Catalytic NIR chemiluminescence sensor with enhanced persistence and intensity for in vivo imaging.

Chemiluminescence (CL) is a self-illumination phenomenon that involves the emission of light from chemical reactions, and it provides favorable spatial and temporal information on biological processes. However, it is still a great challenge to construct effective CL sensors that equip strong CL intensity, long emission wavelength, and persistent luminescence for deep tissue imaging. Here, we report a liposome encapsulated polymer dots (Pdots)-based system using catalytic CL substrates (L-012) as energy donor and fluorescent polymers and dyes (NIR 695) as energy acceptors for efficient Near-infrared (NIR) CL in vivo imaging. Thanks to the modulation of paired donor and acceptor distance and the slow diffusion of biomarker by liposome, the Pdots show a NIR emission wavelength (λ em, max = 720 nm), long CL duration (>24 h), and a high chemiluminescence resonance energy transfer efficiency (46.5 %). Furthermore, the liposome encapsulated Pdots possess excellent biocompatibility, sensitive response to H2O2, and persistent whole-body NIR CL imaging in the drug-induced inflammation and the peritoneal metastatic tumor mouse model. In a word, this NIR-II CL nanoplatform with long-lasting emission and high spatial-temporal resolution will be a concise strategy in deep tissue imaging and clinical diagnostics.

(+)-Borneol Protects Dopaminergic Neuronal Loss in Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease Mice: A Study of Dopamine Level using In Vivo Brain Microdialysis.

Considerable research efforts have been directed toward the symptom relief of Parkinson's disease (PD) by attenuating dopamine (DA) depletion. One common feature of these existing therapies is their unavailability of preventing the neurodegenerative process of dopaminergic neurons. (+)-Borneol, a natural highly lipid-soluble bicyclic monoterpene, has been reported to regulate the levels of monoamine neurotransmitters in the central nervous system and exhibit neuroprotective effects. However, the effect of (+)-borneol on the dopaminergic neuronal loss of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice is not defined. Herein, we first report that 30 mg/kg (+)-borneol significantly attenuated the motor deficits of PD mice, which benefits from markedly increasing the level of DA and decreasing the metabolic rate of DA in the striatum of conscious and freely moving mouse detected by ultraperformance liquid chromatography tandem mass spectrometry online combined with in vivo brain microdialysis sampling. It is worth noting that the enhanced level of DA by (+)-borneol was enabled by the reduction in loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons in the substantia nigra and striatum and promotion of reserpine- or nomifensine-induced DA release in PD mice. Interestingly, (+)-borneol evidently inhibited the decreased expression levels of DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) on the MPTP mouse model of PD. Moreover, (+)-borneol suppressed the neuroinflammation by inhibiting the production of IL-1ß, IL-6, and TNF-α and attenuated oxidative stress by decreasing the level of MDA and increasing the activities of SOD and GSH-px in PD mice. These findings demonstrate that (+)-borneol protects DA neurons by inhibiting neuroinflammation and oxidative stress. Further research work for the neuroprotection mechanism of (+)-borneol will focus on reactive oxygen species-mediated apoptosis. Therefore, (+)-borneol is a potential therapeutic candidate for retarding the neurodegenerative process of PD.

Activating astrocytic α2A adrenoceptors in hippocampus reduces glutamate toxicity to attenuate sepsis-associated encephalopathy in mice.

BACKGROUND: Glutamate metabolism disorder is an important mechanism of sepsis-associated encephalopathy (SAE). Astrocytes regulate glutamate metabolism. In septic mice, α2A adrenoceptor (α2A-AR) activation in the central nervous system provides neuroprotection. α2A-ARs are expressed abundantly in hippocampal astrocytes. This study was performed to determine whether hippocampal astrocytic α2A-AR activation confers neuroprotection against SAE and whether this protective effect is astrocyte specific and achieved by the modulation of glutamate metabolism. METHODS: Male C57BL/6 mice with and without α2A-AR knockdown were subjected to cecal ligation and puncture (CLP). They were treated with intrahippocampal guanfacine (an α2A-AR agonist) or intraperitoneal dexmedetomidine in the presence or absence of dihydrokainic acid [DHK; a glutamate transporter 1 (GLT-1) antagonist] and/or UCPH-101 [a glutamate/aspartate transporter (GLAST) antagonist]. Hippocampal tissue was collected for the measurement of astrocyte reactivity, GLT-1 and GLAST expression, and glutamate receptor subunit 2B (GluN2B) phosphorylation. In vivo real-time extracellular glutamate concentrations in the hippocampus were measured by ultra-performance liquid chromatography tandem mass spectrometry combined with microdialysis, and in vivo real-time hippocampal glutamatergic neuron excitability was assessed by calcium imaging. The mice were subjected to the Barnes maze and fear conditioning tests to assess their learning and memory. Golgi staining was performed to assess changes in the hippocampal synaptic structure. In vitro, primary astrocytes with and without α2A-AR knockdown were stimulated with lipopolysaccharide (LPS) and treated with guanfacine or dexmedetomidine in the presence or absence of 8-bromo- cyclic adenosine monophosphate (8-Br-cAMP, a cAMP analog). LPS-treated primary and BV2 microglia were also treated with guanfacine or dexmedetomidine. Astrocyte reactivity, PKA catalytic subunit, GLT-1 an GLAST expression were determined in primary astrocytes. Interleukin-1ß, interleukin-6 and tumor necrosis factor-alpha in the medium of microglia culture were measured. RESULTS: CLP induced synaptic injury, impaired neurocognitive function, increased astrocyte reactivity and reduced GLT-1 and GLAST expression in the hippocampus of mice. The extracellular glutamate concentration, phosphorylation of GluN2B at Tyr-1472 and glutamatergic neuron excitability in the hippocampus were increased in the hippocampus of septic mice. Intraperitoneal dexmedetomidine or intrahippocampal guanfacine administration attenuated these effects. Hippocampal astrocytes expressed abundant α2A-ARs; expression was also detected in neurons but not microglia. Specific knockdown of α2A-ARs in hippocampal astrocytes and simultaneous intrahippocampal DHK and UCPH-101 administration blocked the neuroprotective effects of dexmedetomidine and guanfacine. Intrahippocampal administration of DHK or UCPH-101 alone had no such effect. In vitro, guanfacine or dexmedetomidine inhibited astrocyte reactivity, reduced PKA catalytic subunit expression, and increased GLT-1 and GLAST expression in primary astrocytes but not in primary astrocytes that received α2A-AR knockdown or were treated with 8-Br-cAMP. Guanfacine or dexmedetomidine inhibited microglial reactivity in BV2 but not primary microglia. CONCLUSIONS: Our results suggest that neurocognitive protection against SAE after hippocampal α2A-AR activation is astrocyte specific. This protection may involve the inhibition of astrocyte reactivity and alleviation of glutamate neurotoxicity, thereby reducing synaptic injury. The cAMP/protein kinase A (PKA) signaling pathway is a potential cellular mechanism by which activating α2A-AR modulates astrocytic function.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

ROS-Responsive Fluorescent Sensor Array for Precise Diagnosis of Cancer via pH-Controlled Multicolor Gold Nanoclusters.

Intracellular reactive oxygen species (ROS) are closely associated with cancer cell types. Therefore, ROS-based pattern recognition is a promising strategy for precise diagnosis of cancer, but such a possibility has never been reported yet. Herein, we proposed an ROS-responsive fluorescent sensor array based on pH-controlled histidine-templated gold nanoclusters (AuNCs@His) to distinguish cancer cell types and their proliferation states. In this strategy, three types of AuNCs@His with diverse fluorescence profiles were first synthesized by only adjusting the pH value. Upon the addition of various ROS, fluorescence quenching of three types of AuNCs@His occurred with different degrees, thereby forming unique optical "fingerprints", which were well-clustered into several separated groups without overlap by principal component analysis (PCA). The sensing mechanism was attributable to the oxidation of AuNCs@His by ROS, as revealed by X-ray photoemission spectroscopy, Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Based on the ROS-responsive sensing pattern, cancer cell types were successfully differentiated via PCA with 100% accuracy. Additionally, the proposed sensor array exhibited excellent performance in distinguishing the proliferation states of cancer cells, which was supported by the results of the Ki-67 immunohistochemistry assay. Overall, the ROS-responsive fluorescent sensor array can serve as a promising tool for precise diagnosis of cancer, indicating great potential for clinical application.

Diazo probe-based chemical isotope labeling assisted liquid chromatography-tandem mass spectrometry analysis for sensitive determination of amino acids in biofluids.

Amino acids are important biomolecules and contribute to essential biological processes. Liquid chromatography tandem mass spectrometry (LC-MS) now is a powerful tool for the analysis of amino acid metabolites; however, the structural similarity and polarity of amino acids can lead to the poor chromatographic retention and low detection sensitivities. In this study, we used a pair of light and heavy isotopomers of diazo probes, d0/d5-2-(diazomethyl)-N-methyl-N-phenyl-benzamide (2-DMBA/d5 -2-DMBA) to label amino acids. The paired MS probes of 2-DMBA and d5 -2-DMBA carry diazo groups that can efficiently and specifically react with the carboxyl group on free amino acid metabolites under mild conditions. Benefiting from the transfer of the 2-DMBA/d5 -2-DMBA to carboxyl group on amino acids, the ionization efficiencies of amino acids presented great enhancement during LC-MS analysis. The results suggested that the detection sensitivities of 17 amino acids increased by 9-133-fold upon 2-DMBA labeling, and the obtained limits of detection (LODs) of amino acids on-column ranged from 0.011 fmol-0.057 fmol. With the application of the developed method, we successfully achieved the sensitive and accurate detection of the 17 amino acids in microliter level of serum sample. Moreover, the contents of most amino acids were different in the serum from normal and B16F10-tumour mice, demonstrating that endogenous amino acids may play important roles in the regulation of tumors development. This developed method of chemical labeling of amino acids with diazo probes assisted LC-MS analysis provides a potentially valuable tool to investigate the relationships between amino acids metabolism and diseases.

EDTA-functionalized silica nanoparticles as a conditioning agent for dentin bonding using etch-and-rinse technique.

OBJECTIVE: This study investigated the possibility of using ethylenediaminetetraacetic acid functionalized silica nanoparticles (EDTA-SiO2) as a dentin-conditioning agent using etch-and-rinse technique to promote the durability of dentin bonding. METHODS: The SiO2-EDTA were synthesized by N- [(3- trimethoxysilyl) propyl] ethylenediamine triacetic acid (EDTA-TMS) and SiO2 (50 nm), then characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The capacity of SiO2-EDTA to chelate calcium ions from dentin was examined by inductively coupled plasma-optic emission spectrometry (ICP-OES). The dentin surfaces conditioned with SiO2-EDTA were detected by field emission scanning electron microscopy (SEM), TEM and microhardness testing. For dentin bonding, dentin surfaces were adopted wet- or dry-bonding technique and bonded with adhesive (AdperTM Single Bond2) and applied composite resin (Filtek Z350) on them. The durability of dentin bonding was evaluated by mircotensile bond strength test, in-situ zymography and nanoleakage testing. RESULTS: FTIR, TGA and XPS results showed that SiO2-EDTA contained N element and carboxyl groups. SEM, TEM and microhardness results indicated that SiO2-EDTA group created extrafibrillar demineralization and retained more intrafibrillar minerals within dentin surface. In the dentin bonding experiment, SiO2-EDTA group achieved acceptable bond strength, and reduced the activity of matrix metalloproteinase and nanoleakage along bonding interface. CONCLUSION: It was possible to generate a feasible dentin conditioning agent (SiO2-EDTA), which could create dentin extrafibrillar demineralization and improve dentin bond durability. CLINICAL SIGNIFICANCE: This study introduces a new dentin conditioning scheme based on SiO2-EDTA to create extrafibrillar demineralization for dentin bonding. This strategy has the potential to be used in clinic to promote the life of restoration bonding.

Perceived Marriage Squeeze and Subjective Well-Being Among Unmarried Rural Men in China: The Mediating Role of Sense of Coherence.

The marriage-squeeze unmarried rural men perceive during their daily life is one of the main stressors severely affecting their subjective well-being under the universal marriage culture. The mechanism of this relationship is still unknown. Based on the Stress Process Model, using data from the "Survey on Rural Family Martial Status," this study examines the relationship between perceived marriage squeeze (PMS) and subjective well-being (SWB) and the mediating effect of sense of coherence (SOC). A sample of 417 Chinese unmarried rural men with an average age of 28.88 years was enrolled in this cross-sectional. Ordinary least square regressions and Bootstrap-mediated effect analysis methods were used to examine the association between PMS, SWB, and SOC. The results show that PMS has significant negative effects on both SWB and SOC of unmarried rural men, and SOC has a significant positive impact on SWB; the more perceived marriage squeeze they have, the lower SWB and SOC they have. The mediated analysis shows that SOC plays a mediating role in the influence of PMS on the SWB of unmarried rural men. This is to say, SOC can mitigate PMS's negative effects on the SWB of unmarried rural men. Our findings highlight the importance of SOC in protecting the SWB of unmarried rural men. Considering the propounding influence of the marriage squeeze, policies that enhance the level of SOC should be implemented to relieve the influence of PMS on vulnerable unmarried rural men's SWB.

Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy.

Piperlongumine (PL) can selectively inhibit the proliferation of various cancer cells by increasing reactive oxygen species (ROS) level to cause a redox imbalance in cancer cells rather than in normal cells. However, the clinical application of PL is limited by its poor cellular uptake. Natural borneol (NB) is extracted from the fresh branches and leaves of Cinnamomum camphora (L.) Presl. with the purity of (+)-borneol no less than 96.0%. NB has been often used as an adjuvant agent to promote the cellular uptake of other drugs. This study aims to investigate the effect of NB on the cellular uptake of PL for improving its antiglioma efficacy and underlying mechanism. NB obviously promoted the cellular uptake of PL with a 1.3-fold increase in the maximum peak concentration and an earlier peak time of 30 min in C6 glioma cells. The cellular uptake of PL was enhanced by NB through down-regulating the expression levels of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). The combination of NB and PL significantly induced higher levels of ROS, which increased apoptosis and enhanced G2/M cycle arrest of C6 glioma cells, compared to PL alone administration. NB-enhanced antiglioma efficacy of PL without side effects was confirmed in tumor-bearing mice, which was attributed to the improved cellular uptake of PL. The distribution of PL in the tumor tissue of combined group increased 2.39 times than that of PL-treated group. We firstly report NB as an adjuvant agent to improve the antiglioma efficacy of PL in a ROS-dependent manner, which is due to the enhanced cellular uptake of PL by NB though down-regulating the expression levels of ABCB1 and ABCG2. This work provides a new strategy to promote the cellular uptake of PL with great potential for the treatment of glioma.

An imidazole-derived polarity sensitive probe for lipid droplet target and in vivo tumor imaging.

Accurate differentiation of tumor cells from normal cells is a fundamental and critical challenge for the early diagnosis of cancer. The intrinsic low-polarity and increased numbers of lipid droplets can be utilized as potential biomarkers for tumor cells. Therefore, we synthesized and screened the polar fluorescent probe (PI-CHO), which exhibiting notable fluorescence color change and spectral shift in solvents of different polarities. PI-CHO has a high sensitivity to polarity changes in the linear range of ET(30) = 37.4-63.1, with a fluorescence enhancement of more than 474-folds. Intracellular imaging experiments showed that PI-CHO has low cytotoxicity, excellent lipid droplet-targeted performance and discernibility between tumor and normal cells. Ex vivo imaging of the tumors and major organs demonstrated the great reliability and sensitive responsiveness of PI-CHO towards tumors. Moreover, the proposed probe was successfully applied to detect tumors in living mice, exhibiting the potential to become a powerful tool in early cancer diagnosis.

The Impact of Internet Use on the Social Networks of the Elderly in China-The Mediating Effect of Social Participation.

INTRODUCTION: Under the overlapping interaction of digitization and aging, the number of elderly Internet users has increased yearly. However, the impact of Internet use on the social networks of the elderly is still unclear. METHODOLOGY: In this study, we utilize the methods of ordinary least square regression (OLS), propensity score matching (PSM), instrumental variable (IV), and Bootstrap-mediated effect analysis methods using data from the Chinese General Social Survey (CGSS) to analyze the impact of Internet use on the social networks of the elderly and examine the mediating effect of social participation. OBJECTIVES: A total of 1363 validated respondents aged 60 or above were included to explore the relationship between Internet use, social networks, and social participation among the elderly in China. RESULTS: The results show that Internet use positively and significantly impacts the social networks of the elderly. Compared to the elderly who do not use the Internet, the elderly who use the Internet have a larger social network size, more significant social network heterogeneity, and higher social network upper reachability. The mediated analysis shows that social participation plays a positive mediating role in the influence of Internet use on the social networks of the elderly. That is, Internet use will benefit the social network of the elderly by improving the level of their social participation. Besides, there also exists heterogeneity in the effect of Internet use on social networks among the elderly with different genders, ages, and places of residence. CONCLUSIONS: Internet use benefits the social network of the elderly, and social participation partially mediates the relationship between Internet use and the social network of the elderly. These findings have implications for formulating public policies aimed at active aging; it is necessary to bridge the "digital divide" and promote the digital integration of the elderly. Let more older adults benefit from Internet use, thus improving the social network and quality of life of the elderly.

Chemical Constituent Analysis of Ranunculus sceleratus L. Using Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.

Right Ventricular Ejection Fraction Assessed by Three-Dimensional Echocardiography Is Associated with Long-Term Adverse Clinical Cardiac Events in Patients with Anthracycline-Induced Cardiotoxicity.

BACKGROUND: Patients with cancer treated with chemotherapy are at risk for cardiovascular toxicity. Global longitudinal strain has been reported to play important roles in predicting cardiovascular adverse events (CAEs) in patients treated with anthracycline. In addition to various left ventricular indicators, the authors hypothesized that right ventricular (RV) parameters might be associated with CAEs related to anthracycline treatment. METHODS: In this retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who received chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) were studied using three-dimensional transthoracic echocardiography. Baseline demographic data and oncologic and echocardiographic parameters were analyzed. The main outcome was the proportion of patients with grade 3 to 5 CAEs. The association of all three-dimensional transthoracic echocardiographic parameters with long-term CAEs was analyzed using Cox proportional-hazard analysis. RESULTS: Over a median follow-up period of 6.1 years (range, 4.9-7.6 years) after the completion of anthracycline chemotherapy, 18 of 96 patients (19%) experienced CAEs. Percentage changes (%Δ) in left ventricular global longitudinal strain (LVGLS), global circumferential strain, RV ejection fraction (RVEF), and RV end-systolic volume were associated with CAEs (P < .05). A relative reduction of RVEF (hazard ratio, 0.847; 95% CI, 0.785-0.915; P < .001) was the strongest associated factor for CAEs. An increase in CAEs was also observed in patients with impaired %ΔLVGLS > 15% and impaired %ΔRVEF > 12.7% compared with those with impaired %ΔLVGLS > 15% and impaired %ΔRVEF < 12.7% (P = .032). CONCLUSIONS: Three-dimensional echocardiography-based assessments of %ΔRVEF and %Δ in RV end-systolic volume were significantly associated with CAEs in patients with lymphoma treated with anthracycline chemotherapy.

A New Ratiometric Fluorescent Probe for Specific Monitoring of hROS under Physiological Conditions Using Boric Acid-Protected l-DOPA Gold Nanoclusters.

The specific monitoring of physiological highly reactive oxygen species (hROS) using fluorescent gold nanoclusters (AuNCs) remains a challenge for scientists. Herein, SLB-AuNC was first synthesized via an ecofriendly one-pot method using starch as a template, l-3,4-dihydroxyphenylalanine (l-DOPA) as a reducing and a capping agent, and boric acid as a protecting agent for the catechol moiety of l-DOPA. The ingenious introduction of starch and boric acid enhanced the dispersibility, quantum yield, and photostability of fluorescent SLB-AuNCs. The obtained SLB-AuNCs possessed good monodispersity with an average diameter of 2.9 ± 0.8 nm and exhibited highly stable fluorescence with maximum emission at 480 nm under physiological conditions. A ratiometric fluorescent probe for hROS was developed through an oxidization-regulated Förster-resonance-energy-transfer process between SLB-AuNCs and 2,3-diaminophenazine (the oxidative product of hROS and o-phenylenediamine, with maximum fluorescence emission at 560 nm). With increasing amount of hROS, the outstanding fluorescence variation of the probe (I560 nm/I480 nm) enhanced about 300-fold, accompanied with a distinguishable color change from cyan to yellow. The detection limits of •OH, ClO-, and ONOO- were calculated as 0.11, 0.50, and 0.69 µM, respectively. High selectivity was achieved using o-phenylenediamine as a specific signal response for hROS to enable no interference reaction of other ROS toward SLB-AuNCs. The practicability of the proposed probe with super biocompatibility was evaluated by measuring exogenous and endogenous hROS levels in HeLa cells through fluorescence imaging. This work provides a novel strategy to design fluorescent AuNC probes for physiological hROS with great potential for the application of bioassay and bioimaging.

Discrimination of cysteamine from mercapto amino acids through isoelectric point-mediated surface ligand exchange of ß-cyclodextrin-modified gold nanoparticles.

The discrimination of cysteamine (CA) from mercapto amino acids (including glutathione, cysteine and homocysteine, GSH/Cys/Hcy) with high efficiency is essential to detect biothiols in a physiological environment. Herein, a nano-assembly was constructed by combining one-pot synthesized ß-cyclodextrin-modified AuNPs and encapsulated rhodamine 6G (R6G-ß-CD@AuNPs) without covalent modification. Interestingly, when the pH value of the tested solution was approximately the isoelectric point (pI) of the biothiol, the quenched fluorescence of R6G-ß-CD@AuNPs was obviously restored by the introduction of the biothiol, which was due to the replacement of the R6G-ß-CD composite by the biothiol on the surfaces of AuNPs via a stronger S-Au bond. The pI-mediated surface ligand exchange process was designed for the first time for the discrimination and detection of CA and GSH/Cys/Hcy at the pH values of 9.5 and 5.5, respectively. Under the optimized conditions, the enhanced fluorescence intensity displayed a good linear response to the concentration of each biothiol, with the detection limits of CA, GSH, Cys and Hcy calculated as 66.8, 417.6, 652.7 and 603.4 nM, respectively. The ingenious fabrication of the R6G-ß-CD@AuNPs sensing platform eliminated the interferences from cholesterol by host-guest interactions and enabled high selectivity for the detection of biothiols in human serum samples. The pI-mediated sensing platform exhibits great potential for biothiol-related therapeutic drug monitoring.

Increased minimum alveolar concentration-awake of Sevoflurane in women of breast surgery with sleep disorders.

BACKGROUND: Sleep disorders are commonly encountered in clinic. Evidences showed that sleep deprivation may modulate the effectiveness of general anesthetics in rats. However, this phenomenon has not been explored in humans. The study aimed to investigate whether the hypnotic potency of sevoflurane in patients with sleep disorders differ from patients with normal sleep habits. METHODS: We recruited 44 patients scheduled for elective breast surgery and eventually analyzed 38 patients, including 19 subjects with normal sleep habits and 19 subjects with sleep disorders. According to the Dixon 'up-and-down' design, patients received sevoflurane at preselected concentrations starting at 1.0 vol%. After a steady-state period, a verbal command for testing awakening was performed. Based on the negative or positive response to the verbal command, we decreased or increased the concentration of sevoflurane by 0.2 vol% in the next patient accordingly. Plasma orexin-A was also measured before observation. RESULTS: The MACawake of sevoflurane was 0.80% [95% confidence interval (CI), 0.683-0.926%] in the sleep disordered group vs 0.60% [95% CI, 0.493-0.689%] in the control group. The relative median potency between groups was 0.750 (95% CI, 0.236-0.969). Patients with sleep disorders had significantly higher orexin-A levels than control (72.17 ± 18.24 vs. 36.16 ± 14.18 pg/mL). A significant, positive relationship was detected between orexin-A level and probability of awakening (OR = 1.081, 95% CI is 1.020-1.146, P = 0.008). CONCLUSIONS: MACawake of sevoflurane is higher in mild-aged women of breast surgery with sleep disorders compared to those with normal sleep habits. The increased anesthetic requirement may be related to changes of orexin-A levels. These findings suggest that sleep may have a potential impact on clinical anesthesia, including changes of sensitivity to anesthetics or postoperative complications. Further research is needed to confirm this hypothesis. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800016022), date of registration 07 May 2018.

TianJiu therapy for α-naphthyl isothiocyanate-induced intrahepatic cholestasis in rats treated with fresh Ranunculus sceleratus L.

ETHNOPHARMACOLOGICAL RELEVANCE: TianJiu (TJ) therapy, one type of cold moxibustion, applies to specific acupuncture points with herbal patches of hot nature, providing a constant irritant to the skin until the presence of hyperemia and blistering. Traditional and clinical reports suggest that TJ is an effective therapy for the treatment of jaundice with fresh Ranunculus sceleratus L. (RS), in which protoanemonin is one of the main irritant constituents. However, the therapeutic effect of TJ treatment with fresh RS against intrahepatic cholestasis has not been studied in animal experiments. AIM OF THE STUDY: Present study was undertaken to investigate the effect of TJ treatment with fresh RS against intrahepatic cholestasis in rats and provide an experimental basis for the underlying mechanism of TJ therapy. MATERIALS AND METHODS: Male intrahepatic cholestatic Sprague-Dawley rats induced by 2% α-naphthylisothiocyanate (ANIT, 80 mg/kg B.W.) were treated by TJ therapy with fresh RS. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL), total bilirubin (TBIL), total bile acid (TBA), hepatic malondialdehyde (MDA) and nitric monoxide (NO), as well as hepatic body ratio, bile flow and hepatic histopathological assay were measured and evaluated to investigate the therapeutic effect of TJ treatment with fresh RS. Phytochemical analysis of fresh and dried RS was performed by gas chromatography-mass spectrometer (GC-MS). RESULTS: After TJ treatment with fresh RS, the abnormally elevated levels of serum AST, ALT, ALP, DBIL, TBIL and TBA, as well as hepatic MDA and NO at 108 h were reduced significantly (versus model group, P < 0.01). The hepatic body ratio, bile flow and hepatic pathological change of cholestatic rats at 108 h in TJ group were restored when compared with those of model group. Thirty-one compounds including lactones, flavonoids and phenolic acids were identified and determined by GC-MS analysis. The content of protoanemonin in fresh RS (9.49%) was about 25-fold higher than that in dried RS (0.38%). CONCLUSIONS: TJ treatment with fresh RS exhibited good therapeutic effect on ANIT-induced intrahepatic cholestasis in rats, which may be due to the attenuated oxidative stress in the liver tissue. It is rational for the ancients to choose fresh RS as TJ herbal patches because of its abundant protoanemonin with the character of irritant. The qualitative and quantitative results of GC-MS analysis provided the chemical basis of TJ therapy with fresh RS, which can be regarded as a simple and efficient method for the treatment of cholestasis hepatitis.

Understanding Bachelorhood in Poverty-stricken and High Sex Ratio Settings: An Exploratory Study in Rural Shaanxi, China.

Coupled with the social practice of female hypergamy, the male surplus within the never-married population means that today's Chinese marriage market is extremely tight in particular for men from a rural background and the least privileged socio-economic categories. Drawing on quantitative data from a survey conducted in 2014-2015, this article sheds light on the situation of single men who are past prime marriage age in three rural districts of Shaanxi particularly affected by this phenomenon. It compares single men's characteristics to those of their married counterparts and offers insights into the heterogeneity of single men with the aim of challenging some commonly accepted assumptions about bachelorhood in rural China. Results suggest a strong internalization of the various characteristics, centred on being able to offer social mobility to a potential wife, that a man is expected to have to be attractive to women in a context where women have more choice in mate selection. We conclude that mate selection is highly marked by class, social norms, social interactions, health, generation and age, and requires the mobilization of certain amounts of individual, social and economic resources. Unwanted bachelorhood would thus be better understood using an intersectional approach rather than mainly in numeric terms.

A pH-Controlled Kit for Total and Direct Bilirubin Built on Mimetic Peroxidase CoFe2O4-DOPA-Catalyzed Fluorescence Enhancement.

Facile and reliable detection of total bilirubin (Bt, summation of indirect and direct bilirubin) and direct bilirubin (Bd) in human serum is of crucial importance to clinical diagnosis. However, it is still a challenge to explore an ideal recognition system for discriminating Bd and indirect bilirubin (Bi). In this work, a dual-functional sensor for Bt and Bd was first built on pH-controlled and mimetic peroxidase-catalyzed fluorescence enhancement. The fluorescence of nitrogen-doped graphene quantum dots (NGQDs) can be effectively quenched by bilirubin through the IFE process. With the catalysis of dopamine-derived magnetic ferrite nanoparticles (CoFe2O4-DOPA), both Bd and Bi were oxidized by H2O2 to colorless and fluorescent oxidates at pH 8.0. Interestingly, only Bd was oxidized at pH 3.5. The discriminating principle of Bd and Bi relied on their pH-controlled oxidation potentials. A sensitive sensor for Bt and Bd was developed on the enhanced fluorescence of the NGQDs/CoFe2O4-DOPA/H2O2 sensing system after bilirubin oxidation, which was originated from a combination of the fluorescence recovery of NGQDs and newly spawned fluorescence of bilirubin oxidates. The designed probe well quantifies Bt and Bd with the detection limits of 10 and 50 nM, respectively. Moreover, a portable diagnostic kit was fabricated and successfully used for the detection of Bt and Bd in 60 unrelated human serum samples, and the obtained results were almost consistent with those measured by biochemistry analyzer. The present kit exhibits the superiorities of high sensitivity and stability, interference-resistant, and green reagents, making it a promising candidate for bilirubin detection in the clinical diagnosis of jaundice.