Dynamic cerebellar and sensorimotor network compensation in tremor-dominated Parkinson's disease.

AIM: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. METHODS: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. RESULTS: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. CONCLUSION: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

A novel derivative synchronous fluorescence method for the rapid, non-destructive and intuitive differentiation of denitrifying bacteria.

It is challenging to differentiate bacteria residing in the same habitat by direct observation. This difficulty impedes the harvest, application and manipulation of functional bacteria in environmental engineering. In this study, we developed a novel method for rapid differentiation of living denitrifying bacteria based on derivative synchronous fluorescence spectroscopy, as exemplified by three heterotrophic nitrification-aerobic denitrification bacteria having the maximum nitrogen removal efficiencies greater than 90%. The intact bacteria and their living surroundings can be analyzed as an integrated target, which eliminates the need for the complex pre-processing of samples. Under the optimal synchronous scanning parameter (Δλ = 40 nm), each bacterium possesses a unique fluorescence spectral structure and the derivative synchronous fluorescence technique can significantly improve the spectral resolution compared to other conventional fluorescence methods, which enables the rapid differentiation of different bacteria through derivative synchronous fluorescence spectra as fast as 2 min per spectrum. Additionally, the derivative synchronous fluorescence technique can extract the spectral signals contributed by bacterial extracellular substances produced in the biological nitrogen removal process. Moreover, the results obtained from our method can reflect the real-time denitrification properties of bacteria in the biological nitrogen removal process of wastewater. All these merits highlight derivative synchronous fluorescence spectroscopy as a promising analytic method in the environmental field.

Multi-process and multi-pollutant control technology for ultra-low emissions in the iron and steel industry.

The iron and steel industry is not only an important foundation of the national economy, but also the largest source of industrial air pollution. Due to the current status of emissions in the iron and steel industry, ultra-low pollutant emission control technology has been researched and developed. Liquid-phase proportion control technology has been developed for magnesian fluxed pellets, and a blast furnace smelting demonstration project has been established to use a high proportion of fluxed pellets (80%) for the first time in China to realize source emission reduction of SO2 and NOx. Based on the characteristics of high NOx concentrations and the coexistence of multiple pollutants in coke oven flue gas, low-NOx combustion coupled with multi-pollutant cooperative control technology with activated carbon was developed to achieve efficient removal of multiple pollutants and resource utilization of sulfur. Based on the characteristics of co-existing multiple pollutants in pellet flue gas, selective non-catalytic reduction (SNCR) coupled with ozone oxidation and spray drying adsorption (SDA) was developed, which significantly reduces the operating cost of the system. In the light of the high humidity and high alkalinity in flue gas, filter materials with high humidity resistance and corrosion resistance were manufactured, and an integrated pre-charged bag dust collector device was developed, which realized ultra-low emission of fine particles and reduced filtration resistance and energy consumption in the system. Through source emission reduction, process control and end-treatment technologies, five demonstration projects were built, providing a full set of technical solutions for ultra-low emissions of dust, SO2, NOx, SO3, mercury and other pollutants, and offering technical support for the green development of the iron and steel industry.

1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.

Label-Free Fluorescent Nanofilm Sensor Based on Surface Plasmon Coupled Emission: In Situ Monitoring the Growth of Metal-Organic Frameworks.

We have proposed a universal label-free fluorescent nanofilm sensor based on surface plasmon coupled emission (SPCE). A metal-dye-dielectric (MDD) structure was fabricated to mediate the label-free monitoring based on SPCE. The nonfluorescent dielectric film smartly borrowed the fluorescence signal from the bottom dye layer and led to a new SPCE response through the adjacent metal film. The fluorescence emission angle and polarization strongly depended on the thickness of the nonfluorescent dielectric film on the MDD structure. As a demonstration, the growth of a two-dimensional zeolitic imidazolate framework film (ZIF-L) was in situ monitored in the liquid phase by MDD-SPCE for the first time. The label-free fluorescent sensors are facilely prepared by a spin coating technique, with the potential to be widely spread for in situ studies, especially toward nanomaterial growth processes.

Machine Learning-Assisted Synchronous Fluorescence Sensing Approach for Rapid and Simultaneous Quantification of Thiabendazole and Fuberidazole in Red Wine.

Rapid analysis of components in complex matrices has always been a major challenge in constructing sensing methods, especially concerning time and cost. The detection of pesticide residues is an important task in food safety monitoring, which needs efficient methods. Here, we constructed a machine learning-assisted synchronous fluorescence sensing approach for the rapid and simultaneous quantitative detection of two important benzimidazole pesticides, thiabendazole (TBZ) and fuberidazole (FBZ), in red wine. First, fluorescence spectra data were collected using a second derivative constant-energy synchronous fluorescence sensor. Next, we established a prediction model through the machine learning approach. With this approach, the recovery rate of TBZ and FBZ detection of pesticide residues in red wine was 101% ± 5% and 101% ± 15%, respectively, without resorting complicated pretreatment procedures. This work provides a new way for the combination of machine learning and fluorescence techniques to solve the complexity in multi-component analysis in practical applications.

Long non-coding RNA maternally expressed 3 (MEG3) regulates isoflurane-induced cognitive dysfunction by targeting miR-7-5p.

This study aimed to investigate the role and mechanism of long non-coding RNA maternally expressed gene 3 (MEG3) in cognitive dysfunction induced by isoflurane (ISO). Morrier water maze analysis was performed to evaluate the cognitive function of rats. Modified modified neurological severity score (mNSS) scores were assessed for neurological damage. The levels of MEG3 in hippocampal tissues of rats and hippocampal neuron cell lines HT22 were examined by reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Moreover, the cell viability and apoptosis were assessed by the Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Indicators of inflammation and oxidative stress were determined using enzyme-linked immunosorbent assay (ELISA) and commercial assay kits. Relationship between MEG3 and microRNA (miR)-7-5p was verified by the dual-luciferase reporter gene assay. MEG3 was increased in hippocampal tissues and HT22 after ISO treatment (p < 0.05). MEG3 downregulation alleviated the increase in neurological severity score and cognitive dysfunction caused by ISO treatment (p < 0.05). In vitro, MEG3 downregulation alleviates the decrease in cell activity and increased apoptosis induced by ISO. What's more, MEG3 reduction eliminated activation of neuroinflammation and oxidative stress promoted by ISO treatment in rats and HT22 (p < 0.05). MEG3 was confirmed to specifically bind to miR-7-5p. Inhibition of miR-7-5p eliminated the alleviating effects of MEG3 downregulation on cognitive dysfunction caused by ISO treatment. Decreased MEG3 alleviates cognitive dysfunction caused by ISO by targeting miR-7-5p and play a neuroprotective effect. We present a strategy for MEG3 as a potential target for brain protection during anesthesia.

Altered effective connectivity in migraine patients during emotional stimuli: a multi-frequency magnetoencephalography study.

BACKGROUND: Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients. METHODS: A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz. RESULTS: The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30-90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1-4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1-4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges. CONCLUSIONS: The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.

Plasmon Coupling Enhanced Micro-Spectroscopy and Imaging for Sensitive Discrimination of Membrane Domains of a Single Cell.

Different cell membrane domains play different roles in many cell processes, and the discrimination of these domains is of considerable importance for the elucidation of cellular functions. However, the strategies available for distinguishing these cell membrane domains are limited. A novel technique called plasmon coupling enhanced micro-spectroscopy and imaging to discriminate basal and lateral membrane domains of a single cell combines the application of an additional plasmonic silver film for surface plasmon (SP) excitation to selectively excite and enhance the basal membranes in the near-field with directional enhanced microscopic imaging and spectroscopy. The SP and critical evanescent fields are induced upon excitation through a silver-coated semitransparent coverslip at the surface plasmon resonance and critical angles, respectively. The basal and lateral membrane domains located within the SP and critical evanescent fields can be selectively excited and distinguished by adjusting the incident angle of laser irradiation. Moreover, the brighter images and more intense spectra of membrane-targeting fluorescence-Raman probes under directional excitation than in conventional EPI mode allow clear identification of the membrane domains.

lncRNA RNCR2 facilitates cell proliferation and epithelial-mesenchymal transition in melanoma through HK2-mediated Warburg effect via targeting miR-495-3p.

Melanoma is a potentially lethal skin cancer with a high death rate. LncRNAs were reported to be implicated in melanoma progression. However, the function and mechanisms of lncRNA RNCR2 in melanoma are little known. In this study, RNCR2, miR-495-3p, and HK2 expression levels were measured in melanoma tissue specimens and cell lines by qPCR. EdU and CCK-8 assays were performed to assess cell proliferation. Enolase activity, ATP level, lactate production, and glucose consumption measurement kits were used to evaluate the glycolysis of tumor cells. Immunofluorescence and western blot were used to detect the expression of epithelial-mesenchymal transition (EMT) and glycolysis-related proteins. Luciferase reporter assay was applied to confirm the target relationships. The role of RNCR2 in tumorigenesis was examined using murine xenograft models. LncRNA RNCR2 was upregulated in melanoma tissues and cell lines. Cell function detection showed that RNCR2 knockdown remarkably inhibited cell proliferation and EMT via glycolysis, as well as reduced the growth of a tumor. Mechanically, RNCR2 was confirmed to bind to miR-495-3p and positively regulated HK2 expression level, and the miR-495-3p level was negatively correlated with RNCR2 or HK2 in melanoma tissues. Further, miR-495-3p downregulation or HK2 upregulation partially reversed RNCR2 knockdown-induced inhibition of melanoma cell growth, EMT, and glycolysis. Collectively, RNCR2 might be an oncogenic lncRNA to promote tumor cell glycolysis and accelerate tumor growth via the miR-495-3p/HK2 axis, providing a promising treatment target for melanoma.

Neuroprotective effect of miR-212-5p on isoflurane-induced cognitive dysfunction by inhibiting neuroinflammation.

BACKGROUND: Isoflurane is a commonly used inhalation anesthetic in the clinic, which can induce cognitive dysfunction and neuroinflammation. miR-212-5p has been demonstrated to be involved in the neuronal system and play vital roles in memory formation. Its function in the learning and memory impairment and neuroinflammation induced by isoflurane was investigated in this study. METHODS: Cognitive dysfunction rat models were established by 3% isoflurane inhalation. The neurological function was evaluated by the modified Neurological Severity Scale. The learning and memory ability of rats was assessed by the Morris water maze test. The expression level of miR-212-5p was analyzed by RT-qPCR, and the protein levels of proinflammatory cytokines were detected by ELISA. RESULTS: Isoflurane induced cognitive dysfunction in rats with the neurological scores and the escape latency increased, and time spent in the target quadrant decreased. The protein levels of IL-1ß, IL-6, and TNF-α were increased in isoflurane treated rats. miR-212-5p was downregulated in cognitive impairment rats. The upregulation of miR-212-5p by the agomir injection decreased the neurological scores of rats and increased the learning and memory ability of impaired rats. Moreover, the neuroinflammation was inhibited by the overexpression of miR-212-5p. CONCLUSION: miR-212-5p showed a neuroprotective effect in isoflurane-induced cognitive dysfunction rats by inhibiting neuroinflammation.

Surface plasmon-coupled emission imaging for biological applications.

Fluorescence imaging technology has been extensively applied in chemical and biological research profiting from its high sensitivity and specificity. Much attention has been devoted to breaking the light diffraction-limited spatial resolution. However, it remains a great challenge to improve the axial resolution in a way that is accessible in general laboratories. Surface plasmon-coupled emission (SPCE), generated by the interactions between surface plasmons and excited fluorophores in close vicinity of the thin metal film, offers an opportunity for optical imaging with potential application in analysis of molecular and biological systems. Benefiting from the highly directional and distance-dependent properties, SPCE imaging (SPCEi) has displayed excellent performance in bioimaging with improved sensitivity and axial confinement. Herein, we give a brief overview of the development of SPCEi. We describe the unique optical characteristics and constructions of SPCEi systems and highlight recent advances in the use of SPCEi for biological applications. We hope this review provides readers with both the insights and future prospects of SPCEi as a new promising imaging platform for potentially widespread applications in biological research and medical diagnostics. Graphical abstract.

In situ and sensitive monitoring of configuration-switching involved dynamic adsorption by surface plasmon-coupled directional enhanced Raman scattering.

Surface adsorption studies play a crucial role in numerous fields from surface catalysis to molecular separation. However, investigation on adsorption mechanisms has been restricted to limited analytes and approaches, which calls for an in situ and sensitive surface analysis technique capable of revealing the mechanisms as well as discriminating different adsorbates and their geometry at different adsorption stages. In this study, we employed surface plasmon-coupled directional enhanced Raman scattering (SPCR), a novel technique developed by coupling surface plasmon-coupled emission with SERS, to study conformation-switching involved dynamic adsorption with background suppression and improved sensitivity (nearly 30-fold). We obtained the isotherms for a conformation-changing Raman model analyte, malachite green. An S-type Langmuir model was fitted from the time-resolved SPCR signals sensitively and without any interference from the bulk solution. The reorientation of the analyte from a predominantly parallel configuration to a perpendicular one was captured by the dramatic increase in the intensity ratios of the adsorption-related peaks to the adsorption-unrelated peak. We believe that this new sensitive and selective SPCR technique will be a promising tool for surface adsorption kinetics analysis.

Variable-Angle Nanoplasmonic Fluorescence Microscopy: An Axially Resolved Method for Tracking the Endocytic Pathway.

The study of endocytosis, which encompasses diverse mechanisms in biology, requires the utilization of high axial resolution to monitor molecular behavior on both the cell surface and interior of the cell. We have designed a novel axially resolved fluorescence microscopic technique, termed variable-angle nanoplasmonic fluorescence microscopy. The proof-of-principle of this approach is achieved by selectively following the events in the vicinity of a cell membrane or in a cell. We use a 30 nm Au-coated semitransparent coverslip as the nanoplasmonic chip to achieve both surface plasmon resonance excitation and critical angle excitation by tuning the incident angles. This approach leads to improved axial resolution compared to total internal reflection fluorescence microscopy, which is a common imaging technique in cell biology. It offers a unique opportunity to semiquantitatively determine fluorophore axial distributions in the cell. Observing the epidermal growth factor receptor-mediated endocytosis in Caski cells clearly demonstrates the potential application of this new method for cell biology studies.

Reversing current rectification to improve DNA-sensing sensitivity in conical nanopores.

Herein, we report the ultrasensitive DNA detection through designing an elegant nanopore biosensor as the first case to realize the reversal of current rectification direction for sensing. Attributed to the unique asymmetric structure, the glass conical nanopore exhibits the sensitive response to the surface charge, which can be facilely monitored by ion current rectification curves. In our design, an enzymatic cleavage reaction was employed to alter the surface charge of the nanopore for DNA sensing. The measured ion current rectification was strongly responsive to DNA concentrations, even reaching to the reversed status from the negative ratio (-6.5) to the positive ratio (+16.1). The detectable concentration for DNA was as low as 0.1 fM. This is an ultrasensitive and label-free DNA sensing approach, based on the rectification direction-reversed amplification in a single glass conical nanopore.

Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease.

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and is involved in pathological angiogenesis associated with chronic liver diseases. However, the precise mechanisms underlying PlGF signalling contributing to liver fibrosis and angiogenesis remain largely unexplored. This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. Fibrosis was induced in mice by carbon tetrachloride (CCl4 ) for 8 weeks, and mice were treated with PlGF siRNA or non-targeting control siRNA starting two weeks after initiating CCl4 injections. The results showed that PlGF was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells (HSCs). PlGF silencing robustly reduced liver inflammation, fibrosis, intrahepatic macrophage recruitment, and inhibited the activation of HSCs in vivo. Moreover, PlGF siRNA-treated fibrotic mice showed diminished hepatic microvessel density and angiogenic factors, such as hypoxia-inducible factor-1α (HIF-1α), VEGF and VEGF receptor-1. Moreover, down-regulation of PlGF with siRNA in HSCs inhibited the activation and proliferation of HSCs. Mechanistically, overexpression of PlGF in activated HSCs was induced by hypoxia dependent on HIF-1α, and PlGF induces HSC activation and proliferation via activation the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathways. These findings indicate that PlGF plays an important role in liver fibrosis-associated angiogenesis and that blockage of PlGF could be an effective strategy for chronic liver disease.

[Pharmacokinetic Effect of Acteoside in Blood Deficiency Rats].

Objective: To study the different pharmacokinetics effect of acteoside extracted from Rehmanniae Radix Preparata in normal and blood deficiency rats. Methods: Injected acetyl phenylhydrazine and cyclophosphamide to make blood deficiency rats models subcutaneously,and gave mice the ethand extracts of Rehmanniae Radix preparata by oral administration,the concentration of acteoside in rats at different time points were detected by HPLC method, pharmacokinetic parameters were calculated by 3p87 software. Results: The determination of acteoside in the linear range were 0. 2 ~ 80 µg / m L, the limit of detection and quantification was 0. 03 and 0. 12µg/m L,respectively. Compared with the normal group,the content of AUC0-tand AUC0-∞of corresponding dose in model group rats increased significantly, and the average dwell time and the elimination half-life prolong significantly. Conclusion: This method has high specificity,high sensitivity and simple operation, which can be used for the determination to pharmacokinetic process of acteoside in blood deficiency model.

Relationships of multimorbidity and income with hospital admissions in 3 health care systems.

Associations of multimorbidity and income with hospital admission were investigated in population samples from 3 widely differing health care systems: Scotland (n = 36,921), China (n = 162,464), and Hong Kong (n = 29,187). Multimorbidity increased odds of admissions in all 3 settings. In Scotland, poorer people were more likely to be admitted (adjusted odds ratio [aOR] = 1.62; 95% CI, 1.41-1.86 for the lowest income group vs the highest), whereas China showed the opposite (aOR = 0.58; 95% CI, 0.56-0.60). In Hong Kong, poorer people were more likely to be admitted to public hospitals (aOR = 1.68; 95% CI, 1.36-2.07), but less likely to be admitted to private ones (aOR = 0.18; 95% CI, 0.13-0.25). Strategies to improve equitable health care should consider the impact of socioeconomic deprivation on the use of health care resources, particularly among populations with prevalent multimorbidity.

[In vivo Pharmacokinetics of Notoginsenoside R1 in Ischemia Rats After Acute Myocardial Infarction].

OBJECTIVE: To establish an HPLC-UV method for determining pharmacokinetic difference of notoginsenoside R1 between normal rats and ischemic rats. METHODS: 48 male SD rats were randomly divided into normal group and acute myocardial ischemia( AMI) model group induced by pituitrin and each group was classified into high,middle and low-dose of groups with notoginsenoside R1 (200, 100 and 50 mg/kg) respectively. Blood samples were collected at different points in time after they were administered once by gavage and separated by Waters symmetry C18 column (250 mm x 4.6 mm, 5 µm) under the detective wavelength 203 nm, the mobile phase was acetonitrile-water with icariin as the internal standard and the pharmacokinetic parameters were calculated by DAS 2. 0. RESULTS: Notoginsenoside R1 had good linearity in the ranges of 0.2~125 µg/mL (R2 = 0.9997) with SNR 1:3 and the lowest detection limit was 0.053 µg/mL, the extraction rate, RSDs of within-day and between-day, specificity, accuracy and precision accorded with the require-ment of bio-sample pretreatment. Compared to the normal group, AUC0-t, and AUC0-∞ was significantly increased (P < 0.01) and the terminal half-life was prolonged markedly (P < 0.01) in AMI group. CONCLUSIONS: The method is simple, accurate and had high specificity and sensitivity, that could be applied in quantitative determination of notoginsenoside R1 and research of pharmacokinetics; the relative bioavailability of notoginsenoside R1 is increased significantly in AMI group,which indicates that notoginsenoside R1 has better effect in model rat.

Label-free aptasensor based on ultrathin-linker-mediated hot-spot assembly to induce strong directional fluorescence.

We have demonstrated the proof-of-concept of a label-free biosensor based on emission induced by an extreme hot-spot plasmonic assembly. In this work, an ultrathin linking layer composed of cationic polymers and aptamers was fabricated to mediate the assembly of a silver nanoparticles (AgNPs)-dyes-gold film with a strongly coupled architecture through sensing a target protein. Generation of directional surface plasmon coupled emission (SPCE) was thus stimulated as a means of reporting biorecognition. Both the biomolecules and the nanoparticles were totally free of labeling, thereby ensuring the activity of biomolecules and allowing the use of freshly prepared metallic nanoparticles with large dimensions. This sensor smartly prevents the plasmonic assembly in the absence of targets, thus maintaining no signal through quenching fluorophores loaded onto a gold film. In the presence of targets, the ultrathin layer is activated to link NPs-film junctions. The small gap of the junction (no greater than 2 nm) and the large diameter of the nanoparticles (~100 nm) ensure that ultrastrong coupling is achieved to generate intense SPCE. A >500-fold enhancement of the signal was observed in the biosensing. This strategy provides a simple, reliable, and effective way to apply plasmonic nanostructures in the development of biosensing.