bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prognostic Utilities of Various Risk Factors for Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Kim Do Hyun , Kim Sung Won , Han Jae Sang , Kim Geun-Jeon , Basurrah Mohammed Abdullah , Hwang Se Hwan
Published: March 2023

Objective: To assess the prognostic utilities of various risk factors for laryngeal squamous cell carcinoma. Methods: Six databases were searched to January 2022. Hazard ratios for overall survival and disease-free survival were collected and study characteristics were recorded. The risk of bias was evaluated using the Newcastle–Ottawa scale. Results: Twenty-eight studies involving 32,128 patients were finally included. In terms of overall survival, older age, a history of alcohol consumption, a high Charlson comorbidity index score, a high TNM stage (III and IV), a high tumor stage (III and IV), nodal involvement, poor pathological differentiation, primary chemoradiotherapy and radiotherapy were associated with increased risks of death. In terms of disease-free survival, older age (≥60 years), TNM stages III and IV, tumor stages III and IV, supraglottic tumors, and nodal involvement all increased the risk of death. Conclusions: The TNM stage importantly predicts overall survival, and tumor location predicts the disease-free survival of patients with laryngeal squamous cell carcinoma. Of patients with risk factors, the Charlson comorbidity index usefully predicts overall survival.
How to Improve Non-Invasive Diagnosis of Endometriosis with Advanced Statistical Methods
Authors: Szubert Maria , Rycerz Aleksander , Wilczyński Jacek R.
Published: March 2023

Background and Objectives: Endometriosis is one of the most common gynecological disorders in women of reproductive age. Causing pelvic pain and infertility, it is considered one of the most serious health problems, being responsible for work absences or productivity loss. Its diagnosis is often delayed because of the need for an invasive laparoscopic approach. Despite years of studies, no single marker for endometriosis has been discovered. The aim of this research was to find an algorithm based on symptoms and laboratory tests that could diagnose endometriosis in a non-invasive way. Materials and Methods: The research group consisted of 101 women hospitalized for diagnostic laparoscopy, among which 71 had confirmed endometriosis. Data on reproductive history were collected in detail. CA125 (cancer antigen-125) level and VEGF1(vascular endothelial growth factor 1) were tested in blood samples. Among the used statistical methods, the LASSO regression—a new important statistical tool eliminating the least useful features—was the only method to have significant results. Results: Out of 19 features based on results of LASSO, 7 variables were chosen: body mass index, age of menarche, cycle length, painful periods, information about using contraception, CA125, and VEGF1. After multivariate logistic regression with a backward strategy, the three most significant features were evaluated. The strongest impact on endometriosis prediction had information about painful periods, CA125 over 15 u/mL, and the lowest BMI, with a sensitivity of 0.8800 and a specificity of 0.8000, respectively. Conclusions: Advanced statistical methods are crucial when creating non-invasive tests for endometriosis. An algorithm based on three easy features, including painful menses, BMI level, and CA125 concentration could have an important place in the non-invasive diagnosis of endometriosis. If confirmed in a prospective study, implementing such an algorithm in populations with a high risk of endometriosis will allow us to cover patients suspected of endometriosis with proper treatment.
Cell Adhesion Molecules in Schizophrenia Patients with Metabolic Syndrome
Authors: Boiko Anastasiia S. , Mednova Irina A. , Kornetova Elena G. , Semke Arkadiy V. , Bokhan Nikolay A. , Ivanova Svetlana A.
Published: March 2023

Metabolic syndrome (MetS) is a common comorbidity of schizophrenia and significantly shortens life expectancy of the patients. Intercellular (ICAM), vascular (VCAM), and neural (NCAM) cell adhesion molecules (CAMs) mediate neuroinflammatory processes, and their soluble forms (e.g., sICAM) in plasma are present in parallel with their cell-bound forms. In this study, their serum levels were examined in 211 white Siberian patients with paranoid schizophrenia (82 patients with and 129 without MetS according to the 2005 International Diabetes Federation criteria). Serum levels of CAMs were determined with Magpix and Luminex 200 (Luminex, Austin, TX, USA) using xMAP Technology. The level of sICAM-1 was significantly higher and that of sVCAM-1 significantly lower in patients with MetS compared to patients without MetS. Levels of NCAM did not differ between the groups. More pronounced Spearman’s correlations between CAMs, age, duration of schizophrenia, and body–mass index were observed among patients without MetS than among patients with MetS. Our results are consistent with MetS’s being associated with endothelial dysfunction along with other components of inflammation. Through these endothelial components of peripheral inflammatory processes, MetS might induce intracerebral neuroinflammatory changes, but further investigation is needed to confirm this.
An Improved Approach for Grasp Force Sensing and Control of Upper Limb Soft Robotic Prosthetics
Authors: Bayoumi Hazem , Awad Mohammed Ibrahim , Maged Shady A.
Published: March 2023

The following research proposes a closed loop force control system, which is implemented on a soft robotic prosthetic hand. The proposed system uses a force sensing approach that does not require any sensing elements to be embedded in the prosthetic’s fingers, therefore maintaining their monolithic structural integrity, and subsequently decreasing the cost and manufacturing complexity. This is achieved by embedding an aluminum test specimen with a full bridge strain gauge circuit directly inside the actuator’s housing rather than in the finger. The location of the test specimen is precisely at the location of the critical section of the bending moment on the actuator housing due to the tension in the driving tendon. Therefore, the resulting loadcell can acquire a signal proportional to the prosthetic’s grasping force. A PI controller is implemented and tested using this force sensing approach. The experiment design includes a flexible test object, which serves to visually demonstrate the force controller’s performance through the deformation that the test object experiences. Setpoints corresponding to “light”, “medium”, and “hard” grasps were tested with pinch, tripod, and full grasps and the results of these tests are documented in this manuscript. The developed controller was found to have an accuracy of ±2%. Additionally, the deformation of the test object increased proportionally with the given grasp force setpoint, with almost no deformation during the light grasp test, slight deformation during the medium grasp test, and relatively large deformation of the test object during the hard grasp test.
Correction: Latov, N. Campylobacter jejuni Infection, Anti-Ganglioside Antibodies, and Neuropathy. Microorganisms 2022, 10, 2139
Authors: Latov Norman
Published: March 2023

The authors wish to make the following corrections to this paper [...]
Meta-Analysis of the Effects of Biochar Application on the Diversity of Soil Bacteria and Fungi
Authors: Wang Mingyu , Yu Xiaoying , Weng Xiaohong , Zeng Xiannan , Li Mengsha , Sui Xin
Published: March 2023

Biochar is increasingly being used for soil improvement, but the effects on microbial diversity in soil are still ambiguous due to contrasting results reported in the literature. We conducted a meta-analysis to clarify the effect of biochar addition on soil bacterial and fungal diversity with an increase in Shannon or Chao1 index as the outcome. Different experimental setups, quantitative levels of biochar addition, various biochar source materials and preparation temperatures, and the effect of natural precipitation in field experiments were the investigated variables. From a total of 95 publications identified for analysis, 384 datasets for Shannon index and 277 datasets for Chao1 index were extracted that described the bacterial diversity in the soils, of which field experiments and locations in China dominated. The application of biochar in soil significantly increased the diversity of soil bacteria but it had no significant effect on the diversity of fungi. Of the different experimental setups, the largest increase in bacterial diversity was seen for field experiments, followed by pot experiments, but laboratory and greenhouse settings did not report a significant increase. In field experiments, natural precipitation had a strong effect, and biochar increased bacterial diversity most in humid conditions (mean annual precipitation, MAP > 800 mm), followed by semi-arid conditions (MAP 200–400 mm). Biochar prepared from herbaceous materials was more effective to increase bacterial diversity than other raw materials and the optimal pyrolysis temperature was 350–550 °C. Addition of biochar at various levels produced inconclusive data for Chao1 and Shannon indices, and its effect was less strong than that of the other assessed variables.
Editorial for Special Issue “Unleashing the Hidden Potential of Anaerobic Fungi”
Authors: Lebuhn Michael , Podmirseg Sabine Marie , Baier Urs
Published: March 2023

Anaerobic fungi (AF) of the phylum Neocallimastigomycota are a very peculiar group of microorganisms [...]
Study on the Pb2+ Consolidation Mechanism of Gangue-Based Cemented Backfill
Authors: Wang Hao , Wang Qi , Hao Yuxin , Wang Yingying , Ta Burui , Meng Jian
Published: March 2023

Coal mining produces a large amount of gangue that pollutes the environment, causing surface subsidence and damaging the groundwater systems. Backfill mining is an effective technology used to solve this problem, but there is a risk of polluting the groundwater due to the heavy metal ions present in the backfill material. Pb2+ has been determined to be a representative element because of its existence in coal gangue samples but not in fly ash. The risk of gangue-based cemented backfill causing groundwater pollution can be evaluated by studying the Pb2+ leaching from gangue under various conditions. When comparing the leaching amounts of Pb2+ from the coal gangue particles and the test blocks, it was found that cement filling has an obvious consolidation effect on the Pb2+ in coal gangue. The above process shows that cemented backfill has an obvious consolidation effect on the Pb2+ in gangue. The results of the theoretical analysis, X-ray, and SEM show that the consolidation mechanism can be divided into four modes: physical encapsulation, ion exchange, ion adsorption, and chemical reaction. The results are of great significance for revealing the leaching mechanism of the heavy metals in coal gangue, assessing the risk of heavy metal pollution in groundwater via gangue-cemented backfill, and improving the mining theory of the gangue-cemented filling and groundwater protection.
A Turn-On Lipid Droplet-Targeted Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Intracellular Carboxylesterases and Cell Viability Imaging
Authors: Li Chenglin , Li Sifan , Li Xinsheng , Yuan Tao , Xu Jialei , Gu Xixin , Hua Jianli
Published: March 2023

Carboxylesterases (CEs) play important physiological roles in the human body and are involved in numerous cellular processes. Monitoring CEs activity has great potential for the rapid diagnosis of malignant tumors and multiple diseases. Herein, we developed a new phenazine-based “turn-on” fluorescent probe DBPpys by introducing 4-bromomethyl-phenyl acetate to DBPpy, which can selectively detect CEs with a low detection limit (9.38 × 10−5 U/mL) and a large Stokes shift (more than 250 nm) in vitro. In addition, DBPpys can also be converted into DBPpy by carboxylesterase in HeLa cells and localized in lipid droplets (LDs), emitting bright near-infrared fluorescence under the irradiation of white light. Moreover, we achieved the detection of cell health status by measuring the intensity of NIR fluorescence after co-incubation of DBPpys with H2O2-pretreated HeLa cells, indicating that DBPpys has great potential applications for assessing CEs activity and cellular health.
Prediction of ADMET Properties of Anti-Breast Cancer Compounds Using Three Machine Learning Algorithms
Authors: Li Xinkang , Tang Lijun , Li Zeying , Qiu Dian , Yang Zhuoling , Li Baoqiong
Published: March 2023

In recent years, machine learning methods have been applied successfully in many fields. In this paper, three machine learning algorithms, including partial least squares-discriminant analysis (PLS-DA), adaptive boosting (AdaBoost), and light gradient boosting machine (LGBM), were applied to establish models for predicting the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET for short) properties, namely Caco-2, CYP3A4, hERG, HOB, MN of anti-breast cancer compounds. To the best of our knowledge, the LGBM algorithm was applied to classify the ADMET property of anti-breast cancer compounds for the first time. We evaluated the established models in the prediction set using accuracy, precision, recall, and F1-score. Compared with the performance of the models established using the three algorithms, the LGBM yielded most satisfactory results (accuracy > 0.87, precision > 0.72, recall > 0.73, and F1-score > 0.73). According to the obtained results, it can be inferred that LGBM can establish reliable models to predict the molecular ADMET properties and provide a useful tool for virtual screening and drug design researchers.
An Innovative Structural Rearrangement in Imine Palladacycle Metaloligand Chemistry: From Single-Nuclear to Double-Nuclear Pseudo-Pentacoordinated Complexes
Authors: al Janabi Basma , Reigosa Francisco , Alberdi Gemma , Ortigueira Juan M. , Vila José M.
Published: March 2023

Treatment of the double nuclear complex 1a, di-μ-cloro-bis[N-(4-formylbenzylidene)cyclohexylaminato-C6, N]dipalladium, with Ph2PCH2CH2)2PPh (triphos) and NH4PF6 gave the single nuclear species 2a, 1-N-(cyclohexylamine)-4-N-(formyl)palladium(triphos)(hexafluorophasphate). Reaction of 2a with Ph2PCH2CH2NH2 in refluxing chloroform via a condensation reaction of the amine and formyl groups to produce the C=N double bond, gave 3a, 1-N-(cyclohexylamine)-4- N-(diphenylphosphinoethylamine)palladium(triphos)(hexafluorophasphate); a potentially bidentate [N,P] metaloligand. However, attempts to coordinate a second metal by treatment of 3a with [PdCl2(PhCN)2] were to no avail. Notwithstanding, complexes 2a and 3a left to stand in solution spontaneously self-transformed to give in either case the double nuclear complex 10, 1,4-N,N-terephthalylidene(cyclohexilamine)-3,6-[bispalladium(triphos)]di(hexafluorophosphate), after undergoing further metalation of the phenyl ring, then bearing two mutually trans [Pd(Ph2PCH2CH2)2PPh)-P,P,P] moieties: an unprecedented and serendipitous result indeed. On the other hand, reaction of the double nuclear complex 1b, di-μ-cloro-bis[N-(3-formylbenzylidene)cyclohexylaminato-C6, N]dipalladium, with Ph2PCH2CH2)2PPh (triphos) and NH4PF6 gave the single nuclear species 2b, 1-N-(cyclohexylamine)-4-N-(formyl)palladium(triphos)(hexafluorophasphate), Treatment of 2b with H2O/glacial MeCOOH gave cleavage of the C=N double bond and of the Pd···N interaction, yielding 5b, isophthalaldehyde-6-palladium(triphos)hexafluorophosphate, which then reacted with Ph2P(CH2)3NH2 to yield complex 6b, N,N-(isophthalylidene(diphenylphosphinopropylamine)-6-(palladiumtriphos)di(hexafluorophosphate), with two pairs of non-coordinated nitrogen and phosphorus donor atoms. Treatment of 6b with [PdCl2(PhCN)2], [PtCl2(PhCN)2], or [PtMe2(COD)] gave the new double nuclear complexes 7b, 8b and 9b, palladiumdichloro-, platinumdichloro- and platinumdimethyl[N,N-(isophthalylidene(diphenylphosphinopropylamine)-6-(palladiumtriphos)(hexafluorophosphate)-P,P], respectively, showing the behavior of 6b as a palladated bidentate [P,P] metaloligand. The complexes were fully characterized by microanalysis, IR, 1H, and 31P NMR spectroscopies, as appropriate. The X-ray single-crystal analyses for compounds 10 and 5b have been previously described as the perchlorate salts by JM Vila et al.
Reconversion of Parahydrogen Gas in Surfactant-Coated Glass NMR Tubes
Authors: Chimenti Robert V. , Daley James , Sack James , Necsutu Jennifer , Whiting Nicholas
Published: March 2023

The application of parahydrogen gas to enhance the magnetic resonance signals of a diversity of chemical species has increased substantially in the last decade. Parahydrogen is prepared by lowering the temperature of hydrogen gas in the presence of a catalyst; this enriches the para spin isomer beyond its normal abundance of 25% at thermal equilibrium. Indeed, parahydrogen fractions that approach unity can be attained at sufficiently low temperatures. Once enriched, the gas will revert to its normal isomeric ratio over the course of hours or days, depending on the surface chemistry of the storage container. Although parahydrogen enjoys long lifetimes when stored in aluminum cylinders, the reconversion rate is significantly faster in glass containers due to the prevalence of paramagnetic impurities that are present within the glass. This accelerated reconversion is especially relevant for nuclear magnetic resonance (NMR) applications due to the use of glass sample tubes. The work presented here investigates how the parahydrogen reconversion rate is affected by surfactant coatings on the inside surface of valved borosilicate glass NMR sample tubes. Raman spectroscopy was used to monitor changes to the ratio of the (J: 0 → 2) vs. (J: 1 → 3) transitions that are indicative of the para and ortho spin isomers, respectively. Nine different silane and siloxane-based surfactants of varying size and branching structures were examined, and most increased the parahydrogen reconversion time by 1.5×–2× compared with equivalent sample tubes that were not treated with surfactant. This includes expanding the pH2 reconversion time from 280 min in a control sample to 625 min when the same tube is coated with (3-Glycidoxypropyl)trimethoxysilane.
Controllable Deposition of Bi onto Pd for Selective Hydrogenation of Acetylene
Authors: Kang Hongquan , Wu Jianzhou , Lou Baohui , Wang Yue , Zhao Yilin , Liu Juanjuan , Zou Shihui , Fan Jie
Published: March 2023

The rational regulation of catalyst active sites at atomic scale is a key approach to unveil the relationship between structure and catalytic performance. Herein, we reported a strategy for the controllable deposition of Bi on Pd nanocubes (Pd NCs) in the priority order from corners to edges and then to facets (Pd NCs@Bi). The spherical aberration-corrected scanning transmission electron microscopy (ac-STEM) results indicated that Bi2O3 with an amorphous structure covers the specific sites of Pd NCs. When only the corners and edges of the Pd NCs were covered, the supported Pd NCs@Bi catalyst exhibited an optimal trade-off between high conversion and selectivity in the hydrogenation of acetylene to ethylene under ethylene-rich conditions (99.7% C2H2 conversion and 94.3% C2H4 selectivity at 170 °C) with remarkable long-term stability. According to the H2-TPR and C2H4-TPD measurements, the moderate hydrogen dissociation and the weak ethylene adsorption are responsible for this excellent catalytic performance. Following these results, the selectively Bi-deposited Pd nanoparticle catalysts showed incredible acetylene hydrogenation performance, which provides a feasible perspective to design and develop highly selective hydrogenation catalysts for industrial applications.
Silica Nanoparticles in Xanthan Gum Solutions: Oil Recovery Efficiency in Core Flooding Tests
Authors: Buitrago-Rincon Dayan L. , Sadtler Véronique , Mercado Ronald A. , Roques-Carmes Thibault , Marchal Philippe , Muñoz-Navarro Samuel F. , Sandoval María , Pedraza-Avella Julio A. , Lemaitre Cécile
Published: March 2023

Polymer flooding is one of the enhanced oil recovery (EOR) methods that increase the macroscopic efficiency of the flooding process and enhanced crude oil recovery. In this study, the effect of silica nanoparticles (NP-SiO2) in xanthan gum (XG) solutions was investigated through the analysis of efficiency in core flooding tests. First, the viscosity profiles of two polymer solutions, XG biopolymer and synthetic hydrolyzed polyacrylamide (HPAM) polymer, were characterized individually through rheological measurements, with and without salt (NaCl). Both polymer solutions were found suitable for oil recovery at limited temperatures and salinities. Then, nanofluids composed of XG and dispersed NP-SiO2 were studied through rheological tests. The addition of nanoparticles was shown to produce a slight effect on the viscosity of the fluids, which was more remarkable over time. Interfacial tension tests were measured in water-mineral oil systems, without finding an effect on the interfacial properties with the addition of polymer or nanoparticles in the aqueous phase. Finally, three core flooding experiments were conducted using sandstone core plugs and mineral oil. The polymers solutions (XG and HPAM) with 3% NaCl recovered 6.6% and 7.5% of the residual oil from the core, respectively. In contrast, the nanofluid formulation recovered about 13% of the residual oil, which was almost double that of the original XG solution. The nanofluid was therefore more effective at boosting oil recovery in the sandstone core.
Surface Modification of Hollow Structure TiO2 Nanospheres for Enhanced Photocatalytic Hydrogen Evolution
Authors: Ning Gaomin , Zhang Yan , Shi Chunjing , Zhao Chen , Liu Mengmeng , Chang Fangfang , Gao Wenlong , Ye Sheng , Liu Jian , Zhang Jing
Published: March 2023

Engineering the surface structure of semiconductor is one of the most promising strategies for improving the separation and transfer efficiency of charge, which is a key issue in photocatalysis. Here, we designed and fabricated the C decorated hollow TiO2 photocatalysts (C–TiO2), in which 3-aminophenol-formaldehyde resin (APF) spheres were used as template and carbon precursor. It was determined that the C content can be easily controlled by calcinating the APF spheres with different time. Moreover, the synergetic effort between the optimal C content and the formed Ti–O–C bonds in C–TiO2 were determined to increase the light absorption and greatly promote the separation and transfer of charge in the photocatalytic reaction, which is verified from UV–vis, PL, photocurrent, and EIS characterizations. Remarkably, the activity of the C–TiO2 is 5.5-fold higher than that of TiO2 in H2 evolution. A feasible strategy for rational design and construction of surface-engineered hollow photocatalysts to improve the photocatalytic performance was provided in this study.
Elementary School-Aged Children’s and Parents’ Report of Health-Related Quality of Life and Relationships with Lifestyle Measures: A Cross-Sectional Study
Authors: Alanne Soili , Koivuniemi Ella , Löyttyniemi Eliisa , Laitinen Kirsi
Published: March 2023

Supporting a child’s health-promoting lifestyle is an investment in their future health and health-related quality of life (HRQoL). Particularly children with overweight and obesity may be at an increased risk of a poor HRQoL. Currently, a comprehensive evaluation of lifestyle factors and age in relation to HRQoL in healthy children and, further, separate child and parental proxy-reports of HRQoL are lacking. The aims of this cross-sectional study in Finland are to compare healthy elementary school-aged children’s and parents’ reports of the child‘s HRQoL, and to view them in relation to lifestyle markers. The HRQoL was measured with Pediatric Quality of Life InventoryTM 4.0, and the following lifestyle markers: leisure-time physical activity as MET, diet quality via a validated index (ES-CIDQ), sleeping time and screen time by questionnaires. Furthermore, age and BMI were recorded. Data were obtained from 270 primary school-aged children (6–13 years). Female gender, the child’s older age (8–13 years), high physical activity level and less screen time were strong predictors of a higher HRQoL in both the child’s and parental proxy-reports. Means to promote healthy lifestyles should be particularly targeted to young children, especially boys, and new ways to promote physical activity and other forms of free-time activities should be sought.
Analysis of Transfer of Tiamulin to Animal Tissue after Oral Administration: An Important Factor for Ensuring Food Safety and Environmental Protection
Authors: Ciucă Viviana Carmen , Rusănescu Carmen Otilia , Safta Victor Viorel
Published: March 2023

The administration of veterinary medicinal products containing tiamulin hydrogen fumarate (THF) leads to the appearance of the following residues in animal tissues: THF and metabolites that can be hydrolyzed to 8-α-hydroxymutilin. The marker residue for tiamulin, according to Regulation EEC 2377/90, is the sum of the metabolites that can be hydrolyzed to 8-α-hydroxymutilin. The main aim of this study was to analyze the depletion of tiamulin residues and metabolites that can be hydrolyzed to 8-α-hydroxymulinin by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in pig, rabbit and bird tissues after tiamulin administration and to determine minimum withdrawal times for products of animal origin intended for human consumption. Tiamulin was administered orally as follows: 12,000 µg/kg body weight/day for 7 days to pigs and rabbits and 20,000 µg tiamulin/kg body weight/day for 7 days to broiler chickens and turkeys. The values found for tiamulin marker residues were 3 times higher in liver than in muscle in pigs, 6 times in rabbits and 8–10 times in birds. The content of tiamulin residues in eggs from laying hens was below 1000 µg/kg at all times of analysis. The minimum withdrawal times for animal products intended for human consumption, resulting from this study, are 5 days for pigs, rabbits and turkeys, 3 days for broiler chickens and 0 days for eggs.
Derivatives of L-Ascorbic Acid in Emulgel: Development and Comprehensive Evaluation of the Topical Delivery System
Authors: Stolić Jovanović Aleksandra , Martinović Milica , Žugić Ana , Nešić Ivana , Tosti Tomislav , Blagojević Stevan , Tadić Vanja M.
Published: March 2023

The dual controlled release of emulgels makes them efficient drug delivery systems of increasing interest. The framework of this study was to incorporate selected L-ascorbic acid derivatives into emulgels. From the formulated emulgels, the release profiles of actives were evaluated considering their different polarities and concentrations, and consequently their effectiveness on the skin via a long-term in vivo study that lasted for 30 days was determined. Skin effects were assessed by measuring the electrical capacitance of the stratum corneum (EC), trans-epidermal water loss (TEWL), melanin index (MI) and skin pH. In addition, the sensory and textural properties of emulgel formulations were compared with each other. The changes in the rate of the release of the L-ascorbic acid derivatives were monitored using the Franz diffusion cells. The obtained data were statistically significant, and indicated an increase in the degree of hydration of the skin and skin whitening potential, while no significant changes in TEWL and pH values were detected. The consistency, firmness and stickiness of the emulgels were estimated by volunteers applying the established sensory evaluation protocol. In addition, it was revealed that the difference in hydrophilic/lipophilic properties of L-ascorbic acid derivatives influenced their release profiles without changing their textural characteristics. Therefore, this study highlighted emulgels as L-ascorbic acid suitable carrier systems and one of the promising candidates as novel drug delivery systems.
Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma
Authors: Oliveira Relton R. , Cintra Emílio R. , Sousa-Junior Ailton A. , Moreira Larissa C. , da Silva Artur C. G. , de Souza Ana Luiza R. , Valadares Marize C. , Carrião Marcus S. , Bakuzis Andris F. , Lima Eliana M.
Published: March 2023

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.
pH-Responsive and Mucoadhesive Nanoparticles for Enhanced Oral Insulin Delivery: The Effect of Hyaluronic Acid with Different Molecular Weights
Authors: Wang Shuangqing , Meng Saige , Zhou Xinlei , Gao Zhonggao , Piao Ming Guan
Published: March 2023

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA–PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA–PDM–INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA–PDM–INS, M-HA–PDM–INS, H-HA–PDM–INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA–PDM–INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA–PDM–INS was investigated. The release of INS from H-HA–PDM–INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA–PDM–INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA–PDM–INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA–PDM–INS, regardless of the MW of HA, was demonstrated using CCK-8 and live–dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA–PDM–INS, M-HA–PDM–INS, and H-HA–PDM–INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA–PDM–INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.
Immunotherapy Resumption/Rechallenge in Melanoma Patients after Toxicity: Do We Have Another Chance?
Authors: España Fernandez Sofia , Sun Chen , Solé-Blanch Carme , Boada Aram , Martínez-Cardús Anna , Manzano José Luis
Published: March 2023

Introduction: Immune checkpoint inhibitors (ICIs) have radically changed the prognosis of several neoplasias, among them metastatic melanoma. In the past decade, some of these new drugs have appeared together with a new toxicity spectrum previously unknown to clinicians, until now. A common situation in daily practice is that a patient experiences toxicity due to this type of drug and we need to resume or rechallenge treatment after resolving the adverse event. Methods: A PubMed literature review was carried out. Results: The published data regarding the resumption or rechallenge of ICI treatment in melanoma patients is scarce and heterogeneous. Depending on the study reviewed, the recurrence incidence of grade 3–4 immune-related adverse events (irAEs) ranged from 18% to 82%. Conclusion: It is possible to resume or rechallenge, but each patient should be evaluated by a multidisciplinary team for close monitoring and assessment of the risk/benefit ratio before initiating treatment.
Development of the First 18F-Labeled Radiohybrid-Based Minigastrin Derivative with High Target Affinity and Tumor Accumulation by Substitution of the Chelating Moiety
Authors: Günther Thomas , Holzleitner Nadine , Di Carlo Daniel , Urtz-Urban Nicole , Lapa Constantin , Wester Hans-Jürgen
Published: March 2023

In order to optimize elevated kidney retention of previously reported minigastrin derivatives, we substituted (R)-DOTAGA by DOTA in (R)-DOTAGA-rhCCK-16/-18. CCK-2R-mediated internalization and affinity of the new compounds were determined using AR42J cells. Biodistribution and µSPECT/CT imaging studies at 1 and 24 h p.i. were carried out in AR42J tumor-bearing CB17-SCID mice. Both DOTA-containing minigastrin analogs exhibited 3- to 5-fold better IC50 values than their (R)-DOTAGA-counterparts. natLu-labeled peptides revealed higher CCK-2R affinity than their natGa-labeled analogs. In vivo, tumor uptake at 24 h p.i. of the most affine compound, [19F]F-[177Lu]Lu-DOTA-rhCCK-18, was 1.5- and 13-fold higher compared to its (R)-DOTAGA derivative and the reference compound, [177Lu]Lu-DOTA-PP-F11N, respectively. However, activity levels in the kidneys were elevated as well. At 1 h p.i., tumor and kidney accumulation of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 and [18F]F-[natLu]Lu-DOTA-rhCCK-18 was high. We could demonstrate that the choice of chelators and radiometals has a significant impact on CCK-2R affinity and thus tumor uptake of minigastrin analogs. While elevated kidney retention of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 has to be further addressed with regard to radioligand therapy, its radiohybrid analog, [18F]F-[natLu]Lu-DOTA-rhCCK-18, might be ideal for positron emission tomography (PET) imaging due to its high tumor accumulation at 1 h p.i. and the attractive physical properties of fluorine-18.
Chemically Enhanced Peptide and Protein Therapeutics
Authors: Díaz-Perlas Cristina , Oller-Salvia Benjamí
Published: March 2023

Proteins and peptides are on the rise as therapeutic agents and represent a higher percentage of approved drugs each year: 24% in 2021 vs [...]
Evaluation of Residual Corneal Stromal Bed Elasticity by Optical Coherence Elastography Based on Acoustic Radiation Force
Authors: Wang Yidi , Zhang Yubao , Shi Gang , Ai Sizhu , Liu Guo , Han Xiao , He Xingdao
Published: March 2023

Despite the rapidly growing popularity of laser vision correction (LVC) in the correction of myopia, its quantitative evaluation has not been thoroughly investigated. In this paper, an acoustic radiation force–optical coherence elastography (ARF-OCE) system was proposed to evaluate LVC by measuring the residual stromal bed (RSB) elasticity, because it is directly relevant to the RSB thickness that is critical to maintaining normal corneal function. As expected, the Young’s modulus of the RSB was calculated, then its relationship with the RSB thickness was determined. More significantly, a specific thickness was revealed in which the Young’s modulus changed dramatically, which may imply that there is a high risk of complication caused by over-cutting of the cornea. To the best of our knowledge, this is the first ARF-OCE imaging of the RSB, which may help to determine the safe RSB thickness and thus may help us to quantitatively assess LVC surgery.
Antioxidant Potential of Glutathione and Crosstalk with Phytohormones in Enhancing Abiotic Stress Tolerance in Crop Plants
Authors: Rai Gyanendra Kumar , Kumar Pradeep , Choudhary Sadiya M. , Singh Hira , Adab Komal , Kosser Rafia , Magotra Isha , Kumar Ranjeet Ranjan , Singh Monika , Sharma Rajni , Corrado Giandomenico , Rouphael Youssef
Published: March 2023

Glutathione (GSH) is an abundant tripeptide that can enhance plant tolerance to biotic and abiotic stress. Its main role is to counter free radicals and detoxify reactive oxygen species (ROS) generated in cells under unfavorable conditions. Moreover, along with other second messengers (such as ROS, calcium, nitric oxide, cyclic nucleotides, etc.), GSH also acts as a cellular signal involved in stress signal pathways in plants, directly or along with the glutaredoxin and thioredoxin systems. While associated biochemical activities and roles in cellular stress response have been widely presented, the relationship between phytohormones and GSH has received comparatively less attention. This review, after presenting glutathione as part of plants’ feedback to main abiotic stress factors, focuses on the interaction between GSH and phytohormones, and their roles in the modulation of the acclimatation and tolerance to abiotic stress in crops plants.
Accuracy of Selection in Early Generations of Field Pea Breeding Increases by Exploiting the Information Contained in Correlated Traits
Authors: Castro-Urrea Felipe A. , Urricariet Maria P. , Stefanova Katia T. , Li Li , Moss Wesley M. , Guzzomi Andrew L. , Sass Olaf , Siddique Kadambot H. M. , Cowling Wallace A.
Published: March 2023

Accuracy of predicted breeding values (PBV) for low heritability traits may be increased in early generations by exploiting the information available in correlated traits. We compared the accuracy of PBV for 10 correlated traits with low to medium narrow-sense heritability (h2) in a genetically diverse field pea (Pisum sativum L.) population after univariate or multivariate linear mixed model (MLMM) analysis with pedigree information. In the contra-season, we crossed and selfed S1 parent plants, and in the main season we evaluated spaced plants of S0 cross progeny and S2+ (S2 or higher) self progeny of parent plants for the 10 traits. Stem strength traits included stem buckling (SB) (h2 = 0.05), compressed stem thickness (CST) (h2 = 0.12), internode length (IL) (h2 = 0.61) and angle of the main stem above horizontal at first flower (EAngle) (h2 = 0.46). Significant genetic correlations of the additive effects occurred between SB and CST (0.61), IL and EAngle (−0.90) and IL and CST (−0.36). The average accuracy of PBVs in S0 progeny increased from 0.799 to 0.841 and in S2+ progeny increased from 0.835 to 0.875 in univariate vs MLMM, respectively. An optimized mating design was constructed with optimal contribution selection based on an index of PBV for the 10 traits, and predicted genetic gain in the next cycle ranged from 1.4% (SB), 5.0% (CST), 10.5% (EAngle) and −10.5% (IL), with low achieved parental coancestry of 0.12. MLMM improved the potential genetic gain in annual cycles of early generation selection in field pea by increasing the accuracy of PBV.
Chitosan-Bead-Encapsulated Polystyrene Sulfonate for Adsorption of Methylene Blue and Regeneration Studies: Batch and Continuous Approaches
Authors: Lau Kam Sheng , Azmi Nur Alia Sahira , Chin Siew Xian , Zakaria Sarani , Chia Chin Hua
Published: March 2023

Textile industrialization causes water pollution due to the discharge of industrial effluents into the environment. To reduce the impact of industrial effluent, it must be treated in wastewater treatment plants before discharge into rivers. Among all wastewater treatment approaches, the adsorption process is one method to remove pollutants from wastewater, but it has some limitations in term of reusability and ionic selective adsorption properties. In this study, we prepared cationic poly (styrene sulfonate) (PSS)-incorporated anionic chitosan beads synthesized using the oil–water emulsion coagulation method. The produced beads were characterized using FESEM and FTIR analysis. In batch adsorption studies, the PSS-incorporated chitosan beads exhibited monolayer adsorption processes, that is, exothermic processes that occur spontaneously at low temperatures, which were analyzed based on the adsorption isotherms, adsorption kinetics, and thermodynamics model fittings. The presence of PSS enables cationic methylene blue dye to adsorb to the anionic chitosan structure via electrostatic interaction between the sulfonic group and the dye molecule. The maximum adsorption capacity of PSS-incorporated chitosan beads achieved 42.21 mg/g, as calculated from the Langmuir adsorption isotherm. Finally, the PSS-incorporated chitosan beads demonstrated good regeneration with different types of reagents, especially using sodium hydroxide as a regeneration reagent. With the use of sodium hydroxide regeneration of this adsorbent material, a continuous adsorption setup also demonstrated that PSS-incorporated chitosan beads can be reused for methylene blue adsorption for up to three cycle processes.
A Self-Healable and Recyclable Zwitterionic Polyurethane Based on Dynamic Ionic Interactions
Authors: Mao Haiyan , Zhang Qun , Lin Ling , He Xuemei , Wang Lili
Published: March 2023

Polyurethanes with self-healing and reprocessing capabilities are promising in eco-friendly applications. Here, a self-healable and recyclable zwitterionic polyurethane (ZPU) was developed by introducing ionic bonds between protonated ammonium groups and sulfonic acid moieties. The structure of the synthesized ZPU was characterized by FTIR and XPS. The thermal, mechanical, self-healing and recyclable properties of ZPU were also investigated in detail. Compared with cationic polyurethane (CPU), ZPU shows similar thermal stability. The physical cross-linking network formed between zwitterion groups can dissipate strain energy as a weak dynamic bond, endowing ZPU with outstanding mechanical and elastic recovery properties, including the high tensile strength of 7.38 MPa, high elongation at a break of 980%, and fast elastic recovery ability. Additionally, ZPU exhibits a healing efficiency of over 93% at 50 °C for 1.5 h as a result of the dynamic reconstruction of reversible ionic bonds. Furthermore, ZPU can be well reprocessed by solution casting and hot-pressing with a recovery efficiency above 88%. The excellent mechanical properties, fast repairing capability, and good recyclability not only enable polyurethane with a promising application in protective coatings for textiles and paints but also make it a superior candidate as stretchable substrates for wearable electronic devices and strain sensors.
Synthesis and Investigation of Physicochemical and Biological Properties of Films Containing Encapsulated Propolis in Hyaluronic Matrix
Authors: Khachatryan Gohar , Khachatryan Karen , Krystyjan Magdalena , Krzemińska-Fiedorowicz Lidia , Lenart-Boroń Anna , Białecka Anna , Krupka Magdalena , Krzan Marcel , Blaszyńska Karolina , Hanula Monika , Juszczak Lesław
Published: March 2023

The dynamic development of nanotechnology has enabled the development of innovative and novel techniques for the production and use of nanomaterials. One of them is the use of nanocapsules based on biodegradable biopolymer composites. Closing compounds with antimicrobial activity inside the nanocapsule cause the gradual release of biologically active substances into the environment, and the effect on pathogens is regular, prolonged and targeted. Known and used in medicine for years, propolis, thanks to the synergistic effect of active ingredients, has antimicrobial, anti-inflammatory and antiseptic properties. Biodegradable and flexible biofilms were obtained, the morphology of the composite was determined using scanning electron microscopy (SEM) and particle size was measured by the dynamic light scattering (DLS) method. Antimicrobial properties of biofoils were examined on commensal skin bacteria and pathogenic Candida isolates based on the growth inhibition zones. The research confirmed the presence of spherical nanocapsules with sizes in the nano/micrometric scale. The properties of the composites were characterized by infrared (IR) and ultraviolet (UV) spectroscopy. It has been proven that hyaluronic acid is a suitable matrix for the preparation of nanocapsules, as no significant interactions between hyaluronan and the tested compounds have been demonstrated. Color analysis and thermal properties, as well as the thickness and mechanical properties of the obtained films, were determined. Antimicrobial properties of the obtained nanocomposites were strong in relation to all analyzed bacterial and yeast strains isolated from various regions of the human body. These results suggest high potential applicability of the tested biofilms as effective materials for dressings to be applied on infected wounds.
Reinforcement Behavior of Chemically Unmodified Cellulose Nanofiber in Natural Rubber Nanocomposites
Authors: Wongvasana Bunsita , Thongnuanchan Bencha , Masa Abdulhakim , Saito Hiromu , Sakai Tadamoto , Lopattananon Natinee
Published: March 2023

We investigated the reinforcement behavior of small amounts of chemically unmodified cellulose nanofiber (CNF) in eco-friendly natural rubber (NR) nanocomposites. For this purpose, NR nanocomposites filled with 1, 3, and 5 parts per hundred rubber (phr) of cellulose nanofiber (CNF) were prepared by a latex mixing method. By using TEM, a tensile test, DMA, WAXD, a bound rubber test, and gel content measurements, the effect of CNF concentration on the structure–property relationship and reinforcing mechanism of the CNF/NR nanocomposite was revealed. Increasing the content of CNF resulted in decreased dispersibility of the nanofiber in the NR matrix. It was found that the stress upturn in the stress–strain curves was remarkably enhanced when the NR was combined with 1–3 phr CNF, and a noticeable increase in tensile strength (an approximately 122% increase in tensile strength over that of NR) was observed without sacrificing the flexibility of the NR in the NR filled with 1 phr CNF, though no acceleration in their strain-induced crystallization was observed. Since the NR chains were not inserted in the uniformly dispersed CNF bundles, the reinforcement behavior by the small content of CNF might be attributed to the shear stress transfer at the CNF/NR interface through the interfacial interaction (i.e., physical entanglement) between the nano-dispersed CNFs and the NR chains. However, at a higher CNF filling content (5 phr), the CNFs formed micron-sized aggregates in the NR matrix, which significantly induced the local stress concentration and promoted strain-induced crystallization, causing a substantially increased modulus but reduced the strain at the rupture of the NR.