bluuebunny/crossref_metadata_2025 huggingface dataset:
Droplet Fate in a Cough Puff
Authors: Martano Paolo
Published: August 2020

The dynamic and thermodynamic evolution of droplets, in a size range characterizing a cough, has been analysed using basic equations of motion and coupled to the evolution of a spherical cloud puff in which they are supposed to be expired. It has been found that the maximum contamination range of the emitted droplets is controlled by two different mechanisms: surface evaporation and inertia-gravitational settling—with a switching threshold between them for a radius around a few tens of microns. For the smallest droplets, the environmental conditions (the temperature and humidity) are found to be very effective in determining the contamination range, even for weak entrainment in the cloud puff. This last fact could be of some relevance in the seasonal behaviour of air-borne epidemics.
A Multiscale Numerical Modeling Study of Smoke Dispersion and the Ventilation Index in Southwestern Colorado
Authors: Kiefer Michael T. , Charney Joseph J. , Zhong Shiyuan , Heilman Warren E. , Bian Xindi , Mathewson Timothy O.
Published: August 2020

The ventilation index (VI) is an index that describes the potential for smoke or other pollutants to disperse from a source. In this study, a Lagrangian particle dispersion model was utilized to examine smoke dispersion and the diagnostic value of VI during a September 2018 prescribed fire in southwestern Colorado. Smoke dispersion in the vicinity of the fire was simulated using the FLEXPART-WRF particle dispersion model, driven by meteorological outputs from Advanced Regional Prediction System (ARPS) simulations of the background (non-fire) conditions. Two research questions are posed: (1) Is a horizontal grid spacing of 4 km comparable to the finest grid spacing currently used in operational weather models and sufficient to capture the spatiotemporal variability in wind and planetary boundary layer (PBL) structure during the fire? (2) What is the relationship between VI and smoke dispersion during the prescribed fire event, as measured by particle residence time within a given horizontal or vertical distance from each particle’s release point? The ARPS no-fire simulations are shown to generally reproduce the observed variability in weather variables, with greatest fidelity to observations found with horizontal grid spacing of approximately 1 km or less. It is noted that there are considerable differences in particle residence time (i.e., dispersion) at different elevations, with VI exhibiting greater diagnostic value in the southern half of the domain, farthest from the higher terrain across the north. VI diagnostic value is also found to vary temporally, with diagnostic value greatest during the mid-morning to mid-afternoon period, and lowest during thunderstorm outflow passage in the late afternoon. Results from this study are expected to help guide the application of VI in complex terrain, and possibly inform development of new dispersion potential metrics.
Chemical Characteristics of Major Inorganic Ions in PM2.5 Based on Year-Long Observations in Guiyang, Southwest China—Implications for Formation Pathways and the Influences of Regional Transport
Authors: Xiao Hao , Xiao Hua-Yun , Zhang Zhong-Yi , Zheng Neng-Jian , Li Qin-kai , Li Xiao-Dong
Published: August 2020

Sulfate, nitrate and ammonium (SNA) are the dominant components of water-soluble ions (WSIs) in PM2.5, which are of great significance for understanding the sources and transformation mechanisms of PM2.5. In this study, daily PM2.5 samples were collected from September 2017 to August 2018 within the Guiyang urban area and the concentrations of the major WSIs in the PM2.5 samples were characterized. The results showed that the average concentration of SNA (SO42−, NO3−, NH4+) was 15.01 ± 9.35 μg m−3, accounting for 81.05% (48.71–93.76%) of the total WSIs and 45.33% (14.25–82.43%) of the PM2.5 and their possible chemical composition in PM2.5 was (NH4)2SO4 and NH4NO3. The highest SOR (sulfur oxidation ratio) was found in summer, which was mainly due to the higher temperature and O3 concentrations, while the lowest NOR (nitrogen oxidation ratio) found in summer may ascribe to the volatilization of nitrates being accelerated at higher temperature. Furthermore, the nitrate formation was more obvious in NH4+-rich environments so reducing NH3 emissions could effectively control the formation of nitrate. The results of the trajectory cluster analysis suggested that air pollutants can be easily enriched over short air mass trajectories from local emission sources, affecting the chemical composition of PM2.5.
Enhanced Thermostability and Enzymatic Activity of cel6A Variants from Thermobifida fusca by Empirical Domain Engineering
Authors: Ali Imran , Rehman Hafiz Muzzammel , Mirza Muhammad Usman , Akhtar Muhammad Waheed , Asghar Rehana , Tariq Muhammad , Ahmed Rashid , Tanveer Fatima , Khalid Hina , Alghamdi Huda Ahmed , Froeyen Matheus
Published: August 2020

Cellulases are a set of lignocellulolytic enzymes, capable of producing eco-friendly low-cost renewable bioethanol. However, low stability and hydrolytic activity limit their wide-scale applicability at the industrial scale. In this work, we report the domain engineering of endoglucanase (cel6A) of Thermobifida fusca to improve their catalytic activity and thermal stability. Later, enzymatic activity and thermostability of the most efficient variant named as cel6A.CBC was analyzed by molecular dynamics simulations. This variant demonstrated profound activity against soluble and insoluble cellulosic substrates like filter paper, alkali-treated bagasse, regenerated amorphous cellulose (RAC), and bacterial microcrystalline cellulose. The variant cel6A.CBC showed the highest catalysis of carboxymethyl cellulose (CMC) and other related insoluble substrates at a pH of 6.0 and a temperature of 60 °C. Furthermore, a sound rationale was observed between experimental findings and molecular modeling of cel6A.CBC which revealed thermostability of cel6A.CBC at 26.85, 60.85, and 74.85 °C as well as structural flexibility at 126.85 °C. Therefore, a thermostable derivative of cel6A engineered in the present work has enhanced biological performance and can be a useful construct for the mass production of bioethanol from plant biomass.
Characterization of Insulin-Like Growth Factor Binding Protein-5 (IGFBP-5) Gene and Its Potential Roles in Ontogenesis in the Pacific Abalone, Haliotis discus hannai
Authors: Sharker Md. Rajib , Kim Soo Cheol , Hossen Shaharior , Kho Kang Hee
Published: August 2020

Insulin-like growth factor binding protein family is known to be involved in regulating biological actions of insulin-like growth factors (IGFs). In the present study, a full-length cDNA encoding the IGFBP-5 gene was cloned and characterized from the cerebral ganglion of Haliotis discus hannai. The 921-bp full-length sequence of Hdh IGFBP-5 cDNA transcript had an open reading frame of 411 bp encoding a predicted polypeptide of 136 amino acids, sharing high sequence identities with IGFBP-5 of H. diversicolor. The deduced Hdh IGFBP-5 protein contained a putative transmembrane domain (13-35 aa) in the N-terminal region. It also possessed a signature domain of IGFBP protein family (IB domain, 45-120 aa). Six cysteine residues (Cys-47, Cys-55, Cys-73, Cys-85, Cys-98, and Cys-118) in this cloned sequence could potentially form an intrachain disulfide bond. Phylogenetic analysis indicated that the Hdh IGFBP-5 gene was robustly clustered with IGFBP-5 of H. diversicolor. Tissue distribution analysis based on qPCR assay showed that Hdh IGFBP-5 was widely expressed in all examined tissues, with significantly (p < 0.05) higher expression in the cerebral ganglion. In male and female gametogenetic cycles, Hdh IGFBP-5 mRNA was expressed at all stages, showing significantly higher level at ripening stage. The expression level of Hdh IGFBP-5 mRNA was significantly higher in the polar body stage than in other ontogenic stages. In situ hybridization revealed that Hdh IGFBP-5 mRNA was present in the neurosecretory cells of the cerebral ganglion. This is the first study describing IGFBP-5 in H. discus hannai that might be synthesized in the neural ganglia. Our results demonstrate Hdh IGFBP-5 is involved in regulating ontogenic development and reproductive regulation of H. discus hannai.
Essentials Oils from Brazilian Eugenia and Syzygium Species and Their Biological Activities
Authors: da Costa Jamile S. , da Cruz Ellen de Nazaré S. , Setzer William N. , da Silva Joyce Kelly do R. , Maia José Guilherme S. , Figueiredo Pablo Luis B.
Published: August 2020

The Eugenia and Syzygium genera include approximately 1000 and 1800 species, respectively, and both belong to the Myrtaceae. Their species present economic and medicinal importance and pharmacological properties. Due to their chemical diversity and biological activity, we are reporting the essential oils of 48 species of these two genera, which grow in South America and found mainly in Brazil. Chemically, a total of 127 oil samples have been described and displayed a higher intraspecific and interspecific diversity for both Eugenia spp. and Syzygium spp., according to the site of collection or seasonality. The main volatile compounds were sesquiterpene hydrocarbons and oxygenated sesquiterpenes, mainly with caryophyllane and germacrane skeletons and monoterpenes of mostly the pinane type. The oils presented many biological activities, especially antimicrobial (antifungal and antibacterial), anticholinesterase, anticancer (breast, gastric, melanoma, prostate), antiprotozoal (Leishmania spp.), antioxidant, acaricidal, antinociceptive and anti-inflammatory. These studies can contribute to the rational and economic exploration of Eugenia and Syzygium species once they have been identified as potent natural and alternative sources to the production of new herbal medicines.
Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer
Authors: Ashrafizadeh Milad , Hushmandi Kiavash , Hashemi Mehrdad , Akbari Mohammad Esmaeil , Kubatka Peter , Raei Mehdi , Koklesova Lenka , Shahinozzaman Md , Mohammadinejad Reza , Najafi Masoud , Sethi Gautam , Kumar Alan Prem , Zarrabi Ali
Published: August 2020

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.
Single and Combined Methods to Specifically or Bulk-Purify RNA–Protein Complexes
Authors: Van Ende Roosje , Balzarini Sam , Geuten Koen
Published: August 2020

The ribonome interconnects the proteome and the transcriptome. Specific biology is situated at this interface, which can be studied in bulk using omics approaches or specifically by targeting an individual protein or RNA species. In this review, we focus on both RNA- and ribonucleoprotein-(RNP) centric methods. These methods can be used to study the dynamics of the ribonome in response to a stimulus or to identify the proteins that interact with a specific RNA species. The purpose of this review is to provide and discuss an overview of strategies to cross-link RNA to proteins and the currently available RNA- and RNP-centric approaches to study RNPs. We elaborate on some major challenges common to most methods, involving RNP yield, purity and experimental cost. We identify the origin of these difficulties and propose to combine existing approaches to overcome these challenges. The solutions provided build on the recently developed organic phase separation protocols, such as Cross-Linked RNA eXtraction (XRNAX), orthogonal organic phase separation (OOPS) and Phenol-Toluol extraction (PTex).
Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan
Authors: Buchanan Jane , Taylor Eric
Published: August 2020

As a nodal mediator of pyruvate metabolism, the mitochondrial pyruvate carrier (MPC) plays a pivotal role in many physiological and pathological processes across the human lifespan, from embryonic development to aging-associated neurodegeneration. Emerging research highlights the importance of the MPC in diverse conditions, such as immune cell activation, cancer cell stemness, and dopamine production in Parkinson’s disease models. Whether MPC function ameliorates or contributes to disease is highly specific to tissue and cell type. Cell- and tissue-specific differences in MPC content and activity suggest that MPC function is tightly regulated as a mechanism of metabolic, cellular, and organismal control. Accordingly, recent studies on cancer and diabetes have identified protein–protein interactions, post-translational processes, and transcriptional factors that modulate MPC function. This growing body of literature demonstrates that the MPC and other mitochondrial carriers comprise a versatile and dynamic network undergirding the metabolism of health and disease.
Marijuana and Opioid Use during Pregnancy: Using Zebrafish to Gain Understanding of Congenital Anomalies Caused by Drug Exposure during Development
Authors: Sarmah Swapnalee , Sales Cadena Marilia Ribeiro , Cadena Pabyton Gonçalves , Marrs James A.
Published: August 2020

Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure to marijuana and opioids. Here, we summarize the current data on the prevalence of marijuana and opioid use among the people of the United States, particularly pregnant mothers. We also summarize the current zebrafish studies used to model and understand the effects of these drug exposures during development and to understand the behavioral changes after exposure. Zebrafish experiments recapitulate the drug effects seen in human addicts and the birth defects seen in human babies prenatally exposed to marijuana and opioids. Zebrafish show great potential as an easy and inexpensive model for screening compounds for their ability to mitigate the drug effects, which could lead to new therapeutics.
TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model
Authors: Bose Dipro , Mondal Ayan , Saha Punnag , Kimono Diana , Sarkar Sutapa , Seth Ratanesh K. , Janulewicz Patricia , Sullivan Kimberly , Horner Ronnie , Klimas Nancy , Nagarkatti Mitzi , Nagarkatti Prakash , Chatterjee Saurabh
Published: August 2020

The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been identified recently. Toll-like receptor 4 (TLR4) antagonism in systemic inflammatory diseases have been tried before with limited success, but strategies with broad-spectrum TLR4 antagonists and their ability to modulate the host-microbiome have been elusive. Using a mouse model of Gulf War Illness, we show that a nutraceutical, derived from a Chinese herb Sparstolonin B (SsnB) presented a unique microbiome signature with an increased abundance of butyrogenic bacteria. SsnB administration restored a normal tight junction protein profile with an increase in Occludin and a parallel decrease in Claudin 2 and inflammatory mediators high mobility group box 1 (HMGB1), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the distal intestine. SsnB also decreased neuronal inflammation by decreasing IL-1β and HMGB1, while increasing brain-derived neurotrophic factor (BDNF), with a parallel decrease in astrocyte activation in vitro. Mechanistically, SsnB inhibited the binding of HMGB1 and myeloid differentiation primary response protein (MyD88) to TLR4 in the intestine, thus attenuating TLR4 downstream signaling. Studies also showed that SsnB was effective in suppressing TLR4-induced nod-like receptor protein 3 (NLRP3) inflammasome activation, a prominent inflammatory disease pathway. SsnB significantly decreased astrocyte activation by decreasing colocalization of glial fibrillary acid protein (GFAP) and S100 calcium-binding protein B (S100B), a crucial event in neuronal inflammation. Inactivation of SsnB by treating the parent molecule by acetate reversed the deactivation of NLRP3 inflammasome and astrocytes in vitro, suggesting that SsnB molecular motifs may be responsible for its anti-inflammatory activity.
Subcortical T1-Rho MRI Abnormalities in Juvenile-Onset Huntington’s Disease
Authors: Tereshchenko Alexander V. , Schultz Jordan L. , Kunnath Ansley J. , Bruss Joel E. , Epping Eric A. , Magnotta Vincent A. , Nopoulos Peg C.
Published: August 2020

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the huntingtin gene. An increased CAG repeat length is associated with an earlier disease onset. About 5% of HD cases occur under the age of 21 years, which are classified as juvenile-onset Huntington’s disease (JOHD). Our study aims to measure subcortical metabolic abnormalities in JOHD participants. T1-Rho (T1ρ) MRI was used to compare brain regions of 13 JOHD participants and 39 controls. Region-of-interest analyses were used to assess differences in quantitative T1ρ relaxation times. We found that the mean relaxation times in the caudate (p < 0.001), putamen (p < 0.001), globus pallidus (p < 0.001), and thalamus (p < 0.001) were increased in JOHD participants compared to controls. Furthermore, increased T1ρ relaxation times in these areas were significantly associated with lower volumes amongst participants in the JOHD group. These findings suggest metabolic abnormalities in brain regions previously shown to degenerate in JOHD. We also analyzed the relationships between mean regional T1ρ relaxation times and Universal Huntington’s Disease Rating Scale (UHDRS) scores. UHDRS was used to evaluate participants’ motor function, cognitive function, behavior, and functional capacity. Mean T1ρ relaxation times in the caudate (p = 0.003), putamen (p = 0.005), globus pallidus (p = 0.009), and thalamus (p = 0.015) were directly proportional to the UHDRS score. This suggests that the T1ρ relaxation time may also predict HD-related motor deficits. Our findings suggest that subcortical metabolic abnormalities drive the unique hypokinetic symptoms in JOHD.
Preliminary Evidence of the Role of Medial Prefrontal Cortex in Self-Enhancement: A Transcranial Magnetic Stimulation Study
Authors: Taylor-Lillquist Birgitta , Kanpa Vivek , Crawford Maya , El Filali Mehdi , Oakes Julia , Jonasz Alex , Disney Amanda , Keenan Julian
Published: August 2020

Humans employ a number of strategies to improve their position in their given social hierarchy. Overclaiming involves presenting oneself as having more knowledge than one actually possesses, and it is typically invoked to increase one’s social standing. If increased expectations to possess knowledge is a perceived social pressure, such expectations should increase bouts of overclaiming. As the medial prefrontal cortex (MPFC) is sensitive to social pressure and disruption of the MPFC leads to decreases in overclaiming, we predicted that transcranial magnetic stimulation (TMS) applied to the MPFC would reduce overclaiming and the effects would be enhanced in the presence of social pressure. Twelve participants were given a test in which half of the words were real and half were fake, and they were asked how well they knew each word. They were not told that any of the words were fake. Half of the participants were exposed to social pressure while the other half were not. Following TMS delivered to the MPFC, overclaiming rates decreased, specifically under conditions of high social pressure. Medial PFC TMS did not influence real word responses and real words did not interact with the MPFC and social pressure. These preliminary findings support the significant role the MPFC plays in social cognition and the importance of the MPFC in mediating socially meaningful situations. We suggest the role of the MPFC as being highly influenced by the premium placed on social manipulation in human evolution.
Distal Aneurysms of Cerebellar Arteries—Case Series
Authors: Krahulik David , Vaverka Miroslav , Hrabálek Lumir , Trnka Štefan , Kocher Martin , Cerna Marie
Published: August 2020

(1) Background: Distal aneurysms of cerebellar arteries are very rare. The authors report their case series of distal aneurysms of the cerebellar arteries solved successfully by microsurgery or by endovascular treatment (Table 1) (2) Materials and Methods: Between January 2010 and March 2020, 346 aneurysms were treated in our institution. Eleven aneurysms in seven patients were located on distal cerebellar arteries and, in three patients, the aneurysms were combined with arteriovenous malformations. There were four women and three men, ranging from 50 to 72 years of age. Five patients presented with different grades of subarachnoid hemorrhage or intraventricular bleeding, and two patients were diagnosed because of headache. Aneurysm location was the posterior inferior cerebellar artery in six cases, the superior cerebellar artery in three cases, and the anterior inferior cerebellar artery in 2 cases. One patient had three aneurysms, and two patients had two aneurysms. (3) Results: Nine aneurysms were treated by microsurgery trapping or clipping and, in two patients, the associated arteriovenous malformation (AVM) was resected. Two aneurysms were treated by endovascular coiling, and one associated AVM was successfully embolized. Clinical follow-up was a mean of 11.5 months (range, 3–45 months). (4) Conclusion: The authors present their experience with the treatment of 11 peripheral aneurysms on distal branches of the cerebellar circulation in seven patients which were excluded from circulation by microsurgery or endovascular treatment. In three patients, the associated AVM was treated (two with microsurgery, one with embolization).
The Mediating Effect of Parental Involvement on School Climate and Behavior Problems: School Personnel Perceptions
Authors: Caridade Sónia Maria Martins , Sousa Hélder Fernando Pedrosa e , Pimenta Dinis Maria Alzira
Published: August 2020

As a reflection of the culture and norms of the school community, the school climate (SC) is a potential factor connected to students’ major behavior problems (BP). Parental involvement (PI) is considered as an essential factor for SC, contributing to promote good students’ educational results, as well as better social functioning. The present study aimed to analyze the mediating effect of PI on the relationship between SC and BP, taking into consideration the school personnel perceptions. A total of 329 school personnel (teachers versus no teachers) aged between 29 and 66 (M = 50.78, SD = 7.56), mainly female (79%), were integrated in the sample. Based on the perception of the school personnel, the results indicate moderate level of PI and SC, as well as the existence of different BP in the school context. The mediating effect of PI in the relationship between the SC and BP has been demonstrated. These results suggest that, if the SC and PI are improved, it could be an effective strategy to enhance the social functioning of students in the school context. This study thus contributes to a comprehensive empirical analysis of how PI can improve the relationship between the SC and the BP of Portuguese students.
Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity
Authors: Sung Ji-Yong , Lim Hee-Woong , Joung Je-Gun , Park Woong-Yang
Published: August 2020

Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism that extends telomeres in cancer cells. It influences tumorigenesis and patient survival. Despite the clinical significance of ALT in tumors, the manner in which ALT is activated and influences prognostic outcomes in distinct cancer types is unclear. In this work, we profiled distinct telomere maintenance mechanisms (TMMs) using 8953 transcriptomes of 31 different cancer types from The Cancer Genome Atlas (TCGA). Our results demonstrated that approximately 29% of cancer types display high ALT activity with low telomerase activity in the telomere-lengthening group. Among the distinct ALT mechanisms, homologous recombination was frequently observed in sarcoma, adrenocortical carcinoma, and kidney chromophobe. Five cancer types showed a significant difference in survival in the presence of high ALT activity. Sarcoma patients with elevated ALT had unfavorable risks (p < 0.038) coupled with a high expression of TOP2A, suggesting this as a potential drug target. On the contrary, glioblastoma patients had favorable risks (p < 0.02), and showed low levels of antigen-presenting cells. Together, our analyses highlight cancer type-dependent TMM activities and ALT-associated genes as potential therapeutic targets.
Donor-Site Morbidity after Fibula Transplantation in Head and Neck Tumor Patients: A Split-Leg Retrospective Study with Focus on Leg Stability and Quality of Life
Authors: Attia Sameh , Diefenbach Jonas , Schmermund Daniel , Böttger Sebastian , Pons-Kühnemann Jörn , Scheibelhut Christine , Heiss Christian , Howaldt Hans-Peter
Published: August 2020

The free fibula flap has been one of the most important microvascular grafts for orofacial reconstruction for more than 30 years. The complication rates at the donor-site reported in literature are considered to be low, but the published data vary greatly in some cases. In particular, restrictions in the stability and balance of the involved leg and their effects on the quality of life have been described very inconsistently to date. Therefore, this study mainly focuses on the stability and balance of the affected leg in a split-leg design. Between December 2014 and January 2018, out of 119 subjects who underwent mainly jaw ablative tumor surgery and reconstruction using a fibula flap, 68 subjects were examined for donor site morbidity. Besides reporting general types of complications, two specific test procedures were used. The Star Excursion Balance Test (SEBT) as a practical test for ankle function and the Foot and Ankle Disability Index (FADI) as a questionnaire in order to assess quality of life, depending on the lower leg function. SEBT revealed an average of 55.3 cm with the operated leg as the supporting leg, which corresponds to 95.5% of 57.9 cm achieved with the healthy leg as the supporting leg. An average FADI score of 89.4% was recorded. SEBT and FADI seem to be suitable methods of examination for subjects post fibular transplantation and pointed out minimal limitations of the involved legs in comparison to the unaffected legs. These limitations were clinically not relevant and they had minor influence on the subjects’ quality of life and their daily activities.
Antibody-Drug Conjugates: A Promising Novel Therapy for the Treatment of Ovarian Cancer
Authors: Manzano Aranzazu , Ocaña Alberto
Published: August 2020

Antibody-drug conjugates (ADCs) represent a novel and promising therapeutic strategy for the treatment of cancer patients. ADCs target antigens highly expressed on the membrane surface of tumor cells to selectively deliver a cytotoxic drug. Ovarian tumors differentially express tumor-specific antigens, which can be used to guide ADCs. This strategy allows for optimizing tumor targeting while minimizing systemic toxicity compared to classical chemotherapeutic agents. ADCs can be improved by using a cleavable linker allowing the delivery of the toxic payload in surrounding cells not expressing the target protein, therefore acting on heterogeneous tumors with different cell populations. Currently, more than 15 ADCs are under preclinical investigation in ovarian cancer, and some of them have already been tested in early-phase clinical trials with promising results. In this review, we summarize the mechanism of action and the toxicity profile of ADCs and discuss the latest preclinical discoveries and forthcoming applications in ovarian cancer.
Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
Authors: Picó María Dolores , Sánchez-Heras Ana Beatriz , Castillejo Adela , Giner-Calabuig Mar , Alustiza Miren , Sánchez Ariadna , Moreira Leticia , Pellise María , Castells Antoni , Llort Gemma , Yagüe Carmen , Ramon y Cajal Teresa , Gisbert-Beamud Alexandra , Cubiella Joaquin , Rivas Laura , Herraiz Maite , Garau Catalina , Salces Inmaculada , Carrillo-Palau Marta , Bujanda Luis , López-Fernández Adriá , Alvarez-Urturi Cristina , López María Jesús , Alenda Cristina , Zapater Pedro , Lacueva Francisco Javier , Balaguer Francesc , Soto Jose-Luis , Murcia Óscar , Jover Rodrigo
Published: August 2020

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk.
Thioxanthone Derivatives as a New Class of Organic Photocatalysts for Photopolymerisation Processes and the 3D Printing of Photocurable Resins under Visible Light
Authors: Hola Emilia , Pilch Maciej , Ortyl Joanna
Published: August 2020

In the present paper, novel thioxanthone-based compounds were synthesised and evaluated as a component of photoredox catalysts/photoinitiating systems for the free-radical polymerisation (FRP) of acrylates and the ring-opening cationic polymerisation (CP) of epoxy monomers. The performance of the obtained thioxanthones in two- and three-component photoinitiating systems, in combination with amines, iodonium or sulphonium salt, as well as with alkyl halide, for photopolymerisation processes upon exposure to light emitting diodes (LEDs) with a maximum emission of 405 nm and 420 nm, was investigated. The studied compounds act also as one-component free-radical photoinitiators. Fourier transform real-time infrared spectroscopy was used to monitor the kinetics of disappearance of the functional groups of the monomers during photoinitiated polymerisation. Excellent photoinitiating efficiency and high final conversions of functional groups were observed. Moreover, the influence of thioxanthone skeleton substitution on photoinitiating efficiency was discussed. The photochemical mechanism was also investigated through cyclic voltammetry. It was discovered that thioxanthone derivatives can be used as a metal-free photoredox catalyst active for both oxidative and reductive cycles. Furthermore, a photopolymerizable system based on novel thioxanthone derivatives in a stereolithography three-dimensional (3D) printing technology under visible sources of light was used. The effects of photoinitiator type system and monomer type in photoresins during 3D printing processes were explored. The outcome of this research is the development of high-performance visible photosensitive resins with improved photosensitivity obtained thanks to the development of entirely novel photoinitiating systems specifically adapted for this application.
Cr-Phthalocyanine Porous Organic Polymer as an Efficient and Selective Catalyst for Mono Carbonylation of Epoxides to Lactones
Authors: Ganesan Vinothkumar , Yoon Sungho
Published: August 2020

A facile, one-pot design strategy to construct chromium(III)-phthalocyanine chlorides (Pc’CrCl) to form porous organic polymer (POP-Pc’CrCl) using solvent knitting Friedel-Crafts reaction (FCR) is described. The generated highly porous POP-Pc’CrCl is functionalized by post-synthetic exchange reaction with nucleophilic cobaltate ions to provide an heterogenized carbonylation catalyst (POP-Pc’CrCo(CO)4) with Lewis acid-base type bimetallic units. The produced porous polymeric catalyst is identical to that homogeneous counterpart in structure and coordination environments. The catalyst is very selective and effective for mono carbonylation of epoxide into corresponding lactone and the activities are comparable to those observed for a homogeneous Pc’CrCo(CO)4 catalyst. The (POP-Pc’CrCo(CO)4) also displayed a good catalytic activities and recyclability upon successive recycles.
“Storage-Discharge” Ethanol Cold Plasma for Synthesizing High Performance Pd/Al2O3 Catalysts
Authors: Wang Hongyang , Zhang Tengda , Zhou Yufa , Zhang Xiuling , Di Lanbo
Published: August 2020

Atmospheric pressure cold plasma is an environmentally friendly and novel method to synthesize supported metal catalysts, which usually uses active hydrogen species to reduce metal ions. Ethanol is a hydrogen-rich renewable liquid hydrogen source, and it is more convenient to store and transport than H2. In this study, a “storage-discharge” ethanol cold plasma was used to prepare Pd/Al2O3-EP catalysts, and the obtained catalysts are used for CO oxidation. The complete oxidation of CO temperature (T100) over Pd/Al2O3-EP was 145 °C, which was comparable to the performance of Pd/Al2O3-HP that was synthesized by atmospheric pressure hydrogen cold plasma. Pd/Al2O3-EP-C obtained by calcining Pd/Al2O3-EP at 450 °C for 2 h in air atmosphere in order to remove residual carbon species showed much higher CO oxidation activity, and T100 was 130 °C. The Pd/Al2O3 catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron diffraction (XPS), Brunauer–Emmett–Teller (BET), and transmission electron microscopy (TEM), and the structure-performance relationship was analyzed. The results indicate that the “storage-discharge” ethanol cold plasma can reduce the Pd precursor ions into metallic Pd state, and the dissociation of ethanol forms lots of highly active chemisorbed oxygen species, which can enhance the performance of Pd/Al2O3-EP for CO oxidation. In contrast, Pd/Al2O3-EP-C shows much higher CO oxidation activity, which is mainly attributed to the removal of the residual carbon species, and the exposure of more Pd active sites and chemisorbed oxygen species. The “storage-discharge” ethanol cold plasma is a safe and efficient novel method for synthesizing supported Pd catalysts, and it has important potential for the preparation and application of supported metal catalysts.
A Review on Catalysts Development for Steam Reforming of Biodiesel Derived Glycerol; Promoters and Supports
Authors: Ghaffari Saeidabad Nasim , Noh Young Su , Alizadeh Eslami Ali , Song Hyun Tae , Kim Hyun Dong , Fazeli Ali , Moon Dong Ju
Published: August 2020

In the last decades, environmental crises and increasing energy demand have motivated researchers to investigate the practical techniques for the production of clean fuels through renewable energy resources. It is essential to develop technologies to utilize glycerol as a byproduct derived from biodiesel. Glycerol is known as a sustainable and clean source of energy, which can be an alternative resource for the production of value-added chemicals and hydrogen. The hydrogen production via steam reforming (SR) of glycerol using Ni-based catalysts is one of the promising approaches for the entry of the hydrogen economy. The purpose of this review paper is to highlight the recent trends in hydrogen production over Ni-based catalysts using the SR of glycerol. The intrinsic ability of Ni to disperse easily over variable supports makes it a more viable active phase for the SR catalysts. The optimal reaction conditions have been indicated as 650–900 °C, 1 bar, and 15 wt% Ni in catalysts for high glycerol conversion. In this review paper, the effects of various supports, different promoters (K, Ca, Sr, Ce, La, Cr, Fe), and process conditions on the catalytic performance have been summarized and discussed to provide a better comparison for the future works. It was found that Ce, Mg, and La have a significant effect on catalytic performance as promoters. Moreover, SR of glycerol over hydrotalcite and perovskite-based catalysts have been reviewed as they suggest high catalytic performance in SR of glycerol with improved thermal stability and coke resistance. More specifically, the Ni/LaNi0.9Cu0.1O3 synthesized using perovskite-type supports has shown high glycerol conversion and sufficient hydrogen selectivity at low temperatures. On the other hand, hydrotalcite-like catalysts have shown higher catalytic stability due to high thermal stability and low coke formation. It is vital to notice that the primary concern is developing a high-performance catalyst to utilize crude glycerol efficiently.
Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis
Authors: Fukai Tohru , Ushio-Fukai Masuko
Published: August 2020

Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). However, how highly diffusible ROS produced from different sources and location can communicate with each other to regulate angiogenesis remains unclear. To detect a localized ROS signal in distinct subcellular compartments in real time in situ, compartment-specific genetically encoded redox-sensitive fluorescence biosensors have been developed. Recently, the intercellular communication, “cross-talk”, between ROS derived from NOX and mitochondria, termed “ROS-induced ROS release”, has been proposed as a mechanism for ROS amplification at distinct subcellular compartments, which are essential for activation of redox signaling. This “ROS-induced ROS release” may represent a feed-forward mechanism of localized ROS production to maintain sustained signaling, which can be targeted under pathological conditions with oxidative stress or enhanced to promote therapeutic angiogenesis. In this review, we summarize the recent knowledge regarding the role of the cross-talk between NOX and mitochondria organizing the sustained ROS signaling involved in VEGF signaling, neovascularization and tissue repair.
Tristetraprolin Posttranscriptionally Downregulates TRAIL Death Receptors
Authors: Lee Won Hyeok , Han Myung Woul , Kim Song Hee , Seong Daseul , An Jae Hee , Chang Hyo Won , Kim Sang Yoon , Kim Seong Who , Lee Jong Cheol
Published: August 2020

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has attracted attention as a potential candidate for cancer therapy. However, many primary cancers are resistant to TRAIL, even when combined with standard chemotherapy. The mechanism of TRAIL resistance in cancer cells has not been fully elucidated. The TRAIL death receptor (DR) 3′-untranslated region (3′-UTR) is reported to contain AU-rich elements (AREs) that are important for regulating DR mRNA stability. However, the mechanisms by which DR mRNA stability is determined by its 3′-UTR are unknown. We demonstrate that tristetraprolin (TTP), an ARE-binding protein, has a critical function of regulating DR mRNA stability. DR4 mRNA contains three AREs and DR5 mRNA contains four AREs in 3′-UTR. TTP bound to all three AREs in DR4 and ARE3 in DR5 and enhanced decay of DR4/5 mRNA. TTP overexpression in colon cancer cells changed the TRAIL-sensitive cancer cells to TRAIL-resistant cells, and down-regulation of TTP increased TRAIL sensitivity via DR4/5 expression. Therefore, this study provides a molecular mechanism for enhanced levels of TRAIL DRs in cancer cells and a biological basis for posttranscriptional modification of TRAIL DRs. In addition, TTP status might be a biomarker for predicting TRAIL response when a TRAIL-based treatment is used for cancer.
Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications
Authors: Lopez-Santalla Mercedes , Fernandez-Perez Raquel , Garin Marina I.
Published: August 2020

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.
Role of Inflammasomes in HIV-1 and Drug Abuse Mediated Neuroinflammaging
Authors: Sil Susmita , Niu Fang , Chivero Ernest T. , Singh Seema , Periyasamy Palsamy , Buch Shilpa
Published: August 2020

Despite the effectiveness of combined antiretroviral therapy (cART) in suppressing virus replication, chronic inflammation remains one of the cardinal features intersecting HIV-1, cART, drug abuse, and likely contributes to the accelerated neurocognitive decline and aging in people living with HIV-1 (PLWH) that abuse drugs. It is also estimated that ~30–60% of PLWH on cART develop cognitive deficits associated with HIV-1-associated neurocognitive disorders (HAND), with symptomatology ranging from asymptomatic to mild, neurocognitive impairments. Adding further complexity to HAND is the comorbidity of drug abuse in PLWH involving activated immune responses and the release of neurotoxins, which, in turn, mediate neuroinflammation. Premature or accelerated aging is another feature of drug abusing PLWH on cART regimes. Emerging studies implicate the role of HIV-1/HIV-1 proteins, cART, and abused drugs in altering the inflammasome signaling in the central nervous system (CNS) cells. It is thus likely that exposure of these cells to HIV-1/HIV-1 proteins, cART, and/or abused drugs could have synergistic/additive effects on the activation of inflammasomes, in turn, leading to exacerbated neuroinflammation, ultimately resulting in premature aging referred to as “inflammaging” In this review, we summarize the current knowledge of inflammasome activation, neuroinflammation, and aging in central nervous system (CNS) cells such as microglia, astrocytes, and neurons in the context of HIV-1 and drug abuse.
Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness
Authors: Su Yu-Kai , Lin Jia Wei , Shih Jing-Wen , Chuang Hao-Yu , Fong Iat-Hang , Yeh Chi-Tai , Lin Chien-Min
Published: August 2020

Background: Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results: Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.