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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In Situ Construction of COF-Based Paper Serving as a Plasmonic Substrate for Enhanced PSI-MS Detection of Polycyclic Aromatic Hydrocarbons.

Accurate detection, quantitation, and differentiation of polycyclic aromatic hydrocarbons (PAHs) and their isomers in diverse samples is elusive for paper spray ionization mass spectrometry (PSI-MS). To address these issues, herein, for the first time, we propose to fabricate a novel, flexible, and stable paper substrate based on covalent organic frameworks (COFs) via an in situ method under room temperature in air. After embedding gold nanoparticles (AuNPs), this paper substrate (COFs-paper) could further serve as a multifunctional plasmonic matrix (AuNPs-COFs-paper) for dual-wavelength laser-assisted PSI-MS detection of PAHs and feasible paper surface-enhanced Raman scattering (pSERS)-aided isomer discrimination. Taking advantage of the synergistic effect between the AuNPs and COFs present on the novel AuNP-embedded COFs-paper substrate, a satisfied LOD of 0.50 ng/µL for phenanthrene was realized, which improved almost 300 times compared with the naked-paper matrix, and the regression coefficient R2 was up to 0.999. Real sample corn oil-containing PAHs can be efficiently detected and identified using this technique. The established platform has promising potential for on-site chemical analysis with portable PSI-MS and pSERS instruments.

Data on the design and operation of drones by both individuals and teams.

Human subject experiments are performed to assess the impact of artificial intelligence (AI) agents on distributed human design teams and individual human designers. In the team experiment, participants in teams of six develop and operate a drone fleet to deliver parcels routed to multiple locations of a target market. Among the design teams in the experiment, half of the design teams are human-only teams with no available AI agent. The other half of the design teams, designated as hybrid teams, have drone design and operation AI agents to advise them. Halfway through the team experiment, team structure is changed unexpectedly, requiring participants to adapt to the change. In the individual experiment, participants develop drones based on given design specifications, either on their own or with the availability of a drone design AI agent to advise them. During these experiments, participants configure, test, and share their designs and communicate with their teammates through an online research platform. The platform collects a step-by-step log of the actions made by participants. This article contains data sets collected from 44 teams (264 participants) in the team experiment and 73 participants in the individual experiment. These data sets can be used for behavioral analysis, sequence-based analysis, and natural language processing.

Synthesis and Properties of Polyimide Silica Nanocomposite Film with High Transparent and Radiation Resistance.

In order to prepare flexible glass cover sheet materials suitable for space solar cells, fluorinated diamine 2,2'-bistrifluoromethyl benzidine (TFDB) and fluorinated dianhydride 4,4' (hexafluoroisopropyl) diphthalic dianhydride (6FDA) as the monomer, polyimide (PI)/SiO2 composite film was synthesized by in situ polymerization, and the influence of coupling agent and SiO2 nanoparticle content on the film structure and properties was studied. The results show that PI synthesized from fluorine-containing monomers has better light transmittance, and the highest transmittance can reach 91.4%. The average visible light transmittance of the composite film decreases with the increase of SiO2 content, and the transmittance of the film decreases less in the high-wavelength region and greatly decreases in the low-wavelength region. The tensile strength and elastic modulus of PI/SiO2 composite film increase with the increase of SiO2 content, first increase and then decrease, reaching the maximum when the content is 10%; while the elongation at break of the composite film gradually increases with the increase of SiO2 content reduce. The thermal stability of PI/SiO2 composite film increases with the increase of SiO2 content. The doping of nano-SiO2 significantly suppresses the influence of irradiation on the mechanical properties of the film.

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.

Fluorescence switch of gold nanoclusters stabilized with bovine serum albumin for efficient and sensitive detection of cysteine and copper ion in mice with Alzheimer's disease.

The near-infrared fluorescence of gold nanoclusters stabilized with bovine serum albumin (BSA -AuNCs) centered at 675 nm could be enhanced by cysteine and then effectively quenched by copper ion (Cu2+), therefore, cysteine and copper ion could be detected in sequence. At "on" state, fluorescence enhancement of BSA-AuNCs is generated due to the reaction between cysteine and BSA-AuNCs, via filling the surface defect of gold nanoclusters, while Cu2+ can further oxidize the reductive sulfydryl of cysteine and interact with amino acids presented in the BSA chain, inducing gold nanoclusters to aggregate, thus causing "off" state with fluorescence quenching. Fluorescence switch of BSA-AuNCs can be used for cysteine and Cu2+ detection in mice brain with Alzheimer's disease (AD) in vitro, with fast response, high chemical stability and sensitivity. Besides, it was able to image the endogenous Cu2+ in liver and heart of AD mice in situ. The results are promising, especially in the framework of early diagnosis of Alzheimer's disease.

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.

Regional difference in global unified efficiency of China-Evidence from city-level data.

As the world's most energy-consuming and carbon-emitting country, China faces enormous pressures on energy conservation and emission reduction, and improving energy efficiency is one of the most important ways to save energy and reduce emissions. Using the city-level panel data in China during 2013-2017, we apply the global non-radial directional distance function (NDDF) to estimate the global unified efficiency (GUE) of each city as well as their driving forces, and identify the change of efficiency performance. The results indicate that the average GUE changed -1.0%, 1.2%, 6.0% and 7.0% during 2013-2014, 2014-2015, 2015-2016 and 2016-2017, respectively. The more developed Central China and the relatively underdeveloped Northwest China have high GUE, while the lower GUE exists in the Northeast and North China regions with greater industrial transformation and upgrading pressures. In general, the global unified efficiency of each region increases over time.

Designing a highly stable coordination-driven metallacycle for imaging-guided photodynamic cancer theranostics.

Coordination-driven self-assembly features good predictability and directionality in the construction of discrete metallacycles and metallacages with well-defined sizes and shapes, but their medicinal application has been limited by their low stability and solubility. Herein, we have designed and synthesized a highly stable coordination-driven metallacycle with desired functionality derived from a perylene-diimide ligand via a spontaneous deprotonation self-assembly process. Brilliant chemical stability and singlet oxygen production ability of this emissive octanuclear organopalladium macrocycle make it a good candidate toward biological studies. After cellular uptake by endocytosis, the metallacycle exhibits potent fluorescence cell imaging properties and cancer photodynamic therapeutic ability through enhancing ROS production, with high biocompatibility and safety. This study not only provides a rational design strategy for highly stable luminescent organopalladium metallacycles, but also sheds light on their application in imaging-guided photodynamic cancer therapy.

A new mitochondrion targetable fluorescent probe for carbon monoxide-specific detection and live cell imaging.

A new mitochondrion targetable molecular probe for carbon monoxide (CO)-specific detection based on palladium-free mediated opening of spirolactam was designed. The turn-on red fluorescence caused by CO enables a safe and powerful method for unravelling the function of CO in biological systems to be established.