bluuebunny/crossref_metadata_2025 huggingface dataset:
Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review
Authors: Rojas-González Alexis , Figueroa-Hernández Claudia Yuritzi , González-Rios Oscar , Suárez-Quiroz Mirna Leonor , González-Amaro Rosa María , Hernández-Estrada Zorba Josué , Rayas-Duarte Patricia
Published: May 2022

The demand of foods with high antioxidant capacity have increased and research on these foods continues to grow. This review is focused on chlorogenic acids (CGAs) from green coffee, which is the most abundant source. The main CGA in coffee is 5-O-caffeoylquinic acid (5-CQA). Coffee extracts are currently the most widely used source to enhance the antioxidant activity of foods. Due to the solubility of CGAs, their extraction is mainly performed with organic solvents. CGAs have been associated with health benefits, such as antioxidant, antiviral, antibacterial, anticancer, and anti-inflammatory activity, and others that reduce the risk of cardiovascular diseases, type 2 diabetes, and Alzheimer’s disease. However, the biological activities depend on the stability of CGAs, which are sensitive to pH, temperature, and light. The anti-inflammatory activity of 5-CQA is attributed to reducing the proinflammatory activity of cytokines. 5-CQA can negatively affect colon microbiota. An increase in anthocyanins and antioxidant activity was observed when CGAs extracts were added to different food matrices such as dairy products, coffee drinks, chocolate, and bakery products. The fortification of foods with coffee CGAs has the potential to improve the functionality of foods.
The Role of Microbiome in Brain Development and Neurodegenerative Diseases
Authors: Nandwana Varsha , Nandwana Nitesh K. , Das Yogarupa , Saito Mariko , Panda Tanisha , Das Sasmita , Almaguel Frankis , Hosmane Narayan S. , Das Bhaskar C.
Published: May 2022

Hundreds of billions of commensal microorganisms live in and on our bodies, most of which colonize the gut shortly after birth and stay there for the rest of our lives. In animal models, bidirectional communications between the central nervous system and gut microbiota (Gut–Brain Axis) have been extensively studied, and it is clear that changes in microbiota composition play a vital role in the pathogenesis of various neurodevelopmental and neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, anxiety, stress, and so on. The makeup of the microbiome is impacted by a variety of factors, such as genetics, health status, method of delivery, environment, nutrition, and exercise, and the present understanding of the role of gut microbiota and its metabolites in the preservation of brain functioning and the development of the aforementioned neurological illnesses is summarized in this review article. Furthermore, we discuss current breakthroughs in the use of probiotics, prebiotics, and synbiotics to address neurological illnesses. Moreover, we also discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. In addition, in the coming years, boron reagents will play a significant role to improve dysbiosis and will open new areas for researchers.
Notoginsenoside R1 Promotes Migration, Adhesin, Spreading, and Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stromal Cells
Authors: Wang Haiyan , Yan Yongyong , Lan Haifeng , Wei Nan , Zheng Zhichao , Wu Lihong , Jaspers Richard T. , Wu Gang , Pathak Janak L.
Published: May 2022

Cellular activities, such as attachment, spreading, proliferation, migration, and differentiation are indispensable for the success of bone tissue engineering. Mesenchymal stromal cells (MSCs) are the key precursor cells to regenerate bone. Bioactive compounds from natural products had shown bone regenerative potential. Notoginsenoside R1 (NGR1) is a primary bioactive natural compound that regulates various biological activities, including cardiovascular protection, neuro-protection, and anti-cancer effects. However, the effect of NGR1 on migration, adhesion, spreading, and osteogenic differentiation of MSCs required for bone tissue engineering application has not been tested properly. In this study, we aimed to analyze the effect of NGR1 on the cellular activities of MSCs. Since human adipose-derived stromal cells (hASCs) are commonly used MSCs for bone tissue engineering, we used hASCs as a model of MSCs. The optimal concentration of 0.05 μg/mL NGR1 was biocompatible and promoted migration and osteogenic differentiation of hASCs. Pro-angiogenic factor VEGF expression was upregulated in NGR1-treated hASCs. NGR1 enhanced the adhesion and spreading of hASCs on the bio-inert glass surface. NGR1 robustly promoted hASCs adhesion and survival in 3D-printed TCP scaffold both in vitro and in vivo. NGR1 mitigated LPS-induced expression of inflammatory markers IL-1β, IL-6, and TNF-α in hASCs as well as inhibited the RANKL/OPG expression ratio. In conclusion, the biocompatible NGR1 promoted the migration, adhesion, spreading, osteogenic differentiation, and anti-inflammatory properties of hASCs.
Aza-Oxa-Triazole Based Macrocycles with Tunable Properties: Design, Synthesis, and Bioactivity
Authors: Cheekatla Subba Rao , Thurakkal Liya , Jose Anna , Barik Debashis , Porel Mintu
Published: May 2022

A modular platform for the synthesis of tunable aza-oxa-based macrocycles was established. Modulations in the backbone and the side-chain functional groups have been rendered to achieve the tunable property. These aza-oxa-based macrocycles can also differ in the number of heteroatoms in the backbone and the ring size of the macrocycles. For the proof of concept, a library of macrocycles was synthesized with various hanging functional groups, different combinations of heteroatoms, and ring sizes in the range of 17–27 atoms and was characterized by NMR and mass spectrometry. In light of the importance of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and the significance of triazole groups for various applications, we employed the click-reaction-based macrocyclization. The competence of the synthesized macrocycles in various biomedical applications was proven by studying the interactions with the serum albumin proteins; bovine serum albumin and human serum albumin. It was observed that some candidates, based on their hanging functional groups and specific backbone atoms, could interact well with the protein, thus improving the bioactive properties. On the whole, this work is a proof-of-concept to explore the backbone- and side-chain-tunable macrocycle for different properties and applications.
Ultrasound-Assisted Extraction of Humic Substances from Peat: Assessment of Process Efficiency and Products’ Quality
Authors: Nieweś Dominik , Huculak-Mączka Marta , Braun-Giwerska Magdalena , Marecka Kinga , Tyc Aleksandra , Biegun Marcin , Hoffmann Krystyna , Hoffmann Józef
Published: May 2022

Results of efficiency of obtaining humic substances (HSs) from peat in traditional alkaline extraction (TAE) and ultrasound-assisted alkaline extraction (UAAE) are presented. The influence of the duration of the process and ultrasound intensity on the efficiency of extraction of humic acids (HAs) and fulvic acids (FAs) extraction was determined. The composition of the fulvic acid fraction was examined depending on the type of eluent used. Fulvic acids were divided into fractions using columns packed with DAX-8 resin. For this process, 0.1 M NaOH and 0.5 M NH3∙H2O were used as eluents. For the quality assessment of specific fulvic acids fractions, spectroscopic methods (UV-Vis and FTIR) were used. Ultrasound had a positive effect on HS extraction efficiency, especially in increasing the amount of a desired hydrophobic fraction of fulvic acids (HPO). However, a negative effect of the excessive prolongation and ultrasound intensity (approximately 400 mW∙cm−2) on the extraction efficiency of HPO eluted with 0.1 M NaOH solution was observed. Using peat as a raw carbon material for the HS extraction process can be used as an alternative industrial application of peat. UAAE may be considered as an alternative method to TAE, which provides a higher efficiency in HS isolation from peat.
Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease
Authors: Pagire Suvarna H. , Pagire Haushabhau S. , Park Kun-Young , Bae Eun Jung , Kim Kwang-eun , Kim Minhee , Yoon Jihyeon , Parameswaran Saravanan , Choi Jun-Ho , Park Sungmi , Jeon Jae-Han , Song Jin Sook , Bae Myung Ae , Lee In-Kyu , Kim Hail , Suh Jae Myoung , Ahn Jin Hee
Published: May 2022

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.
Atomistic Simulations of the Permeability and Dynamic Transportation Characteristics of Diamond Nanochannels
Authors: Li Bingqing , Dong Bin , Shi Tianxiang , Zhan Haifei , Zhang Yongqiang
Published: May 2022

Through atomistic simulations, this work investigated the permeability of hexagonal diamond nanochannels for NaCl solution. Compared with the multilayer graphene nanochannel (with a nominal channel height of 6.8 Å), the diamond nanochannel exhibited better permeability. The whole transportation process can be divided into three stages: the diffusion stage, the transition stage and the flow stage. Increasing the channel height reduced the transition nominal pressure that distinguishes the diffusion and flow stages, and improved water permeability (with increased water flux but reduced ion retention rate). In comparison, channel length and solution concentration exerted ignorable influence on water permeability of the channel. Further simulations revealed that temperature between 300 and 350 K remarkably increased water permeability, accompanied by continuously decreasing transition nominal pressure. Additional investigations showed that the permeability of the nanochannel could be effectively tailored by surface functionalization. This work provides a comprehensive atomic insight into the transportation process of NaCl solution in a diamond nanochannel, and the established understanding could be beneficial for the design of advanced nanofluidic devices.
Novel Fluorescent Probe Based on Rare-Earth Doped Upconversion Nanomaterials and Its Applications in Early Cancer Detection
Authors: Ding Zhou , He Yue , Rao Hongtao , Zhang Le , Nguyen William , Wang Jingjing , Wu Ying , Han Caiqin , Xing Christina , Yan Changchun , Chen Wei , Liu Ying
Published: May 2022

In this paper, a novel rare-earth-doped upconverted nanomaterial NaYF4:Yb,Tm fluorescent probe is reported, which can detect cancer-related specific miRNAs in low abundance. The detection is based on an upconversion of nanomaterials NaYF4:Yb,Tm, with emissions at 345, 362, 450, 477, 646, and 802 nm, upon excitation at 980 nm. The optimal Yb3+:Tm3+ doping ratio is 40:1, in which the NaYF4:Yb,Tm nanomaterials have the strongest fluorescence. The NaYF4:Yb, Tm nanoparticles were coated with carboxylation or carboxylated protein, in order to improve their water solubility and biocompatibility. The two commonly expressed proteins, miRNA-155 and miRNA-150, were detected by the designed fluorescent probe. The results showed that the probes can distinguish miRNA-155 well from partial and complete base mismatch miRNA-155, and can effectively distinguish miRNA-155 and miRNA-150. The preliminary results indicate that these upconverted nanomaterials have good potential for protein detection in disease diagnosis, including early cancer detection.
Co-Based Nanosheets with Transitional Metal Doping for Oxygen Evolution Reaction
Authors: Xiong Chunhua , Cai Chao
Published: May 2022

Activated two-dimension (2D) materials are used in various applications as high-performance catalysts. Breaking the long-range order of the basal plane of 2D materials can highly promote catalytic activity by supplying more active sites. Here we developed a method to synthesize ultrathin MCoOx (M = V, Mn, Fe, Ni, Cu, Zn) amorphous nanosheets (ANSs). These Co-based ANSs show high oxygen evolution reaction (OER) activity in alkaline solution due to the broken long-range order and the presence of abundant low bonded O on the basal plane. The stable Fe1Co1Ox ANSs also show an overpotential of ca. 240 mV of achieving 10 mA/cm2 in OER, better than most reported transition metal-based electrocatalysts.
Computational Analysis for Bioconvection of Microorganisms in Prandtl Nanofluid Darcy–Forchheimer Flow across an Inclined Sheet
Authors: Wang Jianfeng , Mustafa Zead , Siddique Imran , Ajmal Muhammad , Jaradat Mohammed M. M. , Rehman Saif Ur , Ali Bagh , Ali Hafiz Muhammad
Published: May 2022

The two-dimensional boundary layer flow of a Prandtl nanofluid was explored in the presence of an aligned magnetic field over an inclined stretching/shrinking sheet in a non-Darcy permeable medium. To transform the PDEs of the leading equations into ODEs, a coupled boundary value problem was formed and suitable similarity functions were used. To obtain numerical answers, an efficient code for the Runge–Kutta technique with a shooting tool was constructed with a MATLAB script. This procedure is widely used for the solution of such problems as it is efficient and cost-effective with a fifth-order accuracy. The significance of immersed parameters on the velocity, temperature, concentration, and bioconvection is shown through figures. Furthermore, the physical parameters of the skin friction coefficient and the Nusselt numbers are demonstrated in tables. The declining behavior of the flow velocity against the porosity parameter Kp and the local inertia co-efficient Fr is shown, and the both parameters of the Darcy resistance and Darcy–Forchheimer resistance are responsible for slowing the fluid speed. The increasing values of the Schmidt number Sc decrease the concentration of the nano entities.
Graphite-Mediated Microwave-Exfoliated Graphene Fluoride as Supercapacitor Electrodes
Authors: Canever Nicoloò , Chen Xianjue , Wojcik Mark , Zhang Hui , Dai Xinchen , Dubois Marc , Nann Thomas
Published: May 2022

A graphite-mediated microwave-based strategy was used for solid-state exfoliation of graphite fluoride in a few seconds, followed by a simple yet efficient separation to obtain exfoliated materials based on the density difference between graphite and graphene fluoride in solvent. The microwave-exfoliated graphene fluoride was a few layers thick and electrically conductive. The electrochemical testing of pouch-cell supercapacitors assembled by using the exfoliated graphene fluoride electrodes and a novel microemulsion-based electrolyte showed reasonable performance with typical electrical double-layer capacitance behavior and good rate capability (gravimetric specific capacitance: 3.2 F g−1 at 500 mA g−1 and 3.1 F g−1 at 5000 mA g−1). The BET specific surface areas of the as-exfoliated graphene fluoride are ~60–80 m2 g−1, which could be increased by activation using this simple yet versatile microwave-based method for further improvements on the electrochemical performance.
Direct and Sensitive Detection of Dopamine Using Carbon Quantum Dots Based Refractive Index Surface Plasmon Resonance Sensor
Authors: Eddin Faten Bashar Kamal , Fen Yap Wing , Fauzi Nurul Illya Muhamad , Daniyal Wan Mohd Ebtisyam Mustaqim Mohd , Omar Nur Alia Sheh , Anuar Muhammad Fahmi , Hashim Hazwani Suhaila , Sadrolhosseini Amir Reza , Abdullah Huda
Published: May 2022

Abnormality of dopamine (DA), a vital neurotransmitter in the brain’s neuronal pathways, causes several neurological diseases. Rapid and sensitive sensors for DA detection are required for early diagnosis of such disorders. Herein, a carbon quantum dot (CQD)-based refractive index surface plasmon resonance (SPR) sensor was designed. The sensor performance was evaluated for various concentrations of DA. Increasing DA levels yielded blue-shifted SPR dips. The experimental findings revealed an excellent sensitivity response of 0.138°/pM in a linear range from 0.001 to 100 pM and a high binding affinity of 6.234 TM−1. The effects of varied concentrations of DA on the optical characteristics of CQD thin film were further proved theoretically. Increased DA levels decreased the thickness and real part of the refractive index of CQD film, according to fitting results. Furthermore, the observed reduction in surface roughness using AFM demonstrated that DA was bound to the sensor layer. This, in turn, explained the blue shift in SPR reflectance curves. This optical sensor offers great potential as a trustworthy solution for direct measurement due to its simple construction, high sensitivity, and other sensing features.
PdAg/Ag(111) Surface Alloys: A Highly Efficient Catalyst of Oxygen Reduction Reaction
Authors: Hua Minghao , Tian Xuelei , Li Shuo , Lin Xiaohang
Published: May 2022

In this article, the behavior of various Pd ensembles on the PdAg(111) surfaces was systematically investigated for oxygen reduction reaction (ORR) intermediates using density functional theory (DFT) simulation. The Pd monomer on the PdAg(111) surface (with a Pd subsurface layer) has the best predicted performance, with a higher limiting potential (0.82 V) than Pt(111) (0.80 V). It could be explained by the subsurface coordination, which was also proven by the analysis of electronic properties. In this case, it is necessary to consider the influence of the near-surface layers when modeling the single-atom alloy (SAA) catalyst processes. Another important advantage of PdAg SAA is that atomic-dispersed Pd as adsorption sites can significantly improve the resistance to CO poisoning. Furthermore, by adjusting the Pd ensembles on the catalyst surface, an exciting ORR catalyst combination with predicted activity and high tolerance to CO poisoning can be designed.
Enteral Nutrition Overview
Authors: Doley Jennifer
Published: May 2022

Enteral nutrition (EN) provides critical macro and micronutrients to individuals who cannot maintain sufficient oral intake to meet their nutritional needs. EN is most commonly required for neurological conditions that impair swallow function, such as stroke, amytrophic lateral sclerosis, and Parkinson’s disease. An inability to swallow due to mechanical ventilation and altered mental status are also common conditions that necessitate the use of EN. EN can be short or long term and delivered gastrically or post-pylorically. The expected duration and site of feeding determine the type of feeding tube used. Many commercial EN formulas are available. In addition to standard formulations, disease specific, peptide-based, and blenderized formulas are also available. Several other factors should be considered when providing EN, including timing and rate of initiation, advancement regimen, feeding modality, and risk of complications. Careful and comprehensive assessment of the patient will help to ensure that nutritionally complete and clinically appropriate EN is delivered safely.
Long-Term High-Fat High-Fructose Diet Induces Type 2 Diabetes in Rats through Oxidative Stress
Authors: Zhao Yue , Wang Qing-Yu , Zeng Lv-Tao , Wang Jing-Jing , Liu Zhen , Fan Guo-Qing , Li Jin , Cai Jian-Ping
Published: May 2022

Long-term consumption of a Western diet is a major cause of type 2 diabetes mellitus (T2DM). However, the effects of diet on pancreatic structure and function remain unclear. Rats fed a high-fat, high-fructose (HFHF) diet were compared with rats fed a normal diet for 3 and 18 months. Plasma biochemical parameters and inflammatory factors were used to reflect metabolic profile and inflammatory status. The rats developed metabolic disorders, and the size of the islets in the pancreas increased after 3 months of HFHF treatment but decreased and became irregular after 18 months. Fasting insulin, C-peptide, proinsulin, and intact proinsulin levels were significantly higher in the HFHF group than those in the age-matched controls. Plasmatic oxidative parameters and nucleic acid oxidation markers (8-oxo-Gsn and 8-oxo-dGsn) became elevated before inflammatory factors, suggesting that the HFHF diet increased the degree of oxidative stress before affecting inflammation. Single-cell RNA sequencing also verified that the transcriptional level of oxidoreductase changed differently in islet subpopulations with aging and long-term HFHF diet. We demonstrated that long-term HFHF diet and aging-associated structural and transcriptomic changes that underlie pancreatic islet functional decay is a possible underlying mechanism of T2DM, and our study could provide new insights to prevent the development of diet-induced T2DM.
The Role of Phytosterols in Nonalcoholic Fatty Liver Disease
Authors: Frasinariu Otilia , Serban Roxana , Trandafir Laura Mihaela , Miron Ingrith , Starcea Magdalena , Vasiliu Ioana , Alisi Anna , Temneanu Oana Raluca
Published: May 2022

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, β-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.
Resistant Maltodextrin Consumption in a Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes in Potentially Beneficial Gut Bacteria
Authors: Mai Volker , Burns Alyssa M. , Solch Rebecca J. , Dennis-Wall Jennifer C. , Ukhanova Maria , Langkamp-Henken Bobbi
Published: May 2022

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR analyses targeting fecal lactic acid bacteria (LAB), Akkermansia muciniphila, Faecalibacterium prausnitzii and Fusicatenibacter saccharivorans in samples from 49 participants. Results: RMD resulted in an approximately two-fold increase in fecal Fusicatenibacter saccharivorans (p = 0.024 for 15 g/day RMD and p = 0.017 for 25 g/day RMD). For Akkermansia muciniphila and Faecalibacterium prausnitzii, we obtained borderline evidence that showed increased amounts in participants that had low baseline levels of these bacteria (p < 0.1 for 25 g/day RMD). We did not detect any effects of RMD on LAB. Conclusions: RMD supplementation in healthy individuals increases Fusicatenibacter saccharivorans. Albeit to a lesser extent, RMD at the higher intake level may also increase Akkermansia muciniphila and Faecalibacterium prausnitzii in individuals with low baseline levels of those two species. Potential benefits associated with these microbiota changes remain to be established in studies with quantifiable health-related endpoints.
Mega-Dose Vitamin C Ameliorates Nonalcoholic Fatty Liver Disease in a Mouse Fast-Food Diet Model
Authors: Lee Seoung-Woo , Lee Young-Jin , Baek Su-Min , Kang Kyung-Ku , Kim Tae-Un , Yim Jae-Hyuk , Kim Hee-Yeon , Han Se-Hyeon , Choi Seong-Kyoon , Park Sang-Joon , Kim Tae-Hwan , Park Jin-Kyu
Published: May 2022

In previous studies, the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD) has been recognized. However, the specific therapeutic strategies or drugs have not been discovered. Vitamin C is a water-soluble antioxidant and is a cofactor in many important biosynthesis pathways. Recently, many researchers have reported that the mega-dose vitamin C treatment had positive effects on various diseases. However, the precise relationship between mega-dose vitamin C and NAFLD has not been completely elucidated. This study has been designed to discover the effects of mega-dose vitamin C on the progression of NAFLD. Twelve-week-old wild-type C57BL6 mice were fed chow diets and high-fat and high-fructose diet (fast-food diet) ad libitum for 11 weeks with or without of vitamin C treatment. Vitamin C was administered in the drinking water (1.5 g/L). In this study, 11 weeks of the mega-dose vitamin C treatment significantly suppressed the development of nonalcoholic steatohepatitis (NASH) independently of the catabolic process. Vitamin C supplements in fast-food diet fed mice significantly decreased diet ingestion and increased water intake. Histopathological analysis revealed that the mice fed a fast-food diet with vitamin C water had a mild renal injury suggesting osmotic nephrosis due to fructose-mediated purine derivatives. These data suggest that the mega-dose vitamin C treatment suppresses high-fructose-diet-mediated NAFLD progression by decreasing diet ingestion and increasing water intake.
Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD
Authors: Naimimohasses Sara , O’Gorman Philip , Wright Ciara , Ni Fhloinn Deirdre , Holden Dean , Conlon Niall , Monaghan Ann , Kennedy Megan , Gormley John , Beddy Peter , Finn Stephen Patrick , Lysaght Joanne , O’Sullivan Jacintha , Dunne Margaret R. , Norris Suzanne , Moore J. Bernadette
Published: May 2022

Background: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). Methods: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. Results: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. Conclusions: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.
Association between Toxoplasma gondii and Blood Pressure and Hypertension in US Adults
Authors: Erickson Lance D. , Bassett Pierce , White David S. , Gale Shawn D. , Brown Bruce L. , Hedges Dawson W.
Published: May 2022

An intraneuronal parasite infecting approximately one-third of the world’s population, Toxoplasma gondii has been associated with markers of cardiovascular disease. In this study, we used data from the Center for Disease Control and Prevention’s National Health and Nutrition Examination Survey to investigate associations between T. gondii and blood pressure and hypertension. Multiple regression modelling adjusted for a range of covariates showed that T. gondii was associated with lowered probability of elevated blood pressure, with lower probability of Stages 1 and 2 hypertension, and with lower systolic and diastolic blood pressure. These findings suggest that T. gondii might alter hemodynamic regulation, although the clinical relevance of these associations requires additional investigation.
Nitrative Stress and Auditory Dysfunction
Authors: Shahab Monazza , Jamesdaniel Samson
Published: May 2022

Nitrative stress is increasingly recognized as a critical mediator of apoptotic cell death in many pathological conditions. The accumulation of nitric oxide along with superoxide radicals leads to the generation of peroxynitrite that can eventually result in the nitration of susceptible proteins. Nitrotyrosine is widely used as a biomarker of nitrative stress and indicates oxidative damage to proteins. Ototoxic insults, such as exposure to noise and ototoxic drugs, enhance the generation of 3-nitrotyrosine in different cell types in the cochlea. Nitrated proteins can disrupt critical signaling pathways and eventually lead to apoptosis and loss of sensory receptor cells in the cochlea. Accumulating evidence shows that selective targeting of nitrative stress attenuates cellular damage. Anti-nitrative compounds, such as peroxynitrite decomposition catalysts and inducible nitric oxide synthase inhibitors, prevent nitrative stress-mediated auditory damage. However, the role of nitrative stress in acquired hearing loss and its potential significance as a promising interventional target is yet to be fully characterized. This review provides an overview of nitrative stress mechanisms, the induction of nitrative stress in the auditory tissue after ototoxic insults, and the therapeutic value of targeting nitrative stress for mitigating auditory dysfunction.
Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease: Observations and Dilemmas after 10 Years of Real-Life Experience
Authors: Szász József Attila , Constantin Viorelia Adelina , Orbán-Kis Károly , Bancu Ligia Ariana , Bataga Simona Maria , Ciorba Marius , Nagy Előd , Neagoe Mircea Radu , Mihály István , Szász Róbert Máté , Kelemen Krisztina , Simu Mihaela , Szatmári Szabolcs
Published: May 2022

Advanced Parkinson’s disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.
Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives
Authors: Pardo-Moreno Teresa , González-Acedo Anabel , Rivas-Domínguez Antonio , García-Morales Victoria , García-Cozar Francisco Jose , Ramos-Rodríguez Juan Jose , Melguizo-Rodríguez Lucía
Published: May 2022

Alzheimer’s disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-β, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aβ pathology and tau pathology, and which include γ-secretase inhibitors, β-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aβ clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease. Therefore, the aim of this review was to analyze and describe current treatments and possible future alternatives in the therapeutic approach to AD.
Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with 89Zr Radioisotope in Mice and Rats
Authors: Choi Hojun , Kim Myung-Yoon , Kim Dae-Hwan , Yun Hanoul , Oh Byung-Koo , Kim Su-Bin , Song In-Ho , Park Hyun-Soo , Kim Sang-Eun , Park Cheolhyoung , Choi Chulhee
Published: May 2022

For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (89Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total 89Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged 89Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free 89Zr, indicating that exosomes might be rapidly taken up by cells and tissues.
How to Make AlphaGo’s Children Explainable
Authors: Park Woosuk
Published: May 2022

Under the rubric of understanding the problem of explainability of AI in terms of abductive cognition, I propose to review the lessons from AlphaGo and her more powerful successors. As AI players in Baduk (Go, Weiqi) have arrived at superhuman level, there seems to be no hope for understanding the secret of their breathtakingly brilliant moves. Without making AI players explainable in some ways, both human and AI players would be less-than omniscient, if not ignorant, epistemic agents. Are we bound to have less explainable AI Baduk players as they make further progress? I shall show that the resolution of this apparent paradox depends on how we understand the crucial distinction between abduction and inference to the best explanation (IBE). Some further philosophical issues arising from explainable AI will also be discussed in connection with this distinction.
Silicon-on-Insulator Optical Buffer Based on Magneto-Optical 1 × 3 Micro-Rings Array Coupled Sagnac Ring
Authors: Wang Huiying , Wang Zhi , Fu Ziling , Jiang Rui , Liu Lanlan , Wang Jian , Wu Chongqing
Published: May 2022

Optical buffer is a key technology to control optical routing and solve channel competition, which directly determines the performance of information processing and storage. In this study, a switchable optical buffer using the nonreciprocal silicon-on-insulator (SOI) magneto-optical micro-ring (MOMR) array coupled with Sagnac ring was introduced, which can exceed the time-bandwidth limitation. The transmission equations and propagation characteristics of optical signal in 1 × 3 micro-rings and Sagnac ring coupled 1 × 3 micro-rings based on two kinds of phase-change materials were studied. The group time delay, effective buffer time and readout operation in the buffer were also investigated.
Hybrid Films Prepared from a Combination of Electrospinning and Casting for Offering a Dual-Phase Drug Release
Authors: Liu Haoran , Jiang Wenlai , Yang Zili , Chen Xiren , Yu Deng-Guang , Shao Jun
Published: May 2022

One of the most important trends in developments in electrospinning is to combine itself with traditional materials production and transformation methods to take advantage of the unique properties of nanofibers. In this research, the single-fluid blending electrospinning process was combined with the casting film method to fabricate a medicated double-layer hybrid to provide a dual-phase drug controlled release profile, with ibuprofen (IBU) as a common model of a poorly water-soluble drug and ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) K60 as the polymeric excipients. Electrospun medicated IBU-PVP nanofibers (F7), casting IBU-EC films (F8) and the double-layer hybrid films (DHFs, F9) with one layer of electrospun nanofibers containing IBU and PVP and the other layer of casting films containing IBU, EC and PVP, were prepared successfully. The SEM assessments demonstrated that F7 were in linear morphologies without beads or spindles, F8 were solid films, and F9 were composed of one porous fibrous layer and one solid layer. XRD and FTIR results verified that both EC and PVP were compatible with IBU. In vitro dissolution tests indicated that F7 were able to provide a pulsatile IBU release, F8 offered a typical drug sustained release, whereas F9 were able to exhibit a dual-phase controlled release with 40.3 ± 5.1% in the first phase for a pulsatile manner and the residues were released in an extended manner in the second phase. The DHFs from a combination of electrospinning and the casting method pave a new way for developing novel functional materials.
Scalable Manufacture of Curcumin-Loaded Chitosan Nanocomplex for pH-Responsive Delivery by Coordination-Driven Flash Nanocomplexation
Authors: Xia Ziwei , Fu Zhinan , Li Li , Ma Enguang , Sun Liang , Ma Qinyu , Guo Xuhong
Published: May 2022

Metal coordination-driven nanocomplexes are known to be responsive to physiologically relevant stimuli such as pH, redox, temperature or light, making them well-suited for antitumor drug delivery. The ever-growing demand for such nanocomplexes necessitates the design of a scalable approach for their production. In this study, we demonstrate a novel coordination self-assembly strategy, termed flash nanocomplexation (FNC), which is rapid and efficient for the fabrication of drug-loaded nanoparticles (NPs) in a continuous manner. Based on this strategy, biocompatible chitosan (CS) and Cu2+ can be regarded anchors to moor the antitumor drug (curcumin, Cur) through coordination, resulting in curcumin-loaded chitosan nanocomplex (Cur-loaded CS nanocomplex) with a narrow size distribution (PDI < 0.124) and high drug loading (up to 41.75%). Owing to the excellent stability of Cur-loaded CS nanocomplex at neutral conditions (>50 days), premature Cur leakage was limited to lower than 1.5%, and pH-responsive drug release behavior was realized in acidic tumor microenvironments. An upscaled manufacture of Cur-loaded CS nanocomplex is demonstrated with continuous FNC, which shows an unprecedented method toward practical applications of nanomedicine for tumor therapy. Furthermore, intracellular uptake study and cytotoxicity experiments toward H1299 cells demonstrates the satisfied anticancer efficacy of the Cur-loaded CS nanocomplex. These results confirm that coordination-driven FNC is an effective method that enables the rapid and scalable fabrication of antitumor drugs.
Effects of the Temperature and Salt Concentration on the Structural Characteristics of the Protein (PDB Code 1BBL)
Authors: Shao Dongqing , Zhang Qun , Xu Peng , Jiang Zhouting
Published: May 2022

The effect of the temperature and salt solution on the structural characteristics of the protein 1BBL was investigated by molecular dynamics simulations. The paper presents simulation results regarding the non-bonded energy and the structural stability of the protein immersed in salt solutions with different concentrations and temperatures. Our work demonstrates that the electrostatic potential energy and van der Waals energy of the system show the opposite changes with the influence of the external environment. Since the electrostatic potential energy changes more obviously, it is dominated in the non-bonding interactions. The structural parameters, such as the root mean square deviation and the radius of gyration, increased initially and decreased afterward with the increase of the salt concentration. The protein presented the loose structure with a relative low stability when it was immersed in a monovalent solution with a salt concentration of 0.8 mol/L. The salt concentration corresponding to the maximum value of structural parameters in the monovalent salt solution was double that in the divalent salt solution. It was also concluded that the protein presented a compact and stable structure when immersed in salt solutions with a high concentration of 2.3 mol/L. The analysis of the root mean square deviation and root mean square fluctuation of the protein sample also exhibited that the structural stability and chain flexibility are strongly guided by the effect of the temperature. These conclusions help us to understand the structural characteristics of the protein immersed in the salt solutions with different concentrations and temperatures.
Blood-Vessel-Inspired Hierarchical Trilayer Scaffolds: PCL/Gelatin-Driven Protein Adsorption and Cellular Interaction
Authors: Rodriguez-Soto Maria A. , Garcia-Brand Andres J. , Riveros Alejandra , Suarez Natalia A. , Serrano Fidel , Osma Johann F. , Muñoz Camargo Carolina , Cruz Juan C. , Sandoval Nestor , Briceño Juan C.
Published: May 2022

Fabrication of scaffolds with hierarchical structures exhibiting the blood vessel topological and biochemical features of the native extracellular matrix that maintain long-term patency remains a major challenge. Within this context, scaffold assembly using biodegradable synthetic polymers (BSPs) via electrospinning had led to soft-tissue-resembling microstructures that allow cell infiltration. However, BSPs fail to exhibit the sufficient surface reactivity, limiting protein adsorption and/or cell adhesion and jeopardizing the overall graft performance. Here, we present a methodology for the fabrication of three-layered polycaprolactone (PCL)-based tubular structures with biochemical cues to improve protein adsorption and cell adhesion. For this purpose, PCL was backbone-oxidized (O-PCL) and cast over a photolithography-manufactured microgrooved mold to obtain a bioactive surface as demonstrated using a protein adsorption assay (BSA), Fourier transform infrared spectroscopy (FTIR) and calorimetric analyses. Then, two layers of PCL:gelatin (75:25 and 95:5 w/w), obtained using a novel single-desolvation method, were electrospun over the casted O-PCL to mimic a vascular wall with a physicochemical gradient to guide cell adhesion. Furthermore, tensile properties were shown to withstand the physiological mechanical stresses and strains. In vitro characterization, using L929 mouse fibroblasts, demonstrated that the multilayered scaffold is a suitable platform for cell infiltration and proliferation from the innermost to the outermost layer as is needed for vascular wall regeneration. Our work holds promise as a strategy for the low-cost manufacture of next-generation polymer-based hierarchical scaffolds with high bioactivity and resemblance of ECM’s microstructure to accurately guide cell attachment and proliferation.
Synthesis and Study of Physical and Mechanical Properties of Urethane-Containing Elastomers Based on Epoxyurethane Oligomers with Controlled Crystallinity
Authors: Slobodinyuk Alexey , Strelnikov Vladimir , Elchisheva Nadezhda , Kiselkov Dmitriy , Slobodinyuk Daria
Published: May 2022

The influence of the molecular weight of oligoamine, oligoether, and the type of diisocyanate on the physical and mechanical properties of elastomers with urethane hydroxyl hard segments was studied. For this purpose, oligoetherdiamines with molecular weights ~1008 and ~1400 g mol−1 were synthesized by a three-stage method. Epoxyurethane oligomers were synthesized according to a two-step route with an oligodiisocyanate as an intermediate product. A series of 12 elastomers with controlled crystallinity were synthesized from these elastomers and amines. The deformation and strength properties of the elastomers were studied.