bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoceruloplasmin: Abundance, Detection, Formation, and Metabolism
Authors: Linder Maria C.
Published: February 2021

Ceruloplasmin, the main copper-binding protein in blood and some other fluids, is well known for its copper-dependent enzymatic functions and as a source of copper for cells. What is generally unknown or ignored is that, at least in the case of blood plasma and serum, about half of ceruloplasmin is in the apo (copper-free) form. This has led to some misconceptions about the amounts and variations of other copper-binding proteins and so-called “free copper” in the blood that might be indicators of disease states. What is known about the levels, sources, and metabolism of apo versus holo ceruloplasmin and the problems associated with measurements of the two forms is reviewed here.
Trifarotene: A Current Review and Perspectives in Dermatology
Authors: Cosio Terenzio , Di Prete Monia , Gaziano Roberta , Lanna Caterina , Orlandi Augusto , Di Francesco Paolo , Bianchi Luca , Campione Elena
Published: February 2021

Retinoids have numerous applications in inflammatory, dyskeratotic, and oncohematology diseases. Retinoids have now reached the fourth generation, progressively reducing toxicity whilst increasing their efficacy. Trifarotene is a new fourth-generation retinoid with a selective action on RAR-γ. In this review, we reported the trials—both concluded and in progress—including the use of trifarotene in dermatological diseases. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) from 2012 to today and reference lists of respective articles. Only articles published in English language were included. Randomized trials evaluating trifarotene tolerability, safety, and efficacy in congenital ichthyosis and acne have demonstrated great results and mild side effects, leading to the approval by the FDA of trifarotene for the treatment of lamellar ichthyosis in 2014, and of acne vulgaris in October 2019. No high-quality randomized clinical trials have evaluated the treatment of primary cutaneous lymphomas with trifarotene. Finally, we are hypothesizing future perspectives in the treatment of non-melanoma skin cancers, fungal infections, photoaging, and hand-foot skin reactions with trifarotene.
Intensity of Respiratory Cortical Arousals Is a Distinct Pathophysiologic Feature and Is Associated with Disease Severity in Obstructive Sleep Apnea Patients
Authors: Bahr Katharina , Geisler Vincent , Huppertz Tilman , Groppa Sergiu , Matthias Christoph , Gouveris Haralampos , Muthuraman Muthuraman
Published: February 2021

Background: We investigated whether the number, duration and intensity of respiratory arousals (RA) on C3-electroencephalographic (EEG) recordings correlate with polysomnography (PSG)-related disease severity in obstructive sleep apnea (OSA) patients. We also investigated if every patient might have an individual RA microstructure pattern, independent from OSA-severity. Methods: PSG recordings of 20 OSA patients (9 female; age 27–80 years) were analyzed retrospectively. Correlation coefficients were calculated between RA microstructure (duration, EEG-intensity) and RA number and respiratory disturbance index (RDI), oxygen desaturation index (ODI) and arousal index (AI). Intraclass correlations (ICC) for both RA duration and intensity were calculated. Sleep stage-specific and apnea- and hypopnea-specific analyses were also done. The probability distributions of duration and intensity were plotted, interpolated with a kernel which fits the distribution. A Bayesian posterior distribution analysis and pair-wise comparisons of each patient with all other 19 patients were performed. Results: Of the analyzed 2600 RA, strong positive correlations were found between average RA intensity and both RDI and AI. The number of PSG-recorded RA was strongly positively correlated with RDI. Significant correlations between average RA intensity in REM, NREM2 and NREM3 sleep stages and total ODI were identified. No sleep stage-specific correlations of arousal microstructure with age, sex, RDI or AI were identified. Although between-subjects ICC values were <0.25, within-subject ICC values were all >0.7 (all p < 0.05). While apnea-related RA duration did not differ from hypopnea-related RA duration, RA intensity was significantly higher (p = 0.00135) in hypopneas than in apneas. A clear individual pattern of arousal duration for each patient was made distinct. For arousal intensity, a Gaussian distribution was identified in most patients. The Bayesian statistics regarding the arousal microstructure showed significant differences between each pair of patients. Conclusions: Each individual patient with OSA might have an individual pattern of RA intensity and duration indicating a distinct individual pathophysiological feature. Arousal intensity was significantly higher in hypopneic than in apneic events and may be related causally to the diminished (compared to apneas) respiratory distress associated with hypopneas. RA intensity in REM, NREM2 and NREM3 strongly correlated with ODI.
Erratum: Huizeling, E.; et al. Age-Related Changes in Attentional Refocusing during Simulated Driving. Brain Sci. 2020, 10, 530
Authors: Huizeling Eleanor , Wang Hongfang , Holland Carol , Kessler Klaus
Published: February 2021

The authors would like to submit the following corrections to the published paper [...]
Neuroprotective Effect of α-Mangostin in Ameliorating Propionic Acid-Induced Experimental Model of Autism in Wistar Rats
Authors: Tiwari Aarti , Khera Rishabh , Rahi Saloni , Mehan Sidharth , Makeen Hafiz Antar , Khormi Yahya H. , Rehman Muneeb U , Khan Andleeb
Published: February 2021

Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in Autism pathogenesis. Alpha-mangostin (AMG) is a phytoconstituents with anti-oxidants, anti-inflammatory, and ERK inhibition properties in many diseases. Our research aims to investigate the neuroprotective effect of AMG in the rat model of intracerebroventricular-propionic acid (ICV-PPA) induced autism with a confirmation of its effect on the ERK signaling. Autism was induced in Wistar rats (total 36 rats; 18 male/18 female) by multiple doses of PPA through ICV injection for 11 days. Actophotometer and beam walking tasks were used to evaluate animals’ motor abilities, and the Morris water maze task was utilized to confirm the cognition and memory in animals. Long term administration of AMG100 mg/kg and AMG200 mg/kg continued from day 12 to day 44 of the experiment. Before that, animals were sacrificed, brains isolated, morphological, gross pathological studies were performed, and neurochemical analysis was performed in the brain homogenates. Cellular and molecular markers, including ERK, myelin basic protein, apoptotic markers including caspase-3, Bax, Bcl-2, neuroinflammatory markers, neurotransmitters, and oxidative stress markers, have been tested throughout the brain. Thus, AMG reduces the overactivation of the ERK signaling and also restored autism-like behavioral and neurochemical alterations.
Characterization of Motor-Evoked Responses Obtained with Transcutaneous Electrical Spinal Stimulation from the Lower-Limb Muscles after Stroke
Authors: Moon Yaejin , Zuleger Taylor , Lamberti Martina , Bansal Ashir , Mummidisetty Chaithanya K. , McKenzie Kelly A. , Yingling Lindsey , Madhavan Sangeetha , Roth Elliot J. , Lieber Richard L. , Jayaraman Arun
Published: February 2021

An increasing number of studies suggests that a novel neuromodulation technique targeting the spinal circuitry enhances gait rehabilitation, but research on its application to stroke survivors is limited. Therefore, we investigated the characteristics of spinal motor-evoked responses (sMERs) from lower-limb muscles obtained by transcutaneous spinal cord stimulation (tSCS) after stroke compared to age-matched and younger controls without stroke. Thirty participants (ten stroke survivors, ten age-matched controls, and ten younger controls) completed the study. By using tSCS applied between the L1 and L2 vertebral levels, we compared sMER characteristics (resting motor threshold (RMT), slope of the recruitment curve, and latency) of the tibialis anterior (TA) and medial gastrocnemius (MG) muscles among groups. A single pulse of stimulation was delivered in 5 mA increments, increasing from 5 mA to 250 mA or until the subjects reached their maximum tolerance. The stroke group had an increased RMT (27–51%) compared to both age-matched (TA: p = 0.032; MG: p = 0.005) and younger controls (TA: p < 0.001; MG: p < 0.001). For the TA muscle, the paretic side demonstrated a 13% increased latency compared to the non-paretic side in the stroke group (p = 0.010). Age-matched controls also exhibited an increased RMT compared to younger controls (TA: p = 0.002; MG: p = 0.007), suggesting that altered sMER characteristics present in stroke survivors may result from both stroke and normal aging. This observation may provide implications for altered spinal motor output after stroke and demonstrates the feasibility of using sMER characteristics as an assessment after stroke.
Action Observation Therapy for Upper Limb Recovery in Patients with Stroke: A Randomized Controlled Pilot Study
Authors: Mancuso Mauro , Tondo Serena Di , Costantini Enza , Damora Alessio , Sale Patrizio , Abbruzzese Laura
Published: February 2021

Due to the complexity of the interventions for upper limb recovery, at the moment there is a lack of evidence regarding innovative and effective rehabilitative interventions. Action Observation Training (AOT) constitutes a promising rehabilitative method to improve upper limb motor recovery in stroke patients. The aim of the present study was to evaluate the potential efficacy of AOT, both in upper limb recovery and in functional outcomes when compared to patients treated with task oriented training (TOT). Both treatments were added to traditional rehabilitative treatment. Thirty-two acute stroke patients at 15.6 days (±8.3) from onset, with moderate to severe upper limb impairment at baseline following their first-ever stroke, were enrolled and randomized into two groups: 16 in the experimental group (EG) and 16 in the control group (CG). The EG underwent 30 min sessions of AOT, and the CG underwent 30 min sessions of TOT. All participants received 20 sessions of treatment for four consecutive weeks (five days/week). The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Box and Block Test (BBT), Functional Independence Measure (FIM) and Modified Ashworth Scale (MAS) were administered at baseline (T0) and at the end of treatment (T1). No statistical differences were found at T0 for inclusion criteria between the CG and EG, whereas both groups improved significantly at T1. After the treatment period, the rehabilitative gain was greater in the EG compared to the CG for FMA-UE and FIM (all p < 0.05). Our results suggest that AOT can contribute to increased motor recovery in subacute stroke patients with moderate to severe upper limb impairment in the early phase after stroke. The improvements presented in this article, together with the lack of adverse events, confirm that the use of AOT should be broadened out to larger pools of subacute stroke patients.
Motor Chunking in Internally Guided Sequencing
Authors: Bera Krishn , Shukla Anuj , Bapi Raju S.
Published: February 2021

Motor skill learning involves the acquisition of sequential motor movements with practice. Studies have shown that we learn to execute these sequences efficiently by chaining several elementary actions in sub-sequences called motor chunks. Several experimental paradigms, such as serial reaction task, discrete sequence production, and m × n task, have investigated motor chunking in externally specified sequencing where the environment or task paradigm provides the sequence of stimuli, i.e., the responses are stimulus driven. In this study, we examine motor chunking in a class of more realistic motor tasks that involve internally guided sequencing where the sequence of motor actions is self-generated or internally specified. We employ a grid-navigation task as an exemplar of internally guided sequencing to investigate practice-driven performance improvements due to motor chunking. The participants performed the grid-sailing task (GST) (Fermin et al., 2010), which required navigating (by executing sequential keypresses) a 10 × 10 grid from start to goal position while using a particular type of key mapping between the three cursor movement directions and the three keyboard buttons. We provide empirical evidence for motor chunking in grid-navigation tasks by showing the emergence of subject-specific, unique temporal patterns in response times. Our findings show spontaneous chunking without pre-specified or externally guided structures while replicating the earlier results with a less constrained, internally guided sequencing paradigm.
Identification of Breathing Patterns through EEG Signal Analysis Using Machine Learning
Authors: Hong Yong-Gi , Kim Hang-Keun , Son Young-Don , Kang Chang-Ki
Published: February 2021

This study was to investigate the changes in brain function due to lack of oxygen (O2) caused by mouth breathing, and to suggest a method to alleviate the side effects of mouth breathing on brain function through an additional O2 supply. For this purpose, we classified the breathing patterns according to EEG signals using a machine learning technique and proposed a method to reduce the side effects of mouth breathing on brain function. Twenty subjects participated in this study, and each subject performed three different breathings: nose and mouth breathing and mouth breathing with O2 supply during a working memory task. The results showed that nose breathing guarantees normal O2 supply to the brain, but mouth breathing interrupts the O2 supply to the brain. Therefore, this comparative study of EEG signals using machine learning showed that one of the most important elements distinguishing the effects of mouth and nose breathing on brain function was the difference in O2 supply. These findings have important implications for the workplace environment, suggesting that special care is required for employees who work long hours in confined spaces such as public transport, and that a sufficient O2 supply is needed in the workplace for working efficiency.
Under-Treatment of Older Patients with Newly Diagnosed Epithelial Ovarian Cancer Remains an Issue
Authors: Dumas Lucy , Bowen Rebecca , Butler John , Banerjee Susana
Published: February 2021

Older women with ovarian cancer have disproportionately poorer survival outcomes than their younger counterparts and receive less treatment. In order to understand where the gaps lie in the treatment of older patients, studies incorporating more detailed assessment of baseline characteristics and treatment delivery beyond the scope of most cancer registries are required. We aimed to assess the proportion of women over the age of 65 who are offered and receive standard of care for first-line ovarian cancer at two UK NHS Cancer Centres over a 5-year period (December 2009 to August 2015). Standard of care treatment was defined as a combination of cytoreductive surgery and if indicated platinum-based chemotherapy (combination or single-agent). Sixty-five percent of patients aged 65 and above received standard of care treatment. Increasing age was associated with lower rates of receiving standard of care (35% > 80 years old versus 78% of 65–69-year-olds, p = 0.000). Older women were less likely to complete the planned chemotherapy course (p = 0.034). The oldest women continue to receive lower rates of standard care compared to younger women. Once adjusted for Federation of Gynaecology and Obstetrics (FIGO) stage, Eastern Cooperative Oncology Group (ECOG) performance status and first-line treatment received, age was no longer an independent risk factor for poorer overall survival. Optimisation of vulnerable patients utilising a comprehensive geriatric assessment and directed interventions to facilitate the delivery of standard of care treatment could help narrow the survival discrepancy between the oldest patients and their younger counterparts.
Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms
Authors: Jahn Ulrika , Ilan Ezgi , Sandström Mattias , Lubberink Mark , Garske-Román Ulrike , Sundin Anders
Published: February 2021

Dosimetry during peptide receptor radionuclide therapy (PRRT) has mainly focused on normal organs and less on the tumors. The absorbed dose in one target tumor per patient and several response related factors were assessed in 23 pancreatic neuroendocrine neoplasms (P-NENs) and 25 small-intestinal NEN (SI-NENs) during PRRT with 177Lu-DOTATATE. The total administered activity per patient was (mean ± standard error of mean (SEM) 31.8 ± 1.9 GBq for P-NENs and 36 ± 1.94 GBq for SI-NENs. The absorbed tumor dose was 143.5 ± 2 Gy in P-NENs, 168.2 ± 2 Gy in SI-NENs. For both NEN types, a dose–response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in P-NENs. A significant drop in the absorbed dose per cycle was shown during the course of PRRT. Tumor vascularization was higher in P-NENs than in SI-NENs at baseline but equal post-PRRT. The time to progression (RECIST 1.1) was similar for patients with P-NEN (mean ± SEM 30 ± 1 months) and SI-NEN (33 ± 1 months). In conclusion, a dose response relationship was established for both P-NENs and SI-NENs and a significant drop in the absorbed dose per cycle was shown during the course of PRRT, which warrants further investigation to understand the factors impacting PRRT to improve personalized treatment protocol design.
Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers
Authors: Di Francia Raffaele , Crisci Stefania , De Monaco Angela , Cafiero Concetta , Re Agnese , Iaccarino Giancarla , De Filippi Rosaria , Frigeri Ferdinando , Corazzelli Gaetano , Micera Alessandra , Pinto Antonio
Published: February 2021

Cytarabine is a pyrimidine nucleoside analog, commonly used in multiagent chemotherapy regimens for the treatment of leukemia and lymphoma, as well as for neoplastic meningitis. Ara-C-based chemotherapy regimens can induce a suboptimal clinical outcome in a fraction of patients. Several studies suggest that the individual variability in clinical response to Leukemia & Lymphoma treatments among patients, underlying either Ara-C mechanism resistance or toxicity, appears to be associated with the intracellular accumulation and retention of Ara-CTP due to genetic variants related to metabolic enzymes. Herein, we reported (a) the latest Pharmacogenomics biomarkers associated with the response to cytarabine and (b) the new drug formulations with optimized pharmacokinetics. The purpose of this review is to provide readers with detailed and comprehensive information on the effects of Ara-C-based therapies, from biological to clinical practice, maintaining high the interest of both researcher and clinical hematologist. This review could help clinicians in predicting the response to cytarabine-based treatments.
Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth
Authors: Chan Loucia Kit Ying , Lau Tat San , Chung Kit Ying , Tam Chit , Cheung Tak Hong , Yim So Fan , Lee Jacqueline Ho Sze , Leung Ricky Wai Tak , Qin Jing , Or Yvonne Yan Yan , Lo Kwok Wai , Kwong Joseph
Published: February 2021

Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/β, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.
Investigation of the Hβ Molecular Sieve Inactivation Caused by Reactants and Products and Improvement of Continuous Thiophene Acylation
Authors: Yang Shunjin , Zeng Aiwu
Published: February 2021

In this paper, the factors leading to the inactivation of the molecular sieve are explored in the batch thiophene (TH) acylation. The coexistence of acetic anhydride (AC) as the reactant and 2-acetylthiophene (2-ATH) as the product plays a key role in accelerating the inactivation, attributing to the 2-ATH polymerization. According to the molecular simulation, when AC is not present, the energy barrier of 2-ATH polymerization can be reduced from 287.45 kJ/mol to 85.87 kJ/mol. Then, the process of the continuous TH acylation is improved, in which thiophene is excessive (molar ratio). After optimizing the molar ratio and volume flowrate of raw material, the productivity of the catalyst can reach 21.56 g/g, which exceeds the best process previously studied (15.10 g/g). Subsequently, the use of carbon tetrachloride (CT) as a solvent is further studied, hoping to further improve the performance of the catalyst, and a significant advancement is achieved, in which the production capacity of the catalyst exceeds 45 g, and the conversion rate of AC can still be as high as 96% after the reaction is carried out for 15,000 min.
Structure-Catalytic Properties Relationship in Friedel Crafts Alkylation Reaction for MCM-36-Type Zeolites Obtained by Isopropanol-Assisted Pillaring
Authors: Ogorzały Karolina , Węgrzyn Agnieszka , Korzeniowska Aleksandra , Sławek Andrzej , Kowalczyk Andrzej , Gil Barbara , Roth Wiesław J. , Makowski Wacław
Published: February 2021

MWW type zeolites are characterized by the presence of zeolitic layers of 2.5 nm thickness, containing 10-member ring sinusoidal channels inside and supercavities with 12-member ring openings located on their surfaces. Expansion and pillaring of layered zeolites increase the access to active sites and can enable or facilitate catalytic activity towards larger reactant molecules. This goal is explored in this work reporting the pillaring of layered zeolite MCM-56 with MWW topology by tetraethylorthosilicate (TEOS) treatment with the assistance of isopropanol, aimed at obtaining hierarchical micro-mesoporous systems. MCM-56 (Si/Al = 12) was synthesized with hexamethyleneimine as a structure-directing and aniline as a structure-promoting agent. Hierarchical porous systems were obtained using two different pillaring methods: (1) with TEOS only and (2) with TEOS mixed with isopropanol. The MWW framework was preserved during swelling/pillaring in both methods. Pillared zeolites obtained via alcohol-assisted pillaring possessed unique intermediate micro-mesopores with the size of about 2 nm. IR study revealed a decrease in the concentration of accessible acid centers upon pillaring. However, the fraction of acid sites on the external surface, accessible for adsorption of large molecules, increased by up to 90%. Catalytic activity was evaluated in the Friedel-Crafts alkylation of mesitylene with benzyl alcohol. Pillaring resulted in reduction of the acid site concentrations, but the materials retained high catalytic activity. Pillaring in the presence of alcohol produced increased turnover frequency values based on the concentrations of the external acid sites.
Synthesis of N-rGO-MWCNT/CuCrO2 Catalyst for the Bifunctional Application of Hydrogen Evolution Reaction and Electrochemical Detection of Bisphenol-A
Authors: Sakthinathan Subramanian , Keyan Arjunan Karthi , Rajakumaran Ramachandran , Chen Shen-Ming , Chiu Te-Wei , Dong Chaofang , Vinothini Sivaramakrishnan
Published: February 2021

A glassy carbon electrode (GCE) coated with delafossite CuCrO2 loading on the nitrogen-doped reduced graphene oxide (N-rGO) and multiwalled carbon nanotubes (MWCNT) composite (N-rGO-MWCNT/CuCrO2) was applied to the hydrogen evolution reaction and Bisphenol-A (BPA) detection. First, the N-rGO-MWCNT composite was prepared by in situ chemical reduction with caffeic acid as a reducing agent. Then, CuCrO2 was accumulated on the N-rGO-MWCNT surface to form N-rGO-MWCNT/CuCrO2 composite. The morphology structure of the N-rGO-MWCNT/ CuCrO2 composite was analyzed by different characterization techniques. Besides, the GCE/N-rGO-MWCNT/CuCrO2 composite electrode was investigated for hydrogen evolution reaction (HER), which shows an excellent electrocatalytic activity with a low over-potential, increasing reduction current, and a small Tafel slope of 62 mV·dec−1 at 10 mA·cm−2 with long-term stability. Moreover, the electrochemical determination of BPA was in the range of 0.1-110 µM, and low detection limit of 0.033 µM (S/N = 3) with a higher sensitivity of 1.3726 µA µM−1 cm−2. Furthermore, the prepared GCE/N-rGO-MWCNT/CuCrO2 electrode shows effective detection of BPA in food samples with acceptable recoveries. Hence, the finding of GCE/N-rGO-MWCNT/CuCrO2 can be observed as an impressive catalyst to the electrocatalytic activity of HER and BPA oxidation.
Immobilized Alcalase on Micron- and Submicron-Sized Alginate Beads as a Potential Biocatalyst for Hydrolysis of Food Proteins
Authors: Jonović Marko , Žuža Milena , Đorđević Verica , Šekuljica Nataša , Milivojević Milan , Jugović Branimir , Bugarski Branko , Knežević-Jugović Zorica
Published: February 2021

Enzymatic hydrolysis of food proteins is convenient method to improve their functional properties and physiological activity. Herein, the successful covalent attachment of alcalase on alginate micron and submicron beads using the carbodiimide based chemistry reaction and the subsequent application of the beads for egg white and soy proteins hydrolysis were studied. In addition to the electrostatic extrusion technique (EE) previously used by others, the potential utilization of a novel ultrasonic spray atomization technique without drying (UA) and with drying (UAD) for alginate submicron beads production has been attempted. The immobilization parameters were optimized on microbeads obtained by EE technique (803 ± 23 µm) with respect to enzyme loading and alcalase activity. UA and UAD techniques resulted in much smaller particles (607 ± 103 nm and 394 ± 51 nm in diameter, respectively), enabling even higher enzyme loading of 671.6 ± 4 mg g−1 on the carrier and the highest immobilized alcalase activity of 2716.1 IU g−1 in the standard reaction. The UAD biocatalyst exhibited also better performances in the real food system based on egg white or soy proteins. It has been shown that the immobilized alcalase can be reused in seven successive soy protein hydrolysis cycles with a little decrease in the activity.
New Trends in Asymmetric Catalysis
Authors: Schettini Rosaria , Della Sala Giorgio
Published: February 2021

As far back as the mid-nineteenth century, the studies of Louis Pasteur brought to light the essential role of molecular chirality in biology [...]
ω-Transaminase-Mediated Asymmetric Synthesis of (S)-1-(4-Trifluoromethylphenyl)Ethylamine
Authors: Rodrigues Carlos J. C. , Ferrer Manuel , de Carvalho Carla C. C. R.
Published: February 2021

The pivotal role played by ω-transaminases (ω-TAs) in the synthesis of chiral amines used as building blocks for drugs and pharmaceuticals is widely recognized. However, chiral bulky amines are challenging to produce. Herein, a ω-TA (TR8) from a marine bacterium was used to synthesize a fluorine chiral amine from a bulky ketone. An analysis of the reaction conditions for process development showed that isopropylamine concentrations above 75 mM had an inhibitory effect on the enzyme. Five different organic solvents were investigated as co-solvents for the ketone (the amine acceptor), among which 25–30% (v/v) dimethyl sulfoxide (DMSO) produced the highest enzyme activity. The reaction reached equilibrium after 18 h at 30% of conversion. An in situ product removal (ISPR) approach using an aqueous organic two-phase system was tested to mitigate product inhibition. However, the enzyme activity initially decreased because the ketone substrate preferentially partitioned into the organic phase, n-hexadecane. Consequently, DMSO was added to the system to increase substrate mass transfer without affecting the ability of the organic phase to prevent inhibition of the enzyme activity by the product. Thus, the enzyme reaction was maintained, and the product amount was increased for a 62 h reaction time. The investigated ω-TA can be used in the bioconversion of bulky ketones to chiral amines for future bioprocess applications.
Infrared Thermography as an Operando Tool for the Analysis of Catalytic Processes: How to Use it?
Authors: Mutschler Robin , Moioli Emanuele
Published: February 2021

Infrared (IR) thermography is a powerful tool to measure temperature with high space and time resolution. A particularly interesting application of this technology is in the field of catalysis, where the method can provide new insights into dynamic surface reactions. This paper presents guidelines for the development of a reactor cell that can aid in the efficient exploitation of infrared thermography for the investigation of catalytic and other surface reactions. Firstly, the necessary properties of the catalytic reactor are described. Secondly, we analyze the requirements towards the catalytic system to be directly observable by IR thermography. This includes the need for a catalyst that provides a sufficiently high heat production (or absorption) rate. To achieve true operando investigation conditions, some dedicated equipment must be developed. Here, we provide the guidelines to assemble a chemical reactor with an IR transmitting window through which the reaction can be studied with the infrared camera along with other best practice tips to achieve results. Furthermore, we present selected examples of catalytic reactions that can be monitored by IR thermography, showing the potential of the technology in revealing transient and steady state chemical phenomena.
Embryonic Environmental Niche Reprograms Somatic Cells to Express Pluripotency Markers and Participate in Adult Chimaeras
Authors: Żyżyńska-Galeńska Krystyna , Bernat Agnieszka , Piliszek Anna , Karasiewicz Jolanta , Szablisty Ewa , Sacharczuk Mariusz , Brewińska-Olchowik Marta , Bochenek Michał , Grabarek Joanna , Modliński Jacek Andrzej
Published: February 2021

The phenomenon of the reprogramming of terminally differentiated cells can be achieved by various means, like somatic cell nuclear transfer, cell fusion with a pluripotent cell, or the introduction of pluripotency genes. Here, we present the evidence that somatic cells can attain the expression of pluripotency markers after their introduction into early embryos. Mouse embryonic fibroblasts introduced between blastomeres of cleaving embryos, within two days of in vitro culture, express transcription factors specific to blastocyst lineages, including pluripotency factors. Analysis of donor tissue marker DNA has revealed that the progeny of introduced cells are found in somatic tissues of foetuses and adult chimaeras, providing evidence for cell reprogramming. Analysis of ploidy has shown that in the chimaeras, the progeny of introduced cells are either diploid or tetraploid, the latter indicating cell fusion. The presence of donor DNA in diploid cells from chimaeric embryos proved that the non-fused progeny of introduced fibroblasts persisted in chimaeras, which is evidence of reprogramming by embryonic niche. When adult somatic (cumulus) cells were introduced into early cleavage embryos, the extent of integration was limited and only cell fusion-mediated reprogramming was observed. These results show that both cell fusion and cell interactions with the embryonic niche reprogrammed somatic cells towards pluripotency.
NETosis in Wound Healing: When Enough Is Enough
Authors: Sabbatini Maurizio , Magnelli Valeria , Renò Filippo
Published: February 2021

The neutrophils extracellular traps (NETs) are a meshwork of chromatin, histonic and non-histonic proteins, and microbicidal agents spread outside the cell by a series of nuclear and cytoplasmic events, collectively called NETosis. NETosis, initially only considered a defensive/apoptotic mechanism, is now considered an extreme defensive solution, which in particular situations induces strong negative effects on tissue physiology, causing or exacerbating pathologies as recently shown in NETs-mediated organ damage in COVID-19 patients. The positive effects of NETs on wound healing have been linked to their antimicrobial activity, while the negative effects appear to be more common in a plethora of pathological conditions (such as diabetes) and linked to a NETosis upregulation. Recent evidence suggests there are other positive physiological NETs effects on wound healing that are worthy of a broader research effort.
Cells: Are They (Still) Essential for Dental Regeneration?
Authors: Tatullo Marco , Gandolfi Maria Giovanna
Published: February 2021

Tissue regeneration in dentistry has demonstrated impressive progress over during the last decades compared to other medical sciences [...]
Aging-Related Changes in the Ultrastructure of Hepatocytes and Cardiomyocytes of Elderly Mice Are Enhanced in ApoE-Deficient Animals
Authors: Łysek-Gładysińska Małgorzata , Wieczorek Anna , Jóźwik Artur , Walaszczyk Anna , Jelonek Karol , Szczukiewicz-Markowska Grażyna , Horbańczuk Olaf K. , Pietrowska Monika , Widłak Piotr , Gabryś Dorota
Published: February 2021

Biological aging is associated with various morphological and functional changes, yet the mechanisms of these phenomena remain unclear in many tissues and organs. Hyperlipidemia is among the factors putatively involved in the aging of the liver and heart. Here, we analyzed morphological, ultrastructural, and biochemical features in adult (7-month-old) and elderly (17-month-old) mice, and then compared age-related features between wild type (C57Bl/6 strain) and ApoE-deficient (transgenic ApoE−/−) animals. Increased numbers of damaged mitochondria, lysosomes, and lipid depositions were observed in the hepatocytes of elderly animals. Importantly, these aging-related changes were significantly stronger in hepatocytes from ApoE-deficient animals. An increased number of damaged mitochondria was observed in the cardiomyocytes of elderly animals. However, the difference between wild type and ApoE-deficient mice was expressed in the larger size of mitochondria detected in the transgenic animals. Moreover, a few aging-related differences were noted between wild type and ApoE-deficient mice at the level of plasma biochemical markers. Levels of cholesterol and HDL increased in the plasma of elderly ApoE−/− mice and were markedly higher than in the plasma of elderly wild type animals. On the other hand, the activity of alanine transaminase (ALT) decreased in the plasma of elderly ApoE−/− mice and was markedly lower than in the plasma of elderly wild type animals.
High-Sensitivity pH Sensor Based on Coplanar Gate AlGaN/GaN Metal-Oxide-Semiconductor High Electron Mobility Transistor
Authors: Cho Seong-Kun , Cho Won-Ju
Published: February 2021

The sensitivity of conventional ion-sensitive field-effect transistors is limited to the Nernst limit (59.14 mV/pH). In this study, we developed a pH sensor platform based on a coplanar gate AlGaN/GaN metal-oxide-semiconductor (MOS) high electron mobility transistor (HEMT) using the resistive coupling effect to overcome the Nernst limit. For resistive coupling, a coplanar gate comprising a control gate (CG) and a sensing gate (SG) was designed. We investigated the amplification of the pH sensitivity with the change in the magnitude of a resistance connected in series to each CG and SG via Silvaco TCAD simulations. In addition, a disposable extended gate was applied as a cost-effective sensor platform that helped prevent damages due to direct exposure of the AlGaN/GaN MOS HEMT to chemical solutions. The pH sensor based on the coplanar gate AlGaN/GaN MOS HEMT exhibited a pH sensitivity considerably higher than the Nernst limit, dependent on the ratio of the series resistance connected to the CG and SG, as well as excellent reliability and stability with non-ideal behavior. The pH sensor developed in this study is expected to be readily integrated with wide transmission bandwidth, high temperature, and high-power electronics as a highly sensitive biosensor platform.
Improving Surface Imprinting Effect by Reducing Nonspecific Adsorption on Non-Imprinted Polymer Films for 2,4-D Herbicide Sensors
Authors: Yang Jin Chul , Hong Suck Won , Park Jinyoung
Published: February 2021

Surface imprinting used for template recognition in nanocavities can be controlled and improved by surface morphological changes. Generally, the lithographic technique is used for surface patterning concerning sensing signal amplification in molecularly imprinted polymer (MIP) thin films. In this paper, we describe the effects of silanized silica molds on sensing the properties of MIP films. Porous imprinted poly(MAA–co–EGDMA) films were lithographically fabricated using silanized or non-treated normal silica replica molds to detect 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide as the standard template. The silanized mold MIP film (st-MIP) (Δf = −1021 Hz) exhibited a better sensing response than the non-treated normal MIP (n-MIP) (Δf = −978 Hz) because the imprinting effects, which occurred via functional groups on the silica surface, could be reduced through silane modification. Particularly, two non-imprinted (NIP) films (st-NIP and n-NIP) exhibited significantly different sensing responses. The st-NIP (Δfst-NIP = −332 Hz) films exhibited lower Δf values than the n-NIP film (Δfn-NIP = −610 Hz) owing to the remarkably reduced functionality against nonspecific adsorption. This phenomenon led to different imprinting factor (IF) values for the two MIP films (IFst-MIP = 3.38 and IFn-MIP = 1.86), which was calculated from the adsorbed 2,4-D mass per poly(MAA–co–EGDMA) unit weight (i.e., QMIP/QNIP). Moreover, it was found that the st-MIP film had better selectivity than the n-MIP film based on the sensing response of analogous herbicide solutions. As a result, it was revealed that the patterned molds’ chemical surface modification, which controls the surface functionality of imprinted films during photopolymerization, plays a role in fabricating enhanced sensing properties in patterned MIP films.
Diketopyrrolopyrrole Fluorescent Probes, Photophysical and Biological Applications
Authors: Auwalu Muhammad Aminu , Cheng Shanshan
Published: February 2021

Biological applications of fluorescent probes are rapidly increasing in the supramolecular chemistry research field. Several organic dyes are being utilized currently in developing and advancing this attractive research area, of which diketopyrrolopyrrole (DPP) organic dyes show an exceptional photophysical features (high-fluorescence quantum yield (FQY), good photochemical and thermal stability) that are essential properties for biological applications. Great efforts have been made in recent years towards developing novel fluorescent DPPs by different chemists for such applications, and some positive results have been reported. As a result, this review article gives an account of the progress that has so far been made very recently, mainly within the last decade, in that we selectively focus on and discuss more from 2015 to present on some recent scholarly achievements of fluorescent DPPs: quantum yield, aggregation-induced emission (AIE), solid-state emission, bio-imaging, cancer/tumor therapy, mitochondria staining and some polymeric fluorescent DPPs. Finally, this review article highlights researchers working on luminescent DPPs and the future prospects in some key areas towards designing DPP-based fluorescent probes in order to boost their photophysical and biological applications more effectively.
Syntactic Gender Agreement Processing on Direct-Object Clitics by Spanish-Speaking Children with Developmental Language Disorder: Evidence from ERP
Authors: Roa-Rojas Paloma , Grinstead John , Silva-Pereyra Juan , Fernández Thalía , Rodríguez-Camacho Mario
Published: February 2021

Children with developmental language disorder (DLD) have a psycholinguistic profile evincing multiple syntactic processing impairments. Spanish-speaking children with DLD struggle with gender agreement on clitics; however, the existing evidence comes from offline, elicitation tasks. In the current study, we sought to determine whether converging evidence of this deficit can be found. In particular, we use the real-time processing technique of event-related brain potentials (ERP) with direct-object clitic pronouns in Spanish-speaking children with DLD. Our participants include 15 six-year-old Mexican Spanish-speaking children with DLD and 19 typically developing, age-matched (TD) children. Auditory sentences that matched or did not match the gender features of antecedents represented in pictures were employed as stimuli in a visual–auditory gender agreement task. Gender-agreement violations were associated with an enhanced anterior negativity between 250 and 500 ms post-target onset in the TD children group. In contrast, children with DLD showed no such effect. This absence of the left anterior negativity (LAN) effect suggests weaker lexical representation of morphosyntactic gender features and/or non-adult-like morphosyntactic gender feature checking for the DLD children. We discuss the relevance of these findings for theoretical accounts of DLD. Our findings may contribute to a better understanding of syntactic agreement processing and language disorders.
Childhood Obesity and Respiratory Diseases: Which Link?
Authors: di Palmo Emanuela , Filice Emanuele , Cavallo Alessandra , Caffarelli Carlo , Maltoni Giulio , Miniaci Angela , Ricci Giampaolo , Pession Andrea
Published: February 2021

Prevalence of childhood obesity is progressively increasing, reaching worldwide levels of 5.6% in girls and of 7.8% in boys. Several evidences showed that obesity is a major preventable risk factor and disease modifier of some respiratory conditions such as asthma and Obstructive Sleep Apnea Syndrome (OSAS). Co-occurrence of asthma and obesity may be due to common pathogenetic factors including exposure to air pollutants and tobacco smoking, Western diet, and low Vitamin D levels. Lung growth and dysanapsis phenomenon in asthmatic obese children play a role in impaired respiratory function which appears to be different than in adults. Genes involved in both asthma and obesity have been identified, though a gene-by-environment interaction has not been properly investigated yet. The identification of modifiable environmental factors influencing gene expression through epigenetic mechanisms may change the natural history of both diseases. Another important pediatric respiratory condition associated with obesity is Sleep-Disordered Breathing (SDB), especially Obstructive Sleep Apnea Syndrome (OSAS). OSAS and obesity are linked by a bidirectional causality, where the effects of one affect the other. The factors most involved in the association between OSAS and obesity are oxidative stress, systemic inflammation, and gut microbiota. In OSAS pathogenesis, obesity’s role appears to be mainly due to mechanical factors leading to an increase of respiratory work at night-time. However, a causal link between obesity-related inflammatory state and OSAS pathogenesis still needs to be properly confirmed. To prevent obesity and its complications, family education and precocious lifestyle changes are critical. A healthy diet may lead to an improved quality of life in obese children suffering from respiratory diseases. The present review aimed to investigate the links between obesity, asthma and OSAS, focusing on the available evidence and looking for future research fields.
Effectiveness of a Family-Caregiver Training Program in Home-Based Pediatric Palliative Care
Authors: Chocarro González Lourdes , Rigal Andrés Manuel , de la Torre-Montero Julio C. , Barceló Escario Marta , Martino Alba Ricardo
Published: February 2021

Background: Pediatric palliative cares involve the whole family, along with the interdisciplinary pediatric palliative care (PPC) team. The commitment of the PPC team and the engagement of the family at different levels can play a key role in advancing a better quality of life in children and families. Method: A descriptive pre-post educational intervention study was carried out. The creation of a training program (with the term “school” used to denote this effort) strives to prepare caretakers to master the skills as well as provide support for the care of children with serious conditions requiring palliative through home-based initiatives. The analysis includes aspects of learning and satisfaction with the activity in a final sample of 14 families who had one child enrolled into a home-based palliative care program. Results: After the educational intervention in our school, the mean score of the theoretical evaluation was 9.14 points (SD 0.96), showing improvement with respect to the initial assessment, (mean diff. of +0.98 points). Although the analysis of all conceptual areas demonstrates a trend towards a positive impact of the intervention, feeding-related instruction saw the highest level of improvement, with a mean difference of +1.43 points. All enrolled parents expressed having a very positive experience during their participation in the educational program. Conclusions: The educational program showed a positive trend in the acquisition of knowledge and skills, resulting in a positive impact on the self-perception of their abilities. This psycho-educational space allowed them to share their experience of daily care for a child with complex needs with other families, showing them that they were not alone and that they could help each other.