ALDELE: All-Purpose Deep Learning Toolkits for Predicting the Biocatalytic Activities of Enzymes.

Rapidly predicting enzyme properties for catalyzing specific substrates is essential for identifying potential enzymes for industrial transformations. The demand for sustainable production of valuable industry chemicals utilizing biological resources raised a pressing need to speed up biocatalyst screening using machine learning techniques. In this research, we developed an all-purpose deep-learning-based multiple-toolkit (ALDELE) workflow for screening enzyme catalysts. ALDELE incorporates both structural and sequence representations of proteins, alongside representations of ligands by subgraphs and overall physicochemical properties. Comprehensive evaluation demonstrated that ALDELE can predict the catalytic activities of enzymes, and particularly, it identifies residue-based hotspots to guide enzyme engineering and generates substrate heat maps to explore the substrate scope for a given biocatalyst. Moreover, our models notably match empirical data, reinforcing the practicality and reliability of our approach through the alignment with confirmed mutation sites. ALDELE offers a facile and comprehensive solution by integrating different toolkits tailored for different purposes at affordable computational cost and therefore would be valuable to speed up the discovery of new functional enzymes for their exploitation by the industry.

Optimized therapeutic potential of Yinchenhao decoction for cholestatic hepatitis by combined network meta-analysis and network pharmacology.

BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.

Human diet-derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization.

This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-ß, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.

Origin of the enantioselectivity of alcohol dehydrogenase.

Alcohol dehydrogenases (ADH) are a family of enzymes that catalyse the interconversion between ketones/aldehydes and alcohols in the presence of NADPH cofactor. It is challenging to desymmetrise the substituted cyclopentane-1,3-dione by engineering an ADH, while the reaction mechanism of the metal independent ADH remains elusive. Here we measured the conversion of a model substrate 2-benzyl-2-methylcyclopentane-1,3-dione by LbADH and found it predominately gave the (2R,3R) product. Binding mode analysis of the substrate in LbADH from molecular dynamics simulations disclosed the origin of the enantioselectivity of the enzyme; the opening and closing of the loop 191-205 above the substrate are responsible for shaping the binding pocket to orientate the substrate, so as to give different stereoisomer products. Using QM/MM calculations, we elucidated the reaction mechanism of LbADH. Furthermore, we demonstrated the reaction profile corresponding to the production of different stereoisomers, which is in accordance with our experimental observations. This research here will shed a light on the rational engineering of ADH to achieve stereodivergent stereoisomer products.

The biological principles and advanced applications of DSB repair in CRISPR-mediated yeast genome editing.

To improve the performance of yeast cell factories for industrial production, extensive CRISPR-mediated genome editing systems have been applied by artificially creating double-strand breaks (DSBs) to introduce mutations with the assistance of intracellular DSB repair. Diverse strategies of DSB repair are required to meet various demands, including precise editing or random editing with customized gRNAs or a gRNA library. Although most yeasts remodeling techniques have shown rewarding performance in laboratory verification, industrial yeast strain manipulation relies only on very limited strategies. Here, we comprehensively reviewed the molecular mechanisms underlying recent industrial applications to provide new insights into DSB cleavage and repair pathways in both Saccharomyces cerevisiae and other unconventional yeast species. The discussion of DSB repair covers the most frequently used homologous recombination (HR) and nonhomologous end joining (NHEJ) strategies to the less well-studied illegitimate recombination (IR) pathways, such as single-strand annealing (SSA) and microhomology-mediated end joining (MMEJ). Various CRISPR-based genome editing tools and corresponding gene editing efficiencies are described. Finally, we summarize recently developed CRISPR-based strategies that use optimized DSB repair for genome-scale editing, providing a direction for further development of yeast genome editing.

Highly Efficient (>13%) and Robust Flexible Perovskite Solar Cells Using an Ultrasimple All-Carbon-Electrode Configuration.

Fragile and expensive transparent conductive oxide anodes and noble metal cathodes in typical perovskite photovoltaic devices pose unavoidable issues, i.e., poor flexibility and high material cost, making it inaccessible to commercial application. Here, we report an ultrasimple indium tin oxide (ITO)-free and HTL-free all-carbon-electrode flexible perovskite solar cell (AC-F-PSC) with an architecture of PEN/carbon/SnO2/perovskite/carbon which contains an anode made of a carbon-based integrator (CNT-GR) comprising carbon nanotubes and low-dose graphene, and a cathode made of the commonly used conductive carbon. The CNT-GR anode exhibits low sheet resistance, high light transmittance, and superior flexibility beyond ITO. Density functional theory calculations reveal that O atoms from GR anchored onto the interwoven CNT network have strong covalent binding capacity with bond-deficient Sn ions, inhibiting the formation of oxygen vacancies in SnO2. Such a binding effect induces a significant reduction of the conduction band minimum of SnO2, yielding favorable energy level alignment for carrier transport at the SnO2/perovskite interface. Also, a heat-pressing approach as a tiny trick is used to fill the gaps at the perovskite/carbon cathode interface. The resulting AC-F-PSC device attains an efficiency of 13.14%, which is a record value among reported carbon-electrode F-PSCs, with superior mechanical flexibility, i.e., ∼71% of initial efficiency after bending 4000 cycles at 4 mm bending radius. This PSC based on an ultrasimple all-carbon-electrode offers a promising route for robust and cost-effective flexible photovoltaic devices.

Remarkably Selective Binding, Behavior Modification, and Switchable Release of (Bipyridine)3Ru(II) vis-à-vis (Phenanthroline)3Ru(II) by Trimeric Cyclophanes in Water.

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, the more valuable the dream becomes. We now present multianionic trimeric cyclophane receptors with a remarkable ability to bind the iconic (bipyridine)3Ru(II) (with its huge range of applications) while rejecting the nearly equally iconic (phenanthroline)3Ru(II). These receptors not only selectively capture (bipyridine)3Ru(II) but also can be redox-switched to release the guest. 1D- and 2D(ROESY)-NMR spectroscopy, luminescence spectroscopy, and molecular modeling enabled this discovery. This outcome allows the control of these applications, e.g., as a photocatalyst or as a luminescent sensor, by selectively hiding or exposing (bipyridine)3Ru(II). Overall, a 3D nanometric object is selected, picked-up, and dropped-off by a discrete molecular host. The multianionic receptors protect excited states of these metal complexes from phenolate quenchers so that the initial step in photocatalytic phenolate oxidation is retarded by nearly 2 orders of magnitude. This work opens the way for (bipyridine)3Ru(II) to be manipulated in the presence of other functional nano-objects so that many of its applications can be commanded and controlled. We have a cyclophane-based toolkit that can emulate some aspects of proteins that selectively participate in cell signaling and metabolic pathways by changing shape upon environmental commands being received at a location remote from the active site.

Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19.

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety. Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients. Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Multifunctional Histidine Cross-Linked Interface toward Efficient Planar Perovskite Solar Cells.

Interface engineering mediated by a designed chemical agent is of paramount importance for developing high-performance perovskite solar cells (PSCs). It is especially critical for planar SnO2-based PSCs due to the presence of abundant surface defects on SnO2 and/or perovskite surfaces. Herein, a novel multifunctional agent histidine (abbreviated as His) capable of cross-linking SnO2 and perovskite is employed to modify the SnO2/perovskite interface. Density functional theory (DFT) calculations and experimental results demonstrate that the carboxylate oxygen of His can form a Sn-O bond to fill the oxygen vacancies on the surface of SnO2, while its positively charged imidazole ring can occupy the cationic vacancies and its -NH3+ group interacts with the I- ion on the perovskite lattice. This cross-linking contributes to the significantly decreased interfacial trap state density and nonradiative recombination loss. In addition, it facilitates electron extraction/transfer and also improves interfacial contact and the quality of perovskite film. Correspondingly, the His-modified device delivers a superior power conversion efficiency (PCE) of 22.91% (improved from 20.13%) and an excellent open-circuit voltage (Voc) of 1.17 V (improved from 1.11 V), along with significantly suppressed hysteresis. Furthermore, the unencapsulated device based on His modification shows much better humidity and thermal stability than the pristine one. The present work provides guidance for the design of innovative multifunctional interfacial material for highly efficient PSCs.

Spine trabecular bone scores and bone mineral density of postmenopausal Taiwanese women.

OBJECTIVES: The aims of the study were to determine the mean trabecular bone score (TBS) of postmenopausal Taiwanese women and to analyze the value of TBS in predicting osteoporosis. METHODS: A total of 1,915 postmenopausal women with lumbar spine and hip bone mineral density (BMD) and spine TBS were enrolled from a single medical center into this study. The women's BMD and TBS were measured using dual x-ray absorptiometry (Discovery Wi; Hologic, Bedford, Mass) and iNsight software (Med-Imaps SASU, Merignac, France), respectively. The women's demographic characteristics; lumbar spine, total hip, and femoral neck BMD; and lumbar spine TBS were recorded, and correlations among the parameters were identified using a 2-tailed Pearson test, in which a P value less than 0.05 was considered statistically significant. We developed simple linear regression models to represent changes related to TBS and performed an analysis of variance on the selected variables. RESULTS: The average age of the women was 62.5 ± 9.1 years (range, 25.7-93.7 years). The mean TBS was 1.300 ± 0.086 (range, 1.015-1.596). The TBS was weakly and negatively correlated with body mass index ( r = -0.078) and moderately and positively correlated with the lumbar spine BMD ( r = 0.619). The patients' lowest BMD values among those measured at multiple sites revealed a higher rate of osteoporosis (32.5%) than those measured at individual sites. Degraded TBS were noted in 21.2% of the participants, and a combination of BMD and TBS results predicted more individuals (7.8%) at a high risk of fracture than did the BMD result only. The rates of both osteoporosis and degraded TBS increased with age. CONCLUSIONS: Bone mineral density and TBS can be used in combination to predict osteoporosis in a greater number of postmenopausal Taiwanese women. Because the incidence of osteoporosis is the highest among older women, clinicians should pay careful attention to TBS degradation among older patients without low BMD.

Single-Site Mutation Induces Water-Mediated Promiscuity in Lignin Breaking Cytochrome P450GcoA.

Cytochrome P450GcoA is an enzyme that catalyzes the guaiacol unit of lignin during the lignin breakdown via an aryl-O-demethylation reaction. This reaction is intriguing and is of commercial importance for its potential applications in the production of biofuel and plastic from biomass feedstock. Recently, the F169A mutation in P450GcoA elicits a promiscuous activity for syringol while maintaining the native activity for guaiacol. Using comprehensive MD simulations and hybrid QM/MM calculations, we address, herein, the origin of promiscuity in P450GcoA and its relevance to the specific activity toward lignin-derived substrates. Our study shows a crucial role of an aromatic dyad of F169 and F395 by regulating the water access to the catalytic center. The F169A mutation opens a water aqueduct and hence increases the native activity for G-lignin. We show that syringol binds very tightly to the WT enzyme, which blocks the conformational rearrangement needed for the second step of O-demethylation. The F169A creates an extra room favoring the conformational rearrangement in the 3-methoxycatechol (3MC) and second dose of the dioxygen insertion. Therefore, using MD simulations and complemented by thorough QM/MM calculations, our study shows how a single-site mutation rearchitects active site engineering for promiscuous syringol activity.

QSPR study on Hydrophobicity of Pt(II) complexes with surface electrostatic potential-based descriptors.

Pt(II) complexes play an important role in bioinorganic chemistry due to their antitumor activities. In the present study, we focused on building predictive models for the hydrophobicity of Pt(II) complexes. A five-parameter model, integrating frontier orbital energies (EHOMO, ELUMO) and descriptors derived from electrostatic potentials on molecular surface, was firstly constructed by using multiple linear regression (MLR) method. Mechanistic interpretations of the introduced descriptors were elucidated in terms of intermolecular interactions in the n-octanol/water partition system. Then, four up-to-date modeling methods, including support vector machine (SVM), least-squares support vector machine (LSSVM), random forest (RF) and Gaussian process (GP), were utilized to build the nonlinear models. Systematical validations including leave-one-out cross-validation, the validation for test set, as well as a very rigorous Monte Carlo cross-validation (MCCV) were performed to verify the reliability of the constructed models. The peak, median and integralRext2 values of the best GP model are 0.88, 0.86 and 0.84, respectively. The root mean squared errors for the test set (RMSEP) of the MLR, SVM, LSSVM and GP models fall in the range of 0.62-0.71. Although they are not superior to prior models built with the use of a number of descriptors, the results are satisfactory. Applicability domain of the model was evaluated.

Taming Tris(bipyridine)ruthenium(II) and Its Reactions in Water by Capture/Release with Shape-Switchable Symmetry-Matched Cyclophanes.

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These reactions of an iconic class of molecules─polypyridineRu(II)─are now controlled by capturing or releasing three of them with hosts that are shape-switchable. Reversible erection or collapse of the host walls allows such switchability. Some reaction rates are suppressed by factors of up to 120 by inclusive binding of the metal complexes. This puts nanometric coordination chemistry in a box that can be open or shut as necessary. Such second-sphere complexation can allow considerable control to be exerted on photocatalysis, electrocatalysis, and luminescent sensing involving polypyridineRu(II) compounds. The capturing states of hosts are symmetry-matched to guests for selective binding and display submicromolar affinities. A perching complex, which is an intermediate state between capturing and releasing states, is also demonstrated.

Thebaine is Selectively Demethylated by Thebaine 6-O-Demethylase and Codeine-3-O-demethylase at Distinct Binding Sites: A Computational Study.

Two homologous 2-oxoglutarate-dependent (ODD) nonheme enzymes thebaine 6-O-demethylase (T6ODM) and codeine-3-O-demethylase (CODM), are involved in the morphine biosynthesis pathway from thebaine, catalyzing the O-demethylation reaction with precise regioselectivity at C6 and C3 positions of thebaine respectively. We investigated the origin of the regioselectivity of these enzymes by combined molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations and found that Thebaine binds at the two distinct sites of T6ODM and CODM, which determines the regioselectivity of the enzymes. A remarkable oxo rotation is observed in the decarboxylation process. Starting from the closed pentacoordinate configuration, the C-terminal lid adopts an open conformation in the octahedral Fe(IV) = O complex to facilitate the subsequent demethylation. Phe241 and Phe311 stabilize the substrate in the binding pocket, while Arg219 acts as a gatekeeper residue to stabilize the substrate. Our results unravel the regioselectivity in 2-OG dependent nonheme enzymes and may shed light for exploring the substrate scope of these enzymes and developing novel biotechnology for morphine biosynthesis.

Prediction of the hydrophobicity of platinum(IV) complexes based on molecular surface properties.

A quantitative structure-property relationship (QSPR) study was performed for predicting the hydrophobicity of Pt(IV) complexes. Two four-parameter equations, one based solely on structural descriptors derived from electrostatic potentials (ESPs) on molecular surface, and the other integrated ESP descriptors with molecular surface area (AS), were firstly constructed. Mechanistic interpretations of the structural descriptors introduced were elucidated in terms of solute-solvent intermolecular interactions. Subsequently, several up-to-date modeling techniques, including support vector machine (SVM), least-squares support vector machine (LSSVM), random forest (RF) and Gaussian process (GP), were utilized to build the nonlinear models. Systematical validations including leave-one-out cross-validation, the validation for test set, as well as a more rigorous Monte Carlo cross-validation were performed to verify the reliability of the constructed models. The predictive performances of the four different nonlinear modeling methods follow the order of LSSVM≈GP > RF > SVM. The pure-ESP-based models are generally inferior to the AS-integrated ones. Comparisons with previous results were made.

Regio- and stereoselectivity in the CYP450BM3-catalyzed hydroxylation of complex terpenoids: a QM/MM study.

The site-selective C-H oxidation of terpenoids by P450 attracts great attention because of their wide range of biological activities. However, the binding and catalytic mechanism of P450 for the hydroxylation of complex terpenoid substrates remains elusive, which has limited the rational engineering of P450 as a biocatalyst for terpenoid biosynthesis. Here, we studied the origin of the selectivity and reactivity of P450BM3 in the hydroxylation of terpenoids by combining molecular dynamics simulations and QM/MM calculations, using artemisinin as a model compound. We found that the conformational change of the ß1 sheet at the substrate entrance and the displacement of the ß' helix were critical for reshaping the binding pocket to modulate substrate entrance and positioning the C-H to be activated toward the oxidative species of P450 for the subsequent hydrogen abstraction, the rate-determining step of hydroxylation. There is a distinct linear correlation between activation barriers and reaction coordinates, indicating that reaction coordinates can be used as a facile descriptor for predicting the reactivity of P450BM3. These findings would provide valuable guidance for predicting the selectivity and reactivity of P450BM3 for the selective hydroxylation of non-native terpenoid substrates so as to prioritize the rationally designed enzymes for terpenoid biosynthesis.

Unraveling the Photogenerated Electron Localization on the Defect-Free CH3NH3PbI3(001) Surfaces: Understanding and Implications from a First-Principles Study.

The localization of photogenerated electrons in photovoltaic and photocatalytic materials is crucial for reducing the electron-hole recombination rate. Here, the photogenerated electron localization is systematically investigated on the CH3NH3PbI3 (MAPbI3) perovskite using first-principles calculations. It is found that under vacuum conditions, the photogenerated electron is delocalized in the MAPbI3 bulk as well as on the stochiometric MAPbI3(001) surface with the CH3NH3I (MAI) termination, while it is trapped on the defect-free PbI2-terminated surface. Our ab initio molecular dynamics simulations reveal that the introduction of solutions will prompt the formation of localized electronic states. The photogenerated electron is discovered to be localized on both the MAI- and PbI2-terminated surfaces in the presence of solutions with different concentrations of HI, from pure water to the saturated solution. We demonstrate that the Pb-I bond weakening or breaking resulting in an unsaturated coordination of a Pb site is the prerequisite to trap the photogenerated electron.

The mutagenesis of a single site for enhancing or reversing the enantio- or regiopreference of cyclohexanone monooxygenases.

The mutagenesis of a "second sphere" switch residue of CHMOAcineto could control its enantio- and regiopreference. Replacing phenylalanine (F) at position 277 of CHMOAcineto into larger tryptophan (W) enabled a significant enhancement of enantio- or regioselectivity toward structurally diverse substrates, moreover, a complete reversal of enantio- or regiopreference was realized by mutating F277 into a range of smaller amino acids (A/C/D/E/G/H/I/K/L/M/N/P/Q/R/S/T/V).

Determining the Online Measurable Input Variables in Human Joint Moment Intelligent Prediction Based on the Hill Muscle Model.

Introduction: Human joint moment is a critical parameter to rehabilitation assessment and human-robot interaction, which can be predicted using an artificial neural network (ANN) model. However, challenge remains as lack of an effective approach to determining the input variables for the ANN model in joint moment prediction, which determines the number of input sensors and the complexity of prediction. Methods: To address this research gap, this study develops a mathematical model based on the Hill muscle model to determining the online input variables of the ANN for the prediction of joint moments. In this method, the muscle activation, muscle-tendon moment velocity and length in the Hill muscle model and muscle-tendon moment arm are translated to the online measurable variables, i.e. muscle electromyography (EMG), joint angles and angular velocities of the muscle span. To test the predictive ability of these input variables, an ANN model is designed and trained to predict joint moments. The ANN model with the online measurable input variables is tested on the experimental data collected from ten healthy subjects running with the speeds of 2, 3, 4 and 5 m/s on a treadmill. The variance accounted for (VAF) between the predicted and inverse dynamics moment is used to evaluate the prediction accuracy. Results: The results suggested that the method can predict joint moments with a higher accuracy (mean VAF = 89.67±5.56 %) than those obtained by using other joint angles and angular velocities as inputs (mean VAF = 86.27±6.6%) evaluated by jack-knife cross-validation. Conclusions: The proposed method provides us with a powerful tool to predict joint moment based on online measurable variables, which establishes the theoretical basis for optimizing the input sensors and detection complexity of the prediction system. It may facilitate the research on exoskeleton robot control and real-time gait analysis in motor rehabilitation.

Prediction on separation factor of chiral arylhydantoin compounds and recognition mechanism between chiral stationary phase and the enantiomers.

Chiral hydantoins display potential antidepressant and anticancer activities. The quantitative structure property relationship (QSPR) study on chiral compounds plays a key role in predicting the retention factor and the separation factor even the elution order of the enantiomers. In this study, the structures of chiral arylhydantoin compounds have been built to compute molecular structural parameters using VolSurf program. The satisfying models were established between the parameters and the retention factor as well as the separation factor. Analysis on the variables shows that the large difference values of volume, hydrophilic regions and hydrogen bond acceptor and donor regions at some energy levels will result in the large separation factor. The differences of hydrophobic regions and the unbalance between the centre of mass and the barycentre of the hydrophobic region at high energy levels are also favorable to the separation. The differences of surface area, hydrophilic regions and hydrogen bond acceptor and donor regions at other energy levels as well as hydrophobic regions and the unbalance at low energy levels between the enantiomers are disadvantageous to the separation. The analysis on the chiral recognition mechanism demonstrates that the differences of the interaction energies between the enantiomers are mainly affected by the hydrogen bond, π-π interaction and CH3-π interaction. The retention factor and the separation factor, especially the elution order of the enantiomers can be easily predicted using the models. The study provides a helpful guidance for studying other chiral compounds.