bluuebunny/crossref_metadata_2025 huggingface dataset:
Luminescence Enhancement and Temperature Sensing Properties of Hybrid Bismuth Halides Achieved via Tuning Organic Cations
Authors: Zhuang Ting-Hui , Lin Yi-Min , Lin Hao-Wei , Guo Yan-Ling , Li Zi-Wei , Du Ke-Zhao , Wang Ze-Ping , Huang Xiao-Ying
Published: March 2023

Bismuth-halide-based inorganic-organic hybrid materials (Bi-IOHMs) are desirable in luminescence-related applications due to their advantages such as low toxicity and chemical stability. Herein, two Bi-IOHMs of [Bpy][BiCl4(Phen)] (1, Bpy = N-butylpyridinium, Phen = 1,10-phenanthroline) and [PP14][BiCl4(Phen)]·0.25H2O (2, PP14 = N-butyl-N-methylpiperidinium), containing different ionic liquid cations and same anionic units, have been synthesized and characterized. Single-crystal X-ray diffraction reveals that compounds 1 and 2 crystallize in the monoclinic space group of P21/c and P21, respectively. They both possess zero-dimensional ionic structures and exhibit phosphorescence at room temperature upon excitation of UV light (375 nm for 1, 390 nm for 2), with microsecond lifetime (24.13 μs for 1 and 95.37 μs for 2). Hirshfeld surface analysis has been utilized to visually exhibit the different packing motifs and intermolecular interactions in 1 and 2. The variation in ionic liquids makes compound 2 have a more rigid supramolecular structure than 1, resulting in a significant enhancement in photoluminescence quantum yield (PLQY), that is, 0.68% for 1 and 33.24% for 2. In addition, the ratio of the emission intensities for compounds 1 and 2 shows a correlation with temperature. This work provides new insight into luminescence enhancement and temperature sensing applications involving Bi-IOHMs.
Molecular Peptide Grafting as a Tool to Create Novel Protein Therapeutics
Authors: Komar Anton A.
Published: March 2023

The study of peptides (synthetic or corresponding to discrete regions of proteins) has facilitated the understanding of protein structure–activity relationships. Short peptides can also be used as powerful therapeutic agents. However, the functional activity of many short peptides is usually substantially lower than that of their parental proteins. This is (as a rule) due to their diminished structural organization, stability, and solubility often leading to an enhanced propensity for aggregation. Several approaches have emerged to overcome these limitations, which are aimed at imposing structural constraints into the backbone and/or sidechains of the therapeutic peptides (such as molecular stapling, peptide backbone circularization and molecular grafting), therefore enforcing their biologically active conformation and thus improving their solubility, stability, and functional activity. This review provides a short summary of approaches aimed at enhancing the biological activity of short functional peptides with a particular focus on the peptide grafting approach, whereby a functional peptide is inserted into a scaffold molecule. Intra-backbone insertions of short therapeutic peptides into scaffold proteins have been shown to enhance their activity and render them a more stable and biologically active conformation.
Substituent Effects in Tetrel Bonds Involving Aromatic Silane Derivatives: An ab initio Study
Authors: Burguera Sergi , Frontera Antonio , Bauzá Antonio
Published: March 2023

In this manuscript substituent effects in several silicon tetrel bonding (TtB) complexes were investigated at the RI-MP2/def2-TZVP level of theory. Particularly, we have analysed how the interaction energy is influenced by the electronic nature of the substituent in both donor and acceptor moieties. To achieve that, several tetrafluorophenyl silane derivatives have been substituted at the meta and para positions by several electron donating and electron withdrawing groups (EDG and EWG, respectively), such as –NH2, –OCH3, –CH3, –H, –CF3 and –CN substituents. As electron donor molecules, we have used a series of hydrogen cyanide derivatives using the same EDGs and EWGs. We have obtained the Hammett’s plots for different combinations of donors and acceptors and in all cases we have obtained good regression plots (interaction energies vs. Hammet’s σ parameter). In addition, we have used the electrostatic potential (ESP) surface analysis as well as the Bader’s theory of atoms in molecules (AIM) and noncovalent interaction plot (NCI plot) techniques to further characterize the TtBs studied herein. Finally, a Cambridge Structural Database (CSD) inspection was carried out, retrieving several structures where halogenated aromatic silanes participate in tetrel bonding interactions, being an additional stabilization force of their supramolecular architectures.
Infrared Spectroscopy as a Potential Diagnostic Tool for Medulloblastoma
Authors: Łach Kornelia , Kowal Aneta , Perek-Polnik Marta , Jakubczyk Paweł , Arthur Christopher J. , Bal Wioletta , Drogosiewicz Monika , Dembowska-Bagińska Bożenna , Grajkowska Wiesława , Cebulski Józef , Chaber Radosław
Published: March 2023

Introduction: Medulloblastoma (MB) is the most common malignant tumor of the central nervous system in childhood. FTIR spectroscopy provides a holistic view of the chemical composition of biological samples, including the detection of molecules such as nucleic acids, proteins, and lipids. This study evaluated the applicability of FTIR spectroscopy as a potential diagnostic tool for MB. Materials and methods: FTIR spectra of MB samples from 40 children (boys/girls: 31/9; age: median 7.8 years, range 1.5–21.5 years) treated in the Oncology Department of the Children’s Memorial Health Institute in Warsaw between 2010 and 2019 were analyzed. The control group consisted of normal brain tissue taken from four children diagnosed with causes other than cancer. Formalin-fixed and paraffin-embedded tissues were sectioned and used for FTIR spectroscopic analysis. The sections were examined in the mid-infrared range (800–3500 cm−1) by ATR-FTIR. Spectra were analysed using a combination of principal component analysis, hierarchical cluster analysis, and absorbance dynamics. Results: FTIR spectra in MB were significantly different from those of normal brain tissue. The most significant differences related to the range of nucleic acids and proteins in the region 800–1800 cm−1. Some major differences were also revealed in the quantification of protein conformations (α-helices, β-sheets, and others) in the amide I band, as well as in the absorbance dynamics in the 1714–1716 cm−1 range (nucleic acids). It was not, however, possible to clearly distinguish between the various histological subtypes of MB using FTIR spectroscopy. Conclusions: MB and normal brain tissue can be distinguished from one another to some extent using FTIR spectroscopy. As a result, it may be used as a further tool to hasten and enhance histological diagnosis.
One−Step Synthesis of a Non−Precious−Metal Tris (Fe/N/F)−Doped Carbon Catalyst for Oxygen Reduction Reactions
Authors: Yang Huitian , Wu Hao , Yao Lei , Liu Siyan , Yang Lu , Lu Jieling , Peng Hongliang , Lin Xiangcheng , Cai Ping , Zhang Huanzhi , Xu Fen , Zhang Kexiang , Sun Lixian
Published: March 2023

Advancements in inexpensive, efficient, and durable oxygen reduction catalysts is important for maintaining the sustainable development of fuel cells. Although doping carbon materials with transition metals or heteroatomic doping is inexpensive and enhances the electrocatalytic performance of the catalyst, because the charge distribution on its surface is adjusted, the development of a simple method for the synthesis of doped carbon materials remains challenging. Here, a non−precious−metal tris (Fe/N/F)−doped particulate porous carbon material (21P2−Fe1−850) was synthesized by employing a one−step process, using 2−methylimidazole, polytetrafluoroethylene, and FeCl3 as raw materials. The synthesized catalyst exhibited a good oxygen reduction reaction performance with a half−wave potential of 0.85 V in an alkaline medium (compared with 0.84 V of commercial Pt/C). Moreover, it had better stability and methanol resistance than Pt/C. This was mainly attributed to the effect of the tris (Fe/N/F)−doped carbon material on the morphology and chemical composition of the catalyst, thereby enhancing the catalyst’s oxygen reduction reaction properties. This work provides a versatile method for the gentle and rapid synthesis of highly electronegative heteroatoms and transition metal co−doped carbon materials.
TiO2-Modified Montmorillonite-Supported Porous Carbon-Immobilized Pd Species Nanocomposite as an Efficient Catalyst for Sonogashira Reactions
Authors: Chen Yuli , Sun Kailang , Zhang Taojun , Zhou Jie , Liu Yonghong , Zeng Minfeng , Ren Xiaorong , Feng Ruokun , Yang Zhen , Zhang Peng , Wang Baoyi , Cao Xingzhong
Published: March 2023

In this study, a combination of the porous carbon (PCN), montmorillonite (MMT), and TiO2 was synthesized into a composite immobilized Pd metal catalyst (TiO2-MMT/PCN@Pd) with effective synergism improvements in catalytic performance. The successful TiO2-pillaring modification for MMT, derivation of carbon from the biopolymer of chitosan, and immobilization of Pd species for the prepared TiO2-MMT/PCN@Pd0 nanocomposites were confirmed using a combined characterization with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N2 adsorption–desorption isotherms, high-resolution transition electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. It was shown that the combination of PCN, MMT, and TiO2 as a composite support for the stabilization of the Pd catalysts could synergistically improve the adsorption and catalytic properties. The resultant TiO2-MMT80/PCN20@Pd0 showed a high surface area of 108.9 m2/g. Furthermore, it exhibited moderate to excellent activity (59–99% yield) and high stability (recyclable 19 times) in the liquid–solid catalytic reactions, such as the Sonogashira reactions of aryl halides (I, Br) with terminal alkynes in organic solutions. The positron annihilation lifetime spectroscopy (PALS) characterization sensitively detected the development of sub-nanoscale microdefects in the catalyst after long-term recycling service. This study provided direct evidence for the formation of some larger-sized microdefects during sequential recycling, which would act as leaching channels for loaded molecules, including active Pd species.
Tunable Electromagnetic and Microwave Absorption Properties of Magnetic FeNi3 Alloys
Authors: Zheng Yu , Wu Mei , Qian Congyi , Jin Yuxin , Xiao Wei , Liang Xiaohui
Published: March 2023

Magnetic materials have a very broad application prospect in the field of microwave absorption, among which soft magnetic materials become the focus of magnetic materials research because of their high saturation magnetization and low coercivity. FeNi3 alloy has been widely used in soft magnetic materials because of its excellent ferromagnetism and electrical conductivity. In this work, FeNi3 alloy was prepared by the liquid reduction method. The effect of the filling ratio of FeNi3 alloy on the electromagnetic properties of absorbing materials was studied. It is found that the impedance matching ability of FeNi3 alloy is better when the filling ratio is 70 wt% than that of other samples with different filling ratios (30–60 wt%), showing better microwave absorption characteristics. When the matching thickness is 2.35 mm, the minimum reflection loss (RL) of FeNi3 alloy with a 70 wt% filling ratio reaches −40.33 dB, and the effective absorption bandwidth is 5.5 GHz. When the matching thickness is between 2 and 3 mm, the effective absorption bandwidth ranges from 7.21 GHz to 17.81 GHz, almost covering the whole X and Ku bands (8–18 GHz). The results show that FeNi3 alloy has adjustable electromagnetic properties and microwave absorption properties with different filling ratios, which is conducive to selecting excellent microwave absorption materials.
Enhanced Piezoelectricity and Thermal Stability of Electrostrain Performance in BiFeO3-Based Lead-Free Ceramics
Authors: Shi Hongwei , Li Kai , Li Feng , Ma Jianxing , Tu Yubing , Long Mingsheng , Lu Yilin , Gong Weiping , Wang Chunchang , Shan Lei
Published: March 2023

BiFeO3–based ceramics possess an advantage over large spontaneous polarization and high Curie temperature, and are thus widely explored in the field of high–temperature lead–free piezoelectrics and actuators. However, poor piezoelectricity/resistivity and thermal stability of electrostrain make them less competitive. To address this problem, (1 − x) (0.65BiFeO3–0.35BaTiO3)–xLa0.5Na0.5TiO3 (BF–BT–xLNT) systems are designed in this work. It is found that piezoelectricity is significantly improved with LNT addition, which is contributed by the phase boundary effect of rhombohedral and pseudocubic phase coexistence. The small–signal and large–signal piezoelectric coefficient (d33 and d33*) peaks at x = 0.02 with 97 pC/N and 303 pm/V, respectively. The relaxor property and resistivity are enhanced as well. This is verified by Rietveld refinement, dielectric/impedance spectroscopy and piezoelectric force microscopy (PFM) technique. Interestingly, a good thermal stability of electrostrain is obtained at x = 0.04 composition with fluctuation η = 31% (Smax'−SRTSRT×100%), in a wide temperature range of 25–180 °C, which is considered as a compromise of negative temperature dependent electrostrain for relaxors and the positive one for ferroelectric matrix. This work provides an implication for designing high–temperature piezoelectrics and stable electrostrain materials.
Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis
Authors: Gao Yan , Hu Xiaowen , Wang Dandan , Jiang Jie , Li Minghui , Qing Ying , Yang Xuhan , Zhang Juan , Zhang Yue , Wan Chunling
Published: March 2023

Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (rAA = −0.577, p < 0.01; rω-6 LCPUFA = −0.626, p < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (ORAA = 0.986, ORGLA = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia.
Consumption of Coffee and Tea Is Associated with Macular Retinal Nerve Fiber Layer Thickness: Results from the UK Biobank
Authors: Yuan Yixiong , Bulloch Gabriella , Zhang Shiran , Chen Yanping , Yang Shaopeng , Wang Wei , Zhu Zhuoting , He Mingguang
Published: March 2023

Coffee and tea drinking are thought to be protective for the development and progression of neurodegenerative disorders. This study aims to investigate associations between coffee and tea consumption with macular retinal nerve fiber layer (mRNFL) thickness, a marker of neurodegeneration. After quality control and eligibility screening, 35,557 out of 67,321 United Kingdom (UK) Biobank participants from six assessment centers were included in this cross-sectional study. In the touchscreen questionnaire, participants were asked how many cups of coffee and tea were consumed daily on average over the last year. Self-reported coffee and tea consumption were divided into four categories including 0 cup/day, 0.5–1 cups/day, 2–3 cups/day, and ≥4 cups/day, respectively. The mRNFL thickness was measured by the optical coherence tomography (Topcon 3D OCT-1000 Mark II) and automatically analyzed by segmentation algorithms. After adjusting for covariates, coffee consumption was significantly associated with an increased mRNFL thickness (β = 0.13, 95% CI = 0.01~0.25), which was more prominent in those who drank 2~3 cups coffee per day (β = 0.16, 95% CI = 0.03~0.30). The mRNFL thickness was also significantly increased in tea drinkers (β = 0.13, 95% CI = 0.01~0.26), especially for those who drank more than 4 cups of tea per day (β = 0.15, 95% CI = 0.01~0.29). The positive associations with mRNFL thickness, indicating that both coffee and tea consumptions had likely neuroprotective potentials. Causal links and underlying mechanisms for these associations should be explored further.
Quercetin Inhibits Hephaestin Expression and Iron Transport in Intestinal Cells: Possible Role of PI3K Pathway
Authors: Ramavath Hanuma Naik , Konda Venu , Pullakhandam Raghu
Published: March 2023

Previous studies demonstrated that quercetin, a polyphenolic compound, inhibits the transport of iron by down-regulation of ferroportin (FPN1), an iron export protein. We have previously demonstrated that activation of the PI3K signaling pathway by zinc stimulates the intestinal iron uptake and transport by stimulating the expression of iron regulatory protein 2 (IRP2) dependent divalent metal iron transporter 1 (DMT1, apical iron transporter) expression and caudal-related homeobox transcription factor 2 (CDX2) dependent hephaestin (HEPH, basolateral ferroxidase required for iron oxidation) expression, respectively. Since polyphenols are antagonists of the PI3K pathway, we hypothesized that quercetin might inhibit basolateral iron transport via the down-regulation of hephaestin (HEPH). Here in we investigated the effect of quercetin on iron uptake, transport, and expression of iron transporters in intestinal cells. In differentiated Caco-2 cells grown on permeable supports, quercetin inhibited the basolateral iron transport while increasing the iron uptake, possibly due to higher cellular retention. Further, quercetin down-regulated the protein and mRNA expression of HEPH and FPN1 but not that of IRP2 or DMT1. In addition, quercetin also abrogated the zinc-induced Akt, CDX2 phosphorylation, and HEPH expression. Together these results suggest that inhibition of iron transport by quercetin is mediated via the down-regulation of CDX2-dependent HEPH expression via inhibition of the PI3K pathway.
Oral Treatment with the Extract of Euterpe oleracea Mart. Improves Motor Dysfunction and Reduces Brain Injury in Rats Subjected to Ischemic Stroke
Authors: Teixeira Leonan Lima , Alencar Helma Maria Negrão da Silva , Ferreira Luan Oliveira , Rodrigues João Cleiton Martins , de Souza Rafael Dias , Celestino Pinto Laine , Muto Nilton Akio , Rogez Hervé , Martins-Filho Arnaldo Jorge , Joia de Mello Vanessa , Hamoy Moises , Costa Edmar Tavares da , Lopes Dielly Catrina Favacho
Published: March 2023

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.
Mediterranean Diet and Lung Function in Adults Current Smokers: A Cross-Sectional Analysis in the MEDISTAR Project
Authors: Catalin Roxana-Elena , Martin-Lujan Francisco , Salamanca-Gonzalez Patricia , Palleja-Millan Meritxell , Villalobos Felipe , Santigosa-Ayala Antoni , Pedret Anna , Valls-Zamora Rosa M. , Sola Rosa ,   on behalf of the MEDISTAR Research Group Investigators
Published: March 2023

Background: Previous studies have shown that adherence to the Mediterranean Diet (MeDi) has a positive impact on lung function in subjects with lung disease. In subjects free of respiratory diseases, but at risk, this association is not yet well established. Methods: Based on the reference data from the MEDISTAR clinical trial (Mediterranean Diet and Smoking in Tarragona and Reus; ISRCTN 03.362.372), an observational study was conducted with 403 middle-aged smokers without lung disease, treated at 20 centres of primary care in Tarragona (Catalonia, Spain). The degree of MeDi adherence was evaluated according to a 14-item questionnaire, and adherence was defined in three groups (low, medium, and high). Lung function were assessed by forced spirometry. Logistic regression and linear regression models were used to analyse the association between adherence to the MeDi and the presence of ventilatory defects. Results: Globally, the pulmonary alteration prevalence (impaired FEV1 and/or FVC) was 28.8%, although it was lower in participants with medium and high adherence to the MeDi, compared to those with a low score (24.2% and 27.4% vs. 38.5%, p = 0.004). Logistic regression models showed a significant and independent association between medium and high adherence to the MeDi and the presence of altered lung patterns (OR 0.467 [95%CI 0.266, 0.820] and 0.552 [95%CI 0.313, 0.973], respectively). Conclusions: MeDi adherence is inversely associated with the risk impaired lung function. These results indicate that healthy diet behaviours can be modifiable risk factors to protect lung function and reinforce the possibility of a nutritional intervention to increase adherence to MeDi, in addition to promoting smoking cessation.
Use of Caffeine-Containing Energy Drinks by Japanese Middle School Students: A Cross-Sectional Study of Related Factors
Authors: Yamasaki Satoko , Kawasaki Hiromi , Cui Zhengai
Published: March 2023

Excessive consumption of caffeine negatively affects individuals’ health. Therefore, we studied the use of energy drinks and the conditions associated with it among Japanese secondary school students. Participants were 236 students in grades 7–9 who completed anonymous questionnaires at home in July 2018. We measured the basic attributes and dietary, sleeping, and exercise habits. We used Chi-squared tests to compare differences between users and non-users of energy drinks. Logistic regression analyses were used to elucidate the complex association between the variables. The results showed that boys were more willing to consume energy drinks than girls. The reasons were ‘feeling fatigued’, ‘needing to stay awake’, ‘for curiosity’, and ‘to quench one’s thirst’. Among boys, the following were associated with the use of EDs. Buying their own snacks , not understanding nutritional labels on foods, high caffeinated beverage intake, late bed-times on weekdays, always waking up at about the same time, and weight. Health guidance is needed to prevent overconsumption and dependence on energy drinks. The cooperation of parents and teachers is needed to achieve these goals.
Relationships between Obesity, Exercise Preferences, and Related Social Cognitive Theory Variables among Breast Cancer Survivors
Authors: Brown Nashira I. , Pekmezi Dorothy W. , Oster Robert A. , Courneya Kerry S. , McAuley Edward , Ehlers Diane K. , Phillips Siobhan M. , Anton Philip , Rogers Laura Q.
Published: March 2023

Breast cancer survivors with obesity have an increased risk of cancer recurrence, second malignancy, and comorbidities. Though physical activity (PA) interventions are needed, investigation of the relationships between obesity and factors influencing PA program aspects among cancer survivors remain understudied. Thus, we conducted a cross-sectional study examining associations amongst baseline body mass index (BMI), PA program preferences, PA, cardiorespiratory fitness, and related social cognitive theory variables (self-efficacy, exercise barriers interference, social support, positive and negative outcome expectations) from a randomized controlled PA trial with 320 post-treatment breast cancer survivors. BMI was significantly correlated with exercise barriers interference (r = 0.131, p = 0.019). Higher BMI was significantly associated with preference to exercise at a facility (p = 0.038), lower cardiorespiratory fitness (p < 0.001), lower walking self-efficacy (p < 0.001), and higher negative outcome expectations (p = 0.024), independent of covariates (comorbidity score, Western Ontario and McMaster Universities osteoarthritis index score, income, race, education). Those with class I/II obesity reported a higher negative outcome expectations score compared with class III. Location, walking self-efficacy, barriers, negative outcome expectations, and fitness should be considered when designing future PA programs among breast cancer survivors with obesity.
Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD—A Randomized Controlled Trial
Authors: Yang Liu L. , Stiernborg Miranda , Skott Elin , Xu Jingjing , Wu Yujiao , Landberg Rikard , Arefin Samsul , Kublickiene Karolina , Millischer Vincent , Nilsson Ida A. K. , Schalling Martin , Giacobini MaiBritt , Lavebratt Catharina
Published: March 2023

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.
Atypical Staphylococcal Septic Arthritis in a Native Hip: A Case Report and Review
Authors: Glassman Ira , Nguyen Kevin H. , Booth Michelle , Minasyan Marine , Cappadona Abby , Venketaraman Vishwanath
Published: March 2023

Septic arthritis is a synovial fluid and joint tissue infection with significant morbidity and mortality risk if not diagnosed and treated promptly. The most common pathogen to cause septic arthritis is Staphylococcus aureus, a Gram-positive bacterium. Although diagnostic criteria are in place to guide the diagnosis of staphylococcal septic arthritis, there is a lack of adequate sensitivity and specificity. Some patients present with atypical findings which make it difficult to diagnose and treat in time. In this paper, we present the case of a patient with an atypical presentation of recalcitrant staphylococcal septic arthritis in a native hip complicated by uncontrolled diabetes mellitus and tobacco usage. We review current literature on diagnosing S. aureus septic arthritis, novel diagnostic technique performance to guide future research and assist clinical suspicion, and current S. aureus vaccine development for at-risk patients.
Serotypes, Antibiotic Susceptibility, Genotypic Virulence Profiles and SpaA Variants of Erysipelothrix rhusiopathiae Strains Isolated from Pigs in Poland
Authors: Dec Marta , Łagowski Dominik , Nowak Tomasz , Pietras-Ożga Dorota , Herman Klaudia
Published: March 2023

The aim of the study was phenotypic and genotypic characterization of Erysipelothrix rhusiopathiae strains isolated from diseased pigs in Poland and comparison of the SpaA (Surface protective antigen A) sequence of wild-type strains with the sequence of the R32E11 vaccine strain. The antibiotic susceptibility of the isolates was assessed using the broth microdilution method. Resistance genes, virulence genes, and serotype determinants were detected using PCR. The gyrA and spaA amplicons were sequenced to determine nonsynonymous mutations. The E. rhusiopathiae isolates (n = 14) represented serotypes 1b (42.8%), 2 (21.4%), 5 (14.3%), 6 (7.1%), 8 (7.1%), and N (7.1%). All strains were susceptible to β-lactams, macrolides and florfenicol. One isolate showed resistance to lincosamides and tiamulin, and most strains were resistant to tetracycline and enrofloxacin. High MIC values of gentamicin, kanamycin, neomycin, trimethoprim, trimethoprim/sulfadiazine, and rifampicin were recorded for all isolates. Phenotypic resistance was correlated with the presence of the tetM, int-Tn, lasE, and lnuB genes. Resistance to enrofloxacin was due to a mutation in the gyrA gene. All strains contained the spaA gene and several other genes putatively involved in pathogenesis (nanH.1, nanH.2, intl, sub, hlyA, fbpA, ERH_1356, cpsA, algI, rspA and rspB) Seven variants of the SpaA protein were found in the tested strains, and a relationship between the structure of SpaA and the serotype was noted. E. rhusiopathiae strains occurring in pigs in Poland are diverse in terms of serotype and SpaA variant and differ antigenically from the R32E11 vaccine strain. Beta-lactam antibiotics, macrolides, or phenicols should be the first choice for treatment of swine erysipelas in Poland. However, due to the small number of tested strains, this conclusion should be approached with caution.
Dissemination of Clinical Acinetobacter baumannii Isolate to Hospital Environment during the COVID-19 Pandemic
Authors: Pustijanac Emina , Hrenović Jasna , Vranić-Ladavac Mirna , Močenić Martina , Karčić Natalie , Lazarić Stefanović Lorena , Hrstić Irena , Lončarić Jasenka , Šeruga Musić Martina , Drčelić Marina , Majstorović Dijana , Kovačić Ines
Published: March 2023

The aim of this study was to find the source of Acinetobacter baumannii in the intensive care unit (ICU) after an outbreak during the coronavirus disease 2019 (COVID-19) pandemic, as there was no A. baumannii detected on usually screened susceptible surfaces. The screening of the ICU environment was done in April 2021 when eleven different samples were taken. One A. baumannii isolate was recovered from the air conditioner and was compared with four clinical A. baumannii isolates obtained from patients hospitalized in January 2021. Isolates were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), minimum inhibitory concentrations (MICs) were determined, and the multilocus sequence typing (MLST) was performed. The molecular identification of A. baumannii isolates as ST208, the presence of the same blaOXA-23 carbapenemase gene, and the same antibiotic susceptibility profile suggest that the isolate recovered from the air conditioner is the same as the isolates recovered from hospitalized patients. The environmental isolate was recovered three months later than the clinical isolates, emphasizing the ability of A. baumannii to survive on dry abiotic surfaces. The air conditioner in the clinical environment is an important but undoubtedly neglected source of A. baumannii outbreaks, hence, frequent disinfection of hospital air conditioners with appropriate disinfectants is mandatory to mitigate the circulation of A. baumannii between patients and the hospital environment.
First Morphological and Molecular Identification of Demodex injai in Golden Jackal (Canis aureus Linnaeus, 1758) in Romania
Authors: Morariu Sorin , Morariu Florica , Marin Ana-Maria , Moraru Maria Monica Florina , Popovici Dan-Cornel , Imre Mirela , Igna Violeta , Mederle Narcisa
Published: March 2023

Demodicosis is one of the most important external parasitic diseases found in carnivores. Three species of the Demodex mite inhabit the skin of dogs and related species, D. canis being the most prevalent. This paper describes the first case of infestation with D. injai in a golden jackal in Romania. An emaciated golden jackal female body found in Timiș County, western Romania, was examined at Parasitology Department of Faculty of Veterinary Medicine, Timișoara. The gross lesions were present on different regions of the body: feet, tail, axillary and inguinal areas, and skin folds as well, consisting of erythema, extensive severe alopecia with lichenification, seborrhea, and scaling. In order to establish diagnosis, microscopic examination of skin scrapes, trichogram (hair plucking), acetate tape test (impression), fungal culture, and PCR were performed. Both microscopic measurements and PCR analysis have confirmed the presence of D. injai.
One Health—Key to Adequate Intervention Measures against Zoonotic Risks
Authors: Thal Dana A. , Mettenleiter Thomas C.
Published: March 2023

Zoonotic diseases are a heterogenous group of infections transmittable between humans and vertebrate animal species. Globally, endemic and emerging zoonoses are responsible for high social and economic costs. Due to the particular positioning of zoonoses at the human-animal-environment interface, zoonotic disease control is an integral part of One Health, which recognizes the close link between human, animal and ecosystem health. During recent years, the validity of the One Health approach has been recognized by academia and policy makers. However, gaps are still evident, particularly in the implementation of the concept as a unifying, integrated approach for different sectors and disciplines for the control of zoonoses. For example, while cooperation between human and veterinary medicine has made significant progress, networking with environmental sciences leaves room for improvement. Examination of individual intervention measures can help to gain valuable insights for future projects, and help to identify existing gaps. This is also a task for the One Health High-Level Expert Panel, which was established by WHO, OIE, FAO and UNEP to give science-based strategic advice on One Health measures. Overall, we should aim to learn from current situations, and to identify the best practice examples available, to continuously develop and improve One Health concepts for the control of zoonoses.
Solid Lipid Nanoparticles: Multitasking Nano-Carriers for Cancer Treatment
Authors: German-Cortés Júlia , Vilar-Hernández Mireia , Rafael Diana , Abasolo Ibane , Andrade Fernanda
Published: March 2023

Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.
Anionic and Ampholytic High-Amylose Starch Derivatives as Excipients for Pharmaceutical and Biopharmaceutical Applications: Structure-Properties Correlations
Authors: Labelle Marc-André , Ispas-Szabo Pompilia , Tajer Salma , Xiao Yong , Barbeau Benoît , Mateescu Mircea Alexandru
Published: March 2023

Many chemical modifications of starch are realized in organic (mostly methanol) phase, allowing high degrees of substitution (DS). Some of these materials are used as disintegrants. To expand the usage of starch derivative biopolymers as drug delivery system, various starch derivatives obtained in aqueous phase were evaluated with the aim to identify materials and procedures which would generate multifunctional excipients providing gastro-protection for controlled drug delivery. Chemical, structural and thermal characteristics of anionic and ampholytic High Amylose Starch (HAS) derivatives under powder (P), tablet (T) and film (F) forms were evaluated by X-ray Diffraction (XRD), Fourier Transformed Infrared (FTIR) and thermogravimetric analysis (TGA) methods and correlated with the behavior of tablets and films in simulated gastric and intestinal media. At low DS, the HAS carboxymethylation (CMHAS) in aqueous phase, generated tablets and films that were insoluble at ambient conditions. The CMHAS filmogenic solutions, with a lower viscosity, were easier to cast and gave smooth films without the use of plasticizer. Correlations were found between structural parameters and the properties of starch excipients. Compared to other starch modification procedures, the aqueous modification of HAS generated tunable multifunctional excipients that may be recommended for tablets and functional coatings for colon-targeted formulations.
Nanocarriers for the Delivery of Neuroprotective Agents in the Treatment of Ocular Neurodegenerative Diseases
Authors: Patel Chirag , Pande Sonal , Sagathia Vrunda , Ranch Ketan , Beladiya Jayesh , Boddu Sai , Jacob Shery , Al-Tabakha Moawia , Hassan Nageeb , Shahwan Moyad
Published: March 2023

Retinal neurodegeneration is considered an early event in the pathogenesis of several ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and glaucoma. At present, there is no definitive treatment to prevent the progression or reversal of vision loss caused by photoreceptor degeneration and the death of retinal ganglion cells. Neuroprotective approaches are being developed to increase the life expectancy of neurons by maintaining their shape/function and thus prevent the loss of vision and blindness. A successful neuroprotective approach could prolong patients’ vision functioning and quality of life. Conventional pharmaceutical technologies have been investigated for delivering ocular medications; however, the distinctive structural characteristics of the eye and the physiological ocular barriers restrict the efficient delivery of drugs. Recent developments in bio-adhesive in situ gelling systems and nanotechnology-based targeted/sustained drug delivery systems are receiving a lot of attention. This review summarizes the putative mechanism, pharmacokinetics, and mode of administration of neuroprotective drugs used to treat ocular disorders. Additionally, this review focuses on cutting-edge nanocarriers that demonstrated promising results in treating ocular neurodegenerative diseases.
Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development
Authors: Simón Jon Ander , Utomo Emilia , Pareja Félix , Collantes María , Quincoces Gemma , Otero Aarón , Ecay Margarita , Domínguez-Robles Juan , Larrañeta Eneko , Peñuelas Iván
Published: March 2023

The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I− took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.
Multifunctional Mesoporous Silica-Coated Gold Nanorods Mediate Mild Photothermal Heating-Enhanced Gene/Immunotherapy for Colorectal Cancer
Authors: Li Meirong , Yang Jingyu , Yao Xinhuang , Li Xiang , Xu Zhourui , Tang Shiqi , Sun Bangxu , Lin Suxia , Yang Chengbin , Liu Jia
Published: March 2023

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the world. It is urgent to search for safe and effective therapies to address the CRC crisis. The siRNA-based RNA interference targeted silencing of PD-L1 has extensive potential in CRC treatment but is limited by the lack of efficient delivery vectors. In this work, the novel cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs)/siPD-L1 co-delivery vectors AuNRs@MS/CpG ODN@PEG-bPEI (ASCP) were successfully prepared by two-step surface modification of CpG ODNs-loading and polyethylene glycol-branched polyethyleneimine-coating around mesoporous silica-coated gold nanorods. ASCP promoted dendritic cells (DCs) maturation by delivering CpG ODNs, exhibiting excellent biosafety. Next, mild photothermal therapy (MPTT) mediated by ASCP killed tumor cells and released tumor-associated antigens, further promoting DC maturation. Furthermore, ASCP exhibited mild photothermal heating-enhanced performance as gene vectors, resulting in an increased PD-L1 gene silencing effect. Enhanced DCs maturity and enhanced PD-L1 gene silencing significantly promoted the anti-tumor immune response. Finally, the combination of MPTT and mild photothermal heating-enhanced gene/immunotherapy effectively killed MC38 cells, leading to strong inhibition of CRC. Overall, this work provided new insights into the design of mild photothermal/gene/immune synergies for tumor therapy and may contribute to translational nanomedicine for CRC treatment.
Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability
Authors: Hirsch Edit , Nacsa Márió , Pantea Eszter , Szabó Edina , Vass Panna , Domján Júlia , Farkas Attila , Nyíri Zoltán , Eke Zsuzsanna , Vigh Tamás , Andersen Sune Klint , Verreck Geert , Marosi György János , Nagy Zsombor Kristóf
Published: March 2023

The aim of this study was to develop antisense oligonucleotide tablet formulations using high-speed electrospinning. Hydroxypropyl-beta-cyclodextrin (HPβCD) was used as a stabilizer and as an electrospinning matrix. In order to optimize the morphology of the fibers, electrospinning of various formulations was carried out using water, methanol/water (1:1), and methanol as solvents. The results showed that using methanol could be advantageous due to the lower viscosity threshold for fiber formation enabling higher potential drug loadings by using less excipient. To increase the productivity of electrospinning, high-speed electrospinning technology was utilized and HPβCD fibers containing 9.1% antisense oligonucleotide were prepared at a rate of ~330 g/h. Furthermore, to increase the drug content of the fibers, a formulation with a 50% drug loading was developed. The fibers had excellent grindability but poor flowability. The ground fibrous powder was mixed with excipients to improve its flowability, which enabled the automatic tableting of the mixture by direct compression. The fibrous HPβCD–antisense oligonucleotide formulations showed no sign of physical or chemical degradation over the 1-year stability study, which also shows the suitability of the HPβCD matrix for the formulation of biopharmaceuticals. The obtained results demonstrate possible solutions for the challenges of electrospinning such as scale-up and downstream processing of the fibers.
Gene Therapy for Regenerative Medicine
Authors: Hosseinkhani Hossein , Domb Abraham J. , Sharifzadeh Ghorbanali , Nahum Victoria
Published: March 2023

The development of biological methods over the past decade has stimulated great interest in the possibility to regenerate human tissues. Advances in stem cell research, gene therapy, and tissue engineering have accelerated the technology in tissue and organ regeneration. However, despite significant progress in this area, there are still several technical issues that must be addressed, especially in the clinical use of gene therapy. The aims of gene therapy include utilising cells to produce a suitable protein, silencing over-producing proteins, and genetically modifying and repairing cell functions that may affect disease conditions. While most current gene therapy clinical trials are based on cell- and viral-mediated approaches, non-viral gene transfection agents are emerging as potentially safe and effective in the treatment of a wide variety of genetic and acquired diseases. Gene therapy based on viral vectors may induce pathogenicity and immunogenicity. Therefore, significant efforts are being invested in non-viral vectors to enhance their efficiency to a level comparable to the viral vector. Non-viral technologies consist of plasmid-based expression systems containing a gene encoding, a therapeutic protein, and synthetic gene delivery systems. One possible approach to enhance non-viral vector ability or to be an alternative to viral vectors would be to use tissue engineering technology for regenerative medicine therapy. This review provides a critical view of gene therapy with a major focus on the development of regenerative medicine technologies to control the in vivo location and function of administered genes.