Modeling and optimization of the ratio of fluorophores: a step towards enhancing the sensitivity of ratiometric probes.

In the ratiometric fluorescent (RF) strategy, the selection of fluorophores and their respective ratios helps to create visual quantitative detection of target analytes. This study presents a framework for optimizing ratiometric probes, employing both two-component and three-component RF designs. For this purpose, in a two-component ratiometric nanoprobe designed for detecting methyl parathion (MP), an organophosphate pesticide, yellow-emissive thioglycolic acid-capped CdTe quantum dots (Y-QDs) (analyte-responsive), and blue-emissive carbon dots (CDs) (internal reference) were utilized. Mathematical polynomial equations modeled the emission profiles of CDs and Y-QDs in the absence of MP, as well as the emission colors of Y-QDs in the presence of MP separately. In other two-/three-component examples, the detection of dopamine hydrochloride (DA) was investigated using an RF design based on blue-emissive carbon dots (B-CDs) (internal reference) and N-acetyl L-cysteine functionalized CdTe quantum dots with red/green emission colors (R-QDs/G-QDs) (analyte-responsive). The colors of binary/ternary mixtures in the absence and presence of MP/DA were predicted using fitted equations and additive color theory. Finally, the Euclidean distance method in the normalized CIE XYZ color space calculated the distance between predicted colors, with the maximum distance defining the real-optimal concentration of fluorophores. This strategy offers a more efficient and precise method for determining optimal probe concentrations compared to a trial-and-error approach. The model's effectiveness was confirmed through experimental validation, affirming its efficacy.

Non-salt based co-amorphous formulation produced by freeze-drying.

Amino acids-based co-amorphous system (CAM) has shown to be a promising approach to overcome the dissolution challenge of biopharmaceutics classification system class II drugs. To date, most CAM formulations are based on salt formation at a 1:1 M ratio and are prepared by mechanical activation. However, its use in medicinal products is still limited due to the lack of in-depth understanding of non-ionic based molecular interactions. There are also limited studies on the effect of drug-to-co-former ratio, the development of more scalable, less aggressive, manufacturing processes such as freeze drying and its dissolution benefits. This work aims to investigate the effect of the ratio of tryptophan (a model non-ionic amino acid) to indomethacin (a model drug) on a non-salt-based CAM prepared via freeze-drying with the tert-butyl alcohol-water cosolvent system. The CAM material was systemically characterized at various stages of the freeze-drying process using DSC, UV-Vis, FT-IR, NMR, TGA and XRPD. Dissolution performance and physical stability upon storage were also investigated. Freeze-drying using the cosolvent system has been successfully shown to produce CAMs. The molecular interactions involving H-bonding, H/π and π-π between compounds have been confirmed by FT-IR and NMR. The drug release rate for formulations with a 1.5:1 drug: amino acid molar ratio (or 1:0.42 wt ratio) or below is found to be significantly improved compared to the pure crystalline drug. Furthermore, formulation with a 2.3:1 drug:amino acid molar ratio (or 1:0.25 wt ratio) or below have shown to be physically stable for at least 9 months when stored at dry condition (5% relative humidity, 25 °C) compared to the pure amorphous indomethacin. We have demonstrated the potential of freeze-drying using tert-butyl alcohol-water cosolvent system to produce an optimal non-salt-based class II drug-amino acid CAM.

Experimental Investigation of Effect of Flake Silver Powder Content on Sintering Structure and Properties of Front Silver Paste of Silicon Solar Cell.

Optimizing the performance of front silver paste is of great significance in improving the efficiency of the photoelectric conversion of crystalline silicon solar cells. As a conductive functional phase of silver paste, the structure and performance of silver powder have an important influence on the sintering process of silver paste and the conductivity of silver electrodes. Because of their two-dimensional structure, flake silver powders can effectively increase the contact area with other silver powders and silicon cells before sintering. Additionally, flake silver particles have higher surface energy and sintering activity than spherical silver particles of the same particle size. However, recent research has mainly focused on the influence of the particle size of silver powder. This paper fills the research gap regarding the morphology of silver powders and clarifies the influence of flake silver powders on the performance of silver paste. The influence of the ratio of spherical silver powder to flake silver powder in silver paste on the sheet resistance, adhesion, and specific contact resistivity of silver film after sintering at 800 °C was studied, and the optimal ratio was determined according to a cross-sectional contact picture of the silver film. The results showed that with the increase in the mass fraction of the flake silver powder, the sheet resistance of the sintered silver film gradually increased, the adhesion first increased and then decreased, and the specific contact resistance first decreased and then increased. When the flake silver powder content was 0%, the minimum sheet resistance of the silver film was 2.41 m Ω/☐. When the flake silver powder content was 30%, the maximum adhesion of the silver film was 6.07 N. When the flake silver powder content was 50%, the minimum specific contact resistivity of the silver film was 0.25 Ω·cm2. In conclusion, when the flake silver powder content was 30%, the comprehensive performance of the silver film was the best.

The Effect of Circulating Fluidised Bed Bottom Ash Content on the Mechanical Properties and Drying Shrinkage of Cement-Stabilised Soil.

This study aimed to determine the effect of circulating fluidised bed bottom ash (CFB-BA) content on the mechanical properties and drying shrinkage of cement-stabilised soil. Experiments were performed to study the changes in unconfined compressive strength and expansibility of cement-stabilised soil with different CFB-BA contents and the underlying mechanisms based on microscopic properties. The results show that CFB-BA can effectively increase the unconfined compressive strength of the specimen and reduce the amount of cement in the soil. When the combined content of CFB-BA and cement in the soil was 30%, the unconfined compressive strength of the specimen with C/CFB = 2 after 60 days of curing was 10.138 MPa, which is 1.4 times that of the pure cement specimen. However, the CFB-BA does not significantly improve the strength of the soil and cannot be added alone as a cementing material to the soil. Additionally, swelling tests showed that the addition of CFB-BA to cement-stabilised soil can significantly reduce the drying shrinkage. This research project provides reference values for the application of CFB-BA in cement-soil mixing piles, including compressive strength and the reduction in the shrinkage deformation of specimens.

Optimal ratio of 18α- and 18ß-glycyrrhizic acid for preventing alcoholic hepatitis in rats.

The glycyrrhizic acid (GA) epimers 18α- and 18ß-GA exert anti-inflammatory and hepatoprotective activities, which may help to protect against alcoholic liver disease, particularly alcoholic hepatitis (AH). The aim of the present study was to investigate the optimal ratio of 18α- and 18ß-GA for preventing AH in rats. Different groups of rats were administered seven different ratios of 18α- and 18ß-GA (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10; 10.83 mg/kg), vehicle control, or silymarin (22.75 mg/kg) as a positive control, followed by administration of 40% alcohol (10 ml/kg) once a day for four weeks. Subsequently, livers were isolated and routinely processed for histological examination. The serum levels of 23 cytokines and chemokines associated with AH were examined with a Bio-Plex 200 Luminex assay. It was revealed that all ratios of 18α- and 18ß-GA prevented alcohol-induced liver injury, as evidenced by a lesser degree of histopathological changes in the liver as compared with those in the model group. Furthermore, the levels of 15 cytokines/chemokines were significantly altered after alcohol administration, which was significantly inhibited by, pre-treatment with different proportions of 18α- and 18ß-GA, particularly at a ratio of 4:6, for most cytokines/chemokines associated with AH, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-7, IL-6, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-3α, macrophage- and granulocyte macrophage colony-stimulating factor, chemokine (C-X-C motif) ligand 1(GRO/KC), vascular endothelial growth factor and C-C motif chemokine ligand 5 (RANTES). Taken together, based on these results the optimal ratio of 18α- and 18ß-GA to prevent AH in model rats was considered to be 4:6.

Combined administration of naringenin and hesperetin with optimal ratio maximizes the anti-cancer effect in human pancreatic cancer via down regulation of FAK and p38 signaling pathway.

BACKGROUND: We have previously reported the functional anti-cancer effects of the products of enzymatic hydrolysis of Citrus unshiu peel (εCUP) and fermented extraction of Citrus unshiu peel (ƒCUP) in human pancreatic cancer. Despite their different characteristics and effects, the underlying mechanism remains elusive. PURPOSE: In this study, we further demonstrate the impact of ingredient contents of Citrus unshiu peel on the cancer's natural features. METHODS: Anti-pancreatic cancer activities following combined treatment of naringenin and hesperetin were demonstrated in vitro and in vivo experiments. RESULTS: Combined treatment with naringenin and hesperetin inhibited the growth of human pancreatic cancer cells (εCUP mimic condition, p < 0.001 for Miapaca-2 cells) through induction of caspase-3 cleavage compared to separate treatment with naringenin or hesperetin. Combined treatment with naringenin and hesperetin also inhibited the migration (εCUP mimic condition, p < 0.001 for Panc-1 cells) of human pancreatic cancer cells. The εCUP mimic condition had the most effective anti-cancer features; in contrast, which had no inhibitory effect on growth and migration of normal cells (HUVECs and Detroit551 cells). In addition, εCUP mimic condition inhibited the phosphorylation of focal adhesion kinase (FAK) and p38 signaling compared with separate treatment with naringenin or hesperetin. Of note, εCUP mimic condition showed a prominent anti-growth effect (p < 0.001) compared with control or ƒCUP mimic condition in vivo xenograft models. CONCLUSION: These results suggest that combined treatment with naringenin and hesperetin might be a promising anti-cancer strategy for pancreatic cancers without eliciting toxicity on normal cells.

Exploring the optimal ratio of d-glucose/l-aspartic acid for targeting carbon dots toward brain tumor cells.

Targeting imaging to the desired site of action can increase the accuracy and effectiveness of diagnostic and treatment. In this work, a series of fluorescent carbon dots (CDs) were prepared by varying molar ratios of d-glucose (Glu) to l-aspartic acid (Asp). Their photophysical properties, morphologies and structures were investigated in detail. More important, the targeting ability was screened by confocal laser scanning microscopy and flow cytometry. The results indicate that CDs prepared from the optimal molar ratio of Glu/Asp (7:3) exhibit the highest targeting ability on C6 glioma cells. This work highlights the interplay of molecular design and corresponding functions, and open new possibility of developing state-of-art nanoparticles for biomedical applications.

EFFICIENT ALGORITHMS FOR THE OPTIMAL-RATIO REGION DETECTION PROBLEMS IN DISCRETE GEOMETRY WITH APPLICATIONS.

In this paper, we study several interesting optimal-ratio region detection (ORD) problems in d-D (d ≥ 3) discrete geometric spaces, which arise in high dimensional medical image segmentation. Given a d-D voxel grid of n cells, two classes of geometric regions that are enclosed by a single or two coupled smooth heighfield surfaces defined on the entire grid domain are considered. The objective functions are normalized by a function of the desired regions, which avoids a bias to produce an overly large or small region resulting from data noise. The normalization functions that we employ are used in real medical image segmentation. To our best knowledge, no previous results on these problems in high dimensions are known. We develop a unified algorithmic framework based on a careful characterization of the intrinsic geometric structures and a nontrivial graph transformation scheme, yielding efficient polynomial time algorithms for solving these ORD problems. Our main ideas include the following. We observe that the optimal solution to the ORD problems can be obtained via the construction of a convex hull for a set of O(n) unknown 2-D points using the hand probing technique. The probing oracles are implemented by computing a minimum s-t cut in a weighted directed graph. The ORD problems are then solved by O(n) calls to the minimum s-t cut algorithm. For the class of regions bounded by a single heighfield surface, our further investigation shows that the O(n) calls to the minimum s-t cut algorithm are on a monotone parametric flow network, which enables to detect the optimal-ratio region in the complexity of computing a single maximum flow.

Optimization of Compatibility Ratio of Rhizoma Zingiberis and Pericarpium Citri Reticulatae Extracts for Counteracting Rats Myocardial Ischemia by Uniform Design / 中药新药与临床药理

Objective To observe the protective effects of the extracts of Rhizoma Zingiberis and Pericarpium Citri Reticulatae on myocardial ischemia reduced by isoproterenol(ISO) in rats,and to explore their optimal ratio.Methods Acute myocardial ischemia rat model was established by continuously subcutaneous injection of large-dose.Then the content of the serum creatine kinase(CK) within 24 hours in rats were detected,and the optiaml ratio of Rhizoma Zingiberis and Pericarpium Citri Reticulatae was optimized by uniform design.Results Compared with the control group,the content of CK in the model group was significantly increased(P