Simultaneous Detection of Aldehyde Metabolites by Light-Assisted Ambient Ionization Mass Spectrometry.

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.

ICSDA: a multi-modal deep learning model to predict breast cancer recurrence and metastasis risk by integrating pathological, clinical and gene expression data.

Breast cancer patients often have recurrence and metastasis after surgery. Predicting the risk of recurrence and metastasis for a breast cancer patient is essential for the development of precision treatment. In this study, we proposed a novel multi-modal deep learning prediction model by integrating hematoxylin & eosin (H&E)-stained histopathological images, clinical information and gene expression data. Specifically, we segmented tumor regions in H&E into image blocks (256 × 256 pixels) and encoded each image block into a 1D feature vector using a deep neural network. Then, the attention module scored each area of the H&E-stained images and combined image features with clinical and gene expression data to predict the risk of recurrence and metastasis for each patient. To test the model, we downloaded all 196 breast cancer samples from the Cancer Genome Atlas with clinical, gene expression and H&E information simultaneously available. The samples were then divided into the training and testing sets with a ratio of 7: 3, in which the distributions of the samples were kept between the two datasets by hierarchical sampling. The multi-modal model achieved an area-under-the-curve value of 0.75 on the testing set better than those based solely on H&E image, sequencing data and clinical data, respectively. This study might have clinical significance in identifying high-risk breast cancer patients, who may benefit from postoperative adjuvant treatment.

Association between use of antihypertensive drugs and the risk of cancer: a population-based cohort study in Shanghai.

BACKGROUND: Previously studies shown a potential risk of antihypertensive medicines in relation to cancer susceptibility, which creating significant debate in the scientific community and public concern. We sought to investigate the relationship between antihypertensive medicines and cancer risk, by drug type and class. METHODS: We conducted a population-based cohort study and enrolled patients diagnosed with hypertension from community healthcare centers in Changning District, Shanghai, China. Antihypertensive drug administration were classified as five common antihypertensive drugs. The main outcomes were incidence of total cancer and by major cancer type. RESULTS: Between January 2013 and December 2017, a total of 101,370 hypertensive patients were enrolled in this cohort. During a mean follow-up of 5.1 (SD 1.3) years, 4970 cancer cases were newly diagnosed in the cohort. CCBs were the most frequently used antihypertensives which were associated with a moderately increased risk of total cancer (hazard ratio, HR = 1.11, 95% CI: 1.05-1.18). The second commonly used drug ARBs were also associated with increased risk of total cancer (HR = 1.10, 95%CI: 1.03-1.17) as well as lung and thyroid cancers (HR = 1.21, 95%CI: 1.05-1.39; HR = 1.62 95%CI: 1.18-2.21, respectively). No significant association was found between cancer and other antihypertensives. Hypertensive patients who use more than one class of antihypertensives drugs had a higher risk of total cancer (HR: 1.22, 95%CI: 1.10-1.35 for two classes; HR: 1.22, 95%CI: 1.03-1.45 for three or more classes), and a possible dose-response relationship was suggested (P for trend < 0.001). The risk of thyroid cancer was higher in hypertensive patients prescribed with three or more antihypertensive classes. CONCLUSIONS: Use of ARBs or CCBs may be associated with an increased risk of total cancer. Taking more than one class of antihypertensives drugs appeared to have a higher risk for total cancer.

Effect of magnetic fields on simultaneous nitrification and denitrification microbial systems.

Magnetic fields positively influence the nitrogen removal efficiency in activated sludge systems. However, the structural succession pattern of microorganisms by magnetic fields still remains further explored. In this paper, a magnetic simultaneous nitrification and denitrification (MSND) reactor was constructed, and the influence of optimized magnetic field intensity (0, 10, 20 and 30 mT) on the nitrogen removal efficiency was investigated at HRT 6 h, 28.0-30.0 °C, and pH 7.0-8.0. Molecular biology was used to investigate the succession process of the dominant microbial flora and the functional gene structure of MSND systems. The results showed that the denitrification effects of the MSND system were significantly enhanced, which contributed to the lower concentration of total nitrogen in the effluent of the magnetic reactor than that of the nonmagnetic group reactor. The magnetic fields induced the succession of microbial community structure and improved the stability of microbial communities, thereby the relative abundances of nitrifying and denitrifying bacteria, and the functional genes were improved. In particular, the abundance of functional genes related to gene proliferation and transmembrane transport was increased. Therefore, the efficient nitrogen removal was achieved, which gives inspiration in the enhanced wastewater treatment by magnetic fields.

Night shift work and depression among Chinese workers: the mediating role of sleep disturbances.

BACKGROUND: Depression is considered as a global problem. Recently, the prevalence of depression among night shift workers has been attracting people's attention. This study aims to explore the associations among night shift work, shift frequency and depression among Chinese workers and to explore whether sleep disturbances are a critical factor. METHODS: The cross-sectional survey consists of 787 autoworkers from a manufacturing plant in Fuzhou, China. Information about night shift work, shift frequency, depression, and sleep disturbances were collected from work records and responses to the Patient Health Questionnaire (PHQ-9) and the Pittsburgh Sleep Quality Index (PSQI). A mediation model was generated to examine relationship between night shift work, sleep disturbances, and depression. RESULTS: Our results found that night shift work, shift frequency, sleep disturbances, and depression had positive and significant relationships in a sample of Chinese workers. Night shift work, shift frequency and sleep disturbances were associated with an increased risk of depression among workers (OR: 4.23, 95% CI 2.55-7.00; 3.91, 2.31-6.63; 6.91, 4.40-10.86, respectively). Subsequent mediation analysis found that the association between night shift work and depression appeared to be partially mediated by sleep disturbances. CONCLUSION: These findings suggest that appropriate intervention and management strategies should be considered to alleviate the mental health burden of night shift workers.

Fabrication of a "Selenium Signature" Chemical Probe-Modified Paper Substrate for Simultaneous and Efficient Determination of Biothiols by Paper Spray Mass Spectrometry.

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.

Covalent organic frameworks-based paper solid phase microextraction combined with paper spray mass spectrometry for highly enhanced analysis of tetrabromobisphenol A.

How to further improve the sensitivity of paper spray mass spectrometry (PS-MS) is very important for its application in low content substance detection. Covalent organic frameworks (COFs) are a kind of novel crystalline materials that exhibit tremendous potential for multifarious applications. Nevertheless, the applications of COFs in PS-MS are still unexplored. Herein, for the first time, a method that used COFs nanoparticles as a coated matrix of PS-MS coupled with solid phase microextraction (SPME) was developed, and as a proof of concept, it was applied for highly sensitive analysis of pollutant tetrabromobisphenol A (TBBPA) in environmental samples. In order to prepare the COFs-coated papers, a variety of factors, such as starch type and amount, loaded COFs amount and spray solvent, have been explored in detail. Compared with the naked paper substrates, a lower limit of quantitation of 1 nmol L-1 with 50-fold enhancement was achieved using COFs-based paper composites, which indicated that papers decorated with COFs might be a promising candidate for paper spray with high sensitivity in the analysis of environmental samples.

Fluorometric and colorimetric dual-readout alkaline phosphatase activity assay based on enzymatically induced formation of colored Au@Ag nanoparticles and an inner filter effect.

An ultrasensitive fluorometric and colorimetric dual-mode assay is described for the determination of the activity of alkaline phosphatase (ALP). ALP catalyzes the decomposition of 2-phospho-L-ascorbic acid, and the ascorbic acid thus generated reduces silver ions. In the presence of gold nanoparticles, gold-silver nanoparticles (Au@Ag NPs) are formed. This is accompanied by a color change form pink to deep yellow. The Au@Ag NPs reduce the fluorescence of blue fluorescent graphene quantum dots due to spectral overlap. The changes of absorbance (measured at 410 and 520 nm) and fluorescence (measured at excitation/emission wavelengths of 346/415 nm) correlate well with the ALP activity in the 0.01-6 mU·mL-1 (absorption) and 0.01-2 mU·mL-1 (fluorescence) ranges, and the detection limits are 9 and 5 µU·mL-1 individually. Graphical abstract Schematic presentation of colorimetric and fluorometric dual-readout assay for alkaline phosphatase (ALP) activity. It is based on enzymatically induced formation of gold-silver nanoparticles (Au@Ag NPs), and the fluorescence quenching of graphene quantum dots due to inner filter effect.

Self-Assembly of a Tetraphenylethylene-Based Capsule Showing Both Aggregation- and Encapsulation-Induced Emission Properties.

Functional molecular capsules have attracted a lot of attention in recent years because of their potential applications as chemosensors, catalysis, drug carriers, and so on. We report here the coordination-directed self-assembly of a fluorescent-lantern-type molecular capsule from four tetraphenylethylene-based ditopic ligands and two square-planar palladium(II) ions. The capsule has been thoroughly characterized by UV-vis, 1D/2D NMR, electrospray ionization time-of-flight mass spectrometry, and single-crystal X-ray diffraction studies. The aggregation-induced emission performance of the capsule has been studied by tuning the ratio of mixed solvents. Moreover, with an open cavity, the fluorescence of the capsule also displays anion sensitivity, with the best turn-on responsiveness observed for HCO3-, demonstrating for the first time an encapsulation-induced emission property.

Coordination-Enhanced Luminescence on Tetra-Phenylethylene-Based Supramolecular Assemblies.

Materials with aggregation-induced emission (AIE) properties have received increased attention recently due to their potential applications in light-emitting devices, chemo/biosensors and biomedical diagnostics. In general, AIE requires the forced aggregation of the AIEgens induced by the poor solvent or close arrangement of AIEgens covalently attached to polymer chains. Here, we report two coordination-enhanced fluorescent supramolecular complexes featuring hierarchically restricted intramolecular motions via the self-assembly of tetraphenylethylene (TPE)-based tetra-dentate (La) and bidentate (Lb) ligands and the cis-Pd(en)(NO3)2 (en = ethylenediamine) unit. While the free ligands are non-emissive in dilute solution and show typical AIE properties in both mixed solvent system and the solid state, the self-assembled complexes maintain their fluorescent nature in the solution state. In particular, the Pd4(La)2 complex shows remarkable 6-fold fluorescent enhancement over La in dilute solution. We anticipate that these kinds of coordination-enhanced emissive supramolecules will find applications in biomedical sensing or labeling.

A fast, highly sensitive and selective assay of iodide ions with single-stranded DNA-templated copper nanoparticles as a fluorescent probe for its application in Kunming mice samples.

The development of fast, sensitive, selective and flexible methods for the detection of iodide is highly demanded and is of great significance. In this work, single-stranded DNA-templated copper nanoparticles (ssDNA-CuNPs) generated by sodium ascorbate reduction of Cu2+ along the single-stranded DNA of poly-T were utilized as a fluorescent probe for the determination of iodide ions (I-). The detection scheme is based on the instant quenching of the fluorescence of ssDNA-CuNPs by iodide ions. I- can be quantified in the concentration range from 0.050 to 40 µM and from 40 to 80 µM, and the limit of detection is as low as 15 nM. This method provides a simple and convenient strategy for the biochemical assay of I-, which is also helpful for early diagnosis of related diseases. The establishment of a low cost and fast detection method would be particularly important in developing countries where medical supplies are lacking.

Effect of Fu-Zheng-Xiao-Liu Granules on Expression of Human Epidermal Growth Factor Receptor 2 (HER-2) and Proliferation and Apoptosis of Breast Cancer Cell Line SKBR-3.

BACKGROUND Previous research showed that granulized Fu-Zheng-Xiao-Liu has a significant effect on breast cancer. However, it remains unclear whether HER-2 plays a role in this anti-cancer effect. MATERIAL AND METHODS Serum of male SD rats administered Fu-Zheng-Xiao-Liu granules (SF) was prepared and used to treat HER-2 positive breast cancer cell line SKBR-3. PBS and herceptin were used as negative and positive controls, respectively. MTT was used to detect the proliferation of SKBR-3 cells. Flow cytometry was used to measure the apoptosis of SKBR-3 cells. Western blot and immunofluorescence were used to measure the expression change of HER-2. RESULTS Serum of male SD rats administered Fu-Zheng-Xiao-Liu granules had significantly reduced HER-2 expression at both mRNA level and protein level, significantly inhibited proliferation of SKBR-3 cells, and significantly increased apoptosis of SKBR-3 cells, compared to that of the blank control group or serum control group. CONCLUSIONS Fu-Zheng-Xiao-Liu granules affect proliferation and apoptosis through inhibition of HER-2 transcription and translation, providing an experimental basis for further study of the mechanism by which Fu-Zheng-Xiao-Liu granules affect breast cancer.

Stereocontrolled Self-Assembly and Self-Sorting of Luminescent Europium Tetrahedral Cages.

Coordination-directed self-assembly has become a well-established technique for the construction of functional supramolecular structures. In contrast to the most often exploited transition metals, trivalent lanthanides Ln(III) have been less utilized in the design of polynuclear self-assembled structures despite the wealth of stimulating applications of these elements. In particular, stereochemical control in the assembly of lanthanide chiral cage compounds is not easy to achieve in view of the usually large lability of the Ln(III) ions. We report here the first examples of stereoselective self-assembly of chiral luminescent europium coordination tetrahedral cages and their intriguing self-sorting behavior. Two pairs of R and S ligands are designed on the basis of the pyridine-2,6-dicarboxamide coordination unit, bis(tridentate) L1 and tris(tridentate) L2. Corresponding chiral Eu4(L1)6 and Eu4(L2)4 topological tetrahedral cages are independently assembled via edge- and face-capping design strategies, respectively. The chirality of the ligand is transferred during the self-assembly process to give either Δ or Λ metal stereochemistry. The self-assembled cages are characterized by NMR, high-resolution ESI-TOF-MS, and in one case by X-ray crystallography. Strict control of stereoselectivity is confirmed by CD spectroscopy and NMR enantiomeric differentiation experiments. Narcissistic self-sorting is observed in the self-assembly process when two differently shaped ligands L1 and L2 are mixed. More impressively, distinct self-sorting behavior between Eu4(L1)6 and Eu4(L2)4 coordination cages is observed for the first time when racemic mixtures of ligands are used. We envisage that chiral luminescent lanthanide tetrahedral cages could be used in chiroptical probes\sensors and enantioselective catalysis.

Bottom-Up Construction of Mesoporous Nanotubes from 78-Component Self-Assembled Nanobarrels.

Segmental and continuous hexagonal-packed mesoporous metal-organic nanotubes (MMONTs) with outside diameters of up to 4.5 nm and channel sizes of 2.4 nm were hierarchically constructed by a rational multicomponent self-assembly process involving starting from [L2Pd2(NO3)2] (L=o-phenanthroline or 2,2'-bipyridine) and 4-pyridinyl-3-pyrazole. An unprecedented crystallization-driven cross-linking between discrete nanobarrel building units by spontaneous loss of the capping ligands to form infinite nanotubes was observed. Such a barrel-to-tube transformation provides new possibilities for the fabrication of MMONTs using the solution bottom-up approach.

Identification of sulfhydryl-containing proteins and further evaluation of the selenium-tagged redox homeostasis-regulating proteins.

Chemoproteomic profiling of sulfhydryl-containing proteins has consistently been an attractive research hotspot. However, there remains a dearth of probes that are specifically designed for sulfhydryl-containing proteins, possessing sufficient reactivity, specificity, distinctive isotopic signature, as well as efficient labeling and evaluation capabilities for proteins implicated in the regulation of redox homeostasis. Here, the specific selenium-containing probes (Se-probes) in this work displayed high specificity and reactivity toward cysteine thiols on small molecules, peptides and purified proteins and showed very good competitive effect of proteins labeling in gel-ABPP. We identified more than 6000 candidate proteins. In TOP-ABPP, we investigated the peptide labeled by Se-probes, which revealed a distinct isotopic envelope pattern of selenium in both the primary and secondary mass spectra. This unique pattern can provide compelling evidence for identifying redox regulatory proteins and other target peptides. Furthermore, our examiation of post-translational modification (PTMs) of the cysteine site residues showed that oxidation PTMs was predominantly observed. We anticipate that Se-probes will enable broader and deeper proteome-wide profiling of sulfhydryl-containing proteins, provide an ideal tool for focusing on proteins that regulate redox homeostasis and advance the development of innovative selenium-based pharmaceuticals.

Fecal Immunochemical Testing and the Risk of Advanced Colorectal Neoplasia: A Difference-In-Difference Analysis.

PURPOSE: To evaluate the effectiveness of fecal immunochemical testing (FIT) in colorectal cancer screening. METHODS: We conducted a prospective cohort study among 5,598 participants age 40-74 years between 2012 and 2020 in Tianjin, China. Inverse probability weighting was adopted to adjust for potential imbalanced factors between groups. A Cox proportional hazards model was used to estimate the weighted associations between FIT screening and advanced colorectal neoplasia. A difference-in-difference (DID) model was adopted to compare the incidence rates of advanced colorectal neoplasia between groups. RESULTS: In DID analysis, the rate of incidence was reduced by 0.34 cases per person-years in the screening group as compared with the historical FIT screening group (rate ratio [RR], 0.08 [95% CI, 0.07 to 0.10]) and by 0.06 cases per person-years in the non-FIT screening group as compared with the historical non-FIT screening group (RR, 0.37 [95% CI, 0.29 to 0.48]; P < .001 for both comparisons), with a relative reduction of 0.28. Similar benefit effect from FIT screening was observed in sex and age subgroups. CONCLUSION: FIT screening was associated with a reduction in incidence density from advanced colorectal neoplasia.

Data on human decision, feedback, and confidence during an artificial intelligence-assisted decision-making task.

The data are collected from a human subjects study in which 100 participants solve chess puzzle problems with artificial intelligence (AI) assistance. The participants are assigned to one of the two experimental conditions determined by the direction of the change in AI performance at problem 20: 1) high- to low-performing and 2) low- to high-performing. The dataset contains information about the participants' move before an AI suggestion, the goodness evaluation score of these moves, AI suggestion, feedback, and the participants' confidence in AI and self-confidence during three initial practice problems and 30 experimental problems. The dataset contains 100 CSV files, one per participant. There is opportunity for this dataset to be utilized in various domains that research human-AI collaboration scenarios such as human-computer interaction, psychology, computer science, and team management in engineering/business. Not only can the dataset enable further cognitive and behavioral analysis in human-AI collaboration contexts but also provide an experimental platform to develop and test future confidence calibration methods.

Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe.

S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.

The Effect of Silane Coupling Agent on the Texture and Properties of In Situ Synthesized PI/SiO2 Nanocomposite Film.

PI/SiO2 composite films have been prepared by using in situ polymerization. The influences of the dosage of silane coupling agent (KH-560) on the structure and performance of PI/SiO2 composite film have been investigated. The results show that in the components without KH-560, the addition of SiO2 decreases the transmittance of the sample. Compared to the same SiO2 doping amount, the transmittance in the visible light range of the sample using KH-560 is higher than that of the sample without KH-560. After adding KH-560, the tensile strength, the elastic modulus the elongation at break of the sample have largely changed. The thermal stability and the ability to resist ultraviolet radiation of the composite film first increases and then decreases. Furthermore, the optimal dosage of KH-560 is 3%. Moreover, the addition of KH-560 has little effect on the transmittance of the PI/SiO2 composite films before and after UV irradiation.

Palladium(II)-Catalyzed C(sp2)-H Bond Activation/C-N Bond Cleavage Annulation of N-Methoxy Amides and Arynes.

The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.