bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Existing Publications and Most Relevant Projects/Platforms on the Use of Blockchain in Medicine and Neurology
Authors: Hort Jakub , Vališ Martin , Zhang Bing , Kuča Kamil , Angelucci Francesco
Published: March 2021

Background

Blockchain is a new methodology involving a data structure with list of records, called blocks, which are linked using cryptography. The aim of the review is to overview the existing publication, projects, and platforms on the use of blockchain in Medicine and Neurology.

Methods

We searched the bibliographic database of MEDLINE and BASE. We also accessed ICObench, Coinmarketcap, and Mobihealthnews databases to explore upcoming, ongoing, and ended projects.

Results

In medicine, there are many projects related to health care, disease prevention, and promotion of healthy life style. In neurology, only one project looks promising: Neuro, an ongoing scientific-technical project uniting scientists, engineers, and programmers for development of new architectures and algorithms of neural networks. Bibliographic searches found 117 publications on Medline and 203 publications on BASE referring to the use of blockchain technology in medicine. Most of them are presented as reviews (narrative, systematic, or minireview), opinions and hypotheses, commentaries, or perspectives. As for Neurology, only one publication refers to the use of blockchain, specifically to Parkinson’s disease.

Discussion

Among the problems related to medicine, there is the lack of information on the patient’s clinical history that could allow accurate diagnosis and treatment. The possibility of having a register based on blockchain technology could help doctors in many ways, including patient management, choosing and monitoring treatments, and standardization of clinical trials.

Conclusion

The use of the blockchain technology in medicine has been repetitively proposed to solve different problems. In this article, we highlight the possible benefits of this technology, with attention to Neurology. Blockchain use can lead to quantifiable benefits in the treatment of neurodegenerative diseases, especially in clinical trials that can fail because of an incorrect patient recruitment.
Synthesizing Electrodes Into Electrochemical Sensor Systems
Authors: Mourzina Yulia G. , Ermolenko Yuri E. , Offenhäusser Andreas
Published: March 2021

Electrochemical sensors that can determine single/multiple analytes remain a key challenge in miniaturized analytical systems and devices. In this study, we present in situ synthesis and modification of gold nanodendrite electrodes to create an electrochemical system for the analysis of hydrogen peroxide. The sensor system consisted of the reference and counter electrodes as well as the working electrode. Electrochemical reduction of graphene oxide, ErGO, on the thin-film gold and gold nanodendrite working electrodes was used to achieve an efficient sensor interface for the adsorption of a biomimetic electrocatalytic sensor material, Mn(III) meso-tetra(N-methyl-4-pyridyl) porphyrin complex, with as high as 10–10 mol cm−2 surface coverage. The sensor system demonstrated a detection limit of 0.3 µM H2O2 in the presence of oxygen. Electrochemical determination of hydrogen peroxide in plant material in the concentration range from 0.09 to 0.4 µmol (gFW)−1 using the electrochemical sensor system was shown as well as in vivo real-time monitoring of the hydrogen peroxide dynamics as a sign of abiotic stress (intense sunlight). Results of the electrochemical determination were in good agreement with the results of biochemical analysis with the spectrophotometric detection. We anticipate that this method can be extended for the synthesis and integration of multisensor arrays in analytical microsystems and devices for the quantification and real-time in vivo monitoring of other analytes and biomarkers.
Two Novel Bacteriophages Control Multidrug- and Methicillin-Resistant Staphylococcus pseudintermedius Biofilm
Authors: Kim Sang Guen , Giri Sib Sankar , Yun Saekil , Kim Sang Wha , Han Se Jin , Kwon Jun , Oh Woo Teak , Lee Sung Bin , Park Yong Ho , Park Se Chang
Published: March 2021

As a primary bacterial pathogen in companion animals, Staphylococcus pseudintermedius has zoonotic potential. This pathogen exhibits multidrug resistance, including resistance to methicillin, and biofilm-forming ability, making it hard to eradicate with antimicrobial agents. One potential alternative is bacteriophage therapy. In this study, we first characterized the antimicrobial resistance profile of S. pseudintermedius from canine samples and isolated two novel bacteriophages, pSp-J and pSp-S, from canine pet parks in South Korea to potentially control S. pseudintermedius. The biological characteristics of phages were assessed, and the phages could infect most of the methicillin-resistant S. pseudintermedius strains. We found that these phages were stable under the typical environment of the body (~37°C, pH 7). We also assessed bacterial lysis kinetics using the two phages and their cocktail, and found that the phages could prevent biofilm formation at low doses and could degrade biofilm at high doses. Taken together, this study demonstrates that bacteriophages pSp-J and pSp-S isolated in this study can be used to potentially treat methicillin-resistant S. pseudintermedius.
Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection
Authors: Goutelle Sylvain , Conrad Anne , Pouderoux Cécile , Braun Evelyne , Laurent Frédéric , Gagnieu Marie-Claude , Cohen Sabine , Guitton Jérôme , Valour Florent , Ferry Tristan
Published: March 2021

Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.
Mycobacterium tuberculosis Thymidylyltransferase RmlA Is Negatively Regulated by Ser/Thr Protein Kinase PknB
Authors: Qu Dehui , Zhao Xiaohui , Sun Yao , Wu Fan-Lin , Tao Sheng-Ce
Published: March 2021

Ser/Thr phosphorylation by serine/threonine protein kinases (STPKs) plays significant roles in molecular regulation, which allows Mycobacteria to adapt their cell wall structure in response to the environment changes. Identifying direct targets of STPKs and determining their activities are therefore critical to revealing their function in Mycobacteria, for example, in cell wall formation and virulence. Herein, we reported that RmlA, a crucial L-rhamnose biosynthesis enzyme, is a substrate of STPK PknB in Mycobacterium tuberculosis (M. tuberculosis). Mass spectrometry analysis revealed that RmlA is phosphorylated at Thr-12, Thr-54, Thr-197, and Thr-12 is located close to the catalytic triad of RmlA. Biochemical and phenotypic analysis of two RmlA mutants, T12A/T12D, showed that their activities were reduced, and cell wall formation was negatively affected. Moreover, virulence of RmlA T12D mutant was attenuated in a macrophage model. Overall, these results provide the first evidence for the role of PknB-dependent RmlA phosphorylation in regulating cell wall formation in Mycobacteria, with significant implications for pathogenicity.
The Insights of Genomic Synteny and Codon Usage Preference on Genera Demarcation of Iridoviridae Family
Authors: Deng Zhaobin , Wang Jun , Zhang Wenjie , Geng Yi , Zhao Mingde , Gu Congwei , Fu Lu , He Manli , Xiao Qihai , Xiao Wudian , He Lvqin , Yang Qian , Han Jianhong , Yan Xuefeng , Yu Zehui
Published: March 2021

The members of the family Iridoviridae are large, double-stranded DNA viruses that infect various hosts, including both vertebrates and invertebrates. Although great progress has been made in genomic and phylogenetic analyses, the adequacy of the existing criteria for classification within the Iridoviridae family remains unknown. In this study, we redetermined 23 Iridoviridae core genes by re-annotation, core-pan analysis and local BLASTN search. The phylogenetic tree based on the 23 re-annotated core genes (Maximum Likelihood, ML-Tree) and amino acid sequences (composition vector, CV-Tree) were found to be consistent with previous reports. Furthermore, the information provided by synteny analysis and codon usage preference (relative synonymous codon usage, correspondence analysis, ENC-plot and Neutrality plot) also supports the phylogenetic relationship. Collectively, our results will be conducive to understanding the genera demarcation within the Iridoviridae family based on genomic synteny and component (codon usage preference) and contribute to the existing taxonomy methods for the Iridoviridae family.
Inhibition of the NKCC1/NF-κB Signaling Pathway Decreases Inflammation and Improves Brain Edema and Nerve Cell Apoptosis in an SBI Rat Model
Authors: Gong Yating , Wu Muyao , Shen Jinchao , Tang Jiafeng , Li Jie , Xu Jianguo , Dang Baoqi , Chen Gang
Published: March 2021

Surgical brain injury (SBI) triggers microglia to release numerous inflammatory factors, leading to brain edema and neurological dysfunction. Reducing neuroinflammation and protecting the blood-brain barrier (BBB) are key factors to improve the neurological function and prognosis after SBI. Na+-K+-Cl– cotransporter 1 (NKCC1) and nuclear factor κB (NF-κB) have been implicated in the secretion of inflammatory cytokines by microglia in brain injury. This study aimed to establish the role of NKCC1 in inducing inflammation in SBI, as well as to determine whether NKCC1 controls the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) via phosphorylation of NF-κB in microglia, thus affecting BBB permeability and neuronal cell apoptosis. Male Sprague-Dawley (SD) rats were used to establish an SBI model. This study revealed that compared with the sham group, the expression levels of p-NKCC1, p-p65-NF-κB, and related inflammatory factor proteins in SBI model group significantly increased. After p-NKCC1 was inhibited, p-p65-NF-κB, IL-6, IL-1β, and TNF-α were downregulated, and nerve cell apoptosis and BBB permeability were significantly reduced. These findings suggest that the SBI-induced increase in p-NKCC1 exacerbates neuroinflammation, brain edema, and nerve function injury, which may be mediated by regulating the activity of p65-NF-κB that in turn influences the release of inflammatory factors.
The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway
Authors: Yan Limei , He Zeping , Li Wei , Liu Ning , Gao Song
Published: March 2021

Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of Acyl-CoA medium-chain synthetase-3 (ACSM3, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation assay, and cell cycle analysis were carried out to investigate cell proliferation ability. Wound healing assay and transwell assay were subsequently used to assess cell migration and invasion. Mice xenografts were then conducted to measure the effects of ACSM3 on tumor development in vivo. Our bioinformatics analysis suggested that the expression of ACSM3 was down-regulated in ovarian cancer tissues, and the low expression level of ACSM3 might related with poorer overall survival than high mRNA expression of ACSM3 in ovarian cancer patients. We artificially regulated the expression of ACSM3 to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of ACSM3 inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of ACSM3 received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by ACSM3 expression. Moreover, ACSM3 overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of ITG β1 (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of ACSM3. And ACSM3 interference obtained the contrary effects in vivo. In summary, ACSM3 acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer.
LINC00941 Promotes Progression of Non-Small Cell Lung Cancer by Sponging miR-877-3p to Regulate VEGFA Expression
Authors: Ren Min-Huan , Chen Si , Wang Liang-Ge , Rui Wen-Xiu , Li Pei
Published: March 2021

Long noncoding RNAs (lncRNAs) play critical roles in carcinoma occurrence and metastasis. LINC00941 has been found to mediate the development of gastric cancer, and LINC00941 was negatively associated with the longer overall survival of lung adenocarcinoma patients. Herein, our aim was to investigate the effects and mechanisms of LINC00941 in NSCLC progression. Microarray was used to identify the change lncRNAs in NSCLC, LINC00941 was found to increase in tumor tissues and patients’ plasma. Knockdown of LINC00941 didn’t modulate the proliferation of NSCLC cells, but inhibition of LINC00941 in NSCLC cells suppressed the angiogenesis ability of human umbilical vein endothelial cells (HUVECs). Moreover, LINC00941 promoted tumorigenesis in vivo, while si-LINC00941 inhibited tumor development of NSCLC. VEGFA was should to be significantly modulated by LINC00941 in NSCLC cells, then luciferase assay proved that LINC00941 regulated VEGFA expression via interacting with miR-877-3p. Followed functional experiments indicated that overexpression of LINC00941 accelerated angiogenesis and NSCLC tumor progression via miR-877-3p/VEGFA axis both in vitro and in vivo. In conclusion, our results clarified the LINC00941 function for the first time, and LINC00941 promoted the progression of NSCLC, which was mediated by miR-877-3p/VEGFA axis. This study might provide new understanding and targets for NSCLC diagnosis and treatment.
Superconductivity in Cubic A15-type V–Nb–Mo–Ir–Pt High-Entropy Alloys
Authors: Liu Bin , Wu Jifeng , Cui Yanwei , Zhu Qinqing , Xiao Guorui , Wu Siqi , Cao Guanghan , Ren Zhi
Published: March 2021

We report the crystal structure and superconducting properties of new V5+2xNb35−xMo35−xIr10Pt15 high-entropy alloys (HEAs) for x in the range of 0 ≤x≤ 10. These HEAs are found to crystallize in a cubic A15-type structure and have a weakly coupled, fully gapped superconducting state. A maximum Tc of 5.18 K and zero-temperature upper critical field Bc2(0) of 6.4 T are observed at x = 0, and both quantities decrease monotonically with the increase of V content x. In addition, Tc shows an increase with increasing valence electron concentration from 6.4 to 6.5, which is compared with other A15-type HEA and binary superconductors.
Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells: Current Controversies
Authors: Lu Tyler M. , Barcia Durán José Gabriel , Houghton Sean , Rafii Shahin , Redmond David , Lis Raphaël
Published: March 2021

Brain microvascular endothelial cells (BMECs) possess unique properties that are crucial for many functions of the blood-brain-barrier (BBB) including maintenance of brain homeostasis and regulation of interactions between the brain and immune system. The generation of a pure population of putative brain microvascular endothelial cells from human pluripotent stem cell sources (iBMECs) has been described to meet the need for reliable and reproducible brain endothelial cellsin vitro. Human pluripotent stem cells (hPSCs), embryonic or induced, can be differentiated into large quantities of specialized cells in order to study development and model disease. These hPSC-derived iBMECs display endothelial-like properties, such as tube formation and low-density lipoprotein uptake, high transendothelial electrical resistance (TEER), and barrier-like efflux transporter activities. Over time, thede novogeneration of an organotypic endothelial cell from hPSCs has aroused controversies. This perspective article highlights the developments made in the field of hPSC derived brain endothelial cells as well as where experimental data are lacking, and what concerns have emerged since their initial description.
An Overview of Antennal Esterases in Lepidoptera
Authors: Godoy Ricardo , Machuca Juan , Venthur Herbert , Quiroz Andrés , Mutis Ana
Published: March 2021

Lepidoptera are used as a model for the study of insect olfactory proteins. Among them, odorant degrading enzymes (ODEs), that degrade odorant molecules to maintain the sensitivity of antennae, have received less attention. In particular, antennal esterases (AEs; responsible for ester degradation) are crucial for intraspecific communication in Lepidoptera. Currently, transcriptomic and genomic studies have provided AEs in several species. However, efforts in gene annotation, classification, and functional assignment are still lacking. Therefore, we propose to combine evidence at evolutionary, structural, and functional level to update ODEs as well as key information into an easier classification, particularly of AEs. Finally, the kinetic parameters for putative inhibition of ODEs are discussed in terms of its role in future integrated pest management (IPM) strategies.
Political Regimes and External Voting Rights: A Cross-National Comparison
Authors: Umpierrez de Reguero Sebastián A. , Yener-Roderburg Inci Öykü , Cartagena Vivian
Published: March 2021

In this article, we analyze the nexus between political regimes and external voting rights. Using a global longitudinal dataset, we report that higher levels of inclusion and contestation bring higher probabilities that a state adopts and implements emigrant enfranchisement. Taking outliers from our quantitative assessment, we then further examine two liberal democracies, Ireland and Uruguay, and two electoral autocracies, Turkey and Venezuela. These country cases reveal three mechanisms that shed light on the strategic role of political elites in explaining the relation between political regime type and emigrant enfranchisement. First, the democracies under study show us that in certain contexts with a relatively large diaspora size and in which part of the political spectrum is hesitant about the political orientation of nonresident citizens, emigrant enfranchisement is neither necessarily promulgated nor implemented. Second, the autocracies illustrate that when the diaspora favors (or is perceived to favor) the incumbency, then external voting rights are extended; otherwise, third, they are withheld or limited for nonresident citizens.
Associations Between Trauma, Early Maladaptive Schemas, Personality Traits, and Clinical Severity in Eating Disorder Patients: A Clinical Presentation and Mediation Analysis
Authors: Meneguzzo Paolo , Cazzola Chiara , Castegnaro Roberta , Buscaglia Francesca , Bucci Enrica , Pillan Anna , Garolla Alice , Bonello Elisa , Todisco Patrizia
Published: March 2021

Background: The literature has shown a significant association between traumatic experiences and eating psychopathology, showing a greater symptomatology in patients with trauma history. Less is known about the associations between trauma and cognitive schemas, and personality traits and the differences between childhood and adulthood trauma experiences. Thus, this paper aims to assess the clinical and psychological characteristics of eating disorder (ED) patients, looking for differences between patients without a history of trauma and patients with trauma experiences, as well as at possible differences between exposure in childhood, adulthood, or repeated events. Another aim of the paper is to evaluate the possible mediation role of cognitive schemas and personality traits in the relationship between early trauma and eating psychopathology.

Methods: From January to November 2020, 115 consecutive inpatients admitted for a specific multidisciplinary ED treatment in a dedicated Unit were evaluated for trauma, differentiating between trauma occurring in childhood and adulthood. The subjects were evaluated for early maladaptive schemas (EMS), personality traits, trauma symptomatology, quality of life, and specific psychopathologies linked to EDs. Mediation analyses between childhood and adulthood trauma and eating psychopathology were performed, with EMS and personality traits as mediators.

Results: Patients with a history of trauma showed higher physical and psychological symptomatology scores, with a more impaired clinical profile in patients with both childhood and adulthood trauma exposure. The mediation analysis showed a specific mediator role for the “disconnection and rejection (DR)” EMS factor in the relationship between childhood trauma (cT) and eating psychopathology.

Conclusion: Trauma experiences are associated with more severe clinical symptomatology in EDs and may need a specific assessment in patients with failed outpatient standard treatments. Specific cognitive schemas linked to DR domain should be evaluated in treatments for ED patients with history of trauma due to the mediation role between trauma and eating psychopathology. The need for outcome studies about treatment approaches for ED patients with history of trauma is discussed.
Developing and Testing a Local Expert-Based Reading Process for Use to Examine Discrepancies Between Guidelines and Current Clinical Practices
Authors: Cases Cécile , Gallini Adeline , Lafont Rapnouil Stéphanie , Bougon Emmanuelle , Mathur Anjali , Brismontier Ariane , Taib Simon , Sporer Marie , Arbus Christophe , Salles Juliette
Published: March 2021

The use of relevant guidelines is critical in psychiatric clinical practice to ensure the homogeneity of the global care provided. Consequently, it is important to identify whether they are utilized successfully and, if not, why. This would enable pragmatic solutions to be agreed to improve the organization of care and the removal of any barriers to the guidelines' implementation. The first step in this process, before any exploration of the limitations of the guidelines themselves, involves a determination of whether they are actually applied in clinical practice. We therefore evaluated discrepancies between the guidelines relating to patients with borderline personality disorder and current practices in the psychiatric Emergency Department at Toulouse University Hospital. This was achieved using a reading process involving a panel of eight local experts who analyzed relevant medical files extracted from a database. They were guided by, and instructed to answer, six standardized questions in relation to each file to determine the method's feasibility. A total of 333 files were analyzed to determine whether, in the local experts' judgment, the care provided reflected current guidance. This reading process revealed substantial agreement (0.85%; Fleiss Kappa −0.69), which is a promising outcome and suggests that such methods could be used in future protocols. Moreover, the process is practical and reliable and requires very few materials.
Efficient Attention Mechanism for Dynamic Convolution in Lightweight Neural Network
Authors: Ding Enjie , Cheng Yuhao , Xiao Chengcheng , Liu Zhongyu , Yu Wanli
Published: March 2021

Light-weight convolutional neural networks (CNNs) suffer limited feature representation capabilities due to low computational budgets, resulting in degradation in performance. To make CNNs more efficient, dynamic neural networks (DyNet) have been proposed to increase the complexity of the model by using the Squeeze-and-Excitation (SE) module to adaptively obtain the importance of each convolution kernel through the attention mechanism. However, the attention mechanism in the SE network (SENet) selects all channel information for calculations, which brings essential challenges: (a) interference caused by the internal redundant information; and (b) increasing number of network calculations. To address the above problems, this work proposes a dynamic convolutional network (termed as EAM-DyNet) to reduce the number of channels in feature maps by extracting only the useful spatial information. EAM-DyNet first uses the random channel reduction and channel grouping reduction methods to remove the redundancy in the information. As the downsampling of information can lead to the loss of useful information, it then applies an adaptive average pooling method to maintain the information integrity. Extensive experimental results on the baseline demonstrate that EAM-DyNet outperformed the existing approaches, thus it can achieve higher accuracy of the network test and less network parameters.
Overlapping Community Detection of Bipartite Networks Based on a Novel Community Density
Authors: Peng Yubo , Zhang Bofeng , Chang Furong
Published: March 2021

Community detection plays an essential role in understanding network topology and mining underlying information. A bipartite network is a complex network with more important authenticity and applicability than a one-mode network in the real world. There are many communities in the network that present natural overlapping structures in the real world. However, most of the research focuses on detecting non-overlapping community structures in the bipartite network, and the resolution of the existing evaluation function for the community structure’s merits are limited. So, we propose a novel function for community detection and evaluation of the bipartite network, called community density D. And based on community density, a bipartite network community detection algorithm DSNE (Density Sub-community Node-pair Extraction) is proposed, which is effective for overlapping community detection from a micro point of view. The experiments based on artificially-generated networks and real-world networks show that the DSNE algorithm is superior to some existing excellent algorithms; in comparison, the community density (D) is better than the bipartite network’s modularity.
Effects of Edible Insect Tenebrio molitor Larva Fermentation Extract as a Substitute Protein on Hepatosteatogenesis and Proteomic Changes in Obese Mice Induced by High-Fat Diet
Authors: Ham Ju Ri , Choi Ra-Yeong , Lee Yongjin , Lee Mi-Kyung
Published: March 2021

Mealworms (Tenebrio molitor larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the PPARγ, CD36, and DGAT2 gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.
Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium
Authors: Paul Emmanuel N. , Burns Gregory W. , Carpenter Tyler J. , Grey Joshua A. , Fazleabas Asgerally T. , Teixeira Jose M.
Published: March 2021

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.
High ROS Production by Celecoxib and Enhanced Sensitivity for Death Ligand-Induced Apoptosis in Cutaneous SCC Cell Lines
Authors: Zhu Jiaqi , May Stefanie , Ulrich Claas , Stockfleth Eggert , Eberle Jürgen
Published: March 2021

Incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis has increased worldwide, and non-steroidal anti-inflammatory drugs as celecoxib are considered for treatment. We show here strong anti-proliferative effects of celecoxib in four cSCC cell lines, while apoptosis and cell viability largely remained unaffected. Impeded apoptosis was overcome in combinations with agonistic CD95 antibody or TNF-related apoptosis-inducing ligand (TRAIL), resulting in up to 60% apoptosis and almost complete loss of cell viability. Proapoptotic caspase cascades were activated, and apoptosis was suppressed by caspase inhibition. TRAIL receptor (DR5) and proapoptotic Bcl-2 proteins (Puma and Bad) were upregulated, while anti-apoptotic factors (survivin, XIAP, cFLIP, Mcl-1, and Bcl-w) were downregulated. Strongly elevated levels of reactive oxygen species (ROS) turned out as particularly characteristic for celecoxib, appearing already after 2 h. ROS production alone was not sufficient for apoptosis induction but may play a critical role in sensitizing cancer cells for apoptosis and therapy. Thus, the full therapeutic potential of celecoxib may be better used in combinations with death ligands. Furthermore, the immune response against cSCC/AK may be improved by celecoxib, and combinations with checkpoint inhibitors, recently approved for the treatment of cSCC, may be considered.
Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells
Authors: Papasavva Panayiota , Papaioannou Nikoletta , Patsali Petros , Kurita Ryo , Nakamura Yukio , Sitarou Maria , Christou Soteroulla , Kleanthous Marina , Lederer Carsten
Published: March 2021

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.
Effects of Adenine Methylation on the Structure and Thermodynamic Stability of a DNA Minidumbbell
Authors: Wan Liqi , Lam Sik Lok , Lee Hung Kay , Guo Pei
Published: March 2021

DNA methylation is a prevalent regulatory modification in prokaryotes and eukaryotes. N1-methyladenine (m1A) and N6-methyladenine (m6A) have been found to be capable of altering DNA structures via disturbing Watson–Crick base pairing. However, little has been known about their influences on non-B DNA structures, which are associated with genetic instabilities. In this work, we investigated the effects of m1A and m6A on both the structure and thermodynamic stability of a newly reported DNA minidumbbell formed by two TTTA tetranucleotide repeats. As revealed by the results of nuclear magnetic resonance spectroscopic studies, both m1A and m6A favored the formation of a T·m1A and T·m6A Hoogsteen base pair, respectively. More intriguingly, the m1A and m6A modifications brought about stabilization and destabilization effects on the DNA minidumbbell, respectively. This work provides new biophysical insights into the effects of adenine methylation on the structure and thermodynamic stability of DNA.
Comparison of the Dielectric Properties of Ecoflex® with L,D-Poly(Lactic Acid) or Polycaprolactone in the Presence of SWCN or 5CB
Authors: Fryń Patryk , Lalik Sebastian , Górska Natalia , Iwan Agnieszka , Marzec Monika
Published: March 2021

The main goal of this paper was to study the dielectric properties of hybrid binary and ternary composites based on biodegradable polymer Ecoflex®, single walled carbon nanotubes (SWCN), and liquid crystalline 4′-pentyl-4-biphenylcarbonitrile (5CB) compound. The obtained results were compared with other created analogically to Ecoflex®, hybrid layers based on biodegradable polymers such as L,D-polylactide (L,D-PLA) and polycaprolactone (PCL). Frequency domain dielectric spectroscopy (FDDS) results were analyzed taking into consideration the amount of SWCN, frequency, and temperature. For pure Ecoflex®, two relaxation processes (α and β) were identified. It was shown that the SWCN admixture (in the weight ratio 10:0.01) did not change the properties of the Ecoflex® layer, while in the case of PCL and L,D-PLA, the layers became conductive. The dielectric constant increased with an increase in the content of SWCN in the Ecoflex® matrix and the conductive behavior was not visible, even for the greatest concentration (10:0.06 weight ratio). In the case of the Ecoflex® polymer matrix, the conduction relaxation process at a frequency ca. several kilohertz appeared and became stronger with an increase in the SWCN admixture in the matrix. Addition of oleic acid to the polymer matrix had a smaller effect on the increase in the dielectric response than the addition of liquid crystal 5CB. Fourier transform infrared (FTIR) results revealed that the molecular structure and chemical character of the Ecoflex® and PCL matrixes remained unchanged upon the addition of SWCN or 5CB in a weight ratio of 10:0.01 and 10:1, respectively, while molecular interactions appeared between L,D-PLA and 5CB. Moreover, adding oleic acid to pure Ecoflex® as well as the binary and ternary hybrid layers with SWCN and/or 5CB in a weight ratio of Ecoflex®:oleic acid equal to 10:0.3 did not have an influence on the chemical bonding of these materials.
Biochemical Properties and Anti-Biofilm Activity of Chitosan-Immobilized Papain
Authors: Baidamshina Diana R. , Koroleva Victoria A. , Olshannikova Svetlana S. , Trizna Elena Yu. , Bogachev Mikhail I. , Artyukhov Valeriy G. , Holyavka Marina G. , Kayumov Airat R.
Published: March 2021

Chitosan, the product of chitin deacetylation, is an excellent candidate for enzyme immobilization purposes. Here we demonstrate that papain, an endolytic cysteine protease (EC: 3.4.22.2) from Carica papaya latex immobilized on the matrixes of medium molecular (200 kDa) and high molecular (350 kDa) weight chitosans exhibits anti-biofilm activity and increases the antimicrobials efficiency against biofilm-embedded bacteria. Immobilization in glycine buffer (pH 9.0) allowed adsorption up to 30% of the total protein (mg g chitosan−1) and specific activity (U mg protein−1), leading to the preservation of more than 90% of the initial total activity (U mL−1). While optimal pH and temperature of the immobilized papain did not change, the immobilized enzyme exhibited elevated thermal stability and 6–7-fold longer half-life time in comparison with the soluble papain. While one-half of the total enzyme dissociates from both carriers in 24 h, this property could be used for wound-dressing materials design with dosed release of the enzyme to overcome the relatively high cytotoxicity of soluble papain. Our results indicate that both soluble and immobilized papain efficiently destroy biofilms formed by Staphylococcus aureus and Staphylococcus epidermidis. As a consequence, papain, both soluble and immobilized on medium molecular weight chitosan, is capable of potentiating the efficacy of antimicrobials against biofilm-embedded Staphylococci. Thus, papain immobilized on medium molecular weight chitosan appears a presumably beneficial agent for outer wound treatment for biofilms destruction, increasing antimicrobial treatment effectiveness.
Siloxanes in Biogas: Approaches of Sampling Procedure and GC-MS Method Determination
Authors: Piechota Grzegorz
Published: March 2021

A new approach of siloxane sampling based on impinger, micro-impinger, adsorption on active carbon, and direct TedlarBag methods followed by gas chromatography-mass spectrometry (GC-MS) was developed for the analysis of three linear (L2–L4) and four cyclic (D3–D5) volatile methyl siloxanes (VMSs). Three kinds of organic liquid-medium characterized by different polarities, namely acetone, methanol, and d-decane as siloxanes trap were arranged in the experiment which is widely discussed below. Thus, the GC-MS equipped with SUPELCOWAX-10 capillary column was employed to perform monitoring of VMS content in the analyzed biogas samples originating from landfill, wastewater treatment plants, and agriculture biogas plants. In all samples that have undergone the analysis, cyclic and linear VMSs were found in quantities exceeding 107.9 and 3.8 mg/m3, respectively. Significant differences between siloxanes concentrations depending on biogas origin were observed. Moreover, the high range of linearity (0.1 to 70.06 mg/m3), low LoD (0.01 mg/m3), low LoQ (0.04 mg/m3), and high recovery (244.1%) indicate that the procedure and can be applied in sensitive analyses of silica biogas contaminants. In addition to the above, the impinger method of sampling performed better than active-carbon Tube and TedlarBag, particularly for quantifying low concentrations of siloxanes. Overall, the evaluation of sampling methods for biogas collection simplified the analytical procedure by reducing the procedural steps, avoiding the use of solvents, as well as demonstrated its applicability for the testing of biogas quality.
Effect of Substituents of Cerium Pyrazolates and Pyrrolates on Carbon Dioxide Activation
Authors: Bayer Uwe , Jenner Adrian , Riedmaier Jonas , Maichle-Mössmer Cäcilia , Anwander Reiner
Published: March 2021

Homoleptic ceric pyrazolates (pz) Ce(RR’pz)4 (R = R’ = tBu; R = R’ = Ph; R = tBu, R’ = Me) were synthesized by the protonolysis reaction of Ce[N(SiHMe2)2]4 with the corresponding pyrazole derivative. The resulting complexes were investigated in their reactivity toward CO2, revealing a significant influence of the bulkiness of the substituents on the pyrazolato ligands. The efficiency of the CO2 insertion was found to increase in the order of tBu2pz < Ph2pz < tBuMepz < Me2pz. For comparison, the pyrrole-based ate complexes [Ce2(pyr)6(µ-pyr)2(thf)2][Li(thf)4]2 (pyr = pyrrolato) and [Ce(cbz)4(thf)2][Li(thf)4] (cbz = carbazolato) were obtained via protonolysis of the cerous ate complex Ce[N(SiHMe2)2]4Li(thf) with pyrrole and carbazole, respectively. Treatment of the pyrrolate/carbazolate complexes with CO2 seemed promising, but any reversibility could not be observed.
Guanidine–Amide-Catalyzed Aza-Henry Reaction of Isatin-Derived Ketimines: Origin of Selectivity and New Catalyst Design
Authors: He Jiajia , Tang Dianyong , Hu Changwei , Su Zhishan
Published: March 2021

Density functional theory (DFT) calculations were performed to investigate the mechanism and the enantioselectivity of the aza-Henry reaction of isatin-derived ketimine catalyzed by chiral guanidine–amide catalysts at the M06-2X-D3/6-311+G(d,p)//M06-2X-D3/6-31G(d,p) (toluene, SMD) theoretical level. The catalytic reaction occurred via a three-step mechanism: (i) the deprotonation of nitromethane by a chiral guanidine–amide catalyst; (ii) formation of C–C bonds; (iii) H-transfer from guanidine to ketimine, accompanied with the regeneration of the catalyst. A dual activation model was proposed, in which the protonated guanidine activated the nitronate, and the amide moiety simultaneously interacted with the ketimine substrate by intermolecular hydrogen bonding. The repulsion of CPh3 group in guanidine as well as N-Boc group in ketimine raised the Pauli repulsion energy (∆EPauli) and the strain energy (∆Estrain) of reacting species in the unfavorable si-face pathway, contributing to a high level of stereoselectivity. A new catalyst with cyclopropenimine and 1,2-diphenylethylcarbamoyl as well as sulfonamide substituent was designed. The strong basicity of cyclopropenimine moiety accelerated the activation of CH3NO2 by decreasing the energy barrier in the deprotonation step. The repulsion between the N-Boc group in ketimine and cyclohexyl group as well as chiral backbone in the new catalyst raised the energy barrier in C–C bond formation along the si-face attack pathway, leading to the formation of R-configuration product. A possible synthetic route for the new catalyst is also suggested.
A Fluorogenic Assay: Analysis of Chemical Modification of Lysine and Arginine to Control Proteolytic Activity of Trypsin
Authors: More Kunal N. , Lim Tae-Hwan , Kang Julie , Chang Dong-Jo
Published: March 2021

The chemical modification of amino acids plays an important role in the modulation of proteins or peptides and has useful applications in the activation and stabilization of enzymes, chemical biology, shotgun proteomics, and the production of peptide-based drugs. Although chemoselective modification of amino acids such as lysine and arginine via the insertion of respective chemical moieties as citraconic anhydride and phenyl glyoxal is important for achieving desired application objectives and has been extensively reported, the extent and chemoselectivity of the chemical modification of specific amino acids using specific chemical agents (blocking or modifying agents) has yet to be sufficiently clarified owing to a lack of suitable assay methodologies. In this study, we examined the utility of a fluorogenic assay method, based on a fluorogenic tripeptide substrate (FP-AA1-AA2-AA3) and the proteolytic enzyme trypsin, in determinations of the extent and chemoselectivity of the chemical modification of lysine or arginine. As substrates, we used two fluorogenic tripeptide probes, MeRho-Lys-Gly-Leu(Ac) (lysine-specific substrate) and MeRho-Arg-Gly-Leu(Ac) (arginine-specific substrate), which were designed, synthesized, and evaluated for chemoselective modification of specific amino acids (lysine and arginine) using the fluorogenic assay. The results are summarized in terms of half-maximal inhibitory concentrations (IC50) for the extent of modification and ratios of IC50 values (IC50arginine/IC50lysine and IC50lysine/IC50arginine) as a measure of the chemoselectivity of chemical modification for amino acids lysine and arginine. This novel fluorogenic assay was found to be rapid, precise, and reproducible for determinations of the extent and chemoselectivity of chemical modification.
Compressive Sensing-Based Radar Imaging and Subcarrier Allocation for Joint MIMO OFDM Radar and Communication System
Authors: Hwang SeongJun , Seo Jiho , Park Jaehyun , Kim Hyungju , Jeong Byung Jang
Published: March 2021

In this paper, a joint multiple-input multiple-output (MIMO OFDM) radar and communication (RadCom) system is proposed, in which orthogonal frequency division multiplexing (OFDM) waveforms carrying data to be transmitted to the information receiver are exploited to get high-resolution radar images at the RadCom platform. Specifically, to get two-dimensional (i.e., range and azimuth angle) radar images with high resolution, a compressive sensing-based imaging algorithm is proposed that is applicable to the signal received through multiple receive antennas. Because both the radar imaging performance (i.e., the mean square error of the radar image) and the communication performance (i.e., the achievable rate) are affected by the subcarrier allocation across multiple transmit antennas, by analyzing both radar imaging and communication performances, we also propose a subcarrier allocation strategy such that a high achievable rate is obtained without sacrificing the radar imaging performance.