bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Co-Doping on Cu/CaO Catalysts for Selective Furfural Hydrogenation into Furfuryl Alcohol
Authors: Kalong Munsuree , Ratchahat Sakhon , Khemthong Pongtanawat , Assabumrungrat Suttichai , Srifa Atthapon
Published: May 2022

Cu/CaO catalysts with fine-tuned Co-doping for excellent catalytic performance of furfural (FAL) hydrogenation to furfuryl alcohol (FOL) were synthesized by a facile wetness impregnation method. The optimal Co1.40Cu1/CaO catalyst, with a Co to Cu mole ratio of 1.40:1, exhibited a 100% FAL conversion with a FOL yield of 98.9% at 100 °C and 20 bar H2 pressure after 4 h. As gained from catalyst characterizations, Co addition could facilitate the reducibility of the CoCu system. Metallic Cu, Co-Cu alloys, and oxide species with CaO, acting as the major active components for the reaction, were formed after reduction at 500 °C. Additionally, this combination of Co and Cu elements could result in an improvement of catalyst textures when compared with the bare CaO. Smaller catalyst particles were formed after the addition of Co into Cu species. It was found that the addition of Co to Cu on the CaO support could fine-tune the appropriate acidic and basic sites to boost the FOL yield and selectivity with suppression of undesired products. These observations could confirm that the high efficiency and selectivity are mainly attributed to the synergistic effect between the catalytically active Co-Cu species and the CaO basic sites. Additionally, the FAL conversion and FOL yield insignificantly changed throughout the third consecutive run, confirming a high stability of the developed Co1.40Cu1/CaO catalyst.
Highly Sensitive Nanomagnetic Quantification of Extracellular Vesicles by Immunochromatographic Strips: A Tool for Liquid Biopsy
Authors: Bragina Vera A. , Khomyakova Elena , Orlov Alexey V. , Znoyko Sergey L. , Mochalova Elizaveta N. , Paniushkina Liliia , Shender Victoria O. , Erbes Thalia , Evtushenko Evgeniy G. , Bagrov Dmitry V. , Lavrenova Victoria N. , Nazarenko Irina , Nikitin Petr I.
Published: May 2022

Extracellular vesicles (EVs) are promising agents for liquid biopsy—a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification. The tool is demonstrated by detection of EVs isolated from cell culture supernatants and various body fluids using characteristic biomarkers, CD9 and CD81, and a tumor-associated marker—epithelial cell adhesion molecules. The detection limit of 3.7 × 105 EV/µL is one to two orders better than the most sensitive traditional lateral flow system and commercial ELISA kits. The detection specificity is ensured by an isotype control line on the test strip. The tool’s advantages are due to the spatial quantification of EV-bound magnetic nanolabels within the strip volume by an original electronic technique. The inexpensive tool, promising for liquid biopsy in daily clinical routines, can be extended to other relevant biomarkers.
Theory of Excitons in Atomically Thin Semiconductors: Tight-Binding Approach
Authors: Bieniek Maciej , Sadecka Katarzyna , Szulakowska Ludmiła , Hawrylak Paweł
Published: May 2022

Atomically thin semiconductors from the transition metal dichalcogenide family are materials in which the optical response is dominated by strongly bound excitonic complexes. Here, we present a theory of excitons in two-dimensional semiconductors using a tight-binding model of the electronic structure. In the first part, we review extensive literature on 2D van der Waals materials, with particular focus on their optical response from both experimental and theoretical points of view. In the second part, we discuss our ab initio calculations of the electronic structure of MoS2, representative of a wide class of materials, and review our minimal tight-binding model, which reproduces low-energy physics around the Fermi level and, at the same time, allows for the understanding of their electronic structure. Next, we describe how electron-hole pair excitations from the mean-field-level ground state are constructed. The electron–electron interactions mix the electron-hole pair excitations, resulting in excitonic wave functions and energies obtained by solving the Bethe–Salpeter equation. This is enabled by the efficient computation of the Coulomb matrix elements optimized for two-dimensional crystals. Next, we discuss non-local screening in various geometries usually used in experiments. We conclude with a discussion of the fine structure and excited excitonic spectra. In particular, we discuss the effect of band nesting on the exciton fine structure; Coulomb interactions; and the topology of the wave functions, screening and dielectric environment. Finally, we follow by adding another layer and discuss excitons in heterostructures built from two-dimensional semiconductors.
First Report of the Biosynthesis and Characterization of Silver Nanoparticles Using Scabiosa atropurpurea subsp. maritima Fruit Extracts and Their Antioxidant, Antimicrobial and Cytotoxic Properties
Authors: Essghaier Badiaa , Toukabri Nourchéne , Dridi Rihab , Hannachi Hédia , Limam Inès , Mottola Filomena , Mokni Mourad , Zid Mohamed Faouzi , Rocco Lucia , Abdelkarim Mohamed
Published: May 2022

Candida and dermatophyte infections are difficult to treat due to increasing antifungal drugs resistance such as fluconazole, as well as the emergence of multi-resistance in clinical bacteria. Here, we first synthesized silver nanoparticles using aqueous fruit extracts from Scabiosa atropurpurea subsp. maritima (L.). The characterization of the AgNPs by means of UV, XRD, FTIR, and TEM showed that the AgNPs had a uniform spherical shape with average sizes of 40–50 nm. The biosynthesized AgNPs showed high antioxidant activity when investigated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The AgNPs displayed strong antibacterial potential expressed by the maximum zone inhibition and the lowest MIC and MBC values. The AgNPs revealed a significant antifungal effect against the growth and biofilm of Candida species. In fact, the AgNPs were efficient against Trichophyton rubrum, Trichophyton interdigitale, and Microsporum canis. The antifungal mechanisms of action of the AgNPs seem to be due to the disruption of membrane integrity and a reduction in virulence factors (biofilm and hyphae formation and a reduction in germination). Finally, the silver nanoparticles also showed important cytotoxic activity against the human multiple myeloma U266 cell line and the human breast cancer cell line MDA-MB-231. Therefore, we describe new silver nanoparticles with promising biomedical application in the development of novel antimicrobial and anticancer agents.
High-Efficiency Crystalline Silicon-Based Solar Cells Using Textured TiO2 Layer and Plasmonic Nanoparticles
Authors: Elrashidi Ali , Elleithy Khaled
Published: May 2022

A high-efficiency crystalline silicon-based solar cell in the visible and near-infrared regions is introduced in this paper. A textured TiO2 layer grown on top of the active silicon layer and a back reflector with gratings are used to enhance the solar cell performance. The given structure is simulated using the finite difference time domain (FDTD) method to determine the solar cell’s performance. The simulation toolbox calculates the short circuit current density by solving Maxwell’s equation, and the open-circuit voltage will be calculated numerically according to the material parameters. Hence, each simulation process calculates the fill factor and power conversion efficiency numerically. The optimization of the crystalline silicon active layer thickness and the dimensions of the back reflector grating are given in this work. The grating period structure of the Al back reflector is covered with a graphene layer to improve the absorption of the solar cell, where the periodicity, height, and width of the gratings are optimized. Furthermore, the optimum height of the textured TiO2 layer is simulated to produce the maximum efficiency using light absorption and short circuit current density. In addition, plasmonic nanoparticles are distributed on the textured surface to enhance the light absorption, with different radii, with radius 50, 75, 100, and 125 nm. The absorbed light energy for different nanoparticle materials, Au, Ag, Al, and Cu, are simulated and compared to determine the best performance. The obtained short circuit current density is 61.9 ma/cm2, open-circuit voltage is 0.6 V, fill factor is 0.83, and the power conversion efficiency is 30.6%. The proposed crystalline silicon solar cell improves the short circuit current density by almost 89% and the power conversion efficiency by almost 34%.
Mechanism-Enhanced Active Attapulgite-Supported Nanoscale Zero-Valent Iron for Efficient Removal of Pb2+ from Aqueous Solution
Authors: Dai Liang , Meng Kai , Zhao Weifan , Han Tao , Lei Zhenle , Ma Gui , Tian Xia , Ren Jun
Published: May 2022

In this study, attapulgite-supported nano zero-valent iron (nZVI@ATP) was synthesized by a liquid-phase reduction method using active attapulgite (ATP) as raw material, and used for Pb2+ remediation in aqueous solution. To understand the mechanism of Pb2+ removal, various techniques were used to characterize nZVI@ATP. The results showed that spherical nZVI particles were uniformly dispersed on the surface of ATP, and the agglomeration of nZVI particles was significantly weakened. The adsorption performance of nZVI@ATP for Pb2+ was greatly improved compared with that of ATP ore, in which the Fe/ATP mass ratio of 1:2 was the best loading ratio. Under the conditions of a temperature of 25 °C and a pH of 5.00, the initial concentration of Pb2+ was 700 mg/L, and the Pb2+ removal rate of nZVI@ATP was 84.47%. The adsorption of nZVI@ATP to Pb2+ was mainly a spontaneous endothermic reaction of heterogeneous surfaces, and the adsorption rate of nZVI@ATP to Pb2+ was proportional to pH in the range of 2–5.5. The presence of Na+, Mg2+, and Ca2+ can inhibit the removal of Pb2+, and Ca2+ has the strongest inhibition effect on the removal of Pb2+. The removal mechanism of Pb2+ by nZVI@ATP obtained from SEM-EDS, BET, XRD, FTIR and XPS included reduction, precipitation, and the formation of complexes.
Iron Single Atoms Anchored on Nitrogen-Doped Carbon Matrix/Nanotube Hybrid Supports for Excellent Oxygen Reduction Properties
Authors: Jia Yining , Shi Chunjing , Zhang Wei , Xia Wei , Hu Ming , Huang Rong , Qi Ruijuan
Published: May 2022

Single-atom non-precious metal oxygen reduction reaction (ORR) catalysts have attracted much attention due to their low cost, high selectivity, and high activity. Herein, we successfully prepared iron single atoms anchored on nitrogen-doped carbon matrix/nanotube hybrid supports (FeSA-NC/CNTs) by the pyrolysis of Fe-doped zeolitic imidazolate frameworks. The nitrogen-doped carbon matrix/carbon nanotube hybrid supports exhibit a specific surface area of 1626.814 m2 g−1, which may facilitate electron transfer and oxygen mass transport within the catalyst and be beneficial to ORR performance. Further electrochemical results revealed that our FeSA-NC/CNTs catalyst exhibited excellent ORR activity (half-wave potential: 0.86 V; kinetic current density: 39.3 mA cm−2 at 0.8 V), superior to that of commercial Pt/C catalyst (half-wave potential: 0.846 V; kinetic current density: 14.4 mA cm−2 at 0.8 V). It also has a great stability, which makes it possible to be a valuable non-noble metal electrode material that may replace the latest commercial Pt/C catalyst in the future.
Oxidative Stress and Total Phenolics Concentration in COPD Patients—The Effect of Exercises: A Randomized Controlled Trial
Authors: Domaszewska Katarzyna , Górna Sara , Pietrzak Malwina , Podgórski Tomasz
Published: May 2022

Patients with chronic obstructive pulmonary disease (COPD) suffer from exercise intolerance, the sensation of dyspnea, and fatigue, which are the main reasons for limiting their physical activity. In addition to changes in the respiratory and circulatory systems in patients with COPD, peripheral muscle dysfunction, with numerous metabolic dysfunctions, is observed. One of the symptoms of the described anomalies, among others, is an antioxidative and prooxidative imbalance. The aim of the study was to demonstrate the impact of endurance training, carried out in the extended pulmonary rehabilitation program in COPD patients, on the imbalance between prooxidants and antioxidants in their bodies. Methods: The tests were carried out on a group of patients (n = 32) with COPD; 20 randomly selected people underwent a modified rehabilitation program during their rehabilitation stay, and the obtained results were compared with the results of 12 patients (control group) who were treated without endurance training. At the beginning and at the end of the study, spirometry and cardiopulmonary exercise tests (CPET) were performed. Oxidative stress (allantoin (All) and substances which react with thiobarbituric acid) and antioxidant (ferric reducing ability of plasma and total phenolics) parameters’ concentrations were determined in the venous blood. Results: In the study group, greater post-training increases of VO2max (p = 0.0702) and FEV1/FVC (p < 0.05; ES: 0.436) were reported. The applied CPET at each time caused an increase in the All concentration (p < 0.05) in the study and control groups. Conclusions: Endurance training applied as a part of the rehabilitation process did not cause the additional aggravation of oxidative stress and blood total phenolics concentration.
Prader–Willi Syndrome: Possibilities of Weight Gain Prevention and Treatment
Authors: Erhardt Éva , Molnár Dénes
Published: May 2022

Prader–Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to summarize current knowledge on dietary management and treatment of PWS and, in particular, to prevent excessive weight gain. Growth hormone (GH) therapy is the recommended standard treatment for PWS children, because it improves body composition (by changing the proportion of body fat and lean body mass specifically by increasing muscle mass and energy expenditure), linear growth, and in infants, it promotes psychomotor and IQ development. In early childhood, the predominant symptom is hyperphagia which can lead to early onset, severe obesity with different obesity-related comorbidities. There are several studies on anti-obesity medications (metformin, topiramate, liraglutide, setmelanotide). However, these are still limited, and no widely accepted consensus guideline exists concerning these drugs in children with PWS. Until there is a specific treatment for hyperphagia and weight gain, weight must be controlled with the help of diet and exercise. Below the age of one year, children with PWS have no desire to eat and will often fail to thrive, despite adequate calories. After the age of two years, weight begins to increase without a change in calorie intake. Appetite increases later, gradually, and becomes insatiable. Managing the progression of different nutritional phases (0–4) is really important and can delay the early onset of severe obesity. Multidisciplinary approaches are crucial in the diagnosis and lifelong follow-up, which will determine the quality of life of these patients.
Associations between Meat and Vegetable Intake, Cooking Methods, and Asthenozoospermia: A Hospital-Based Case–Control Study in China
Authors: Liu Ya-Shu , Zhang Yi-Xiao , Wang Xiao-Bin , Wu Qi-Jun , Liu Fang-Hua , Pan Bo-Chen , Zhao Yu-Hong
Published: May 2022

Background: The role of meat and vegetable intake in the development of asthenozoospermia has been controversial, and the role of cooking methods for meat and vegetables in the association has yet to be determined. The present study aimed to illuminate the relationship between the consumption and cooking methods of meat and vegetables and the risk of asthenozoospermia. Methods: In this hospital-based case–control study, we enrolled 552 patients with asthenozoospermia and 585 healthy controls. Dietary information was assessed using a validated self-administered food frequency questionnaire. Asthenozoospermia was diagnosed according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Results: Participants in the highest tertile of total meat and unprocessed meat intake had a 44% and 39% lower risk of asthenozoospermia than those in the lowest tertile (OR = 0.56, 95% CI: 0.37, 0.87 and OR = 0.61, 95% CI: 0.40, 0.93), respectively. Participants with the highest processed meat consumption showed higher risk (OR = 1.44, 95% CI: 1.01, 2.06). Raw vegetable consumption was negatively associated with the risk of asthenozoospermia (OR = 0.67, 95% CI: 0.45, 0.98). The stir-frying cooking method for meat was associated with increased risk of asthenozoospermia (OR = 1.58, 95% CI: 1.02, 2.46). Conclusions: Intake of total meat, unprocessed meat, and raw vegetable may reduce asthenozoospermia risk, while higher consumption of processed meat may increase the risk. Cooking methods may play a role in these associations. These findings need to be confirmed in large and prospective cohort studies.
Maternal Consumption of a Cafeteria Diet during Lactation Leads to Altered Diet-Induced Thermogenesis in Descendants after Exposure to a Western Diet in Adulthood
Authors: Pomar Catalina Amadora , Picó Catalina , Palou Andreu , Sánchez Juana
Published: May 2022

This study investigates the ability of a maternal cafeteria diet during lactation to program brown adipose tissue (BAT) metabolic responses to an obesogenic diet re-exposure in the adult offspring after consuming a standard diet (SD). Nursing rats were fed an SD or a cafeteria diet during lactation. Their offspring (O-C and O-CAF, respectively) were weaned onto an SD, and at 16 weeks of age they were switched to a Western diet until week 24. Gene and protein expression in BAT were measured at PN22 and at 24 weeks. At PN22, compared to controls, O-CAF rats displayed lower mRNA levels of lipogenesis-related genes (Fasn), and higher expression of genes related to lipolysis (Pnpla2), fatty acid uptake (Cd36, Lpl), and oxidation (Cpt1b). Additionally, O-CAF animals displayed increased mRNA levels of Adrb3, Ucp1, and Cidea. In adulthood, these animals maintained lower mRNA levels of lipogenesis-related genes (Pparg, Srebf1, Fasn), but displayed lower expression of genes related to fatty acid uptake (Cd36), fatty acid oxidation (Cpt1b), lipolysis (Pnpla2), Adrb3, Ucp1, and Cidea. Thus, exposure to an obesogenic diet in nursing rats can affect long-term lipid metabolism and attenuate diet-induced thermogenesis in BAT in response to a new obesogenic dietary challenge later in life.
A Fatty Diet Induces a Jejunal Ketogenesis Which Inhibits Local SGLT1-Based Glucose Transport via an Acetylation Mechanism—Results from a Randomized Cross-Over Study between Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers
Authors: Elebring Erik , Wallenius Ville , Casselbrant Anna , Docherty Neil , le Roux Carel , Marschall Hanns-Ulrich , Fändriks Lars
Published: May 2022

Background and aims: Insights into the nature of gut adaptation after different diets enhance the understanding of how food modifications can be used to treat type 2 diabetes and obesity. The aim was to understand how diets, enriched in fat or carbohydrates, affect glucose absorption in the human healthy jejunum, and what mechanisms are involved. Methods: Fifteen healthy subjects received, in randomised order and a crossover study design, two weeks of iso-caloric high-fat diet (HFD) and high-carbohydrate diet (HCD). Following each dietary period, jejunal mucosa samples were retrieved and assessed for protein expression using immunofluorescence and western blotting. Functional characterisation of epithelial glucose transport was assessed ex vivo using Ussing chambers. Regulation of SGLT1 through histone acetylation was studied in vitro in Caco-2 and human jejunal enteroid monolayer cultures. Results: HFD, compared to HCD, decreased jejunal Ussing chamber epithelial glucose transport and the expression of apical transporters for glucose (SGLT1) and fructose (GLUT5), while expression of the basolateral glucose transporter GLUT2 was increased. HFD also increased protein expression of the ketogenesis rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and decreased the acetylation of histone 3 at lysine 9 (H3K9ac). Studies in Caco-2 and human jejunal enteroid monolayer cultures indicated a ketogenesis-induced activation of sirtuins, in turn decreasing SGLT1 expression. Conclusion: Jejunal glucose absorption is decreased by a fat-enriched diet, via a ketogenesis-induced alteration of histone acetylation responsible for the silencing of SGLT1 transcription. The work relates to a secondary outcome in ClinicalTrials.gov (NCT02088853).
Behavioral Health Risk Factors and Motivation to Change among Cardiovascular General Hospital Patients Aged 50 to 79 Years
Authors: Siewert-Markus Ulrike , Ulbricht Sabina , Gaertner Beate , Zyriax Birgit-Christiane , Dörr Marcus , Tobschall Stefanie , Baumann Sophie , John Ulrich , Freyer-Adam Jennis
Published: May 2022

Little is known about the (co-)occurrence of smoking, alcohol at-risk drinking, physical inactivity and overweight, and the motivation to change these behavioral health risk factors (HRFs) in older general hospital patients with cardiovascular disease. Between October and December 2016, all consecutively admitted patients aged 50 to 79 years were proactively recruited on 3 cardiology wards and asked to participate in a survey on HRFs and behavior change motivation. Of the eligible patients, 80.4% participated in the survey (n = 328). The mean age was 66.5 years (standard deviation 9.0), and 65.5% were male. At least 1 HRF was present in 91.8% (n = 280), at least 2 HRFs in 54.4% (n = 166), and 3 or 4 HRFs in 12.1% (n = 37) of participants. The proportion of older adults who contemplated or were changing or planning to change their behavior to meet health behavior recommendations ranged between 66.0% (smoking) and 93.2% (alcohol consumption). The results indicate a notable co-occurrence of behavioral HRFs in older patients with cardiovascular disease. The majority of older adults were at least considering changing the respective behavior. To prevent and treat diseases efficiently, hospitalization may be a suitable moment for systematic multiple HRF screening and intervention.
Family Food Environments and Their Association with Primary and Secondary Students’ Food Consumption in Beijing, China: A Cross-Sectional Study
Authors: Zhang Rong , Yu Xiaohui , Yu Yingjie , Guo Dandan , He Hairong , Zhao Yao , Zhu Wenli
Published: May 2022

Family is the most fundamental and proximal context for children, and children’s eating behavior occurs mostly in the home or together with family members. With this study, we aimed to evaluate the distribution of family food environment dimensions and their relationship with healthy and unhealthy food consumption in primary and secondary students in order to provide evidence in the Chinese context and explore environmental solutions for improved child nutrition. Multi-stage stratified cluster sampling was used to conduct a cross-sectional survey among students in Beijing, China, from September 2020 to June 2021. Family food environment (FFE) was measured by the validated Family Food Environment Questionnaire for Chinese School-age Children, which was self-administered by the children’s caregivers. The students were asked to answer questions about food consumption frequencies in the past 7 days. Binary logistic regression models were used to investigate the relationships between food consumption frequency and FFE, and odds ratios (ORs) with 95% confidence intervals (CI) were computed for independent variables. Among the study population, 9686 students in grades 3–12 and their caregivers completed the survey. The mean score of FFE was 65.7 (±8.4) out of a total possible score of 100, with 76.6% of students categorized as relatively healthier according to their FFE score (≥ 60). Compared with the reference group, students in primary schools and those cared for principally by parents were more likely to be in a healthy FFE category (p < 0.05). Daily consumption of fruits and vegetables was reported by 62.6% and 71.6% of students, respectively, and weekly sugared soft drink consumption was reported by 70.9% of the students. Students with a healthier FFE score (≥60) were more likely to consume fruits (OR = 1.578, 95% CI: 1.428~1.744) and vegetables (OR = 1.402, 95% CI: 1.263~1.556) but less likely to consume sugared soft drinks (OR = 0.592, 95% CI: 0.526~0.667). Family food availability (β = 0.137), caregivers’ nutritional literacy (β = 0.093), meal practices (β = 0.079) and food rules (β = 0.050) were positively correlated with food consumption behavior (p < 0.05). The students with healthier FFE scores (OR = 1.130, 95% CI: 1.014~1.258) and whose caregiver was obese (OR = 2.278, 95% CI: 1.973~2.631) were more likely to be overweight. The family food environment plays an important role in shaping food consumption in children. Provision of healthy foods instead of unhealthy foods, positive meal practices and food rules, and nutrition education for parents can promote healthy eating in children.
Pfkelch13 Plasmodium falciparum Mutations in Huambo, Angola
Authors: Rodrigues Ana Beatriz Batista , de Abreu-Fernandes Rebecca , Neto Zoraima , Jandondo Domingos , Almeida-de-Oliveira Natália Ketrin , de Lavigne Mello Aline Rosa , Morais Joana , Daniel-Ribeiro Cláudio Tadeu , Menard Didier , Ferreira-da-Cruz Maria de Fátima
Published: May 2022

Artemisinin (ART) is recommended as the first-line drug for P. falciparum infections combined with a long-acting partner drug. The emergence of P. falciparum resistance to ART (ARTR) is a concern for malaria. The most feared threat remains the spread of ARTR from Southeast Asia to Africa or the independent emergence of ARTR in Africa, where malaria accounts for 93% of all malaria cases and 94% of deaths. To avoid this worst-case scenario, surveillance of Pfkelch13 mutations is essential. We investigated mutations of Pfkelch13 in 78 P. falciparum samples from Huambo, Angola. Most of the parasites had a wild-type Pfkelch13 allele. We identified one synonymous mutation (R471R) in 10 isolates and one non-synonymous mutation (A578S) in two samples. No Pfkelch13 validated or candidate ARTR mutants were identified. The finding suggests that there is little polymorphism in Pfkelch13 in Huambo. Since cases of late response to ART in Africa and the emergence of ARTR mutations in Rwanda and Uganda have been reported, efforts should be made toward continuous molecular surveillance of ARTR. Our study has some limitations. Since we analyzed P. falciparum parasites from a single health facility, the study may not be representative of all Angolan endemic areas.
Lupus Nephritis, Autoantibody Production and Kidney Outcomes in Males with Childhood-Onset Systemic Lupus Erythematosus
Authors: Wenderfer Scott E. , Orjuela Alvaro , Bekheirnia Mir Reza , Pereira Maria , Muscal Eyal , Braun Michael C. , De Guzman Marietta
Published: May 2022

Childhood-onset systemic lupus erythematosus (cSLE) only represents 20% of all SLE patients, and males with SLE only represent 10%. To study this rare SLE subset, males diagnosed with cSLE over a 30-year period were identified. Organ involvement, autoantibody production, hypocomplementemia, and kidney biopsy findings were compared to cSLE females. Outcomes were assessed using SLE Disease Activity Index scores, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and Childhood Arthritis and Rheumatology Research Alliance definitions for nephritis responsiveness. Of 95 males and 545 females with cSLE, 62% and 57% developed nephritis, respectively. Median age of cSLE onset was 14 years in both genders. Among males, 80% of non-Hispanic whites, 64% of blacks, 59% of Hispanics, and 50% of Asians developed nephritis. The prevalence of pure and mixed class V membranous nephritis was 33%. Median follow-up was 3.2 years (range 0.1–18). Complete kidney responses were seen in 70% after a median 24 months; however, relapse rates were 46%. Kidney disease flares were 56% nephritic and 44% proteinuric. Males and females with cSLE present with comparable rates and nephritis class. While overall and kidney response rates are favorable, kidney disease relapses are common among males.
Advances in Research on Antiviral Activities of Sulfated Polysaccharides from Seaweeds
Authors: Wei Qiang , Fu Guoqiang , Wang Ke , Yang Qiong , Zhao Jiarui , Wang Yuan , Ji Kai , Song Shuliang
Published: May 2022

In recent years, various viral diseases have suddenly erupted, resulting in widespread infection and death. A variety of biological activities from marine natural products have gradually attracted the attention of people. Seaweeds have a wide range of sources, huge output, and high economic benefits. This is very promising in the pharmaceutical industry. In particular, sulfated polysaccharides derived from seaweeds, considered a potential source of bioactive compounds for drug development, have shown antiviral activity against a broad spectrum of viruses, mainly including common DNA viruses and RNA viruses. In addition, sulfated polysaccharides can also improve the body’s immunity. This review focuses on recent advances in antiviral research on the sulfated polysaccharides from seaweeds, including carrageenan, galactan, fucoidan, alginate, ulvan, p-KG03, naviculan, and calcium spirulan. We hope that this review will provide new ideas for the development of COVID-19 therapeutics and vaccines.
Purinoceptor Targeted Cytotoxicity of Adenosine Triphosphate-Conjugated Biogenic Selenium Nanoparticles in Human Colon Cancer Cells
Authors: Saravanakumar Kandasamy , Sathiyaseelan Anbazhagan , Zhang Xin , Park Soyoung , Wang Myeong-Hyeon
Published: May 2022

The adenosine triphosphate (ATP)-conjugated biogenic selenium nanoparticles (SeNPs) for P2 (purinoceptors) receptor-targeted anti-colon cancer activity were developed in this study. First, the SeNPs were synthesized using Trichoderma extracts (TE) and then conjugated with ATP to enhance their anticancer activity. The developed SeNPs had an oval crystalline structure with an average diameter size of 26.45 ± 1.71 d. nm, while the ATP-SeNPs were 78.6 ± 2.91 d. nm. The SeNPs contain Se, and less persistence of P while the ATP-SeNPs have high level of P, and Se in the energy-dispersive spectroscopy (EDS). Further, both nanoparticles exhibited larger sizes in the dynamic light scattering (DLS) analysis than in the transmission electron microscopy (TEM) analysis. The DLS and Fourier transform infrared spectroscopy (FTIR) results provide evidence that the amine group (–NH2) of ATP might bind with the negatively charged SeNPs through covalent bonding. The IC50 concentration was 17.25 ± 1.16 µg/mL for ATP-SeNPs and 61.24 ± 2.08 µg/mL against the caco-2 cell line. The IC50 results evidenced the higher cytotoxicity of ATP-SeNPs in the caco-2 cell line than in HEK293 cells. ATP-SeNPs trigger the anticancer activity in the caco-2 cell line through the induction of mitochondrial membrane potential (MMP) loss and nucleus damage. The biocompatibility test of hemolysis and the egg CAM assay confirmed the non-toxicity of these nanoparticles. Overall, the results proved that the newly developed ATP-SeNPs exhibited higher cytotoxicity in the caco-2 cell line than SeNPs. However, further molecular and in vivo experiments are required to develop the ATP-SeNPs as a candidate drug for cancer-targeted therapeutics.
Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers
Authors: Arranz Maria J. , Salazar Juliana , Bote Valentin , Artigas-Baleri Alicia , Serra-LLovich Alexandre , Triviño Emma , Roige Jordi , Lombardia Carlos , Cancino Martha , Hernandez Marta , Cendros Marc , Duran-Tauleria Enric , Maraver Natalia , Hervas Amaia
Published: May 2022

BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30–50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24–48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: −0.87, SD 9.4, p = 1 × 10−5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10−8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.
Glioblastoma-Derived Exosomes as Nanopharmaceutics for Improved Glioma Treatment
Authors: Lee Hyeji , Bae Kanghye , Baek Ah-Rum , Kwon Eun-Bin , Kim Yeoun-Hee , Nam Sung-Wook , Lee Gang Ho , Chang Yongmin
Published: May 2022

The use of cancer-derived exosomes has been studied in several cancer types, but the cancer-targeting efficacy of glioma-derived exosomes has not been investigated in depth for malignant glioblastoma (GBM) cells. In this study, exosomes were derived from U87MG human glioblastoma cells, and selumetinib, a new anticancer drug, was loaded into the exosomes. We observed the tropism of GBM-derived exosomes in vitro and in vivo. We found that the tropism of GBM-derived exosomes is in contrast to the behavior of non-exosome-enveloped drugs and non-GBM-specific exosomes in vitro and in vivo in an animal GBM model. We found that the tropism exhibited by GBM-derived exosomes can be utilized to shuttle selumetinib, with no specific targeting moiety, to GBM tumor sites. Therefore, our findings indicated that GBM-derived exosomes loaded with selumetinib had a specific antitumor effect on U87MG cells and were non-toxic to normal brain cells. These exosomes offer improved therapeutic prospects for glioblastoma therapy.
Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways
Authors: Abbas Haidy , Sayed Nesrine S El , Youssef Nancy Abdel Hamid Abou , M. E. Gaafar Passent , Mousa Mohamed R. , Fayez Ahmed M. , Elsheikh Manal A
Published: May 2022

Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer’s disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer’s disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators’ levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.
Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach
Authors: Liu Qingxia , Huang Huiping , Xu Baohua , Li Dandan , Liu Maobai , Shaik Imam H. , Wu Xuemei
Published: May 2022

The revised consensus guidelines for optimizing vancomycin doses suggest that maintaining the area under the concentration-time curve to minimal inhibitory concentration ratio (AUC/MIC) of 400–600 mg·h/L is the target pharmacokinetic/pharmacodynamic (PK/PD) index for efficacy. AUC-guided dosing approach uses a first-order pharmacokinetics (PK) equation to estimate AUC using two samples obtained at steady state and one-compartment model, which can cause inaccurate AUC estimation and fail to achieve the effective PK/PD target early in therapy (days 1 and 2). To achieve an efficacy target from the third or fourth dose, two innovative approaches (Method 1 and Method 2) to estimate vancomycin AUC at steady state (AUCSS) using two-compartment model and three or four levels after the first dose are proposed. The feasibility of the proposed methods was evaluated and compared with another published dosing algorithm (Method 3), which uses two samples and a one-compartment approach. Monte Carlo simulation was performed using a well-established population PK model, and concentration-time profiles for virtual patients with various degrees of renal function were generated, with 1000 subjects per group. AUC extrapolated to infinity (AUC0–∞) after the first dose was estimated using the three methods, whereas reference AUC (AUCref) was calculated using the linear-trapezoidal method at steady state after repeated doses. The ratio of AUC0–∞: AUCref and % bias were selected as the indicators to evaluate the accuracy of three methods. Sensitivity analysis was performed to examine the influence of change in each sampling time on the estimated AUC0–∞ using the two proposed approaches. For simulated patients with various creatinine clearance, the mean of AUC0–∞: AUCref obtained from Method 1, Method 2 and Method 3 ranged between 0.98 to 1, 0.96 to 0.99, and 0.44 to 0.69, respectively. The mean bias observed with the three methods was −0.10% to −2.09%, −1.30% to −3.59% and −30.75% to −55.53%, respectively. The largest mean bias observed by changing sampling time while using Method 1 and Method 2 were −4.30% and −10.50%, respectively. Three user-friendly and easy-to-use excel calculators were built based on the two proposed methods. The results showed that our approaches ensured sufficient accuracy and achieved target PK/PD index early and were superior to the published methodologies. Our methodology has the potential to be used for vancomycin dose optimization and can be easily implemented in clinical practice.
Translational Value of the Transdermal Administration of Bergamot Essential Oil and of Its Fractions
Authors: Scuteri Damiana , Rombolà Laura , Crudo Michele , Watanabe Chizuko , Mizoguchi Hirokazu , Sakurada Shinobu , Hamamura Kengo , Sakurada Tsukasa , Morrone Luigi Antonio , Tonin Paolo , Bagetta Giacinto , Corasaniti Maria Tiziana
Published: May 2022

The essential oil of bergamot (BEO) has consistently proven antinociceptive and antiallodynic properties. Accordingly, the analgesic efficacy of the decolored essential oil (DEC), with higher levels of limonene, and the deterpenated (DET) fraction, with higher levels of linalool and linalyl acetate, was investigated using a formalin test after inhalation. The present study was aimed at characterizing the effects of BEO, its components with the highest pharmacological activity (represented by linalool, limonene, and linalyl acetate), and its DEC and DET fractions on the formalin test after transdermal administration relevant to clinical translation through topical application. To this aim, the schedule of intervention involved administration immediately after formalin injection or as a 5 min pretreatment followed by washout in ddY-strain mice. This study demonstrates, for the first time, the significant analgesic effect of all three constituents in the first and second phases, accounting for the efficacy of the essential oil in the formalin test. While all fractions revealed equal activity toward the phytocomplex in the early phase, the reduction in time of licking/biting during the late phase was more markedly induced by DEC. Moreover, pretreatment with BEO and its fractions followed by washout did not produce a significant reduction in licking/biting time in both phases of formalin-induced nociceptive response.
123I-BMIPP, a Radiopharmaceutical for Myocardial Fatty Acid Metabolism Scintigraphy, Could Be Utilized in Bacterial Infection Imaging
Authors: Muranaka Yuka , Mizutani Asuka , Kobayashi Masato , Nakamoto Koya , Matsue Miki , Takagi Fumika , Okazaki Kenichi , Nishi Kodai , Yamazaki Kana , Nishii Ryuichi , Shikano Naoto , Okamoto Shigefumi , Maki Hideki , Kawai Keiichi
Published: May 2022

In this study, we evaluated the use of 15-(4-123I-iodophenyl)-3(R,S)-methylpentadecanoic acid (123I-BMIPP) to visualize fatty acid metabolism in bacteria for bacterial infection imaging. We found that 123I-BMIPP, which is used for fatty acid metabolism scintigraphy in Japan, accumulated markedly in Escherichia coli EC-14 similar to 18F-FDG, which has previously been studied for bacterial imaging. To elucidate the underlying mechanism, we evaluated changes in 123I-BMIPP accumulation under low-temperature conditions and in the presence of a CD36 inhibitor. The uptake of 123I-BMIPP by EC-14 was mediated via the CD36-like fatty-acid-transporting membrane protein and accumulated by fatty acid metabolism. In model mice infected with EC-14, the biological distribution and whole-body imaging were assessed using 123I-BMIPP and 18F-FDG. The 123I-BMIPP biodistribution study showed that, 8 h after infection, the ratio of 123I-BMIPP accumulated in infected muscle to that in control muscle was 1.31 at 60 min after 123I-BMIPP injection. In whole-body imaging 1.5 h after 123I-BMIPP administration and 9.5 h after infection, infected muscle exhibited a 1.33-times higher contrast than non-infected muscle. Thus, 123I-BMIPP shows potential for visualizing fatty acid metabolism of bacteria for imaging bacterial infections.
Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review
Authors: Marquez-Megias Silvia , Nalda-Molina Ricardo , Sanz-Valero Javier , Más-Serrano Patricio , Diaz-Gonzalez Marcos , Candela-Boix Maria Remedios , Ramon-Lopez Amelia
Published: May 2022

Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.
Effect of Penetration Enhancers and Safety on the Transdermal Delivery of Apremilast in Skin
Authors: Sarango-Granda Paulo , Espinoza Lupe Carolina , Díaz-Garrido Natalia , Alvarado Helen , Rodríguez-Lagunas María J. , Baldomá Laura , Calpena Ana
Published: May 2022

The poor water solubility of apremilast (APR) is the main impediment to the penetration of the drug through the skin barrier. The objective of this study was to evaluate the permeability of APR in different solutions enriched with penetration promoters in ex vivo samples of human skin, and additionally assess its tolerance in vivo. To this end, APR solutions with 5% promoter were developed, and the drug’s ability to penetrate human abdominal skin samples was evaluated; the coefficients of permeability, cumulated amounts permeated, and flow were some of the parameters evaluated; likewise, the in vitro and in vivo tolerance of the solutions was evaluated. The results obtained showed that the solutions containing squalene as a promoter improved the penetration of APR compared to the other promoters evaluated; in the same way, on an in vitro scale in HaCaT cells, the promoters were not toxic, finding a cell viability greater than 80% at the different dilutions evaluated. In the in vivo tests carried out with the solution that presented the best results (APR-Squalene solution), it was observed that it does not cause irritation or erythema on the skin after its colorimetric and histological evaluation of the dorsal region of rats after its application. Squalene becomes an excellent candidate to improve the permeability of the drug in the case of the development of a topical formulation; in addition, it was confirmed that this penetration enhancer is neither toxic nor irritating when in contact with the skin in in vivo tests.
Effects of BMSC-Derived EVs on Bone Metabolism
Authors: Zhou Xuchang , Cao Hong , Guo Jianming , Yuan Yu , Ni Guoxin
Published: May 2022

Extracellular vesicles (EVs) are small membrane vesicles that can be secreted by most cells. EVs can be released into the extracellular environment through exocytosis, transporting endogenous cargo (proteins, lipids, RNAs, etc.) to target cells and thereby triggering the release of these biomolecules and participating in various physiological and pathological processes. Among them, EVs derived from bone marrow mesenchymal stem cells (BMSC-EVs) have similar therapeutic effects to BMSCs, including repairing damaged tissues, inhibiting macrophage polarization and promoting angiogenesis. In addition, BMSC-EVs, as efficient and feasible natural nanocarriers for drug delivery, have the advantages of low immunogenicity, no ethical controversy, good stability and easy storage, thus providing a promising therapeutic strategy for many diseases. In particular, BMSC-EVs show great potential in the treatment of bone metabolic diseases. This article reviews the mechanism of BMSC-EVs in bone formation and bone resorption, which provides new insights for future research on therapeutic strategies for bone metabolic diseases.