GCMSFormer: A Fully Automatic Method for the Resolution of Overlapping Peaks in Gas Chromatography-Mass Spectrometry.

Gas chromatography-mass spectrometry (GC-MS) is one of the most important instruments for analyzing volatile organic compounds. However, the complexity of real samples and the limitations of chromatographic separation capabilities lead to coeluting compounds without ideal separation. In this study, a Transformer-based automatic resolution method (GCMSFormer) is proposed to resolve mass spectra from GC-MS peaks in an end-to-end manner, predicting the mass spectra of components directly from the raw overlapping peaks data. Furthermore, orthogonal projection resolution (OPR) was integrated into GCMSFormer to resolve minor components. The GCMSFormer model was trained, validated, and tested using 100,000 augmented data. It achieves 99.88% of the bilingual evaluation understudy (BLEU) value on the test set, significantly higher than the 97.68% BLEU value of the baseline sequence-to-sequence model long short-term memory (LSTM). GCMSFormer was also compared with two nondeep learning resolution tools (MZmine and AMDIS) and two deep learning resolution tools (PARAFAC2 with DL and MSHub/GNPS) on a real plant essential oil GC-MS data set. Their resolution results were compared on evaluation metrics, including the number of compounds resolved, mass spectral match score, correlation coefficient, explained variance, and resolution speed. The results demonstrate that GCMSFormer has better resolution performance, higher automation, and faster resolution speed. In summary, GCMSFormer is an end-to-end, fast, fully automatic, and accurate method for analyzing GC-MS data of complex samples.

[Application of speech induced ABR in rehabilitation intervention for hearing impaired children].

Objective:Exploring the electrophysiological changes of auditory rehabilitation in young children with hearing impairment, providing more methods for early assessment and intervention. Methods:Twenty children aged 2-4 were enrolled, with moderate hearing loss and no other abnormalities in the ears. Divide them into group 1 with normal hearing, group 2 with abnormal hearing, group 3 with abnormal hearing receiving hearing aid intervention for one year, and group 4 with abnormal hearing receiving hearing aid and language training rehabilitation for one year. The SmartEP auditory evoked potential instrument was used to detect speech induced ABR and conduct screening for 'Standards and Evaluating Hearing and Language Abilities of Children with Hearing Impairment in 80 enrolled children after rehabilitation training, and the latency、amplitude of speech induced ABR waveform and evaluation scale scores for each group after rehabilitation intervention were compared. Results:Compared with the normal group, the latency of each wave in the other three groups was prolonged. The differences in each wave between Group 2 and Group 3 were statistically significant, while the differences in D and F waves between Group 3 and Group 4 were statistically significant. Compared with the normal group, the maximum amplitude at F0 decreased in the other three groups, and the differences in maximum amplitude between Group 2 and Group 3, Group 2 and Group 4, and Group 3 and Group 4 were statistically significant. Compared with the normal group, the scores of the auditory language assessment scale in the hearing intervention group and the hearing aid plus language training group were significantly higher than those in the abnormal group in terms of recognition rate. The recognition rates of hearing impaired children with language training foundation are similar to those of the normal group of children. Conclusion:Auditory rehabilitation can alter the electrophysiological aspects of hearing and serve as a basis for early assessment and intervention in young children.

Anthraquinone-based covalent organic framework as a recyclable direct hydrogen atom transfer photocatalyst for C-H functionalization.

Photocatalytic direct hydrogen atom transfer (d-HAT) is a synthetically important strategy to convert C-H bonds to useful C-X bonds. Herein we report the synthesis of an anthraquinone-based two-dimensional covalent organic framework, DAAQ-COF, as a recyclable d-HAT photocatalyst for C-H functionalization. Powder X-ray diffraction, N2 sorption isotherms, solid-state NMR spectra, infrared spectra, and thermogravimetric analysis characterized DAAQ-COF as a crystalline, porous COF with a stable ketoenamine linkage and strong absorption in the visible region. Under visible light irradiation, DAAQ-COF is photo-excited to cleave C(sp3)-H or C(sp2)-H bonds via HAT to generate reactive carbon radicals, which add to different radical acceptors to achieve C-N or C-C coupling reactions. DAAQ-COF is easily recovered from the reaction mixture via centrifugation or filtration and used in six consecutive reaction runs without any decrease in catalytic efficiency. The ease of catalyst separation allows sequential conversion of the C-N coupling intermediate to synthetically useful amide, ester, or thioester products. Photophysical and isotope labelling experiments support the d-HAT mechanism of DAAQ-COF-catalyzed C-H bond functionalization.

Metal-Organic Layers with Photosensitizer and Pyridine Pairs Activate Alkyl Halides for Photocatalytic Heck-Type Coupling with Olefins.

Photochemical generation of alkyl radicals from haloalkanes often requires strong energy input from ultraviolet light or a strong photoreductant. Haloalkanes can alternatively be activated with nitrogen-based nucleophiles through a sequential SN2 reaction and single-electron reduction to access alkyl radicals, but these two reaction steps have opposite steric requirements on the nucleophiles. Herein, we report the design of Hf12 metal-organic layers (MOLs) with iridium-based photosensitizer bridging ligands and secondary-building-unit-supported pyridines for photocatalytic alkyl radical generation from haloalkanes. By bringing the photosensitizer and pyridine pairs in proximity, the MOL catalysts allowed facile access to the pyridinium salts from SN2 reactions between haloalkanes and pyridines and at the same time enhanced electron transfer from excited photosensitizers to pyridinium salts to facilitate alkyl radical generation. Consequentially, the MOLs efficiently catalyzed Heck-type cross-coupling reactions between haloalkanes and olefinic substrates to generate functionalized alkenes. The MOLs showed 4.6 times higher catalytic efficiency than the homogeneous counterparts and were recycled and reused without a loss of catalytic activity.

A comprehensive review of toxicity of coal fly ash and its leachate in the ecosystem.

Coal fly ash (CFA), a byproduct of coal combustion, is a hazardous industrial solid waste. Its excessive global production, coupled with improper disposal practices, insufficient utilization and limited awareness of its inherent hazards, poses a significant threat to both ecological environment and human health. Based on the physicochemical properties of CFA and its leachates, we elucidate the forms of CFA and potential pathways for its entry into the human body, as well as the leaching behavior, maximum tolerance and biological half-life of toxic elements present in CFA. Furthermore, we provide an overview of current strategies and methods for mitigating the leaching of these harmful elements from CFA. Moreover, we systemically summarize toxic effect of CFA on organisms across various tiers of complexity, analyze epidemiological findings concerning the human health implications resulting from CFA exposure, and delve into the biotoxicological mechanisms of CFA and its leachates at cellular and molecular levels. This review aims to enhance understanding of the potential toxicity of CFA, thereby promoting increased public awareness regarding the disposal and management of this industrial waste.

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy.

Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a two-dimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.

Search for Dark-Matter-Nucleon Interactions with a Dark Mediator in PandaX-4T.

We report results of a search for dark-matter-nucleon interactions via a dark mediator using optimized low-energy data from the PandaX-4T liquid xenon experiment. With the ionization-signal-only data and utilizing the Migdal effect, we set the most stringent limits on the cross section for dark matter masses ranging from 30 MeV/c^{2} to 2 GeV/c^{2}. Under the assumption that the dark mediator is a dark photon that decays into scalar dark matter pairs in the early Universe, we rule out significant parameter space of such thermal relic dark-matter model.

A Spirobifluorene-Based Covalent Organic Framework for Dual Photoredox and Nickel Catalysis.

Covalent organic frameworks (COFs) have emerged as tunable, crystalline, and porous functional organic materials, but their application in photocatalysis has been limited by rapid excited-state quenching. Herein, we report the first example of dual photoredox/nickel catalysis by an sp2 carbon-conjugated spirobifluorene-based COF. Constructed from spirobifluorene and nickel-bipyridine linkers, the NiSCN COF adopted a two-dimensional structure with staggered stacking. Under light irradiation, NiSCN catalyzed amination and etherification/esterification reactions of aryl halides through the photoredox mechanism, with a catalytic efficiency more than 23-fold higher than that of its homogeneous control. NiSCN was used in five consecutive reactions without a significant loss of catalytic activity.

Search for Light Dark Matter from the Atmosphere in PandaX-4T.

We report a search for light dark matter produced through the cascading decay of η mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasielastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne·year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross section is set at 5.9×10^{-37} cm^{2} for a dark matter mass of 0.1 MeV/c^{2} and mediator mass of 300 MeV/c^{2}. The lowest upper limit of η to the dark matter decay branching ratio is 1.6×10^{-7}.

Search for Light Dark Matter with Ionization Signals in the PandaX-4T Experiment.

We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.

Generation and Stabilization of a Dinickel Catalyst in a Metal-Organic Framework for Selective Hydrogenation Reactions.

Although many monometallic active sites have been installed in metal-organic frameworks (MOFs) for catalytic reactions, there are no effective strategies to generate bimetallic catalysts in MOFs. Here we report the synthesis of a robust, efficient, and reusable MOF catalyst, MOF-NiH, by adaptively generating and stabilizing dinickel active sites using the bipyridine groups in MOF-253 with the formula of Al(OH)(2,2'-bipyridine-5,5'-dicarboxylate) for Z-selective semihydrogenation of alkynes and selective hydrogenation of C=C bonds in α,ß-unsaturated aldehydes and ketones. Spectroscopic studies established the dinickel complex (bpy⋅- )NiII (µ2 -H)2 NiII (bpy⋅- ) as the active catalyst. MOF-NiH efficiently catalyzed selective hydrogenation reactions with turnover numbers of up to 192 and could be used in five cycles of hydrogenation reactions without catalyst leaching or significant decrease of catalytic activities. The present work uncovers a synthetic strategy toward solution-inaccessible Earth-abundant bimetallic MOF catalysts for sustainable catalysis.

Sequential Modifications of Metal-Organic Layer Nodes for Highly Efficient Photocatalyzed Hydrogen Atom Transfer.

Herein, we report the synthesis of a bifunctional photocatalyst, Zr-OTf-EY, through sequential modifications of metal cluster nodes in a metal-organic layer (MOL). With eosin Y and strong Lewis acids on the nodes, Zr-OTf-EY catalyzes cross-coupling reactions between various C-H compounds and electron-deficient alkenes or azodicarboxylate to afford C-C and C-N coupling products, with turnover numbers of up to 1980. In Zr-OTf-EY-catalyzed reactions, Lewis acid sites bind the alkenes or azodicarboxylate to increase their local concentrations and electron deficiency for enhanced radical additions, while EY is stabilized by site isolation on the MOL to afford a long-lived catalyst for hydrogen atom transfer. The proximity between photostable EY sites and Lewis acids on the nodes of Zr-OTf-EY enhances the catalytic efficiency by approximately 400 times over the homogeneous counterpart in the cross-coupling reactions.

A Switching Memory-Based Event-Trigger Scheme for Synchronization of Lur'e Systems With Actuator Saturation: A Hybrid Lyapunov Method.

This article is concerned with the event-triggered synchronization of Lur'e systems subject to actuator saturation. Aiming at reducing control costs, a switching-memory-based event-trigger (SMBET) scheme, which allows a switching between the sleeping interval and the memory-based event-trigger (MBET) interval, is first presented. In consideration of the characteristics of SMBET, a piecewise-defined but continuous looped-functional is newly constructed, under which the requirement of positive definiteness and symmetry on some Lyapunov matrices is dropped within the sleeping interval. Then, a hybrid Lyapunov method (HLM), which bridges the gap between the continuous-time Lyapunov theory (CTLT) and the discrete-time Lyapunov theory (DTLT), is used to make the local stability analysis of the closed-loop system. Meanwhile, using a combination of inequality estimation techniques and the generalized sector condition, two sufficient local synchronization criteria and a codesign algorithm for the controller gain and triggering matrix are developed. Furthermore, two optimization strategies are, respectively, put forward to enlarge the estimated domain of attraction (DoA) and the allowable upper bound of sleeping intervals on the premise of ensuring local synchronization. Finally, a three-neuron neural network and the classical Chua's circuit are used to carry out some comparison analyses and to display the advantages of the designed SMBET strategy and the constructed HLM, respectively. Also, an application to image encryption is provided to substantiate the feasibility of the obtained local synchronization results.

A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy.

We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT.

Metal-Organic Layer Delivers 5-Aminolevulinic Acid and Porphyrin for Dual-Organelle-Targeted Photodynamic Therapy.

The efficacy of photodynamic therapy (PDT) depends on the subcellular localization of photosensitizers. Herein, we report a dual-organelle-targeted nanoparticle platform for enhanced PDT of cancer. By grafting 5-aminolevulinic acid (ALA) to a Hf12 -based nanoscale metal-organic layer (Hf-MOL) via carboxylate coordination, ALA/Hf-MOL enhanced ALA delivery and protoporphyrin IX (PpIX) synthesis in mitochondria, and trapped the Hf-MOL comprising 5,15-di-p-benzoatoporphyrin (DBP) photosensitizers in lysosomes. Light irradiation at 630 nm simultaneously excited PpIX and DBP to generate singlet oxygen and rapidly damage both mitochondria and lysosomes, leading to synergistic enhancement of the PDT efficacy. The dual-organelle-targeted ALA/Hf-MOL outperformed Hf-MOL in preclinical PDT studies, with a 2.7-fold lower half maximal inhibitory concentration in cytotoxicity assays in vitro and a 3-fold higher cure rate in a colon cancer model in vivo.

Molecular Engineering of Metal-Organic Layers for Sustainable Tandem and Synergistic Photocatalysis.

Metal-organic layers (MOLs), a monolayered version of metal-organic frameworks (MOFs), have recently emerged as a novel two-dimensional molecular material platform to design multifunctional catalysts. MOLs inherit the intrinsic molecular tunability of MOFs and yet have more accessible and modifiable building blocks. Here we report molecular engineering of six MOLs via modulated solvothermal synthesis between HfCl4 and three photosensitizing ligands followed by postsynthetic modification with two carboxylate-containing cobaloximes for tandem and synergistic photocatalysis. Morphological and structural characterization by transmission electron microscopy and atomic force microscopy and compositional analysis by inductively coupled plasma-mass spectrometry and nuclear magnetic resonance spectroscopy establish the MOLs as flat nanoplates with a periodic lattice structure of hexagonal symmetry. The MOLs efficiently catalyze tandem dehydrogenative coupling reactions and synergistic Heck-type coupling reactions. The most active MOL catalyst was used for the gram-scale synthesis of vesnarinone, a cardiotonic agent, in 80% yield with a turnover number of 400 and in eight consecutive reaction cycles without significant loss of activities.

Pharmacological ascorbate potentiates combination nanomedicines and reduces cancer cell stemness to prevent post-surgery recurrence and systemic metastasis.

Conventional chemotherapy targets proliferative cancer cells to halt tumor progression or regress tumors. However, the plasticity of tumor cells enables their phenotypical changes to acquire chemo-resistance, leading to treatment failure or tumor recurrence after a successful treatment course. Here, we report the use of high-dose pharmacologic ascorbate to potentiate treatment efficacy of nanoscale coordination polymers (NCPs) delivering two clinical combinations of chemotherapeutics, carboplatin/docetaxel and oxaliplatin/SN38, and to target metabolic plasticity of tumor cells. Combination treatments of high-dose ascorbate and NCPs overcome multi-drug resistance by significantly reducing the abundance of cancer stem cells (CSCs) in solid tumors, as evidenced by reduced expression of tumor pluripotency factors. The clearance of CSCs inhibits post-surgery recurrence and systemic metastasis in multiple mouse models of cancer.

Enhanced Energy Transfer in A π-Conjugated Covalent Organic Framework Facilitates Excited-State Nickel Catalysis.

Covalent organic frameworks (COFs) have received broad interest owing to their permanent porosity, high stability, and tunable functionalities. COFs with long-range π-conjugation and photosensitizing building blocks have been explored for sustainable photocatalysis. Herein, we report the first example of COF-based energy transfer Ni catalysis. A pyrene-based COF with sp2 carbon-conjugation was synthesized and used to coordinate NiII centers through bipyridine moieties. Under light irradiation, enhanced energy transfer in the COF facilitated the excitation of Ni centers to catalyze borylation and trifluoromethylation reactions of aryl halides. The COF showed two orders of magnitude higher efficiency in these reactions than its homogeneous control and could be recovered and reused without significant loss of catalytic activity.

Deep learning-based method for automatic resolution of gas chromatography-mass spectrometry data from complex samples.

Modern gas chromatography-mass spectrometry (GC-MS) is the workhorse for the high-throughput profiling of volatile compounds in complex samples. It can produce a considerable amount of two-dimensional data, and automatic methods are required to distill chemical information from raw GC-MS data efficiently. In this study, we proposed an Automatic Resolution method (AutoRes) based on pseudo-Siamese convolutional neural networks (pSCNN) to extract the meaningful features swamped by the noises, baseline drifts, retention time shifts, and overlapped peaks. Two pSCNN models were trained with 400,000 augmented spectral pairs, respectively. They can predict the selective region (pSCNN1) and elution region (pSCNN2) of compounds in an untargeted manner. The accuracies of the pSCNN1 model and the pSCNN2 model on their test sets are 99.9% and 92.6%, respectively. Then, the chromatographic profile of each component was automatically resolved by full rank resolution (FRR) based on the predicted regions by these models. The performance of AutoRes was evaluated on the simulated and plant essential oil datasets. Compared to AMDIS and MZmine, AutoRes resolves more reasonable mass spectra, chromatograms, and peak areas to identify and quantify compounds. The average match scores of AutoRes (925 and 936) outperformed AMDIS (909 and 925) and MZmine (888 and 916) when resolving mass spectra from overlapped peaks on the Set Ⅰ and Set Ⅱ of plant essential oil dataset and matching them against the NIST17 library. It extracted peak areas and mass spectra automatically from 10 GC-MS files of plant essential oils, and the entire process was completed in 8 min without any prior information or manual intervention. It is implemented in Python and is available as an open-source package at https://github.com/dyjfan/AutoRes.

Search for Solar

A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c^{2}.