bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification of LATERAL ORGAN BOUNDARIES DOMAIN (LBD) Transcription Factors and Screening of Salt Stress Candidates of Rosa rugosa Thunb
Authors: Wang Jianwen , Zhang Weijie , Cheng Yufei , Feng Liguo
Published: October 2021

LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factors are regulators of lateral organ morphogenesis, boundary establishment, and secondary metabolism in plants. The responsive role of LBD gene family in plant abiotic stress is emerging, whereas its salt stress responsive mechanism in Rosa spp. is still unclear. The wild plant of Rosa rugosa Thunb., which exhibits strong salt tolerance to stress, is an ideal material to explore the salt-responsive LBD genes. In our study, we identified 41 RrLBD genes based on the R. rugosa genome. According to phylogenetic analysis, all RrLBD genes were categorized into Classes I and II with conserved domains and motifs. The cis-acting element prediction revealed that the promoter regions of most RrLBD genes contain defense and stress responsiveness and plant hormone response elements. Gene expression patterns under salt stress indicated that RrLBD12c, RrLBD25, RrLBD39, and RrLBD40 may be potential regulators of salt stress signaling. Our analysis provides useful information on the evolution and development of RrLBD gene family and indicates that the candidate RrLBD genes are involved in salt stress signaling, laying a foundation for the exploration of the mechanism of LBD genes in regulating abiotic stress.
Functionalization of Biotinylated Polyethylene Glycol on Live Magnetotactic Bacteria Carriers for Improved Stealth Properties
Authors: Chaturvedi Richa , Kang Yumin , Eom Yunji , Torati Sri Ramulu , Kim CheolGi
Published: October 2021

The early removal of drug delivery agents before reaching the affected target remains an area of interest to researchers. Several magnetotactic bacteria (MTB) have been used as self-propelled drug delivery agents, and they can also be controlled by an external magnetic field. By attaching the PEG–biotin polymer, the bacteria are turned into a stealth material that can escape from the phagocytosis process and reach the area of interest with the drug load. In the study, we developed a potential drug carrier by attaching the PEG–biotin to the MTB-through-NHS crosslinker to form a MTB/PEG–biotin complex. The attachment stability, efficacy, and bacterial viability upon attachment of the PEG–biotin polymer were investigated. Biological applications were carried out using a cytotoxicity assay of THP-1 cells, and the results indicate that the MTB/PEG–biotin complex is less harmful to cell viability compared to MTB alone. Along with cytotoxicity, an assay for cell association was also evaluated to assess the complex as a potential stealth material. The development of these complexes focuses on an easy, time-saving, and stable technique of polymer attachment with the bacteria, without damaging the cell’s surface, so as to make it a strong and reliable delivery agent.
Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
Authors: Mäki-Nevala Satu , Ukwattage Sanjeevi , Wirta Erkki-Ville , Ahtiainen Maarit , Ristimäki Ari , Seppälä Toni T. , Lepistö Anna , Mecklin Jukka-Pekka , Peltomäki Päivi
Published: October 2021

Immunological and epigenetic changes are interconnected and contribute to tumorigenesis. We determined the immunoprofiles and promoter methylation of inflammation-related genes for colitis-associated colorectal carcinomas (CA-CRC). The results were compared with Lynch syndrome (LS)-associated colorectal tumors, which are characterized by an active immune environment through inherited mismatch repair defects. CA-CRCs (n = 31) were immunohistochemically evaluated for immune cell scores (ICSs) and PDCD1 and CD274 expression. Seven inflammation-associated genes (CD274, NTSR1, PPARG, PTGS2, PYCARD, SOCS1, and SOCS2), the repair gene MGMT, and eight standard marker genes for the CpG Island Methylator Phenotype (CIMP) were investigated for promoter methylation in CA-CRCs, LS tumors (n = 29), and paired normal mucosae by multiplex ligation-dependent probe amplification. All but one CA-CRCs were microsatellite-stable and all LS tumors were microsatellite-unstable. Most CA-CRCs had a high ICS (55%) and a positive CD274 expression in immune cells (52%). NTSR1 revealed frequent tumor-specific hypermethylation in CA-CRC and LS. When compared to LS mucosae, normal mucosae from patients with CA-CRC showed significantly higher methylation of NTSR1 and most CIMP markers. In conclusion, CA-CRCs share a frequent ICShigh/CD274pos expression pattern with LS tumors. Elevated methylation in normal mucosa may indicate field cancerization as a feature of CA-CRC-associated tumorigenesis.
Modeling Functional Limitations, Gait Impairments, and Muscle Pathology in Alzheimer’s Disease: Studies in the 3xTg-AD Mice
Authors: Castillo-Mariqueo Lidia , Pérez-García M. José , Giménez-Llort Lydia
Published: October 2021

Gait impairments in Alzheimer’s disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual’s biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals’ gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.
Extracellular Vesicle-Based Therapy for COVID-19: Promises, Challenges and Future Prospects
Authors: Karn Vamika , Ahmed Shaista , Tsai Lung-Wen , Dubey Rajni , Ojha Shreesh , Singh Himanshu , Kumar Mukesh , Gupta Piyush , Sadhu Soumi , Jha Niraj , Kumar Ashutosh , Pandit Soumya , Kumar Sanjay
Published: October 2021

The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.
Advances in Nanotechnology-Based Biosensing of Immunoregulatory Cytokines
Authors: Lohcharoenkal Warangkana , Abbas Zareen , Rojanasakul Yon
Published: October 2021

Cytokines are a large group of small proteins secreted by immune and non-immune cells in response to external stimuli. Much attention has been given to the application of cytokines’ detection in early disease diagnosis/monitoring and therapeutic response assessment. To date, a wide range of assays are available for cytokines detection. However, in specific applications, multiplexed or continuous measurements of cytokines with wearable biosensing devices are highly desirable. For such efforts, various nanomaterials have been extensively investigated due to their extraordinary properties, such as high surface area and controllable particle size and shape, which leads to their tunable optical emission, electrical, and magnetic properties. Different types of nanomaterials such as noble metal, metal oxide, and carbon nanoparticles have been explored for various biosensing applications. Advances in nanomaterial synthesis and device development have led to significant progress in pushing the limit of cytokine detection. This article reviews currently used methods for cytokines detection and new nanotechnology-based biosensors for ultrasensitive cytokine detection.
Distinguishing Amyloid β-Protein in a Mouse Model of Alzheimer’s Disease by Label-Free Vibrational Imaging
Authors: Li Shaowei , Luo Ziyi , Zhang Renlong , Xu Hao , Zhou Ting , Liu Liwei , Qu Junle
Published: October 2021

Due to the increase in the average age of humans, Alzheimer’s disease (AD) has become one of the disorders with the highest incidence worldwide. Abnormal amyloid β protein (Aβ) accumulation is believed to be the most common cause of AD. Therefore, distinguishing the lesion areas can provide clues for AD diagnosis. Here, we present an optical spectroscopy and imaging approach based on coherent anti-Stokes Raman scattering (CARS). Label-free vibrational imaging of Aβ in a mouse model of AD was performed to distinguish the lesion areas by studying the spectra of regions with and without Aβ plaques. Raman spectra in Aβ and non-Aβ regions exhibited a specific difference in the intensity ratio of the wave peaks detected at 2850 and 2930 cm−1. In the non-Aβ region, the ratio of the peak intensity at 2850 cm−1 to that at 2930 cm−1 was approximately 1, whereas that in the Aβ region was 0.8. This label-free vibrational imaging may provide a new method for the clinical diagnosis and basic research of AD.
Effects of Web Height Reduction and Skew Angle Variation on Behavior of RC Inverted T-Beams
Authors: El-Ariss Bilal , Mansour Moustafa , El-Maaddawy Tamer
Published: October 2021

The use of precast inverted T-beams has been frequently used to minimize construction activities and installation time. However, shipping and placement of large invert T-beams can become challenging tasks due to their weight. Decreasing the web height of the beam can be effective in reducing the beam weight. This paper considers inverted T-beams with two overhangs, negative moment regions, and one span, a positive moment region. The examined parameters were the web height and skew angle of the inverted T-beams. To avoid high costs of testing beams and to save time, the application of numerical modeling is, hence, inevitable. A calibrated 3D nonlinear numerical model, using ATENA software, was further used to numerically investigate the effects of reducing the weight, by decreasing the web height and varying the skew angle of inverted T-beams on their structural performance. The outcomes of this study indicated that reducing the web height of the beam was an effective tool to reduce the weight without jeopardizing the strength of the beams. Increasing the skew angle of the inverted T-beam also decreased their ductility.
The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer
Authors:   Group Young Researchers in Inflammatory Carcinogenesis, Wandmacher Anna Maxi , Mehdorn Anne-Sophie , Sebens Susanne
Published: October 2021

Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at advanced stages and most anti-cancer therapies have failed to substantially improve prognosis of PDAC patients. As a result, PDAC is still one of the deadliest tumors. Tumor heterogeneity, manifesting at multiple levels, provides a conclusive explanation for divergent survival times and therapy responses of PDAC patients. Besides tumor cell heterogeneity, PDAC is characterized by a pronounced inflammatory stroma comprising various non-neoplastic cells such as myofibroblasts, endothelial cells and different leukocyte populations which enrich in the tumor microenvironment (TME) during pancreatic tumorigenesis. Thus, the stromal compartment also displays a high temporal and spatial heterogeneity accounting for diverse effects on the development, progression and therapy responses of PDAC. Adding to this heterogeneity and the impact of the TME, the microbiome of PDAC patients is considerably altered. Understanding this multi-level heterogeneity and considering it for the development of novel therapeutic concepts might finally improve the dismal situation of PDAC patients. Here, we outline the current knowledge on PDAC cell heterogeneity focusing on different stromal cell populations and outline their impact on PDAC progression and therapy resistance. Based on this information, we propose some novel concepts for treatment of PDAC patients.
Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy
Authors: Ronga Maria Grazia , Cavallone Marco , Patriarca Annalisa , Leite Amelia Maia , Loap Pierre , Favaudon Vincent , Créhange Gilles , De Marzi Ludovic
Published: October 2021

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.
SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation
Authors: Mir Cristina , Garcia-Mayea Yoelsis , Garcia Laia , Herrero Pol , Canela Nuria , Tabernero Rocío , Lorente Juan , Castellvi Josep , Allonca Eva , García-Pedrero Juana , Rodrigo Juan Pablo , Carracedo Ángel , LLeonart Matilde Esther
Published: October 2021

To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance.
Synthesis of 2-Methylquinoxaline Derivatives from Glycerol and Diamines Catalyzed by Iridium Complexes Bearing an N-Heterocyclic Carbene Ligand
Authors: Tanaka Toshiki , Enomoto Akane , Furukawa Shohichi , Fujita Ken-ichi
Published: October 2021

2-Methylquinoxaline derivatives are widely used as intermediates in the synthesis of pharmaceuticals, natural products, and dyes; however, their syntheses usually require excess reagents, making them environmentally burdensome. Meanwhile, glycerol can be sustainably obtained in large quantities as a by-product in the production of biodiesel fuel using waste oil as a raw material. Thus, it is worthwhile to develop a new catalytic system that utilizes glycerol as a C3 source. In this study, an efficient catalytic system was developed to obtain 2-methylquinoxaline derivatives from glycerol and 1,2-phenylenediamines. This system is beneficial because it is environmentally friendly and has excellent atom efficiency.
A Human 3D Cardiomyocyte Risk Model to Study the Cardiotoxic Influence of X-rays and Other Noxae in Adults
Authors: Smit Timo , Schickel Esther , Azimzadeh Omid , von Toerne Christine , Rauh Oliver , Ritter Sylvia , Durante Marco , Schroeder Insa S.
Published: October 2021

The heart tissue is a potential target of various noxae contributing to the onset of cardiovascular diseases. However, underlying pathophysiological mechanisms are largely unknown. Human stem cell-derived models are promising, but a major concern is cell immaturity when estimating risks for adults. In this study, 3D aggregates of human embryonic stem cell-derived cardiomyocytes were cultivated for 300 days and characterized regarding degree of maturity, structure, and cell composition. Furthermore, effects of ionizing radiation (X-rays, 0.1–2 Gy) on matured aggregates were investigated, representing one of the noxae that are challenging to assess. Video-based functional analyses were correlated to changes in the proteome after irradiation. Cardiomyocytes reached maximum maturity after 100 days in cultivation, judged by α-actinin lengths, and displayed typical multinucleation and branching. At this time, aggregates contained all major cardiac cell types, proven by the patch-clamp technique. Matured and X-ray-irradiated aggregates revealed a subtle increase in beat rates and a more arrhythmic sequence of cellular depolarisation and repolarisation compared to non-irradiated sham controls. The proteome analysis provides first insights into signaling mechanisms contributing to cardiotoxicity. Here, we propose an in vitro model suitable to screen various noxae to target adult cardiotoxicity by preserving all the benefits of a 3D tissue culture.
The Flagellin:Allergen Fusion Protein rFlaA:Betv1 Induces a MyD88− and MAPK-Dependent Activation of Glucose Metabolism in Macrophages
Authors: Lin Yen-Ju , Papp Garibald , Miskey Csaba , Fiedler Anna , Goretzki Alexandra , Wolfheimer Sonja , Zimmermann Jennifer , Crauwels Peter , Ivics Zoltán , van Zandbergen Ger , Vieths Stefan , Scheurer Stephan , Schülke Stefan
Published: October 2021

TLR5 ligand flagellin-containing fusion proteins are potential vaccine candidates for many diseases. A recombinant fusion protein of flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) modulates immune responses in vitro and in vivo. We studied the effects of rFlaA:Betv1 on bone marrow-derived macrophages (BMDMs). BMDMs differentiated from BALB/c, C57BL/6, TLR5−/−, or MyD88−/− mice were pre-treated with inhibitors, stimulated with rFlaA:Betv1 or respective controls, and analyzed for activation, cytokine secretion, metabolic state, RNA transcriptome, and modulation of allergen-specific Th2 responses. Stimulation of BMDMs with rFlaA:Betv1 resulted in MyD88-dependent production of IL-1β, IL-6, TNF-α, IL-10, CD69 upregulation, and a pronounced shift towards glycolysis paralleled by activation of MAPK, NFκB, and mTOR signaling. Inhibition of either mTOR (rapamycin) or SAP/JNK-MAPK signaling (SP600125) resulted in dose-dependent metabolic suppression. In BMDM and T cell co-cultures, rFlaA:Betv1 stimulation suppressed rBet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. mRNA-Seq analyses showed HIF-1a, JAK, STAT, phagosome, NLR, NFκB, TNF, TLR, and chemokine signaling to participate in the interplay of cell activation, glycolysis, and immune response. rFlaA:Betv1 strongly activated BMDMs, resulting in MyD88−, MAPK−, and mTOR-dependent enhancement of glucose metabolism. Our results suggest macrophages are important target cells to consider during restauration of allergen tolerance during AIT.
Local Defence System in Healthy Lungs
Authors: Lohova Elizabeta , Vitenberga-Verza Zane , Kazoka Dzintra , Pilmane Mara
Published: October 2021

Background: The respiratory system is one of the main entrance gates for infection. The aim of this work was to compare the appearance of specific mucosal pro-inflammatory and common anti-microbial defence factors in healthy lung tissue, from an ontogenetic point of view. Materials and methods: Healthy lung tissues were collected from 15 patients (three females and 12 males) in the age range from 18 to 86. Immunohistochemistry to human β defensin 2 (HBD-2), human β defensin 3 (HBD-3), human β defensin 4 (HBD-4), cathelicidine (LL-37) and interleukine 17A (IL-17A) were performed. Results: The lung tissue material contained bronchial and lung parenchyma material in which no histological changes, connected with the inflammatory process, were detected. During the study, various statistically significant differences were detected in immunoreactive expression between different factors in all lung tissue structures. Conclusion: All healthy lung structures, but especially the cartilage, alveolar epithelium and the alveolar macrophages, are the main locations for the baseline synthesis of antimicrobial proteins and IL-17A. Cartilage shows high functional plasticity of this structure, including significant antimicrobial activity and participation in local lung protection response. Interrelated changes between antimicrobial proteins in different tissue confirm baseline synergistical cooperation of all these factors in healthy lung host defence.
Plasma Enhanced Atomic Layer Deposition of Tantalum (V) Oxide
Authors: Fedorov Pavel , Nazarov Denis , Medvedev Oleg , Koshtyal Yury , Rumyantsev Aleksander , Tolmachev Vladimir , Popovich Anatoly , Maximov Maxim Yu
Published: October 2021

The tantalum oxide thin films are promising materials for various applications: as coatings in optical devices, as dielectric layers for micro and nanoelectronics, and for thin-films solid-state lithium-ion batteries (SSLIBs). This article is dedicated to the Ta-O thin-film system synthesis by the atomic layer deposition (ALD) which allows to deposit high quality films and coatings with excellent uniformity and conformality. Tantalum (V) ethoxide (Ta(OEt)5) and remote oxygen plasma were used as tantalum-containing reagent and oxidizing co-reagent, respectively. The influence of deposition parameters (reactor and evaporator temperature, pulse and purge times) on the growth rate were studied. The thickness of the films were measured by spectroscopic ellipsometry, scanning electron microscopy and X-ray reflectometry. The temperature range of the ALD window was 250–300 °C, the growth per cycle was about 0.05 nm/cycle. Different morphology of films deposited on silicon and stainless steel was found. According to the X-ray diffraction data, the as-prepared films were amorphous. But the heat treatment study shows crystallization at 800 °C with the formation of the polycrystalline Ta2O5 phase with a rhombic structural type (Pmm2). The results of the X-ray reflectometry show the Ta-O films’ density is 7.98 g/cm3, which is close to the density of crystalline Ta2O5 of the rhombic structure (8.18 g/cm3). The obtained thin films have a low roughness and high uniformity. The chemical composition of the surface and bulk of Ta-O coatings was studied by X-ray photoelectron spectroscopy and energy-dispersive X-ray spectroscopy. Surface of the films contain Ta2O5 and some carbon contamination, but the bulk of the films does not contain carbon and any precursor residues. Cyclic voltammetry (CVA) showed that there is no current increase for tantalum (V) oxide in a potential window of 3–4.2 V and has prospects of use as protective coatings for cathode materials of SSLIBs.
DFT Calculation, Hirshfeld Analysis and X-Ray Crystal Structure of Some Synthesized N-alkylated(S-alkylated)-[1,2,4]triazolo[1,5-a]quinazolines
Authors: Abuelizz Hatem A. , Soliman Saied M. , Ghabbour Hazem A. , Marzouk Mohamed , Abdellatif Mohamed M. , Al-Salahi Rashad
Published: October 2021

The present work aimed to synthesize 2-methylthio-triazoloquinazoline derivatives and study their X-ray, NMR, DFT and Hirshfeld characteristics. The cyclocondensation of dimethyl-N-cyanodithiocarbonate with 2-hydrazinobenzoic acid hydrochloride resulted in an intermediate, 2-methylthio-[1,2,4]triazolo[1,5-a]quinazolin-5-one (A), which upon treatment with phosphorus pentasulfide, transformed into the 2-methylthio-[1,2,4]triazolo[1,5-a]quinazolin-5-thione (B). Reaction of 2-methylthio-triazoloquinazolines (A&B) with alkyl halides (allyl bromide and ethyl iodide) in basic medium afforded 4-allyl-2-methylthio-[1,2,4]triazolo[1,5-a]quinazolin-5-one (1; N-alkylated) and 5-ethylthio-2-methylthio-[1,2,4]triazolo[1,5-a]quinazoline (2; S-alkylated), respectively. Their molecular and supramolecular structures were presented. Unambiguously, the molecular structures of 1 and 2 were confirmed via NMR and single-crystal X-ray diffraction. The resulting findings confirmed the structures of 1 and 2 and determined their crystalized system (monoclinic system; P21/n space group). Hirshfeld analysis of 1 revealed the importance of the significantly short O···H (6.7%), S···S (1.2%) and C···C (2.8%); however, the short H···H (42.6%), S···H (16.3%) and C···C (4.3%) were showed in 2 by intermolecular interactions in the molecular packing. The 1,2,4-triazoloquinzolines (1&2) were anticipated to be relatively polar compounds with net dipole moments of 2.9284 and 4.2127 Debye, respectively. The molecular electrostatic potential, atomic charge distribution maps and reactivity descriptors for 1 and 2 were also determined. The calculated nuclear magnetic resonance spectra of the targets 1 and 2 were well correlated with the experimental data.
Assessment of the Sedia HIV Self-Test Device: Usability and Performance in the Hands of Untrained Users in Johannesburg, South Africa
Authors: Majam Mohammed , Rhagnath Naleni , Msolomba Vanessa , Singh Leanne , Urdea Michael S. , Lalla-Edward Samanta Tresha
Published: October 2021

The prevalence of HIV across South Africa places a strain on testing facilities. The use of HIV self-testing (HIVST) devices has been identified as a strategy to ease the burden on these facilities. The usability and performance of the Asante HIV−1/2 Oral Self-Test (Asante) (Sedia Biosciences, Portland OR, USA) device by novice users was assessed and reported on, to inform for the implementation of such devices in South Africa and elsewhere. Convenience sampling was used. Participants used the Asante HIVST device and recorded their interpretation of their results. Participants’ interpretations were compared with those of trained professionals and, thereafter, verified using the rapid diagnostic testing algorithm. Out of the eligible participants, 410 of the 524 (78.2%) were between the ages of 18–35. The usability assessment indicates that 100% of participants used the HIVST device’s information leaflet. However, 19/524 (3.6%) of participants who yielded an invalid result due to critical errors were excluded from the primary efficacy analysis. The average usability score was 98.1%. The sensitivity and specificity results were, 94.7% and 99.8%, respectively. This study shows that the Asante HIV self-test, and similar devices, can be valuable in providing convenient HIV self-testing and immediately available results. To accommodate a greater number of inexperienced users, the instructions may need to be revised.
The Diagnostic Accuracy of LOGIQ S8 and E9 Shear Wave Elastography for Staging Hepatic Fibrosis, in Comparison with Transient Elastography
Authors: Yoo Jeong-Ju , Kim Sang Gyune , Kim Young Seok
Published: October 2021

Background: The aim of this study was to evaluate the usefulness of two different types of 2-dimensional shear wave elastography (2D-SWE) for predicting liver fibrosis stages in comparison to transient elastography (TE), using a histologic METAVIR scoring system as the reference method. Methods: A total of 203 patients with chronic liver disease were prospectively enrolled in the study. Two different 2D-SWEs (LOGIQ S8 and E9 systems, GE Healthcare, Chalfont St Giles, UK) were assessed for liver stiffness in patients with chronic liver diseases. Patients received 2D-SWE examinations with the S8 and E9 systems, and also underwent TE (FibroScan®, Echosens, France) tests and liver biopsies on the same day. Results: The most common etiology of chronic liver disease was non-alcoholic fatty liver disease (28.7%), followed by chronic hepatitis B (25.1%). Liver fibrosis stages consisted of F0 (22.6%), F1 (29.7%), F2 (16.9%), F3 (12.8%) and F4 (17.9%). Overall, S8 and E9 were well correlated with the histologic fibrosis stages. The optimal cut-off values for S8 and E9 to differentiate significant fibrosis (≥F2) were 6.70 kPa and 6.42 kPa, respectively, while the cut-off values for S8 and E9 in distinguishing liver cirrhosis were 9.15 kPa and 8.88 kPa, respectively. Among the 195 patients who had successful measurements in both S8 and E9, liver stiffness showed good inter-equipment correlation (ICC: 0.900, p < 0.001). Regarding diagnostic ability, upon comparison (FibroScan®), there were no significant differences between 2D-SWEs and TE for detecting every stage of liver fibrosis. Conclusion: In comparison to TE, 2D-SWE with LOGIQ S8 and E9 (GE Healthcare) are useful non-invasive tools for predicting significant fibrosis and liver cirrhosis.
Human Prion Disorders: Review of the Current Literature and a Twenty-Year Experience of the National Surveillance Center in the Czech Republic
Authors: Jankovska Nikol , Rusina Robert , Bruzova Magdalena , Parobkova Eva , Olejar Tomas , Matej Radoslav
Published: October 2021

Human prion disorders (transmissible spongiform encephalopathies, TSEs) are unique, progressive, and fatal neurodegenerative diseases caused by aggregation of misfolded prion protein in neuronal tissue. Due to the potential transmission, human TSEs are under active surveillance in a majority of countries; in the Czech Republic data are centralized at the National surveillance center (NRL) which has a clinical and a neuropathological subdivision. The aim of our article is to review current knowledge about human TSEs and summarize the experience of active surveillance of human prion diseases in the Czech Republic during the last 20 years. Possible or probable TSEs undergo a mandatory autopsy using a standardized protocol. From 2001 to 2020, 305 cases of sporadic and genetic TSEs including 8 rare cases of Gerstmann–Sträussler–Scheinker syndrome (GSS) were confirmed. Additionally, in the Czech Republic, brain samples from all corneal donors have been tested by the NRL immunology laboratory to increase the safety of corneal transplants since January 2007. All tested 6590 corneal donor brain tissue samples were negative for prion protein deposits. Moreover, the routine use of diagnostic criteria including biomarkers are robust enough, and not even the COVID-19 pandemic has negatively impacted TSEs surveillance in the Czech Republic.
Studying and Challenging Racism in Higher Education: Naming Bad Faith to Understand the “Logic” of Racism
Authors: Tichavakunda Antar A.
Published: October 2021

In this conceptual essay, the author argues that bad faith is a valuable concept in understanding and challenging racism in higher education. The philosopher Lewis Gordon argues that racism is a manifestation of bad faith. For the actor who sees Black people as less than human, for example, no evidence will allow the actor to see otherwise. Bad faith is the disavowal of any disconfirming evidence which allows actors to maintain their worldviews. The author draws from high profile examples of racism in higher education as conceptual cases to make his argument. Specifically, the author demonstrates how attacks upon Critical Race Theory in education, the currency of critiques of microaggressions research, and the perennial difficulty to name racist violence on campus as hate crimes operate upon a logic of racism through bad faith.
Coculture Strategy for Developing Lactobacillus paracasei PS23 Fermented Milk with Anti-Colitis Effect
Authors: Lee Kai-Yi , Tsai Ying-Chieh , Wang Sheng-Yao , Chen Yen-Po , Chen Ming-Ju
Published: October 2021

Few studies have documented the effects of fermented milk on intestinal colitis, which are mediated by regulating various microbial and inflammatory processes. Here, we investigated the effects of fermented milk with Lactobacillus paracasei PS23 on intestinal epithelial cells in vitro and dextran sulfate sodium (DSS)-induced colitis in vivo. As L. paracasei PS23 grew poorly in milk, a coculture strategy with yogurt culture was provided to produce fermented milk (FM). The results indicated that the coculture exhibited a symbiotic effect, contributing to the better microbial and physicochemical property of the fermented milk products. We further evaluated the anti-colitis effect of fermented milk with L. paracasei PS23 in vitro. Both PS23-fermented milk (PS23 FM) and its heat-killed counterpart (HK PS23 FM) could protect or reverse the increased epithelial permeability by strengthening the epithelial barrier function in vitro by increasing transepithelial electrical resistance (TEER). In vivo analysis of the regulation of intestinal physiology demonstrated that low-dose L. paracasei PS23-fermented ameliorated DSS-induced colitis, with a significant attenuation of the bleeding score and reduction of fecal calprotectin levels. This anti-colitis effect may be exerted by deactivating the inflammatory cascade and strengthening the tight junction through the modification of specific cecal bacteria and upregulation of short-chain fatty acids. Our findings can clarify the role of L. paracasei PS23 in FM products when cocultured with yogurt culture and can elucidate the mechanisms of the anti-colitis effect of L. paracasei PS23 FM, which may be considered for therapeutic intervention.
Is Current Research on How Climate Change Impacts Global Food Security Really Objective?
Authors: Liu Wangang , Chen Yiping , He Xinhua , Mao Ping , Tian Hanwen
Published: October 2021

Global food insecurity is becoming more severe under the threat of rising global carbon dioxide concentrations, increasing population, and shrinking farmlands and their degeneration. We acquired the ISI Web of Science platform for over 31 years (1988–2018) to review the research on how climate change impacts global food security, and then performed cluster analysis and research hotspot analysis with VosViewer software. We found there were two drawbacks that exist in the current research. Firstly, current field research data were defective because they were collected from various facilities and were hard to integrate. The other drawback is the representativeness of field research site selection as most studies were carried out in developed countries and very few in developing countries. Therefore, more attention should be paid to developing countries, especially some African and Asian countries. At the same time, new modified mathematical models should be utilized to process and integrate the data from various facilities and regions. Finally, we suggested that governments and organizations across the world should be united to wrestle with the impact of climate change on food security.
Carcass Yields and Physical-Chemical Meat Quality Characteristics of Namibian Red Hartebeest (Alcelaphus buselaphus) as Influenced by Sex and Muscle
Authors: Hoffman Louwrens C. , van Schalkwyk Diana L. , Muller Magdalena , Needham Tersia , McMillin Kenneth W.
Published: October 2021

This study determined the carcass yields of red hartebeest from Namibia and compared the physical-chemical meat quality characteristics of six different muscles (biceps femoris, infraspinatus, longissimus thoracis et lumborum, semimembranosus, semitendinosus, and supraspinatus) for both males and females. Red hartebeest males were heavier (133.92 kg) than females (114.20 kg) but the average dressing percentage did not differ between the two sexes. Muscles from females had a lower mean shear force value of 3.59 kg/1.27 cm ø, compared to males (4.23 kg/1.27 cm ø). The most tender muscle was the infraspinatus of the female treatment group, while the semimembranosus of the male treatment group was the least tender muscle. Drip loss, cooking loss and L* (lightness) values were not affected by sex. The largest hue angle was observed in the semitendinosus muscle of the female treatment group (28.94°), and it was thus the lightest red muscle. The highest chroma values (17.3) were observed in the semimembranosus muscle. Muscle protein content averaged 20.5% over all treatment combinations, and the mean intra-muscular fat content for both male and female muscles was low (2.4%). The shoulder muscles, infraspinatus and supraspinatus, of the females had the highest fat content (2.7%). The results indicate that red hartebeest meat should be market according to specific muscles and that sex of the animals need not be considered during marketing.
Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Lamberto Federica , Peral-Sanchez Irene , Muenthaisong Suchitra , Zana Melinda , Willaime-Morawek Sandrine , Dinnyés András
Published: October 2021

Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics.
Ectopic Overexpression of Maize Heat Stress Transcription Factor ZmHsf05 Confers Drought Tolerance in Transgenic Rice
Authors: Si Weina , Liang Qizhi , Chen Li , Song Feiyang , Chen You , Jiang Haiyang
Published: October 2021

Drought is a key factor affecting plant growth and development. Heat shock transcription factors (Hsfs) have been reported to respond to diverse abiotic stresses, including drought stress. In the present study, functional characterization of maize heat shock transcription factor 05 (ZmHsf05) gene was conducted. Homologous analysis showed that ZmHsf05 belongs to Class A2 Hsfs. The mRNA expression level of ZmHsf05 can be affected by drought, high temperature, salt, and abscisic acid (ABA) treatment. Ectopic overexpression of ZmHsf05 in rice (Oryza sativa) could significantly enhance the drought tolerance. Faced with drought stress, transgenic rice exhibited better phenotypic performance, higher survival rate, higher proline content, and lower leaf water loss rate, compared with wild-type plant Zhonghua11. Additionally, we assessed the agronomic traits of seven transgenic rice lines overexpressing ZmHsf05 and found that ZmHsf05 altered agronomical traits in the field trials. Moreover, rice overexpressing ZmHsf05 was more sensitive to ABA and had either a lower germination rate or shorter shoot length under ABA treatment. The transcription level of key genes in the ABA synthesis and drought-related pathway were significantly improved in transgenic rice after drought stress. Collectively, our results showed that ZmHsf05 could improve drought tolerance in rice, likely in an ABA-dependent manner.
Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia
Authors: Zhang Pan , Perez Olivia C. , Southey Bruce R. , Sweedler Jonathan V. , Pradhan Amynah A. , Rodriguez-Zas Sandra L.
Published: October 2021

Prolonged use of opioids can cause opioid-induced hyperalgesia (OIH). The impact of alternative splicing on OIH remains partially characterized. A study of the absolute and relative modes of action of alternative splicing further the understanding of the molecular mechanisms underlying OIH. Differential absolute and relative isoform profiles were detected in the trigeminal ganglia and nucleus accumbens of mice presenting OIH behaviors elicited by chronic morphine administration relative to control mice. Genes that participate in glutamatergic synapse (e.g., Grip1, Grin1, Wnk3), myelin protein processes (e.g., Mbp, Mpz), and axon guidance presented absolute and relative splicing associated with OIH. Splicing of genes in the gonadotropin-releasing hormone receptor pathway was detected in the nucleus accumbens while splicing in the vascular endothelial growth factor, endogenous cannabinoid signaling, circadian clock system, and metabotropic glutamate receptor pathways was detected in the trigeminal ganglia. A notable finding was the prevalence of alternatively spliced transcription factors and regulators (e.g., Ciart, Ablim2, Pbx1, Arntl2) in the trigeminal ganglia. Insights into the nociceptive and antinociceptive modulatory action of Hnrnpk were gained. The results from our study highlight the impact of alternative splicing and transcriptional regulators on OIH and expose the need for isoform-level research to advance the understanding of morphine-associated hyperalgesia.
Tectonic Transport Directions, Shear Senses and Deformation Temperatures Indicated by Quartz c-Axis Fabrics and Microstructures in a NW-SE Transect across the Moine and Sgurr Beag Thrust Sheets, Caledonian Orogen of Northern Scotland
Authors: Law Richard D. , Thigpen J. Ryan , Mazza Sarah E. , Mako Calvin A. , Krabbendam Maarten , Spencer Brandon M. , Ashley Kyle T. , Strachan Robin A. , Davis Ella F.
Published: October 2021

Moine metasedimentary rocks of northern Scotland are characterized by arcuate map patterns of mineral lineations that swing progressively clockwise from orogen-perpendicular E-trending lineations in greenschist facies mylonites above the Moine thrust on the foreland edge of the Caledonian Orogen, to S-trending lineations at higher structural levels and metamorphic grades in the hinterland. Quartz c-axis fabrics measured on a west to east coast transect demonstrate that the lineations developed parallel to the maximum principal extension direction and therefore track the local tectonic transport direction. Microstructures and c-axis fabrics document a progressive change from top to the N shearing in the hinterland to top to the W shearing on the foreland edge. Field relationships indicate that the domain of top to the N shearing was at least 55 km wide before later horizontal shortening on km-scale W-vergent folds that detach on the underlying Moine thrust. Previously published data from the Moine thrust mylonites demonstrate that top to the W shearing had largely ceased by 430 Ma, while preliminary isotopic age data suggest top to the N shearing occurred at ~470–450 Ma. In addition, data from the east coast end of our transect indicate normal-sense top down-SE shearing at close to peak temperatures at ~420 Ma that may be related to the closing stages of Scandian deformation, metamorphism and cooling/exhumation.
Morphotectonic Evolution of an Alluvial Fan: Results of a Joint Analog and Numerical Modeling Approach
Authors: Garcia-Estève Clément , Caniven Yannick , Cattin Rodolphe , Dominguez Stéphane , Sylvain Romain
Published: October 2021

Surface topography results from complex couplings and feedbacks between tectonics and surface processes. We combine analog and numerical modeling, sharing similar geometry and boundary conditions, to assess the topographic evolution of an alluvial fan crossed by an active thrust fault. This joint approach allows the calibration of critical parameters constraining the river deposition–incision laws, such as the settling velocity of suspended sediments, the bed-rock erodibility, or the slope exponent. Comparing analog and numerical models reveals a slope-dependent threshold process, where a critical slope of ca. 0.081 controls the temporal evolution of the drainage network. We only evidence minor topographic differences between stable and stick-slip fault behavior localized along the fault scarp. Although this topographic signature may increase with the slip rate and the return period of slip events, it remains slight compared to the cumulated displacement along the fault scarp. Our results demonstrate that the study of morphology cannot be used alone to study the slip mode of active faults but can be a valuable tool complementing stratigraphic and geodetic observations. In contrast, we underline the significant signature of the distance between the fault and the sediment source, which controls the degree of channels incision and the density of the drainage network.