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Li6ZnO4 was chemically modified by nickel addition, in order to develop different compositions of the solid solution Li6Zn1-xNixO4. These materials were evaluated bifunctionally; analyzing their CO2 capture performances, as well as on their catalytic properties for H2 production via dry reforming of methane (DRM). The crystal structures of Li6Zn1-xNixO4 solid solution samples were determined through X-ray diffraction, which confirmed the integration of nickel ions up to a concentration around 20 mol%, meanwhile beyond this value, a secondary phase was detected. These results were supported by XPS and TEM analyses. Then, dynamic and isothermal thermogravimetric analyses of CO2 capture revealed that Li6Zn1-xNixO4 solid solution samples exhibited good CO2 chemisorption efficiencies, similarly to the pristine Li6ZnO4 chemisorption trends observed. Moreover, a kinetic analysis of CO2 isothermal chemisorptions, using the Avrami-Erofeev model, evidenced an increment of the constant rates as a function of the Ni content. Since Ni2+ ions incorporation did not reduce the CO2 capture efficiency and kinetics, the catalytic properties of these materials were evaluated in the DRM process. Results demonstrated that nickel ions favored hydrogen (H2) production over the pristine Li6ZnO4 phase, despite a second H2 production reaction was determined, methane decomposition. Thereby, Li6Zn1-xNixO4 ceramics can be employed as bifunctional materials.
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Dióxido de Carbono , Hidrogênio , Metano , Hidrogênio/química , Metano/química , Dióxido de Carbono/química , Níquel/química , Catálise , Modelos QuímicosRESUMO
Red mud and phosphogypsum are two of the most typical bulk industrial solid wastes. How they can be efficiently recycled as resources on a large scale and at low costs has always been a global issue that urgently needs to be solved. By constructing a small-scale test site and preparing two types of artificial soils using red mud and phosphogypsum, this study simulated their engineering applications in vegetation restoration and ecological reconstruction. According to the results of this study, the artificial soils contained a series of major elements (e.g. O, Si, Al, Fe, Ca, Na, K, and Mg) similar to those in common natural soil, and preliminarily possessed basic physicochemical properties (pH, moisture, organic matter, and cation exchange capacity), main nutrient conditions (nitrogen, phosphorus and potassium), and biochemical characteristics that could meet the demands of plant growth. A total of 18 different types of adaptable plants (e.g. wood, herbs, flowers, succulents, etc) grew in the test sites, indicating that the artificial soils could be used for vegetation greening and landscaping. The preliminary formation of microbial (fungal and bacterial) community diversity and the gradually enriched arthropod community diversity reflected the constantly improving quality of the artificial soils, suggesting that they could be used for the gradual construction of artificial soil micro-ecosystems. Overall, the artificial soils provided a feasible solution for the large-scale, low-cost, and highly efficient synergistic disposal of red mud and phosphogypsum, with enormous potential for future engineering applications. They are expected to be used for vegetation greening, landscaping, and ecological environment improvement in tailings, collapse, and soil-deficient areas, as well as along municipal roads.
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Xylanases (EC 3.2.1.8) catalyze the breakdown of xylan, which is the second most abundant polysaccharide in plant cell walls. Biological catalysts have gained greater global attention than chemical catalysts in different industrial processes because they are highly selective, easy to control and have a negligible environmental impact. The aim of this study was to investigate the xylanolytic potential of white-rot fungi, optimize their physicochemical conditions and characterize the resulting xylanase. Sixty-eight white-rot fungus (WRF) isolates were screened for their xylanolytic potential and growth conditions for maximal xylanase production using cheap agricultural residue (wheat straw) as the sole carbon source. Five WRF isolates with high xylanase yields (73.63 ± 0.0283-63.6 ± 0.01247 U/ml) were selected by qualitative and quantitative screening methods. The optimum xylanase production occurred at pH 5.0 and 28 °C. Solid-state fermentation (SSF) yielded a high amount of xylanase. The highest xylanase activity (80.9-61.274 U/mL) was recorded in the pH range of 5.0-6.5 and at 50 °C. The metal ions Mg2+, Ca2+ and Mn2+ enhanced the activity of xylanase (127.28-110.06 %), while Cu2+, Fe2+ and K+ inhibited the activity with 43.4-17 % losses. The km and Vmax were 0.32-0.545 mg/mL and 86.95-113.63 µmol/min/mg, respectively. This finding indicates that wheat straw can be used for large-scale xylanase production under SSF conditions. The pH and temperature profiles and stabilities indicate that the xylanase produced in the present study can be applied in food and animal feed industries.
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Waste-to-energy (WtE) power plants, supplied mainly with municipal solid waste (MSW) and refuse-derived fuel (RDF), which convert waste into electricity, have emerged as a solution to Thailand's waste management problems. This study focused on identifying and studying the critical success factors (CSFs) that influence the success of MSW and RDF power plants in Thailand. This study employed interpretive structural Modelling and cross-impact matrix multiplication applied to a classification analysis to evaluate the impact of these CSFs on the development of WtE projects. The results showed that, for MSW, most CSFs were related to energy and waste management policies, followed by waste quality for electricity generation. In addition, strong financial resources and appropriate power plant locations are important for MSW management success. Conversely, for RDF, most CSFs were sufficient waste quality for electricity generation and performed well according to licensing conditions. In this study, high-level CSFs indicated that these factors were crucial for MSW and RDF development. CSFs differ based on specific technologies and regulations. However, sufficient waste quality (heating value and moisture content) is a common CSF in the MSW and RDF technologies. This study provides valuable insights into the CSFs that affect the development of WtE. Understanding and addressing these CSFs is essential for the development and operation of WtE power plants in Thailand and other countries with similar conditions. Thus, policy-makers and other stakeholders can make informed decisions to ensure the success of WtE projects.
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The development of efficient and high-performance electric vehicle (EV) batteries relies on improving various components, such as the anode and cathode electrodes, separators, and electrolytes. This review paper offers an elaborate overview of different materials for these components, emphasizing their respective contributions to the improvement of EV battery performance. Carbon-based materials, metal composites, and polymer nanocomposites are explored for the anode, offering high energy density and capacity. However, they are noted to be susceptible to Li plating. Unique structures, such as Titanium niobium oxide (TiNb2O7), offer high theoretical capacity, quick Li+ intercalation, and an extended lifecycle. Meanwhile, molybdenum disulfide (MoS2), with 2D and 3D structures, exhibits high reversible specific capacity, outstanding rate performance, and cyclic stability, showing promising properties as anode material. For cathodes, lithium-iron phosphate (LFP), lithium-cobalt oxide (LCO), lithium-nickel-cobalt-aluminum oxide (NCA), lithium-nickel-manganese-cobalt oxide (NMC), and cobalt-free lithium-nickel-manganese oxide (NMO) are considered, offering specific energy and capacity advantages. For instance, LFP cathode electrodes show good thermal stability, good electrochemical performance, and long lifespan, while NMC exhibits high specific energy, relatively high capacity, and cost savings. NCA has a high specific energy, decent specific power, large capacity, and a long lifecycle. NMO shows excellent rate capability, cyclic stability, and cost-effectiveness but with limited cycle performance. Separator innovations, including polyolefin materials, nanofiber separators, graphene-based composites, and ceramic-polymer composites, are analyzed for use as separators, considering mechanical strength, porosity, wettability with the electrolyte, electrolytic absorption, cycling efficiency, and ionic conductivity. The electrolyte comprises lithium salts such as lithium tetrafluoroborate (LiBF4), lithium hexafluorophosphate (LiPF6), and other salts dissolved in carbonate solvents. This improves energy density, capacity, and cycling stability and provides high ion mobility and resistance to decomposition. By examining the existing literature, this review also explores research on the solid electrolyte interface (SEI) and lithium plating, providing valuable insights into understanding and mitigating these critical issues. Despite the progress, limitations such as practical implementation challenges, potential cost implications, and the need for further research on scale-up feasibility and long-term durability are acknowledged. These efforts to enhance the electrochemical characteristics of key battery parameters-positive and negative electrodes, separators, and electrolytes-aim to improve capacity, specific energy density, and overall energy density. These continuous endeavours strive for faster charging of EV batteries and longer travel ranges, contributing to the ongoing evolution of EV energy storage systems. Thus, this review paper not only explores remarkable strides in EV battery technology but also underscores the imperative of addressing challenges and propelling future research for sustainable and high-performance electric vehicle energy storage systems.
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Asparagine and glutamine depletion operated by the drug Asparaginase (ASNase) has revolutionized therapy in pediatric patients affected by Acute Lymphoblastic Leukemia (ALL), bringing remissions to a remarkable 90 % of cases. However, the knowledge of the proproliferative role of asparagine in adult and solid tumors is still limited. We have here analyzed the effect of ASNase on three adenocarcinoma cell lines (A549, lung adenocarcinoma, MCF-7, breast cancer, and 786-O, kidney cancer). In contrast to MCF-7 cells, 786-O and A549 cells proved to be a relevant target for cell cycle perturbation by asparagine and glutamine shortage. Indeed, when the cell-cycle was analyzed by flow cytometry, A549 showed a canonical response to asparaginase, 786-O cells, instead, showed a reduction of the percentage of cells in the G1 phase and an increase of those in the S-phase. Despite an increased number of PCNA and RPA70 positive nuclear foci, BrdU and EdU incorporation was absent or strongly delayed in treated 786-O cells, thus indicating a readiness of replication forks unmatched by DNA synthesis. In 786-O asparagine synthetase was reduced following treatment and glutamine synthetase was totally absent. Interestingly, DNA synthesis could be recovered by adding Gln to the medium. MCF-7 cells showed no significant changes in the cell cycle phases, in DNA-bound PCNA and in total PCNA, but a significant increase in ASNS and GS mRNA and protein expression. The collected data suggest that the effect observed on 786-O cells following ASNase treatment could rely on mechanisms which differ from those well-known and described for leukemic blasts, consisting of a complete block in the G1/S transition in proliferating cells and on an increase on non-proliferative (G0) blasts.
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Quaternary phosphonium compounds (QPCs) and phosphine oxides (POs) are emerging contaminants that are attracting increasing attention. In the present study, a method for the quantification of QPCs and POs in multiple environmental media was developed using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analytes were extracted from water samples using solid phase extraction, and for the solid samples, ultrasonic extraction was employed. Compared with analytical methods established by previous studies, the approach developed in this study is more suitable for the quantitative analysis of compounds along with high sensitivity. The method quantification limit reached 0.12-2.55 ngâ L-1 in water samples and 0.004-0.10 ngâ g-1 in solid samples. The recoveries of target analytes spiked at low, medium and high concentrations in water and solid samples were in the range of 56.4-120 %, with relative standard deviations below 20 % (n = 6). Furthermore, the validated method succeeded in applying to analyse of eight QPCs and four POs in real environmental samples. At least five QPCs and two POs were detected in each environmental medium. This quantitative method would assist in further investigations on the occurrence, migration and the source of QPCs and POs.
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This work presents a methodology integrating Non-Linear Programming (NLP) for multi-objective and multi-period optimization, addressing sustainable waste management and energy conversion challenges. It integrates waste-to-energy (WtE) technologies such as Anaerobic Digestion (AD), Incineration (Inc), Gasification (Gsf), and Pyrolysis (Py), and considers thermochemical, technical, economic, and environmental considerations through rigorous non-linear functions. Using Mexico City as a case study, the model develops waste management strategies that balance environmental and economic aims, considering social impacts. A trade-off solution is proposed to address the conflict between objectives. The economical optimal solution generates 1.79M$ with 954 tons of CO2 emissions while the environmental one generates 0.91M$ and reduces emissions by 54%, where 40% is due to gasification technology. Moreover, the environmentally optimal solution, with incineration and gasification generates 9500 MWh/day and 5960 MWh/day, respectively, demonstrates the capacity of the model to support sustainable energy strategies. Finally, this work presents an adaptable framework for sustainable waste management decision-making.
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PURPOSE: To summarize the abdominal computed tomography (CT) imaging and clinicopathological data of patients with SPNs of the pancreas and analyze the accuracy of preoperative CT diagnosis and features. MATERIALS AND METHODS: Between June 2006 and June 2023, CT images of 120 histopathologically proven SPNs in the pancreas were retrospectively reviewed. Fifteen features, including age, sex, and CT-determined features, were included in a multiple stepwise regression analysis. The correlations between features and SPNs, including odds ratios (ORs) and 95% confidence intervals (CIs), were evaluated. RESULTS: Among the 120 patients, the diagnostic accuracy of CT was 43.3%. The baseline CT results of patients with a correct diagnosis and misdiagnosis revealed significant differences in sex (P = 0.043), age (P = 0.004), boundary (P = 0.037) and encapsulation (P = 0.002) between the two groups. The preoperative imaging diagnostic accuracy was significantly greater in females than in males (47.9% vs. 25.0%, P = 0.043). The immunohistochemical indices did not significantly differ between the two groups. The results of univariate analysis revealed significant differences in sex (P = 0.048), age (P = 0.014), tumor length (P = 0.023), tumor boundaries (P = 0.039) and capsule type (P = 0.003). The results of multivariate analysis revealed that encapsulation was closely related to the diagnostic accuracy of CT (P = 0.04). CONCLUSIONS: The accuracy of CT in the diagnosis of SPNs is low, but a lengthâdiameter ratio of the tumor approaching 1.0, encapsulation and clear boundaries are important CT-determined features. The capsule is an independent CT predictor in the diagnosis of SPNs.
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Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Prognóstico , Idoso , Seguimentos , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/diagnósticoRESUMO
3D electron diffraction (3DED) is increasingly employed to determine molecular and crystal structures from micro-crystals. Indomethacin is a well known, marketed, small-molecule non-steroidal anti-inflammatory drug with eight known polymorphic forms, of which four structures have been elucidated to date. Using 3DED, we determined the structure of a new ninth polymorph, σ, found within an amorphous solid dispersion, a product formulation sometimes used for active pharmaceutical ingredients with poor aqueous solubility. Subsequently, we found that σ indomethacin can be produced from direct solvent evaporation using dichloromethane. These results demonstrate the relevance of 3DED within drug development to directly probe product formulations.
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Simulated body fluid (SBF) and artificial saliva (AS) are used in biomedical and dental research to mimic the physiological conditions of the human body. In this study, the biomimetic precipitation of double-doped amorphous calcium phosphate in SBF and AS are compared by thermodynamic modelling of chemical equilibrium in the SBF/AS-CaCl2-MgCl2-ZnCl2-K2HPO4-H2O and SBF/AS-CaCl2-MgCl2-ZnCl2-K2HPO4-Glycine/Valine-H2O systems. The saturation indices (SIs) of possible precipitate solid phases at pH 6.5, close to pH of AS, pH 7.5, close to pH of SBF, and pH 8.5, chosen by us based on our previous experimental data, were calculated. The results show possible precipitation of the same salts with almost equal SIs in the two biomimetic environments at the studied pHs. A decrease in the saturation indices of magnesium and zinc phosphates in the presence of glycine is a prerequisite for reducing their concentrations in the precipitates. Experimental studies confirmed the thermodynamic predictions. Only X-ray amorphous calcium phosphate with incorporated Mg (5.86-8.85 mol%) and Zn (0.71-2.84 mol%) was obtained in the experimental studies, irrespective of biomimetic media and synthesis route. Solid-state nuclear magnetic resonance (NMR) analysis showed that the synthesis route affects the degree of structural disorder of the precipitates. The lowest concentration of dopant ions was obtained in the presence of glycine. Further, the behaviour of the selected amorphous phase in artificial saliva was studied. The dynamic of Ca2+, Mg2+, and Zn2+ ions between the solid and liquid phases was monitored. Both direct excitation 31P NMR spectra and 1H-31P CP-MAS spectra proved the increase in the nanocrystalline hydroxyapatite phase upon increasing the incubation time in AS, which is more pronounced in samples with lower additives. The effect of the initial concentration of doped ions on the solid phase transformation was assessed by solid-state NMR.
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The convenient and sensitive detection of metabolites is of great significance for understanding human health status and drug development. Solid-phase electrochemiluminescence (ECL) enzyme electrodes show great potential in metabolite detection based on the enzyme-catalyzed reaction product hydrogen peroxide (H2O2). Herein, a solid-phase ECL enzyme sensor was fabricated based on a confined emitter and an immobilized enzyme using electrostatic nanocage array, constructing a platform for the sensitive detection of cholesterol. The electrostatic cage nanochannel consists of a bipolar and bilayer vertically aligned mesoporous silica film (bp-VMSF). The upper layer of bp-VMSF is an amino-modified, positively charged VMSF (p-VMSF), and the lower layer is a negatively charged VMSF (n-VMSF). The most commonly used ECL probe tris(bipyridine)ruthenium(II) (Ru(bpy)32+) is fixed in n-VMSF by electrostatic adsorption from n-VMSF and electrostatic repulsion from the upper p-VMSF, generating significantly enhanced and stable ECL signals. The successful preparation of the electrostatic cage was characterized by scanning electron microscopy (SEM) and electrochemical methods. After amino groups on the outer surface of bp-VMSF were derivatized with aldehyde, cholesterol oxidase (ChOx) molecules were covalently immobilized. The successful construction of the enzyme electrode was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). When the corresponding enzyme substrate, cholesterol, was present in the solution, the ECL signal of Ru(bpy)32+ was quenched by the enzyme-catalyzed reaction product H2O2, enabling the high-sensitivity detection of cholesterol. The linear range for detecting cholesterol was from 0.05 mM to 5.0 mM, with a limit of detection (LOD) of 1.5 µM.
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Técnicas Biossensoriais , Colesterol , Técnicas Eletroquímicas , Eletrodos , Colesterol/análise , Enzimas Imobilizadas/química , Medições Luminescentes , Peróxido de Hidrogênio/análise , Humanos , Dióxido de Silício/química , Colesterol OxidaseRESUMO
Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.
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Infecções por Citomegalovirus , Citomegalovirus , Transplantados , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transplante de Órgãos/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Idoso , DNA Viral , Células Dendríticas/imunologia , ELISPOT , Testes Imunológicos/métodos , Citocinas/metabolismoRESUMO
High-shear (HS) melt granulation and hot melt extrusion (HME) were compared as perspective melt-based technologies for preparation of amorphous solid dispersions (ASDs). ASDs were prepared using mesoporous carriers (Syloidâ 244FP or Neusilinâ US2), which were loaded with carvedilol dispersed in polymeric matrix (polyethylene glycol 6000 or Soluplusâ). Formulations with high carvedilol content were obtained either by HME (11 extrudates with polymer:carrier ratio 1:1) or HS granulation (6 granulates with polymer:carrier ratio 3:1). DSC and XRD analysis confirmed the absence of crystalline carvedilol for the majority of prepared ADSs, thus confirming the stabilizing effect of selected polymers and carriers over amorphous carvedilol. HME produced larger particles compared to HS melt granulation, which was in line with better flow time and Carr index of extrudates. Moreover, SEM images revealed smoother surface of ASDs obtained by HME, contributing to less obstructed flow. The rougher and more porous surface of HS granules was correlated to larger granule specific surface area, manifesting in faster carvedilol release from Syloidâ 244FP-based granules, as compared to their HME counterparts. Regarding dissolution, the two HS-formulations performed superior to pure crystalline carvedilol, thereby confirming the suitability of HS melt granulation for developing dosage forms with improved carvedilol dissolution.
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Hyperphosphorylation of the protein tau is one of the biomarkers of neurodegenerative diseases in the category of tauopathies. However, the molecular level, mechanistic, role of this common post-translational modification (PTM) in enhancing or reducing the aggregation propensity of tau is unclear, especially considering that combinatorial phosphorylation of multiple sites can have complex, non-additive, effects on tau protein aggregation. Since tau proteins stack in register and parallel to elongate into pathological fibrils, phosphoryl groups from adjacent tau strands with 4.8 Å separation must find an energetically favorable spatial arrangement. At first glance, this appears to be an unfavorable configuration due to the proximity of negative charges between phosphate groups from adjacent neighboring tau fibrils. However, this study tests a counterhypothesis that phosphoryl groups within the fibril core-forming segments favorably assemble into highly ordered, hydrogen-bonded, one-dimensionally extended wires under biologically relevant conditions. We selected two phosphorylation sites associated with neurodegeneration, serine 305 (S305p) and tyrosine 310 (Y310p), on a model tau peptide jR2R3-P301L (tau295-313) spanning the R2/R3 splice junction of tau, that readily aggregate into a fibril with characteristics of a seed-competent mini prion. Using multiple quantum spin counting (MQ-SC) by 31P solid-state NMR of phosphorylated jR2R3-P301L tau peptide fibrils, enhanced by dynamic nuclear polarization, we find that at least six phosphorous spins must neatly arrange in 1D within fibrils or in 2D within a protofibril to yield the experimentally observed MQ-coherence orders of four. We found that S305p stabilizes the tau fibrils and leads to more seeding-competent fibrils compared to jR2R3 P301L or Y310p. This study introduces a new concept that phosphorylation of residues within a core forming tau segment can mechanically facilitate fibril registry and stability due a hitherto unrecognized role of phosphoryl groups to form highly ordered, extended, 1D wires that stabilize pathological tau fibrils.
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Aim: Phenol red is commonly used in cell culture media, but can be detrimental to bioanalysis of in vitro samples as it may impact instrument reliability. Many researchers do their final stage of culture in 'phenol red free' media, but in collaborative work this is not always feasible.Materials & methods: A comparison was made between typical extraction methods to reduce phenol red matrix interferences, including organic solvent precipitation and solid phase extraction.Results: The final method was demonstrated to be precise and accurate for the measurement of a target analyte by LC-MS/MS, and was applied to an in vitro ADC deconjugation study.Conclusion: This method allows for for continued bioanalytical support of in vitro models used in drug development.
[Box: see text].
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Meios de Cultura , Imunoconjugados , Fenolsulfonaftaleína , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Fenolsulfonaftaleína/química , Meios de Cultura/química , Imunoconjugados/química , Imunoconjugados/análise , Humanos , Extração em Fase Sólida/métodos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Increasing attention is being afforded to understanding the bidirectional relationship that exists between oral drugs and the gut microbiota. Often overlooked, however, is the impact that pharmaceutical excipients exert on the gut microbiota. Subsequently, in this study, we contrasted the pharmacokinetic performance and gut microbiota interactions between two commonly employed formulations for poorly soluble compounds, namely 1) an amorphous solid dispersion (ASD) stabilised by poly(vinyl pyrrolidone) K-30, and 2) a lipid nanoemulsion (LNE) comprised of medium chain glycerides and lecithin. The poorly soluble antipsychotic, lurasidone, was formulated with ASD and LNE due to its rate-limiting dissolution, poor oral bioavailability, and significant food effect. Both the ASD and LNE were shown to facilitate lurasidone supersaturation within in vitro dissolution studies simulating the gastrointestinal environment. This translated into profound improvements in oral pharmacokinetics in rats, with the ASD and LNE exerting comparableâ¯â¼â¯2.5-fold improvements in lurasidone bioavailability, compared to the pure drug. The oral formulations imparted contrasting effects on the gut microbiota, with the LNE depleting the richness and abundance of the microbial ecosystem, as evidenced through reductions in alpha diversity (Chao1 index) and operational taxonomical units (OTUs). In contrast, the ASD exerted a 'gut neutral' effect, whereby a mild enrichment of alpha diversity and OTUs was observed. Importantly, this suggests that ASDs are effective solubility-enhancing formulations that can be used without comprising the integrity of the gut microbiota - an integral consideration in the treatment of mental health disorders, such as schizophrenia, due to the role of the gut microbiota in regulating mood and cognition.
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In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to "off-the-shelf" therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.
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In the United States, illicit fentanyl is often trafficked as blue tablets mimicking the legitimate M-30 oxycodone tablet produced by Mallinckrodt. The analysis of dyes extracted from seized fentanyl tablets could provide a useful tool for law enforcement to establish linkages between cases and could prove useful for attributing a seizure to a given trafficking organization. Fentanyl tablet seizures associated with a particular drug trafficking organization (DTO), either through investigative or intelligence information, were used as the sample set for this study. The blue dye from the tablets was isolated by solid phase extraction and then qualitatively and quantitatively analyzed via ultraviolet-visible spectroscopy. This research revealed that the illicit tableting facilities use a different dye than several known pharmaceutical companies. The concentration of dye in individual tablets within a seizure proved to be very minimal, and the small sample size made it difficult to draw linkages from case to case. Analysis of the dyes could not effectively differentiate between the drug trafficking organizations in the tested population due to each DTO using the same dye; however, it is important to note that the dye found was consistent between illicit tablets.
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Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.