NIR-II Fluorescence Sensor Based on Steric Hindrance Regulated Molecular Packing for In Vivo Epilepsy Visualization.

Fluorescence sensing is crucial to studying biological processes and diagnosing diseases, especially in the second near-infrared (NIR-II) window with reduced background signals. However, it's still a great challenge to construct "off-on" sensors when the sensing wavelength extends into the NIR-II region to obtain higher imaging contrast, mainly due to the difficult synthesis of spectral overlapped quencher. Here, we present a new fluorescence quenching strategy, which utilizes steric hindrance quencher (SHQ) to tune the molecular packing state of fluorophores and suppress the emission signal. Density functional theory (DFT) calculations further reveal that large SHQs can competitively pack with fluorophores and prevent their self-aggregation. Based on this quenching mechanism, a novel activatable "off-on" sensing method is achieved via bio-analyte responsive invalidation of SHQ, namely the Steric Hindrance Invalidation geNerated Emission (SHINE) strategy. As a proof of concept, the ClO--sensitive SHQ lead to the bright NIR-II signal release in epileptic mouse hippocampus under the skull and high photon scattering brain tissue, providing the real-time visualization of ClO- generation process in living epileptic mice.

A Novel Near-Infrared Ratiometric Fluorescence Probe for Hg2+ Based on Quinoline-Fused Rhodamine Dye.

As one of the most toxic metals, Mercury ions cause serious environmental pollution and threaten the health of living organisms. Hence, we designed and synthesised a new near-infrared (NIR) ratiometric fluorescent probe toward monitoring of Hg2+ based on quinoline-fused rhodamine dye. Owing to the specific spirolactam ring-opening reaction, the probe exhibits a ratiometric fluorescent change after treatment of Hg2+ with increased emission in NIR and significantly reduced emission in visible region. The specific response mechanism and dual-channel fluorescence change allow the probe to have remarkable detection selectivity, fast response and high detection sensitivity. Moreover, with the properties of excellent cell permeability and low cytotoxicity, probe can be applied as detection tool for mercury ions with dual-channel ratiometric fluorescence imaging in living cell.

A Chitosan-Based Fluorescent Probe Combined with Smartphone Technology for the Detection of Hypochlorite in Pure Water.

Using chitosan as a raw material, 1,8-naphthimide as the fluorescent chromophore, and sulfur-containing compounds as the recognition groups, a novel naphthimide-functionalized chitosan probe, CS-BNS, for the detection of ClO- was successfully synthesized. The modification of chitosan was verified by SEM, XRD, FTIR, mapping, 13C-NMR, TG and the structure of the probe molecule was characterized. The identification performance of the probes was studied using UV and fluorescence spectrophotometers. The results show that CS-BNS exhibits a specific response to ClO- based on the oxidative reaction of ClO- to the recognition motifs, as well as a good resistance to interference. And the probe has high sensitivity and fast response time, and can complete the detection of ClO- in a pure water system within 60 s. The probe can also quantify ClO- (y = 30.698x + 532.37, R2 = 0.9833) with a detection limit as low as 0.27 µM. In addition, the combination of the probe with smartphone technology enables the visualization and real-time monitoring of ClO-. Moreover, an identification system for ClO- was established by combining the probe with smartphone technology, which realized the visualization and real-time monitoring of ClO-.

Nucleophilic functionalizations of indole derivatives using the aromatic Pummerer reaction.

Because of the electron-rich property of indoles, direct functionalization strategies towards indoles generally involve electrophilic substitutions. In this paper, an efficient protocol for nucleophilic hydroxylation, halogenation and esterification of indoles via the aromatic Pummerer process was developed. With the advantages of readily accessible starting materials, simple operation and mild conditions, this protocol should be of interest to synthetic scientists.

A prognostic nomogram for stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgical resection.

BACKGROUND: The purpose of this study was to develop a large population-based nomogram incorporating the log odds of positive nodes (LODDS) for predicting the overall survival (OS) of stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgical resection. METHODS: The Surveillance, Epidemiology, and End Results database was used to collect information on patients diagnosed with stage II/III rectal cancer between 2010 and 2015 and treated with NCRT followed by surgical resection. The Cox regression analyses were performed to determine the independent prognostic factors. In this study, LODDS was employed instead of American Joint Committee on Cancer (AJCC) 7th N stage to determine lymph node status. Then a nomogram integrating independent prognostic factors was developed to predict the 24-, 36-, and 60-month overall survival. The receiver operating characteristic (ROC) curves and calibration curves were used to validate the nomogram. Furthermore, patients were stratified into three risk groups (high-, middle-, and low-risk) based on the total points obtained from the nomogram. And Kaplan-Meier curves were plotted to compare the OS of the three groups. RESULTS: A total of 3829 patients were included in the study. Race, sex, age, marital status, T stage, tumor grade, tumor size, LODDS, CEA level, and postoperative chemotherapy were identified as independent prognostic factors, based on which the prognostic nomogram was developed. The area under curve values of the nomogram for the 24-, 36-, and 60-month OS in the training cohort were 0.736, 0.720, and 0.688, respectively; and 0.691, 0.696, and 0.694 in the validation cohort, respectively. In both the validation and training cohorts, the calibration curves showed a high degree of consistency between actual and nomogram-predicted survival rates. The Kaplan-Meier curves showed that the three risk groups had significant differences in overall survival (P < 0.001). CONCLUSION: A large population-based nomogram incorporating LODDS was developed to assist in evaluating the prognosis of stage II/III rectal cancer patients treated with NCRT followed by surgical resection. The nomogram showed a satisfactorily discriminative and stable ability to predict the OS for those patients.

A New Ratiometric Fluorescent Probe Based on BODIPY for Highly Selective Detection of Hydrogen Sulfide.

Hydrogen sulfide (H2S) as small molecular signal messenger plays key functions in numerous biological processes. The imaging detection of intracellular hydrogen sulfide is of great significance. In this work, a ratiometric fluorescent probe BH based on an asymmetric BODIPY dye for detection of H2S was designed and synthesized. After the interaction with hydrogen sulfide, probe display colorimetric and ratiometric fluorescence response, with its maximum emission fluorescence wavelength red-shifted from 542 nm to 594 nm, which is attributed to the sequential nucleophilic reaction of H2S leading to enhanced molecular conjugation after ring formation of the BODIPY skeleton. A special response mechanism has been fully investigated by NMR titration and MS, so that the probe has excellent detection selectivity. Furthermore, probe BH has low cytotoxicity and fluorescence imaging experiments indicate that it can be used to monitor hydrogen sulfide in living cells.

Sesquiterpene glucosides from Shenzhou honey peach fruit showed the anti-aging activity in the evaluation system using yeasts.

One new (1, SZMT01) and one known (2) anti-aging substances were isolated from Shenzhou honey peach fruit. Their structures were elucidated by spectroscopic methods and chemical derivatization, and the result reveals that these two compounds are sesquiterpene glucosides. SZMT01 possesses a new glycosylation with an ester linkage at one terminal in an acyclic sesquiterpenoid which is the end of a double bond at another terminal. Both compounds extend the replicative lifespan of K6001 yeast strain at doses of 7.5 and 25 µM. Then, to understand the action mechanism involved, we performed an anti-oxidative experiment on SZMT01. The result revealed that treatment with SZMT01 increased the survival rate of yeast under oxidative stress. Moreover, the lifespans of sod1 and sod2 mutant yeast strains with a K6001 background were not affected by SZMT01. These results demonstrate that anti-oxidative stress performs important roles in anti-aging effects of SZMT01.

TNF-alpha promotes lymphangiogenesis and lymphatic metastasis of gallbladder cancer through the ERK1/2/AP-1/VEGF-D pathway.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α), a key player in cancer-related inflammation, was recently demonstrated to be involved in the lymphatic metastasis of gallbladder cancer (GBC). Vascular endothelial growth factor D (VEGF-D) is a key lymphangiogenic factor that is associated with lymphangiogenesis and lymph node metastasis in GBC. However, whether VEGF-D is involved in TNF-α-induced lymphatic metastasis of GBC remains undetermined. METHODS: The expression of VEGF-D in patient specimens was detected by immunohistochemistry and the relationship between VEGF-D in the tissue and TNF-α in the bile of the matching patients was analyzed. The VEGF-D mRNA and protein levels after treatment with exogenous TNF-α in NOZ, GBC-SD and SGC-996 cell lines were measured by real-time PCR and ELISA. The promoter activity and transcriptional regulation of VEGF-D were analyzed with the relative luciferase reporter assay, mutant constructs, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, RNA interference and Western blotting. Inhibitors of JNK, p38 MAPK and ERK1/2 were used to explore the upstream signaling effector of AP-1. We used lentiviral vector expressing a VEGF-D shRNA construct to knockdown VEGF-D gene in NOZ and GBC-SD cells. The role of the TNF-α-VEGF-D axis in the tube formation of human dermal lymphatic endothelial cells (HDLECs) was determined using a three-dimensional coculture system. The role of the TNF-α - VEGF-D axis in lymphangiogenesis and lymph node metastasis was studied via animal experiment. RESULTS: TNF-α levels in the bile of GBC patients were positively correlated with VEGF-D expression in the clinical specimens. TNF-α can upregulate the protein expression and promoter activity of VEGF-D through the ERK1/2 - AP-1 pathway. Moreover, TNF-α can promote tube formation of HDLECs, lymphangiogenesis and lymph node metastasis of GBC by upregulation of VEGF-D in vitro and in vivo. CONCLUSION: Taken together, our data suggest that TNF-α can promote lymphangiogenesis and lymphatic metastasis of GBC through the ERK1/2/AP-1/VEGF-D pathway.

Sterols from Mytilidae show anti-aging and neuroprotective effects via anti-oxidative activity.

For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.

[Causes and affecting factors of unplanned reoperations in cancer patients].

OBJECTIVE: To investigate the causes and affecting factors of unplanned reoperations in cancer patients. METHODS: All patients, who underwent surgery and unplanned surgical reoperations in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between November 1, 2012 and October 1, 2013, were included in this study. The causes and affecting factors of unplanned reoperations were retrospectively analyzed with logistic regression model. RESULTS: A total of 16, 362 operations were performed in that period, in which 126 cases underwent unplanned reoperation. The incidence rate of unplanned reoperation was 0.77%. The top three causes for unplanned reoperation were bleeding or hematoma in 44 cases (34.92%), wound infection or split in 37 cases (29.37%), and anastomotic leak in 14 cases (11.11%). Logistic regression analysis showed that tumor classification, surgery grade and gender were independent factors for the unplanned reoperations. CONCLUSIONS: The main causes of unplanned reoperation are bleeding or hematoma, wound infection or split and anastomotic leak. Tumor classification, surgery grade and gender are the independent factors for unplanned reoperations.

Single-Trial EEG Classification Using Spatio-Temporal Weighting and Correlation Analysis for RSVP-Based Collaborative Brain Computer Interface.

OBJECTIVE: Since single brain computer interface (BCI) is limited in performance, it is necessary to develop collaborative BCI (cBCI) systems which integrate multi-user electroencephalogram (EEG) information to improve system performance. However, there are still some challenges in cBCI systems, including effective discriminant feature extraction of multi-user EEG data, fusion algorithms, time reduction of system calibration, etc. Methods: This study proposed an event-related potential (ERP) feature extraction and classification algorithm of spatio-temporal weighting and correlation analysis (STC) to improve the performance of cBCI systems. The proposed STC algorithm consisted of three modules. First, source extraction and interval modeling were used to overcome the problem of inter-trial variability. Second, spatio-temporal weighting and temporal projection were utilized to extract effective discriminant features for multi-user information fusion and cross-session transfer. Third, correlation analysis was conducted to match target/non-target templates for classification of multi-user and cross-session datasets. RESULTS: The collaborative cross-session datasets of rapid serial visual presentation (RSVP) from 14 subjects were used to evaluate the performance of the EEG classification algorithm. For single-user/collaborative EEG classification of within-session and cross-session datasets, STC had significantly higher performance than the existing state-of-the-art machine learning algorithms. CONCLUSION: It was demonstrated that STC was effective to improve the classification performance of multi-user collaboration and cross-session transfer for RSVP-based BCI systems, and was helpful to reduce the system calibration time.

Multi-source domain adaptation based tempo-spatial convolution network for cross-subject EEG classification in RSVP task.

Objective.Many subject-dependent methods were proposed for electroencephalogram (EEG) classification in rapid serial visual presentation (RSVP) task, which required a large amount of data from new subject and were time-consuming to calibrate system. Cross-subject classification can realize calibration reduction or zero calibration. However, cross-subject classification in RSVP task is still a challenge.Approach.This study proposed a multi-source domain adaptation based tempo-spatial convolution (MDA-TSC) network for cross-subject RSVP classification. The proposed network consisted of three modules. First, the common feature extraction with multi-scale tempo-spatial convolution was constructed to extract domain-invariant features across all subjects, which could improve generalization of the network. Second, the multi-branch domain-specific feature extraction and alignment was conducted to extract and align domain-specific feature distributions of source and target domains in pairs, which could consider feature distribution differences among source domains. Third, the domain-specific classifier was exploited to optimize the network through loss functions and obtain prediction for the target domain.Main results.The proposed network was evaluated on the benchmark RSVP dataset, and the cross-subject classification results showed that the proposed MDA-TSC network outperformed the reference methods. Moreover, the effectiveness of the MDA-TSC network was verified through both ablation studies and visualization.Significance.The proposed network could effectively improve cross-subject classification performance in RSVP task, and was helpful to reduce system calibration time.

Environmental and economic analysis of the transformation of paper mill sludge treatment technologies in China.

Paper mill sludge (PMS) is featured with a high content of cellulose and hemicellulose, and using its characteristics to make paperboard can achieve a high-value utilization of PMS, which has attracted growing interest. In this study, currently prevalent landfill, incineration technologies (generating heat and electricity by incineration), and three paperboard technologies (medium density fiberboard, pulp board, and corrugated paper) were evaluated and compared via life cycle assessment (LCA) and life cycle costing (LCC) methods. LCA results show that the PMS-to-pulp board outperforms others with an energy conservation and emission reduction (ECER) value of - 2.86 × 10-8, while the landfill exhibits the highest overall environmental impact with an ECER value of 4.80 × 10-9. LCC results reveal that the PMS-to-pulp board delivers the highest economic profit with $257.357, while the landfill is the lowest with $ - 35.63. The PMS paperboard technologies are more economically friendly than the incineration technologies due to additional electricity/steam consumption during the PMS pre-drying process in incineration. In addition, different scenarios were set up to explore national GHG emission reduction potential by increasing paperboard technologies application rate and reducing the proportion of landfill and incineration. The scenario analysis suggests that replacing 90% of landfill and incineration ratio with PMS paperboard technologies could tremendously improve the overall emission reduction performance with - 9.08 × 1010 kg CO2 eq. This result indicates that the PMS treatment technology transformation has a significant favorable impact on the achievement of the "carbon neutrality" target.

Chitosan-based fluorescent probe for the detection of Fe3+ in real water and food samples.

Iron ions play a crucial role in the environment and the human body. Therefore, developing an effective detection method is crucial. In this paper, we report CNS2, a chitosan-based fluorescent probe utilizing naphthalimide as a fluorophore. CNS2 is designed to "quench" its own yellow fluorescence through the specific binding of compounds containing enol structures to Fe3+. Studying the fluorescence lifetime of CNS2 in the presence or absence of Fe3+ reveals that the quenching mechanism is static. The presence of multiple recognition sites on the chitosan chain bound to Fe3+ gave CNS2 rapid recognition (1 min) and high sensitivity, with a detection limit as low as 0.211 µM. Moreover, the recognition of Fe3+ by CNS2 had a good specificity and was not affected by interferences. More importantly, in this study, CNS2 was successfully utilised to prepare fluorescent composite membranes and to detect Fe3+ in real water samples and a variety of food samples. The results show that the complex sample environment still does not affect the recognition of Fe3+ by CNS2. All the above experiments obtained more satisfactory results, which provide strong support for the detection of Fe3+ by the probe CNS2 in practical applications.

An activated near-infrared mitochondrion-targetable fluorescent probe for rapid detection of NADH.

A novel NIR fluorescent probe based on quinoline-conjugated benzo[cd]indol dual-salt for NADH was developed. This probe swiftly detects and responds sensitively to both endogenous and exogenous NADH alterations, enabling imaging of NADH fluctuations in type II diabetic and AD model cells.

Effect of separation pretreatment on environmental and economic performance of sludge resource utilization.

As a new technology for accurate utilization of sludge resources, sludge inorganic-organic matter separation (IOMS) has attracted wide attention. This study examined the impact of this pretreatment on environmental and economic performance of sludge composting and incineration using life cycle assessment (LCA) and whole life costing (WLC). LCA results indicated that IOMS pretreatment reduced the energy conservation and emission reduction (ECER) values of composting and incineration by 56 % and 76 %, respectively. Meanwhile, WLC exhibited that IOMS pretreatment could cut the break-even year of incineration from 11 years to 4 years. The combination of organic sludge incineration/composting with inorganic sludge sintering ceramsite reveals excellent environmental and economic performance. The application optimization hypothesis analysis of these two routes in various provinces of China indicates that Jiangsu has the greatest development potential and should become a major promotion region.

A novel red-to-near-infrared AIE fluorescent probe for detection of Hg2+ with large Stokes shift in plant and living cells.

Due to the highly toxic nature of mercury ions to living organisms, accurately detecting Hg2+ in water samples and biological systems is of great significance. In this study, we designed and synthesized a novel red-to-near-infrared Aggregation-Induced Emission (AIE) fluorescent probe (named as DS) based Fluorene derivatives on specifically for Hg2+ detection. Probe DS can visually identify Hg2+ through an red-to-near-infrared fluorescence enhancement change, characterized by a large Stokes shift (130 nm) and AIE feature. This probe offers a fast response, high selectivity and sensitivity. The Hg2+-induced deprotection reaction of the thioketal mechanism was thoroughly investigated using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) calculation. Additionly, dynamic light scattering (DLS) results indicated that the aggregation states changes of the molecular play a crucial role in the AIE fluorescence response of probe DS toward Hg2+. The red-to-near-infrared response with AIE feature not only avoids the interference of auto-fluorescence signals in complex environments, but also reduces the fluorescence quenching caused by probe molecular aggregation. This makes probe DS highly suitable for high-quality imaging detection of Hg2+ in aqueous environments. Furthermore, probe DS demonstrates the capability for visual fluorescence detection of Hg2+ concentrations in water sample, plant roots and living cells.

A flavonol-labelled cellulose fluorescent probe combined with composite fluorescent film imaging and smartphone technology for the detection of Fe3.

Fe3+ is one of the most widely distributed and abundant elements on earth. Realizing efficient and real-time monitoring of Fe3+ is of great significance for the natural environment and the health of living organisms. In this paper, a flavonol-labelled cellulose-based fluorescent probe (ACHM) was synthesized by using dialdehyde cellulose (DAC) as the backbone and combining with flavonol derivatives (AHM - 1). The mechanism of recognizing Fe3+ was verified by characterizing the structure of ACHM by NMR, HRMS (High Resolution Mass Spectrometry), FTIR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), TG (Thermogravimetry) and SEM (Scanning Electron Microscopy). The H2O solution of the probe ACHM showed good fluorescence properties. It has quenching fluorescence properties for Fe3+, with a low limit of detection (LOD) of 0.10 µM and a fast response time of only 20 s. In addition, in order to expand the application range of the probe, ACHM was prepared as a fluorescent composite film with an average tensile strength of 32.9 MPa and an average elongation at break of 3.39 %. It shows its superiority in mechanical properties. The probe also demonstrated its practical application value for detecting Fe3+ in smartphone imaging applications.

Synthesis and application of hypochlorite ratiometric fluorescence probe based on cellulose.

Cellulose is the most abundant natural polymer with good biocompatibility and easy modification characteristics. In this paper, a novel cellulose fluorescence probe CNS for detecting ClO- was prepared by modifying microcrystalline cellulose (MCC). The fluorescence detection results indicate that CNS exhibits a highly specific "ratiometric" and "colorimetric" fluorescence response to ClO-. In the presence of ClO-, the fluorescence color changes from green to cyan. In addition, the color of the solution changes from yellow to colorless, which can be observed with the "naked eye". Considering the good selectivity and anti-interference ability of CNS, the probe can be used for the detection of ClO- in real water samples. Importantly, CNS composite films and test papers were prepared and showed practicability in the detection of ClO-, highlighting its broad application potentials.

Federated learning with hyper-network-a case study on whole slide image analysis.

Federated learning(FL) is a new kind of Artificial Intelligence(AI) aimed at data privacy preservation that builds on decentralizing the training data for the deep learning model. This new technique of data security and privacy sheds light on many critical domains with highly sensitive data, including medical image analysis. Developing a strong, scalable, and precise deep learning model has proven to count on a variety of high-quality data from different centers. However, data holders may not willing to share their data considering the restriction of privacy. In this paper, we approach this challenge with a federated learning paradigm. Specifically, we present a case study on the whole slide image classification problem. At each local client center, a multiple-instance learning classifier is developed to conduct whole slide image classification. We introduce a privacy-preserving federated learning framework based on hyper-network to update the global model. Hyper-network is deployed at the global center that produces the weights of the local network conditioned on its input. In this way, hyper-networks can simultaneously learn a family of the local client networks. Instead of communicating raw data with the local client, only model parameters injected with noise are transferred between the local client and the global model. By using a large scale of whole slide images with only slide-level labels, we mensurated our way on two different whole slide image classification problems. The results demonstrate that our proposed federated learning model based on hyper-network can effectively leverage multi-center data to develop a more accurate model which can be used to classify a whole slide image. Its improvements in terms of over the isolated local centers and the commonly used federated averaging baseline are significant. Code will be available.