A fluorescent probe for specific dual recognition of Ni2+ and pH.

Nickel ion (Ni2+) and pH play an important role in environment and living organisms. A fluorescent probe "naphthalimide- s-triazine" (NCNS) for targeted dual detection of Ni2+ and pH was synthesized. As a result, NCNS exhibits excellent optical properties: a much larger Stokes shift (140 nm), eminent changes of fluorescence intensity and significant red-shift both for Ni2+ and pH. As for the detection of Ni2+, the selectivity is high and the anti-interference is strong. NCNS can fluorescently detect Ni2+ in a wider pH range from 4.0 to 10.5. It provides a much lower limit of detection (LOD, 20.03 nM), a rapid response time (150 s) and six times reversibility, showing the high sensitivity. Particularly, NCNS can be applied to fluorescently detect Ni2+ in actual water samples and HA-VSMC imaging. In the detection of pH, the probe generates a ratiometric fluorescence in a wide pH range (3.0 âˆ¼ 12.3). NCNS has been successfully made test paper both for Ni2+ and pH. The mechanisms of the double recognition are verified by the density functional theory (DFT) calculations and the nuclear magnetic resonance (NMR) titration experiments.

The raphe nuclei are the early lesion site of gastric α-synuclein propagation to the substantia nigra.

Parkinson's disease (PD) is a neurodegeneration disease with α-synuclein accumulated in the substantia nigra pars compacta (SNpc) and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with PD. Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy. Although the "gut-brain" hypothesis is proposed to explain the underlying mechanism, where the earlier lesioned site in the brain of gastric α-synuclein and how α-synuclein further spreads are not fully understood. Here we report that caudal raphe nuclei (CRN) are the early lesion site of gastric α-synuclein propagating through the spinal cord, while locus coeruleus (LC) and substantia nigra pars compacta (SNpc) were further affected over a time frame of 7 months. Pathological α-synuclein propagation via CRN leads to neuron loss and disordered neuron activity, accompanied by abnormal motor and non-motor behavior. Potential neuron circuits are observed among CRN, LC, and SNpc, which contribute to the venerability of dopaminergic neurons in SNpc. These results show that CRN is the key region for the gastric α-synuclein spread to the midbrain. Our study provides valuable details for the "gut-brain" hypothesis and proposes a valuable PD model for future research on early PD intervention.

A Fluorescent Probe for Hg2+ Specific Recognition Based on Xanthene and its Application in Food Detection and Cell Imaging.

The mercury-loving unit aminothiourea was introduced into the xanthene fluorophore to synthesized the probe molecule NXH. NXH has a specific response to Hg2+, and with the addition of (0 ~ 50 µM) Hg2+, the fluorescence intensity of the probe solution was quenched from 2352 a.u. to about 308 a.u. NXH exhibited excellent detection performance of high sensitivity (LOD = 96.3 nM), real-time response (105 s), wide pH range (2.1 ~ 9.3), and strong anti-interference ability for Hg2+. At the same time, NXH has wide range of applications for Hg2+ detection, which can fluorescence imaging of Hg2+ in Hela cells and tea samples, and can also be made into Hg2+ detection test paper.

Synthesis and application of hypochlorite mediated acylhydrazone fluorescence probes.

Hypochlorous acid (HClO/ClO- ) is one of the important reactive oxygen species (ROS). It acts as a second signaling molecule within and between cells and is an indispensable active molecule in living organisms to regulate physiological and pathological processes. In this article, two fluorescent probes (PTF and PTA) for highly selective fluorescent recognition of ClO- were successfully synthesized based on the ICT mechanism by condensing phenothiazines with two hydrazides via the hydrazide structure (). PTF can identify different concentrations of ClO- in two steps. Due to its ClO- two site recognition, the probe exhibited good selectivity (specific recognition of ClO- over a wide concentration range), a fast time response (rapid recognition in seconds), a sufficiently low detection limit (3.6 and 11.0 nM), and large Stokes shifts (180 and 145 nm). Furthermore, the recognition of ClO- by contrasting probes with different substituents exhibited different fluorescence changes of ratiometric type and turn-off. PTF successfully achieves the detection of exogenous and endogenous ClO- in aqueous solution and living cells.

A Dual Functional Fluorescent Probe Based on Phenothiazine for Detecting Hg2+ and ClO- and its Applications.

For the efficient detection of Hg2+ and ClO-, a double-analyte-responsive fluorescent probe PTB was successfully synthesized by combining N-butyl-3-formyl phenothiazine with hydrazine benzothiazole, and designing a specific reaction site for recognizing two analytes (Hg2+ and ClO-) in a compound. It was shown that probe PTB successfully formed a stable complex with Hg2+ in the coordination ratio of 2:1 by using the strong sulfur affinity of Hg2+, which resulted in a remarkable "turn-off" effect, with a quenching efficiency of 92.5% and four reversible cycles of Hg2+ fluorescence detection. For the fluorescence detection of Hg2+, the response time is fast (≤ 2 min) and the detection limit is low (7.8 nM), showing extremely high sensitivity, and the performance is obviously better than that of the reported fluorescent probes for detecting Hg2+. In particular, probe PTB has low toxicity and good biocompatibility, and has been successfully used for imaging of Hg2+ in living cells. Moreover, probe PTB uses thioether bond and carbon-nitrogen double bond as reaction sites to detect ClO-, which has large Stokes Shift (149 nm), good selectivity, high quenching efficiency (96.5%) and fast time response (about 10 s), and successfully detects ClO- in actual water samples. The dual functional fluorescent probe PTB is sensitive for Hg2+ and ClO-. It has been successfully used for making pH fluorescent test paper and imaging detection of exogenous Hg2+ in VSMC cells with low toxicity.

Mesoporous MOF Based on a Hexagonal Bipyramid Co8-Cluster: High Catalytic Efficiency on the Cycloaddition Reaction of CO2 with Bulky Epoxides.

A mesoporous cobalt-based metal-organic framework (LCU-606) was synthesized based on a hexagonal bipyramid Co8(µ4-O)3 cluster and an N,N,N',N'-tetrakis-(4-benzoic acid)-1,4-phenylenediamine ligand (H4TBAP). LCU-606 featuring large pore diameters of 21.7 Å and exposed Lewis-acid metal sites could serve as an excellent heterogeneous catalyst for CO2 cycloaddition reaction with various epoxide substrates under mild conditions (1 atm CO2, 60 °C, and solvent free). In particular, when extending the substrates to bulkier ones, LCU-606 still shows high catalytic efficiency on account of the large pore aperture. Also, LCU-606 demonstrates high recyclability and stability in consecutive catalytic runs. Therefore, the high efficiency, recyclability, and generality on CO2 catalytic cycloaddition make LCU-606 a very promising heterogeneous catalyst for CO2 chemical fixation.

A novel fluorescent probe based on naphthimide for H2S identification and application.

In view of the superior chemical activity of selenoether bond (-Se-) and the excellent optical properties of naphthimide, a novel fluorescent probe (NapSe) with near-rectangular structure, which contains double naphthimide fluorophores linked by selenoether bond, is designed for specific fluorescence detection of hydrogen sulfide (H2S). NapSe has excellent optical properties: super large Stokes Shift (190 nm) and good stability in a wide pH range. The selectivity of NapSe fluorescence detection of H2S is high, and displays excellent "turn-on" phenomenon and strong anti-interference. And the fluorescence intensity increased obviously, reaching 42 times. The time response of probe NapSe is very rapid (3 min) compared with other fluorescence probes that respond to H2S. It shows high sensitivity by calculating the detection limit (LOD) as low as 5.4 µM. Notably, the identification of H2S by probe NapSe has been successfully applied to the detection of test paper and the detection of exogenous and endogenous fluorescence imaging of MCF-7 breast cancer cells.

Psychological Journey and Coping Styles of Parents of Infants With Biliary Atresia: A Single-Center Qualitative Study.

BACKGROUND: Biliary atresia is a rare and serious neonatal disease that affects the quality of life of both infants and parents. There is currently limited literature on the experiences of parents with infants diagnosed with biliary atresia. PURPOSE: To explore the psychological journey and coping styles of parents of infants with biliary atresia in a single center in Shanghai, China. METHODS: A qualitative study design was used. Face-to-face and semistructured interviews were conducted with 10 parents of infants with biliary atresia. Colaizzi's method of data analysis was utilized, using NVivo 11.0 software. RESULTS: The psychological journey and coping styles of parents could be divided into 4 stages. Different themes were extracted at different stages: before diagnosis, parents experienced complex emotions and actively sought treatment; at the diagnosis stage, negative emotions dominated and parents convinced themselves to accept reality; in the postoperative stage, positive emotions, accepting reality, active response, and the need to learn to take care of their infant gradually appeared; and at the discharge stage, parents accepted the coexistence of positive and negative emotions and the variety of needs that emerged. IMPLICATIONS FOR PRACTICE: The findings of the study may help healthcare professionals identify and focus on the psychological needs of parents of infants with biliary atresia, leading them to implement effective coping strategies to increase the caregiving ability of parents. IMPLICATIONS FOR RESEARCH: Future research should explore the effects of supportive interventions for parents of infants with serious chronic illnesses.

Two novel fluorescent probes based on quinolinone for continuous recognition of Al3+ and ClO.

On the basis of classical Schiff base reaction, two novel and efficient fluorescent probes (DQNS, DQNS1) were designed and synthesized by introducing Schiff base structure into dis-quinolinone unit for structural modification, which can be used to detect Al3+ and ClO-. Because the power supply capacity of H is weaker than that of methoxy, DQNS shows better optical performance: a large Stokes Shift (132 nm), identify Al3+ and ClO- with high sensitivity and selectivity, low detection limit (29.8 nM and 25 nM) and fast response time (10 min and 10 s). Through the working curve and NMR titration experiment, the recognition mechanism of Al3+ and ClO- (PET and ICT) probes are confirmed. Meanwhile, it is speculated that the probe has continuity for the detection of Al3+ and ClO-. Furthermore, DQNS detection of Al3+ and ClO- was applied to real water samples and living cell imaging.

Correlation Analysis between Muskrat (Ondatra zibethicus) Musk and Traditional Musk.

Muskrat musk is considered to be a potential substitute for traditional musk. However, little is known about the similarity between muskrat musk and musk, and whether it is related to muskrat age. In this study, muskrat musk (MR1, MR2, and MR3) were from 1, 2, and 3-year-old muskrats, respectively, and white musk (WM) and brown musk (BM) were picked from male forest musk deer. The results indicated that muskrat musk had higher similarity to WM than BM. Further research showed that RM3 had the highest matched degree with WM. By significantly different metabolite analysis, we found that 52 metabolites continue to increase from 1- to 3-year-old muskrats. In total, 7 and 15 metabolites were significantly decreased in RM1 vs. RM2 and RM2 vs. RM3, respectively. Meanwhile, 30 and 17 signaling pathways were observed from increased and decreased metabolites, respectively. The increased metabolites mainly entailed enrichment in amino acid biosynthesis and metabolism, steroid hormone biosynthesis, and fatty acid biosynthesis. In conclusion, muskrat musk from three-year-old muskrat is a relatively good substitute for white musk, and the result also implies that these biological processes of amino acid biosynthesis and metabolism, steroid hormone biosynthesis, and fatty acid biosynthesis are beneficial to the secretion of muskrat musk.

A fluorescent probe based on phenothiazine for detection of ClO- with naked-eye color change properties.

Hypochlorite (ClO-) plays a key role in life systems and it is necessary to develop an effective detection method. In view of the significant advantages of the fluorescent probe, we have synthesized a naked-eye recognition fluorescent probe NNCF for the detection of ClO- based on phenothiazine and naphthalimide. The probe NNCF is sensitive (LOD = 9.5 nM) and fast for ClO- (within 30 s), and its Stokes shift is as large as 161 nm. In addition, the probe NNCF has been successfully used for imaging detection of exogenous ClO- in MCF-7 cells with low toxicity.

Sequential Nano-Penetrators of Capillarized Liver Sinusoids and Extracellular Matrix Barriers for Liver Fibrosis Therapy.

During liver fibrogenesis, liver sinusoidal capillarization and extracellular matrix (ECM) deposition construct dual pathological barriers to drug delivery. Upon capillarization, the vanished fenestrae in liver sinusoidal endothelial cells (LSECs) significantly hinder substance exchange between blood and liver cells, while excessive ECM further hinders the delivery of nanocarriers to activated hepatic stellate cells (HSCs). Herein, an efficient nanodrug delivery system was constructed to sequentially break through the capillarized LSEC barrier and the deposited ECM barrier. For the first barrier, LSEC-targeting and fenestrae-repairing nanoparticles (named HA-NPs/SMV) were designed on the basis of the modification with hyaluronic acid and the loading of simvastatin (SMV). For the second barrier, collagenase I and vitamin A codecorated nanoparticles with collagen-ablating and HSC-targeting functions (named CV-NPs/siCol1α1) were prepared to deliver siCol1α1 with the goal of inhibiting collagen generation and HSC activation. Our in vivo results showed that upon encountering the capillarized LSEC barrier, HA-NPs/SMV rapidly released SMV and exerted a fenestrae-repairing function, which allowed more CV-NPs/siCol1α1 to enter the space of Disse to degrade deposited collagen and finally to achieve higher accumulation in activated HSCs. Scanning electronic microscopy images showed the recovery of liver sinusoids, and analysis of liver tissue sections demonstrated that HA-NPs/SMV and CV-NPs/siCol1α1 had a synergetic effect. Our pathological barrier-normalization strategy provides an antifibrotic therapeutic regimen.

A super large Stokes shift ratiometric fluorescent probe for highly selective sensing of ClO- in bio-imaging and real water samples.

Based on the fluorescence resonance energy transfer (FRET), a ratiometric fluorescent probe (NQ) was successfully designed and synthesized, in which quinolinone moiety was selected as the energy donor and naphthalimide block as the energy acceptor. NQ has a super large Stokes shift (231 nm) and a big quantum yield (0.463). Compared with previously reported probes with similar recognition sites, NQ can high sensitively and selectively recognize ClO- with a much low limit of detection (LOD = 21 nM) and extremely rapid response time (20 s). NQ has a strong anti-interference effect and a color change in the solution which can be seen by the "naked eye". Moreover, NQ can be applied to detect ClO- in real water samples and living cells imaging.

Evaluation of the clinical application of the Postpartum Depression Predictors Inventory-Revised for postpartum women in China.

AIM: This study was designed to assess the clinical applicability of the Postpartum Depression Predictors Inventory-Revised (PDPI-R) during the 1st month following delivery among women in China and to survey the prevalence of postpartum depression (PPD)-related risk factors included in the PDPI-R in this population. METHODS: This was a cross-sectional study which recruited 447 women from the People's Liberation Army Hospital in Hefei of Anhui province. All participants completed the Chinese version of the PDPI-R (PDPI-R-C) and the Chinese version of the Edinburgh Postnatal Depression Scale (C-EPDS) within 1 month of delivery. The predictive ability of the PDPI-R was then evaluated through receiver operating characteristic (ROC) curve analyses. RESULTS: The PDPI-R-C was able to accurately predict 73.2% of PPD cases (area under the ROC curve = 0.732; 95% CI 0.69-0.78) using a cut-off score of 5.5, as defined by a C-EPDS score of ≥10 (sensitivity = 62.8%; specificity = 73.5%; positive predictive value = 74.5%; negative predictive value = 61.5%). All 13 risk factors in the PDPI-R-C other than socioeconomic status and marital status were associated with the risk of PPD. CONCLUSIONS: The PDPI-R-C was found to be an effective and easy-to-implement tool that has promise as a means of screening for PPD in Chinese populations.

Progress in drug delivery system for fibrosis therapy.

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer, which is a serious disease threatening human health. Recent studies have shown that the early treatment of fibrosis is turning point and particularly important. Therefore, how to reverse fibrosis has become the focus and research hotspot in recent years. So far, the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery. Moreover, the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects. Herein, this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver, pulmonary, and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms, which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.

Research on developing drugs for Parkinson's disease.

Current treatments for Parkinson's disease (PD) are mainly dopaminergic drugs. However, dopaminergic drugs are only symptomatic treatments and limited by several side effects. Recent studies into drug development focused on emerging new molecular mechanisms, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nuclear receptor-related 1 (Nurr1), adenosine receptor A2, nicotine receptor, metabotropic glutamate receptors (mGluRs), and glucocerebrosidase (GCase). Also, immunotherapy and common pathological mechanisms shared with Alzheimer's Disease (AD) and diabetes have attracted much attention. In this review, we summarized the development of preclinical and clinical studies of novel drugs and the improvement of dopaminergic drugs to provide a prospect for PD treatment.

A bibenzyl compound 20C protects rats against 6-OHDA-induced damage by regulating adaptive immunity associated molecules.

Parkinson's disease (PD) is a neurodegenerative disease with complicated pathogenesis. A novel bibenzyl compound 2-[4-hydroxy-3-(4-hydroxyphenyl)benzyl]-4-(4-hydroxyphenyl)phenol (20C) has been shown to have some neuroprotective effects, and its mechanism still needs further research. In this study, we used a 6-hydroxydopamine (6-OHDA)-induced PD rat model to evaluate the protective effect of 20C. Our study found that 20C could improve behavioral defects in 6-OHDA-lesion rats, decrease neuroinflammation and protect their DA neurons. It could inhibit the activity of inducible nitric oxide synthase (iNOS) induced by 6-OHDA, and lead to a decrease in the expression of nitrated-α-synuclein. When exposed to AMT-an inhibitor of iNOS, the nitrated-α-synuclein in PC12 decreased, and 20C demonstrated the same function on nitrated-α-synuclein as AMT. Besides, we also found that nitrated-α-synuclein was displayed in microglia. And 20C could decrease the expression of antigen-presenting molecule major histocompatibility complex I (MHC I) in dopamine (DA) neurons and MHC II in microglia induced by 6-OHDA. So, these imply that nitrated-α-synuclein might act as an endogenous antigen activating adaptive immunity, and the neuroprotection of 20C might be associated with inhibiting the activity of iNOS, decreasing the expression of the antigen molecule nitrated-α-synuclein and the antigen presenting molecule MHC. Our results indicated that inhibiting iNOS might be an effective strategy to protect neurons from oxidative stress.

Internet-based intervention for postpartum depression in China ("Mommy go"): Protocol for a randomized controlled trial.

AIM: The purpose of this study is to design a research protocol for the clinical testing of the "Mommy go" for pregnant women with a risk of postpartum depression. DESIGN: A non-blinded randomized controlled trial. METHODS: A randomized controlled study will be performed from January 2018 to the completion of the study. The intervention group will follow the "Mommy go" protocol and the control group will receive traditional support. We will use the Edinburgh Postpartum Depression Scale and the Chinese version of the Postpartum Depression Predictors Inventory-Revised to measure the risk of postpartum depression in pregnant women. The outcomes are clinical data, postpartum depressive mood, self-efficacy, and infant temperament. Outcomes will be assessed using questionnaires and through data generated by digital technologies. DISCUSSION: The expected outcomes are increased self-efficacy and infant temperament, reduced postpartum depressive mood, and improvements to postpartum depression. We expect the study to have a clinical impact on future online interventions for postpartum depression in China. IMPACT: This study will provide an internet-based intervention for postpartum depression in China. It will be implemented in clinical practice if it can effectively improve postpartum depression. TRIAL REGISTRATION: Registered at the Chinese Clinical Trials.gov (ChiCTR1800018804).

Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis.

Liver fibrosis leads to over one million deaths annually worldwide. Hepatic stellate cells (HSCs) have been identified as the main executors of liver fibrosis. Unfortunately, no drug has yet been approved for clinical use against liver fibrosis, largely because the tested drugs have been unable to access HSCs and efficiently remove the collagen accumulation involved in fibrogenesis. Here, we designed an efficient HSC-targeting lipid delivery system that carried dual siRNAs intended to both inhibit collagen synthesis and promote collagen degradation, with the goal of realizing enhanced anti-liver fibrosis by bidirectional regulation of collagen accumulation. The delivery system was constructed by using amphiphilic cationic hyperbranched lipoids (C15-PA) for siRNA complexation and helper lipoids (cholesterol-polyethylene glycol-vitamin A, Chol-PEG-VA) for HSCs targeting. The generated vitamin A-decorated and hyperbranched lipoid-based lipid nanoparticles (VLNPs) showed excellent gene-binding ability and transfection efficiency, and enhanced the delivery of siRNAs to HSCs. Fibrotic mice treated with dual siRNA-loaded VLNPs showed a great reduction in the collagen accumulation seen in this model; the enhanced effect of bidirectional regulation reduced the collagen accumulation level in treated mice to almost that seen in normal mice. There was no notable sign of toxicity or tissue inflammation in mice exposed to repeated intravenous administration of the dual siRNA-loaded VLNPs. In conclusion, our results indicate that biocompatible VLNPs designed to exploit precise targeting and an effective bidirectional regulation strategy hold promise for treating liver fibrosis.