Robust Oxidase-Mimetic Supramolecular Nanocatalyst for Lignin Biodegradation.

Enzymatic catalysis presents an eco-friendly, energy-efficient method for lignin degradation. However, challenges arise due to the inherent incompatibility between enzymes and native lignin. In this work, we introduce a supramolecular catalyst composed of fluorenyl-modified amino acids and Cu2+, designed based on the aromatic stacking of the fluorenyl group, which can operate in ionic liquid environments suitable for the dissolution of native lignin. Amino acids and halide anions of ionic liquids shape the copper site's coordination sphere, showcasing remarkable catechol oxidase-mimetic activity. The catalyst exhibits thermophilic property, and maintains oxidative activity up to 75 °C, which allows the catalyzed degradation of the as-dissolved native lignin with high efficiency even without assistance of the electron mediator. In contrast, at this condition, the native copper-dependent oxidase completely lost its activity. This catalyst with superior stability and activity offer promise for sustainable lignin valorization through biocatalytic routes compatible with ionic liquid pretreatment, addressing limitations in native enzymes for industrially relevant conditions.

Self-Assembly of Designed Peptides with DNA to Accelerate the DNA Strand Displacement Process for Dynamic Regulation of DNAzymes.

Toehold-mediated DNA strand displacement (TMSD) is a powerful tool for controlling DNA-based molecular reactions and devices. However, the slow kinetics of TMSD reactions often limit their efficiency and practical applications. Inspired by the chemical structures of natural DNA-operating enzymes (e.g., helicase), we designed lysine-rich peptides to self-assemble with DNA-based systems. Our approach allows for accelerating the TMSD reactions, even during multiple displacement events, enhancing their overall efficiency and utility. We found that the acceleration is dependent on the peptide's sequence, length, and concentration as well as the length of the DNA toehold domain. Molecular dynamics simulations revealed that the peptides promote toehold binding between the double-stranded target and the single-stranded invader, thereby facilitating strand displacement. Furthermore, we integrated our approach into a horseradish peroxidase-mimicking DNAzyme, enabling the dynamic modulation of enzymatic functions on and off. We anticipate that the established acceleration of strand displacement reactions and the modulation of enzymatic activities offer enhanced functionality and control in the design of programmable DNA-based nanodevices.

Histidine-Based Supramolecular Nanoassembly Exhibiting Dual Enzyme-Mimetic Functions: Altering the Tautomeric Preference of Histidine to Tailor Oxidative/Hydrolytic Catalysis.

Challenges persist in replicating enzyme-like active sites with functional group arrangements in supramolecular catalysis. In this study, we present a supramolecular material comprising Fmoc-modified histidine and copper. We also investigated the impact of noncanonical amino acids (δmH and εmH), isomers of histidine, on the catalytic process. The Fmoc-δmH-based nanoassembly exhibits an approximately 15-fold increase in oxidative activity and an ∼50-fold increase in hydrolytic activity compared to Fmoc-εmH (kcat/Km). This distinction arises from differences in basicity and ligation properties between the ε- and δ-nitrogen of histidine. The addition of guanosine monophosphate further enhances the oxidative activity of the histidine- and methylated histidine-based catalysts. The Fmoc-δmH/Cu2+-based nanoassembly catalyzes the oxidation/hydrolysis cascade of 2',7'-dichlorofluorescein diacetate, benefiting from the synergistic effect between the copper center and the nonligating ε-nitrogen of histidine. These findings advance the biomimetic catalyst design and provide insights into the mechanistic role of essential residues in natural systems.

A designed DNA/amino acid amphiphile-based supramolecular oxidase-mimetic catalyst for colorimetric DNA detection.

DNA is self-assembled with Fmoc-amino acids and Cu2+ to construct a supramolecular catechol oxidase-mimetic catalyst, which exhibits remarkable activity in catalyzing colorimetric reactions. This catalytic system is used for the detection of DNA hybridization with a high selectivity and a low detection limit.

Establishment of a model for predicting preterm birth based on the machine learning algorithm.

BACKGROUND: The purpose of this study was to construct a preterm birth prediction model based on electronic health records and to provide a reference for preterm birth prediction in the future. METHODS: This was a cross-sectional design. The risk factors for the outcomes of preterm birth were assessed by multifactor logistic regression analysis. In this study, a logical regression model, decision tree, Naive Bayes, support vector machine, and AdaBoost are used to construct the prediction model. Accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. RESULTS: A total of 5411 participants were included and were used for model construction. AdaBoost model has the best prediction ability among the five models. The accuracy of the model for the prediction of "non-preterm birth" was the highest, reaching 100%, and that of "preterm birth" was 72.73%. CONCLUSIONS: By constructing a preterm birth prediction model based on electronic health records, we believe that machine algorithms have great potential for preterm birth identification. However, more relevant studies are needed before its application in the clinic.

A nucleotide-copper(II) complex possessing a monooxygenase-like catalytic function.

The de novo design of artificial biocatalysts with enzyme-like active sites and catalytic functions has long been an attractive yet challenging goal. In this study, we present a nucleotide-Cu2+ complex, synthesized through a one-pot approach, capable of catalyzing ortho-hydroxylation reactions resembling those of minimalist monooxygenases. Both experimental and theoretical findings demonstrate that the catalyst, in which Cu2+ coordinates with both the nucleobase and phosphate moieties, forms a ternary-complex intermediate with H2O2 and tyramine substrates through multiple weak interactions. The subsequent electron transfer and hydrogen (or proton) transfer steps lead to the ortho-hydroxylation of tyramine, where the single copper center exhibits a similar function to natural dicopper sites. Moreover, Cu2+ bound to nucleotides or oligonucleotides exhibits thermophilic catalytic properties within the temperature range of 25 °C to 75 °C, while native enzymes are fully deactivated above 35 °C. This study may provide insights for the future design of oxidase-mimetic catalysts and serve as a guide for the design of primitive metallocentre-dependent enzymes.

A supramolecular metalloenzyme possessing robust oxidase-mimetic catalytic function.

Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes.

Thiol-Aldehyde Polycondensation for Bio-based Adaptable and Degradable Phenolic Polymers.

Designing sustainable materials with tunable mechanical properties, intrinsic degradability, and recyclability from renewable biomass through a mild process has become vital in polymer science. Traditional phenolic resins are generally considered to be not degradable or recyclable. Here we report the design and synthesis of linear and network structured phenolic polymers using facile polycondensation between natural aldehyde-bearing phenolic compounds and polymercaptans. Linear phenolic products are amorphous with Tg between -9 °C and 12 °C. Cross-linked networks from vanillin and its di-aldehyde derivative exhibited excellent mechanical strength between 6-64 MPa. The connecting dithioacetals are associatively adaptable strong bonds and susceptible to degradation in oxidative conditions to regenerate vanillin. These results highlight the potential of biobased sustainable phenolic polymers with recyclability and selective degradation, as a complement to the traditional phenol-formaldehyde resins.

Succession of endophytic bacterial community and its contribution to cinnamon oil production during cinnamon shade-drying process.

Cinnamon oil is a blend of secondary metabolites and is widely used as spice. Endophytic bacteria are always related to the secondary metabolites production. However, the potential of endophytic bacteria communities for cinnamon oil production during cinnamon shade-drying process is still not clear. In this study, we investigated the composition and metabolic function of endophytic bacterial community during 80-day shade-drying process. The temporal dynamics of essential oil content and its dominant constituents were analyzed. The succession of endophytic bacterial community from d0 to d80 was identified. The influence of endophytic bacterial community evolution on cinnamon oil is significant positive. Predictive functional analysis indicated that shade-drying process was rich in Saccharopolyspora that produce enzymes for the conversion of phenylalanine to cinnamaldehyde. These findings enhance our understanding of the functional bacterial genera and functional genes involved in the production of cinnamon oil during cinnamon shade-drying process.

Synthesis, Herbicidal Activity and Toxicity Evaluation of Secondary Ammonium Salts from Turpentine Oil for Sustainable Weed Control.

Three series of secondary ammonium chloride from turpentine were synthesized and evaluated as botanical herbicides. The preemergence herbicidal activities against ryegrass (Loliun multiflorum) and barnyard grass (Echinochloa crus-galli) were investigated using water as the only solvent. Their toxicity was evaluated by cytotoxicity assays. Preliminary results demonstrated that the herbicidal performance of the prepared salts was similar or much higher than that of corresponding secondary amines and even commercial herbicide glyphosate. Promisingly, compound 14e containing a cyclohexyl-substituted p-menthene skeleton with an IC50 value of 0.0014 mM against root growth of ryegrass showed 39-fold higher herbicidal activity than glyphosate. Besides, this compound was found to be nontoxic to human and animal cells, indicating the potential application as a water-soluble herbicide for ryegrass control.

Hashing-Based Undersampling Ensemble for Imbalanced Pattern Classification Problems.

Undersampling is a popular method to solve imbalanced classification problems. However, sometimes it may remove too many majority samples which may lead to loss of informative samples. In this article, the hashing-based undersampling ensemble (HUE) is proposed to deal with this problem by constructing diversified training subspaces for undersampling. Samples in the majority class are divided into many subspaces by a hashing method. Each subspace corresponds to a training subset which consists of most of the samples from this subspace and a few samples from surrounding subspaces. These training subsets are used to train an ensemble of classification and regression tree classifiers with all minority class samples. The proposed method is tested on 25 UCI datasets against state-of-the-art methods. Experimental results show that the HUE outperforms other methods and yields good results on highly imbalanced datasets.

Development and validation of ferroptosis-related lncRNAs signature for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world. However, there is no research to establish a ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC. Therefore, this study was designed to establish a novel FRlncRNAs signature to predict the survival of patients with HCC. METHOD: The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. FRlncRNAs co-expressed with ferroptosis-related genes were utilized to establish a signature. Cox regression was used to construct a novel three FRlncRNAs signature in the TCGA cohort, which was verified in the GEO validation cohort. RESULTS: Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature. According to the FRlncRNAs signature, the patients with HCC could be divided into low- and high-risk groups. Patients with HCC in the high-risk group displayed shorter overall survival (OS) contrasted with those in the low-risk group (P < 0.001 in TCGA cohort and P = 0.045 in GEO cohort). This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, P < 0.001), which was verified to a certain extent in the GEO cohort (univariate HR > 1, P < 0.05). Meanwhile, it was also a useful tool in predicting survival among each stratum of gender, age, grade, stage, and etiology,etc. This signature was connected with immune cell infiltration (i.e., Macrophage, Myeloid dendritic cell, and Neutrophil cell, etc.) and immune checkpoint blockade targets (PD-1, CTLA-4, and TIM-3). CONCLUSION: The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.

Effects of treatment status and life quality on anxiety in MMT patients.

BACKGROUND: Anxiety, an important factor that affects the therapeutic effect and preservation rate of methadone maintenance treatment, has a high prevalence among MMT patients. This study aims to investigate the effects of treatment status and life quality on anxiety in MMT patients. METHODS: One hundred and Seventy-seven methadone maintenance treatment users in Guangzhou, China were evaluated. The socio-demographic, duration and MMT-related characteristics were documented. Anxiety level and quality of life were evaluated by Beck Anxiety inventory (BAI) and the Quality of Life-Drug Addiction (QOL-DA) respectively. The correlation between different factors and BAI score was also analyzed. RESULTS: The BAI total score and the QOL-DA score were 7.1±8.2, 163.5±21.4 respectively. 30.5% of the subjects showed mild to severe anxiety. Treatment interruption and QOL-DA score had strong correlations with the score of BAI, with correlation coefficients of 0.17 and - 0.08 respectively. CONCLUSIONS: Anxiety symptoms were commonly presented in MMT patients. Treatment interruption and quality of life are two major factors affecting anxiety of MMT patients.

Design, synthesis, and herbicidal activity of sec-p-menthane-7-amine derivatives as botanical herbicides.

In this study, a series of novel p-menthane type secondary amines (sec-p-menthane-7-amine derivatives 3a-3y) were synthesized and then characterized by FTIR, 1H NMR, 13C NMR, and HRMS. The post-emergence herbicidal activities of these amines against barnyard grass and rape were evaluated by the culture dish method. Most of the sec-p-menthane-7-amine derivatives showed excellent herbicidal activities equivalent to or even higher than either diuron or glyphosate. The alkyl-substituted derivatives were more active than the phenyl-substituted derivatives. The herbicidal activities of compounds 3p, 3r, 3u, and 3w against the root growth of barnyard grass were 404% higher, respectively, than those of glyphosate. The herbicidal activities of compounds 3q, 3v, 3w, and 3x against the root growth of rape were 561%, 494%, 491%, and 544% higher, respectively, than those of diuron, and 484%, 760%, 423%, and 665% higher respectively, than those of diuron against shoot growth of rape. In addition, compounds 3p, 3u, and 3v are almost harmless to rice, wheat, sorghum, maize, and peanuts at a concentration of 100 mg L-1. Most of the compounds are nontoxic to HUVEC-C and BALB/c 3T3 cells. It is indicated that the title compounds could be utilized as botanical herbicides for future weed control.

Synthesis and biological activity of pyridine acylhydrazone derivatives of isopimaric acid.

Pyridine acylhydrazone derivatives of isopimaric acid were synthesized and characterized. The minimum inhibitory concentrations of the compounds against five bacteria were determined and most of the compounds displayed some degree of antibacterial activity. The results showed that antimicrobial activity against Streptococcus pneumoniae improved when halogen atoms were introduced into the isopimaric acid, especially when one bromine atom was introduced in the para-position of isopimaric acid. Compound isopimaric acid (5-bromo pyridine-2-formaldehyde) acylhydrazone exhibited a significant antitumorial activity against hepatocarcioma cells (HepG-2) and breast cancer cells (MDA-MB-231), with inhibition degrees of 74.21% and 70.39%, respectively, at 100 µM.[Formula: see text].

Effect of acupuncture for methadone maintenance treatment patients: study protocol of a randomized clinical trial.

BACKGROUND: Opioid dependence is an increasing public health problem all over the world. Patients with opioid dependence have to receive methadone maintenance therapy (MMT) as replacement therapy for years or even for their entire life. Acupuncture as a kind of therapy has been used to treat substance dependence for many years. Jin's three-needle acupuncture (JTN), a type of acupuncture technique, has been applied to treat various diseases for several decades. However, JTN as an acupuncture technique has not been used to treat patients receiving MMT. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. METHODS/DESIGN: This study is a parallel-arm, randomized controlled trial that aims to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. A total of 140 eligible participants who range in age from 18 to 60 years and fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), for opiate dependence will be enrolled into this study. All eligible participants will be randomly assigned to the acupuncture group or routine group in a 1:1 allocation ratio. Participants who are enrolled in the acupuncture group will receive MMT and JTN treatment for 30 min per session. Meanwhile, those who are assigned to the routine arm will receive MMT only. All 18 sessions of JTN treatment will be delivered over 6 weeks (3 per week) and followed by a 4-week follow-up period. The primary outcome measure will be the visual analogue scale (VAS) for drug craving and the daily consumption of methadone (DCOM). Secondary outcome measures will include the urine test for opioid use, the 36-item Short Form Survey (SF-36), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II) and Pittsburgh sleep quality index (PSQI). VAS, DCOM, BAI, BDI-II and the urine test for opioid use will be evaluated at baseline, the second week, the fourth week, the sixth week and the tenth week. SF-36 and PSQI will be assessed at baseline, the fourth week, the sixth week and the tenth week. DISCUSSION: The results of this trial will provide evidence on the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026357 . Registered on 2 October 2019.

Turpentine Derived Secondary Amines for Sustainable Crop Protection: Synthesis, Activity Evaluation and QSAR Study.

In this study, we will report on the synthesis and application of efficient botanical agrochemicals from turpentine for sustainable crop protection. Two series of turpentine derived secondary amines were synthesized and identified by FT-IR, 1H NMR, 13C NMR, and HRMS. The herbicidal activities against Echinochloa crus-galli were evaluated. The potential toxicity of the synthesized compounds was tested by MTT cytotoxicity analysis. The effect of structure of the synthesized secondary amines and corresponding Schiff base compounds on their activities was investigated by quantitative structure-activity relationship (QSAR) study. All target products were found to be low toxicity, with similar or higher herbicidal activities than commercial herbicides diuron and Glyphosate. Results of QSAR study showed that a best four-descriptor QSAR model with R2 of 0.880 and Rloo2 of 0.818 was obtained. The four descriptors most relevant to the herbicidal activities are the min valency of a N atom, the max total interaction for a C-H bond, the relative number of aromatic bonds, and the min partial charge (Qmin).

Radial Basis Function Neural Network with Localized Stochastic-Sensitive Autoencoder for Home-Based Activity Recognition.

Over the past few years, the Internet of Things (IoT) has been greatly developed with one instance being smart home devices gradually entering into people's lives. To maximize the impact of such deployments, home-based activity recognition is required to initially recognize behaviors within smart home environments and to use this information to provide better health and social care services. Activity recognition has the ability to recognize people's activities from the information about their interaction with the environment collected by sensors embedded within the home. In this paper, binary data collected by anonymous binary sensors such as pressure sensors, contact sensors, passive infrared sensors etc. are used to recognize activities. A radial basis function neural network (RBFNN) with localized stochastic-sensitive autoencoder (LiSSA) method is proposed for the purposes of home-based activity recognition. An autoencoder (AE) is introduced to extract useful features from the binary sensor data by converting binary inputs into continuous inputs to extract increased levels of hidden information. The generalization capability of the proposed method is enhanced by minimizing both the training error and the stochastic sensitivity measure in an attempt to improve the ability of the classifier to tolerate uncertainties in the sensor data. Four binary home-based activity recognition datasets including OrdonezA, OrdonezB, Ulster, and activities of daily living data from van Kasteren (vanKasterenADL) are used to evaluate the effectiveness of the proposed method. Compared with well-known benchmarking approaches including support vector machine (SVM), multilayer perceptron neural network (MLPNN), random forest and an RBFNN-based method, the proposed method yielded the best performance with 98.35%, 86.26%, 96.31%, 92.31% accuracy on four datasets, respectively.