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OBJECTIVE: This study aimed to determine suitable combinations of text and pictogram sizes for older adults and investigated the visual prioritization of pictogram versus text. BACKGROUND: Icons have become an indispensable part of application (app) design. Pictogram size and text size of icons influence the usability of apps, especially by aged users. However, few studies have investigated the influences of different pictogram and text size combinations on readability, legibility, and visual search performance for older adults. METHOD: This study used eye-tracking technology to investigate the effects of different pictogram and text size combinations as well as familiarity on readability, legibility, and visual search performance for older adults. A 3 (pictogram size) × 3 (text size) × 2 (familiarity) repeated-measures experimental design was used. RESULTS: The results of this study suggest that pictogram size and text size significantly affect visual search performance and that familiarity moderates the effect of text size on distribution of fixation duration proportion for text and pictograms. CONCLUSION: Large pictogram and text sizes improved the readability and legibility of icons for older adults. Furthermore, the older adults fixated the area of text prior to pictograms when the pictogram size was larger than 72 × 72 px (1.38° × 1.38°) in the visual search task. APPLICATION: The results of this study suggest using different combinations of pictogram and text sizes for older adults under different scenarios. The findings of this study act as practical support for designers and developers of mobile apps for older adults.
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Compreensão , Aplicativos Móveis , Idoso , Humanos , Design de SoftwareRESUMO
OBJECTIVE: The purpose of this study was to investigate the effects of semantic congruence and incongruence on sign identification by using event-related potentials (ERPs). BACKGROUND: Sign systems have crucial roles in public spaces and traffic facilities. Poorly designed signs can easily confuse pedestrians and drivers and reduce the efficiency of public activities and urban administration. METHOD: Thirty-one participants completed a sign identification experiment independently in a laboratory setting. Experimental materials were selected from GB/T 10001, a Chinese national recommendation standard that is officially named Public Information Graphical Symbols for Use on Signs. All ERP data were processed using MATLAB 13b, and behavioral data were analyzed using Stata 14. RESULTS: N170, P200, N300, and N400 components were induced during semantic processing. Statistical analysis revealed that semantic congruence has a main effect on N300 in the frontal region and has a main effect on N400 at FZ in the frontal region, CPZ in the parietal-central region, and PZ in the parietal region. Amplitudes of N300 induced by picture-word matching were considerably different between the two experimental conditions at electrodes FZ and FCZ. Amplitudes of N400 were significantly larger in the incongruent condition than in the congruent condition. CONCLUSION: The study demonstrated that N300 and N400 are promising indicators for measuring semantic congruence in future sign design. APPLICATION: Our findings provide ERP indicators for measuring the semantic congruence of sign design, which can be easily applied to improve the efficiency of sign design and sign comprehension.
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Compreensão , Potenciais Evocados , Diretórios de Sinalização e Localização , Semântica , China , Cognição , Eletroencefalografia , Humanos , Monitorização Fisiológica , Adulto JovemRESUMO
Mononuclear iron-containing oxygenases conduct a diverse variety of oxidation functions in biology, including the oxidative demethylation of methylated nucleic acids and histones. Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids, which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes. Here we present structural characterization of oxidation intermediates for these demethylases. Using a chemical cross-linking strategy, complexes of AlkB-double stranded DNA (dsDNA) containing 1,N(6)-etheno adenine (εA), N(3)-methyl thymine (3-meT) and N(3)-methyl cytosine (3-meC) are stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and α-ketoglutarate (αKG), to dioxygen initiates oxidation in crystallo. Glycol (from εA) and hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the oxidative demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is oxidatively removed from different biological substrates.
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Reparo do DNA , Dioxigenases/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , Ferro/metabolismo , Oxigenases de Função Mista/metabolismo , Homólogo AlkB 2 da Dioxigenase Dependente de alfa-Cetoglutarato , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato , Catálise , Reagentes de Ligações Cruzadas/química , Cristalização , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dioxigenases/química , Proteínas de Escherichia coli/química , Humanos , Ácidos Cetoglutáricos/metabolismo , Metilação , Oxigenases de Função Mista/química , Modelos Moleculares , Oxirredução , Eletricidade Estática , Especificidade por SubstratoRESUMO
The first step for the hydrolysis of a phosphate monoester (pNPP(2-)) in enzymes of the alkaline phosphatase (AP) superfamily, R166S AP and wild-type NPP, is studied using QM/MM simulations based on an approximate density functional theory (SCC-DFTBPR) and a recently introduced QM/MM interaction Hamiltonian. The calculations suggest that similar loose transition states are involved in both enzymes, despite the fact that phosphate monoesters are the cognate substrates for AP but promiscuous substrates for NPP. The computed loose transition states are clearly different from the more synchronous ones previously calculated for diester reactions in the same AP enzymes. Therefore, our results explicitly support the proposal that AP enzymes are able to recognize and stabilize different types of transition states in a single active site. Analysis of the structural features of computed transition states indicates that the plastic nature of the bimetallic site plays a minor role in accommodating multiple types of transition states and that the high degree of solvent accessibility of the AP active site also contributes to its ability to stabilize diverse transition-state structures without the need of causing large structural distortions of the bimetallic motif. The binding mode of the leaving group in the transition state highlights that vanadate may not always be an ideal transition state analog for loose phosphoryl transfer transition states.
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Fosfatase Alcalina/química , Teoria Quântica , Fosfatase Alcalina/metabolismo , Domínio Catalítico , Estabilidade Enzimática , Escherichia coli/enzimologia , Modelos Moleculares , Estrutura MolecularRESUMO
Dangerous goods marks are the most effective means of alerting individuals to the potential dangers associated with the transport of dangerous goods. In order to gain a better understanding of how dangerous goods marks convey risk information, the cognitive processing of dangerous goods marks was examined by measuring event-related potentials (ERPs). We recruited 23 participants, and their ERP data were recorded. We discovered that the dangerous goods marks elicited a larger P200 amplitude and a smaller N300 amplitude, indicating that, compared to other marks, the dangerous goods marks exhibited stronger warning information and drew more attention from the subjects. Simultaneously, dangerous goods marks elicited insufficient emotional arousal in individuals. Therefore, these findings suggest that the designs of dangerous goods marks need to be improved, such as improving the graphic consistency. Changes in ERP patterns can be used to measure the risk perception level of dangerous goods marks, which can be used as an accurate indicator of the effectiveness of warning sign design. In addition, this study provides a theoretical foundation for the cognitive understanding mechanism of dangerous goods marks.
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Eletroencefalografia , Potenciais Evocados , Humanos , Emoções , Processos Mentais , Reconhecimento PsicológicoRESUMO
Several members of the Alkaline Phosphatase (AP) superfamily exhibit a high level of catalytic proffciency and promiscuity in structurally similar active sites. A thorough characterization of the nature of transition state for different substrates in these enzymes is crucial for understanding the molecular mechanisms that govern those remarkable catalytic properties. In this work, we study the hydrolysis of a phosphate diester, MpNPP(-), in solution, two experimentally well-characterized variants of AP (R166S AP, R166S/E322Y AP) and wild type Nucleotide pyrophosphatase/phosphodiesterase (NPP) by QM/MM calculations in which the QM method is an approximate density functional theory previously parametrized for phosphate hydrolysis (SCC-DFTBPR). The general agreements found between these calculations and available experimental data for both solution and enzymes support the use of SCC-DFTBPR/MM for a semiquantitative analysis of the catalytic mechanism and nature of transition state in AP and NPP. Although phosphate diesters are cognate substrates for NPP but promiscuous substrates for AP, the calculations suggest that their hydrolysis reactions catalyzed by AP and NPP feature similar synchronous transition states that are slightly tighter in nature compared to that in solution, due in part to the geometry of the bimetallic zinc motif. Therefore, this study provides the first direct computational support to the hypothesis that enzymes in the AP superfamily catalyze cognate and promiscuous substrates via similar transition states to those in solution. Our calculations do not support the finding of recent QM/MM studies by López-Canut and co-workers, who suggested that the same diester substrate goes through a much looser transition state in NPP/AP than in solution, a result likely biased by the large structural distortion of the bimetallic zinc site in their simulations. Finally, our calculations for different phosphate diester orientations and phosphorothioate diesters highlight that the interpretation of thio-substitution experiments is not always straightforward.
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Fosfatase Alcalina/metabolismo , Biocatálise , Fosfatos/química , Fosfatos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/metabolismo , Teoria Quântica , Fosfatase Alcalina/química , Fosfatase Alcalina/genética , Hidrólise , Modelos Moleculares , Mutação , Diester Fosfórico Hidrolases/química , Conformação Proteica , Pirofosfatases/química , Soluções , Especificidade por Substrato , Termodinâmica , Zinco/químicaRESUMO
With the global society aging, it is necessary to investigate suitable font size based on reading time/speed, readability and legibility for older adults. This study used a systematic review of previous and existing relevant research on font size for older adults and research on the psychophysics of reading and analyzed the outcomes based on reading time/speed, readability, legibility and the usability evaluation methods employed. Studies were selected from databases GOOGLE SCHOLAR, WEB OF SCIENCE, PUBMED, and SCIENCE DIRECT. An inclusion criterion was used to remove duplicates and avoid inconsistencies. Results suggest that older adults preferred larger font sizes. However, there exists a critical size at which readability declines. Inconsistencies in evaluation methods and experimental procedures were observed in the selected articles. This study suggested a reusable catalog of usability evaluation methods, eye tracking for user testing and a questionnaire for inquiry as suitable usability evaluation methods, a uniform metrics to measure font size (visual angle of font) in arcminutes and parameters to consider when investigating font size for older adults to ensure consistency in future studies.
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With the increasingly powerful functions of vehicle-mounted entertainment facilities, people (especially young drivers) like to listen to music while driving to render different atmospheres and emotions. However, emotions are important factors affecting drivers' decisions, behavior and may reduce drivers' hazard perception (HP), even promote dangerous driving behaviors of drivers. The purpose of this study is to explore the young and elderly drivers in assessing the HP difference under different emotional states. We conducted a 3 × 2 mixed experimental design with emotion as a within-participants variable and age as a between-participants factor. A sample of 14 young drivers (mean age = 22.21, SD = 1.05) and 13 elderly drivers (mean age = 54.08, SD = 2.72) completed the HP self-assessment of road traffic warning signs under negative emotion, neutral emotion, and positive emotion, randomly. The results showed that the young had the highest self-assessment HP under the negative emotion arousal condition, while the old had the highest self-assessment HP under the positive emotion arousal condition. In addition, When both groups were in a positive arousal state, the older group perceived more hazards than the young group. The results could help designers create driving emotions suitable for different driver groups, thus improving their perception of hazards and reducing risky driving.
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Vehicle "faces" are a crucial factor influencing consumer intention to purchase gasoline and electric vehicles. However, little empirical evidence has demonstrated whether people process a vehicle's face similarly to a human's face. We investigated the neural processing relationship among human facial emotions and facial emotions of gasoline and electric vehicles using a 2 (emotional) × 3 (face type) repeated measures design and electroencephalograph (EEG) recordings. The results showed that human faces appear to share a partly similar neural processing mechanism in the latency of 100-300 ms, and that both human and vehicle faces elicited the ERP components N170, EPN, and P2. The large EPN and P2 suggest that gasoline vehicle facial emotions can be perceived more efficiently than those of electric vehicles. These findings provide an insight for vehicle designers to better understand the facial emotions presented by cars.
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BACKGROUND: Circular RNA (circRNA) has been shown to be associated with osteoarthritis (OA) progression. Circ_0116061 has been found to be highly expressed in OA cartilage tissues, but its role and mechanism in OA progression remain unclear. METHODS: Expression levels of circ_0116061, microRNA (miR)-200b-5p, and Smad ubiquitin regulatory factor 2 (SMURF2) were detected using quantitative real-time PCR. The proliferation and apoptosis of cells were measured using cell counting kit 8 (CCK8) assay, colony formation assay, and flow cytometry. Furthermore, the protein levels of proliferation-related marker, apoptosis-related markers, inflammatory factors, and SMURF2 were tested using western blot (WB) analysis. In addition, the interaction between miR-200b-3p and circ_0116061 or SMURF2 was examined using dual-luciferase reporter assay and biotin-labeled RNA pull-down assay. RESULTS: Circ_0116061 and SMURF2 were highly expressed, and miR-200b-3p was lowly expressed in OA cartilage tissues. Knockdown of circ_0116061 could promote the proliferation and inhibit the apoptosis and inflammation of OA chondrocytes. MiR-200b-3p could be sponged by circ_0116061, and its inhibitor could reverse the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes. SMURF2 was a target of miR-200b-3p, and its expression was positively regulated by circ_0116061. Silencing of SMURF2 also could enhance the proliferation and suppress the apoptosis and inflammation of OA chondrocytes. Furthermore, the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes also could be reversed by SMURF2 overexpression. CONCLUSION: Our data showed that circ_0116061 might regulate the miR-200b-3p/SMURF2 axis to promote the progression of OA.
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Apoptose/genética , Proliferação de Células/genética , Condrócitos/patologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Osteoartrite/patologia , RNA Circular/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Idoso , Apoptose/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Condrócitos/metabolismo , Progressão da Doença , Expressão Gênica/fisiologia , Humanos , Pessoa de Meia-Idade , Osteoartrite/metabolismo , RNA Circular/metabolismo , RNA Circular/fisiologiaRESUMO
Design aesthetics play a crucial role in product design. Stakeholders expect to develop highly valuable premium products by improving the design aesthetics of products. Nevertheless, the question of how to evaluate the value of design aesthetics has not been fully addressed. In this study, the effects of design aesthetics on the evaluation of the value of a product were investigated through a strictly controlled experiment in which the neural responses of the participants were measured. Forty participants completed the design aesthetics experiment in a laboratory setting. Images of products were divided into two categories: those representing high- and low-design-aesthetic stimuli. Both types of images were labeled with the same price. Overall, the images representing high design aesthetics elicited smaller N100 and lower P200 amplitudes than did the images representing low design aesthetics. This finding indicates that low design aesthetics attracted more attention than high design aesthetics did and that high design aesthetics triggered positive emotions. Low-design-aesthetic products elicited a larger N400 amplitude. This finding reveals the inconsistency between labeled and expected prices. The present study indicates that the N400 component can be used as an indicator for measuring the perceived value of a product in a future product design study. Our study provides event-related potential indicators that can be easily applied in decision making for measuring the perceived value of a product's design.
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BACKGROUND: Circular RNAs (circRNAs) are associated with rheumatoid arthritis (RA) development. The purpose of this study is to explore the function and mechanism of circRNA fragile mental retardation 2 (circ-AFF2) in the processes of rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). METHODS: Circ-AFF2, microRNA (miR)-650, and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) levels were determined in synovial tissues of RA and RAFLSs by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell proliferation, inflammatory response, apoptosis, caspase3 activity, migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated using Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), flow cytometry, Transwell, and Western blotting analyses. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and pull-down assays were performed to assess the binding relationship. RESULTS: Circ-AFF2 expression level was enhanced in synovial tissues of RA and RAFLSs. Circ-AFF2 overexpression facilitated cell proliferation, inflammatory response, migration, invasion, and EMT and repressed apoptosis in RAFLSs. Circ-AFF2 downregulation played an opposite role. Circ-AFF2 targeted miR-650, and miR-650 downregulation reversed the effect of circ-AFF2 interference on RAFLS processes. CNP was targeted by miR-650, and circ-AFF2 increased CNP expression by regulating miR-650. MiR-650 overexpression constrained cell proliferation, inflammatory response, migration, invasion, and EMT and contributed to apoptosis by decreasing CNP in RAFLSs. CONCLUSION: Circ-AFF2 promoted proliferation, inflammatory response, migration, and invasion of RAFLSs by modulating the miR-650/CNP axis.
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2',3'-Nucleotídeo Cíclico 3'-Fosfodiesterase/fisiologia , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Fibroblastos/patologia , Expressão Gênica , Inflamação/genética , Inflamação/patologia , MicroRNAs/fisiologia , Proteínas Nucleares/fisiologia , RNA Circular/fisiologia , Sinoviócitos/patologia , 2',3'-Nucleotídeo Cíclico 3'-Fosfodiesterase/genética , 2',3'-Nucleotídeo Cíclico 3'-Fosfodiesterase/metabolismo , Células Cultivadas , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Fibroblastos/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Sinoviócitos/metabolismoRESUMO
The interaction between children and books is an essential part of the reading experience. Publishers all over the world are working to cultivate reading habits in children and attract attention to traditional books. Considering the invaluable nature of these early reading experiences. This paper investigated the effects of book interaction design on 5-6 years old children, taking into account reading preferences, measuring reading time, and emotional response to improve their reading experience and potentially design books according to these interactions. The results showed that preschool children (5-6 years old) prefer sensory interaction, and that book interaction design has a significant influence on reading time, affective experience, and subjective ratings. Girls around 5-6 years preferred folding interaction and pop-up interaction in reading. This study summarizes these results in order to provide practical guidelines for book publishers, enabling them to design better books for children.
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For early-stage diagnostics, there is a strong demand for sensors that can rapidly detect biomarkers at ultralow concentration or even at the single-molecule level. Compared with other types of sensors, optical microfibers are more convenient for use as point-of-care devices in early-stage diagnostics. However, the relatively low sensitivity strongly hinders their use. To this end, an optical microfiber is functionalized with a plasmonic nanointerface consisting of black phosphorus-supported Au nanohybrids. The microfiber is able to detect epidermal growth factor receptor (ErbB2) at concentrations ranging from 10 zM to 100 nM, with a detection limit of 6.72 zM, enabling detection at the single-molecule level. The nanointerface-sensitized microfiber is capable of differentiating cancer cells from normal cells and treating cancer cells through cellular photothermal therapy. This work opens up a possible approach for the integration of cellular diagnosis and treatment.
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Biomarcadores , Técnicas Biossensoriais , Nanotecnologia , Fibras Ópticas , Imagem Individual de Molécula/métodos , Algoritmos , Humanos , Hipertermia Induzida/métodos , Modelos Teóricos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Fototerapia/métodos , Receptor ErbB-2 , Sensibilidade e Especificidade , Imagem Individual de Molécula/instrumentaçãoRESUMO
The translocation of cytochrome c (cyt c) from mitochondria and out of cell is an important signal of cell apoptosis. Monitoring this process extracellularly without invasion and cytotoxicity to cells is of great importance to understand certain diseases at the cellular level; however, it requires sensors with ultrahigh sensitivity and miniature size. This study reports an optical microfiber aptasensor with a silver-decorated graphene (Ag@RGO) nanointerface for real-time cellular cyt c monitoring. Owing to an interfacial sensitization effect coupled with the plasmonic electromagnetic enhancement of silver nanoparticles and chemical enhancement of graphene platforms, which enhances the energy density on microfiber surface obviously, the lowest limit of detection achieved is 6.82 × 10-17 m, which is approximately five orders of magnitude lower than those of existing methods. This microfiber successfully detects the ultralow concentrations of cyt c present during the initial stage of apoptosis in situ. As the microfiber functionalized by Ag@RGO nanointerface can be varied to meet any specific detection objective, this work opens up new opportunities to quantitatively monitor biological functions occurring at the cellular level.
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To improve the description of electrostatic interaction between QM and MM atoms when the QM is SCC-DFTB, we adopt a Klopman-Ohno (KO) functional form which considers the finite size of the QM and MM charge distributions. Compared to the original implementation that used a simple Coulombic interaction between QM Mulliken and MM point charges, the KO based QM/MM scheme takes charge penetration effect into consideration and therefore significantly improves the description of QM/MM interaction at short range, especially when the QM region is highly charged. To be consistent with the third-order formulation of SCC-DFTB, the Hubbard parameter in the KO functional is dependent on the QM charge. As a result, the effective size of the QM charge distribution naturally adjusts as the QM region undergoes chemical transformations, making the KO based QM/MM scheme particularly attractive for describing chemical reactions in the condensed phase. Together with the van der Waals parameters for the QM atom, the KO based QM/MM model introduces four parameters for each element type. They are fitted here based on microsolvation models of small solutes, focusing on negatively charged molecular ions, for elements O, C, H and P with a specific version of SCC-DFTB (SCC-DFTBPR). Test calculations confirm that the KO based QM/MM scheme significantly improves the interactions between QM and MM atoms over the original point charge based model and it is transferable due to the small number of parameters. The new form of QM/MM Hamiltonian will greatly improve the applicability of SCC-DFTB based QM/MM methods to problems that involve highly charged QM regions, such as enzyme catalyzed phosphoryl transfers.
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Motivated by the need of rapidly exploring the potential energy surface of chemical reactions that involve highly charged species, we have developed an implicit solvent model for the approximate density functional theory, SCC-DFTB. The solvation free energy is calculated using the popular model that employs Poisson-Boltzmann for electrostatics and a surface-area term for non-polar contributions. To balance the treatment of species with different charge distributions, we make the atomic radii that define the dielectric boundary and solute cavity depend on the solute charge distribution. Specifically, the atomic radii are assumed to be linearly dependent on the Mulliken charges and solved self-consistently together with the solute electronic structure. Benchmark calculations indicate that the model leads to solvation free energies of comparable accuracy to the SM6 model (especially for ions), which requires much more expensive DFT calculations. With analytical first derivatives and favorable computational speed, the SCC-DFTB based solvation model can be effectively used, in conjunction with high-level QM calculations, to explore the mechanism of solution reactions. This is illustrated with a brief analysis of the hydrolysis of mono-methyl mono-phosphate ester (MMP) and tri-methyl mono-phosphate ester (TMP). Possible future improvements are also briefly discussed.