. Herein, we demonstrated a lighting device incorporating a phenoxazine-based host material, 3,3-bis(phenoxazin-10-ylmethyl)oxetane (BPMO), with the use of orange-red and yellow phosphorescent dyes to mimic candlelight. The resultant BPMO-based simple structured candlelight organic LED device permitted a maximum exposure limit of 57,700 s, much longer than did a candle (2750 s) or an incandescent bulb (1100 s) at 100 lx. The resulting device showed a color temperature of 1690 K, which is significantly much lower than that of oil lamps (1800 K), candles (1900 K), or incandescent bulbs (2500 K). The device showed a melatonin suppression sensitivity of 1.33%, upon exposure for 1.5 h at night, which is 66% and 88% less than the candle and incandescent bulb, respectively. Its maximum power efficacy is 23.1 lm/W, current efficacy 22.4 cd/A, and external quantum efficiency 10.2%, all much higher than the CBP-based devices. These results encourage a scalable synthesis of novel host materials to design and manufacture high-efficiency candlelight organic LEDs.
Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy
Authors: Tatli Ozge , Dinler Doganay Gizem
Published: December 2021

Aberrant activity of oncogenic rat sarcoma virus (RAS) protein promotes tumor growth and progression. RAS-driven cancers comprise more than 30% of all human cancers and are refractory to frontline treatment strategies. Since direct targeting of RAS has proven challenging, efforts have been centered on the exploration of inhibitors for RAS downstream effector kinases. Two major RAS downstream signaling pathways, including the Raf/MEK/Erk cascade and the phosphatidylinositol-3-kinase (PI3K) pathway, have become compelling targets for RAS-driven cancer therapy. However, the main drawback in the blockade of a single RAS effector is the multiple levels of crosstalk and compensatory mechanisms between these two pathways that contribute to drug resistance against monotherapies. A growing body of evidence reveals that the sequential or synergistic inhibition of multiple RAS effectors is a more convenient route for the efficacy of cancer therapy. Herein, we revisit the recent developments and discuss the most promising modalities targeting canonical RAS downstream effectors for the treatment of RAS-driven cancers.
Analysis of Cyanogenic Compounds Derived from Mandelonitrile by Ultrasound-Assisted Extraction and High-Performance Liquid Chromatography in Rosaceae and Sambucus Families
Authors: Rodríguez Madrera Roberto , Suárez Valles Belén
Published: December 2021

An analytical method for extraction and quantitative determination of amygdalin, prunasin, and sambunigrin in plant material is described. The method is based on extraction with high-power ultrasound (UAE), with acidified water as solvent and quantification by HPLC–DAD. The best extraction conditions were: 80% sonication amplitude, 55 s extraction time, 70% duty cycle, 0.1 g sample mass, and 10 mL acidified water (0.1% perchloric acid). Once developed, the method was validated in terms of accuracy and precision. Good linearity was obtained, with correlation coefficients exceeding 0.999 and the quantification limits ranged from 2.2 μg/g (amygdalin) to 9.6 μg/g (sambunigrin). The accuracy (recovery study) ranged between 90 and 104% and the reproducibility of the method was always <2.3% (RSD). Special attention should be paid to the ratio sample/solvent in samples with potential β-glucosidase activity to avoid degradation of the cyanogenic glycosides (CNGs). The proposed method was used to evaluate the content of CNGs in kernels of Prunus genera, apple seeds, apple pomace, and different plant materials of Sambucus nigra.
AZO-Based ZnO Nanosheet MEMS Sensor with Different Al Concentrations for Enhanced H2S Gas Sensing
Authors: Nagarjuna Yempati , Lin Jun-Cong , Wang Sheng-Chang , Hsiao Wen-Tse , Hsiao Yu-Jen
Published: December 2021

The properties of H2S gas sensing were investigated using a ZnO nanostructure prepared with AZO (zinc oxide with aluminium) and Al surfaces which were developed on a MEMS (Micro Electromechanical System) device. Hydrothermal synthesis was implemented for the deposition of the ZnO nanostructure. To find the optimal conditions for H2S gas sensing, different ZnO growth times and different temperatures were considered and tested, and the results were analysed. At 250 °C and 90 min growth time, a ZnO sensor prepared with AZO and 40 nm Al recorded an 8.5% H2S gas-sensing response at a 200 ppb gas concentration and a 14% sensing response at a gas concentration of 1000 ppb. The dominant sensing response provided the optimal conditions for the ZnO sensor, which were 250 °C temperature and 90 min growth time. Gas sensor selectivity was tested with five different gases (CO, SO2, NO2, NH3 and H2S) and the sensor showed great selectivity towards H2S gas.
Phase-Controlled NiO Nanoparticles on Reduced Graphene Oxide as Electrocatalysts for Overall Water Splitting
Authors: Jo Seung Geun , Kim Chung-Soo , Kim Sang Jun , Lee Jung Woo
Published: December 2021

Efficient water electrolysis is one of the key issues in realizing a clean and renewable energy society based on hydrogen fuel. However, several obstacles remain to be solved for electrochemical water splitting catalysts, which are the high cost of noble metals and the high overpotential of alternative catalysts. Herein, we suggest Ni-based alternative catalysts that have comparable performances with precious metal-based catalysts and could be applied to both cathode and anode by precise phase control of the pristine catalyst. A facile microwave-assisted procedure was used for NiO nanoparticles anchored on reduced graphene oxide (NiO NPs/rGO) with uniform size distribution in ~1.8 nm. Subsequently, the Ni-NiO dual phase of the NPs (A-NiO NPs/rGO) could be obtained via tailored partial reduction of the NiO NPs/rGO. Moreover, we demonstrate from systematic HADDF-EDS and XPS analyses that metallic Ni could be formed in a local area of the NiO NP after the reductive annealing procedure. Indeed, the synergistic catalytic performance of the Ni-NiO phase of the A-NiO NPs/rGO promoted hydrogen evolution reaction activity with an overpotential as 201 mV at 10 mA cm−2, whereas the NiO NPs/rGO showed 353 mV. Meanwhile, the NiO NPs/rGO exhibited the most excellent oxygen evolution reaction performance among all of the Ni-based catalysts, with an overpotential of 369 mV at 10 mA cm−2, indicating that they could be selectively utilized in the overall water splitting. Furthermore, both catalysts retained their activities over 12 h with constant voltage and 1000 cycles under cyclic redox reaction, proving their high durability. Finally, the full cell capability for the overall water electrolysis system was confirmed by observing the generation of hydrogen and oxygen on the surface of the cathode and anode.
An In Vitro Approach to Studying the Microbial Community and Impact of Pre and Probiotics under Anorexia Nervosa Related Dietary Restrictions
Authors: Liu Litai , Poveda Carlos , Jenkins Paul E. , Walton Gemma E.
Published: December 2021

Individuals with anorexia nervosa (AN) often suffer psychological and gastrointestinal problems consistent with a dysregulated gut microbial community. Psychobiotics have been postulated to modify microbiota and improve mental well-being and gut symptoms, but there is currently a lack of evidence for such approaches in AN. The aim of this study was to use an in vitro colonic model to evaluate the impact of dietary restrictions associated with AN on the intestinal ecosystem and to assess the impact of pre and probiotic intervention. Bacteriology was quantified using flow cytometry combined with fluorescence in situ hybridisation and metabolic end products (including neurotransmitters) by gas chromatography and liquid chromatography mass spectrometry Consistent with previous research, the nutritional changes significantly reduced total microbiota and metabolites compared with healthy conditions. Pre and probiotic supplementation on restricted conditions enhanced the microbial community and modulated metabolic activity to resemble that of a healthy diet. The model system indicates that nutritional changes associated with AN can impact the microbial community, and that these changes can, at least in part, be restored through the use of pre and probiotic interventions.
Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis
Authors: Park Woo Yong , Song Gahee , Noh Joon Hak , Kim Taegon , Kim Jae Jin , Hong Seokbeom , Park Jinbong , Um Jae-Young
Published: December 2021

In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and β-oxidation. Importantly, RSWE decreased the mRNA expression of de novo lipogenesis-related genes, such as Srebf1, Cebpa, Pparg, and Lpin1, as well as the protein levels of these factors, in the liver of AFLD mice. That these actions of RSWE affect lipogenesis was confirmed using PA-induced steatosis HepG2 cells. Overall, our findings suggest that RSWE has the potential for improvement of AFLD by inhibiting de novo lipogenesis.
Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study
Authors: de Mello Vanessa Derenji , Selander Tuomas , Lindström Jaana , Tuomilehto Jaakko , Uusitupa Matti , Kaarniranta Kai
Published: December 2021

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40–64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.
Survival of Fiber-Reinforced Composite Resin Post-Restored vs. Cast Post-and-Core-Restored Teeth: A Retrospective Clinical Study
Authors: Bunz Oskar , Iwantschenko Darja , Tulka Sabrina , Barthel-Zimmer Claudia , Piwowarczyk Andree
Published: December 2021

Objective: The question of whether classic cast post-and-core (CPC) or fiber-reinforced composite resin posts (FRCP) are the best clinical decision has still not been fully solved. Materials and Methods: One hundred and sixty-two teeth were restored with FRCP, and 162 CPC restored teeth were included in this study with a matched-pair design. In a primary analysis, the survival rates after one year (primary endpoint) were compared. The additional analysis included an evaluation of tooth- and construction-specific variables and an illustration of the survival up to 60 months via Kaplan-Meier curves. Results: FRCP showed lower failure risk considering the definitive prosthetic restoration and tooth type compared to CPC restored teeth. In total, 17 failures were observed in the FRCP group and 35 failures in the CPC group. A 60-month survival rate of 79.3% for FRCP and 64.5% for CPC was observed. Teeth serving as abutments for telescopic dentures were more likely to be affected by failure compared to teeth restored with single crowns. Conclusion: Within the limitations of this study, the FRCP showed a lower failure risk compared to the CPC, considering the definitive prosthetic restoration and tooth type within the observation period.
Unravelling the Interaction of Piperlongumine with the Nucleotide-Binding Domain of HSP70: A Spectroscopic and In Silico Study
Authors: Povinelli Ana Paula Ribeiro , Zazeri Gabriel , Jones Alan M. , Cornélio Marinnio Lopes
Published: December 2021

Piperlongumine (PPL) is an alkaloid extracted from several pepper species that exhibits anti-inflammatory and anti-carcinogenic properties. Nevertheless, the molecular mode of action of PPL that confers such powerful pharmacological properties remains unknown. From this perspective, spectroscopic methods aided by computational modeling were employed to characterize the interaction between PPL and nucleotide-binding domain of heat shock protein 70 (NBD/HSP70), which is involved in the pathogenesis of several diseases. Steady-state fluorescence spectroscopy along with time-resolved fluorescence revealed the complex formation based on a static quenching mechanism. Van’t Hoff analyses showed that the binding of PPL toward NBD is driven by equivalent contributions of entropic and enthalpic factors. Furthermore, IDF and Scatchard methods applied to fluorescence intensities determined two cooperative binding sites with Kb of (6.3 ± 0.2) × 104 M−1. Circular dichroism determined the thermal stability of the NBD domain and showed that PPL caused minor changes in the protein secondary structure. Computational simulations elucidated the microenvironment of these interactions, showing that the binding sites are composed mainly of polar amino acids and the predominant interaction of PPL with NBD is Van der Waals in nature.
Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database
Authors: Toriumi Shinya , Kobayashi Akinobu , Sueki Hitoshi , Yamamoto Munehiro , Uesawa Yoshihiro
Published: December 2021

Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.
Large-Scale Evaluation of Collision Cross Sections to Investigate Blood-Brain Barrier Permeation of Drugs
Authors: Guntner Armin Sebastian , Bögl Thomas , Mlynek Franz , Buchberger Wolfgang
Published: December 2021

Successful drug administration to the central nervous system requires accurate adjustment of the drugs’ molecular properties. Therefore, structure-derived descriptors of potential brain therapeutic agents are essential for an early evaluation of pharmacokinetics during drug development. The collision cross section (CCS) of molecules was recently introduced as a novel measurable parameter to describe blood-brain barrier (BBB) permeation. This descriptor combines molecular information about mass, structure, volume, branching and flexibility. As these chemical properties are known to influence cerebral pharmacokinetics, CCS determination of new drug candidates may provide important additional spatial information to support existing models of BBB penetration of drugs. Besides measuring CCS, calculation is also possible; but however, the reliability of computed CCS values for an evaluation of BBB permeation has not yet been fully investigated. In this work, prediction tools based on machine learning were used to compute CCS values of a large number of compounds listed in drug libraries as negative or positive with respect to brain penetration (BBB+ and BBB− compounds). Statistical evaluation of computed CCS and several other descriptors could prove the high value of CCS. Further, CCS-deduced maximum molecular size of BBB+ drugs matched the dimensions of BBB pores. A threshold for transcellular penetration and possible permeation through pore-like openings of cellular tight-junctions is suggested. In sum, CCS evaluation with modern in silico tools shows high potential for its use in the drug development process.
Phyto-Phospholipid Conjugated Scorpion Venom Nanovesicles as Promising Carrier That Improves Efficacy of Thymoquinone against Adenocarcinoma Human Alveolar Basal Epithelial Cells
Authors: Asfour Hani Z. , Fahmy Usama A. , Alharbi Waleed S. , Almehmady Alshaimaa M. , Alamoudi Abdulmohsin J. , Tima Singkome , Mansouri Rasha A. , Omar Ulfat M. , Ahmed Osama A. A. , Zakai Shadi A. , Aldarmahi Ahmed A. , Bagalagel Alaa , Diri Reem , Alhakamy Nabil A.
Published: December 2021

Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ’s cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.
Etched 3D-Printed Polycaprolactone Constructs Functionalized with Reduced Graphene Oxide for Enhanced Attachment of Dental Pulp-Derived Stem Cells
Authors: Bow Austin J. , Masi Thomas J. , Dhar Madhu S.
Published: December 2021

A core challenge in the field of tissue engineering is the ability to establish pipeline workflows for the design and characterization of scaffold technologies with clinically translatable attributes. The parallel development of biomaterials and stem cell populations represents a self-sufficient and streamlined approach for establishing such a pipeline. In the current study, rat dental pulp stem cell (rDPSC) populations were established to assess functionalized polycaprolactone (PCL) constructs. Initial optimization and characterization of rDPSC extraction and culture conditions confirmed that cell populations were readily expandable and demonstrated surface markers associated with multi-potency. Subset populations were transduced to express DsRed fluorescent protein as a mechanism of tracking both cells and cell-derived extracellular matrix content on complex scaffold architecture. Thermoplastic constructs included reduced graphene oxide (rGO) as an additive to promote cellular attachment and were further modified by surface etching a weak acetic acid solution to roughen surface topographical features, which was observed to dramatically improve cell surface coverage in vitro. Based on these data, the modified rGO-functionalized PCL constructs represent a versatile platform for bone tissue engineering, capable of being applied as a standalone matrix or in conjunction with bio-active payloads such as DPSCs or other bio-inks.
Improving Multiphoton Microscopy by Combining Spherical Aberration Patterns and Variable Axicons
Authors: Bueno Juan M. , Hernández Geovanni , Skorsetz Martin , Artal Pablo
Published: December 2021

Multiphoton (MP) microscopy is a well-established method for the non-invasive imaging of biological tissues. However, its optical sectioning capabilities are reduced due to specimen-induced aberrations. Both the manipulation of spherical aberration (SA) and the use of axicons have been reported to be useful techniques to bypass this limitation. We propose the combination of SA patterns and variable axicons to further improve the quality of MP microscopy images. This approach provides enhanced images at different depth locations whose quality is better than those corresponding to the use of SA or axicons separately. Thus, the procedure proposed herein facilitates the visualization of details and increases the depth observable at high resolution.
Composite Micro-Nanoarchitectonics of MMT-SiO2: Space Charge Characteristics under Tensile State
Authors: Jiang Hongtao , Gao Junguo , Zhang Xiaohong , Guo Ning
Published: December 2021

Low density polyethylene (LDPE) is a good insulating material which is widely used in cable materials due to its excellent insulation and processability. However, in the DC high voltage environment, pure polyethylene materials still face many problems, the most serious of which is space charge accumulation. The cable will inevitably be subjected to tensile stress during production, installation and operation. Therefore, it is of great significance to study the effect of stretching on the microstructure and space charge characteristics for polymers and their composites. In this paper, MMT/LDPE micro-composites, SiO2/LDPE nano-composites and MMT-SiO2/LDPE micro-nano-composites were prepared by melt blending. Mechanical stretching was carried out on pure LDPE materials and the above three kinds of composite materials. Each material was stretched according to four stretching ratios, which are 0%, 5%, 10% and 20%. The crystal morphology was observed by polarizing microscope (PLM), the crystallization perfection was tested by differential scanning calorimetry (DSC), and the space charge distribution inside each sample was measured by pulsed electro-acoustic (PEA) method. At the same time, the average charge density and apparent charge mobility for samples during depolarization were calculated and analyzed. The experimental results show that when the pure low density polyethylene sample is not stretched, its crystal structure is loose. Tensile stress can make the loose molecular chains align in LDPE and improve its crystalline structure, which is helpful to restrain the accumulation of space charge inside the sample. For MMT/LDPE, SiO2/LDPE and MMT-SiO2/LDPE composites, their internal crystal structure is compact. Stretching will destroy their original crystal structure at first, and then disorder molecular chains inside the three composite materials. With the increase of stretching ratio, the molecular chains begin to orient along the direction of force, the crystallization tends to be perfect gradually, and the space charge accumulation in samples also decreases. From the calculation results of apparent charge mobility for each sample, with the increase of stretching ratio, the trap depth and trap density inside samples firstly increased and then decreased.
Determination of the Degree of Crystallinity of Poly(2-methyl-2-oxazoline)
Authors: Chistyakov Evgeniy M. , Filatov Sergey N. , Sulyanova Elena A. , Volkov Vladimir V.
Published: December 2021

A new method for purification of 2-methyl-2-oxazoline using citric acid was developed and living cationic ring-opening polymerization of 2-methyl-2-oxazoline was carried out. Polymerization was conducted in acetonitrile using benzyl chloride—boron trifluoride etherate initiating system. According to DSC data, the temperature range of melting of the crystalline phase of the resulting polymer was 95–180 °C. According to small-angle X-ray scattering and wide-angle X-ray diffraction data, the degree of crystallinity of the polymer was 12%. Upon cooling of the polymer melt, the polymer became amorphous. Using thermogravimetric analysis, it was found that the thermal destruction of poly(2-methyl-2-oxazoline) started above 209 °C.
Casein Micelles as Nanocarriers for Benzydamine Delivery
Authors: Zahariev Nikolay , Marudova Maria , Milenkova Sophia , Uzunova Yordanka , Pilicheva Bissera
Published: December 2021

The aim of the present work was to optimize the process parameters of the nano spray drying technique for the formulation of benzydamine-loaded casein nanoparticles and to investigate the effect of some process variables on the structural and morphological characteristics and release behavior. The obtained particles were characterized in terms of particle size and size distribution, surface morphology, production yield and encapsulation efficiency, drug-polymer compatibility, etc., using dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, and Fourier transformed infrared spectroscopy. Production yields of the blank nanoparticles were significantly influenced by the concentration of both casein and the crosslinking agent. The formulated drug-loaded nanoparticles had an average particle size of 135.9 nm to 994.2 nm. Drug loading varied from 16.02% to 57.41% and the encapsulation efficiency was in the range 34.61% to 78.82%. Our study has demonstrated that all the investigated parameters depended greatly on the polymer/drug ratio and the drug release study confirmed the feasibility of the developed nanocarriers for prolonged delivery of benzydamine.
Morphology and Degradation of Multicompartment Microparticles Based on Semi-Crystalline Polystyrene-block-Polybutadiene-block-Poly(L-lactide) Triblock Terpolymers
Authors: Janoszka Nicole , Azhdari Suna , Hils Christian , Coban Deniz , Schmalz Holger , Gröschel André H.
Published: December 2021

The confinement assembly of block copolymers shows great potential regarding the formation of functional microparticles with compartmentalized structure. Although a large variety of block chemistries have already been used, less is known about microdomain degradation, which could lead to mesoporous microparticles with particularly complex morphologies for ABC triblock terpolymers. Here, we report on the formation of triblock terpolymer-based, multicompartment microparticles (MMs) and the selective degradation of domains into mesoporous microparticles. A series of polystyrene-block-polybutadiene-block-poly(L-lactide) (PS-b-PB-b-PLLA, SBL) triblock terpolymers was synthesized by a combination of anionic vinyl and ring-opening polymerization, which were transformed into microparticles through evaporation-induced confinement assembly. Despite different block compositions and the presence of a crystallizable PLLA block, we mainly identified hexagonally packed cylinders with a PLLA core and PB shell embedded in a PS matrix. Emulsions were prepared with Shirasu Porous Glass (SPG) membranes leading to a narrow size distribution of the microparticles and control of the average particle diameter, d ≈ 0.4 µm–1.8 µm. The core–shell cylinders lie parallel to the surface for particle diameters d < 0.5 µm and progressively more perpendicular for larger particles d > 0.8 µm as verified with scanning and transmission electron microscopy and particle cross-sections. Finally, the selective degradation of the PLLA cylinders under basic conditions resulted in mesoporous microparticles with a pronounced surface roughness.
Design Rule for Constructing Buckling-Free Polymeric Stencil with Microdot Apertures
Authors: Kim Minju , Lee Jinwon , Kim Junsoo , Jang Segeun , Kim Sang Moon
Published: December 2021

A polymeric stencil with microdot apertures made by using polydimethylsiloxane (PDMS) molds with pillar patterns has many advantages, including conformal contact, easy processability, flexibility, and low cost compared to conventional silicon-based membranes. However, due to the inherent deformability of PDMS materials in response to external pressure, it is challenging to construct structurally stable stencils with high structural fidelity. Here, we propose a design rule on the buckling pressure for constructing polymeric stencils without process failure. To investigate the critical buckling pressure (Pcr), stencils are fabricated by using different PDMS molds with aspect ratio variations (AR: 1.6, 2.0, 4.0, and 5.3). By observing the buckled morphology of apertures, the structures can be classified into two groups: low (AR 1.6 and 2.0) and high (AR 4.0 and 5.3) AR groups, and Pcr decreases as AR increases in each group. To investigate the results theoretically, the analysis based on Euler’s buckling theory and slenderness ratio is conducted, indicating that the theory is only valid for the high-AR group herein. Besides, considering the correction factor, Pcr agrees well with the experimental results.
Redox/pH-Responsive 2-in-1 Chimeric Nanoparticles for the Co-Delivery of Doxorubicin and siRNA
Authors: Wu Hsi-Chin , Kuo Wei-Ting
Published: December 2021

The co-delivery of chemotherapy drugs and gene-suppressing small interfering RNA (siRNA) show promise for cancer therapy. The key to the clinical realization of this treatment model will be the development of a carrier system enabling the simultaneous delivery (“co-delivery” instead of combinatorial delivery) of chemotherapy and siRNA agents to cancer. In this study, a co-delivery system was developed from two individual components to form one integrated nanovehicle through a redox-sensitive thiol–disulfide bond for the synergistic delivery of chemotherapy and RNA silencing: doxorubicin (Dox)-loaded N,O-carboxymethyl chitosan (NOCC) complex with a thiolated hyaluronic acid (HA-SH) nanocarrier and dopamine (Dopa)-conjugated thiolated hyaluronic acid (SH-HA-Dopa)-coated calcium phosphate (CaP)-siRNA nanocarrier. The 2-in-1 chimeric nanoparticles (NPs) were structurally stable together in the storage environment and in the circulation. This smart system selectively releases Dox and siRNA into the cytosol. Furthermore, equipped with the tumor-targeting component HA, the co-delivery system shows specific targeting and high cellular uptake efficiency by receptor-mediated endocytosis. In summary, these dual-responsive (redox and pH), tumor-targeting smart 2-in-1 chimeric NPs show promise to be employed in functional co-delivery and tumor therapy.
Green Synthesis and Characterization of Copper Nanoparticles Using Fortunella margarita Leaves
Authors: Amjad Rutaba , Mubeen Bismillah , Ali Syed Shahbaz , Imam Syed Sarim , Alshehri Sultan , Ghoneim Mohammed M. , Alzarea Sami I. , Rasool Rabia , Ullah Inam , Nadeem Muhammad Shahid , Kazmi Imran
Published: December 2021

The use of biomaterials in the synthesis of nanoparticles is one of the most up-to-date focuses in modern nanotechnologies and nanosciences. More and more research on green methods of producing metal oxide nanoparticles (NP) is taking place, with the goal to overcome the possible dangers of toxic chemicals for a safe and innocuous environment. In this study, we synthesized copper nanoparticles (CuNPs) using Fortunella margarita leaves’ extract, which reflects its novelty in the field of nanosciences. The visual observation of a color change from dark green to bluish green clearly shows the instant and spontaneous formation of CuNPs when the phytochemicals of F. margarita come in contact with Cu+2 ions. The synthesis of CuNPs was carried out at different conditions, including pH, temperature, concentration ratio and time, and were characterized with UV-Vis absorption spectra, scanning electron microscope (SEM) and X-ray diffraction (XRD). The UV-Vis analysis reveals the surface plasmon resonance property (SPR) of CuNPs, showing a characteristic absorption peak at 679 nm, while SEM reveals the spherical but agglomerated shape of CuNPs of the size within the range of 51.26–56.66 nm.
Characterization of Birch Wood Residue after 2-Furaldehyde Obtaining, for Further Integration in Biorefinery Processing
Authors: Puke Maris , Godina Daniela , Kirpluks Mikelis , Brazdausks Prans , Rizikovs Janis
Published: December 2021

Latvia is a large manufacturer of plywood in Eastern Europe, with an annual production of 250,000 m3. In Latvia’s climatic conditions, birch (Betula pendula) is the main tree species that is mainly used for plywood production. A significant part of the processed wood makes up residues like veneer shorts, cores, and cut-offs (up to 30%), which have a high potential for value-added products. The aim of this research was to comprehensively characterize lignocellulosic (LC) biomass that was obtained after 2-furaldehyde production in terms of further valorization of this resource. The polymeric cellulose-enriched material can be used in the new biorefinery concept for the production of 2-furaldehyde, acetic acid, cellulose pulp, thermomechanical (TMP) and an alkaline peroxide mechanical (APMP) pulping process. In addition, we experimentally developed the best 2-furaldehyde production conditions to optimize the purity and usability of cellulose in the leftovers of the LC material. The best experimental results in terms of both 2-furaldehyde yield and the purity of residual lignocellulose were obtained if the catalyst concentration was 70%, the catalyst amount was 4 wt.%, the reaction temperature was 175 °C,and the treatment time was 60 min. After process optimization with DesignExpert11, we concluded that the best conditions for maximal glucose content (as cellulose fibers) was a catalyst concentration of 85%, a catalyst amount of 5 wt.%, a temperature of 164 °C, and a treatment time of 52 min.