bluuebunny/crossref_metadata_2025 huggingface dataset:
PM2.5 Exacerbates Oxidative Stress and Inflammatory Response through the Nrf2/NF-κB Signaling Pathway in OVA-Induced Allergic Rhinitis Mouse Model
Authors: Piao Chun Hua , Fan Yanjing , Nguyen Thi Van , Shin Hee Soon , Kim Hyoung Tae , Song Chang Ho , Chai Ok Hee
Published: July 2021

Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 μg/mouse PM with a less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM2.5 exposed AR mice. Furthermore, PM2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM2.5 exposure.
Comparison of Cr(VI) Adsorption Using Synthetic Schwertmannite Obtained by Fe3+ Hydrolysis and Fe2+ Oxidation: Kinetics, Isotherms and Adsorption Mechanism
Authors: Ulatowska Justyna , Stala Łukasz , Polowczyk Izabela
Published: July 2021

Good sorption properties and simple synthesis route make schwertmannite an increasingly popular adsorbent. In this work, the adsorption properties of synthetic schwertmannite towards Cr(VI) were investigated. This study aimed to compare the properties and sorption performance of adsorbents obtained by two methods: Fe3+ hydrolysis (SCHA) and Fe2+ oxidation (SCHB). To characterise the sorbents before and after Cr(VI) adsorption, specific surface area, particle size distribution, density, and zeta potential were determined. Additionally, optical micrographs, SEM, and FTIR analyses were performed. Adsorption experiments were performed in varying process conditions: pH, adsorbent dosage, contact time, and initial concentration. Adsorption isotherms were fitted by Freundlich, Langmuir, and Temkin models. Pseudo-first-order, pseudo-second-order, intraparticle diffusion, and liquid film diffusion models were used to fit the kinetics data. Linear regression was used to estimate the parameters of isotherm and kinetic models. The maximum adsorption capacity resulting from the fitted Langmuir isotherm is 42.97 and 17.54 mg·g−1 for SCHA and SCHB. Results show that the adsorption kinetics follows the pseudo-second-order kinetic model. Both iron-based adsorbents are suitable for removing Cr(VI) ions from aqueous solutions. Characterisation of the adsorbents after adsorption suggests that Cr(VI) adsorption can be mainly attributed to ion exchange with SO42− groups.
Transient Receptor Potential Channels in the Epithelial-to-Mesenchymal Transition
Authors: Van den Eynde Charlotte , De Clercq Katrien , Vriens Joris
Published: July 2021

The epithelial-to-mesenchymal transition (EMT) is a strictly regulated process that is indispensable for normal development, but it can result in fibrosis and cancer progression. It encompasses a complete alteration of the cellular transcriptomic profile, promoting the expression of genes involved in cellular migration, invasion and proliferation. Extracellular signaling factors driving the EMT process require secondary messengers to convey their effects to their targets. Due to its remarkable properties, calcium represents an ideal candidate to translate molecular messages from receptor to effector. Therefore, calcium-permeable ion channels that facilitate the influx of extracellular calcium into the cytosol can exert major influences on cellular phenotype. Transient receptor potential (TRP) channels represent a superfamily of non-selective cation channels that decode physical and chemical stimuli into cellular behavior. Their role as cellular sensors renders them interesting proteins to study in the context of phenotypic transitions, such as EMT. In this review, we elaborate on the current knowledge regarding TRP channel expression and activity in cellular phenotype and EMT.
Novel Nontoxic 5,9-Disubstituted SN38 Derivatives: Characterization of Their Pharmacological Properties and Interactions with DNA Oligomers
Authors: Bednarek Elżbieta , Bocian Wojciech , Urbanowicz Magdalena , Sitkowski Jerzy , Naumczuk Beata , Kozerski Lech
Published: July 2021

Novel nontoxic derivatives of SN38 with favorable antineoplastic properties were characterized in water solution using NMR. The phenomena observed by NMR were linked to basic pharmacological properties, such as solubility, bioavailability, chemical and stereochemical stability, and binding to natural DNA oligomers through the terminal G-C base pair, which is commonly considered a biological target of Topo I inhibitors. Compound 1, with bulky substituents at both C5(R) and C20(S) on the same side of a camptothecin core, manifests self-association, whereas diastereomers 2, with bulky C5(S) and C20(S) substituents are mostly monomeric in solution. The stereogenic center at C5 is stable in water solution at pH 5–6. The compound with an (N-azetidinyl)methyl substituent at C9 can undergo the retro Mannich reaction after a prolonged time in water solution. Both diastereomers exhibit different abilities in terms of binding to DNA oligomers: compound 1 is strongly bound, whereas the binding of compound 2 is rather weak. Molecular modeling produced results consistent with NMR experiments. These complementary data allow linking of the observed phenomena in NMR experiments to basic preliminary information on the pharmacodynamic character of compounds and are essential for planning further development research.
Genome-Wide Association Study in Rice Revealed a Novel Gene in Determining Plant Height and Stem Development, by Encoding a WRKY Transcription Factor
Authors: Wei Xiaoshuang , Zhou Hailian , Xie Deying , Li Jianguo , Yang Mingchong , Chang Tianli , Wang Dongxin , Hu Lihua , Xie Guosheng , Wang Jihong , Wang Lingqiang
Published: July 2021

Semi-dwarfism is a main agronomic trait in crop breeding. In this study, we performed genome-wide association study (GWAS) and identified a new quantitative trait nucleotide (QTN) for rice shoot length. The peak QTN (C/T) was located in the first coding region of a group III WRKY transcription factor OsWRKY21 (LOC_Os01g60640). Interestingly, further haplotype analysis showed that C/T difference only existed in the indica group but not in the japonica group, resulting in significant differences in plant height among the different indica rice varieties. OsWRKY21 was expressed in embryo, radicle, shoots, leaves, and stems. Most notably, overexpressing OsWRKY21 resulted in the semi-dwarf phenotype, early heading date and short internodes compared to the wild type, while the knockout mutant plants by CRISPR/Cas9 technology yielded the opposite. The overexpressing lines exhibited the decreased length of the cells near sclerenchyma epidermis, accompanied with the lower levels of indole-3-acetic acid (IAA) and gibberellin 3 (GA3), but increased levels of the abscisic acid (ABA) and salicylic acid (SA) in the internodes at heading stage. Moreover, the semi-dwarf phenotype could be fully rescued by exogenous GA3 application at seedling stage. The RNA-seq and qRT-PCR analysis confirmed the differential expression levels of genes in development and the stress responses in rice, including GA metabolism (GA20ox2, GA2ox6, and YABY1) and cell wall biosynthesis (CesA4, 7, and 9) and regulation (MYB103L). These data suggest the essential role of OsWRKY21 in regulation of internode elongation and plant height in rice.
Waterlogging-Stress-Responsive LncRNAs, Their Regulatory Relationships with miRNAs and Target Genes in Cucumber (Cucumis sativus L.)
Authors: Kęska Kinga , Szcześniak Michał Wojciech , Adamus Adela , Czernicka Małgorzata
Published: July 2021

Low oxygen level is a phenomenon often occurring during the cucumber cultivation period. Genes involved in adaptations to stress can be regulated by non-coding RNA. The aim was the identification of long non-coding RNAs (lncRNAs) involved in the response to long-term waterlogging stress in two cucumber haploid lines, i.e., DH2 (waterlogging tolerant—WL-T) and DH4 (waterlogging sensitive—WL-S). Plants, at the juvenile stage, were waterlogged for 7 days (non-primed, 1xH), and after a 14-day recovery period, plants were stressed again for another 7 days (primed, 2xH). Roots were collected for high-throughput RNA sequencing. Implementation of the bioinformatic pipeline made it possible to determine specific lncRNAs for non-primed and primed plants of both accessions, highlighting differential responses to hypoxia stress. In total, 3738 lncRNA molecules were identified. The highest number (1476) of unique lncRNAs was determined for non-primed WL-S plants. Seventy-one lncRNAs were depicted as potentially being involved in acquiring tolerance to hypoxia in cucumber. Understanding the mechanism of gene regulation under long-term waterlogging by lncRNAs and their interactions with miRNAs provides sufficient information in terms of adaptation to the oxygen deprivation in cucumber. To the best of our knowledge, this is the first report concerning the role of lncRNAs in the regulation of long-term waterlogging tolerance by priming application in cucumber.
Exercise Pills for Drug Addiction: Forced Moderate Endurance Exercise Inhibits Methamphetamine-Induced Hyperactivity through the Striatal Glutamatergic Signaling Pathway in Male Sprague Dawley Rats
Authors: Jung Suryun , Kim Youjeong , Kim Mingyu , Seo Minjae , Kim Suji , Kim Seungju , Lee Sooyeun
Published: July 2021

Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3β expression. However, the phosphorylation levels of Ser9-GSK-3β were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3β activation by the regulation of the striatal glutamate signaling pathway.
Maintenance of Ligament Homeostasis of Spheroid-Colonized Embroidered and Functionalized Scaffolds after 3D Stretch
Authors: Gögele Clemens , Konrad Jens , Hahn Judith , Breier Annette , Schröpfer Michaela , Meyer Michael , Merkel Rudolf , Hoffmann Bernd , Schulze-Tanzil Gundula
Published: July 2021

Anterior cruciate ligament (ACL) ruptures are usually treated with autograft implantation to prevent knee instability. Tissue engineered ACL reconstruction is becoming promising to circumvent autograft limitations. The aim was to evaluate the influence of cyclic stretch on lapine (L) ACL fibroblasts on embroidered scaffolds with respect to adhesion, DNA and sulphated glycosaminoglycan (sGAG) contents, gene expression of ligament-associated extracellular matrix genes, such as type I collagen, decorin, tenascin C, tenomodulin, gap junctional connexin 43 and the transcription factor Mohawk. Control scaffolds and those functionalized by gas phase fluorination and cross-linked collagen foam were either pre-cultured with a suspension or with spheroids of LACL cells before being subjected to cyclic stretch (4%, 0.11 Hz, 3 days). Stretch increased significantly the scaffold area colonized with cells but impaired sGAGs and decorin gene expression (functionalized scaffolds seeded with cell suspension). Stretching increased tenascin C, connexin 43 and Mohawk but decreased decorin gene expression (control scaffolds seeded with cell suspension). Pre-cultivation of functionalized scaffolds with spheroids might be the more suitable method for maintaining ligamentogenesis in 3D scaffolds compared to using a cell suspension due to a significantly higher sGAG content in response to stretching and type I collagen gene expression in functionalized scaffolds.
Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review
Authors: Yu Tien-Wei , Lane Hsien-Yuan , Lin Chieh-Hsin
Published: July 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and accounts for most cases of dementia. The prevalence of AD has increased in the current rapidly aging society and contributes to a heavy burden on families and society. Despite the profound impact of AD, current treatments are unable to achieve satisfactory therapeutic effects or stop the progression of the disease. Finding novel treatments for AD has become urgent. In this paper, we reviewed novel therapeutic approaches in five categories: anti-amyloid therapy, anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, and brain stimulation. The trend of therapeutic development is shifting from a single pathological target to a more complex mechanism, such as the neuroinflammatory and neurodegenerative processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), also have the potential for clinical application. In the future, it is possible for physicians to choose appropriate interventions individually on the basis of precision medicine.
Impact of Diabetes Mellitus on Cervical Spine Surgery for Ossification of the Posterior Longitudinal Ligament
Authors: Kimura Atsushi , Takeshita Katsushi , Yoshii Toshitaka , Egawa Satoru , Hirai Takashi , Sakai Kenichiro , Kusano Kazuo , Nakagawa Yukihiro , Wada Kanichiro , Katsumi Keiichi , Fujii Kengo , Furuya Takeo , Nagoshi Narihito , Kanchiku Tsukasa , Nagamoto Yukitaka , Oshima Yasushi , Nakashima Hiroaki , Ando Kei , Takahata Masahiko , Mori Kanji , Nakajima Hideaki , Murata Kazuma , Matsunaga Shunji , Kaito Takashi , Yamada Kei , Kobayashi Sho , Kato Satoshi , Ohba Tetsuro , Inami Satoshi , Fujibayashi Shunsuke , Katoh Hiroyuki , Kanno Haruo , Watanabe Kota , Imagama Shiro , Koda Masao , Kawaguchi Yoshiharu , Nakamura Masaya , Matsumoto Morio , Yamazaki Masashi , Okawa Atsushi
Published: July 2021

Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (≤30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up.
Zonisamide Therapy Reduces Metabolic Consequences and Diminishes Nonalcoholic Fatty Liver Disease in Patients with Epilepsy
Authors: Huang Chi-Ren , Chuang Hung-Yi , Chen Nai-Ching , Chen Shu-Fang , Hsu Chung-Yao , Chuang Yao-Chung
Published: July 2021

Antiepileptic drugs that can reduce aberrant metabolism are beneficial for patients. Zonisamide (ZNS) is a chemical with antiepileptic and antioxidant activities. Here, we evaluate the efficacy of ZNS therapy on reducing obesity and decreasing risks of vascular diseases and hepatic steatosis. Clinical and metabolic indicators including body weight, body mass index (BMI), serum lipid profiles, glycated hemoglobin (HbA1c), homocysteine, and an inflammatory marker, high-sensitivity C-reactive protein (hs-CRP), were assessed at baseline and at the end of 12 and 24 weeks of treatment. Nonalcoholic fatty liver disease was evaluated using the hepatic steatosis index (HSI). A body weight reduction of ≥5% was observed in 24.6% and 32.8% of patients after 12 and 24 weeks of ZNS treatment, respectively. After adjusting for age, sex, time, and the corresponding dependent variable at baseline, the generalized estimating equation analysis revealed that the body weight, BMI, serum levels of HbA1c, triglycerides, hs-CRP, and the index for HSI were significantly declined. These results suggest that ZNS provides benefits in patients with obesity and metabolic syndrome at high vascular risk.
Prognostic Effects of Vasomotor Reactivity during Targeted Temperature Management in Post-Cardiac Arrest Patients: A Retrospective Observational Study
Authors: Choi Mun Hee , Lee Sung Eun , Choi Jun Young , Lee Seong-Joon , Kim Da Sol , Chae Minjung Kathy , Park Eun Jung , Hong Ji Man
Published: July 2021

Early and precise neurological prognostication without self-fulfilling prophecy is challenging in post-cardiac arrest syndrome (PCAS), particularly during the targeted temperature management (TTM) period. This study aimed to investigate the feasibility of vasomotor reactivity (VMR) using transcranial Doppler (TCD) to determine whether final outcomes of patients with comatose PCAS are predicted. This study included patients who had out-of-hospital cardiac arrest in a tertiary referral hospital over 4 years. The eligible criteria included age ≥18 years, successful return of spontaneous circulation, TTM application, and bedside TCD examination within 72 h. Baseline demographics and multimodal prognostic parameters, including imaging findings, electrophysiological studies, and TCD-VMR parameters, were assessed. The final outcome parameter was cerebral performance category scale (CPC) at 1 month. Potential determinants were compared between good (CPC 1–2) and poor (CPC 3–5) outcome groups. The good outcome group (n = 41) (vs. poor (n = 117)) showed a higher VMR value (54.4% ± 33.0% vs. 25.1% ± 35.8%, p < 0.001). The addition of VMR to conventional prognostic parameters significantly improved the prediction power of good outcomes. This study suggests that TCD-VMR is a useful tool at the bedside to evaluate outcomes of patients with comatose PCAS during the TTM.
Special Issue: Formation and Function of Fungal Ascospores
Authors: Neiman Aaron M.
Published: July 2021

I wish to thank all of the authors who contributed papers to this Special Issue on the Formation and Function of Ascospores [...]
Soil Redox Controls CO2, CH4 and N2O Efflux from White-Rot Fungi in Temperate Forest Ecosystems
Authors: Merino Carolina , Jofré Ignacio , Matus Francisco
Published: July 2021

Microaerophilic white-rot fungi (WRF) are impacted by oxygen depletion because of fluctuating redox occurrence in southern temperate forest soils of Chile (1500–5000 mm year−1). How these conditions influence WRF survival has been scarcely examined. We explored the contributions of WRF to greenhouse gas (GHG) emissions of N2O and CH4 and soil organic C oxidation (CO2) in five sterilized and inoculated forest soils derived from various parent materials and climates. The soil was incubated for 20 days following (i) oxic, (ii) anoxic, and (iii) fluctuating redox conditions. Fungi contributed to 45% of the total GHG under redox fluctuating conditions, including the contribution of bacteria, while the opposite (26%) was valid for oxic treatment. On average, the highest gas emission (62%) was N2O for WRF under redox treatment, followed by anoxic (22%) and oxic (16%) treatments, while CO2 and CH4 emissions followed oxic > redox > anoxic. These data suggest that indigenous microbial WRF communities are well adapted to fluctuating redox milieu with a significant release of GHG emissions in humid temperate forests of the southern cone.
Fit-for-Purpose, Private-Sector Led Land Regularization and Financing of Informal Settlements in Brazil
Authors: Childress Malcolm , Carter Selina , Barki Edgard
Published: July 2021

This paper aims to analyze the financial and operational approach to land regularization and financing used in Brazil by an innovative private social enterprise in order to demonstrate that the approach widens the concept fit-for-purpose land regularization to include fit-for-purpose land financing, with relevance for wider efforts in informal settlement regularization and upgrading. In this approach, the enterprise acts as a coordinator and broker to organize the residents of informal settlements to regularize their settlements by negotiating buyouts of the underlying private owners at discounted values, handling titling and registration of the occupants, and coordinating with municipal governments to provide infrastructure. The analysis of parcel-level repayment and price data provides evidence of the sustainability of the business model and increase of property values of the regularized parcels. The results presented from the enterprise’s own repayment data demonstrate that under (non-pandemic) historical conditions residents are largely able to pay an affordable monthly payment over 7–10 years to the enterprise for the service to purchase the plots and maintain the enterprise. In operation since 2001, the enterprise has regularized over 20,000 parcels in more than 30 settlements, primarily in the cities of Sao Paolo and Curitiba in Brazil. The approach suggests that it could be widely replicable and add to the set of options for regularizing informal settlements, especially when purchase of private land is required.
Changes in the Spatial Development of a Satellite Town under the Impact of a Metropolitan City—Evidence from Pruszcz Gdański (Poland)
Authors: Świątkiewicz Anna , Połom Marcin , Puzdrakiewicz Krystian
Published: July 2021

Nowadays, large cities are becoming troublesome to live in in many respects. Due to the high prices of real estate, they are not attractive to young people. The literature often presents analyses of the phenomenon of urban sprawl to suburbia, but the subject of the impact of a metropolitan city on the functioning and changes in spatial development of satellite towns is rarely discussed. This study attempts to describe and to determine factors conducive to this process by identifying, through participant observation, the potential phenomenon of the influence of Gdańsk as a city with metropolitan functions on Pruszcz Gdański, a town directly adjacent to it. The article uses two main groups of methods: (a) a comparative analysis of orthophotomaps from 2005–2020 which allowed for recreating the dynamics of housing development, supported by land mapping as part of field research; (b) a structured internet survey on a sample of 393 residents which allowed identifying the factors influencing the spatial development of Pruszcz Gdański and the perception of this phenomenon, as well as an in-depth interview with a group of 6 residents which allowed obtaining detailed information on the quality of life in Pruszcz Gdański and the factors that determine living in this town. The proximity of both cities and much lower real estate prices in Pruszcz Gdański, which still has most of the functions of an independent town, is beneficial to settling down of migrants from the core of the metropolis. This process particularly applies to young people of working age who cannot afford to buy a new flat in Gdańsk. Building new multi-family housing estates close to the border with Gdańsk has created a kind of new service band or, in a sense, a “town within a town”.
Genome Characterization, Comparison and Phylogenetic Analysis of Complete Mitochondrial Genome of Evolvulus alsinoides Reveals Highly Rearranged Gene Order in Solanales
Authors: Shidhi Pattayampadam Ramakrishnan , Biju Vadakkemukadiyil Chellappan , Anu Sasi , Vipin Chandrasekharan Laila , Deelip Kumar Raveendran , Achuthsankar Sukumaran Nair
Published: July 2021

Mitogenome sequencing provides an understanding of the evolutionary mechanism of mitogenome formation, mechanisms driving plant gene order, genome structure, and migration sequences. Data on the mitochondrial genome for family Convolvulaceae members is lacking. E. alsinoides, also known as shankhpushpi, is an important medicinal plant under the family Convolvulaceae, widely used in the Ayurvedic system of medicine. We identified the mitogenome of E. alsinoides using the Illumina mate-pair sequencing platform, and annotated using bioinformatics approaches in the present study. The mitogenome of E. alsinoides was 344184 bp in length and comprised 46 unique coding genes, including 31 protein-coding genes (PCGs), 12 tRNA genes, and 3 rRNA genes. The secondary structure of tRNAs shows that all the tRNAs can be folded into canonical clover-leaf secondary structures, except three trnW, trnG, and trnC. Measurement of the skewness of the nucleotide composition showed that the AT and GC skew is positive, indicating higher A’s and G’s in the mitogenome of E. alsinoides. The Ka/Ks ratios of 11 protein-coding genes (atp1, ccmC, cob, cox1, rps19, rps12, nad3, nad9, atp9, rpl5, nad4L) were <1, indicating that these genes were under purifying selection. Synteny and gene order analysis were performed to identify homologous genes among the related species. Synteny blocks representing nine genes (nad9, nad2, ccmFc, nad1, nad4, nad5, matR, cox1, nad7) were observed in all the species of Solanales. Gene order comparison showed that a high level of gene rearrangement has occurred among all the species of Solanales. The mitogenome data obtained in the present study could be used as the Convolvulaceae family representative for future studies, as there is no complex taxonomic history associated with this plant.
Prevalence of Bladder and Bowel Dysfunction in Duchenne Muscular Dystrophy Using the Childhood Bladder and Bowel Dysfunction Questionnaire
Authors: Lionarons Judith M. , de Groot Imelda J. M. , Fock Johanna M. , Klinkenberg Sylvia , Vrijens Desiree M. J. , Vreugdenhil Anita C. E. , Medici-van den Herik Evita G. , Cuppen Inge , Jaeger Bregje , Niks Erik H. , Hoogerhuis Rinske , Platte-van Attekum Nicky , Feron Frans J. M. , Faber Catharina G. , Hendriksen Jos G. M. , Vles Johan S. H.
Published: July 2021

Introduction: Lower urinary tract symptoms (LUTS) and gastrointestinal (GI) problems are common in Duchenne muscular dystrophy (DMD), but not systematically assessed in regular care. We aimed to determine the prevalence of bladder and bowel dysfunction (BBD) in DMD patients compared with healthy controls (HC). Methods: The Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ) based on the International Rome III criteria and the International Children’s Continence Society was filled out by 57 DMD patients and 56 HC. Additionally, possible associations of BBD with, for example, medication use or quality of life were evaluated in an additional questionnaire developed by experts. Results: In 74% of patients versus 56% of HC ≥ 1 LUTS (n.s.) were reported, 68% of patients versus 39% of HC reported ≥1 bowel symptom (p = 0.002) and 53% of patients versus 30% of HC reported combined LUTS and bowel symptoms (p = 0.019). A negative impact of BBD on daily life functioning was reported by 42% of patients. Conclusions: These data underscore that standard screening for BBD is needed and that the CBBDQ could be of added value to optimize DMD care.
Drug Repurposing for the Management of Depression: Where Do We Stand Currently?
Authors: Mohammad Sadeghi Hosna , Adeli Ida , Mousavi Taraneh , Daniali Marzieh , Nikfar Shekoufeh , Abdollahi Mohammad
Published: July 2021

A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies of approving these medications. A deeper understanding of the pathogenesis of depression encourages novel discoveries through drug repurposing and drug repositioning to treat depression. In addition to reducing neurotransmitters like epinephrine and serotonin, other mechanisms such as inflammation, insufficient blood supply, and neurotoxicants are now considered as the possible involved mechanisms. Considering the mentioned mechanisms has resulted in repurposed medications to treat treatment-resistant depression (TRD) as alternative approaches. This review aims to discuss the available treatments and their progress way during repositioning. Neurotransmitters’ antagonists, atypical antipsychotics, and CNS stimulants have been studied for the repurposing aims. However, they need proper studies in terms of formulation, matching with regulatory standards, and efficacy.
Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
Authors: Yu Chunsong , An Myunggi , Li Meng , Manke Charles , Liu Haipeng
Published: July 2021

Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.
Nano-Bainitic Steels: Acceleration of Transformation by High Aluminum Addition and Its Effect on Their Mechanical Properties
Authors: Akram Mohamad , Soliman Mohamed , Palkowski Heinz
Published: July 2021

Additions of 3 and 5 wt.% Al have been investigated as a low-cost method for transformation acceleration in nano-bainitic steels. For both Al contents, two groups of steels with C-content in the range ~0.7 to ~0.95 wt.% were studied. Thermodynamic and physical simulations were used in alloy and heat treatment design. Characterization was performed via dilatometry, scanning and transmission electron microscopy, Synchrotron X-ray diffraction, and tensile and impact testing. Fast bainitic-transformation time-intervals ranging from 750–4600 s were recorded and tensile strengths up to 2000 MPa at a ductility of ~10 elongation percent were attainable for the 3 wt.% Al group at an austempering temperature of 265 °C. Higher Al additions were found to perform better than their lower Al counterparts as the austempering temperature is dropped. However, Al lowered the austenite stability, increased the martensite start temperature, austenitization temperatures and, consequently, the prior austenite grain size, as well as limiting the austempering temperatures to higher ones. Additionally, the lowered austenite stability coupled with higher additions of hardenability elements (here carbon) to maintain the martensite start at around 300 °C, causing the 5 wt.% Al group to have a large amount of low stability retained austenite (and consequently brittle martensite) in their microstructure, leading to a low elongation of around 5%.
Homogenisation Efficiency Assessed with Microstructure Analysis and Hardness Measurements in the EN AW 2011 Aluminium Alloy
Authors: Vončina Maja , Nagode Aleš , Medved Jožef , Paulin Irena , Žužek Borut , Balaško Tilen
Published: July 2021

When extruding the casted rods from EN AW 2011 aluminium alloys, not only their homogenized structure, but also their extrudable properties were significantly influenced by the hardness of the alloy. In this study, the object of investigations was the EN AW 2011 aluminium alloy, and the effect of homogenisation time on hardness was investigated. First, homogenisation was carried out at 520 °C for different times, imitating industrial conditions. After homogenisation, the samples were analysed by hardness measurements and further characterised by microscopy and image analysis to verify the influence of homogenisation on the resulting microstructural constituents. In addition, non-equilibrium solidification was simulated using the program Thermo-Calc and phase formation during solidification was investigated. The homogenisation process enabled more rounded shape of the Al2Cu eutectic phase, equilibrium formation of the phases, and the precipitation in the matrix, leading to a significant increase in the hardness of the EN AW 2011 aluminium alloy. The experimental data revealed a suitable homogenisation time of 4–6 h at a temperature of 520 °C, enabling optimal extrusion properties.
Publisher’s Note: Methane—An Open Access Journal
Authors: Lin Shu-Kun , Witkowska Agnieszka , Ribar Peter
Published: July 2021

During his doctoral studies (July 1989–January 1993) at the ETH Zurich, under the supervision of Prof [...]
Dynamic Information Flow Tracking: Taxonomy, Challenges, and Opportunities
Authors: Chen Kejun , Guo Xiaolong , Deng Qingxu , Jin Yier
Published: July 2021

Dynamic information flow tracking (DIFT) has been proven an effective technique to track data usage; prevent control data attacks and non-control data attacks at runtime; and analyze program performance. Therefore, a series of DIFT techniques have been developed recently. In this paper, we summarize the current DIFT solutions and analyze the features and limitations of these solutions. Based on the analysis, we classify the existing solutions into three categories, i.e., software, hardware, software and hardware co-design. We discuss the DIFT design from the perspective of whole system and point out the limitations of current DIFT frameworks. Potential enhancements to these solutions are also presented. Furthermore, we present suggestions about the possible future direction of DIFT solutions so that DIFT can help improve security levels.
Rapid Microfluidic Mixing Method Based on Droplet Rotation Due to PDMS Deformation
Authors: Wei Chunyang , Yu Chengzhuang , Li Shanshan , Pan Feng , Li Tiejun , Wang Zichao , Li Junwei
Published: July 2021

Droplet-based micromixers have shown great prospects in chemical synthesis, pharmacology, biologics, and diagnostics. When compared with the active method, passive micromixer is widely used because it relies on the droplet movement in the microchannel without extra energy, which is more concise and easier to operate. Here we present a droplet rotation-based microfluidic mixer that allows rapid mixing within individual droplets efficiently. PDMS deformation is used to construct subsidence on the roof of the microchannel, which can deviate the trajectory of droplets. Thus, the droplet shows a rotation behavior due to the non-uniform distribution of the flow field, which can introduce turbulence and induce cross-flow enhancing 3D mixing inside the droplet, achieving rapid and homogenous fluid mixing. In order to evaluate the performance of the droplet rotation-based microfluidic mixer, droplets with highly viscous fluid (60% w/w PEGDA solution) were generated, half of which was seeded with fluorescent dye for imaging. Mixing efficiency was quantified using the mixing index (MI), which shows as high as 92% mixing index was achieved within 12 mm traveling. Here in this work, it has been demonstrated that the microfluidic mixing method based on the droplet rotation has shown the advantages of low-cost, easy to operate, and high mixing efficiency. It is expected to find wide applications in the field of pharmaceutics, chemical synthesis, and biologics.
Molecular Characterization of Novel Family IV and VIII Esterases from a Compost Metagenomic Library
Authors: Park Jong-Eun , Jeong Geum-Seok , Lee Hyun-Woo , Kim Hoon
Published: July 2021

Two novel esterase genes, est8L and est13L, were isolated and identified from a compost metagenomic library. The encoded Est8L and Est13L had molecular masses of 33,181 and 44,913 Da consisting of 314 and 411 amino acids, respectively, without signal peptides. Est8L showed the highest identity (32.9%) to a hyper-thermophilic carboxylesterase AFEST from Archaeoglobus fulgidus compared to other esterases reported and was classified to be a novel member of family IV esterases with conserved regions such as HGGG, DY, GXSXG, DPL, and GXIH. Est13L showed the highest identity (98.5%) to the family VIII esterase Est7K from the metagenome library. Est8L and Est13L had the highest activities for p-nitrophenyl butyrate (C4) and p-nitrophenyl caproate (C6), respectively, and Est13L showed a broad substrate specificity for p-nitrophenyl substrates. Est8L and Est13L effectively hydrolyzed glyceryl tributyrate. The optimum temperatures for activities of Est8L and Est13L were identical (40 °C), and the optimum pH values were 9.0 and 10.0, respectively. Est13L showed higher thermostability than Est8L. Sephacryl S-200 HR chromatography showed that the native form of Est8L was a dimer. Interestingly, Est13L was found to be a tetramer, contrary to other family VIII esterases reported. Est8L was inhibited by 30% isopropanol, methanol, and acetonitrile; however, Est13L was activated to 182.9% and 356.1%, respectively, by 30% isopropanol and methanol. Est8L showed enantioselectivity for the S-form, but Est13L showed no enantioselectivity. These results show that intracellular Est8L and/or Est13L are oligomeric in terms of native forms and can be used for pharmaceutical and industrial applications with organic solvents under alkaline conditions.
Antimicrobial Effects of Potential Probiotics of Bacillus spp. Isolated from Human Microbiota: In Vitro and In Silico Methods
Authors: Torres-Sánchez Alfonso , Pardo-Cacho Jesús , López-Moreno Ana , Ruiz-Moreno Ángel , Cerk Klara , Aguilera Margarita
Published: July 2021

The variable taxa components of human gut microbiota seem to have an enormous biotechnological potential that is not yet well explored. To investigate the usefulness and applications of its biocompounds and/or bioactive substances would have a dual impact, allowing us to better understand the ecology of these microbiota consortia and to obtain resources for extended uses. Our research team has obtained a catalogue of isolated and typified strains from microbiota showing resistance to dietary contaminants and obesogens. Special attention was paid to cultivable Bacillus species as potential next-generation probiotics (NGP) together with their antimicrobial production and ecological impacts. The objective of the present work focused on bioinformatic genome data mining and phenotypic analyses for antimicrobial production. In silico methods were applied over the phylogenetically closest type strain genomes of the microbiota Bacillus spp. isolates and standardized antimicrobial production procedures were used. The main results showed partial and complete gene identification and presence of polyketide (PK) clusters on the whole genome sequences (WGS) analysed. Moreover, specific antimicrobial effects against B. cereus, B. circulans, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Serratia marcescens, Klebsiella spp., Pseudomonas spp., and Salmonella spp. confirmed their capacity of antimicrobial production. In conclusion, Bacillus strains isolated from human gut microbiota and taxonomic group, resistant to Bisphenols as xenobiotics type endocrine disruptors, showed parallel PKS biosynthesis and a phenotypic antimicrobial effect. This could modulate the composition of human gut microbiota and therefore its functionalities, becoming a predominant group when high contaminant exposure conditions are present.
Ammonia Production by Streptomyces Symbionts of Acromyrmex Leaf-Cutting Ants Strongly Inhibits the Fungal Pathogen Escovopsis
Authors: Dhodary Basanta , Spiteller Dieter
Published: July 2021

Leaf-cutting ants live in mutualistic symbiosis with their garden fungus Leucoagaricus gongylophorus that can be attacked by the specialized pathogenic fungus Escovopsis. Actinomyces symbionts from Acromyrmex leaf-cutting ants contribute to protect L. gongylophorus against pathogens. The symbiont Streptomyces sp. Av25_4 exhibited strong activity against Escovopsis weberi in co-cultivation assays. Experiments physically separating E. weberi and Streptomyces sp. Av25_4 allowing only exchange of volatiles revealed that Streptomyces sp. Av25_4 produces a volatile antifungal. Volatile compounds from Streptomyces sp. Av25_4 were collected by closed loop stripping. Analysis by NMR revealed that Streptomyces sp. Av25_4 overproduces ammonia (up to 8 mM) which completely inhibited the growth of E. weberi due to its strong basic pH. Additionally, other symbionts from different Acromyrmex ants inhibited E. weberi by production of ammonia. The waste of ca. one third of Acomyrmex and Atta leaf-cutting ant colonies was strongly basic due to ammonia (up to ca. 8 mM) suggesting its role in nest hygiene. Not only complex and metabolically costly secondary metabolites, such as polyketides, but simple ammonia released by symbionts of leaf-cutting ants can contribute to control the growth of Escovopsis that is sensitive to ammonia in contrast to the garden fungus L. gongylophorus.
A Hierarchical Approach to Improve the Interpretability of Causality Maps for Plant-Wide Fault Identification
Authors: van Zijl Natali , Bradshaw Steven Martin , Auret Lidia , Louw Tobias Muller
Published: July 2021

Modern mineral processing plants utilise fault detection and diagnosis to minimise time spent under faulty conditions. However, a fault originating in one plant section (PS) can propagate throughout the entire plant, obscuring its root cause. Causality analysis identifies the cause–effect relationships between process variables and presents them in a causality map to inform root cause identification. This paper presents a novel hierarchical approach for plant-wide causality analysis that decreases the number of nodes in a causality map, improving interpretability and enabling causality analysis as a tool for plant-wide fault diagnosis. Two causality maps are constructed in subsequent stages: first, a dimensionally reduced, plant-wide causality map used to localise the fault to a PS; second, a causality map of the identified PS used to identify the root cause. The hierarchical approach accurately identified the true root cause in a well-understood case study; its plant-wide map consisted of only three nodes compared to 15 nodes in the standard causality map and its transitive reduction. The plant-wide map required less fault-state data, time series in the order of hours or days instead of weeks or months, further motivating its application in rapid root cause analysis.
“Horsetail” Inclusions in the Ural Demantoids: Growth Formations
Authors: Kissin Aleksander Yurevich , Murzin Valery Vasilevich , Karaseva Elizaveta Sergeevna
Published: July 2021

The term “demantoid”, first proposed in 1856 by the famous Finnish mineralogist Nils von Nordensheld, refers to a highly dispersed yellow-green mineral from the Central Urals placers. In 1874, it was found to be a gem variety of andradite garnet. “Horsetail” inclusions are considered a sign of the Ural type demantoid. Although these inclusions are large (visible to the naked eye), their diagnostics remains debatable: some researchers attribute them to byssolite (amphibole-asbestos), others consider them chrysotile. We investigated the horsetail inclusions in the Ural demantoids through various methods: optical microscopy, scanning electron microscopy (SEM), Raman spectrometry, X-ray powder diffraction, and thermal analysis. In most cases, “horsetail” inclusions in the Ural demantoid were represented by hollow channels and only the outcrops, on the demantoid surface, were occasionally filled with serpentine (established by SEM); in one case, magnetite was observed. Hollow canals were usually collected not in bundles, such as a “horsetail”, but in fans, sometimes curved into cones. The structure of the grains was spheroidal, sectorial, and sometimes had induction surfaces, which, to the periphery of the grain, were replaced by tubular channels assembled in a fan. The specifics of the growth of the “horsetail” inclusions of the demantoid grains can be explained by the decompression conditions that arose when the ultrabasites (a crust-mantle mixture) were squeezed upwards during collision.
Strigolactones, from Plants to Human Health: Achievements and Challenges
Authors: Dell’Oste Valentina , Spyrakis Francesca , Prandi Cristina
Published: July 2021

Strigolactones (SLs) are a class of sesquiterpenoid plant hormones that play a role in the response of plants to various biotic and abiotic stresses. When released into the rhizosphere, they are perceived by both beneficial symbiotic mycorrhizal fungi and parasitic plants. Due to their multiple roles, SLs are potentially interesting agricultural targets. Indeed, the use of SLs as agrochemicals can favor sustainable agriculture via multiple mechanisms, including shaping root architecture, promoting ideal branching, stimulating nutrient assimilation, controlling parasitic weeds, mitigating drought and enhancing mycorrhization. Moreover, over the last few years, a number of studies have shed light onto the effects exerted by SLs on human cells and on their possible applications in medicine. For example, SLs have been demonstrated to play a key role in the control of pathways related to apoptosis and inflammation. The elucidation of the molecular mechanisms behind their action has inspired further investigations into their effects on human cells and their possible uses as anti-cancer and antimicrobial agents.