bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Noble-Metal-Free Mo2C/CdIn2S4 Heterojunction Composites with Elevated Carrier Separation for Photocatalytic Hydrogen Production
Authors: Qiu Hong , Ma Xiaohui , Fan Hongxia , Fan Yueyan , Li Yajie , Zhou Hualei , Li Wenjun
Published: March 2023

Molybdenum-based cocatalyst being used to construct heterojunctions for efficient photocatalytic H2 production is a promising research hotspot. In this work, CdIn2S4 was successfully closely supported on bulk Mo2C via the hydrothermal method. Based on their matching band structures, they formed a Type Ⅰ heterojunction after the combination of Mo2C (1.1 eV, −0.27 V, 0.83 V) and CdIn2S4 (2.3 eV, −0.74 V, 1.56 V). A series of characterizations proved that the heterojunction composite had higher charge separation efficiency compared to a single compound. Meanwhile, Mo2C in heterojunction could act as an active site for hydrogen production. The photocatalytic H2 production activity of the heterojunction composites was significantly improved, and the maximum activity was up to 1178.32 μmmol h−1 g−1 for 5Mo2C/CdIn2S4 composites. 5Mo2C/CdIn2S4 heterojunction composites possess excellent durability in three cycles (loss of 6%). Additionally, the mechanism of increased activity for composites was also investigated. This study provides a guide to designing noble-metal-free photocatalyst for highly efficient photocatalytic H2 evolution.
Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles
Authors: Elsayim Rasha , Aloufi Abeer S. , Modafer Yosra , Eltayb Wafa Ali , Alameen Alaa Alnoor , Abdurahim Samah Awad
Published: March 2023

To prevent the rapidly increasing prevalence of bacterial resistance, it is crucial to discover new antibacterial agents. The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been associated with a higher mortality rate in gulf union countries and worldwide. Compared to physical and chemical approaches, green zinc oxide nanoparticle (ZnO-NP) synthesis is thought to be significantly safer and more ecofriendly. The present study used molecular dynamics (MD) to examine how ZnO-NPs interact with porin protein (GLO21), a target of β-lactam antibiotics, and then tested this interaction in vitro by determining the zone of inhibition (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), as well as the alteration of KPC’s cell surface. The nanoparticles produced were characterized by UV-Vis spectroscopy, zetasizer, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). In silico investigation was conducted using a variety of computational techniques, including Autodock Vina for protein and ligand docking and Desmond for MD simulation. The candidate ligands that interact with the GLO21 protein were biosynthesized ZnO-NPs, meropenem, imipenem, and cefepime. Analysis of MD revealed that the ZnO-NPs had the highest log P value (−9.1 kcal/mol), which indicates higher permeability through the bacterial surface, followed by cefepime (−7.9 kcal/mol), meropenem (−7.5 kcal/mol), and imipenem (−6.4 kcal/mol). All tested compounds and ZnO-NPs possess similar binding sites of porin proteins. An MD simulation study showed a stable system for ZnO-NPs and cefepime, as confirmed by RMSD and RMSF values during 100 ns trajectories. The test compounds were further inspected for their intersection with porin in terms of hydrophobic, hydrogen, and ionic levels. In addition, the stability of these bonds were measured by observing the protein–ligand contact within 100 ns trajectories. ZnO-NPs showed promising results for fighting KPC, represented in MIC (0.2 mg/mL), MBC (0.5 mg/mL), and ZI (24 mm diameter). To draw the conclusion that ZnO-NP is a potent antibacterial agent and in order to identify potent antibacterial drugs that do not harm human cells, further in vivo studies are required.
Integrating Untargeted and Targeted Metabolomics Coupled with Pathway Analysis Reveals Muscle Disorder in Osteoporosis on Orchiectomized Mice
Authors: Ge Fei , Wei Ziheng , Che Yanting , Qian Qingqing , Song Jinfei , Zhao Hongxia , Wu Si , Dong Xin
Published: March 2023

Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.
Supermolecule—Drug Conjugates Based on Acid-Degradable Polyrotaxanes for pH-Dependent Intracellular Release of Doxorubicin
Authors: Tamura Atsushi , Osawa Mamoru , Yui Nobuhiko
Published: March 2023

Doxorubicin (DOX)-conjugated acid-degradable polyrotaxanes (PRXs) were designed as supramolecular drug carriers capable of releasing drugs in acidic cellular environments. Acid-degradable PRXs composed of α-cyclodextrin (α-CD) as a cyclic molecule, poly(ethylene glycol) (PEG) as a polymer axis, and N-triphenylmethyl (N-Trt) groups as an acid-labile stopper molecules were synthesized and DOX was conjugated with the threaded α-CDs in the PRXs. Because the acid-induced cleavage of N-Trt groups in PRXs leads to PRX dissociation, the DOX-modified α-CDs were released under acidic conditions (pH 5.0). The cytotoxicity of DOX-conjugated PRXs in colon-26 cells revealed significant cell death for DOX-conjugated PRXs after 48 h of treatment. Confocal laser scanning microscopy (CLSM) analysis revealed that the fluorescence signals derived from DOX-conjugated PRXs were observed in cellular nuclei after 48 h, suggesting that the DOX-modified α-CDs were released and accumulated in cellular nuclei. These results confirmed that acid-degradable PRXs can be utilized as drug carriers capable of releasing drug-modified α-CDs in acidic lysosomes and eliciting cytotoxicity. Overall, acid-degradable PRXs represent a promising supramolecular framework for the delivery and intracellular release of drug-modified α-CDs, and PRX–drug conjugates are expected to contribute to the development of pH-responsive drug carriers for cancer therapy.
Comparative Study of Molecular Descriptors of Pent-Heptagonal Nanostructures Using Neighborhood M-Polynomial Approach
Authors: Xavier D. Antony , Ghani Muhammad Usman , Imran Muhammad , Nair A. Theertha , Varghese Eddith Sarah , Baby Annmaria
Published: March 2023

In this article, a novel technique to evaluate and compare the neighborhood degree molecular descriptors of two variations of the carbon nanosheet C5C7(a,b) is presented. The conjugated molecules follow the graph spectral theory, in terms of bonding, non-bonding and antibonding Ruckel molecular orbitals. They are demonstrated to be immediately determinable from their topological characteristics. The effort of chemical and pharmaceutical researchers is significantly increased by the need to conduct numerous chemical experiments to ascertain the chemical characteristics of such a wide variety of novel chemicals. In order to generate novel cellular imaging techniques and to accomplish the regulation of certain cellular mechanisms, scientists have utilized the attributes of nanosheets such as their flexibility and simplicity of modification, out of which carbon nanosheets stand out for their remarkable strength, chemical stability, and electrical conductivity. With efficient tools like polynomials and functions that can forecast compound features, mathematical chemistry has a lot to offer. One such approach is the M-polynomial, a fundamental polynomial that can generate a significant number of degree-based topological indices. Among them, the neighborhood M-polynomial is useful in retrieving neighborhood degree sum-based topological indices that can help in carrying out physical, chemical, and biological experiments. This paper formulates the unique M-polynomial approach which is used to derive and compare a variety of neighborhood degree-based molecular descriptors and the corresponding entropy measures of two variations of pent-heptagonal carbon nanosheets. Furthermore, a regression analysis on these descriptors has also been carried out which can further help in the prediction of various properties of the molecule.
Recent Advances in Mycotoxin Determination in Fish Feed Ingredients
Authors: Vardali Sofia , Papadouli Christina , Rigos George , Nengas Ioannis , Panagiotaki Panagiota , Golomazou Eleni
Published: March 2023

Low-cost plant-based sources used in aquaculture diets are prone to the occurrence of animal feed contaminants, which may in certain conditions affect the quality and safety of aquafeeds. Mycotoxins, a toxic group of small organic molecules produced by fungi, comprise a frequently occurring plant-based feed contaminant in aquafeeds. Mycotoxin contamination can potentially cause significant mortality, reduced productivity, and higher disease susceptibility; thus, its timely detection is crucial to the aquaculture industry. The present review summarizes the methodological advances, developed mainly during the past decade, related to mycotoxin detection in aquafeed ingredients, namely analytical, chromatographic, and immunological methodologies, as well as the use of biosensors and spectroscopic methods which are becoming more prevalent. Rapid and accurate mycotoxin detection is and will continue to be crucial to the food industry, animal production, and the environment, resulting in further improvements and developments in mycotoxin detection techniques.
Interactions between Beer Compounds and Human Salivary Proteins: Insights toward Astringency and Bitterness Perception
Authors: Gonçalves Leonor , Jesus Mónica , Brandão Elsa , Magalhães Paulo , Mateus Nuno , Freitas Victor de , Soares Susana
Published: March 2023

Beer is one of the most consumed beverages worldwide with unique organoleptic properties. Bitterness and astringency are well-known key features and, when perceived with high intensity, could lead to beer rejection. Most studies on beer astringency and bitterness use sensory assays and fail to study the molecular events that occur inside the oral cavity responsible for those perceptions. This work focused on deepening this knowledge based on the interaction of salivary proteins (SP) and beer phenolic compounds (PCs) and their effect toward these two sensory attributes. The astringency and bitterness of four different beers were assessed by a sensory panel and were coupled to the study of the SP changes and PC profile characterization of beers. The human SP content was measured before (basal) and after each beer intake using HPLC analysis. The beers’ PC content and profile were determined using Folin–Ciocalteu and LC-MS spectrometry, respectively. The results revealed a positive correlation between PCs and astringency and bitterness and a negative correlation between SP changes and these taste modalities. Overall, the results revealed that beers with higher PC content (AAL and IPA) are more astringent and bitter than beers with a lower PC content (HL and SBO). The correlation results suggested that an increase in whole SP content, under stimulation, should decrease astringency and bitterness perception. No correlation was found between the changes in specific families of SP and astringency and bitterness perception.
Incorporation of Moringa oleifera Leaf Extract in Yoghurts to Mitigate Children’s Malnutrition in Developing Countries
Authors: Gomes Sandra M. , Leitão Anabela , Alves Arminda , Santos Lúcia
Published: March 2023

Moringa oleifera, which is rich in bioactive compounds, has numerous biological activities and is a powerful source of antioxidants and nutrients. Therefore, M. oleifera can be incorporated into food to mitigate children’s malnutrition. In this work, the bioactive compounds were extracted from M. oleifera leaf powder by ultrasound-assisted solid-liquid extraction. The antioxidant and antimicrobial activities and the phenolic composition of the extract were evaluated. The extract presented a total phenolic content of 54.5 ± 16.8 mg gallic acid equivalents/g and IC50 values of 133.4 ± 12.3 mg/L for DPPH and 60.0 ± 9.9 mg/L for ABTS. Catechin, chlorogenic acid, and epicatechin were the main phenolics identified by HPLC-DAD. The obtained extract and M. oleifera leaf powder were incorporated into yoghurts and their physicochemical and biological properties were studied. The incorporation of M. oleifera did not impair the yoghurts’ stability over eight weeks when compared to both negative and positive controls. The extract presented higher stability regarding syneresis but lower stability regarding TPC compared to the powder. Also, the fortified yoghurts presented higher antioxidant properties than the negative control. These findings highlight the potential use of M. oleifera powder and extract as natural additives to produce fortified foods that can be used in the mitigation of malnutrition.
Natural Plasmodium falciparum Infection Stimulates Human Antibodies to MSP1 Epitopes Identified in Mice Infection Models upon Non-Natural Modified Peptidomimetic Vaccination
Authors: Rodríguez Zully Johana , Melo Fredy Leonardo , Torres Angela , Agrawal Nikhil , Cortés-Vecino Jesús Alfredo , Lozano José Manuel
Published: March 2023

(1) Background: Malaria, a vector-borne infectious disease, is caused by parasites of the Plasmodium genus, responsible for increased extreme morbidity and mortality rates. Despite advances in approved vaccines, full protection has not yet been achieved upon vaccination, thus the development of more potent and safe immuno-stimulating agents for malaria prevention is a goal to be urgently accomplished. We have focused our research on a strategy to identify Plasmodium spp. epitopes by naturally acquired human antibodies and rodent malaria infection models immunized with site-directed non-natural antigens. (2) Methods: Some predictive algorithms and bioinformatics tools resembling different biological environments, such as phagosome-lysosome proteolytic degradation, affinity, and the high frequency of malaria-resistant and -sensitive HLA-II alleles were regarded for the proper selection of epitopes and potential testing. Each epitope’s binding profile to both host cells and HLA-II molecules was considered for such initial screening. (3) Results: Once selected, we define each epitope-peptide to be synthesized in terms of size and hydrophobicity, and introduced peptide-bond surrogates and non-natural amino acids in a site-directed fashion, and then they were produced by solid-phase peptide synthesis. Molecules were then tested by their antigenic and immunogenic properties compared to human sera from Colombian malaria-endemic areas. The antigenicity and protective capacity of each epitope-peptide in a rodent infection model were examined. The ability of vaccinated mice after being challenged with P. berghei ANKA and P. yoelii 17XL to control malaria led to the determination of an immune stimulation involving Th1 and Th1/Th2 mechanisms. In silico molecular dynamics and modeling provided some interactions insights, leading to possible explanations for protection due to immunization. (4) Conclusions: We have found evidence for proposing MSP1-modified epitopes to be considered as neutralizing antibody stimulators that are useful as probes for the detection of Plasmodium parasites, as well as for sub-unit components of a site-directed designed malaria vaccine candidate.
Delivery of Active Peptides by Self-Healing, Biocompatible and Supramolecular Hydrogels
Authors: Shariati Pour Seyedeh Rojin , Oddis Sara , Barbalinardo Marianna , Ravarino Paolo , Cavallini Massimiliano , Fiori Jessica , Giuri Demetra , Tomasini Claudia
Published: March 2023

Supramolecular and biocompatible hydrogels with a tunable pH ranging from 5.5 to 7.6 lead to a wide variety of formulations useful for many different topical applications compatible with the skin pH. An in vitro viability/cytotoxicity test of the gel components demonstrated that they are non-toxic, as the cells continue to proliferate after 48 h. An analysis of the mechanical properties demonstrates that the hydrogels have moderate strength and an excellent linear viscoelastic range with the absence of a proper breaking point, confirmed with thixotropy experiments. Two cosmetic active peptides (Trifluoroacetyl tripeptide-2 and Palmitoyl tripeptide-5) were successfully added to the hydrogels and their transdermal permeation was analysed with Franz diffusion cells. The liquid chromatography-mass spectrometry (HPLC-MS) analyses of the withdrawn samples from the receiving solutions showed that Trifluoroacetyl tripeptide-2 permeated in a considerable amount while almost no transdermal permeation of Palmitoyl tripeptide-5 was observed.
Metrological Protocols for Reaching Reliable and SI-Traceable Size Results for Multi-Modal and Complexly Shaped Reference Nanoparticles
Authors: Feltin Nicolas , Crouzier Loïc , Delvallée Alexandra , Pellegrino Francesco , Maurino Valter , Bartczak Dorota , Goenaga-Infante Heidi , Taché Olivier , Marguet Sylvie , Testard Fabienne , Artous Sébastien , Saint-Antonin François , Salzmann Christoph , Deumer Jérôme , Gollwitzer Christian , Koops Richard , Sebaïhi Noham , Fontanges Richard , Neuwirth Matthias , Bergmann Detlef , Hüser Dorothee , Klein Tobias , Hodoroaba Vasile-Dan
Published: March 2023

The study described in this paper was conducted in the framework of the European nPSize project (EMPIR program) with the main objective of proposing new reference certified nanomaterials for the market in order to improve the reliability and traceability of nanoparticle size measurements. For this purpose, bimodal populations as well as complexly shaped nanoparticles (bipyramids, cubes, and rods) were synthesized. An inter-laboratory comparison was organized for comparing the size measurements of the selected nanoparticle samples performed with electron microscopy (TEM, SEM, and TSEM), scanning probe microscopy (AFM), or small-angle X-ray scattering (SAXS). The results demonstrate good consistency of the measured size by the different techniques in cases where special care was taken for sample preparation, instrument calibration, and the clear definition of the measurand. For each characterization method, the calibration process is described and a semi-quantitative table grouping the main error sources is proposed for estimating the uncertainties associated with the measurements. Regarding microscopy-based techniques applied to complexly shaped nanoparticles, data dispersion can be observed when the size measurements are affected by the orientation of the nanoparticles on the substrate. For the most complex materials, hybrid approaches combining several complementary techniques were tested, with the outcome being that the reliability of the size results was improved.
Release and MMP-9 Inhibition Assessment of Dental Adhesive Modified with EGCG-Encapsulated Halloysite Nanotubes
Authors: Alhijji Saleh , Platt Jeffrey A. , Alhotan Abdulaziz , Labban Nawaf , Bottino Marco C. , Windsor L. Jack
Published: March 2023

Degradation of the collagen fibrils at the dentin–resin interface by the enzymatic activity of matrix metalloproteinases (MMPs) has been known to permit some dental restoration complications, such as microleakage, secondary caries, and, ultimately, restoration failures. This study aimed to evaluate a modified adhesive by adding an MMP inhibitor from green tea extract with and without nanotube encapsulation to sustain the drug release. Epigallocatechin-3-gallate (EGCG) and Halloysite nanotubes (HNTs) were prepared to produce three variant combinations of modified adhesive (EGCG, EGCG-encapsulated HNT, and EGCG-free HNT). The drug loading efficiency and EGCG release over time were evaluated using UV-vis spectrometry. MMP-mediated β-casein (BCN) cleavage rate assays were used to determine the ability of the EGCG in eluates of the adhesive to inhibit MMP-9 activities. For up to 8 weeks, HNT encapsulation reduced release to a statistically significant level. MMP-mediated β-casein cleavage rate assays showed a significant decrease for the EGCG groups compared to the non-EGCG adhesive groups. Furthermore, the use of HNT for EGCG encapsulation to modify a dental adhesive helped slow down the rate of EGCG release without impacting its MMP inhibitory capabilities, which may help to maintain the dentin–resin interface’s integrity over the long term after dental restoration placement.
3D Nanocomposite with High Aspect Ratio Based on Polyaniline Decorated with Silver NPs: Synthesis and Application as Electrochemical Glucose Sensor
Authors: Vasileva Anna A. , Mamonova Daria V. , Mikhailovskii Vladimir , Petrov Yuri V. , Toropova Yana G. , Kolesnikov Ilya E. , Leuchs Gerd , Manshina Alina A.
Published: March 2023

In this paper, we present a new methodology for creating 3D ordered porous nanocomposites based on anodic aluminum oxide template with polyaniline (PANI) and silver NPs. The approach includes in situ synthesis of polyaniline on templates of anodic aluminum oxide nanomembranes and laser-induced deposition (LID) of Ag NPs directly on the pore walls. The proposed method allows for the formation of structures with a high aspect ratio of the pores, topological ordering and uniformity of properties throughout the sample, and a high specific surface area. For the developed structures, we demonstrated their effectiveness as non-enzymatic electrochemical sensors on glucose in a concentration range crucial for medical applications. The obtained systems possess high potential for miniaturization and were applied to glucose detection in real objects—laboratory rat blood plasma.
Comparison of Weight Reduction, Change in Parameters and Safety of a Very Low Carbohydrate Diet in Comparison to a Low Carbohydrate Diet in Obese Japanese Subjects with Metabolic Disorders
Authors: Kikuchi Takako , Kushiyama Akifumi , Yanai Miho , Kashiwado Chieko , Seto Takeshi , Kasuga Masato
Published: March 2023

Recently, low-carbohydrate diets (LCDs) have gained worldwide attention. LCDs are potentially effective for Japanese overweight and obese individuals with metabolic disorders. However, few randomized trials of LCDs have focused on the difference between LCDs and VLCDs. We conducted a randomized, prospective study of 42 Japanese, obese adults aged 28–65 years to evaluate the efficacy and safety of LCD and VLCD. To ensure the accuracy of the study, all test meals were provided, and compliance was checked using a smartphone app. Body composition measurements and blood tests were performed before and after the 2-month dietary intervention. The results showed that both methods significantly reduced body weight and fat, and also improved lipid abnormalities and liver function. In the current study, the reductions in weight and fat were comparable. The results of a questionnaire at the end of the study indicated that the LCD was easier to carry out than the VLCD, suggesting that the LCD was sustainable. The present study was unique in that it was a randomized, prospective study of Japanese subjects and that accurate data were obtained by providing meals.
Healthy Diet, Polygenic Risk Score, and Upper Gastrointestinal Cancer Risk: A Prospective Study from UK Biobank
Authors: Liu Wenmin , Wang Tianpei , Zhu Meng , Jin Guangfu
Published: March 2023

Dietary and genetic factors are considered to be associated with UGI cancer risk. However, examinations of the effect of healthy diet on UGI cancer risk and the extent to which healthy diet modifies the impact of genetic susceptibility on UGI cancer remains limited. Associations were analyzed through Cox regression of the UK Biobank data (n = 415,589). Healthy diet, based on “healthy diet score,” was determined according to fruit, vegetables, grains, fish, and meat consumption. We compared adherence to healthy diet and the risk of UGI cancer. We also constructed a UGI polygenic risk score (UGI-PRS) to assess the combined effect of genetic risk and healthy diet. For the results high adherence to healthy diet reduced 24% UGI cancer risk (HR high-quality diet: 0.76 (0.62–0.93), p = 0.009). A combined effect of high genetic risk and unhealthy diet on UGI cancer risk was observed, with HR reaching 1.60 (1.20–2.13, p = 0.001). Among participants with high genetic risk, the absolute five-year incidence risk of UGI cancer was significantly reduced, from 0.16% to 0.10%, by having a healthy diet. In summary, healthy diet decreased UGI cancer risk, and individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy diet.
Regulation of Paracellular Fluxes of Amino Acids by Claudin-8 in Normal Mouse Intestinal MCE301 Cells
Authors: Okamoto Ema , Matsuda Shunsuke , Yoshino Yuta , Morikawa Yoshifumi , Suenami Koichi , Tabuchi Yoshiaki , Matsunaga Toshiyuki , Ikari Akira
Published: March 2023

The ingested proteins are catabolized to di/tri-peptides and amino acids (AAs), which are absorbed through various transporters in the small intestinal and colonic epithelial cells. Tight junctions (TJs) are formed between neighboring cells and restrict paracellular fluxes to mineral ions and aqueous molecules. However, it is unknown whether the TJs are implicated in the control of paracellular fluxes to AAs. The paracellular permeability is controlled by claudins (CLDNs), which comprise a family of over 20 members. Here, we found that CLDN8 expression is decreased by AAs deprivation in normal mouse colon-derived MCE301 cells. The reporter activity of CLDN8 was not significantly changed by AAs deprivation, whereas the stability of CLDN8 protein was decreased. MicroRNA analysis showed that AAs deprivation increases the expression of miR-153-5p which targets CLDN8. The AAs deprivation-induced decline of CLDN8 expression was reversed by a miR-153-5p inhibitor. The CLDN8 silencing enhanced the paracellular fluxes to AAs, especially middle molecular size AAs. The expression levels of colonic CLDN8 and miR-153-5p in aged mice were lower and higher than those in young mice, respectively. We suggest that AAs deprivation downregulates CLDN8-dependent barrier function, mediated by the elevation of miR-153-5p expression in the colon, in order to enhance the AAs absorption.
Assessment of Protein Nutritional Quality of Novel Hairless Canary Seed in Comparison to Wheat and Oat Using In Vitro Static Digestion Models
Authors: L’Hocine Lamia , Achouri Allaoua , Mason Emily , Pitre Mélanie , Martineau-Côté Delphine , Sirois Stéphane , Karboune Salwa
Published: March 2023

Hairless canary seed (Phalaris canariensis L.) is a novel true cereal that is now approved for human consumption in Canada and the United States. This true cereal grain has higher protein content (22%) than oat (13%) and wheat (16%) and represents a valuable source of plant proteins. Assessment of canary seed protein quality is therefore essential to evaluate its digestibility and ability to provide sufficient amounts of essential amino acids for human requirements. In this study, the protein nutritional quality of four hairless canary seed varieties (two brown and two yellow) were evaluated in comparison to oat and wheat. The assessment of anti-nutrients contents (phytate, trypsin inhibitor activity, and polyphenols) showed that brown canary seed varieties had the highest content in phytate and oat the highest in polyphenols. Trypsin inhibitor level was comparable among studied cereals, but slightly higher in the brown canary seed Calvi variety. In regard to protein quality, canary seed had a well-balanced amino acid profile and was particularly high in tryptophan, an essential amino acid normally lacking in cereals. The in vitro protein digestibility of canary seeds as determined by both the pH-drop and INFOGEST (international network of excellence on the fate of food in the gastrointestinal tract) protocols appears slightly lower than wheat and higher than oat. The yellow canary seed varieties showed better overall digestibility than the brown ones. For all studied cereal flours, the limiting amino acid was lysine. The calculated in vitro PDCAAS (protein digestibility corrected amino acid score) and DIAAS (digestible indispensable amino acid score) were higher for the yellow C05041 cultivar than the brown Bastia, similar to those of wheat, but lower than those of oat proteins. This study demonstrates the feasibility and utility of in vitro human digestion models for the assessment of protein quality for comparison purpose.
Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?
Authors: Martinelli Romina P. , Rayego-Mateos Sandra , Alique Matilde , Márquez-Expósito Laura , Tejedor-Santamaria Lucia , Ortiz Alberto , González-Parra Emilio , Ruiz-Ortega Marta
Published: March 2023

As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.
Co-Immunization Efficacy of Recombinant Antigens against Rhipicephalus microplus and Hyalomma anatolicumTick Infestations
Authors: Parthasarathi Balasamudram Chandrasekhar , Kumar Binod , Bhure S. K. , Sharma Anil Kumar , Manisha  , Nagar Gaurav , Kumar Sachin , Nandi Abhijit , Manjunathachar Haranahally Vasanthachar , Chigure Gajanan M. , Shakya Mukesh , Sankar Muthu , Fuente José de la , Ghosh Srikant
Published: March 2023

The immunoprophylactic management of ticks is the most effective option to control tick infestations and counter spread the acaricide resistance problem worldwide. Several researchers reported an inconsistent efficacy of the single antigen-based immunization of hosts against different tick species. In the present study, to develop a multi-target immunization protocol, proteins from Rhipicephalus microplus BM86 and Hyalomma anatolicum subolesin (SUB) and tropomyosin (TPM) were targeted to evaluate the cross-protective potential. The sequence identities of the BM86, SUB, and TPM coding genes amongst Indian tick isolates of targeted species were 95.6–99.8%, 98.7–99.6%, and 98.9–99.9%, respectively, while at the predicted amino acid level, the identities were 93.2 to 99.5, 97.6 to 99.4, and 98.2 to 99.3%. The targeted genes were expressed in the eukaryotic expression system, pKLAC2-Kluyveromyces lactis, and 100 µg each of purified recombinant protein (Bm86-89 kDa, SUB-21 kDa, and TPM-36 kDa) mixed with adjuvant was injected individually through the intramuscular route at different sites of the body on days 0, 30, and 60 to immunize cross-bred cattle. Post-immunization, a statistically significant (p < 0.001) antibody response (IgG, IgG1, and IgG2) in comparison to the control, starting from 15 to 140 days, against each antigen was recorded. Following multi-antigen immunization, the animals were challenged twice with the larvae of R. microplus and H. anatolicum and theadults of H. anatolicum, and a significant vaccine efficacy of 87.2% and 86.2% against H. anatolicum larvae and adults, respectively, and 86.7% against R. microplus was obtained. The current study provides significant support to develop a multi-antigen vaccine against cattle tick species.
Simulation of Foot-and-Mouth Disease Spread and Effects of Mitigation Strategies to Support Veterinary Contingency Planning in Denmark
Authors: Conrady Beate , Mortensen Sten , Nielsen Søren Saxmose , Houe Hans , Calvo-Artavia Francisco Fernando , Ellis-Iversen Johanne , Boklund Anette
Published: March 2023

To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario 1), or in one specific livestock production system within each of the three species geographically distributed throughout Denmark (Scenario 2). When additional mitigation strategies were implemented on top of basic control strategies in the European foot-and-mouth disease spread model (EuFMDiS), no significant benefits were predicted in terms of the number of infected farms, the epidemic control duration, and the total economic cost. Further, the model results indicated that the choice of index herd, the resources for outbreak control, and the detection time of FMD significantly influenced the course of an epidemic. The present study results emphasise the importance of basic mitigation strategies, including an effective back-and-forward traceability system, adequate resources for outbreak response, and a high level of awareness among farmers and veterinarians concerning the detection and reporting of FMD at an early stage of an outbreak for FMD control in Denmark.
Benefits of a Wearable Cyborg HAL (Hybrid Assistive Limb) in Patients with Childhood-Onset Motor Disabilities: A 1-Year Follow-Up Study
Authors: Kuroda Mayumi Matsuda , Iwasaki Nobuaki , Mutsuzaki Hirotaka , Yoshikawa Kenichi , Takahashi Kazushi , Nakayama Tomohiro , Nakayama Junko , Takeuchi Ryoko , Mataki Yuki , Ohguro Haruka , Tomita Kazuhide
Published: March 2023

Rehabilitation robots have shown promise in improving the gait of children with childhood-onset motor disabilities. This study aimed to investigate the long-term benefits of training using a wearable Hybrid Assistive Limb (HAL) in these patients. Training using a HAL was performed for 20 min a day, two to four times a week, over four weeks (12 sessions in total). The Gross Motor Function Measure (GMFM) was the primary outcome measure, and the secondary outcome measures were gait speed, step length, cadence, 6-min walking distance (6MD), Pediatric Evaluation of Disability Inventory, and Canadian Occupational Performance Measure (COPM). Patients underwent assessments before the intervention, immediately after the intervention, and at 1-, 2-, 3-month and 1-year follow-ups. Nine participants (five males, four females; mean age: 18.9 years) with cerebral palsy (n = 7), critical illness polyneuropathy (n = 1), and encephalitis (n = 1) were enrolled. After training using HAL, GMFM, gait speed, cadence, 6MD, and COPM significantly improved (all p < 0.05). Improvements in GMFM were maintained one year after the intervention (p < 0.001) and in self-selected gait speed and 6MD three months after the intervention (p < 0.05). Training using HAL may be safe and feasible for childhood-onset motor disabilities and may maintain long-term improvements in motor function and walking ability.
Moroccan Experience of Targeted Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry
Authors: Meiouet Faïza , El Kabbaj Sâad , Abilkassem Rachid , Boemer François
Published: March 2023

Background: Expanded newborn screening using tandem mass spectrometry (MS/MS) for inborn errors of metabolism (IEM), such as organic acidemias (OAs), fatty acid oxidation disorders (FAODs), and amino acid disorders (AAs), is increasingly popular but has not yet been introduced in Africa. With this study, we aim to establish the disease spectrum and frequency of inborn errors of OAs, FAODs, and AAs in Morocco. Methods: Selective screening was performed among infants and children suspected to be affected with IEM between 2016 and 2021. Amino acids and acylcarnitines spotted on filter paper were analyzed using MS/MS. Results: Out of 1178 patients with a clinical suspicion, 137 (11.62%) were diagnosed with IEM, of which 121 (88.3%) patients suffered from amino acids disorders, 11 (8%) were affected by FAOD, and 5 (3.7%) by an OA. Conclusions: This study shows that various types of IEM are also present in Morocco. Furthermore, MS/MS is an indispensable tool for early diagnosis and management of this group of disorders.
Individual Treatment Trials—Do Experts Know and Use This Option to Improve the Treatability of Mucopolysaccharidosis?
Authors: Wiesinger Anna-Maria , Strobl Hannah , Lagler Florian B.
Published: March 2023

Mucopolysaccharidoses (MPS) are a group of rare, heterogeneous, lysosomal storage disorders. Patients show a broad spectrum of clinical features with a substantial unmet medical need. Individual treatment trials (ITTs) might be a valid, time- and cost-efficient way to facilitate personalized medicine in the sense of drug repurposing in MPS. However, this treatment option has so far hardly been used—at least hardly been reported or published. Therefore, we aimed to investigate the awareness and utilization of ITTs among MPS clinicians, as well as the potential challenges and innovative approaches to overcome key hurdles, by using an international expert survey on ITTs, namely, ESITT. Although 74% (20/27) were familiar with the concept of ITTs, only 37% (10/27) ever used it, and subsequently only 15% (2/16) published their results. The indicated hurdles of ITTs in MPS were mainly the lack of time and know-how. An evidence-based tool, which provides resources and expertise needed for high-quality ITTs, was highly appreciated by the vast majority (89%; 23/26). The ESITT highlights a serious deficiency of ITT implementation in MPS—a promising option to improve its treatability. Furthermore, we discuss the challenges and innovative approaches to overcome key barriers to ITTs in MPS.
Pharmacology and Emerging Therapies for Group 3 Pulmonary Hypertension Due to Chronic Lung Disease
Authors: Gonzales Janae , Fraidenburg Dustin R.
Published: March 2023

Pulmonary hypertension (PH) frequently complicates chronic lung disease and is associated with high morbidity and poor outcomes. Individuals with interstitial lung disease and chronic obstructive pulmonary disease develop PH due to structural changes associated with the destruction of lung parenchyma and vasculature with concurrent vasoconstriction and pulmonary vascular remodeling similar to what is observed in idiopathic pulmonary arterial hypertension (PAH). Treatment for PH due to chronic lung disease is largely supportive and therapies specific to PAH have had minimal success in this population with exception of the recently FDA-approved inhaled prostacyclin analogue treprostinil. Given the significant disease burden of PH due to chronic lung diseases and its associated mortality, a great need exists for improved understanding of molecular mechanisms leading to vascular remodeling in this population. This review will discuss the current understanding of pathophysiology and emerging therapeutic targets and potential pharmaceuticals.
Development of the 99mTc-Labelled SST2 Antagonist TECANT-1 for a First-in-Man Multicentre Clinical Study
Authors: Novak Doroteja , Janota Barbara , Hörmann Anton Amadeus , Sawicka Agnieszka , Kroselj Marko , Hubalewska-Dydejczyk Alicja , Fani Melpomeni , Mikolajczak Renata , Kolenc Petra , Decristoforo Clemens , Garnuszek Piotr
Published: March 2023

Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.
Evaluation of Pharmacobezoar Formation from Suspensions of Spray-Dried Amorphous Solid Dispersions: An MRI Study in Rats
Authors: Gierke Hannes , Mouchantat Susan , Berg Sabine , Grimm Michael , Hadlich Stefan , Kromrey Marie-Luise , Nolte Thomas , Pfrommer Teresa , Rönnpagel Vincent , Rump Adrian , Schaefer Kerstin , Willmann Ann-Cathrin , Weitschies Werner
Published: March 2023

Spray-dried amorphous solid dispersions of new chemical entities and pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were found to form solid agglomerates in the gastrointestinal tract of rodents after oral administration. These agglomerates, referring to descriptions of intra-gastrointestinal aggregated oral dosage forms termed pharmacobezoars, represent a potential risk for animal welfare. Previously, we introduced an in vitro model to assess the agglomeration potential of amorphous solid dispersions from suspensions and how it can be reduced. In this work, we investigated if the in vitro effective approach of viscosity enhancement of the vehicle used to prepare suspensions of amorphous solid dispersions could reduce the pharmacobezoar formation potential following repeated daily oral dosing to rats as well. The dose level of 2400 mg/kg/day used in the main study was determined in a dose finding study carried out in advance. In the dose finding study, MRI investigations were carried out at short time intervals to gain insights into the process of pharmacobezoar formation. Whereas MRI investigations underlined the importance of the forestomach for the formation of pharmacobezoars, viscosity enhancement of the vehicle reduced the incidence of pharmacobezoars, delayed the onset of pharmacobezoar formation and reduced the overall mass of pharmacobezoars found at necropsy.
A Review of the Benefits 3D Printing Brings to Patients with Neurological Diseases
Authors: Gander Christine , Shi Kejing , Nokhodchi Ali , Lam Matthew
Published: March 2023

This interdisciplinary review focuses on how flexible three-dimensional printing (3DP) technology can aid patients with neurological diseases. It covers a wide variety of current and possible applications ranging from neurosurgery to customizable polypill along with a brief description of the various 3DP techniques. The article goes into detail about how 3DP technology can aid delicate neurosurgical planning and its consequent outcome for patients. It also covers areas such as how the 3DP model can be utilized in patient counseling along with designing specific implants involved in cranioplasty and customization of a specialized instrument such as 3DP optogenetic probes. Furthermore, the review includes how a 3DP nasal cast can contribute to the development of nose-to-brain drug delivery along with looking into how bioprinting could be used for regenerating nerves and how 3D-printed drugs could offer practical benefits to patients suffering from neurological diseases via polypill.
Recent Preclinical and Clinical Progress in Liposomal Doxorubicin
Authors: Aloss Kenan , Hamar Peter
Published: March 2023

Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in research due to its high efficacy despite dose-limiting toxicities. Several strategies have been exploited to enhance the efficacy and safety profile of DOX. Liposomes are the most established approach. Despite the improvement in safety properties of liposomal encapsulated DOX (in Doxil and Myocet), the efficacy is not superior to conventional DOX. Functionalized (targeted) liposomes present a more effective system to deliver DOX to the tumor. Moreover, encapsulation of DOX in pH-sensitive liposomes (PSLs) or thermo-sensitive liposomes (TSLs) combined with local heating has improved DOX accumulation in the tumor. Lyso-thermosensitive liposomal DOX (LTLD), MM-302, and C225-immunoliposomal(IL)-DOX have reached clinical trials. Further functionalized PEGylated liposomal DOX (PLD), TSLs, and PSLs have been developed and evaluated in preclinical models. Most of these formulations improved the anti-tumor activity compared to the currently available liposomal DOX. However, the fast clearance, the optimization of ligand density, stability, and release rate need more investigations. Therefore, we reviewed the latest approaches applied to deliver DOX more efficiently to the tumor, preserving the benefits obtained from FDA-approved liposomes.
The Roles of Gibberellins in Regulating Leaf Development
Authors: Ritonga Faujiah Nurhasanah , Zhou Dandan , Zhang Yihui , Song Runxian , Li Cheng , Li Jingjuan , Gao Jianwei
Published: March 2023

Plant growth and development are correlated with many aspects, including phytohormones, which have specific functions. However, the mechanism underlying the process has not been well elucidated. Gibberellins (GAs) play fundamental roles in almost every aspect of plant growth and development, including cell elongation, leaf expansion, leaf senescence, seed germination, and leafy head formation. The central genes involved in GA biosynthesis include GA20 oxidase genes (GA20oxs), GA3oxs, and GA2oxs, which correlate with bioactive GAs. The GA content and GA biosynthesis genes are affected by light, carbon availability, stresses, phytohormone crosstalk, and transcription factors (TFs) as well. However, GA is the main hormone associated with BR, ABA, SA, JA, cytokinin, and auxin, regulating a wide range of growth and developmental processes. DELLA proteins act as plant growth suppressors by inhibiting the elongation and proliferation of cells. GAs induce DELLA repressor protein degradation during the GA biosynthesis process to control several critical developmental processes by interacting with F-box, PIFS, ROS, SCLl3, and other proteins. Bioactive GA levels are inversely related to DELLA proteins, and a lack of DELLA function consequently activates GA responses. In this review, we summarized the diverse roles of GAs in plant development stages, with a focus on GA biosynthesis and signal transduction, to develop new insight and an understanding of the mechanisms underlying plant development.