EISA-EXPOSOME: One Highly Sensitive and Autonomous Exposomic Platform with Enhanced in-Source Fragmentation/Annotation.

Lacking a highly sensitive exposome screening technique is one of the biggest challenges in moving exposomic research forward. Enhanced in-source fragmentation/annotation (EISA) has been developed to facilitate molecular identification in untargeted metabolomics and proteomics. In this work, with a mixture of 50 pesticides at three concentration levels (20, 4, and 0.8 ppb), we investigated the analytical performance of the EISA technique over the well-accepted targeted MS/MS mode (TMM) in the detection and identification of chemicals at low levels using a quadrupole time-of-flight (qTOF) instrument. Compared with the TMM method, the EISA technique can recognize additional 1, 20, and 23 chemicals, respectively, at the three concentration levels (20, 4, and 0.8 ppb, respectively) investigated. At the 0.8 ppb level, intensities of precursor ions and fragments observed using the EISA technique are 30-1,154 and 3-80 times higher, respectively, than those observed at the TMM mode. A higher matched fragment ratio (MFR) between the EISA technique and the TMM method was recognized for most chemicals. We further developed a chemical annotation informatics algorithm, EISA-EXPOSOME, which can automatically search each precursor ion (m/z) in the MS/MS library against the EISA MS1 spectra. This algorithm then calculated a weighted score to rank the candidate features by comparing the experimental fragment spectra to those in the library. The peak intensity, zigzag index, and retention time prediction model as well as the peak correlation coefficient were further adopted in the algorithm to filter false positives. The performance of EISA-EXPOSOME was demonstrated using a pooled dust extract with a pesticide mixture (n = 200) spiked at 5 ppb. One urine sample spiked with a contaminant mixture (n = 50) at the 5 ppb level was also used for the validation of the pipeline. Proof-of-principal application of EISA-EXPOSOME in the real sample was further evaluated on the pooled dust sample with a modified T3DB database (n = 1650). Our results show that the EISA-EXPOSOME algorithm can remarkably improve the detection and annotation coverage at trace levels beyond the traditional approach as well as facilitate the high throughput screening of suspected chemicals.

Unveiling the Microfiber Release Footprint: Guiding Control Strategies in the Textile Production Industry.

Microplastic fibers from textiles have been known to significantly contribute to marine microplastic pollution. However, little is known about the microfiber formation and discharge during textile production. In this study, we have quantified microfiber emissions from one large and representative textile factory during different stages, spanning seven different materials, including cotton, polyester, and blended fabrics, to further guide control strategies. Wet-processing steps released up to 25 times more microfibers than home laundering, with dyeing contributing to 95.0% of the total emissions. Microfiber release could be reduced by using white coloring, a lower dyeing temperature, and a shorter dyeing duration. Thinner, denser yarns increased microfiber pollution, whereas using tightly twisted fibers mitigated release. Globally, wet textile processing potentially produced 6.4 kt of microfibers in 2020, with China, India, and the US as significant contributors. The study underlined the environmental impact of textile production and the need for mitigation strategies, particularly in dyeing processes and fiber choice. In addition, no significant difference was observed between the virgin polyesters and the used ones. Replacing virgin fibers with recycled fibers in polyester fabrics, due to their increasing consumption, might offer another potential solution. The findings highlighted the substantial impact of textile production on microfiber released into the environment, and optimization of material selection, knitting technologies, production processing, and recycled materials could be effective mitigation strategies.

Chiral NHC-catalyzed 1,3-dipolar [3 + 2] cycloaddition of azomethine imines with α-chloroaldehydes for the synthesis of bicyclic pyrazolidinones.

A chiral N-heterocyclic carbene (NHC)-catalyzed 1,3-dipolar [3 + 2] cycloaddition reaction of 3-oxopyrazolidin-1-ium-2-ides and α-chloroaldehydes was developed for the synthesis of pyrazolo[1,2-a]pyrazole-1,7-diones in moderate to good yields (up to 76%) with good enantioselectivities (up to 98% ee) and diastereoselectivities (up to 8 : 1 dr).

Correction: Chiral NHC-catalyzed 1,3-dipolar [3 + 2] cycloaddition of azomethine imines with α-chloroaldehydes for the synthesis of bicyclic pyrazolidinones.

Correction for 'Chiral NHC-catalyzed 1,3-dipolar [3 + 2] cycloaddition of azomethine imines with α-chloroaldehydes for the synthesis of bicyclic pyrazolidinones' by Limin Yang, et al., Org. Biomol. Chem., 2018, 16, 4433-4438.

An optimized band-target entropy minimization for mass spectral reconstruction of severely co-eluting and trace-level components.

Gas chromatography-mass spectrometry (GC-MS) is a versatile analytical method but its data is usually complicated by the presence of severely co-eluting and trace-level components. In this work, we introduce an optimized band-target entropy minimization approach for the analysis of complex mass spectral data. This new approach enables an automated mass spectral analysis which does not require any user-dependent inputs. Moreover, the approach provides improved sensitivity and accuracy for mass spectral reconstruction of severely co-eluting and trace-level components. The accuracy of our approach is compared to the automatic mass spectral deconvolution and identification system (AMDIS) with two controlled mixtures and a sample of Eucalyptus essential oil. Our approach was able to putatively identify 130 compounds in Eucalyptus essential oil, which was 46% in excess of that identified by AMDIS. This new approach is expected to benefit GC-MS analysis of complex mixtures such as biological samples and essential oils, in which the data are often complicated by co-eluting and trace-level components. Graphical abstract ᅟ.

Controllable synthesis of ZnO nanoparticles with high intensity visible photoemission and investigation of its mechanism.

ZnO is known as a good photoluminescent semiconductor due to its ability to emit visible light. However, the visible emission mechanism is still under debate. In this work, we have successfully synthesized nanoparticles using LiOH, KOH and NaOH as bases and have achieved visible emission of various colours, such as blue, cyan, green and orange. We demonstrate that LiOH is the most efficient base to control the properties of ZnO nanoparticle emission by varying LiOH concentration. Moreover, detailed studies by TEM, UV and XRD show that ZnO particle size plays an important role in the colour of the emitted light and smaller particles tend to emit shorter wavelength photons. The visible emission is suggested to arise from an electron transition from the conduction band to a deep-trapped defect state. Our experimental results suggest the presence of oxygen vacancies on the ZnO nanoparticle surface.

Dose-response metabolomics and pathway sensitivity to map molecular cartography of bisphenol A exposure.

In the toxicological regime, the toxicological endpoint and its dose-response relationship are two of the most prominent characters in conducting a risk assessment for chemical exposure. Systems biological methods have been used to comprehensively characterize the impact of toxicants on the biochemical pathways. However, the majority of the current studies are only based on single-dose, and limited information can be extrapolated to other doses from these experiments, regardless of the sensitivity of each endpoint. This study aims to understand the dose-response metabolite dysregulation pattern and metabolite sensitivity at the system-biological level. Here, we applied bisphenol A (BPA), an endocrine-disrupting chemical (EDC), as the model chemical. We first employed the global metabolomics method to characterize the metabolome of breast cancer cells (MCF-7) upon exposure to different doses (0, 20, 50, and 100 µM) of BPA. The dysregulated features with a clear dose-response relationship were also effectively picked up with an R-package named TOXcms. Overall, most metabolites were dysregulated by showing a significant dose-dependent behaviour. The results suggested that BPA exposure greatly perturbed purine metabolism and pyrimidine metabolism. Interestingly, most metabolites within the purine metabolism were described as a biphasic dose-response relationship. With the established dose-response relationship, we were able to fully map the metabolite cartography of BPA exposure within a wide range of concentrations and observe some unique patterns. Furthermore, an effective concentration of certain fold changes (e.g., EC+10 means the dose at which metabolite is 10% upregulated) and metabolite sensitivity were defined and introduced to this dose-response omics information. The result showed that the purine metabolism pathway is the most venerable target of BPA, which can be a potential endogenous biomarker for its exposure. Overall, this study applied the dose-response metabolomics method to fully understand the biochemical pathway disruption of BPA treatment at different doses. Both dose-response omics strategy and metabolite sensitivity analysis can be further considered and emphasized in future chemical risk assessments.

Extremely low frequency alternating magnetic field-triggered and MRI-traced drug delivery by optimized magnetic zeolitic imidazolate framework-90 nanoparticles.

An extremely low frequency alternating magnetic field (ELF-AMF) was demonstrated to be able to effectively trigger drug release from carefully engineered magnetic ZIF-90 nanoparticles. The embedded Fe3O4 nanoparticles or alternatively Gd2O3 nanoparticles serve as effective MRI tracers for potential visualization of drug delivery to ensure drug delivery accuracy.

Designed Construction of a Graphene and Iron Oxide Freestanding Electrode with Enhanced Flexible Energy-Storage Performance.

In this work, a bendable graphene@iron oxide hybrid film (GFeF) electrode was fabricated through a filtration-assisted self-assembly method. Morphological characterization of GFeF revealed a uniform distribution of iron oxide nanoparticles between graphene nanosheets. Surface chemical characterization confirmed that graphene oxide in the as-prepared hybrid film was effectively reduced after thermal reduction. The electrochemical performance of a GFeF half-cell versus Li/Li(+) exhibited high gravimetric capacity (855.2 mAh g(-1) at 0.02 A g(-1)), high volumetric capacity (1949.9 mAh cm(-3) at 0.02 A g(-1)), and superior cycling stability (93% capacitance retention after 500 cycles). On the basis of such a bendable electrode, a hybrid Li-ion supercapacitor that offers an operation voltage of 3.5 V and delivers a high energy density (129.6 Wh kg(-1)) like a Li-ion battery combined with a high power density (1870 W kg(-1)) like a supercapacitor was fabricated. In addition to the superior energy-storage capability, the as-fabricated prototype pouch cell also exhibited excellent mechanical flexibility and stable electrochemical performances under dynamic bending. The viability of such an energy-storage device provides a possible design pathway for future wearable electronics.

Asymmetric NHC-catalyzed aza-Diels-Alder reactions: highly enantioselective route to α-amino acid derivatives and DFT calculations.

A facile N-heterocyclic carbene catalytic enantioselective aza-Diels-Alder reaction of oxodiazenes with α-chloroaldehydes as dienophile precursors is reported, with excellent enantioselectivity (ee > 99%) and excellent yield (up to 93%). DFT study showed that cis-TSa, formed from a top face approach of oxodiazene to cis-IIa, is the most favorable transition state and is consistent with the experimental observations.

Assessment of RANTES levels as the indicators of plaque vulnerability in rabbit models of atherosclerosis.

The aim of the present study was to determine the chemokine RANTES (regulated on activation, normal T-cell expressed, and secreted) levels in plasma and atherosclerotic plaques and to assess their diagnostic efficacy in the evaluation of vulnerable plaques. The rabbit models of vulnerable atherosclerotic plaque (VAP) were established by high fat diet and pharmaceutical triggering. The serum RANTES levels of VAP group (91.97 ± 8.51 ng/ml) were significantly higher than those of AS (atherosclerosis) group (50.03 ± 2.92 ng/ml). Consistently, the mRNA and protein of RANTES in vulnerable atherosclerotic plaques were also obviously up-regulated compared to AS group (P < 0.01). Moreover, corrected plaque area and vulnerability index of VAP group proved to be significantly higher than AS group. The correlation coefficient between RANTES and plaque vulnerability indicated that RANTES, especially plaque RANTES, was positively correlated with VAP. In addition, increased expression of nuclear factor kappa B p65 (NF-κB p65) was observed in VAP group compared to AS group (P < 0.05), which partly accounted for the increased RANTES levels. In conclusion, positive associations between RANTES and plaque vulnerability suggest that higher RANTES levels may be associated with atherosclerosis and high-risk plaques. Our study highlights the utility of both serum and plaque RANTES levels as indicators of plaque vulnerability in the field of preventive cardiology.

Manipulating the surface coating of ultra-small Gd2O3 nanoparticles for improved T1-weighted MR imaging.

In this report, monodispersed ultra-small Gd2O3 nanoparticles capped with hydrophobic oleic acid (OA) were synthesized with average particle size of 2.9 nm. Two methods were introduced to modify the surface coating to hydrophilic for bio-applications. With a hydrophilic coating, the polyvinyl pyrrolidone (PVP) coated Gd2O3 nanoparticles (Gd2O3-PVP) showed a reduced longitudinal T1 relaxation time compared with OA and cetyltrimethylammonium bromide (CTAB) co-coated Gd2O3 (Gd2O3-OA-CTAB) in the relaxation study. The Gd2O3-PVP was thus chosen for its further application study in MRI with an improved longitudinal relaxivity r1 of 12.1 mM(-1) s(-1) at 7 T, which is around 3 times as that of commercial contrast agent Magnevist(®). In vitro cell viability in HK-2 cell indicated negligible cytotoxicity of Gd2O3-PVP within preclinical dosage. In vivo MR imaging study of Gd2O3-PVP nanoparticles demonstrated considerable signal enhancement in the liver and kidney with a long blood circulation time. Notably, the OA capping agent was replaced by PVP through ligand exchange on the Gd2O3 nanoparticle surface. The hydrophilic PVP grants the Gd2O3 nanoparticles with a polar surface for bio-application, and the obtained Gd2O3-PVP could be used as an in vivo indicator of reticuloendothelial activity.

N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective oxo-Diels-Alder reactions for synthesis of fused pyrano[2,3-b]indoles.

A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2-oxoindolin-3-ylidenes and α-chloroaldehydes was developed for the synthesis of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).

Diastereoselective HOTf-catalyzed three-component one-pot 1,3-dipolar cycloaddition of alpha-diazo ester, nitrosobenzene and electron-deficient alkene.

A novel HOTf-catalyzed three-component one-pot cycloaddition of alpha-diazo ester, nitrosobenzene and electron deficient alkene has been developed. This catalysis is very simple to operate and tolerant to moisture/oxygen to afford the product with high to excellent diastereoselectivity in good to excellent yield, thus providing a useful and convenient method for the preparation of diverse functionalized isoxazolidines under very mild conditions.