bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Properties and Microstructure of Iron Tailings Cemented Paste Backfills Using Carbide Slag-Activated Ground Granulated Blast-Furnace Slag as Alternative Binder
Authors: Feng Yabin , Li Feng , Qi Wenyue , Ren Qiangsheng , Qi Wenyan , Duan Ge , Zheng Kailin , Han Yongji , Pang Haotian
Published: November 2022

For rational disposal of solid wastes, low-cost cemented paste backfills (CPB) were prepared with iron tailings, ground granulated blast-furnace slag (GGBS), and calcium carbide slag (CS). To ensure that CPB can be effectively utilized in mine backfill projects, the effects of solid contents, GGBS content, CS/GGBS ratio, and mixing water on the workability and mechanical properties of CPB were investigated. The results indicated that when the solid content was 70%, the GGBS content was 14%, the CS/GGBS ratio was 0.4, the mixing water was tap water, the fluidity of fresh CPB slurry was 167 mm, and 28d unconfined compressive strength (UCS) of CPB reached 2.89 MPa, at which time the effect of the activation of the GGBS with CS was optimal. The analysis of X-ray diffraction (XRD), scanning electron microscopic imaging (SEM), thermogravimetric analysis (TG-DTG), and Fourier transform infrared spectroscopy (FTIR) demonstrated that the hydration products are mainly C-S-H gels, C-A-S-H, hemicarbonate, and hydrotalcite in CS-GGBS cementitious material. The C-S-H gel content gradually increased with increasing curing time and CS content (15%–35%). When the CS content was increased to 25%, the C-S-H gel content significantly increased, which improved the overall structural compactness and increased the UCS of CPB.
Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents
Authors: Silva Laís Peres , Santos Ivanilson Pimenta , Silva Dahara Keyse Carvalho , dos Reis Bruna Padilha Zurita Claro , Meira Cássio Santana , Castro Marcos Venícius Batista de Souza , dos Santos Filho José Maurício , Araujo-Neto João Honorato de , Ellena Javier Alcides , Silveira Rafael Gomes da , Soares Milena Botelho Pereira
Published: November 2022

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141–156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.
Studying miRNA–mRNA Interactions: An Optimized CLIP-Protocol for Endogenous Ago2-Protein
Authors: Stebel Sophie , Breuer Janina , Rossbach Oliver
Published: November 2022

Transcriptome-wide analysis of RNA-binding partners is commonly achieved using UV crosslinking and immunoprecipitation (CLIP). Individual-nucleotide-resolution CLIP (iCLIP)enables identification of the specific position of the protein–RNA interaction. In addition to RNA-binding proteins (RBPs), microRNA (miRNA)–mRNA interactions also play a crucial role in the regulation of gene expression. Argonaute-2 (Ago2) mediates miRNA binding to a multitude of mRNA target sites, enabling the identification of miRNA–mRNA interactions by employing modified Ago2-CLIP protocols. Here, we describe an Ago2-specific CLIP protocol optimized for the use of small quantities of cell material, targeting endogenous Ago2 while avoiding possible methodological biases such as metabolic labeling or Ago2 overexpression and applying the latest advances in CLIP library preparation, the iCLIP2 protocol. In particular, we focus on the optimization of lysis conditions and improved radioactive labeling of the 5′ end of the miRNA.
Influence of Modified Carbon Black on Nylon 6 Nonwoven Fabric and Performance as Adsorbent Material
Authors: Andrade-Guel Marlene , Reyes-Rodríguez Pamela Yajaira , Cabello-Alvarado Christian J. , Cadenas-Pliego Gregorio , Ávila-Orta Carlos Alberto
Published: November 2022

The number of chronic kidney disease (CKD) persons continues to rise in Mexico. They require renal replacement therapy, and in the absence of it, hemodialysis is the major option for their survival. The uremic toxins present in the blood are removed by hemodialysis, which involve membranes. In this study, nonwoven fabrics with modified carbon black nanoparticles in a matrix polymer of Nylon 6 were obtained and evaluated as an adsorbent material of uremic toxins. All nonwoven fabrics were characterized by FTIR, XRD, TGA, SEM, and contact angle measurements and were evaluated as an adsorbent material for the urea toxin and as an albumin retainer. The findings suggest their potential application as a hemodialysis membrane. Nanocomposites had a higher hydrophilic characteristic compared to pure Nylon 6. The average diameter size of the fibers was in the range of 5 to 50 μm. All nanocomposites nonwoven fabrics showed high removal percentages of inulin in a range of 80–85% at 15 min of contact. Most Ny6 Zytel/CB nanocomposites showed a high percentage of urea removal (80 to 90%).
Ultra-Low-Voltage-Triggered Silicon Controlled Rectifier ESD Protection Device for 2.5 V Nano Integrated Circuit
Authors: Chen Ruibo , Wei Hao , Liu Hongxia , Liu Zhiwei , Chen Yaolin
Published: November 2022

In this paper, an improved low-voltage-triggered silicon-controlled rectifier (LVTSCR) called an ultra-low-voltage-triggered SCR (ULVTSCR) is proposed and fabricated in a 40-nm CMOS process. By adding an external NMOSs-chain triggering component to the conventional LVTSCR, the proposed ULVTSCR can realize ~2 V lower trigger voltage. Meanwhile, the trigger voltage of the ULVTSCR is adjustable with the number of its incorporated NMOS transistors. Compared with the existing Diodes-chain Triggered SCR (DTSCR) scheme, the NMOSs-chain triggered ULVTSCR possesses a 25% lowered overshoot voltage in the same area consumption, and thus it is more suitable for 2.5 V circuits ESD protections considering the CDM protection applications.
Design and Parametric Analysis of a Wide-Angle and Polarization Insensitive Ultra-Broadband Metamaterial Absorber for Visible Optical Wavelength Applications
Authors: Chowdhury Md Zikrul Bari , Islam Mohammad Tariqul , Hoque Ahasanul , Alshammari Ahmed S. , Alzamil Ahmed , Alsaif Haitham , Alshammari Badr M. , Hossain Ismail , Samsuzzaman Md
Published: November 2022

Researchers are trying to work out how to make a broadband response metamaterial absorber (MMA). Electromagnetic (EM) waves that can pass through the atmosphere and reach the ground are most commonly used in the visible frequency range. In addition, they are used to detect faults, inspect tapped live-powered components, electrical failures, and thermal leaking hot spots. This research provides a numerical analysis of a compact split ring resonator (SRR) and circular ring resonator (CRR) based metamaterial absorber (MMA) using a three-layer substrate material configuration for wideband visible optical wavelength applications. The proposed metamaterial absorber has an overall unit cell size of 800 nm × 800 nm × 175 nm in both TE and TM mode simulations and it achieved above 80% absorbance in the visible spectrums from 450 nm to 650 nm wavelength. The proposed MA performed a maximum absorptivity of 99.99% at 557 nm. In addition, the steady absorption property has a broad range of oblique incidence angle stability. The polarization conversion ratio (PCR) is evaluated to ensure that the MMA is perfect. Both TM and TE modes can observe polarization insensitivity and wide-angle incidence angle stability with 18° bending effects. Moreover, a structural study using electric and magnetic fields was carried out to better understand the MMA’s absorption properties. The observable novelty of the proposed metamaterial is compact in size compared with reference paper, and it achieves an average absorbance of 91.82% for visible optical wavelength. The proposed MMA also has bendable properties. The proposed MMA validation has been done by two numerical simulation software. The MMA has diverse applications, such as color image, wide-angle stability, substantial absorption, absolute invisible layers, thermal imaging, and magnetic resonance imaging (MRI) applications.
Effects of Typical Solvents on the Structural Integrity and Properties of Activated Kaolinite by Wet Ball Milling
Authors: Luo Shunjie , Chen Yang , Xu Weiting , Wei Jiangxiong , Li Zhaoheng , Huang Shiqing , Huang Haoliang , Zhang Junlu , Yu Qijun
Published: November 2022

The influence of organic solvents on the structural integrity and properties of activated kaolinite were compared and analyzed via characterization techniques and molecular dynamics (MD) simulation. The results revealed that the organic intercalators can be easily inserted into the interlayer spaces of activated kaolinite within a short time of the wet ball milling. The DMSO intercalated kaolinites maintained structural integrity due to the high intercalation rate and the excellent buffering effect against the crushing force of milling during the delamination/exfoliation process. The delaminated layers of the DMSO–kaolinite complex exhibited a high specific surface area of 99.12 m2/g and a low average thickness of 35.21 nm. The calculated elastic properties of the organo-kaolinite complex manifested the intercalation of DMSO into a kaolinite interlayer, which could improve the compressibility and structural integrity of kaolinite nanosheets. The DMSO–kaolinite complex was easier to peel off when compared to the other organic intercalators due to its more intercalated molecules.
MOF-Derived MnO/C Nanocomposites for High-Performance Supercapacitors
Authors: Qiao Yuqing , Li Na , Dong Mingwei , Jia Peng , Ma Chongchong , Zhang Tong , Jiao Tifeng
Published: November 2022

As ordered porous materials, metal–organic frameworks (MOFs) have attracted tremendous attention in the field of energy conversion and storage due to their high specific surface area, permanent porosity, and tunable pore sizes. Here, MOF-derived MnO/C nanocomposites with regular octahedral shape were synthesized using a Mn-based analogue of the MIL-100 framework (Mn-MIL-100, MIL: Matérial Institut Lavoisier) as the precursor. Using aberration-corrected environmental transmission electron microscopy (ETEM), MnO nanocages with a diameter of approximately 20 nm were recognized in the MnO/C nanocomposites fabricated, dispersed in a microporous carbon matrix homogeneously. The nanocages are composed of MnO nanoparticles with a diameter of approximately 2 nm and with a single crystal structure. The specific surface area of the as-prepared MnO/C octahedra decreases to 256 m2 g−1 from 507 m2 g−1 of the Mn-MIL-100 precursor, whereas the total pore volume increases to 0.245 cm3 g−1, which is approximately 29% higher than that of the precursor (0.190 cm3 g−1). Additionally, when utilized as an electrode for supercapacitors, the MOF-derived MnO/C nanocomposite demonstrates a towering specific capacitance of 421 F g−1 at 0.5 A g−1 and good cycle stability (94%) after 5000 cycles. Our work reveals that the MnO nanoparticles in MOF-derived MnO/C nanocomposites exhibit nanocage structure characteristics, which might be inherited from the Mn-MIL-100 precursor with analogous supertetrahedron units.
Analysis of Thermal Stress in Vanadium Dioxide Thin Films by Finite Element Method
Authors: Wang Yuemin , Wang Lebin , Gu Jinxin , Yan Xiangqiao , Lu Jiarui , Dou Shuliang , Li Yao , Wang Lei
Published: November 2022

The buckling, de-lamination, and cracking of the thin film/substrate system caused by thermal stress is the main obstacle for functional failure. Moreover, the thermal stress of vanadium dioxide (VO2) thin film may be more complicated due to the stress re-distribution caused by phase transition. Therefore, the thermal stress of VO2 thin films deposited on four substrates with different materials (fused silica, silicon slice, sapphire, and glass) has been studied by finite element method in the present work. The influences of external temperature, substrate, and interlayer on thermal stress were analyzed. It was found that the substrates can greatly affect the thermal stresses, which were mainly caused by the mismatch of coefficient of thermal expansion (CTE). The thermal stress had a linear relationship with the external temperature, but this tendency would be redistributed or even change direction when phase transition occurred. The simulated results were in tandem with the analytical method. Meanwhile, the radial stress and shear stress distribution under the influence of phase transition were calculated. In addition, the reduction of thermal stress and shear stress showed that the appropriate interlayer can enhance the adhesive strength effectively.
Solid Lipid Nanoparticles Based on Monosubstituted Pillar[5]arenes: Chemoselective Synthesis of Macrocycles and Their Supramolecular Self-Assembly
Authors: Filimonova Darya , Nazarova Anastasia , Yakimova Luidmila , Stoikov Ivan
Published: November 2022

Novel monosubstituted pillar[5]arenes with one or two terminal carboxyl groups were synthesized by the reaction of succinic anhydride with pillar[5]arene derivative containing a diethylenetriamine function. The ability for non-covalent self-assembly in chloroform, dimethyl sulfoxide, as well as in tetrahydrofuran-water system was studied. The ability of the synthesized macrocycles to form different types of associates depending on the substituent nature was established. The formation of stable particles with average diameter of 192 nm in chloroform and of 439 nm in DMSO was shown for pillar[5]arene containing two carboxyl fragments. Solid lipid nanoparticles (SLN) based on monosubstituted pillar[5]arenes were synthesized by nanoprecipitation in THF-water system. Minor changes in the structure of the macrocycle substituent can dramatically influence the stability and shape of SLN (spherical and rod-like structures) accordingly to DLS and TEM. The presence of two carboxyl groups in the macrocycle substituent leads to the formation of stable spherical SLN with an average hydrodynamic diameter of 364–454 nm. Rod-like structures are formed by pillar[5]arene containing one carboxyl fragment, which diameter is about of 50–80 nm and length of 700–1000 nm. The synthesized stable SLN open up great prospects for their use as drug storage systems.
Manufacturing Functional Polymer Surfaces by Direct Laser Interference Patterning (DLIP): A Polymer Science View
Authors: Barbero Cesar Alfredo , Acevedo Diego Fernando
Published: November 2022

Direct laser interference patterning (DLIP) involves the formation of patterns of light intensity using coherent laser light beams that interfere between them. Light on the ultraviolet (<350 nm) and NIR (800–2000 nm) is absorbed in chromophores present in the polymer structure or in loaded absorbing species (dyes, polymers, nanoparticles). The absorbed light induces photothermal/photochemical processes, which alter permanently the topography of the polymer surface. The success of DLIP at different wavelengths is discussed in relation to the optical/thermal properties of the polymers and previous data on laser ablation of polymers. The size of the pattern is related directly to the wavelength of the light and inversely to the sine of the angle between beams and the refractive index of the external medium. In that way, nanometric structures (<100 nm) could be produced. Since the patterning occurs in a single short pulse (<10 ns), large surfaces can be modified. Both bacterial biofilm inhibition and human cell differentiation/orientation have been achieved. Large improvements in technological devices (e.g., thin film solar cells) using DLIP structured surfaces have also been demonstrated. Prospective application of DLIP to common polymers (e.g., Teflon®) and complex polymeric systems (e.g., layer-by-layer multilayers) is discussed on the basis of reported polymer data.
Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report
Authors: Tsouris Zisis , Provatas Antonios , Bakirtzis Christos , Aloizou Athina-Maria , Siokas Vasileios , Tsimourtou Vana , Grigoriadis Nikolaos , Hadjigeorgiou Georgios M. , Dardiotis Efthimios
Published: November 2022

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease.
The Interactions of Food Security, Health, and Loneliness among Rural Older Adults before and after the Onset of COVID-19
Authors: Howe-Burris Mecca , Giroux Stacey , Waldman Kurt , DeBruicker Valliant Julia , Babb Angela , Czebotar Kamila , Fobi Daniel , Stafford Phil , Knudsen Daniel C.
Published: November 2022

Older adults and those living in rural areas face unique challenges to health and food security which were exacerbated during the COVID-19 pandemic. We examine the interrelationships among food security, physical health, and loneliness among rural older adults before the onset of and during the COVID-19 pandemic. Using data from a cross-sectional household survey of older adults in rural Indiana, administered May 2020 through July 2020, our results show a higher prevalence of food insecurity, poorer physical health, and increased loneliness after the onset of the pandemic. Path analyses confirmed the interrelationship between food security, health, and the absence of loneliness before and after the onset of COVID-19. Loneliness emerged as a major pathway through which the pandemic impacted quality of life, particularly affecting older women and physical health. Policy initiatives should consider the unique experiences and challenges associated with rural life among older adults and create food security initiatives that incorporate socialization while also considering the challenges associated with poor physical health in older age. Furthermore, our analysis shows that those who are vulnerable to food security, poor health, and loneliness in the absence of a global pandemic remain vulnerable during a pandemic.
The Impact of the COVID-19 Pandemic on the Food Security of UK Adults Aged 20–65 Years (COVID-19 Food Security and Dietary Assessment Study)
Authors: Thomas Michelle , Eveleigh Elizabeth , Vural Zeynep , Rose Peter , Avery Amanda , Coneyworth Lisa , Welham Simon
Published: November 2022

The first UK lockdown greatly impacted the food security status of UK adults. This study set out to establish if food procurement was adapted differently for different income groups and if this impacted dietary intakes disproportionately. Adults (n = 515) aged 20–65 years participated in an online survey with 56 completing a 3–4 day diet diary. Food availability was a significant factor in the experience of food insecurity. Similar proportions of food secure and food insecure adapted food spend during lockdown, spending similar amounts. Food insecure (n = 85, 18.3%) had a 10.5% lower income and the money spent on food required a greater proportion of income. Access to food was the biggest driver of food insecurity but monetary constraint was a factor for the lowest income group. The relative risk of food insecurity increased by 0.07-fold for every 1% increase in the proportion of income spent on food above 10%. Micronutrient intakes were low compared to the reference nutrient intake (RNI) for most females, with riboflavin being 36% lower in food insecure groups (p = 0.03), whilst vitamin B12 was 56% lower (p = 0.057) and iodine 53.6% lower (p = 0.257) these were not significant. Coping strategies adopted by food insecure groups included altering the quantity and variety of fruit and vegetables which may have contributed to the differences in micronutrients.
Promoting Protein Intake in an Ageing Population: Product Design Implications for Protein Fortification
Authors: Norton Victoria , Lignou Stella , Methven Lisa
Published: November 2022

Protein is a macronutrient of interest for an ageing population and intake requirements increase with age. Accordingly, protein is often fortified into products for older adults to help alleviate malnutrition and impede sarcopenia. However, more emphasis needs to be placed upon designing protein-fortified products to ensure suitability for older adults. This study involved a two-stage approach: (1) an initial review of products commonly fortified with protein and (2) two questionnaires for younger and older adults (n = 73; 18–30; 65+) to investigate optimal portion sizes (drinks and cakes) as well as attitudes, consumption habits and preferences towards protein fortification. The initial literature and market review demonstrated protein-fortified products are typically in liquid or snack format; however, there is considerable variability in terms of product types, serving size and protein sources. There were no age-related differences found for ideal cakes portion size whereas there were for liquids. Older adults are typically not consuming protein-fortified products; therefore, more importance should be placed on the consumption moment (breakfast or as snacks between meals) and on cereals, pasta, porridge, cakes, and biscuits. Older adults need increased awareness of, and more education on, the benefits of protein consumption, coupled with products tailored and designed to encourage intake.
Food Environment around Schools: A Systematic Scope Review
Authors: França Fabiana Chagas Oliveira de , Andrade Iziane da Silva , Zandonadi Renata Puppin , Sávio Karin Eleonora , Akutsu Rita de Cassia Coelho de Almeida
Published: November 2022

The present systematic scope review intended to compile state-of-the-art information about the food environment around schools, exploring the main methods used to describe the food environment around schools as well as the possible effects that this environment can promote on the health of children and adolescents. The preferred reporting items for systematic reviews and meta-analyses—extension for scoping reviews (PRISMA-ScR) checklist and guidelines were followed to ensure a robust and repeatable methodological process. A systematic search was performed in the following electronic databases: MEDLINE, Embase, Science Direct, Web of Science, LILACS, and Scopus, as well as in related articles, a manual search of reference lists and gray literature. Forty-six studies were selected. There was no standardization regarding distances from food establishments to schools, methods of analysis, and software used. The food environment around the schools was characterized by the wide availability of food establishments, especially fast food, convenience stores, supermarkets, and grocery stores known for offering a wide variety of unhealthy foods. Regarding the correlations with the health of children and adolescents, the evidence points to possible interferences of the food environment known as obesogenic, but it cannot be related only to the school environment since most of the acquisition and consumption of food usually happens around family homes. Conducting standardized and comprehensive studies evaluating food choices in the school environment and their interrelationships is very important to ensure children’s food and nutrition security and minimize negative health outcomes in the medium and long term.
The Association between SARS-CoV-2 Infection and Diabetic Ketoacidosis in Patients with New-Onset Diabetes: A Retrospective Study from a Diabetic Center in Saudi Arabia
Authors: Hurissi Eman , Alameer Mohammed , Ageeli Fadiyah , Allami Maram , Alharbi Mohammed , Suhail Hussam , Albeishy Hadeel , Oraibi Omar , Somaili Mohammed , Hummadi Abdulrahman , Alhazmi Abdulaziz H.
Published: November 2022

Background: Various reports described new-onset diabetes during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with no previous history of diabetes or glucocorticoid use. Further, SARS-CoV-2 could increase the risk of diabetes, including diabetic ketoacidosis (DKA). However, data on the relationship between new-onset diabetes and COVID-19 are still limited in our region. Thus, we aimed in this study to evaluate the association between new-onset diabetes and DKA in patients with COVID-19. Methods: A retrospective, cross-sectional study was conducted at a diabetic center in Jazan province, Saudi Arabia, between 2020 and 2021. Demographic data, COVID-19 status, and DKA incidence were collected and verified manually from diabetic patients’ medical records. Data were analyzed using a t-test and chi-square test. Results: We included 54 diabetic patients diagnosed during the COVID-19 pandemic, with a median age of 17 years. The majority of patients were females (57.4%). About 38.8% were diagnosed with COVID-19, and 16.6% reported having DKA. About 33.3% of the patients who experienced DKA reported being COVID-19-positive. However, only 6% of patients who denied contracting SARS-CoV-2 developed DKA (p-value = 0.020). Conclusions: Patients with newly diagnosed diabetes due to COVID-19 seem at a higher risk of developing DKA. Further epidemiological and molecular studies are required for a better understanding of the correlation between DKA in patients with diabetes and COVID-19.
Effects of o,p’-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line
Authors: Bach Camila , Corso Claudia Rita , Veiga Alan de Almeida , Paraizo Mariana Martins , de Souza Lauro Mera
Published: November 2022

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the β-hydroxylation, which yields the final product o,p’-DDA, and the α-hydroxylation, which will give the final product o,p’-DDE. It is speculated that o,p’-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p’-DDE and o,p’-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP’s involved in the steroidogenic process in the H295R cell line. It was found that o,p’-DDE had a different effect than the o,p’-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p’-DDD, the o,p’-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP’s, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p’-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter.
Nanoparticle-Delivered Transforming Growth Factor-β1 siRNA Induces PD-1 against Gastric Cancer by Transforming the Phenotype of the Tumor Immune Microenvironment
Authors: Wu Fenglei , Xu Xiujuan , Li Wei , Hong Yidong , Lai Huan , Zhang Jingzhou , Wu Xueyu , Zhou Kangjie , Hu Nan
Published: November 2022

Immune checkpoint blockade (ICB) is currently considered to be an important therapeutic method, which obtained FDA approval for clinical use in gastric cancer in 2017. As a new mechanism, it was found that the effect of αPDL1 could be improved by blocking the TGF-β1 signaling pathway, which converts the tumor immune microenvironment from the “immune-excluded phenotype” to the “immune-inflamed phenotype”. Based on this phenomenon, this project was designed to prepare TGF-β1-siRNA-loaded PEG-PCL nanoparticles conjugated to αPDL1 (siTGF-β1-αPDL1-PEG-PCL) since we have linked similar antibodies to PEG-PCL previously. Therefore, MFC tumor-engrafted mice were established to simulate the biological characteristics of converting the phenotype of the immune microenvironment, and to study the anti-tumor effect and possible molecular mechanism. In this study, αPDL1 antibody conjugates markedly increased the cell uptake of NPs. The produced αPDL1-PEG-PCL NPs efficiently reduced the amounts of TGF-β1 mRNA in MFC cells, converting the immune microenvironment of MFC tumors engrafted mice from the “immune-excluded phenotype” to the “immune-inflamed phenotype”. PDL1-harboring gastric cancer had increased susceptibility to αPDL1. The value of this drug-controlled release system targeting the tumor microenvironment in immune checkpoint therapy of gastric cancer would provide a scientific basis for clinically applying nucleic acid drugs.
In Vitro Investigation of the Anticancer Properties of Ammodaucus Leucotrichus Coss. & Dur.
Authors: Lenzi Monia , Turrini Eleonora , Catanzaro Elena , Cocchi Veronica , Guerrini Alessandra , Hrelia Patrizia , Gasperini Sofia , Stefanelli Claudio , Abdi Bellau Mohamed Lamin , Pellicioni Valentina , Tacchini Massimo , Greco Giulia , Fimognari Carmela
Published: November 2022

Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy.
4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers
Authors: Paškan Martin , Rimpelová Silvie , Svobodová Pavlíčková Vladimíra , Spálovská Dita , Setnička Vladimír , Kuchař Martin , Kohout Michal
Published: November 2022

New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18–65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA).
Lactic Acidosis Related to Pharmacotherapy and Human Diseases
Authors: Zanza Christian , Facelli Valentina , Romenskaya Tastiana , Bottinelli Maria , Caputo Giorgia , Piccioni Andrea , Franceschi Francesco , Saviano Angela , Ojetti Veronica , Savioli Gabriele , Longhitano Yaroslava
Published: November 2022

Lactic acidosis represents one of the most common conditions that can compromise the health of intensive care unit (ICU) patients, increasing the mortality of patients with high levels of Lactate who do not receive a proper treatment within the first 6 h of hospitalization. There are two enantiomers of lactic acid: L-lactic acid (when the concentration increases, it can lead to a state of severe acidemia risking cardiovascular collapse, causing an increase in mortality in ICU patients) and D lactic acid (produced in the human organism by microbiota and its production increases during some pathological status). Generally, increased levels of serum lactic acid could be due to numerous factors, including hypoxia (caused for example by septic/cardiogenic/hypovolemic or obstructive shock), specific pathologies (e.g., liver disease), use of some drugs (e.g., metformin), presence of toxins, and trauma. Since the underlying cause could be fatal for the ICU patient, it is important to understand the root of this clinical status with a view to correct it and prevent the risk of a poor clinical outcome. Prevention and early treatment are the keys to control the negative clinical consequences. The aim of this review is to revise the scientific literature for further confirmation about the importance of early identification of acidotic statuses and to underline how an early diagnosis can prevent the worst clinical outcome, especially for ICU patients who are more fragile compared to the general population.
Photodynamic Therapy with Nebulized Nanocurcumin on A549 Cells, Model Vessels, Macrophages and Beyond
Authors: Altube María Julia , Caputo Ezequiel Nicolás , Rivero Martín Nicolás , Gutiérrez María Laura , Romero Eder Lilia
Published: November 2022

This study aimed to determine the damage mechanisms caused by naturally targeted nanoarchaeosomes made of diether lipids from Halorubrum tebenquichense loaded with curcumin (CUR, nATC), which mediated photodynamic therapy (PDT) on A549 cells and on THP-1-macrophages, two cell types found in airway cancers. The effect of nATC- PDT on vessels modeled with a chicken embryo chorioallantoic membrane (CAM), after dropping the formulations on its surface covered with mucins, was also determined. nATCs are known to efficiently trap CUR for at least six months, constituting easy-to-prepare, stable formulations suitable for nebulization. CUR instead, is easily released from carriers such as liposomes made of ordinary phospholipids and cholesterol after a few weeks. Irradiated at 9 J/cm2, nATC (made of archaeolipids: Tween 80: CUR at 1:0.4:0.04 w:w, size 180 ± 40 nm, ζ potential −24 mV, 150 μg CUR/15 mg lipids/mL) was phototoxic (3.7 ± 0.5 μM IC50), on A549 cells after 24 h. The irradiation reduced mitochondrial membrane potential (ΔΨm), ATP levels and lysosomal functionalism, and caused early apoptotic death and late necrosis of A549 cells upon 24 h. nATC induced higher extra and intracellular reactive oxygen species (ROS) than free CUR. nATC-PDT impaired the migration of A549 cells in a wound healing assay, reduced the expression of CD204 in THP-1 macrophages, and induced the highest levels of IL-6 and IL-8, suggesting a switch of macrophage phenotype from pro-tumoral M2 to antitumoral M1. Moreover, nATC reduced the matrix metalloproteinases (MMP), −2 and −9 secretion, by A549 cells with independence of irradiation. Finally, remarkably, upon irradiation at 9 J/cm2 on the superficial vasculature of a CAM covered with mucins, nATC caused the vessels to collapse after 8 h, with no harm on non-irradiated zones. Overall, these results suggest that nebulized nATC blue light-mediated PDT may be selectively deleterious on superficial tumors submerged under a thick mucin layer.
Polymeric Nanoparticles for Drug Delivery in Osteoarthritis
Authors: Pontes Adriano P. , Welting Tim J. M. , Rip Jaap , Creemers Laura B.
Published: November 2022

Osteoarthritis (OA) is a degenerative musculoskeletal disorder affecting the whole synovial joint and globally impacts more than one in five individuals aged 40 and over, representing a huge socioeconomic burden. Drug penetration into and retention within the joints are major challenges in the development of regenerative therapies for OA. During the recent years, polymeric nanoparticles (PNPs) have emerged as promising drug carrier candidates due to their biodegradable properties, nanoscale structure, functional versatility, and reproducible manufacturing, which makes them particularly attractive for cartilage penetration and joint retention. In this review, we discuss the current development state of natural and synthetic PNPs for drug delivery and OA treatment. Evidence from in vitro and pre-clinical in vivo studies is used to show how disease pathology and key cellular pathways of joint inflammation are modulated by these nanoparticle-based therapies. Furthermore, we compare the biodegradability and surface modification of these nanocarriers in relation to the drug release profile and tissue targeting. Finally, the main challenges for nanoparticle delivery to the cartilage are discussed, as a function of disease state and physicochemical properties of PNPs such as size and surface charge.
The Diphtheria Toxin Translocation Domain Impairs Receptor Selectivity in Cancer Cell-Targeted Protein Nanoparticles
Authors: Voltà-Durán Eric , Sánchez Julieta M. , Parladé Eloi , Serna Naroa , Vazquez Esther , Unzueta Ugutz , Villaverde Antonio
Published: November 2022

Protein-based materials intended as nanostructured drugs or drug carriers are progressively gaining interest in nanomedicine, since their structure, assembly and cellular interactivity can be tailored by recruiting functional domains. The main bottleneck in the development of deliverable protein materials is the lysosomal degradation that follows endosome maturation. This is especially disappointing in the case of receptor-targeted protein constructs, which, while being highly promising and in demand in precision medicines, enter cells via endosomal/lysosomal routes. In the search for suitable protein agents that might promote endosome escape, we have explored the translocation domain (TD) of the diphtheria toxin as a functional domain in CXCR4-targeted oligomeric nanoparticles designed for cancer therapies. The pharmacological interest of such protein materials could be largely enhanced by improving their proteolytic stability. The incorporation of TD into the building blocks enhances the amount of the material detected inside of exposed CXCR4+ cells up to around 25-fold, in absence of cytotoxicity. This rise cannot be accounted for by endosomal escape, since the lysosomal degradation of the new construct decreases only moderately. On the other hand, a significant loss in the specificity of the CXCR4-dependent cellular penetration indicates the unexpected role of the toxin segment as a cell-penetrating peptide in a dose-dependent and receptor-independent fashion. These data reveal that the diphtheria toxin TD displayed on receptor-targeted oligomeric nanoparticles partially abolishes the exquisite receptor specificity of the parental material and it induces nonspecific internalization in mammalian cells.
Nanomaterials-Incorporated Chemically Modified Gelatin Methacryloyl-Based Biomedical Composites: A Novel Approach for Bone Tissue Engineering
Authors: Herrera-Ruiz Abigail , Tovar Benjamín Betancourt , García Rubén Gutiérrez , Tamez María Fernanda Leal , Mamidi Narsimha
Published: November 2022

Gelatin methacryloyl (GelMA)-based composites are evolving three-dimensional (3D) networking hydrophilic protein composite scaffolds with high water content. These protein composites have been devoted to biomedical applications due to their unique abilities, such as flexibility, soft structure, versatility, stimuli-responsiveness, biocompatibility, biodegradability, and others. They resemble the native extracellular matrix (ECM) thanks to their remarkable cell-adhesion and matrix-metalloproteinase (MMP)-responsive amino acid motifs. These favorable properties promote cells to proliferate and inflate within GelMA-protein scaffolds. The performance of GelMA composites has been enriched using cell-amenable components, including peptides and proteins with a high affinity to harmonize cellular activities and tissue morphologies. Due to their inimitable merits, GelMA systems have been used in various fields such as drug delivery, biosensor, the food industry, biomedical, and other health sectors. The current knowledge and the role of GelMA scaffolds in bone tissue engineering are limited. The rational design and development of novel nanomaterials-incorporated GelMA-based composites with unique physicochemical and biological advantages would be used to regulate cellular functionality and bone regeneration. Substantial challenges remain. This review focuses on recent progress in mitigating those disputes. The study opens with a brief introduction to bone tissue engineering and GelMA-based composites, followed by their potential applications in bone tissue engineering. The future perspectives and current challenges of GelMA composites are demonstrated. This review would guide the researchers to design and fabricate more efficient multifunctional GelMA-based composites with improved characteristics for their practical applications in bone tissue engineering and biomedical segments.
Spray-Dried Inhalable Powder Formulations of Gentamicin Designed for Pneumonic Plague Therapy in a Mouse Model
Authors: Zhu Menghuan , Zhang Dongna , Zhang Lili , Zhao Liangliang , Xu Likun , Wang Baogang , Zhang Xinyu , Chen Jinwei , Bei Zhuchun , Wang Hong , Zhou Dongsheng , Yang Wenhui , Song Yabin
Published: November 2022

Infection with Yersinia pestis (Y. pestis) may cause pneumonic plague, which is inevitably fatal without treatment. Gentamicin (GM), an aminoglycoside antibiotic, is a drug commonly used in the treatment of plague. However, it requires repeated intramuscular or intravenous administration. Pulmonary drug delivery is noninvasive, with the advantages of local targeting and reduced risk of systemic toxicity. In this study, GM powders were prepared using spray-drying technology. The powders displayed good physical and chemical properties and met the requirements for human pulmonary inhalation. The formulation of the powders was optimized using a 32 full factorial design. A formulation of 15% (w/w) of L-leucine was prepared, and the spray-drying process parameters using an inlet temperature of 120°C and a 15% pump rate were determined to produce the best powder. In addition, the optimized GM spray-dried powders were characterized in terms of morphology, crystallinity, powder fluidity, and aerodynamic particle size distribution analysis. In a mouse model of pneumonic plague, we compared the therapeutic effects among three administration routes, including subcutaneous injection, liquid atomization, and dry powder atomization. In conclusion, our data suggest that inhalation therapy with GM spray-dried powders is an effective treatment for pneumonic plague.
Caveolae-Mediated Extracellular Vesicle (CMEV) Signaling of Polyvalent Polysaccharide Vaccination: A Host–Pathogen Interface Hypothesis
Authors: Li Shengwen Calvin , Kabeer Mustafa H.
Published: November 2022

We published a study showing that improvement in response to splenectomy associated defective, in regards to the antibody response to Pneumovax® 23 (23-valent polysaccharides, PPSV23), can be achieved by splenocyte reinfusion. This study triggered a debate on whether and how primary and secondary immune responses occur based on humoral antibody responses to the initial vaccination and revaccination. The anti-SARS-CoV-2 vaccine sheds new light on the interpretation of our previous data. Here, we offer an opinion on the administration of the polyvalent polysaccharide vaccine (PPSV23), which appears to be highly relevant to the primary vaccine against SARS-CoV-2 and its booster dose. Thus, we do not insist this is a secondary immune response but an antibody response, nonetheless, as measured through IgG titers after revaccination. However, we contend that we are not sure if these lower but present IgG levels against pneumococcal antigens are clinically protective or are equally common in all groups because of the phenomenon of “hyporesponsiveness” seen after repeated polysaccharide vaccine challenge. We review the literature and propose a new mechanism—caveolae memory extracellular vesicles (CMEVs)—by which polysaccharides mediate prolonged and sustained immune response post-vaccination. We further delineate and explain the data sets to suggest that the dual targets on both Cav-1 and SARS-CoV-2 spike proteins may block the viral entrance and neutralize viral load, which minimizes the immune reaction against viral attacks and inflammatory responses. Thus, while presenting our immunological opinion, we answer queries and responses made by readers to our original statements published in our previous work and propose a hypothesis for all vaccination strategies, i.e., caveolae-mediated extracellular vesicle-mediated vaccine memory.