bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of Circularly Polarized Quasi-Non-Diffractive Vortex Wave via a Microwave Holographic Metasurface Integrated with a Monopole
Authors: Zhang Chen , Deng Li , Wang Ling , Chen Xue , Li Shufang
Published: August 2021

In this paper, a novel method for generating a circularly polarized (CP) quasi-non-diffractive vortex wave carrying orbital angular momentum (OAM), based on the microwave holographic metasurface integrated with a monopole, is proposed. This method is the combination of the non-diffraction theory and the principle of waveguide-fed-based holography and is equivalent to a superposition of two scalar impedance modulation surfaces. To verify the proposed method, a holographic metasurface generating a left-handed circularly polarized (LHCP) quasi-non-diffractive vortex wave carrying −1 mode OAM at the normal direction, was simulated and analyzed. The metasurface consisted of inhomogeneous slot units on a grounded substrate and a monopole excitation. Moreover, the location distribution of slots was determined by a computed interferogram between the reference wave and the object wave with the non-diffractive feature. Compared with an ordinary vortex wave, the quasi-non-diffractive wave obtained by our proposed method possessed a smaller divergence radius and a stronger electric field strength in the 9 times wavelength range. It paved a new path for manipulating the non-diffractive vortex wave in medium distance without using an external feeding source, which holds great potential for the miniaturization devices applied in medium-distance high-capacity secure communication, high-resolution imaging and intelligent detection.
A New Understanding and Modelling of TSP and BP Indices Compared to Safety IMO Ship Requirements
Authors: Pérez-Canosa José M. , Orosa José A. , Pacheco Eliseo A.
Published: August 2021

Due to the lack of information about the concept of Tons of Steering Pull (TSP) of many escort tugs, and the lack of research works relating the TSP demanded by a tethered vessel with respect to the TSP provided by tugs, the present paper shows an original study with mathematical models on how to solve these problems. What is more, an important percentage of the towing sector always employs Bollard Pull (BP), which is considered the only parameter capable of defining performance, so this paper aims to relate BP with TSP. The present research was carried out based on more than 25 escort tugs of different towing companies. Furthermore, a real case study of different tanker vessels was used for modelling purposes of tethered vessels’ TSP. Finally, once the proposed models were obtained, they were compared with International Maritime Organization (IMO) guidelines. The results showed charts with the main independent variables of tugs and vessels in order to be as useful and practical as possible to the shipping industry, mainly to ship owners and tug operators, from a safety point of view.
Characteristics of Particulate Matter at Different Pollution Levels in Chengdu, Southwest of China
Authors: Huang Yi , Wang Li , Cheng Xin , Wang Jinjin , Li Ting , He Min , Shi Huibin , Zhang Meng , Hughes Scott S. , Ni Shijun
Published: August 2021

Air pollution is becoming increasingly serious along with social and economic development in the southwest of China. The distribution characteristics of particle matter (PM) were studied in Chengdu from 2016 to 2017, and the changes of PM bearing water-soluble ions and heavy metals and the distribution of secondary ions were analyzed during the haze episode. The results showed that at different pollution levels, heavy metals were more likely to be enriched in fine particles and may be used as a tracer of primary pollution sources. The water-soluble ions in PM2.5 were mainly Sulfate-Nitrate-Ammonium (SNA) accounting for 43.02%, 24.23%, 23.50%, respectively. SO42−, NO3−, NH4+ in PM10 accounted for 34.56%, 27.43%, 19.18%, respectively. It was mainly SO42− in PM at Clean levels (PM2.5 = 0~75 μg/m3, PM10 = 0~150 μg/m3), and mainly NH4+ and NO3− at Light-Medium levels (PM2.5 = 75~150 μg/m3, PM10 = 150~350 μg/m3). At Heavy levels (PM2.5 = 150~250 μg/m3, PM10 = 350~420 μg/m3), it is mainly SO42− in PM2.5, and mainly NH4+ and NO3− in PM10. The contribution of mobile sources to the formation of haze in the study area was significant. SNA had significant contributions to the PM during the haze episode, and more attention should be paid to them in order to improve air quality.
Reduced Sea-Surface Roughness Length at a Coastal Site
Authors: He Yuncheng , Fu Jiyang , Chan Pak Wai , Li Qiusheng , Shu Zhenru , Zhou Kang
Published: August 2021

Sea-surface roughness length is a key parameter for characterizing marine atmospheric boundary layer. Although aerodynamic roughness lengths for homogeneous land and open water surfaces have been examined extensively, the extension of relevant knowledge to the highly inhomogeneous coastal area is problematic due to the complex mechanisms controlling coastal meteorology. This study presented a lidar-based observational analysis of sea-surface roughness length at a coastal site in Hong Kong, in which the wind data recorded from March 2012 to November 2015 were considered and analyzed. The results indicated the turning of wind near the land-sea boundary, leading to a dominative wind direction parallel to the coastline and an acceleration in wind. Moreover, the roughness lengths corresponding to two representative azimuthal sectors were compared, in which the roughness lengths for the onshore wind sector (i.e., 120°–240°) appear to be larger than the constant value (z0 = 0.2 mm) recommended in much existing literature, whereas the values for the alongshore wind sector (i.e., 60°–90°) are significantly smaller, i.e., about two orders of magnitude less than that of a typical sea surface. However, it is to be noted that the effect of atmospheric stability, which is of crucial importance in governing the marine atmospheric boundary layer, is not taken into account in this study.
Experimental Comparative Study between Conventional and Green Parking Lots: Analysis of Subsurface Thermal Behavior under Warm and Dry Summer Conditions
Authors: Bouzouidja Ryad , Leconte François , Kiss Márton , Pierret Margaux , Pruvot Christelle , Détriché Sébastien , Louvel Brice , Bertout Julie , Aketouane Zakaria , Vogt Wu Tingting , Goiffon Rémy , Colin Baptiste , Pétrissans Anélie , Lagière Philippe , Pétrissans Mathieu
Published: August 2021

Green infrastructure has a role to play in climate change adaptation strategies in cities. Alternative urban spaces should be designed considering new requirements in terms of urban microclimate and thermal comfort. Pervious pavements such as green parking lots can contribute to this goal through solar evaporative cooling. However, the cooling benefits of such systems remain under debate during dry and warm periods. The aim of this study was to compare experimentally the thermal behavior of different parking lot types (PLTs) with vegetated urban soil. Four parking lots were instrumented, with temperature probes buried at different depths. Underground temperatures were measured during summer 2019, and the hottest days of the period were analyzed. Results show that the less mineral used in the surface coating, the less it warms up. The temperature difference at the upper layer can reach 10 °C between mineral and non-mineral PLTs. PLTs can be grouped into three types: (i) high surface temperature during daytime and nighttime, important heat transfer toward the sublayers, and low time shift (asphalt system); (ii) high (resp. low) surface temperature during daytime (resp. nighttime), weak heat transfer toward the sublayers, and important time shift (paved stone system); and (iii) low surface temperature during daytime and nighttime, weak heat transfer toward the sublayers, and important time shift (vegetation and substrate system, wood chips system, vegetated urban soil). The results of this study underline that pervious pavements demonstrate thermal benefits under warm and dry summer conditions compared to conventional parking lot solutions. The results also indicate that the hygrothermal properties of urban materials are crucial for urban heat island mitigation.
A Study of the Effects of Rain, Snow and Hail on the Atmospheric Electric Field near Ground
Authors: Karagioras Athanasios , Kourtidis Konstantinos
Published: August 2021

The purpose of the present study is to investigate the impact of rain, snow and hail on potential gradient (PG), as observed in a period of ten years in Xanthi, northern Greece. An anticorrelation between PG and rainfall was observed for rain events that lasted several hours. When the precipitation rate was up to 2 mm/h, the decrease in PG was between 200 and 1300 V/m, in most cases being around 500 V/m. An event with rainfall rates up to 11 mm/h produced the largest drop in PG, of 2 kV/m. Shortly after rain, PG appeared to bounce back to somewhat higher values than the ones of fair-weather conditions. A decrease in mean hourly PG was observed, which was around 2–4 kV/m during the hail events which occurred concurrently with rain and from 0 to 3.5 kV/m for hail events with no rain. In the case of no drop, no concurrent drop in temperature was observed, while, for the other cases, it appeared that, for each degree drop in temperature, the drop in hourly mean PG was 1000 V/m; hence, we assume that the intensity of the hail event regulates the drop in PG. The frequency distribution of 1-minute PG exhibits a complex structure during hail events and extend from −18 to 11 kV/m, with most of the values in the negative range. During snow events, 1-minute PG exhibited rapid fluctuations between high positive and high negative values, its frequency distribution extending from −10 to 18 kV/m, with peaks at −10 and 3 kV/m.
Purification and Characterization of Antibodies Directed against the α-Gal Epitope
Authors: Zappe Andreas , Rosenlöcher Julia , Kohla Guido , Hinderlich Stephan , Parr Maria Kristina
Published: August 2021

The α-Gal epitope is an immunogen trisaccharide structure consisting of N-acetylglucosamine (GlcNAc)β1,4-galactose (Gal)α1,3-Gal. It is presented as part of complex-type glycans on glycoproteins or glycolipids on cell surfaces of non-primate mammalians. About 1% of all antibodies in human sera are specific toward α1,3-Gal and are therefore named as anti-α-Gal antibodies. This work comprises the purification and characterization of anti-α-Gal antibodies from human immunoglobulin G (IgG). A synthetically manufactured α Gal epitope affinity resin was used to enrich anti-α-Gal antibodies. Selectivity experiments with purified antibodies were carried out using enzyme-linked immunosorbent assays (ELISA), Western blotting, and erythrocyte agglutination. Furthermore, binding affinities toward α-Gal were determined by surface plasmon resonance (SPR) and the IgG distribution of anti α Gal antibodies (83% IgG2, 14% IgG1, 2% IgG3, 1% IgG4) was calculated applying ELISA and immunodiffusion. A range of isoelectric points from pH 6 to pH 8 was observed in 2D gel electrophoresis. Glycan profiling of anti α Gal antibodies revealed complex biantennary structures with high fucosylation grades (86%). Additionally, low amounts of bisecting GlcNAc (15%) and sialic acids (13%) were detected. The purification of anti-α-Gal antibodies from human IgG was successful, and their use as detection antibodies for α Gal-containing structures was evaluated.
Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer
Authors: Reang Jurnal , Sharma Prabodh Chander , Thakur Vijay Kumar , Majeed Jaseela
Published: August 2021

Cancer, a fatal disease, is also one of the main causes of death worldwide. Despite various developments to prevent and treat cancer, the side effects of anticancer drugs remain a major concern. Ascorbic acid is an essential vitamin required by our bodies for normal physiological function and also has antioxidant and anticancer activity. Although the body cannot synthesize ascorbic acid, it is abundant in nature through foods and other natural sources and also exists as a nutritional food supplement. In anticancer drug development, ascorbic acid has played an important role by inhibiting the development of cancer through various mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS and encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving as an epigenetic regulator, and regulating the expression of HIF in tumour cells. Several ascorbic acid analogues have been produced to date for their anticancer and antioxidant activity. The current review summarizes the mechanisms behind ascorbic acid’s antitumor activity, presents a compilation of its derivatives and their biological activity as anticancer agents, and discusses delivery systems such as liposomes, nanoparticles against cancer, and patents on ascorbic acid as anticancer agents.
A Chitosan–Agarose Polysaccharide-Based Hydrogel for Biomimetic Remineralization of Dental Enamel
Authors: Muşat Viorica , Anghel Elena , Zaharia Agripina , Atkinson Irina , Mocioiu Oana , Buşilă Mariana , Alexandru Petrică
Published: August 2021

Developing multifunctional systems for the biomimetic remineralization of human enamel is a challenging task, since hydroxyapatite (HAP) rod structures of tooth enamel are difficult to replicate artificially. The paper presents the first report on the simultaneous use of chitosan (CS) and agarose (A) in a biopolymer-based hydrogel for the biomimetic remineralization of an acid-etched native enamel surface during 4–10-day immersion in artificial saliva with or without (control group) fluoride. Scanning electron microscopy coupled with energy-dispersive X-ray spectrometry, Fourier transform infrared and Raman spectroscopies, X-ray diffraction, and microhardness tests were applied to investigate the properties of the acid-etched and remineralized dental enamel layers under A and CS-A hydrogels. The results show that all biomimetic epitaxial reconstructed layers consist mostly of a similar hierarchical HAP structure to the native enamel from nano- to microscale. An analogous Ca/P ratio (1.64) to natural tooth enamel and microhardness recovery of 77.4% of the enamel-like layer are obtained by a 7-day remineralization process in artificial saliva under CS-A hydrogels. The CS component reduced carbonation and moderated the formation of HAP nanorods in addition to providing an extracellular matrix to support growing enamel-like structures. Such activity lacked in samples exposed to A-hydrogel only. These data suggest the potential of the CS-A hydrogel in guiding the formation of hard tissues as dental enamel.
Phytoplankton of the Curonian Lagoon as a New Interesting Source for Bioactive Natural Products. Special Impact on Cyanobacterial Metabolites
Authors: Overlingė Donata , Toruńska-Sitarz Anna , Cegłowska Marta , Błaszczyk Agata , Szubert Karolina , Pilkaitytė Renata , Mazur-Marzec Hanna
Published: August 2021

The bioprospecting of marine and brackish water systems has increased during the last decades. In this respect, microalgae, including cyanobacteria, and their metabolites are one of the most widely explored resources. Most of the bioactive compounds are isolated from ex situ cultures of microorganisms; however, analysis of field samples could also supply valuable information about the metabolic and biotechnological potential of microalgae communities. In this work, the activity of phytoplankton samples from the Curonian Lagoon was studied. The samples were active against antibiotic resistant clinical and environmental bacterial strains as well as against serine proteases and T47D human breast adenocarcinoma cells. No significant effect was found on Daphnia magna. In addition, using LC-MS/MS, we documented the diversity of metabolites present in field samples. A list of 117 detected cyanopeptides was presented. Cyanopeptolins constituted the largest class of cyanopeptides. As complex bloom samples were analyzed, no link between the observed activity and a specific sample component can be established. However, the results of the study showed a biotechnological potential of natural products from the Curonian Lagoon.
DNA Hypermethylation Involves in the Down-Regulation of Chloride Intracellular Channel 4 (CLIC4) Induced by Photodynamic Therapy
Authors: Chiang Pei-Chi , Li Pei-Tzu , Lee Ming-Jen , Chen Chin-Tin
Published: August 2021

The altered expression of chloride intracellular channel 4 (CLIC4) was reported to correlate with tumor progression. Previously, we have shown that the reduced cellular invasion induced by photodynamic therapy (PDT) is associated with suppression of CLIC4 expression in PDT-treated cells. Herein, we attempted to decipher the regulatory mechanisms involved in PDT-mediated CLIC4 suppression in A375 and MDA-MB-231 cells in vitro. We found that PDT can increase the expression and enzymatic activity of DNA methyltransferase 1 (DNMT1). Bisulfite sequencing PCR further revealed that PDT can induce hypermethylation in the CLIC4 promoter region. Silencing DNMT1 rescues the PDT-induced CLIC4 suppression and inhibits hypermethylation in its promoter. Furthermore, we found tumor suppressor p53 involves in the increased DNMT1 expression of PDT-treated cells. Finally, by comparing CLIC4 expression in lung malignant cells and normal lung fibroblasts, the extent of methylation in CLIC4 promoter was found to be inversely proportional to its expression. Taken together, our results indicate that CLIC4 suppression induced by PDT is modulated by DNMT1-mediated hypermethylation and depends on the status of p53, which provides a possible mechanistic basis for regulating CLIC4 expression in tumorigenesis.
Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes
Authors: Lugo-Fabres Pavel H. , Otero-Sastre Leslie M. , Bernáldez-Sarabia Johanna , Camacho-Villegas Tanya A. , Sánchez-Campos Noemi , Serrano-Bello Janeth , Medina Luis A. , Muñiz-Hernández Saé , de la Cruz Lizbeth , Arenas Isabel , Barajas-Martínez Antonio , Garcia David E. , Nuñez-Garcia Linda , González-Canudas Jorge , Licea-Navarro Alexei F.
Published: August 2021

The FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas’s capability to produce insulin is still effective.
Sarcotubular Myopathy Due to Novel TRIM32 Mutation in Association with Multiple Sclerosis
Authors: Marchuk Margarita , Dovbonos Tetiana , Makukh Halyna , Semeryak Orest , Sharhorodska Yevheniya
Published: August 2021

Azerbaijani 28-year-old female showed weakness (MRC (Medical Research Council Scale for Muscle Strength) grade 4 in the proximal part of the upper and MRC grade 2–3 in the lower extremities), difficulty in stair lifting, positive symptom of Hoover’s rising, «waddling gait», decline deep reflexes symmetrical, lack of surface reflexes, positive Babinsky’s reflex on the right, urinary incontinence during sneezing, prolonged walking and exercise from puberty. Additional methods made it possible to identify minor violations of conduction of the left ventricle, electromyography signs of primary muscular disease with predominant involvement of the proximal muscles of the lower extremities, elevation of serum creatine kinase (746.81 U/l), active foci of demyelination in the left frontal lobe, intrathecal synthesis of oligoclonal IgG bands (type 2) in cerebrospinal fluid, atrophy and fatty degeneration of all muscles of the shins, homozygous Variant of Uncertain Significance (VUS) c.1855C > T (p.Pro619Ser) in TRIM32 gene and heterozygous VUS c.2300C > G (p.Thr767Arg) in KIF5A, c.2840G > A (p.Arg947Lys) in MYH2, c.1502G > C (p.Gly501Ala) in POMT1 genes. Comparison of the phenotypes of the mutations that have been identified with the clinical picture of the patient suggests that VUS c.1855C > T (p.Pro619Ser) in the TRIM32 gene can be pathological. Summarizing, it can be argued that the cause of the identified disorders is a homozygous variant c.1855C > T (p.Pro619Ser) in TRIM32 gene that causes LGMDR8 in a patient with MS.
The Assessment of Serum Concentrations of AGEs and Their Soluble Receptor (sRAGE) in Multiple Sclerosis Patients
Authors: Damasiewicz-Bodzek Aleksandra , Łabuz-Roszak Beata , Kumaszka Bartłomiej , Tadeusiak Bartosz , Tyrpień-Golder Krystyna
Published: August 2021

Background: Advanced glycation end products (AGEs) are involved in the pathogenesis of many diseases, including neurodegenerative diseases such as multiple sclerosis (MS). The aim of the study was to determine serum concentrations of AGEs and their soluble receptor (sRAGE) in MS patients and healthy controls and to investigate their possible influence on disease activity. Methods: Serum concentrations of AGE and sRAGE in patients with MS and healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Results: The mean serum AGE concentration in patients with MS was higher than in healthy controls, whereas the mean serum sRAGE concentration was lower than in the control group. However, the differences were not statistically significant. In MS patients, serum AGE and sRAGE concentrations did not differ significantly, depending on the duration of the disease and the Expanded Disability Status Scale (EDSS) score. Conclusions: Multiple sclerosis may be accompanied by disturbances of the AGE-sRAGE axis. However, further studies are warranted to confirm it. The duration of the disease and the degree of disability do not seem to affect the progression of the glycation process, particularly in the stable phase of the disease.
Evaluation of Participant Success in Gamified Drone Training Simulator Using Brain Signals and Key Logs
Authors: Koç Durmuş , Seçkin Ahmet Çağdaş , Satı Zümrüt Ecevit
Published: August 2021

The risk of accidents while operating a drone is quite high. The most important solution is training for drone pilots. Drone pilot training can be done in both physical and virtual environments, but the probability of an accident is higher for pilot trainees, so the first method is to train in a virtual environment. The purpose of this study is to develop a new system to collect data on students’ educational development performance of students during the use of Gamified Drone Training Simulator and objectively analyze students’ development. A multimodal recording system that can collect simulator, keystroke, and brain activity data has been developed to analyze the cognitive and physical activities of participants trained in the gamified drone simulator. It was found that as the number of trials increased, participants became accustomed to the cognitive load of visual/auditory tasks and therefore the power in the alpha and beta bands decreased. It was observed that participants’ meditation and attention scores increased with the number of repetitions of the educational game. It can be concluded that the number of repetitions lowers stress and anxiety levels, increases attention, and thus enhances game performance.
Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing
Authors: Dragoj Miodrag , Stojkovska Jasmina , Stanković Tijana , Dinić Jelena , Podolski-Renić Ana , Obradović Bojana , Pešić Milica
Published: August 2021

Background: Various three-dimensional (3D) glioblastoma cell culture models have a limited duration of viability. Our aim was to develop a long-term 3D glioblastoma model, which is necessary for reliable drug response studies. Methods: Human U87 glioblastoma cells were cultured in alginate microfibers for 28 days. Cell growth, viability, morphology, and aggregation in 3D culture were monitored by fluorescent and confocal microscopy upon calcein-AM/propidium iodide (CAM/PI) staining every seven days. The glioblastoma 3D model was validated using temozolomide (TMZ) treatments 3 days in a row with a recovery period. Cell viability by MTT and resistance-related gene expression (MGMT and ABCB1) by qPCR were assessed after 28 days. The same TMZ treatment schedule was applied in 2D U87 cell culture for comparison purposes. Results: Within a long-term 3D model system in alginate fibers, U87 cells remained viable for up to 28 days. On day 7, cells formed visible aggregates oriented to the microfiber periphery. TMZ treatment reduced cell growth but increased drug resistance-related gene expression. The latter effect was more pronounced in 3D compared to 2D cell culture. Conclusion: Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization.
Superficially Invasive Vulvar Squamous Cell Carcinoma: A 37-Year-Long Experience of a Tertiary Referral Center
Authors: Preti Mario , Borella Fulvio , Gallio Niccolò , Bertero Luca , Heller Debra Sandra , Vieira-Baptista Pedro , Cosma Stefano , Bevilacqua Federica , Privitera Sebastiana , Micheletti Leonardo , Benedetto Chiara
Published: August 2021

Superficially, invasive vulvar squamous cell carcinoma (SISCCA) (FIGO stage IA) is a rare subset of vulvar cancer defined as a single lesion measuring ≤2 cm with a depth of invasion of ≤1.0 mm. This is a retrospective study performed on 48 patients with SISCCA, surgically treated between 1981 and 2018 at the S. Anna Hospital, University of Turin, to evaluate pathological characteristics and prognosis of these tumors. Ten patients (21%) recurred: seven (14%) as SISCCA and three (7%) as deeply invasive carcinoma. One case with perineural invasion and groin node metastasis at recurrence. No patient had groin lymph node metastases at initial diagnosis. Site of SISCCA, type of surgery, status of surgical margins, and histopathological features did not differ between recurrent and non-recurrent patients. We observed a non-significant trend towards an increase of recurrences in younger women (median age: 63 years vs. 70 years, p = 0.09), while, surprisingly, smaller tumors (<12 mm) were significantly related to tumor relapse (p = 0.03). Overall, SISCCA has a good long-term prognosis, regardless of the pathological characteristics and the type of surgical treatment. We recommend close follow-up, especially for younger patients and for small tumors, due to the possibility of recurrence or re-occurrence even after years.
Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors
Authors: Rabab’h Omar , Gharaibeh Abeer , Al-Ramadan Ali , Ismail Manar , Shah Jawad
Published: August 2021

Neurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions.
Mass Spectrometry-Based Proteomic Discovery of Prognostic Biomarkers in Adrenal Cortical Carcinoma
Authors: Jang Han Na , Moon Sun Joon , Jung Kyeong Cheon , Kim Sang Wan , Kim Hyeyoon , Han Dohyun , Kim Jung Hee
Published: August 2021

Adrenal cortical carcinoma (ACC) is an extremely rare disease with a variable prognosis. Current prognostic markers have limitations in identifying patients with a poor prognosis. Herein, we aimed to investigate the prognostic protein biomarkers of ACC using mass-spectrometry-based proteomics. We performed the liquid chromatography–tandem mass spectrometry (LC–MS/MS) using formalin-fixed paraffin-embedded (FFPE) tissues of 45 adrenal tumors. Then, we selected 117 differentially expressed proteins (DEPs) among tumors with different stages using the machine learning algorithm. Next, we conducted a survival analysis to assess whether the levels of DEPs were related to survival. Among 117 DEPs, HNRNPA1, C8A, CHMP6, LTBP4, SPR, NCEH1, MRPS23, POLDIP2, and WBSCR16 were significantly correlated with the survival of ACC. In age- and stage-adjusted Cox proportional hazard regression models, only HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 expression remained significant. These five proteins were also validated in TCGA data as the prognostic biomarkers. In this study, we found that HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 were protein biomarkers for predicting the prognosis of ACC.
Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer
Authors: Lehtomäki Kaisa , Mustonen Harri , Kellokumpu-Lehtinen Pirkko-Liisa , Joensuu Heikki , Hermunen Kethe , Soveri Leena-Maija , Boisen Mogens Karsbøl , Dehlendorff Christian , Johansen Julia Sidenius , Haglund Caj , Osterlund Pia
Published: August 2021

In colorectal cancer (CRC), 20–50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II–IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32–11.69); 3.72 (1.99–6.95); 2.58 (1.18–5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64–5.73); 3.41 (1.55–7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38–7.04) and OS, HR 3.20 (1.39–7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0–53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.
Soluble SIGLEC5: A New Prognosis Marker in Colorectal Cancer Patients
Authors: Montalbán-Hernández Karla , Cantero-Cid Ramón , Lozano-Rodríguez Roberto , Pascual-Iglesias Alejandro , Avendaño-Ortiz José , Casalvilla-Dueñas José Carlos , Bonel Pérez Gloria Cristina , Guevara Jenny , Marcano Cristóbal , Barragán Cristina , Valentín Jaime , del Fresno Carlos , Aguirre Luis Augusto , López Collazo Eduardo
Published: August 2021

Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.
Multicatalytic Hybrid Materials for Biocatalytic and Chemoenzymatic Cascades—Strategies for Multicatalyst (Enzyme) Co-Immobilization
Authors: Júnior Aldo Araújo da Trindade , Ladeira Yan Ferraz Ximenes , França Alexandre da Silva , Souza Rodrigo Octavio Mendonça Alves de , Moraes Adolfo Henrique , Wojcieszak Robert , Itabaiana Ivaldo , Miranda Amanda Silva de
Published: August 2021

During recent decades, the use of enzymes or chemoenzymatic cascades for organic chemistry has gained much importance in fundamental and industrial research. Moreover, several enzymatic and chemoenzymatic reactions have also served in green and sustainable manufacturing processes especially in fine chemicals, pharmaceutical, and flavor/fragrance industries. Unfortunately, only a few processes have been applied at industrial scale because of the low stabilities of enzymes along with the problematic processes of their recovery and reuse. Immobilization and co-immobilization offer an ideal solution to these problems. This review gives an overview of all the pathways for enzyme immobilization and their use in integrated enzymatic and chemoenzymatic processes in cascade or in a one-pot concomitant execution. We place emphasis on the factors that must be considered to understand the process of immobilization. A better understanding of this fundamental process is an essential tool not only in the choice of the best route of immobilization but also in the understanding of their catalytic activity.
Hydrochar: A Review on Its Production Technologies and Applications
Authors: Masoumi Shima , Borugadda Venu Babu , Nanda Sonil , Dalai Ajay K.
Published: August 2021

Recently, due to the escalating usage of non-renewable fossil fuels such as coal, natural gas and petroleum coke in electricity and power generation, and associated issues with pollution and global warming, more attention is being paid to finding alternative renewable fuel sources. Thermochemical and hydrothermal conversion processes have been used to produce biochar and hydrochar, respectively, from waste renewable biomass. Char produced from the thermochemical and hydrothermal decomposition of biomass is considered an environmentally friendly replacement for solid hydrocarbon materials such as coal and petroleum coke. Unlike thermochemically derived biochar, hydrochar has received little attention due to the lack of literature on its production technologies, physicochemical characterization, and applications. This review paper aims to fulfill these objectives and fill the knowledge gaps in the literature relating to hydrochar. Therefore, this review discusses the most recent studies on hydrochar characteristics, reaction mechanisms for char production technology such as hydrothermal carbonization, as well as hydrochar activation and functionalization. In addition, the applications of hydrochar, mainly in the fields of agriculture, pollutant adsorption, catalyst support, bioenergy, carbon sequestration, and electrochemistry are reviewed. With advancements in hydrothermal technologies and other environmentally friendly conversion technologies, hydrochar appears to be an appealing bioresource for a wide variety of energy, environmental, industrial, and commercial applications.
Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation
Authors: Chitranshi Nitin , Kumar Ashutosh , Sheriff Samran , Gupta Veer , Godinez Angela , Saks Danit , Sarkar Soumalya , Shen Ting , Mirzaei Mehdi , Basavarajappa Devaraj , Abyadeh Morteza , Singh Sachin K. , Dua Kamal , Zhang Kam Y. J. , Graham Stuart L. , Gupta Vivek
Published: August 2021

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.
2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases
Authors: Jaafar Mariam , Paraqindes Hermes , Gabut Mathieu , Diaz Jean-Jacques , Marcel Virginie , Durand Sébastien
Published: August 2021

Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2′O-ribose methylation (2′Ome), intrinsically occur in many organisms. In the last 5 years, accumulating reports have illustrated that rRNA 2′Ome varies in human cell lines but also in living organisms (yeast, plant, zebrafish, mouse, human) during development and diseases. These rRNA 2′Ome variations occur either within a single cell line, organ, or patient’s sample (i.e., intra-variability) or between at least two biological conditions (i.e., inter-variability). Thus, the ribosomes can tolerate the absence of 2′Ome at some specific positions. These observations question whether variations in rRNA 2′Ome could provide ribosomes with particular translational regulatory activities and functional specializations. Here, we compile recent studies supporting the heterogeneity of ribosome composition at rRNA 2′Ome level and provide an overview of the natural diversity in rRNA 2′Ome that has been reported up to now throughout the kingdom of life. Moreover, we discuss the little evidence that suggests that variations of rRNA 2′Ome can effectively impact the ribosome activity and contribute to the etiology of some human diseases.
cAMP Compartmentalization in Cerebrovascular Endothelial Cells: New Therapeutic Opportunities in Alzheimer’s Disease
Authors: Viña Dolores , Seoane Nuria , Vasquez Elisardo C. , Campos-Toimil Manuel
Published: August 2021

The vascular hypothesis used to explain the pathophysiology of Alzheimer’s disease (AD) suggests that a dysfunction of the cerebral microvasculature could be the beginning of alterations that ultimately leads to neuronal damage, and an abnormal increase of the blood–brain barrier (BBB) permeability plays a prominent role in this process. It is generally accepted that, in physiological conditions, cyclic AMP (cAMP) plays a key role in maintaining BBB permeability by regulating the formation of tight junctions between endothelial cells of the brain microvasculature. It is also known that intracellular cAMP signaling is highly compartmentalized into small nanodomains and localized cAMP changes are sufficient at modifying the permeability of the endothelial barrier. This spatial and temporal distribution is maintained by the enzymes involved in cAMP synthesis and degradation, by the location of its effectors, and by the existence of anchor proteins, as well as by buffers or different cytoplasm viscosities and intracellular structures limiting its diffusion. This review compiles current knowledge on the influence of cAMP compartmentalization on the endothelial barrier and, more specifically, on the BBB, laying the foundation for a new therapeutic approach in the treatment of AD.
An Electrophysiological and Pharmacological Study of the Properties of Human iPSC-Derived Neurons for Drug Discovery
Authors: Halliwell Robert F. , Salmanzadeh Hamed , Coyne Leanne , Cao William S.
Published: August 2021

Human stem cell-derived neurons are increasingly considered powerful models in drug discovery and disease modeling, despite limited characterization of their molecular properties. Here, we have conducted a detailed study of the properties of a commercial human induced Pluripotent Stem Cell (iPSC)-derived neuron line, iCell [GABA] neurons, maintained for up to 3 months in vitro. We confirmed that iCell neurons display neurite outgrowth within 24 h of plating and label for the pan-neuronal marker, βIII tubulin within the first week. Our multi-electrode array (MEA) recordings clearly showed neurons generated spontaneous, spike-like activity within 2 days of plating, which peaked at one week, and rapidly decreased over the second week to remain at low levels up to one month. Extracellularly recorded spikes were reversibly inhibited by tetrodotoxin. Patch-clamp experiments showed that iCell neurons generated spontaneous action potentials and expressed voltage-gated Na and K channels with membrane capacitances, resistances and membrane potentials that are consistent with native neurons. Our single neuron recordings revealed that reduced spiking observed in the MEA after the first week results from development of a dominant inhibitory tone from GABAergic neuron circuit maturation. GABA evoked concentration-dependent currents that were inhibited by the convulsants, bicuculline and picrotoxin, and potentiated by the positive allosteric modulators, diazepam, chlordiazepoxide, phenobarbital, allopregnanolone and mefenamic acid, consistent with native neuronal GABAA receptors. We also show that glycine evoked robust concentration-dependent currents that were inhibited by the neurotoxin, strychnine. Glutamate, AMPA, Kainate and NMDA each evoked concentration-dependent currents in iCell neurons that were blocked by their selective antagonists, consistent with the expression of ionotropic glutamate receptors. The NMDA currents required the presence of the co-agonist glycine and were blocked in a highly voltage-dependent manner by Mg2+ consistent with the properties of native neuronal NMDA receptors. Together, our data suggest that such human iPSC-derived neurons may have significant value in drug discovery and development and may eventually largely replace the need for animal tissues in human biomedical research.
CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen
Authors: Manfrevola Francesco , Ferraro Bruno , Sellitto Carolina , Rocco Domenico , Fasano Silvia , Pierantoni Riccardo , Chianese Rosanna
Published: August 2021

The etiology of human asthenozoospermia is multifactorial. The need to unveil molecular mechanisms underlying this state of infertility is, thus, impelling. Circular RNAs (circRNAs) are involved in microRNA (miRNA) inhibition by a sponge activity to protect mRNA targets. All together they form the competitive endogenous RNA network (ceRNET). Recently, we have identified differentially expressed circRNAs (DE-circRNAs) in normozoospermic and asthenozoospermic patients, associated with high-quality (A-spermatozoa) and low-quality (B-spermatozoa) sperm. Here, we carried out a differential analysis of CRISP2, CATSPER1 and PATE1 mRNA expression in good quality (A-spermatozoa) and low quality (B-spermatozoa) sperm fractions collected from both normozoospermic volunteers and asthenozoospermic patients. These sperm fractions are usually separated on the basis of morphology and motility parameters by a density gradient centrifugation. B-spermatozoa showed low levels of mRNAs. Thus, we identified the possible ceRNET responsible for regulating their expression by focusing on circTRIM2, circEPS15 and circRERE. With the idea that motility perturbations could be rooted in quantitative changes of transcripts in sperm, we evaluated circRNA and mRNA modulation in A-spermatozoa and B-spermatozoa after an oral amino acid supplementation known to improve sperm motility. The profiles of CRISP2, CATSPER1 and PATE1 proteins in the same fractions of sperm well matched with the transcript levels. Our data may strengthen the role of circRNAs in asthenozoospermia and shed light on the molecular pathways linked to sperm motility regulation.
The Impact of Glucose-Lowering Drugs on Sarcopenia in Type 2 Diabetes: Current Evidence and Underlying Mechanisms
Authors: Massimino Elena , Izzo Anna , Riccardi Gabriele , Della Pepa Giuseppe
Published: August 2021

The age-related decrease in skeletal muscle mass together with the loss of muscle power and function is defined sarcopenia. Mounting evidence suggests that the prevalence of sarcopenia is higher in patients with type 2 diabetes mellitus (T2DM), and different mechanisms may be responsible for this association such as impaired insulin sensitivity, chronic hyperglycemia, advanced glycosylation end products, subclinical inflammation, microvascular and macrovascular complications. Glucose-lowering drugs prescribed for patients with T2DM might impact on these mechanisms leading to harmful or beneficial effect on skeletal muscle. Importantly, beyond their glucose-lowering effects, glucose-lowering drugs may affect per se the equilibrium between protein anabolism and catabolism through several mechanisms involved in skeletal muscle physiology, contributing to sarcopenia. The aim of this narrative review is to provide an update on the effects of glucose-lowering drugs on sarcopenia in individuals with T2DM, focusing on the parameters used to define sarcopenia: muscle strength (evaluated by handgrip strength), muscle quantity/quality (evaluated by appendicular lean mass or skeletal muscle mass and their indexes), and physical performance (evaluated by gait speed or short physical performance battery). Furthermore, we also describe the plausible mechanisms by which glucose-lowering drugs may impact on sarcopenia.