bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic and Extrahepatic Sources and Manifestations in Endoplasmic Reticulum Storage Diseases
Authors: Callea Francesco , Francalanci Paola , Giovannoni Isabella
Published: May 2021

Alpha-1-antitrypsin (AAT) and fibrinogen are secretory acute phase reactant proteins. Circulating AAT and fibrinogen are synthesized exclusively in the liver. Mutations in the encoding genes result in conformational abnormalities of the two molecules that aggregate within the rough endoplasmic reticulum (RER) instead of being regularly exported. That results in AAT-deficiency (AATD) and in hereditary hypofibrinogenemia with hepatic storage (HHHS). The association of plasma deficiency and liver storage identifies a new group of pathologies: endoplasmic reticulum storage disease (ERSD).
CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer
Authors: Makhale Ashwini , Nanayakkara Devathri , Raninga Prahlad , Khanna Kum Kum , Kalimutho Murugan
Published: May 2021

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapy. Here, we evaluated the anti-cancer activity of APR-246, a P53 activator, and CX-5461, a RNA polymerase I inhibitor, in the treatment of TNBC cells. We tested the efficacy of individual and combination therapy of CX-5461 and APR-246 in vitro, using a panel of breast cancer cell lines. Using publicly available breast cancer datasets, we found that components of RNA Pol I are predominately upregulated in basal-like breast cancer, compared to other subtypes, and this upregulation is associated with poor overall and relapse-free survival. Notably, we found that the treatment of breast cancer cells lines with CX-5461 significantly hampered cell proliferation and synergistically enhanced the efficacy of APR-246. The combination treatment significantly induced apoptosis that is associated with cleaved PARP and Caspase 3 along with Annexin V positivity. Likewise, we also found that combination treatment significantly induced DNA damage and replication stress in these cells. Our data provide a novel combination strategy by utilizing APR-246 in combination CX-5461 in killing TNBC cells that can be further developed into more effective therapy in TNBC therapeutic armamentarium.
Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure
Authors: Perez Dianne M.
Published: May 2021

The heart has a reduced capacity to generate sufficient energy when failing, resulting in an energy-starved condition with diminished functions. Studies have identified numerous changes in metabolic pathways in the failing heart that result in reduced oxidation of both glucose and fatty acid substrates, defects in mitochondrial functions and oxidative phosphorylation, and inefficient substrate utilization for the ATP that is produced. Recent early-phase clinical studies indicate that inhibitors of fatty acid oxidation and antioxidants that target the mitochondria may improve heart function during failure by increasing compensatory glucose oxidation. Adrenergic receptors (α1 and β) are a key sympathetic nervous system regulator that controls cardiac function. β-AR blockers are an established treatment for heart failure and α1A-AR agonists have potential therapeutic benefit. Besides regulating inotropy and chronotropy, α1- and β-adrenergic receptors also regulate metabolic functions in the heart that underlie many cardiac benefits. This review will highlight recent studies that describe how adrenergic receptor-mediated metabolic pathways may be able to restore cardiac energetics to non-failing levels that may offer promising therapeutic strategies.
Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application
Authors: Buskaran Kalaivani , Hussein Mohd Zobir , Moklas Mohamad Aris Mohd , Masarudin Mas Jaffri , Fakurazi Sharida
Published: May 2021

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75–90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide–polyethylene glycol (GOP)–PCA/CA–FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP–PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.
Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents
Authors: Mieremet Arnout , Helder Richard W. J. , Nadaban Andreea , Boiten Walter A. , Gooris Gert S. , El Ghalbzouri Abdoelwaheb , Bouwstra Joke A.
Published: May 2021

In vitro skin tissue engineering is challenging due to the manifold differences between the in vivo and in vitro conditions. Yet, three-dimensional (3D) human skin equivalents (HSEs) are able to mimic native human skin in many fundamental aspects. However, the epidermal lipid barrier formation, which is essential for the functionality of the skin barrier, remains compromised. Recently, HSEs with an improved lipid barrier formation were generated by (i) incorporating chitosan in the dermal collagen matrix, (ii) reducing the external oxygen level to 3%, and (iii) inhibiting the liver X receptor (LXR). In this study, we aimed to determine the synergic effects in full-thickness models (FTMs) with combinations of these factors as single-, double-, and triple-targeted optimization approaches. The collagen–chitosan FTM supplemented with the LXR inhibitor showed improved epidermal morphogenesis, an enhanced lipid composition, and a better lipid organization. Importantly, barrier functionality was improved in the corresponding approach. In conclusion, our leading optimization approach substantially improved the epidermal morphogenesis, barrier formation, and functionality in the FTM, which therefore better resembled native human skin.
Coralyne Radiosensitizes A549 Cells by Upregulation of CDKN1A Expression to Attenuate Radiation Induced G2/M Block of the Cell Cycle
Authors: Węgierek-Ciuk Aneta , Arabski Michał , Ciepluch Karol , Brzóska Kamil , Lisowska Halina , Czerwińska Malwina , Stępkowski Tomasz , Lis Krzysztof , Lankoff Anna
Published: May 2021

Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle progression of irradiated A549 cells. A clonogenic assay revealed that coralyne pretreatment decreased the viability of A549 cells in a time- and dose-dependent manner. Moreover, exposure to coralyne and ionizing radiation (IR) markedly altered the filamentous actin cytoskeletal architecture and integrin-β binding sites of A549 cells. Treatment with 1–25 µM coralyne in combination with 2 Gy of IR significantly reduced the percentage of cells in G2/M phase compared with 2 Gy IR alone. These results indicate that coralyne is a potent radiosensitizing agent that may find an application in medicine.
Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer
Authors: Pisani Laura Francesca , Tontini Gian Eugenio , Gentile Carmine , Marinoni Beatrice , Teani Isabella , Nandi Nicoletta , Creo Pasquale , Asti Emanuele , Bonavina Luigi , Vecchi Maurizio , Pastorelli Luca
Published: May 2021

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.
The Role of IL-17-Producing Cells in Cutaneous Fungal Infections
Authors: Sawada Yu , Setoyama Ayako , Sakuragi Yumiko , Saito-Sasaki Natsuko , Yoshioka Haruna , Nakamura Motonobu
Published: May 2021

The skin is the outermost layer of the body and is exposed to many environmental stimuli, which cause various inflammatory immune responses in the skin. Among them, fungi are common microorganisms that colonize the skin and cause cutaneous fungal diseases such as candidiasis and dermatophytosis. The skin exerts inflammatory responses to eliminate these fungi through the cooperation of skin-component immune cells. IL-17 producing cells are representative immune cells that play a vital role in anti-fungal action in the skin by producing antimicrobial peptides and facilitating neutrophil infiltration. However, the actual impact of IL-17-producing cells in cutaneous fungal infections remains unclear. In this review, we focused on the role of IL-17-producing cells in a series of cutaneous fungal infections, the characteristics of skin infectious fungi, and the recognition of cell components that drive cutaneous immune cells.
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Authors: Lee Banseok , Shin Myeongcheol , Park Youngjae , Won So-Yoon , Cho Kyoung Sang
Published: May 2021

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.
Plasma Extracellular Vesicle miRNAs Can Identify Lung Cancer, Current Smoking Status, and Stable COPD
Authors: O’Farrell Hannah E. , Bowman Rayleen V. , Fong Kwun M. , Yang Ian A.
Published: May 2021

Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.
Eco-Friendly Speed Control Algorithm Development for Autonomous Vessel Route Planning
Authors: Kim Sewon , Yun Sangwoong , You Youngjun
Published: May 2021

The upcoming autonomous vessel voyage is promising future in the maritime sector. However, so far, the contemporary route decision making technologies rely on human intervention. Therefore, this manuscript proposes the two newly developed speed algorithms: the modified fixed speed control and the wave feed forward speed control in the route decision making procedure for the autonomous vessels. These two algorithms can control the vessel’s speed without human intervention in eco-friendly and economic manner. The first algorithm is the wave feed forward speed control that can predict the speed change according to wave loads and compensate it to reduce the fluctuation of speed, power, and fuel consumption. To develop this algorithm, the real time modeling of the wave added resistance and the wave real time effect on propulsion are analyzed. The efficacy of the developed wave feed forward scheme is validated using the in-house route optimization simulation program through comparisons with the results of conventional speed governor control case. The developed schemes are applied to a 173 K LNG (Liquefied Natural Gas) carrier with twin propulsion. The other proposed speed control algorithm is the modified fixed control algorithm. This algorithm improves the conventional fixed power control algorithm by adding a time marching module to satisfy the required time arrival of the voyage. The two proposed methods are analyzed in the various simulations—ideal environmental conditions and real voyage environments: The Pacific and the Atlantic cases. Based on the results, the suggested methods can reduce fuel oil consumption, gas emission, and wear and tear problem of the propulsion devise of ship. In the study, it is clearly demonstrated that the developed wave feed forward speed control and modified fixed power scheme perform much better than the conventional speed governor control case.
The Feasibility of Monoculture and Polyculture of Striped Catfish and Nile Tilapia in Different Proportions and Their Effects on Growth Performance, Productivity, and Financial Revenue
Authors: Mansour Abdallah Tageldein , Allam Belal Wagih , Srour Tarek Mohamed , Omar Eglal Ali , Nour Abdel Aziz Mousa , Khalil Hala Saber
Published: May 2021

Cultivation of species of high growth rates is a key achievement of sustainable aquaculture development, with the aim of increasing animal protein per capita, maintaining food security and preserving freshwater usage. The present study was conducted to evaluate the feasibility of monoculture and polyculture of striped catfish, Pangasianodon hypophthalmus, and Nile tilapia, Oreochromis niloticus, in different proportions and their effect on growth performance, survival, productivity, feed utilization, body composition, and financial revenue. Five experimental treatments were designed as follows: monoculture of striped catfish (100%), Nile tilapia (100%) and polyculture in different proportions of striped catfish and Nile tilapia (25%:75%; 50%:50%; 75%:25%, respectively), each in three replicates. The fish feeding regime consisted of isonitrogenous (307.80 g kg−1) and isocaloric (19.27 kJ g−1) diets for 14 weeks. The results revealed that the highest growth performance, feed utilization, survival of striped catfish were obtained in monoculture, followed by polyculture of striped catfish and Nile tilapia (in low proportions) (75%:25%). The total production per m3 reached 5.41 kg m−3 in the monoculture of striped catfish, this production decreased in polyculture by 52%, 46% and 23% with 25%; 50%; 75% of striped catfish. The gross margin significantly increased, in case of striped catfish farmed in monoculture, compared to other polyculture proportions. While the gross margin per m−3 of water was 6, 0.5, 1 and 3 $ in monoculture and different polyculture proportions, respectively. Moreover, the feed cost per kilogram of protein gain significantly decreased in the monoculture of striped catfish compared to other polyculture treatments. The growth performance and survival of tilapia showed no significant difference among different treatments. In addition, the proximate chemical composition did not differ in respect to species in different studied treatments. Monoculture of striped catfish is recommended to achieve high production and improve financial revenue per water unit (m−3), for better sustainable development of aquaculture.
Prospecting Biomarkers for Diagnostic and Therapeutic Approaches in Pythiosis
Authors: Chechi Jéssica Luana , Rotchanapreeda Tiwa , da Paz Giselle Souza , Prado Ana Carolina , Oliveira Alana Lucena , Vieira José Cavalcante Souza , Buzalaf Marília Afonso Rabelo , Rodrigues Anderson Messias , Santos Lucilene Delazari dos , Krajaejun Theerapong , Bosco Sandra de Moraes Gimenes
Published: May 2021

Pythiosis, whose etiological agent is the oomycete Pythium insidiosum, is a life-threatening disease that occurs mainly in tropical and subtropical countries, affecting several animal species. It is frequently found in horses in Brazil and humans in Thailand. The disease is difficult to diagnose because the pathogen’s hyphae are often misdiagnosed as mucoromycete fungi in histological sections. Additionally, there is no specific antigen to use for rapid diagnosis, the availability of which could improve the prognosis in different animal species. In this scenario, we investigated which P. insidiosum antigens are recognized by circulating antibodies in horses and humans with pythiosis from Brazil and Thailand, respectively, using 2D immunoblotting followed by mass spectrometry for the identification of antigens. We identified 23 protein spots, 14 recognized by pooled serum from horses and humans. Seven antigens were commonly recognized by both species, such as the heat-shock cognate 70 KDa protein, the heat-shock 70 KDa protein, glucan 1,3-beta-glucosidase, fructose-bisphosphate aldolase, serine/threonine-protein phosphatase, aconitate hydratase, and 14-3-3 protein epsilon. These results demonstrate that there are common antigens recognized by the immune responses of horses and humans, and these antigens may be studied as biomarkers for improving diagnosis and treatment.
Repositioning Lopinavir, an HIV Protease Inhibitor, as a Promising Antifungal Drug: Lessons Learned from Candida albicans—In Silico, In Vitro and In Vivo Approaches
Authors: Santos André L. S. , Braga-Silva Lys A. , Gonçalves Diego S. , Ramos Lívia S. , Oliveira Simone S. C. , Souza Lucieri O. P. , Oliveira Vanessa S. , Lins Roberto D. , Pinto Marcia R. , Muñoz Julian E. , Taborda Carlos P. , Branquinha Marta H.
Published: May 2021

The repurposing strategy was applied herein to evaluate the effects of lopinavir, an aspartic protease inhibitor currently used in the treatment of HIV-infected individuals, on the globally widespread opportunistic human fungal pathogen Candida albicans by using in silico, in vitro and in vivo approaches in order to decipher its targets on fungal cells and its antifungal mechanisms of action. Secreted aspartic proteases (Saps) are the obviously main target of lopinavir. To confirm this hypothesis, molecular docking assays revealed that lopinavir bound to the Sap2 catalytic site of C. albicans as well as inhibited the Sap hydrolytic activity in a typically dose-dependent manner. The inhibition of Saps culminated in the inability of C. albicans yeasts to assimilate the unique nitrogen source (albumin) available in the culture medium, culminating with fungal growth inhibition (IC50 = 39.8 µM). The antifungal action of lopinavir was corroborated by distinct microscopy analyses, which evidenced drastic and irreversible changes in the morphology that justified the fungal death. Furthermore, our results revealed that lopinavir was able to (i) arrest the yeasts-into-hyphae transformation, (ii) disturb the synthesis of neutral lipids, including ergosterol, (iii) modulate the surface-located molecules, such as Saps and mannose-, sialic acid- and N-acetylglucosamine-containing glycoconjugates, (iv) diminish the secretion of hydrolytic enzymes, such as Saps and esterase, (v) negatively influence the biofilm formation on polystyrene surface, (vi) block the in vitro adhesion to epithelial cells, (vii) contain the in vivo infection in both immunocompetent and immunosuppressed mice and (viii) reduce the Sap production by yeasts recovered from kidneys of infected animals. Conclusively, the exposed results highlight that lopinavir may be used as a promising repurposing drug against C. albicans infection as well as may be used as a lead compound for the development of novel antifungal drugs.
Intellectual Capital and Knowledge Management Research towards Value Creation. From the Past to the Future
Authors: Abeysekera Indra
Published: May 2021

Over the past decade, the body of literature on intellectual capital and knowledge management has grown exponentially, responding to the growing knowledge-based and digital economy. This article reviews the concepts and applications proposed at the initial stages of the launch of these two research paradigms. It then examines the interconnection between the two. The study selected a set of articles on intellectual capital and knowledge management that forward concepts and applications vital to the inception of these two research domains. The analytical review demonstrates that these concepts and applications, although considered separately in research, are interconnected and inform each other. The paper analyzes, discusses, and forms conclusions based on the self-selected literature with informed research knowledge.
Forests, Farms, and Fallows: The Dynamics of Tree Cover Transition in the Southern Part of the Uluguru Mountains, Tanzania
Authors: Mpanda Mathew , Kashindye Almas , Aynekulu Ermias , Jonas Elvis , Rosenstock Todd S. , Giliba Richard A.
Published: May 2021

Forests and woodlands remain under threat in tropical Africa due to excessive exploitation and inadequate management interventions, and the isolated success stories of tree retention and tree cover transition on African agricultural land are less well documented. In this study, we characterize the status of tree cover in a landscape that contains forest patches, fallows, and farms in the southern part of Uluguru Mountains. We aimed to unveil the practices of traditional tree fallow system which is socially acceptable in local settings and how it provides a buffering effects to minimize forest disturbances and thus represents an important step towards tree cover transition. We assessed land cover dynamics for the period of 1995 to 2020 and compared tree stocking for forest patches, fallows, and farms. We found that tree biomass carbon stocks were 56 ± 5 t/ha in forest patches, 33 ± 7 t/ha in fallows, and 9 ± 2 t/ha on farms. In terms of land cover, farms shrank at intensifying rates over time for the entire assessment period of 1995–2020. Forest cover decreased from 1995–2014, with the reduction rate slowing from 2007–2014 and the trend reversing from 2014–2020, such that forest cover showed a net increase across the entire study period. Fallow consistently and progressively increased from 1995–2020. We conclude that traditional tree fallows in the study site remain a significant element of land management practice among communities, and there appears to be a trend towards intensified tree-based farming. The gains in fallowed land represent an embracing of a traditional land management system that supports rotational and alternate uses of cropping space as well as providing a buffering effect to limit over-exploitation of forests. In order to maximize tree cover and carbon stocks in the farm landscape, this well-known traditional tree fallow system can be further optimized through the incorporation of additional innovations.
Crystal-to-Crystal Transformation from K2[Co(C2O4)2(H2O)2]·4H2O to K2[Co(μ-C2O4)(C2O4)]
Authors: Zhang Bin , Zhang Yan , Chang Guangcai , Wang Zheming , Zhu Daoben
Published: May 2021

Crystal-to-crystal transformation is a path to obtain crystals with different crystal structures and physical properties. K2[Co(C2O4)2(H2O)2]·4H2O (1) is obtained from K2C2O4·2H2O, CoCl2·6H2O in H2O with a yield of 60%. It is crystallized in the triclinic with space group P1 and cell parameters: a = 7.684(1) Å, b = 9.011(1) Å, c = 10.874(1) Å, α = 72.151(2)°, β = 70.278(2)°, γ = 80.430(2)°, V = 670.0(1) Å3, Z = 2 at 100 K. 1 is composed of K+, mononuclear anion [Co(C2O4)2(H2O)22−] and H2O. Co2+ is coordinated by two bidentated oxalate anion and two H2O in an octahedron environment. There is a hydrogen bond between mononuclear anion [Co(C2O4)2(H2O)22−] and H2O. K2[Co(μ-C2O4)(C2O4)] (2) is obtained from 1 by dehydration. The cell parameters of 2 are a = 8.460(5) Å, b = 6.906 (4) Å, c = 14.657(8) Å, β = 93.11(1)°, V = 855.0(8) Å3 at 100 K, with space group in P2/c. It is composed of K+ and zigzag [Co(μ-C2O4)(C2O42−]n chain. Co2+ is coordinated by two bisbendentate oxalate and one bidentated oxalate anion in trigonal-prism. 1 is an antiferromagnetic molecular crystal. The antiferromagnetic ordering at 8.2 K is observed in 2.
A Latency-Optimized Network-on-Chip with Rapid Bypass Channels
Authors: Ma Wenheng , Gao Xiyao , Gao Yudi , Yu Ningmei
Published: May 2021

Network-on-Chips with simple topologies are widely used due to their scalability and high bandwidth. The transmission latency increases greatly with the number of on-chip nodes. A NoC, called single-cycle multi-hop asynchronous repeated traversal (SMART), is proposed to solve the problem by bypassing intermediate routers. However, the bypass setup request of SMART requires additional pipeline stages and wires. In this paper, we present a NoC with rapid bypass channels that integrates the bypass information into each flit. In the proposed NoC, all the bypass requests are delivered along with flits at the same time reducing the transmission latency. Besides, the bypass request is unicasted in our design instead of broadcasting in SMART leading to a great reduction in wire overhead. We evaluate the NoC in four synthetic traffic patterns. The result shows that the latency of our proposed NoC is 63.54% less than the 1-cycle NoC. Compared to SMART, more than 80% wire overhead and 27% latency are reduced.
Macro Modeling of V-Shaped Electro-Thermal MEMS Actuator with Human Error Factor
Authors: Zhang Dongpeng , Cai Anjiang , Zhao Yulong , Hu Tengjiang
Published: May 2021

The V-shaped electro-thermal MEMS actuator model, with the human error factor taken into account, is presented in this paper through the cascading ANSYS simulation model and the Fuzzy mathematics calculation model. The Fuzzy mathematics calculation model introduces the human error factor into the MEMS actuator model by using the BP neural network, which effectively reduces the error between ANSYS simulation results and experimental results to less than 1%. Meanwhile, the V-shaped electro-thermal MEMS actuator model, with the human error factor included, will become more accurate as the database of the V-shaped electro-thermal actuator model grows.
Food Contact Materials: Migration and Analysis. Challenges and Limitations on Identification and Quantification
Authors: Tsochatzis Emmanouil D.
Published: May 2021

Food contact materials (FCM) are defined as the objects and materials intended to come into direct or indirect contact with foodstuff, while food contact articles are defined as objects, being equipment, containers, packaging and various utensils which are clearly intended to be used for the manufacture, preparation, conservation, flow, transport or handling of foodstuffs [...]
Deep Learning Insights into Lanthanides Complexation Chemistry
Authors: Mitrofanov Artem A. , Matveev Petr I. , Yakubova Kristina V. , Korotcov Alexandru , Sattarov Boris , Tkachenko Valery , Kalmykov Stepan N.
Published: May 2021

Modern structure–property models are widely used in chemistry; however, in many cases, they are still a kind of a “black box” where there is no clear path from molecule structure to target property. Here we present an example of deep learning usage not only to build a model but also to determine key structural fragments of ligands influencing metal complexation. We have a series of chemically similar lanthanide ions, and we have collected data on complexes’ stability, built models, predicting stability constants and decoded the models to obtain key fragments responsible for complexation efficiency. The results are in good correlation with the experimental ones, as well as modern theories of complexation. It was shown that the main influence on the constants had a mutual location of the binding centers.
Size- and Surface- Dual Engineered Small Polyplexes for Efficiently Targeting Delivery of siRNA
Authors: Liu Shuang , Deng Shaohui , Li Xiaoxia , Cheng Du
Published: May 2021

Though siRNA-based therapy has achieved great progress, efficient siRNA delivery remains a challenge. Here, we synthesized a copolymer PAsp(-N=C-PEG)-PCys-PAsp(DETA) consisting of a poly(aspartate) block grafted with comb-like PEG side chains via a pH-sensitive imine bond (PAsp(-N=C-PEG) block), a poly(l-cysteine) block with a thiol group (PCys block), and a cationic poly(aspartate) block grafted with diethylenetriamine (PAsp(DETA) block). The cationic polymers efficiently complexed siRNA into polyplexes, showing a sandwich-like structure with a PAsp(-N=C-PEG) out-layer, a crosslinked PCys interlayer, and a complexing core of siRNA and PAsp(DETA). Low pH-triggered breakage of pH-sensitive imine bonds caused PEG shedding. The disulfide bond-crosslinking and pH-triggered PEG shedding synergistically decreased the polyplexes’ size from 75 nm to 26 nm. To neutralize excessive positive charges and introduce the targeting ligand, the polyplexes without a PEG layer were coated with an anionic copolymer modified with the targeting ligand lauric acid. The resulting polyplexes exhibited high transfection efficiency and lysosomal escape capacity. This study provides a promising strategy to engineer the size and surface of polyplexes, allowing long blood circulation and targeted delivery of siRNA.
Free-Standing rGO-CNT Nanocomposites with Excellent Rate Capability and Cycling Stability for Na2SO4 Aqueous Electrolyte Supercapacitors
Authors: Du Xiaohan , Qin Zhen , Li Zijiong
Published: May 2021

Facing the increasing demand for various renewable energy storage devices and wearable and portable energy storage systems, the research on electrode materials with low costs and high energy densities has attracted great attention. Herein, free-standing rGO-CNT nanocomposites have been successfully synthesized by a facile hydrothermal method, in which the hierarchical porous network nanostructure is synergistically assembled by rGO nanosheets and CNT with interlaced network distribution. The rGO-CNT composite electrodes with synergistic enhancement of rGO and CNT exhibit high specific capacitance, excellent rate capability, exceptional conductivity and outstanding long-term cycling stability, especially for the optimal rGO-CNT30 electrode. Applied to a symmetric supercapacitor systems (SSS) assembled with an rGO-CNT30 electrode and with 1 M Na2SO4 aqueous solution as the electrolyte, the SSS possesses a high energy density of 12.29 W h kg−1 and an outstanding cycling stability, with 91.42% of initial specific capacitance after 18,000 cycles. Results from these electrochemical properties suggest that the rGO-CNT30 nanocomposite electrode is a promising candidate for the development of flexible and lightweight high-performance supercapacitors.
Development of a Nanocrystal Formulation of a Low Melting Point API Following a Quality by Design Approach
Authors: Ouranidis Andreas , Gkampelis Nikos , Markopoulou Catherine , Nikolakakis Ioannis , Kachrimanis Kyriakos
Published: May 2021

Preparation of nanocrystal formulations by wet media milling and spray-drying is a reliable technique to enhance dissolution and ameliorate absorption limitations of poorly soluble BCS II drugs. However, when thermosensitive compositions are dried at high temperatures, the risks of particle aggregation and thermal degradation must be considered. The present study investigates the effects of nanosuspension formulation variables when performing the spray drying process at equidistant temperatures above and below the melting point. Towards this purpose, Fenofibrate is exploited as a model drug of unfavorable pharmacokinetic profile and low melting point (79–82 °C), properties that render thermal processing a nontrivial task. Rationalizing the system’s behavior by combining molecular simulations with QbD methodology, the preparation of stable nanocrystals can be “steered” in order to avoid undesirable melting. The statistically resolved operational conditions showed that Fenofibrate Critical Quality Attribute–compliant nanosuspensions i.e., bearing hydrodynamic diameter and ζ-potential of 887 nm and −16.49 mV, respectively, were obtained by wet milling drug to Pharmacoat and mannitol weighted optimum ratios of 4.075% and 0.75%, after spray drying at the desired temperature of 77 °C. In conclusion, we present a quality assurance methodology of nano-comminution generally applicable for thermo-labile BCS II drugs.
Zolmitriptan Intranasal Spanlastics for Enhanced Migraine Treatment; Formulation Parameters Optimized via Quality by Design Approach
Authors: Saleh Asmaa , Khalifa Maha , Shawky Seham , Bani-Ali Amjaad , Eassa Heba
Published: May 2021

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.
Effective Implementation of Urban Agendas through Urban Action Structures (UAS): The Case of the Basque Country
Authors: Otamendi-Irizar Irati , Grijalba Olatz , Arias Alba , Pennese Claudia , Hernández Rufino
Published: May 2021

Cities are the main contributors to pollution, resource consumption and social inequalities. Therefore, they should play a key role in the path towards a more sustainable scenario in line with SDGs and different Urban Agendas. However, there are still difficulties in their implementation and citizen can play a central role. This paper presents the Urban Action Structures (UAS), understood as entities with a catalytic capacity with respect to innovative urban policies. Methodologically, firstly, a prospective analysis from regional to international level has been developed, making it possible to identify innovative lines of action in the field of sustainable cities. Secondly, the study has focused on identifying and studying UAS that can make it possible to implement the lines of action previously identified. This paper has shown that there are already social structures that can be understood as UAS, since they implement actions aligned with the priorities of the Urban Agenda for the Basque Country and, therefore, of the SDGs. The research concludes that UAS can play a key role in facilitating the implementation of Urban Agendas. Hence, urban policies should favor the generation of UAS, in order to promote long-term urban development and to foster a more sustainable spatial planning.
Fragmented Forest Patches in the Indian Himalayas Preserve Unique Components of Biodiversity: Investigation of the Floristic Composition and Phytoclimate of the Unexplored Bani Valley
Authors: Singh Sumit , Singh Bikarma , Surmal Opender , Bhat Mudasir Nazir , Singh Bishander , Musarella Carmelo Maria
Published: May 2021

Subtropical and temperate forests are amongst the most threatened habitats of Asia, due to large-scale habitat loss and the fragmentation of landscapes. Inspite of these, the Asiatic regions preserve their endemic biodiversity, and provide a favorable environment for the abundant growth of vegetation. In the Himalayas, many interior regions are still unexplored from a biodiversity perspective, due to remote locations and high snow-clad mountains. In this study, we investigated the unexplored Bani Valley in order to reduce the gap of uninventorized areas of rich biodiversity in the Himalayas and formulate plant conservation and management strategies. Thirteen field expedition tours were undertaken during 2017 and 2020 for data collection in different growing seasons in the study area. All plant species were collected as voucher samples, identified, and deposited in the internationally recognized Janaki Ammal Herbarium (acronym RRLH). GPS points were recorded in order to study the forest types and vegetation components of the study area. A total of 196 plant species belonging to 166 genera and 68 families were identified in Bani Valley, covering a total area of 2651 km2. Approximately 70.62% of the species were native and 29.38% were non-native. In total, 46% of species were Indo-Malayan, followed by 22% Palearctic species. In angiosperms, dicotyledon species (68.37%) dominated. Poales were the most dominant order, with 38 species (19.38%). The most abundant families were Poaceae with 29 species (14.79%), Fabaceae (17, 8.67%), Rosaceae, Cyperaceae, and Asteraceae (9, 4.59% each). The life form analysis showed 50% of species as phanerophytes, followed by therophytes (25.77%). The leaf size spectra show mesophyllous species (34.69%) as the dominant group. The IUCN Red List of Threatened Plants categorized Ailanthus altissima as endangered (EN), Aegle marmelos and Quercus oblongata as near threatened (NT), Ulmus wallichiana and Plantago lanceolata as vulnerable (VU), Taxus baccata and 75 other species as least concern (LC), and 2 species as data deficient (DD). The remaining 113 species of plants had not been evaluated according to the IUCN Red List of Threatened Species. This study will help to shape conservation and management plans for threatened species for future implementation, and will help in biodiversity conservation. This study will serve as a database for future reference materials in terms of biodiversity management.
Relational Embeddedness and BOP-Oriented Dynamic Capability—A Multi-Case Study
Authors: Zhang Yina , Long Jiancheng , Zhao Wu
Published: May 2021

The Bottom of the Pyramid (BOP) market is composed of a large number of low-income groups around the world and contains huge wealth that has not yet been discovered. An exploratory multi-case study was conducted to analyze the impact of relational embeddedness on dynamic capability (DC). On the basis of theoretical presuppositions, based on the intra- and inter-case analysis of six companies in the China BOP market, this paper explores how relational embeddedness affects the DC of companies through exploitative learning and exploratory learning. Twelve research propositions are presented and the theoretical framework of relational embeddedness affecting the DC of enterprises is constructed. The study found that mutual trust and reciprocity norms in the BOP cooperation network can promote the acquisition and utilization of existing knowledge and new knowledge of the enterprise, thereby enhancing the enterprise environmental sensing, environmental adaptive, and environmental shaping capabilities.
Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure
Authors: Wang Shufeng , Yang Xin , Liu Feng , Wang Xinzheng , Zhang Xuemin , He Kun , Wang Hongxia
Published: May 2021

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.
Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?
Authors: Crawford Sue E. , Ramani Sasirekha , Blutt Sarah E. , Estes Mary K.
Published: May 2021

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.