bluuebunny/crossref_metadata_2025 huggingface dataset:
Fumigant Activity of Bacterial Volatile Organic Compounds against the Nematodes Caenorhabditis elegans and Meloidogyne incognita
Authors: Diyapoglu Ali , Chang Tao-Ho , Chang Pi-Fang Linda , Yen Jyh-Herng , Chiang Hsin-I , Meng Menghsiao
Published: July 2022

Plant-parasitic nematodes infect a diversity of crops, resulting in severe economic losses in agriculture. Microbial volatile organic compounds (VOCs) are potential agents to control plant-parasitic nematodes and other pests. In this study, VOCs emitted by a dozen bacterial strains were analyzed using solid-phase microextraction followed by gas chromatography–mass spectrometry. Fumigant toxicity of selected VOCs, including dimethyl disulfide (DMDS), 2-butanone, 2-pentanone, 2-nonanone, 2-undecanone, anisole, 2,5-dimethylfuran, glyoxylic acid, and S-methyl thioacetate (MTA) was then tested against Caenorhabditis elegans. DMDS and MTA exhibited much stronger fumigant toxicity than the others. Probit analysis suggested that the values of LC50 were 8.57 and 1.43 μg/cm3 air for DMDS and MTA, respectively. MTA also showed stronger fumigant toxicity than DMDS against the root-knot nematode Meloidogyne incognita, suggesting the application potential of MTA.
Food Industry Byproducts as Starting Material for Innovative, Green Feed Formulation: A Sustainable Alternative for Poultry Feeding
Authors: Brunetti Leonardo , Leuci Rosalba , Colonna Maria Antonietta , Carrieri Rossana , Celentano Francesco Emanuele , Bozzo Giancarlo , Loiodice Fulvio , Selvaggi Maria , Tufarelli Vincenzo , Piemontese Luca
Published: July 2022

Rising global populations and enhanced standards of living in so-called developing countries have led to an increased demand of food, in particular meat, worldwide. While increasing the production of broiler meat could be a potential solution to this problem, broiler meat is plagued by health concerns, such as the development of antimicrobial resistance and lower meat quality. For this reason, the supplementation of poultry feed with vitamins and antioxidant compounds, such as polyphenols, has become an attractive prospect for research in this sector. Such supplements could be obtained by extraction of agricultural byproducts (in particular, grape pomaces and artichoke leaves and bracts), thus contributing to reductions in the total amount of waste biomass produced by the agricultural industry. In this review, the effects of poultry feed supplementation with bioactive extracts from grape pomace (skins and/or seeds), as well as extracts from artichoke leaves and bracts, were explored. Moreover, the various methods that have been employed to obtain extracts from these and other agricultural byproducts were listed and described, with a particular focus on novel, eco-friendly extraction methods (using, for example, innovative and biocompatible solvents like Deep Eutectic Solvents (DESs)) that could reduce the costs and energy consumption of these procedures, with similar or higher yields compared to standard methods.
AuAg Nanoparticles Grafted on TiO2@N-Doped Porous Carbon: Improved Depletion of Ciprofloxacin under Visible Light through Plasmonic Photocatalysis
Authors: Jiménez-Salcedo Marta , Monge Miguel , Tena María Teresa
Published: July 2022

TiO2 nanoparticles (NPs) were modified to obtain photocatalysts with different composition sophistication and displaying improved visible light activity. All of them were evaluated in the photodegradation of ciprofloxacin. The band gap of TiO2 NPs was successfully tailored by the formation of an N-doped porous carbon (NPC)-TiO2 nanohybrid through the pyrolysis of melamine at 600 °C, leading to a slight red-shift of the absorption band edge for nanohybrid NPC-TiO2 1. In addition, the in-situ formation and grafting of plasmonic AuAg NPs at the surface of NPC sheets and in close contact with TiO2 NPs leads to AuAg-NPC-TiO2 nanohybrids 2–3. These nanohybrids showed superior photocatalytic performance for the degradation of ciprofloxacin under visible light irradiation, compared to pristine P25 TiO2 NPs or to AuAg-PVP-TiO2 nanohybrid 4 in which polyvinylpyrrolidone stabilized AuAg NPs were directly grafted to TiO2 NPs. The materials were characterized by transmission electron microscope (TEM), High Angle Annular Dark Field—Scanning Transmission Electron Microscopy—Energy Dispersive X-ray Spectroscopy HAADF-STEM-EDS, X-ray photoelectron spectroscopy and solid UV-vis spectroscopy. Moreover, the active species involved in the photodegradation of ciprofloxacin using AuAg-NCS-TiO2 nanohybrids were evaluated by trapping experiments to propose a mechanism for the degradation.
Enhanced Visible-Light-Driven Photocatalysis of Ag/Ag2O/ZnO Nanocomposite Heterostructures
Authors: Loka Chadrasekhar , Lee Kee-Sun
Published: July 2022

Visible-light-driven photocatalysis is one promising and efficient approach for decontaminating pollutants. Herein, we report the combination of localized surface plasmon resonance (LSPR) and p-n heterojunction structure Ag-Ag2O-ZnO nanocomposite synthesized by a hydrothermal process for the suppression of photogenerated electron-hole pair recombination rates, the extension of the absorption edge to the visible region, and the enhancement of photocatalytic efficiency. The prepared nanocomposites were investigated by standard analytical techniques and the results revealed that the synthesized powders were comprised of Ag, Ag2O, and ZnO phases. Photocatalytic activity of the photocatalyst tested for methylene blue, methyl orange, and rhodamine B showed the highest photocatalytic degradation efficiency: 97.3%, 91.1%, and 94.8% within 60 min under visible-light irradiation. The average lifetime of the photogenerated charge carriers was increased twofold in the Ag-Ag2O-ZnO photocatalyst (~10 ns) compared to the pure ZnO (~5.2 ns). The enhanced photocatalytic activity resulted from a decrease of the charge carrier recombination rate as inferred from the steady-state and time-resolved photoluminescence investigations, and the increased photoabsorption ability. The Ag-Ag2O-ZnO photocatalyst was stable over five repeated cyclic photodegradation tests without showing any significant changes in performance. Additionally, the structure indicated a potential for application in environmental remediation. The present study showcases the robust design of highly efficient and reusable visible-light-active photocatalysts via the combination of p-n heterojunction and LSPR phenomena.
Adsorption of Methylene Blue from Aqueous Solution Using Gelatin-Based Carboxylic Acid-Functionalized Carbon Nanotubes@Metal–Organic Framework Composite Beads
Authors: Zhang Yang , Li Yanhui , Wang Mingzhen , Chen Bing , Sun Yaohui , Chen Kewei , Du Qiujv , Pi Xinxin , Wang Yuqi
Published: July 2022

A novel gelatin-based functionalized carbon nanotubes@metal–organic framework (F-CNTs@MOF@Gel) adsorbent was prepared by the green and simple method for the adsorption of methylene blue (MB). Cu-BTC (also known as HKUST-1) was selected as the MOF type. F-CNTs@Cu-BTC particles were fixed by gelatin, thus avoiding the secondary pollution of carbon nanomaterial particles to the environment. CNTs were used as the connecting skeleton to make more effective adsorption sites exposed on the surface of the internal pore structure of the adsorbent. In this paper, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), thermogravimetry (TGA) and BET analysis methods were used to characterize the new adsorbent. The effects of time, temperature, pH, dosage and initial concentration on the adsorption process were investigated by batch adsorption experiments. The adsorption mechanism was further analyzed by several commonly used kinetic and isotherm models, and the reliability of several fitting models was evaluated by the Akaike information criterion (AIC), Bayesian information criterion (BIC) and Hannan information criterion (HIC). After five regeneration experiments, the adsorbent still had 61.23% adsorption capacity. In general, the new adsorbent studied in this paper has an optimistic application prospect.
Systematic Microwave-Assisted Postsynthesis of Mn-Doped Cesium Lead Halide Perovskites with Improved Color-Tunable Luminescence and Stability
Authors: Zhang Yaheng , Fan Chao , Tang Jianghong , Huang Gaoming , Qiang Xinfa , Fu Yu , Zhou Wenjuan , Wu Juan , Huang Shouqiang
Published: July 2022

The metal doping at the Pb2+ position provides improved luminescence performance for the cesium lead halide perovskites, and their fabrication methods assisted by microwave have attracted considerable attention due to the advantages of fast heating and low energy consumption. However, the postsynthetic doping strategy of the metal-doped perovskites driven by microwave heating still lacks systematic research. In this study, the assembly of CsPbBr3/CsPb2Br5 with a strong fluorescence peak at 523 nm is used as the CsPbBr3 precursor, and through the optimization of the postsynthetic conditions such as reaction temperatures, Mn2+/Pb2+ feeding ratios, and Mn2+ sources, the optimum Mn2+-doped product (CsPb(Cl/Br)3:Mn) is achieved. The exciton fluorescence peak of CsPb(Cl/Br)3:Mn is blueshifted to 437 nm, and an obvious fluorescence peak attributing to the doped Mn2+ ions at 597 nm is obtained. Both the CsPbBr3 precursor and CsPb(Cl/Br)3:Mn have high PLQY and stability because there are CsPb2Br5 microcubic crystals to well disperse and embed the CsPbBr3 nanocrystals (NCs) in the precursor, and after Mn2+-doping, this structure is maintained to form CsPb(Cl/Br)3:Mn NCs on the surface of their microcrystals. The exploration of preparation parameters in the microwave-assisted method provides insights into the enhanced color-tunable luminescence of the metal-doped perovskite materials.
Porous TiO2/Carbon Dot Nanoflowers with Enhanced Surface Areas for Improving Photocatalytic Activity
Authors: Song Fengyan , Sun Hao , Ma Hailong , Gao Hui
Published: July 2022

Electron–hole recombination and the narrow-range utilization of sunlight limit the photocatalytic efficiency of titanium oxide (TiO2). We synthesized carbon dots (CDs) and modified TiO2 nanoparticles (NPs) with a flower-like mesoporous structure, i.e., porous TiO2/CDs nanoflowers. Among such hybrid particles, the CDs worked as photosensitizers for the mesoporous TiO2 and enabled the resultant TiO2/CDs nanoflowers with a wide-range light absorption. Rhodamine B (Rh-B) was employed as a model organic pollutant to investigate the photocatalytic activity of the TiO2/CDs nanoflowers. The results demonstrated that the decoration of the CDs on both the TiO2 nanoflowers and the (commercially available AEROXIDE TiO2) P25 NPs enabled a significant improvement in the photocatalytic degradation efficiency compared with the pristine TiO2. The TiO2/CDs nanoflowers, with their porous structure and larger surface areas compared to P25, showed a higher efficiency to prevent local aggregation of carbon materials. All of the results revealed that the introduced CDs, with the unique mesoporous structure, large surface areas and loads of pore channels of the prepared TiO2 NPs, played important roles in the enhancement of the photocatalytic efficiency of the TiO2/CDs hybrid nanoflowers.
Antibacterial Bio-Nanocomposite Textile Material Produced from Natural Resources
Authors: Marković Darka , Zille Andrea , Ribeiro Ana Isabel , Mikučioniene Daiva , Simončič Barbara , Tomšič Brigita , Radetić Maja
Published: July 2022

Growing demand for sustainable and green technologies has turned industries and research toward the more efficient utilization of natural and renewable resources. In an effort to tackle this issue, we developed an antibacterial textile nanocomposite material based on cotton and peat fibers with immobilized Cu-based nanostructures. In order to overcome poor wettability and affinity for Cu2+-ions, the substrate was activated by corona discharge and coated with the biopolymer chitosan before the in situ synthesis of nanostructures. Field emission scanning electron microscopy (FESEM) images show that the application of gallic or ascorbic acid as green reducing agents resulted in the formation of Cu-based nanosheets and mostly spherical nanoparticles, respectively. X-ray photoelectron spectroscopy (XPS) analysis revealed that the formed nanostructures consisted of Cu2O and CuO. A higher-concentration precursor solution led to higher copper content in the nanocomposites, independent of the reducing agent and chitosan deacetylation degree. Most of the synthesized nanocomposites provided maximum reduction of the bacteria Escherichia coli and Staphylococcus aureus. A combined modification using chitosan with a higher deacetylation degree, a 1 mM solution of CuSO4 solution, and gallic acid resulted in an optimal textile nanocomposite with strong antibacterial activity and moderate Cu2+-ion release in physiological solutions. Finally, the Cu-based nanostructures partially suppressed the biodegradation of the textile nanocomposite in soil.
Enhancement of Exchange Bias and Perpendicular Magnetic Anisotropy in CoO/Co Multilayer Thin Films by Tuning the Alumina Template Nanohole Size
Authors: Salaheldeen Mohamed , Nafady Ayman , Abu-Dief Ahmed M. , Díaz Crespo Rosario , Fernández-García María Paz , Andrés Juan Pedro , López Antón Ricardo , Blanco Jesús A. , Álvarez-Alonso Pablo
Published: July 2022

The interest in magnetic nanostructures exhibiting perpendicular magnetic anisotropy and exchange bias (EB) effect has increased in recent years owing to their applications in a new generation of spintronic devices that combine several functionalities. We present a nanofabrication process used to induce a significant out-of-plane component of the magnetic easy axis and EB. In this study, 30 nm thick CoO/Co multilayers were deposited on nanostructured alumina templates with a broad range of pore diameters, 34 nm ≤ Dp ≤ 96 nm, maintaining the hexagonal lattice parameter at 107 nm. Increase of the exchange bias field (HEB) and the coercivity (HC) (12 times and 27 times, respectively) was observed in the nanostructured films compared to the non-patterned film. The marked dependence of HEB and HC with antidot hole diameters pinpoints an in-plane to out-of-plane changeover of the magnetic anisotropy at a nanohole diameter of ∼75 nm. Micromagnetic simulation shows the existence of antiferromagnetic layers that generate an exceptional magnetic configuration around the holes, named as antivortex-state. This configuration induces extra high-energy superdomain walls for edge-to-edge distance >27 nm and high-energy stripe magnetic domains below 27 nm, which could play an important role in the change of the magnetic easy axis towards the perpendicular direction.
Progress in Antiviral Fullerene Research
Authors: Xu Piao-Yang , Li Xiao-Qing , Chen Wei-Guang , Deng Lin-Long , Tan Yuan-Zhi , Zhang Qianyan , Xie Su-Yuan , Zheng Lan-Sun
Published: July 2022

Unlike traditional small molecule drugs, fullerene is an all-carbon nanomolecule with a spherical cage structure. Fullerene exhibits high levels of antiviral activity, inhibiting virus replication in vitro and in vivo. In this review, we systematically summarize the latest research regarding the different types of fullerenes investigated in antiviral studies. We discuss the unique structural advantage of fullerenes, present diverse modification strategies based on the addition of various functional groups, assess the effect of structural differences on antiviral activity, and describe the possible antiviral mechanism. Finally, we discuss the prospective development of fullerenes as antiviral drugs.
Acute Carbamazepine Intoxication
Authors: Gallego María Dolores Calabria , García Mónica Alañá
Published: July 2022

Carbamazepine is an anticonvulsant drug with multiple mechanisms of action, which condition the presence of a characteristic clinical picture after the overingestion of the drug. We expose a case report about a patient who, in the context of an attempted suicide, presented acute intoxication by benzodiazepines and carbamazepine, presenting the characteristic clinical picture of fluctuations in the level of consciousness, even presenting gaze deconjugation, almost unreactive coma and generalized hypotonia.
Mulberry Leaf and Neochlorogenic Acid Alleviates Glucolipotoxicity-Induced Oxidative Stress and Inhibits Proliferation/Migration via Downregulating Ras and FAK Signaling Pathway in Vascular Smooth Muscle Cell
Authors: Yang Tsung-Yuan , Wu Yi-Liang , Yu Meng-Hsun , Hung Tung-Wei , Chan Kuei-Chuan , Wang Chau-Jong
Published: July 2022

Mulberry leaf (Morus alba L.) has been used as a health food and in traditional medicine to treat several metabolic diseases, including diabetes, hypertension, and hyperlipidemia. However, the mechanism by which mulberry leaf and its functional components mediate atherosclerosis remains unclear. This study aimed to determine the effect of mulberry leaf extract (MLE) and its major component, neochlorogenic acid (nCGA), on the proliferation and migration of rat aortic vascular smooth muscle cells (VSMCs, A7r5 cell line) under diabetic cultured conditions (oleic acid and high glucose, OH). Our findings showed that MLE and nCGA significantly inhibited cell proliferation and migration in A7r5 cells as determined by a scratch wound assay and a Transwell assay. Furthermore, we observed MLE and nCGA inhibited cell proliferation and migration, such as reducing the phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), focal adhesion kinase (FAK), and small GTPase proteins using Western blot analysis. In conclusion, we confirmed the anti-atherosclerotic effects of MLE and nCGA in reducing vascular smooth muscle cell (VSMC) migration and proliferation under diabetic cultured conditions via inhibition of FAK/small GTPase proteins, PI3K/Akt, and Ras-related signaling.
Tea Polyphenols as Prospective Natural Attenuators of Brain Aging
Authors: Hong Mengyu , Yu Jing , Wang Xuanpeng , Liu Yanan , Zhan Shengnan , Wu Zufang , Zhang Xin
Published: July 2022

No organism can avoid the process of aging, which is often accompanied by chronic disease. The process of biological aging is driven by a series of interrelated mechanisms through different signal pathways, including oxidative stress, inflammatory states, autophagy and others. In addition, the intestinal microbiota play a key role in regulating oxidative stress of microglia, maintaining homeostasis of microglia and alleviating age-related diseases. Tea polyphenols can effectively regulate the composition of the intestinal microbiota. In recent years, the potential anti-aging benefits of tea polyphenols have attracted increasing attention because they can inhibit neuroinflammation and prevent degenerative effects in the brain. The interaction between human neurological function and the gut microbiota suggests that intervention with tea polyphenols is a possible way to alleviate brain-aging. Studies have been undertaken into the possible mechanisms underpinning the preventative effect of tea polyphenols on brain-aging mediated by the intestinal microbiota. Tea polyphenols may be regarded as potential neuroprotective substances which can act with high efficiency and low toxicity.
Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy
Authors: Tziridis Konstantin , Schulze Holger
Published: July 2022

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses.
Dietary Patterns Derived from Reduced Rank Regression Are Associated with the 5-Year Occurrence of Metabolic Syndrome: Aichi Workers’ Cohort Study
Authors: Li Yuanying , Yatsuya Hiroshi , Wang Chaochen , Uemura Mayu , Matsunaga Masaaki , He Yupeng , Khine Maythet , Ota Atsuhiko
Published: July 2022

The aim of the present study was to derive dietary patterns to explain variation in a set of nutrient intakes or in the measurements of waist circumference (WC) and fasting blood glucose (FBG) using reduced rank regression (RRR) and to prospectively investigate these patterns in relation to the risk of developing metabolic syndrome (MetS) and its components during the follow-up. The study participants were comprised of 2944 government employees aged 30–59 years without MetS. RRR was applied with 38 food groups as predictors and with two sets of response variables. The first set included intake of putatively beneficial nutrients, and the first factor retained was named the Healthy Dietary Pattern (HDP). The second one included baseline WC and FBG, and the first factor was named the Unhealthy Dietary Pattern (UHDP). Multivariable Cox proportional hazard model was used to estimate hazard ratio and 95% confidence intervals with adjustments for age, sex, total energy consumption and other potential confounders. During the 5-year median follow-up, we ascertained 374 cases of MetS. The HDP score was inversely associated with the incidence of MetS (p-trend = 0.009) and hypertension (p-trend = 0.002) and marginally significantly associated with elevated triglyceride and decreased high-density lipoprotein cholesterol (p-trend = 0.08). The UHDP score was linearly positively associated with the incidence of MetS and all its components (all p-trend < 0.05). Both the HDP and UHDP predicted the development of MetS and its components.
mTORC1 and mTORC2 Complexes Regulate the Untargeted Metabolomics and Amino Acid Metabolites Profile through Mitochondrial Bioenergetic Functions in Pancreatic Beta Cells
Authors: Soliman Ghada A. , Abzalimov Rinat R. , He Ye
Published: July 2022

Background: Pancreatic beta cells regulate bioenergetics efficiency and secret insulin in response to glucose and nutrient availability. The mechanistic Target of Rapamycin (mTOR) network orchestrates pancreatic progenitor cell growth and metabolism by nucleating two complexes, mTORC1 and mTORC2. Objective: To determine the impact of mTORC1/mTORC2 inhibition on amino acid metabolism in mouse pancreatic beta cells (Beta-TC-6 cells, ATCC-CRL-11506) using high-resolution metabolomics (HRM) and live-mitochondrial functions. Methods: Pancreatic beta TC-6 cells were incubated for 24 h with either: RapaLink-1 (RL); Torin-2 (T); rapamycin (R); metformin (M); a combination of RapaLink-1 and metformin (RLM); Torin-2 and metformin (TM); compared to the control. We applied high-resolution mass spectrometry (HRMS) LC-MS/MS untargeted metabolomics to compare the twenty natural amino acid profiles to the control. In addition, we quantified the bioenergetics dynamics and cellular metabolism by live-cell imaging and the MitoStress Test XF24 (Agilent, Seahorse). The real-time, live-cell approach simultaneously measures the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to determine cellular respiration and metabolism. Statistical significance was assessed using ANOVA on Ranks and post-hoc Welch t-Tests. Results: RapaLink-1, Torin-2, and rapamycin decreased L-aspartate levels compared to the control (p = 0.006). Metformin alone did not affect L-aspartate levels. However, L-asparagine levels decreased with all treatment groups compared to the control (p = 0.03). On the contrary, L-glutamate and glycine levels were reduced only by mTORC1/mTORC2 inhibitors RapaLink-1 and Torin-2, but not by rapamycin or metformin. The metabolic activity network model predicted that L-aspartate and AMP interact within the same activity network. Live-cell bioenergetics revealed that ATP production was significantly reduced in RapaLink-1 (122.23 ± 33.19), Torin-2 (72.37 ± 17.33) treated cells, compared to rapamycin (250.45 ± 9.41) and the vehicle control (274.23 ± 38.17), p < 0.01. However, non-mitochondrial oxygen consumption was not statistically different between RapaLink-1 (67.17 ± 3.52), Torin-2 (55.93 ± 8.76), or rapamycin (80.01 ± 4.36, p = 0.006). Conclusions: Dual mTORC1/mTORC2 inhibition by RapaLink-1 and Torin-2 differentially altered the amino acid profile and decreased mitochondrial respiration compared to rapamycin treatment which only blocks the FRB domain on mTOR. Third-generation mTOR inhibitors may alter the mitochondrial dynamics and reveal a bioenergetics profile that could be targeted to reduce mitochondrial stress.
Effectiveness of Dietary Interventions in Prevention and Treatment of Iron-Deficiency Anemia in Pregnant Women: A Systematic Review of Randomized Controlled Trials
Authors: Skolmowska Dominika , Głąbska Dominika , Kołota Aleksandra , Guzek Dominika
Published: July 2022

Pregnant women are among the population groups most vulnerable to the development of anemia, as the overall iron requirement during pregnancy is significantly higher than in non-pregnant women. The aim of the systematic review was to assess the effectiveness of dietary interventions in the prevention and treatment of iron-deficiency anemia in pregnant women based on randomized-controlled trials. The systematic review was based on the PRISMA guidelines and is registered in the PROSPERO database (CRD42021261235). The search was conducted within PubMed and Web of Science databases for the period until June 2021. The included randomized controlled trials presented effectiveness of dietary interventions in prevention and treatment of iron-deficiency anemia in pregnant women. From the total number of 7825 screened records, the final number of seven studies were included in the systematic review. The procedure of screening, inclusion, reporting, and assessment of the risk of bias while using the revised Cochrane risk of bias tool for randomized trials was conducted by two independent researchers. The studies included in the systematic review were conducted in populations of anemic pregnant women, or mixed populations of anemic and non-anemic pregnant women. The interventions described within the studies were associated with including fortified products, regular products, or dietary counselling. They were based on providing an increased amount of iron, providing an increased amount of multiple nutrients, or general counselling only, while effectiveness was compared with effectiveness of the placebo, supplementation, or control group. The study duration was diversified from a few weeks to half a year or longer. The major biochemical measure assessed within the included studies was hemoglobin. All applied dietary interventions, based on providing increased amount of iron, providing increased amount of multiple nutrients, or general counselling only, were effective. The majority of included studies were assessed as ones of a medium risk of bias. For some studies a high risk of bias was indicated, which resulted from a risk of bias arising from the randomization process, due to deviations from the intended interventions, and in selection of the reported result. Considering this fact, more randomized controlled trials should be planned and conducted in a rigorous manner to confirm the formulated observations of effectiveness of the studied interventions based on providing an increased amount of iron, providing an increased amount of multiple nutrients, or general counselling only.
Effects of Rehabilitation on Long-COVID-19 Patient’s Autonomy, Symptoms and Nutritional Observance
Authors: Ghanem Jeyniver , Passadori Anne , Severac François , Dieterlen Alain , Geny Bernard , Andrès Emmanuel
Published: July 2022

Background: Despite significant improvements in COVID-19 therapy, many patients still present with persistent symptoms and quality-of-life alterations. The aim of this study was to simultaneously investigate the long-term evolution of autonomy, malnutrition and long-lasting symptoms in people infected with COVID-19 and hospitalized in the ICU. Method: Patients’ clinical characteristics; extent of their loss of autonomy based on “Autonomie Gérontologie Groupes Iso-Ressources” (AG-GIR) classification; nutritional status while following the French and Global Leadership Initiative on Malnutrition (GLIM) recommendations; and symptom evolutions before infection, during hospitalization and rehabilitation, and up to 6 months after returning home were determined in thirty-seven patients. Results: Prior to a COVID-19 infection, all patients were autonomous, but upon admission to the rehabilitation center (CRM), 39% of them became highly dependent. After discharge from the center and 6 months after returning home, only 6 and 3%, respectively, still required considerable assistance. Of these thirty-seven patients, 11% were moderately malnourished and 81% presented with severe malnutrition, with a significant correlation being observed between malnutrition and autonomy (p < 0.05). Except for fatigue, which persisted in 70% of the patients 6 months after discharge from rehabilitation, all other symptoms decreased significantly. Conclusions: This study shows a striking decrease in autonomy associated with malnutrition after hospitalization for a COVID-19 infection and a clear beneficial effect from personalized rehabilitation. However, although almost all patients regained autonomy 6 months after returning home, they often still suffer from fatigue. Patient compliance with their nutritional recommendations deserves further improvement, preferably through personalized and persistent follow-up with the patient.
Machine Learning-Based Prediction of In-Hospital Complications in Elderly Patients Using GLIM-, SGA-, and ESPEN 2015-Diagnosed Malnutrition as a Factor
Authors: Ren Shan-Shan , Zhu Ming-Wei , Zhang Kai-Wen , Chen Bo-Wen , Yang Chun , Xiao Rong , Li Peng-Gao
Published: July 2022

Background: Malnutrition is prevalent in elderly inpatients and is associated with various adverse outcomes during their hospital stay, but the diagnosis of malnutrition still lacks widely applicable criteria. This study aimed to investigate the association of malnutrition diagnosed with the SGA, ESPEN 2015, and GLIM criteria, respectively, with in-hospital complications in elderly patients. Method: Hospitalized patients over 65 years old who had been assessed with the SGA guideline for malnutrition at admission were retrospectively recruited from a large observational cohort study conducted in 34 level-A tertiary hospitals in 18 cities in China from June to September 2014. Malnutrition was then retrospectively diagnosed using the GLIM and ESPEN 2015 criteria, respectively, for comparison with the results of the SGA scale. The risk factors for malnutrition were analyzed using logistic regression, and the value of the three diagnostic criteria in predicting the in-hospital complications was subsequently explored using multivariate regression and the random forest machine learning algorithm. Results: A total of 2526 subjects who met the inclusion and exclusion criteria of the study were selected from the 7122 patients in the dataset, with an average age of 74.63 ± 7.12 years, 59.2% male, and 94.2% married. According to the GLIM, SGA, and ESPEN 2015 criteria, the detection rates of malnutrition were 37.8% (956 subjects), 32.8% (829 subjects), and 17.0% (429 subjects), respectively. The diagnostic consistency between the GLIM and the SGA criteria is better than that between the ESPEN 2015 and the SGA criteria (Kappa statistics, 0.890 vs. 0.590). Logistic regression showed that the risk of developing complications in the GLIM-defined malnutrition patients is 2.414 times higher than that of normal patients, higher than those of the ESPEN 2015 and SGA criteria (1.786 and 1.745 times, respectively). The random forest classifications show that the GLIM criteria have a higher ability to predict complications in these elderly patients than the SGA and ESPEN 2015 criteria with a mean decrease in accuracy of 12.929, 10.251, and 5.819, respectively, and a mean decrease in Gini of 2.055, 1.817, and 1.614, respectively. Conclusion: The prevalence of malnutrition diagnosed with the GLIM criteria is higher than that of the SGA and the ESPEN 2015 criteria. The GLIM criteria are better than the SGA and the ESPEN 2015 criteria for predicting in-hospital complications in elderly patients.
The Impact of RNA Interference in Tick Research
Authors: de la Fuente José , Kocan Katherine M.
Published: July 2022

Over the past two decades, RNA interference (RNAi) in ticks, in combination with omics technologies, have greatly advanced the discovery of tick gene and molecular function. While mechanisms of RNAi were initially elucidated in plants, fungi, and nematodes, the classic 2002 study by Aljamali et al. was the first to demonstrate RNAi gene silencing in ticks. Subsequently, applications of RNAi have led to the discovery of genes that impact tick function and tick-host-pathogen interactions. RNAi will continue to lead to the discovery of an array of tick genes and molecules suitable for the development of vaccines and/or pharmacologic approaches for tick control and the prevention of pathogen transmission.
Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway
Authors: Abdelzaher Walaa Yehia , Mostafa-Hedeab Gomaa , Bahaa Haitham Ahmed , Mahran Ahmad , Atef Fawzy Michael , Abdel Hafez Sara Mohamed Naguib , Welson Nermeen N. , Rofaeil Remon Roshdy
Published: July 2022

Aims: To investigate the potential protective role of montelukast (Mont) in the pre-eclampsia rat model induced by L-NG-Nitro arginine methyl ester (L-NAME). Methods and materials: Thirty-two pregnant female albino Wistar rats were assigned to four groups: the control group: pregnant rats received vehicles; the Mont group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation; the L-NAME group: pregnant rats received L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation; the Mont/L-NAME group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation and L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation. Placental, hepatic, and renal malondialdehyde (MDA), total nitrites (NOx), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α were determined. Serum alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, 24-h urinary protein, and the placental growth factor (PGF) were measured. Histopathological examinations of the placental, hepatic, and renal tissues were also performed. In addition, placental, hepatic, and renal Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (STAT3) immunoblotting were performed. Key findings: Mont improves oxidative stress, IL-6, TNF-α, ALT, AST, creatinine, urea, 24-h urinary protein, PGF, Jak2, and STAT3 which were all affected by L-NAME. Moreover, the histopathological assessment indicated that Mont restored the normal architecture that was markedly disturbed by L-NAME. Significance: Mont exerted the biochemical and histopathological amelioration of L-NAME-caused pre-eclampsia through its anti-inflammatory, anti-oxidant function and suppression of the IL-6/Jak2/STAT3 signaling pathway.
Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis
Authors: Taha Medhat , Elazab Sara T. , Badawy Alaa. M. , Saati Abdullah A. , Qusty Naeem F. , Al-Kushi Abdullah G. , Sarhan Anas , Osman Amira , Farage Amira E.
Published: July 2022

Chemo fog is one of the most serious health concerns encountered by cancer survivors receiving doxorubicin (DOX)-based chemotherapy. Oxidative stress, neuroinflammation, apoptosis and impairment of synaptic plasticity are regarded as the key factors implicated in DOX-induced cognitive impairment. This research aimed to assess the possible neuroprotective effect of cerium oxide nanoparticles (CeNPs) against DOX-induced neurotoxicity. Forty-eight rats were divided into four groups (12 rats/group): control group, CeNPs group (received oral CeNPs solution (35 mg/kg) daily for 4 weeks), and DOX group (were administered DOX intraperitoneally (2 mg/kg, once/week for 4 weeks)) and DOX+ CeNPs group. The findings revealed that CeNPs mitigated behavioral alterations in DOX-induced cognitive deficit. Additionally, CeNPs alleviated the histopathological abnormalities in hippocampus and ameliorated DOX-induced neuroinflammation by downregulating the expression of NF-κB, TNF-α, IL-1β and IL6. In addition, CeNPs antagonized the apoptosis through reducing the protein expression of cytochrome c and caspase 3. In addition, it stimulated the antioxidant defense, as indicated by upregulating the expression of the Nrf2, HO-1 and PGC-1α genes. CeNPs improved synaptic plasticity via acting on the BDNF. These actions were related through the modification of SIRT-1 expression. Based on the aforementioned results, CeNPs antagonized the doxorubicin-induced neurodegeneration by its antioxidant, anti-inflammatory and antiapoptotic effects, alongside its SIRT-1 mediated mechanisms.
Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality
Authors: Stepien Konrad , Nowak Karol , Kachnic Natalia , Horosin Grzegorz , Walczak Piotr , Karcinska Aleksandra , Schwarz Tomasz , Wojtas Mariusz , Zalewska Magdalena , Pastuszak Maksymilian , Wegrzyn Bogdan , Nessler Jadwiga , Zalewski Jarosław
Published: July 2022

Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients were observed within a median follow-up of 69.2 (37.8–79.9) months. On discharge, statins were prescribed less frequently in MI patients with cancer as compared to the non-cancer MI population (79.9% vs. 91.4%, p < 0.001). The most common statin in both groups was atorvastatin. The long-term mortality was higher in MI patients not treated vs. those treated with statins, both in non-cancer (29.5%/year vs. 6.7%/year, p < 0.001) and cancer groups (53.9%/year vs. 24.9%/year, p < 0.05), respectively. Patient’s age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.03–1.05, p < 0.001, per year), an active cancer (HR 2.42, 95% CI 1.89–3.11, p < 0.001), hemoglobin level (HR 1.14, 95% CI 1.09–1.20, p < 0.001, per 1 g/dL decrease), and no statin on discharge (HR 2.13, 95% CI 1.61–2.78, p < 0.001) independently increased long-term mortality. In MI patients, simultaneous diagnosis of an active cancer was associated with less frequently prescribed statins on discharge. Irrespective of cancer diagnosis, no statin use was found as an independent predictor of increased long-term mortality.
Thermosensitive PLGA–PEG–PLGA Hydrogel as Depot Matrix for Allergen-Specific Immunotherapy
Authors: Heine Sonja , Aguilar-Pimentel Antonio , Russkamp Dennis , Alessandrini Francesca , Gailus-Durner Valerie , Fuchs Helmut , Ollert Markus , Bredehorst Reinhard , Ohnmacht Caspar , Zissler Ulrich M. , Hrabě de Angelis Martin , Schmidt-Weber Carsten B. , Blank Simon
Published: July 2022

Allergen-specific immunotherapy (AIT) is the only currently available curative treatment option for allergic diseases. AIT often includes depot-forming and immunostimulatory adjuvants, to prolong allergen presentation and to improve therapeutic efficacy. The use of aluminium salts in AIT, which are commonly used as depot-forming adjuvants, is controversially discussed, due to health concerns and Th2-promoting activity. Therefore, there is the need for novel delivery systems in AIT with similar therapeutic efficacy compared to classical AIT strategies. In this study, a triblock copolymer (hydrogel) was assessed as a delivery system for AIT in a murine model of allergic asthma. We show that the hydrogel combines the advantages of both depot function and biodegradability at the same time. We further demonstrate the suitability of hydrogel to release different bioactive compounds in vitro and in vivo. AIT delivered with hydrogel reduces key parameters of allergic inflammation, such as inflammatory cell infiltration, mucus hypersecretion, and allergen-specific IgE, in a comparable manner to standard AIT treatment. Additionally, hydrogel-based AIT is superior in inducing allergen-specific IgG antibodies with potentially protective functions. Taken together, hydrogel represents a promising delivery system for AIT that is able to combine therapeutic allergen administration with the prolonged release of immunomodulators at the same time.
Itraconazole Nanosuspensions via Dual Centrifugation Media Milling: Impact of Formulation and Process Parameters on Particle Size and Solid-State Conversion as Well as Storage Stability
Authors: Willmann Ann-Cathrin , Berkenfeld Kai , Faber Thilo , Wachtel Herbert , Boeck Georg , Wagner Karl G.
Published: July 2022

Nanocrystal suspensions proved to be a potent enabling principle for biopharmaceutics classification system class II drugs with dissolution limited bioavailability. In the example of itraconazole (ITZ) as a model drug combined with electrosteric stabilization using hydroxypropyl cellulose (HPC-SL), sodium dodecyl sulfate (SDS) and polysorbate 80 (PS80), the impacts of formulation and process parameters of a dual centrifugal mill on material attributes such as particle size, zeta potential, particle morphology, storage stability and especially solid-state characteristics were evaluated. A minimal concentration of 0.9% (w/w) HPC-SL, 0.14% (w/w) SDS and 0.07% (w/w) PS80 was necessary for sufficient nanoparticle stabilization. Despite the minor effect of PS80, its presence was beneficial for electrosteric stabilization. Choosing lower stabilizer concentrations resulted in a pronounced increase in particle size due to agglomeration, which was confirmed by SEM imaging and a decrease in zeta potential in combination with an amorphization of the particles. Milling temperature had no significant impact on the particle size, whereas milling speed and the size of the milling beads used were found to have a strong impact on the critical material attributes such as particle size and polydispersity index. The smallest particle sizes could be obtained by using the smallest milling bead size. However, the smallest obtainable particle size could only be achieved by using two-fold stabilizer concentrations, as smaller particles exhibit a larger specific surface area.
Machine Learning and Pharmacometrics for Prediction of Pharmacokinetic Data: Differences, Similarities and Challenges Illustrated with Rifampicin
Authors: Keutzer Lina , You Huifang , Farnoud Ali , Nyberg Joakim , Wicha Sebastian G. , Maher-Edwards Gareth , Vlasakakis Georgios , Moghaddam Gita Khalili , Svensson Elin M. , Menden Michael P. , Simonsson Ulrika S. H. ,   on behalf of the UNITE4TB Consortium
Published: July 2022

Pharmacometrics (PM) and machine learning (ML) are both valuable for drug development to characterize pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetic/pharmacodynamic (PKPD) analysis using PM provides mechanistic insight into biological processes but is time- and labor-intensive. In contrast, ML models are much quicker trained, but offer less mechanistic insights. The opportunity of using ML predictions of drug PK as input for a PKPD model could strongly accelerate analysis efforts. Here exemplified by rifampicin, a widely used antibiotic, we explore the ability of different ML algorithms to predict drug PK. Based on simulated data, we trained linear regressions (LASSO), Gradient Boosting Machines, XGBoost and Random Forest to predict the plasma concentration-time series and rifampicin area under the concentration-versus-time curve from 0–24 h (AUC0–24h) after repeated dosing. XGBoost performed best for prediction of the entire PK series (R2: 0.84, root mean square error (RMSE): 6.9 mg/L, mean absolute error (MAE): 4.0 mg/L) for the scenario with the largest data size. For AUC0–24h prediction, LASSO showed the highest performance (R2: 0.97, RMSE: 29.1 h·mg/L, MAE: 18.8 h·mg/L). Increasing the number of plasma concentrations per patient (0, 2 or 6 concentrations per occasion) improved model performance. For example, for AUC0–24h prediction using LASSO, the R2 was 0.41, 0.69 and 0.97 when using predictors only (no plasma concentrations), 2 or 6 plasma concentrations per occasion as input, respectively. Run times for the ML models ranged from 1.0 s to 8 min, while the run time for the PM model was more than 3 h. Furthermore, building a PM model is more time- and labor-intensive compared with ML. ML predictions of drug PK could thus be used as input into a PKPD model, enabling time-efficient analysis.