bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Study of Interfacial Micromechanical Behaviors of 6H-SiC/Al Composites under Uniaxial Tensile Deformation
Authors: Feng Kai , Wang Jiefang , Hao Shiming , Xie Jingpei
Published: January 2023

This paper investigated the micromechanical behavior of different 6H-SiC/Al systems during the uniaxial tensile loading by using molecular dynamics simulations. The results showed that the interface models responded diversely to the tensile stress when the four low-index surfaces of the Al were used as the variables of the joint surfaces. In terms of their stress–strain properties, the SiC(0001)/Al(001) models exhibited the highest tensile strength and the smallest elongation, while the other models produced certain deformations to relieve the excessive strain, thus increasing the elongation. The SiC(0001)/Al(110) models exhibited the largest elongations among all the models. From the aspect of their deformation characteristics, the SiC(0001)/Al(001) model performed almost no plastic deformation and dislocations during the tensile process. The deformation of the SiC(0001)/Al(110) model was dominated by the slip of the 1/6 <112> Shockley partial dislocations, which contributed to the intersecting stacking faults in the model. The SiC(0001)/Al(111) model produced a large number of dislocations under the tensile loading. Dislocation entanglement was also found in the model. Meanwhile, a unique defect structure consisting of three 1/6 <110> stair-rod dislocations and three stacking faults were found in the model. The plastic deformation in the SiC(0001)/Al(112) interface model was restricted by the L-C lock and was carried out along the 1/6 <110> stair-rod dislocations’ direction. These results reveal the interfacial micromechanical behaviors of the 6H-SiC/Al composites and demonstrate the complexity of the deformation systems of the interfaces under stress.
Emerging and Promising Multifunctional Nanomaterial for Textile Application Based on Graphitic Carbon Nitride Heterostructure Nanocomposites
Authors: Glažar Dominika , Jerman Ivan , Tomšič Brigita , Chouhan Raghuraj Singh , Simončič Barbara
Published: January 2023

Nanocomposites constructed with heterostructures of graphitic carbon nitride (g-C3N4), silver (Ag), and titanium dioxide (TiO2) have emerged as promising nanomaterials for various environmental, energy, and clinical applications. In the field of textiles, Ag and TiO2 are already recognized as essential nanomaterials for the chemical surface and bulk modification of various textile materials, but the application of composites with g-C3N4 as a green and visible-light-active photocatalyst has not yet been fully established. This review provides an overview of the construction of Ag/g-C3N4, TiO2/g-C3N4, and Ag/TiO2/g-C3N4 heterostructures; the mechanisms of their photocatalytic activity; and the application of photocatalytic textile platforms in the photochemical activation of organic synthesis, energy generation, and the removal of various organic pollutants from water. Future prospects for the functionalization of textiles using g-C3N4-containing heterostructures with Ag and TiO2 are highlighted.
A Novel Hydrothermal CdS with Enhanced Photocatalytic Activity and Photostability for Visible Light Hydrogenation of Azo Bond: Synthesis and Characterization
Authors: Milani Martina , Mazzanti Michele , Magnacca Giuliana , Caramori Stefano , Molinari Alessandra
Published: January 2023

A good photocatalyst maximizes the absorption of excitation light while reducing the recombination of photogenerated carriers. Among visible light responsive materials, CdS has good carrier transport capacity; however, its photostability is poor and limits its use. Here, the synthesis of a new hydrothermal CdS is reported, and post-synthesis annealing determines crystal properties and spectroscopic characteristics. The introduction of sulfur vacancies as intra band gap states is the key factor for the enhancement of photocatalytic activity. In fact, by spectroscopic and photo-electrochemical experiments, we demonstrate that sulfur vacancies act as an electron sink, favoring the charge transfer process to methyl orange. In addition, the studied hydrothermal CdS is characterized by very high stability, thus enabling a visible-light active photocatalyst that is overall recyclable, stable and more efficient than the commercial benchmark.
Development of Electromagnetic-Wave-Shielding Polyvinylidene Fluoride–Ti3C2Tx MXene–Carbon Nanotube Composites by Improving Impedance Matching and Conductivity
Authors: Zhang Qimei , Cui Jian , Zhao Shuai , Zhang Guangfa , Gao Ailin , Yan Yehai
Published: January 2023

Absorption-dominated electromagnetic interference (EMI) shielding is attained by improving impedance matching and conductivity through structural design. Polyvinylidene fluoride (PVDF)–Ti3C2Tx MXene–single-walled carbon nanotubes (SWCNTs) composites with layered heterogeneous conductive fillers and segregated structures were prepared through electrostatic flocculation and hot pressing of the PVDF composite microsphere-coated MXene and SWCNTs in a layer-by-layer fashion. Results suggest that the heterogeneous fillers improve impedance matching and layered coating, and hot compression allows the MXene and SWCNTs to form a continuous conducting network at the PVDF interface, thereby conferring excellent conductivity to the composite. The PVDF-MXene-SWCNTs composite showed a conductivity of 2.75 S cm−1 at 2.5% MXene and 1% SWCNTs. The EMI shielding efficiency (SE) and contribution from absorption loss to the total EMI SE of PVDF-MXene-SWCNTs were 46.1 dB and 85.7%, respectively. Furthermore, the PVDF-MXene-SWCNTs composite exhibited excellent dielectric losses and impedance matching. Therefore, the layered heteroconductive fillers in a segregated structure optimize impedance matching, provide excellent conductivity, and improve absorption-dominated electromagnetic shielding.
Metal Halide Perovskite Nanowires: Controllable Synthesis, Mechanism, and Application in Optoelectronic Devices
Authors: Lu Yangbin , Qu Kang , Zhang Tao , He Qingquan , Pan Jun
Published: January 2023

Metal halide perovskites are promising energy materials because of their high absorption coefficients, long carrier lifetimes, strong photoluminescence, and low cost. Low-dimensional halide perovskites, especially one-dimensional (1D) halide perovskite nanowires (NWs), have become a hot research topic in optoelectronics owing to their excellent optoelectronic properties. Herein, we review the synthetic strategies and mechanisms of halide perovskite NWs in recent years, such as hot injection, vapor phase growth, selfassembly, and solvothermal synthesis. Furthermore, we summarize their applications in optoelectronics, including lasers, photodetectors, and solar cells. Finally, we propose possible perspectives for the development of halide perovskite NWs.
In Situ Photodeposition of Cobalt Phosphate (CoHxPOy) on CdIn2S4 Photocatalyst for Accelerated Hole Extraction and Improved Hydrogen Evolution
Authors: Xu Jiachen , Li Qinran , Sui Dejian , Jiang Wei , Liu Fengqi , Gu Xiuquan , Zhao Yulong , Ying Pengzhan , Mao Liang , Cai Xiaoyan , Zhang Junying
Published: January 2023

The ternary metal sulfide CdIn2S4 (CIS) has great application potential in solar-to-hydrogen conversion due to its suitable band gap, good stability and low cost. However, the photocatalytic hydrogen (H2) evolution performance of CIS is severely limited by the rapid electron–hole recombination originating from the slow photogenerated hole transfer kinetics. Herein, by simply depositing cobalt phosphate (CoHxPOy, noted as Co-Pi), a non-precious co-catalyst, an efficient pathway for accelerating the hole transfer process and subsequently promoting the H2 evolution reaction (HER) activity of CIS nanosheets is developed. X-ray photoelectron spectroscopy (XPS) reveals that the Co atoms of Co-Pi preferentially combine with the unsaturated S atoms of CIS to form Co-S bonds, which act as channels for fast hole extraction from CIS to Co-Pi. Electron paramagnetic resonance (EPR) and time-resolved photoluminescence (TRPL) showed that the introduction of Co-Pi on ultrathin CIS surface not only increases the probability of photogenerated holes arriving the catalyst surface, but also prolongs the charge carrier’s lifetime by reducing the recombination of electrons and holes. Therefore, Co-Pi/CIS exhibits a satisfactory photocatalytic H2 evolution rate of 7.28 mmol g−1 h−1 under visible light, which is superior to the pristine CIS (2.62 mmol g−1 h−1) and Pt modified CIS (3.73 mmol g−1 h−1).
Rheology and Phase Behavior of Surfactant–Oil–Water Systems and Their Relationship with O/W Nano-Emulsion’s Characteristics Obtained by Dilution
Authors: Guevara Mairis , Mercado Ronald , Vega Katty , Cardenas Antonio , Forgiarini Ana
Published: January 2023

In order to study the relationship between the rheology of a surfactant’s concentrated dispersions and the oil and water liquid crystals from which O/W nanoemulsions (NEs) can be produced by water dilution, the phase diagram of a model SOW (surfactant–oil–water) system was constructed. The dispersion’s compositions to be characterized by rheology were chosen in the diagram’s regions that contain liquid crystal phases. For this, the dilution lines S/O = 25/75, 55/45, and 70/30 with a water content of 20 and 40 wt% (corresponding to surfactant concentrations between 15 and 55 wt%) were chosen. By adding these dispersions to a water pool, NEs were obtained, and it was shown that droplet size distribution depends on the amount of the liquid crystal phase in the initial dispersion and its rheology. The study of the oscillatory amplitude of the dispersion showed a linear viscoelastic plateau (G’ > G”) and a softening deformation region (G” > G’), indicating a viscoelastic behavior of the dispersions. The study was carried out at a constant temperature of 30 °C, and the results show that rheological characterization by itself is not enough to predict that monomodal droplet distributions are obtained. However, the presence and quantity of lamellar liquid crystal phase are important to obtain monodisperse and kinetically stable NEs.
Effect of the Ketogenic Diet on the Prophylaxis and Treatment of Diabetes Mellitus: A Review of the Meta-Analyses and Clinical Trials
Authors: Dyńka Damian , Kowalcze Katarzyna , Ambrozkiewicz Filip , Paziewska Agnieszka
Published: January 2023

The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue; its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.
L-Fucose Suppresses Lipid Accumulation via the AMPK Pathway in 3T3-L1 Adipocytes
Authors: Nakao Tomohiko , Otaki Shiro , Kominami Yuri , Watanabe Soichi , Ito Miho , Aizawa Teruki , Akahori Yusuke , Ushio Hideki
Published: January 2023

L-fucose (Fuc), a monosaccharide with different biological functions in various organisms, exhibits potent anti-obesity effects in obese mice. However, the mechanisms underlying its anti-obesity effects remain largely unknown. In this study, we aimed to investigate the effects of Fuc on lipid metabolism and insulin signaling in 3T3-L1 adipocytes. We found that Fuc treatment suppressed lipid accumulation during adipocyte differentiation. Additionally, Fuc treatment enhanced the phosphorylation of AMP-activated kinase (AMPK) and its downstream pathways, responsible for the regulation of fatty acid oxidation and lipolysis. Furthermore, Fuc-induced activation of the AMPK pathway was diminished by the AMPK inhibitor Compound C, and Fuc treatment considerably promoted glucose uptake via Akt activation in an insulin-resistant state. These findings provide a basis for elucidating the mechanism underlying the anti-obesity effect of Fuc, which may, in the future, be considered as a therapeutic compound for treating obesity and related diseases.
Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias
Authors: Bordat Claire , Vairo Donato , Cuerq Charlotte , Halimi Charlotte , Peiretti Franck , Penhoat Armelle , Vieille-Marchiset Aurélie , Gonzalez Teresa , Michalski Marie-Caroline , Nowicki Marion , Peretti Noël , Reboul Emmanuelle
Published: January 2023

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (−57.0 ± 2.6% to −83.9 ± 1.6%) and cholesterol (−35.3 ± 4.4% to −60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (−41.5 ± 3.7% to −97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.
Development of a Semi-Quantitative Food Frequency Questionnaire to Estimate Macronutrient Intake among Type 2 Diabetes Mellitus Patients in Malaysia
Authors: Amsah Norizzati , Md Isa Zaleha , Ahmad Norfazilah
Published: January 2023

The Food Frequency Questionnaire (FFQ) is one of the most frequently used instruments in epidemiological studies for evaluating dietary intake. Because of the variety of dietary habits within different populations, an FFQ must be tailored to the specific group. To date, no specific FFQ has been developed for type 2 diabetes mellitus (T2DM) patients in Malaysia. In this study, we developed a semi-quantitative FFQ to estimate macronutrient intake among T2DM patients. The development of the FFQ was based on the data acquired from 150 respondents with T2DM from the southern part of Peninsular Malaysia who completed the three-day 24-h dietary recalls. The respondents were selected by convenience sampling. The mean intake from each food item and the proportions of macronutrients were calculated. The approach from a previous study was used to compile a list of foods items with a cumulative 90% macronutrient contribution that is significant for the nutrient of interest. In conclusion, we have successfully developed a new semi-quantitative FFQ with a total of 79 food items and nine food groups. The frequencies of the FFQ were divided into nine categories and this FFQ represents the usual food intake of T2DM patients in Malaysia. However, this tool has yet to be validated in patients with T2DM in Malaysia.
Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults
Authors: Mott Melanie M. , Zhou Xinyi , Bradlee M. Loring , Singer Martha R. , Yiannakou Ioanna , Moore Lynn L.
Published: January 2023

The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30–64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazard’s models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (p = 0.0004) and SBP (p = 0.0284) after four years of follow-up. Higher egg intakes led to lower risks of developing IFG or T2D (HR: 0.72; 95% CI: 0.51–1.03) and high blood pressure (HBP) (HR: 0.68; 0.50–0.93). The beneficial effects of egg consumption were stronger in combination with other healthy dietary patterns. This study found that regular egg consumption as part of a healthy diet had long-term beneficial effects on blood pressure and glucose metabolism and lowered the long-term risks of high blood pressure and diabetes.
Utilizing the Off-Target Effects of T1R3 Antagonist Lactisole to Enhance Nitric Oxide Production in Basal Airway Epithelial Cells
Authors: McMahon Derek B. , Jolivert Jennifer F. , Kuek Li Eon , Adappa Nithin D. , Palmer James N. , Lee Robert J.
Published: January 2023

Human airway sweet (T1R2 + T1R3), umami (T1R1 + T1R3), and bitter taste receptors (T2Rs) are critical components of the innate immune system, acting as sensors to monitor pathogenic growth. T2Rs detect bacterial products or bitter compounds to drive nitric oxide (NO) production in both healthy and diseased epithelial cell models. The NO enhances ciliary beating and also directly kills pathogens. Both sweet and umami receptors have been characterized to repress bitter taste receptor signaling in healthy and disease models. We hypothesized that the sweet/umami T1R3 antagonist lactisole may be used to alleviate bitter taste receptor repression in airway basal epithelial cells and enhance NO production. Here, we show that lactisole activates cAMP generation, though this occurs through a pathway independent of T1R3. This cAMP most likely signals through EPAC to increase ER Ca2+ efflux. Stimulation with denatonium benzoate, a bitter taste receptor agonist which activates largely nuclear and mitochondrial Ca2+ responses, resulted in a dramatically increased cytosolic Ca2+ response in cells treated with lactisole. This cytosolic Ca2+ signaling activated NO production in the presence of lactisole. Thus, lactisole may be useful coupled with bitter compounds as a therapeutic nasal rinse or spray to enhance beneficial antibacterial NO production in patients suffering from chronic inflammatory diseases such as chronic rhinosinusitis.
Narrow Leafed Lupin (Lupinus angustifolius L.) β-Conglutin Seed Proteins as a New Natural Cytotoxic Agents against Breast Cancer Cells
Authors: Escudero-Feliu Julia , García-Costela María , Moreno-SanJuan Sara , Puentes-Pardo Jose D. , Arrabal Sandra Ríos , González-Novoa Paula , Núñez María Isabel , Carazo Ángel , Jimenez-Lopez Jose C. , León Josefa
Published: January 2023

Breast cancer (BC) is the most widespread tumor in women and the second type of most common cancer worldwide. Despite all the technical and medical advances in existing therapies, between 30 and 50% of patients with BC will develop metastasis, which contributes to the failure of existing treatments. This situation urges the need to find more effective prevention and treatment strategies like the use of plant-based nutraceutical compounds. In this context, we purified three Narrow Leafed Lupin (NLL) β-conglutins isoforms using affinity-chromatography and evaluated their effectiveness in terms of viability, proliferation, apoptosis, stemness properties, and mechanism of action on both BC cell lines and a healthy one. NLL β-conglutins proteins have very promising effects at the molecular level on BC cells at very low concentrations, emerging as a potential natural cytotoxic agent and preserving the viability of healthy cells. These proteins could act through a dual mechanism involving tumorigenic and stemness-related genes such as SIRT1 and FoxO1, depending on the state of p53. More studies must be carried out to completely understand the underlying mechanisms of action of these nutraceutical compounds in BC in vitro and in vivo, and their potential use for the inhibition of other cancer cell types.
β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review
Authors: Jayashankar Siva Shantini , Tajul Arifin Khaizurin Tajul , Nasaruddin Muhammad Luqman
Published: January 2023

This scoping review aimed to summarise the effects of the ketone body β-hydroxybutyrate. The review details the revealed pathways and functional properties following its intervention in the context of neurodegenerative diseases. In this study, 5 research publications that met the inclusion and exclusion criteria were shortlisted. Following the intervention, we discovered a tendency of reduced inflammatory status in microglia, as evidenced by lower levels of pro-inflammatory mediators produced, reduced microgliosis in afflicted tissues, and enhanced cognitive functions in neurodegenerative models. We found that there is a significant overlap in the mechanism of action of β-hydroxybutyrate (BHB) via activation of the G-protein-Coupled Receptor 109A (GPR109a) receptor and deactivation of the inflammasome complex. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we have assembled here were consistent, giving us confidence in the intervention’s efficacy. We also discussed new studies where BHB is involved in various roles in regulating inflammation in microglia, allowing for fresh therapeutic targets against neurodegeneration. This brief review provides evidence to support the huge potential of BHB in the treatment of neurodegenerative illnesses.
Thwarting Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) with Common Bean: Dose- and Sex-Dependent Protection against Hepatic Steatosis
Authors: Lutsiv Tymofiy , McGinley John N. , Neil Elizabeth S. , Foster Michelle T. , Thompson Henry J.
Published: January 2023

Hepatic steatosis signifies onset of metabolic dysfunction-associated fatty liver disease (MAFLD) caused by disrupted metabolic homeostasis compromising liver function. Regular consumption of common beans reduces the risk of metabolic impairment, but its effective dose, the impact of biological sex, and underlying mechanisms of action are unknown. We fed female and male C57BL6/J mice with obesogenic yet isocaloric diets containing 0%, 17.5%, 35%, and 70% of total dietary protein derived from cooked whole common beans. Liver tissue was collected for histopathology, lipid quantification, and RNA-seq analyses. Beans qualitatively and quantitatively diminished hepatic fat deposition at the 35% dose in female and 70% dose in male mice. Bean-induced differentially expressed genes (DEGs) most significantly mapped to hepatic steatosis and revealed dose-responsive inhibition of de novo lipogenesis markers (Acly, Acaca, Fasn, Elovl6, Scd1, etc.) and triacylglycerol biosynthesis, activation of triacylglycerol degradation, and downregulation of sterol regulatory element-binding transcription factor 1 (SREBF1) signaling. Upregulated fatty acid β-oxidation was more prominent in females, while suppression of Cd36-mediated fatty acid uptake—in males. Sex-dependent bean effects also involved DEGs patterns downstream of peroxisome proliferator-activated receptor α (PPARα) and MLX-interacting protein-like (MLXIPL). Therefore, biological sex determines amount of common bean in the diet required to prevent hepatic lipid accumulation.
Spin–Orbital Coupling and Conservation Laws in Electromagnetic Waves Propagating through Chiral Media
Authors: Lee Hyoung-In
Published: January 2023

This study examines the characteristics of the electromagnetic waves that propagate through an unbounded space filled with a homogeneous isotropic chiral medium. The resulting characters are compared to those of the electromagnetic waves propagating through an achiral free space. To this goal, we form energy conservation laws for key bilinear parameters in a chiral case. Due to a nonzero medium chirality, conservation laws turn out to contain extra terms that are linked to the spin–orbit coupling, which is absent for an achiral case. In this way, we identified where the neat hierarchy exhibited by the achiral case among the key bilinear parameters is destroyed by a medium chirality. As an example, we took a plane wave for the chiral case to evaluate those bilinear parameters. Resultantly, the conservation laws for a chiral case are found to reveal inconsistencies among several bilinear parameters that constitute the conservation laws, thereby prompting us to establish partial remedies for formulating proper wave-propagation problems. Therefore, adequate applications of boundary conditions are found to be necessary after examining typical problems available from the literature.
Acknowledgment to the Reviewers of Osteology in 2022
Authors:   Osteology Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Co-Infection with Cryptosporidium meleagridis and Enterocytozoon bieneusi in an HIV+ Colombian Patient
Authors: Hernández-Castro Carolina , Martínez-Rosado Larry L. , Dashti Alejandro , Köster Pamela C. , Bailo Begoña , Orozco María C. , Santín Mónica , González-Barrio David , Carmena David
Published: January 2023

A 44-year-old human immunodeficiency virus-infected (HIV+) female with severe immunodeficiency Category 3 (C3) diagnosed in 2010 was admitted to hospital with acute diarrhoea. She was non-adherent to antiretroviral therapy (ART) and had a previous suspicion of respiratory symptoms with a cough that had been persisting for 15 days. Clinical examination revealed severe immune deterioration (viral load: 109,655 copies/mL; CD4+ count: 14 cells/mm3), respiratory symptoms (negative sputum Gram stain and tuberculosis culture), and neurological deterioration (serological assays negative for Cryptococcus spp. and Toxoplasma gondii). A coproculture was negative for Campylobacter spp., Salmonella spp., and Shigella spp. Ziehl–Neelsen staining of faecal smears revealed the presence of Cryptosporidium spp. oocysts. PCR testing and sequencing confirmed a concomitant infection with C. meleagridis and Enterocytozoon bieneusi. The patient was treated with metronidazole (500 mg every 8 h for 5 days) and nitazoxanide (500 mg every 12 h for 14 days). After requesting voluntary discharge and abandoning ART and parasiticidal treatments, she experienced a dramatic deterioration of her state of health and contact with her was lost. Our results have demonstrated that molecular-based testing improves the detection of opportunistic pathogens that are difficult to detect by routine microscopy, allows for transmission dynamics investigations, and assists in choosing the best chemotherapeutical option.
Comparison of Analytical Sensitivity (Limit of Detection) of Xpert MTB/RIF and Xpert MTB/RIF Ultra for Non-Sputum Specimens
Authors: Nielsen Marisa C. , Clarner Paula , Paroha Ruchi , Lee Sunhee , Thwe Phyu M. , Ren Ping
Published: January 2023

Tuberculosis (TB) is a significant public health threat and has remained a leading cause of death in many parts of the world. Rapid and accurate testing and timely diagnosis can improve treatment efficacy and reduce new exposures. The Cepheid Xpert® MTB/RIF tests have two marketed products (US-IVD and Ultra) that are widely accepted for diagnosis of TB but have not yet been approved for non-sputum specimens. Despite numerous studies in the literature, no data for the analytical sensitivity of these two products on the non-sputum samples are available to date. This is the first study that systematically determined the analytical sensitivities of both US-IVD and Ultra tests on cerebrospinal fluid (CSF), tissue, and bronchoalveolar lavage (BAL). The limits of detection (LoDs) on the US-IVD test for both Mycobacterium tuberculosis and rifampin resistance in CFU/mL, respectively, were as follows: CSF (3.3 and 4.6), tissue (15 and 23), and bronchoalveolar lavage (BAL) (45 and 60), and on the Ultra test: CSF (0.16 and 2.7), tissue (0.11 and 12), and BAL (0.65, and 7.5). Overall, the analytical sensitivities of the Ultra test were substantially better than US-IVD for all sample types tested. This study provided a foundation for using either the US-IVD or Ultra test for the early detection of both pulmonary and extrapulmonary (EP) TB. Furthermore, using Ultra could result in higher TB case detection rates in subjects with paucibacillary TB and EP TB, positively impacting WHO goals to eradicate TB.
Acknowledgment to the Reviewers of Pathogens in 2022
Authors:   Pathogens Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Added Value of Scintillating Element in Cerenkov-Induced Photodynamic Therapy
Authors: Schneller Perrine , Collet Charlotte , Been Quentin , Rocchi Paul , Lux François , Tillement Olivier , Barberi-Heyob Muriel , Schohn Hervé , Daouk Joël
Published: January 2023

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (68Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from 68Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free 68Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during 68Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of 68Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to 68Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT.
Fabrication of Gastro-Floating Famotidine Tablets: Hydroxypropyl Methylcellulose-Based Semisolid Extrusion 3D Printing
Authors: Yang Hyun Seok , Kim Dong Wuk
Published: January 2023

Semisolid extrusion (SSE) three-dimensional (3D) printing uses drug-loaded paste for the printing process, which is capable of constructing intricate 3D structures. This research presents a unique method for fabricating gastro-floating tablets (GFT) using SSE. Paste-loaded famotidine with a matrix made of hydroxypropyl methylcellulose (HPMC) were prepared. Nine 3D printed tablets were developed with different HPMC concentrations and infill percentages and evaluated to determine their physicochemical properties, content uniformity, dissolution, and floating duration. The crystallinity of the drug remained unchanged throughout the process. Dissolution profiles demonstrated the correlation between the HPMC concentration/infill percentage and drug release behavior over 10 h. All the fabricated GFTs could float for 10 h and the Korsmeyer-Peppas model described the dissolution kinetics as combination of non-Fickian or anomalous transport mechanisms. The results of this study provided insight into the predictability of SSE 3D printability, which uses hydro-alcoholic gel-API blend materials for GFTs by controlling traditional pharmaceutical excipients and infill percentages. SSE 3D printing could be an effective blueprint for producing controlled-release GFTs, with the additional benefits of simplicity and versatility over conventional methods.
Inclisiran—Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
Authors: Wołowiec Łukasz , Osiak Joanna , Wołowiec Anna , Wijata Aleksandra , Grześk Elżbieta , Kozakiewicz Mariusz , Banach Joanna , Nowaczyk Alicja , Nowaczyk Jacek , Grześk Grzegorz
Published: January 2023

Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.
pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance
Authors: Teixeira Patrícia V. , Adega Filomena , Martins-Lopes Paula , Machado Raul , Lopes Carla M. , Lúcio Marlene
Published: January 2023

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.
Photothermally Controlled Drug Release of Poly(d,l-lactide) Nanofibers Loaded with Indocyanine Green and Curcumin for Efficient Antimicrobial Photodynamic Therapy
Authors: Gutberlet Bernd , Preis Eduard , Roschenko Valeri , Bakowsky Udo
Published: January 2023

Chronic wound infections with antibiotic-resistant bacteria have become a significant problem for modern healthcare systems since they are often associated with high costs and require profound topical wound management. Successful wound healing is achieved by reducing the bacterial load of the wound and providing an environment that enhances cell growth. In this context, nanofibers show remarkable success because their structure offers a promising drug delivery platform that can mimic the native extracellular matrix and accelerate cell proliferation. In our study, single-needle electrospinning, a versatile and cost-efficient technique, was used to shape polymers into an applicable and homogeneous fleece capable of a photothermally triggered drug release. It was combined with antimicrobial photodynamic therapy, a promising procedure against resistant bacteria. Therefore, poly(d,l-lactide) nanofibers loaded with curcumin and indocyanine green (ICG) were produced for local antimicrobial treatment. The mesh had a homogeneous structure, and the nanofibers showed a smooth surface. Recordings with a thermal camera showed that near-infrared light irradiation of ICG increased the temperature (>44 °C) in the surrounding medium. Release studies confirmed more than 29% enhanced curcumin release triggered by elevated temperature. The antimicrobial activity was tested against the gram-positive strain Staphylococcus saprophyticus subsp. bovis and the gram-negative strain Escherichia coli DH5 alpha. The nanofibers loaded with both photosensitizers and irradiated with both wavelengths reduced the bacterial viability (~4.4 log10, 99.996%) significantly more than the nanofibers loaded with only one photosensitizer (<1.7 log10, 97.828%) or irradiated with only one wavelength (<2.0 log10, 98.952%). In addition, our formulation efficiently eradicated persistent adhered bacteria by >4.3 log10 (99.995%), which was also confirmed visually. Finally, the produced nanofibers showed good biocompatibility, proven by the cellular viability of mouse fibroblasts (L929). The data demonstrate that we have developed a new economic nanofiber formulation, which offers a triggered drug release, excellent antimicrobial properties, and good biocompatibility.
Comparing Salivary Caffeine Kinetics of 13C and 12C Caffeine for Gastric Emptying of 50 mL Water
Authors: Grimm Michael , Rump Adrian , Meilicke Lisa , Feldmüller Maximilian , Keßler Rebecca , Scheuch Eberhard , Tzvetkov Mladen Vassilev , Weitschies Werner
Published: January 2023

Gastric water emptying as a critical parameter for oral drug absorption can be investigated by several imaging techniques or by the interpretation of pharmacokinetics of appropriate substances. Recently introduced salivary caffeine kinetics is a valuable tool, but the required caffeine abstinence limits its applicability. To avoid the caffeine abstinence, stable isotope-labeled caffeine might be used, but the representability and transferability of kinetics for evaluation of gastric emptying must be demonstrated. Thus, salivary caffeine pharmacokinetics were compared for naturally occurring 12C-caffeine and 13C3-caffeine after the administration of water under fasting conditions in six healthy young subjects. For this purpose, an ice capsule containing the two caffeine species was administered with 50 mL tap water. Gastric water emptying was simultaneously quantified using magnetic resonance imaging (MRI). Gastric emptying of 50 mL of water could be successfully evaluated. The salivary caffeine kinetics of 13C3- and 12C-caffeine were nearly congruent and showed good linear correlations in all subjects, with a mean correlation coefficient of 0.96 in pooled data. Thus, the substitution of natural 12C caffeine with stable isotope-labeled 13C3-caffeine offers the opportunity for broader application of the salivary caffeine gastric emptying technique and increases the robustness of the method against environmental contamination with caffeine.
The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
Authors: Sterenczak Katharina A. , Fuellen Georg , Jünemann Anselm , Guthoff Rudolf F. , Stachs Oliver , Stahnke Thomas
Published: January 2023

One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TGF)-β1-mediated fibroblast model was evaluated in vitro. Primary ocular fibroblasts were isolated, cultivated and a dose–response test including determination of the half maximal effective concentration (EC50) for KM was conducted. Transformation of fibroblasts into myofibroblasts was induced by TGF-β1and immunofluorescence (IF), and Western blot (WB) analyses were performed with fibroblasts and myofibroblasts. IF analyses were carried out using antibodies against α-smooth muscle actin (α-SMA) and fibronectin, and protein detection of intracellular and extracellular proteins was performed by WB. Using the dose–response test, the viability, cytotoxicity and EC50 of KM after 24 and 48 h were determined. Fibroblasts exposed to various KM concentrations showed no increase in α-SMA and extracellular matrix expression. In TGF-ß1-stimulated myofibroblasts, KM inhibited the expression of α-SMA and fibronectin in a concentration-dependent manner. These findings demonstrate that KM could impair the transformation of fibroblasts into myofibroblasts and the expression of proteins involved in fibrotic processes, representing a potential agent for specific fibrosis prevention in future therapeutic concepts.
Current Challenges and Opportunities of Photodynamic Therapy against Cancer
Authors: Huis in ‘t Veld Ruben V. , Heuts Jeroen , Ma Sen , Cruz Luis J. , Ossendorp Ferry A. , Jager Martine J.
Published: January 2023

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor vasculature and induce the release and/or exposure of damage-associated molecular patterns (DAMPs) that may initiate an antitumor immune response. However, there are currently several challenges of PDT that limit its widespread application for certain indications in the clinic. METHODS: A literature study was conducted to comprehensively discuss these challenges and to identify opportunities for improvement. RESULTS: The most notable challenges of PDT and opportunities to improve them have been identified and discussed. CONCLUSIONS: The recent efforts to improve the current challenges of PDT are promising, most notably those that focus on enhancing immune responses initiated by the treatment. The application of these improvements has the potential to enhance the antitumor efficacy of PDT, thereby broadening its potential application in the clinic.
Acknowledgment to the Reviewers of Pharmaceutics in 2022
Authors:   Pharmaceutics Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Protein Biocargo and Anti-Inflammatory Effect of Tomato Fruit-Derived Nanovesicles Separated by Density Gradient Ultracentrifugation and Loaded with Curcumin
Authors: Mammadova Ramila , Maggio Serena , Fiume Immacolata , Bokka Ramesh , Moubarak Maneea , Gellén Gabriella , Schlosser Gitta , Adamo Giorgia , Bongiovanni Antonella , Trepiccione Francesco , Guescini Michele , Pocsfalvi Gabriella
Published: January 2023

Plant-derived nanovesicles (PDNVs) have become attractive alternatives to mammalian cell-derived extracellular vesicles (EVs) both as therapeutic approaches and drug-delivery vehicles. In this study, we isolated tomato fruit-derived NVs and separated them by the iodixanol density gradient ultracentrifugation (DGUC) into twelve fractions. Three visible bands were observed at densities 1.064 ± 0.007 g/mL, 1.103 ± 0.006 g/mL and 1.122 ± 0.012 g/mL. Crude tomato PDNVs and DGUC fractions were characterized by particle size-distribution, concentration, lipid and protein contents as well as protein composition using mass spectrometry-based proteomics. Cytotoxicity and anti-inflammatory activity of the DGUC fractions associated to these bands were assessed in the lipopolysaccharide (LPS)-stimulated human monocytic THP-1 cell culture. The middle and the low-density visible DGUC fractions of tomato PDNVs showed a significant reduction in LPS-induced inflammatory IL-1β cytokine mRNA production. Functional analysis of proteins identified in these fractions reveals the presence of 14-3-3 proteins, endoplasmic reticulum luminal binding proteins and GTP binding proteins associated to gene ontology (GO) term GO:0050794 and the regulation of several cellular processes including inflammation. The most abundant middle-density DGUC fraction was loaded with curcumin using direct loading, sonication and extrusion methods and anti-inflammatory activity was compared. The highest entrapment efficiency and drug loading capacity was obtained by direct loading. Curcumin loaded by sonication increased the basal anti-inflammatory activity of tomato PDNVs.
Antiseptic-Loaded Casein Hydrogels for Wound Dressings
Authors: Garcia Leonor Vasconcelos , Silva Diana , Costa Maria Madalena , Armés Henrique , Salema-Oom Madalena , Saramago Benilde , Serro Ana Paula
Published: January 2023

Chronic wound treatment accounts for a substantial percentage of the medical expenses worldwide. Improving and developing novel wound care systems can potentially help to handle this problem. Wound dressings loaded with antiseptics may be an important tool for wound care, as they inhibit bacterial growth at the wound site. The goal of the present work was to investigate the potential of using casein hydrogel dressings loaded with two antiseptic drugs, Octiset® or polyhexanide, to treat chronic wounds. Casein-based hydrogels are inexpensive and have several properties that make them suitable for biomedical applications. Two types of casein were used: casein sodium salt and acid casein, with the formulations being labelled CS and C, respectively. The hydrogels were characterised with respect to their physical properties (swelling capacity, water content, morphology, mechanical resistance, and stability), before and after sterilisation, and they showed adequate values for the intended application. The hydrogels of both formulations were able to sustain controlled drug-release for, at least, 48 h. They were demonstrated to be non-irritant, highly haemocompatible, and non-cytotoxic, and revealed good antimicrobial properties against Staphylococcus aureus and Pseudomonas aeruginosa. Steam-heat sterilisation did not compromise the material’s properties. The in vivo performance of C hydrogel loaded with Octiset® was evaluated in a case study with a dog. The efficient recovery of the wounds confirms its potential as an alternative for wound treatment. To our knowledge, this is the first time that wound dressings loaded with Octiset®, one of the most efficient drugs for wound treatment, were prepared and tested.