A new resorcylic acid lactone from the endophytic fungus Chaetosphaeronema sp.

A new 14-membered resorcylic acid lactone (RAL14), chaetolactone A (1), along with three known ones (2-4), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR),13C NMR chemical shifts calculations coupled with the DP4+ probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines.

Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp2)-H/C-5(sp3)-H Functionalization.

With in-depth research on 1,2-difunctionalization, remote difunctionalization has garnered widespread attention for achieving multifunctionality. Herein, we report a strategy for achieving remote difunctionalization under mild conditions. This strategy exhibited good substrate suitability and functional group tolerance. In addition, the significance of this method is further evidenced by its successful application in scaling up and conducting additional transformations of target compounds. Mechanistic studies showed that a radical might be involved in this process.

Synthesis of cis-(8b,14a)-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones via photo cascade reaction.

A concise method for the synthesis of cis-(8b,14a)-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones 2 via photo-induced 3-([1,1'-biphenyl]-2-yl)-1-(2-hydroxyethyl)pyridin-2(1H)-ones 1 was developed. Irradiation of 1 in the solution of toluene with a 313 nm UV light in the presence of HCl gave cis-(8b,14a)-9a-α-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinoli n-14-ones and cis-(8b,14a)-9a-ß-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones 2 (2-α and 2-ß) in good yields. The protocol simultaneously constructs dearomatized phenanthrene ring and oxindolizidinones ring by photo cascade reaction to achieve high bonding efficiency and high atomic efficiency. Additionally, the antitumor activities of 2 was evaluated and compounds 2b-α, 2b-ß, 2j-ß and 2 k-α showed similar or better activity compared to the cisplatin against tumor cell lines of Leukemia HL-60, lung cancer A594, liver cancer SMMC-7721 and breast cancer MDA-MB-231.

Single cell glycan-linkages profiling for hepatocellular carcinoma early diagnosis using lanthanide encoded bacteriophage MS2 based ICP-MS.

Early diagnosis is paramount for enhancing survival rates and prognosis in the context of malignant diseases. Hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths worldwide, poses significant challenges for its early detection. In this study, we present an innovative approach which contributed to the early diagnosis of HCC. By lanthanide encoding signal amplification to map glycan-linkages at the single-cell level, the minute quantities of "soft" glycan-linkages on single cell surface were converted into "hard" elemental tags through the use of an MS2 signal amplifier. Harnessing the power of lanthanides encoded within MS2, we achieve nearly three orders of magnitude signal amplification. These encoded tags are subsequently quantified using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). Linear discriminant analysis (LDA) identifies seven specific glycan-linkages (α-2,3-Sia, α-Gal, α-1,2-Fuc, α-1,6-Fuc, α-2,6-Sia, α-GalNAc, and Gal-ß-1,3-GalNAc) as biomarkers. Our methodology is initially validated at the cellular level with 100% accuracy in discriminating between hepatic carcinoma HepG2 cells and their normal HL7702 cells. We apply this approach to quantify and classify glycan-linkages on the surfaces of 55 clinical surgical HCC specimens. Leveraging these seven glycan-linkages as biomarkers, we achieve precise differentiation between 8 normal hepatic specimens, 40 early HCC specimens, and 7 colorectal metastasis HCC specimens. This pioneering work represents the first instance of employing single-cell glycan-linkages as biomarkers promising for the early diagnosis of HCC with a remarkable 100% predictive accuracy rate, which holds immense potential for enhancing the feasibility and precision of HCC diagnosis in clinical practice.

Stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals.

C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we design a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1-H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereochemistry. The results of density functional theory (DFT) calculations support oxidative addition mechanism of alkenyl-norbornyl-palladacycle (ANP) intermediate with α-mannofuranose chloride and the high stereoselectivity of glycosylation is due to steric hindrance.

Chemoenzymatic Installation of Site-Specific Chemical Groups on DNA Enhances the Catalytic Activity.

Functional DNAs are valuable molecular tools in chemical biology and analytical chemistry but suffer from low activities due to their limited chemical functionalities. Here, we present a chemoenzymatic method for site-specific installation of diverse functional groups on DNA, and showcase the application of this method to enhance the catalytic activity of a DNA catalyst. Through chemoenzymatic introduction of distinct chemical groups, such as hydroxyl, carboxyl, and benzyl, at specific positions, we achieve significant enhancements in the catalytic activity of the RNA-cleaving deoxyribozyme 10-23. A single carboxyl modification results in a 100-fold increase, while dual modifications (carboxyl and benzyl) yield an approximately 700-fold increase in activity when an RNA cleavage reaction is catalyzed on a DNA-RNA chimeric substrate. The resulting dually modified DNA catalyst, CaBn, exhibits a kobs of 3.76 min-1 in the presence of 1 mM Mg2+ and can be employed for fluorescent imaging of intracellular magnesium ions. Molecular dynamics simulations reveal the superior capability of CaBn to recruit magnesium ions to metal-ion-binding site 2 and adopt a catalytically competent conformation. Our work provides a broadly accessible strategy for DNA functionalization with diverse chemical modifications, and CaBn offers a highly active DNA catalyst with immense potential in chemistry and biotechnology.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Copper-Catalyzed Selective Three-Component 1,2-Phosphonoazidation of 1,3-Dienes.

We report a copper-catalyzed selective 1,2-phosphonoazidation of conjugated dienes. This three-component reaction is achieved by using readily available P(O)-H compounds and bench-stable NaN3. Salient features of this strategy include its mild reaction conditions, broad functional group tolerance, and high chemoselectivity and regioselectivity. Moreover, the compatibility with the late-stage functionalization of drug molecules, the potential for scalable production, and the feasibility of further modifications of the products underscore the practical utility of this protocol in synthetic applications.

A high-precision, effective method for extraction and identification of small-sized microplastics from soil.

A growing evidence showed that the terrestrial ecosystem was a greater sink for microplastics (MPs) compared with ocean. Owing to the limitation of pretreatment methods, there are few reports on the identification of small-sized MPs(<60 µm) in soil currently, which may led to an underestimation of the environmental risk of MPs in soil system. In this study, we established an efficient pretreatment method for MPs in soils by developing a novel device, Plastic Flotation and Separator system (PFSS). The device integrated the suspension, digestion and filtration procedures into one system, reducing the losses of pretreatment process. It was shown that the recovery of MPs with size of 45 µm was 90%, significantly surpassing that of the traditional pretreatment methods in this particle size range. Combined with the SEM-Raman technique, MPs with small size were accurately determined. This work provides an effective method for the extraction and determination of MPs in soils and is of significance for the risk assessment of MPs in soil system.

A Practical and Regioselective Strategy for Aromatic C-H Difunctionalization via Site-Selective C-H Thianthrenation.

Herein, we present a novel Catellani-type reaction that employed aryl-thianthrenium salts as aryl substrates to trigger the subsequent palladium/norbornene cooperatively catalyzed progress. This strategy can achieve site-selective C-H difunctionalization of aryl compounds without directing groups or a known initiating reagent. A series of functionalized syntheses of bioactive molecules further demonstrated the potential of this strategy.

In situ growth of BiOBr on copper foam conductive substrate with enhanced photocatalytic performance.

Photocatalysis technology based on solar-powered semiconductors is widely recognized as a promising approach for achieving eco-friendly, secure, and sustainable degradation of organic contaminants. Nevertheless, conventional photocatalysts exhibit drawbacks such as a wide bandgap, and rapid recombination of photoinduced electron/hole pairs, in addition to complicated separation and recovery procedures. In this research, we cultivated BiOBr in situ on the surface of copper foam to fabricate a functional photocatalyst (denoted as BiOBr/Cu foam), which was subsequently employed for the photodegradation of Methylene Blue. Based on photodegradation experiments, the 0.3 BiOBr/Cu foam demonstrates superior photocatalytic efficacy compared to other photocatalysts under solar light irradiation. Furthermore, its ease of separation from the solution enhances its potential for reuse. The analysis of charge transfer revealed that the copper foam functions as an effective electron scavenger within the BiOBr/Cu foam, thereby facilitating charge separation and the generation of photo-induced holes. This phenomenon contributes to a significantly enhanced production of hydroxyl radicals. This study provides a valuable perspective on the design and synthesis of photocatalysts with heightened practicality, employing a conductive substrate.

Oligo-PROTAC strategy for cell-selective and targeted degradation of activated STAT3.

Decoy oligodeoxynucleotides (ODNs) allow targeting undruggable transcription factors, such as STAT3, but their limited potency and lack of delivery methods hampered translation. To overcome these challenges, we conjugated a STAT3-specific decoy to thalidomide, a ligand to cereblon in E3 ubiquitin ligase complex, to generate a proteolysis-targeting chimera (STAT3DPROTAC). STAT3DPROTAC downregulated STAT3 in target cells, but not STAT1 or STAT5. Computational modeling of the STAT3DPROTAC ternary complex predicted two surface lysines, K601 and K626, in STAT3 as potential ubiquitination sites. Accordingly, K601/K626 point mutations in STAT3, as well as proteasome inhibition or cereblon deletion, alleviated STAT3DPROTAC effect. Next, we conjugated STAT3DPROTAC to a CpG oligonucleotide targeting Toll-like receptor 9 (TLR9) to generate myeloid/B cell-selective C-STAT3DPROTAC. Naked C-STAT3DPROTAC was spontaneously internalized by TLR9+ myeloid cells, B cells, and human and mouse lymphoma cells but not by T cells. C-STAT3DPROTAC effectively decreased STAT3 protein levels and also STAT3-regulated target genes critical for lymphoma cell proliferation and/or survival (BCL2L1, CCND2, and MYC). Finally, local C-STAT3DPROTAC administration to human Ly3 lymphoma-bearing mice triggered tumor regression, while control C-STAT3D and C-SCR treatments had limited effects. Our results underscore the feasibility of using a PROTAC strategy for cell-selective, decoy oligonucleotide-based STAT3 targeting of and potentially other tumorigenic transcription factors for cancer therapy.

Screening of Sugarcane Proteins Associated with Defense against Leifsonia xyli subsp. xyli, Agent of Ratoon Stunting Disease.

Sugarcane is the most important sugar crop and one of the leading energy-producing crops in the world. Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, poses a huge threat to ratoon crops, causing a significant yield loss in sugarcane. Breeding resistant varieties is considered the most effective and fundamental approach to control RSD in sugarcane. The exploration of resistance genes forms the foundation for breeding resistant varieties through molecular technology. The pglA gene is a pathogenicity gene in L. xyli subsp. xyli, encoding an endopolygalacturonase. In this study, the pglA gene from L. xyli subsp. xyli and related microorganisms was analyzed. Then, a non-toxic, non-autoactivating pglA bait was successfully expressed in yeast cells. Simultaneously the yeast two-hybrid library was generated using RNA from the L. xyli subsp. xyli-infected sugarcane. Screening the library with the pglA bait uncovered proteins that interacted with pglA, primarily associated with ABA pathways and the plant immune system, suggesting that sugarcane employs these pathways to respond to L. xyli subsp. xyli, triggering pathogenicity or resistance. The expression of genes encoding these proteins was also investigated in L. xyli subsp. xyli-infected sugarcane, suggesting multiple layers of regulatory mechanisms in the interaction between sugarcane and L. xyli subsp. xyli. This work promotes the understanding of plant-pathogen interaction and provides target proteins/genes for molecular breeding to improve sugarcane resistance to L. xyli subsp. xyli.

Direct observation and measurement of circumlental space and its relation to anterior chamber angle characteristics in iridotomized phakic eyes with primary angle closure disease.

Primary angle closure disease (PACD) is a major cause of blindness worldwide. It has a high prevalence in East Asia, especially in China, which leads to a higher incidence of blindness than open-angle glaucoma. The aim of this study was to directly observe the circumlental space (CLS) in laser peripheral iridotomized eyes with PACD and to determine whether this structure plays a role in the pathogenesis of PACD. Fifty eyes of 50 patients with PACD, who had received laser peripheral iridotomy performed with neodymium:yttrium-aluminum-garnet were recruited from glaucoma clinics from March 2021 to May 2022, including 17 primary angle closure suspect (PACS), 16 primary angle closure (PAC) and 17 primary angle closure glaucoma (PACG). They were classified into two groups based on whether the ciliary process and the crystalline lens equator were in contact using slit-lamp photograph: the attached group and the unattached group. The demographic, clinical characteristics and anterior segment parameters measured from ultrasound biomicroscopy were compared between the attached group and the unattached group. Thirty-three eyes were assigned to the attached group and 17 eyes belonged to the unattached group. In the unattached group, the mean CLS was 0.10 ± 0.07 mm. No significant differences were identified between the different diagnosis groups in age, sex, best-corrected visual acuity, intraocular pressure, white-to-white, axial length, central corneal thickness, anterior chamber depth, flat keratometry, steep keratometry or iridotomy diameter (p > 0.05). The unattached group had shorter trabecular-ciliary process distance (p = 0.021) and larger ciliary process area (p = 0.001) compared with the attached group. Small CLS and its potential effect (partial ciliary block) might be considered as one of the mechanisms of PACD.

Efficacy and safety of intercostal nerve anastomosis in immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy: a randomized, controlled, open-label clinical study.

Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.

MUMA: a multi-omics meta-learning algorithm for data interpretation and classification.

Multi-omics data integration is a promising field combining various types of omics data, such as genomics, transcriptomics, and proteomics, to comprehensively understand the molecular mechanisms underlying life and disease. However, the inherent noise, heterogeneity, and high dimensionality of multi-omics data present challenges for existing methods to extract meaningful biological information without overfitting. This paper introduces a novel Multi-Omics Meta-learning Algorithm (MUMA) that employs self-adaptive sample weighting and interaction-based regularization for enhanced diagnostic performance and interpretability in multi-omics data analysis. Specifically, MUMA captures crucial biological processes across different omics layers by learning a flexible sample reweighting function adaptable to various noise scenarios. Additionally, MUMA incorporates an interaction-based regularization term, encouraging the model to learn from the relationships among different omics modalities. We evaluate MUMA using simulations and eighteen real datasets, demonstrating its superior performance compared to state-of-the-art methods in classifying biological samples (e.g., cancer subtypes) and selecting relevant biomarkers from noisy multi-omics data. As a powerful tool for multi-omics data integration, MUMA can assist researchers in achieving a deeper understanding of the biological systems involved. The source code for MUMA is available at https://github.com/bio-ai-source/MUMA.

Individualized small bowel preparation for computed tomography enterography: A prospective randomized controlled trial.

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2 , 1500 mL for patients with 18.5 kg/m2  ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2 ) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2 , 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2 , 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

Screening of the Antagonistic Activity of Potential Bisphenol A Alternatives toward the Androgen Receptor Using Machine Learning and Molecular Dynamics Simulation.

Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants. However, related experimental evaluations of BPA alternatives have not been systematically implemented for the assessment of chemical safety and the effects of structural characteristics on the antagonistic activity of the AR. To promote the green development of BPA alternatives, high-throughput toxicological screening is fundamental for prioritizing chemical tests. Therefore, we proposed a hybrid deep learning architecture that combines molecular descriptors and molecular graphs to predict AR antagonistic activity. Compared to previous models, this hybrid architecture can extract substantial chemical information from various molecular representations to improve the model's generalization ability for BPA alternatives. Our predictions suggest that lignin-derivable bisguaiacols, as alternatives to BPA, are likely to be nonantagonist for AR compared to bisphenol analogues. Additionally, molecular dynamics (MD) simulations identified the dihydrotestosterone-bound pocket, rather than the surface, as the major binding site of bisphenol analogues. The conformational changes of key helix H12 from an agonistic to an antagonistic conformation can be evaluated qualitatively by accelerated MD simulations to explain the underlying mechanism. Overall, our computational study is helpful for toxicological screening of BPA alternatives and the design of environmentally friendly BPA alternatives.

NeuTox: A weighted ensemble model for screening potential neuronal cytotoxicity of chemicals based on various types of molecular representations.

Chemical-induced neurotoxicity has been widely brought into focus in the risk assessment of chemical safety. However, the traditional in vivo animal models to evaluate neurotoxicity are time-consuming and expensive, which cannot completely represent the pathophysiology of neurotoxicity in humans. Cytotoxicity to human neuroblastoma cell line (SH-SY5Y) is commonly used as an alternative to animal testing for the assessment of neurotoxicity, yet it is still not appropriate for high throughput screening of potential neuronal cytotoxicity of chemicals. In this study, we constructed an ensemble prediction model, termed NeuTox, by combining multiple machine learning algorithms with molecular representations based on the weighted score of Particle Swarm Optimization. For the test set, NeuTox shows excellent performance with an accuracy of 0.9064, which are superior to the top-performing individual models. The subsequent experimental verifications reveal that 5,5'-isopropylidenedi-2-biphenylol and 4,4'-cyclo-hexylidenebisphenol exhibited stronger SH-SY5Y-based cytotoxicity compared to bisphenol A, suggesting that NeuTox has good generalization ability in the first-tier assessment of neuronal cytotoxicity of BPA analogs. For ease of use, NeuTox is presented as an online web server that can be freely accessed via http://www.iehneutox-predictor.cn/NeuToxPredict/Predict.

Aptamer-functionalized gold nanoparticles for mercury ion detection in a colorimetric assay based on color change time as signal readout.

A universal strategy for a rapid colorimetric method for Hg2+ in an aqueous solution is described. The specific binding of Hg2+ (thymine-Hg2+-thymine) with thiolated DNA-functionalized gold nanoparticles (AuNPs) via Au-S bonds increases the spatial hindrance of the AuNP surface, resulting in a weakened catalytic ability of AuNPs to catalyze the reaction between p-nitrophenol and NaBH4. Therefore, the color change time (CCT) of the solution from yellow to colorless becomes longer. Based on the kinetic curve of absorbance over time measured by a UV spectrometer, the level of Hg2+ in aqueous solutions can be easily quantified. A linear relationship between CCT and Hg2+ concentration was obtained in the 10-600-nM range with a detection limit of 0.20 nM, which is much lower than the limit value (10 nM) defined by the US Environmental Protection Agency for Hg2+ in drinking water. The excellent sensitivity comes from CCT as the signal output of the probe, rather than the absorbance or wavelength change used in traditional colorimetric probes as the signal output.