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In this study, we have for the first time constructed a ratiometric ECL biosensor for the ultrasensitive detection of microRNAs (miRNAs) using gold nanoparticles (Au NPs) to trigger both the low-potential emission from conjugated polymer poly(9,9-dioctylfluorene-2,7-diyl) dots (PFO Pdots) and the LSPR-ECL effect with sulfur-doped boron nitride quantum dots (S-BN QDs). PFO Pdots were first applied to the Au NPs-modified electrode, followed by covalent binding to capture the hairpin H1. Immediately thereafter, a small amount of miRNA-141 was able to generate a large amount of output DNA (OP) by traversing the target cycle. OP, H3-S-BN QDs, and H4-glucose oxidase (H4-GOD) were then added sequentially to the Au NPs-modified electrode surface, and the hybridization chain reaction (HCR) was initiated. This resulted in the introduction of a large amount of GOD into the system, which catalyzed the in situ formation of the co-reactant hydrogen peroxide (H2O2) from the substrate glucose. Due to the electron transfer effect, the production of H2O2 led to the ECL quenching of PFO Pdots. Meanwhile, H2O2 served as a co-reactant of S-BN QDs, resulting in strong ECL emission of S-BN QDs at the cathode. Furthermore, the cathodic ECL intensity of S-BN QDs was further enhanced by an LSPR-ECL mechanism between Au NPs and S-BN QDs. By measuring the ratio of ECL intensities at two excitation potentials, this approach could provide sensitive and reliable detection of miRNA-141 in the range of 0.1 fM ∼10 nM, with a detection limit of 0.1 fM.

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In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.

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A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.

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Research on modeling and mechanisms of the brain remains the most urgent and challenging task. The customized embedded neuromorphic system is one of the most effective approaches for multi-scale simulations ranging from ion channel to network. This paper proposes BrainS, a scalable multi-core embedded neuromorphic system capable of accommodating massive and large-scale simulations. It is designed with rich external extension interfaces to support various types of input/output and communication requirements. The 3D mesh-based topology with an efficient memory access mechanism makes exploring the properties of neuronal networks possible. BrainS operates at 168 MHz and contains a model database ranging from ion channel to network scale within the Fundamental Computing Unit (FCU). At the ion channel scale, the Basic Community Unit (BCU) can perform real-time simulations of a Hodgkin-Huxley (HH) neuron with 16000 ion channels, using 125.54 KB of the SRAM. When the number of ion channels is within 64000, the HH neuron is simulated in real-time by 4 BCUs. At the network scale, the basal ganglia-thalamus (BG-TH) network consisting of 3200 Izhikevich neurons, providing a vital motor regulation function, is simulated in 4 BCUs with a power consumption of 364.8 mW. Overall, BrainS has an excellent performance in real-time and flexible configurability, providing an embedded application solution for multi-scale simulation.

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OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation.@*METHODS@#Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups.@*RESULTS@#After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment (P<0.01, P<0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group (P<0.05). After treatment, GAS scores were higher than before treatment in both groups (P<0.001), and the score in the treatment group was higher than the control group (P<0.05).@*CONCLUSION@#TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.

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According to the theory of acupuncture-moxibustion for the treatment of spirit, starting from the relationship between eye movement and spirit, the application of electrooculogram (EOG) signal acquisition and analysis technology for the clinical treatment of spirit by acupuncture-moxibustion is discussed. Based on the nonlinear dynamic characteristics of EOG signals, it is proposed to apply the approximate entropy algorithm to extract the EOG signal characteristics in autism spectrum disorder children under different behavior states, which could realize the preliminary exploration of the correlation between EOG signals and cognitive activities. This could provide a possibility to objectively reflect the patient' s current mental state, and could be used as a potential method to grasp spirit in clinical acupuncture- moxibustion treatment. Furthermore, considering the characteristics of acupoint stimulation on the body surface, the EOG signal acquisition and analysis technology could further be combined with biofeedback technology, and a new idea for clinical acupuncture-moxibustion to treat spirit guided by biofeedback of EOG is proposed.

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An auxiliary dining robot is designed in this paper, which implements the humanoid feeding function with theory of inventive problem solving (TRIZ) theory and aims at the demand of special auxiliary nursing equipment. Firstly, this robot simulated the motion function of human arm by using the tandem joints of the manipulator. The end-effector used a motor-driven spoon to simulate the feeding actions of human hand. Meanwhile, the eye in hand installation style was adopted to instead the human vision to realize its automatic feeding action. Moreover, the feeding and drinking actions of the dining robot were considered comprehensively with the flexibility of spatial movement under the lowest degree of freedom (DOF) configuration. The structure of the dining robot was confirmed by analyzing its stresses and discussing the specific application scenarios under this condition. Finally, the simulation results demonstrate high-flexibility of the dining robot in the workspace with lowest DOF configuration.

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Objective@#This study analyzes the development of school doctor personnel since the implementation of the national "School Health Work Regulations", from the salary of school doctors, followed by the management system of school doctors in primary and middle schools.@*Methods@#Representative provinces in the eastern, central and western regions of China were selected and surveyed through quantitative and qualitative method.@*Results@#The proportion of school doctors with medical background accounted for 33.64%, 31.6% school doctors had t o be established. A huge gap between income, bonus distribution and appraisal exsited between school doctors and school teachers. Wages of school doctors was much lower than that of education and social health sectors. The salary level showed regional imbalance, relatively higher in the eastern region and lower in the in the central and western regions with few exceptions. There were significant differences between medical background school doctors and non medical background school doctors in the highest educational background, income level, job nature, job placement, career development opportunity, income satisfaction, welfare and training satisfaction( χ 2=10.73,26.64,313.44,14.13,29.14,13.22,12.97,19.44, P < 0.05 ).@*Conclusion@#Government needs to pay attention to the school doctors in primary and secondary schools, integreate school health into public health management system. Relevant policies regarding school doctor management authority, school clinic and health center guideline, salary standards, as well as professional career development, are expected.

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The densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22 N-glycosites and site-specific N-glycans in the S protein protomer. Herein, we report the comprehensive and precise site-specific O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized using high-resolution mass spectrometry. Following digestion using trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the mucin-type (GalNAc-type) O-glycosylation pattern of S proteins, including unambiguous O-glycosites and the 6 most common O-glycans occupying them, via Byonic identification and manual validation. Finally, 43 O-glycosites were identified in the insect cell-expressed S protein. Most glycosites were modified by non-sialylated O-glycans such as HexNAc(1) and HexNAc(1)Hex(1). In contrast, 30 O-glycosites were identified in the human cell-expressed S protein S1 subunit. Most glycosites were modified by sialylated O-glycans such as HexNAc(1)Hex(1)NeuAc(1) and HexNAc(1)Hex(1)NeuAc(2). Our results are the first to reveal that the SARS-CoV-2 S protein is a mucin-type glycoprotein; clustered O-glycans often occur in the N- and the C-termini of the S protein, and the O-glycosite and O-glycan compositions vary with the host cell type. These site-specific O-glycosylation landscapes of the SARS-CoV-2 S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs.

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SummaryThe glycoprotein spike (S) on the surface of SARS-CoV-2 is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunits. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, primarily of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsACE2angiotensin-converting enzyme IICryo-EMcryoelectron microscopyEenvelope proteinHCoV-NL63human coronavirus NL63Mmembrane proteinMSmass spectrometryMERS-CoVMiddle East respiratory syndrome coronavirusNnucleocapsid proteinRBDreceptor-binding domainSspike proteinSARS-CoV-2severe acute respiratory syndrome coronavirusSCEstepped collision energyZic-HILICzwitterionic hydrophilic interaction liquid chromatographyView Full Text

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A simple and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was de-veloped and validated for simultaneous determination of acetaminophen and oxycodone in human plasma. Acetaminophen-d4 and oxycodone-d3 were used as internal standards. The challenge en-countered in the method development that the high plasma concentration level of acetaminophen made the MS response saturated while the desired lower limit of quantification (LLOQ) for oxycodone was hard to reach was well solved. The analytes were extracted by protein precipitation using acetonitrile. The matrix effect of the analytes was avoided by chromatographic separation using a hydrophilic C18 column coupled with gradient elution. Multiple reaction monitoring in positive ion mode was performed on tandem mass spectrometer employing electrospray ion source. The calibration curves were linear over the concentration ranges of 40.0–8000 ng/mL and 0.200–40.0 ng/mL for acetaminophen and oxycodone, respectively. This method, which could contribute to high throughput analysis and better clinical drug monitoring, was successfully applied to a pharmacokinetic study in healthy Chinese volunteers.

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Objective To investigate the filtration roles of microporous membranes with different pore sizes in the tumor cells with different diameters,and effects on the filtered cells.Methods Three kinds of tumor cells with different cell diameters and same concentrations,including Jurkat,K562 and A549,were filtered by the polycarbonate microporous membranes with different pore sizes such as 1,3,5,8 and 10 μm,respectively,and their filtration rates were determined.The diameters of three kinds of tumor cells before and after filtration,and the fixed K562 cells with formaldehyde,were measured by an optical microscope.The activity of the filtered K562 cells were detected by the trypan blue staining.After the filtered K562 cells were re-cultured,their proliferation activity was analyzed by the growth curve.Results Jurkat,K562 and A549 cells couldn't pass the filter membrane with 1 μm of pore size.The filtration rates of three kinds of tumor cells passing the fliter membranes with 3 μm,5 μm,8 μm and 10 μm of pore sizes increased in turn.The survival rate of K562 cells filtered by 3 μm of pore size of membrane was 92.0％,and the proliferation acticity of re-cultured K562 cells was still strong.The filtration rate of the fixed K562 cells with formaldehyde was significantly decreased,and the average diameter of the filtered cells had no obvious change.Conclusion The living cells are able to pass the membranes with the pore sizes less than their diameters.The living cells passed the filter membranes may still maintain their growth and proliferation activity.However,the fixation of formaldehyde may significantly reduce the number of cells passed the membrane.

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Aim To identify the potential biomarkers associated with carbon tetrachloride(CCl 4 )-induced a-cute hepatic injury in rats and explore the therapeutic effect of Hugan Tablets(HGT). Methods The model was established by intraperitoneal injection of CCl4 in oil(1 : 1,V/ V)with a dosage of 1 mL·kg - 1 body weight to rats once. The levels of aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),alka-line phosphatase (ALP ) and lactate dehydrogenase (LDH)in serum of rats were determined. Moreover,a proton nuclear magnetic resonance (1 H-NMR)based metabonomic approach in combination with multivariate data analysis was applied to demonstrate CCl4-induced acute hepatic injury metabolic perturbations in rat urine and feces and identify the corresponding metabolic bio-markers. The intervention effect of HGT was evaluated based on the changes of metabolic phenotype and po-tential biomarkers related to acute hepatic injury. Re-sults The levels of AST,ALT,ALP and LDH in ser-um of rats with acute hepatic injury were significantly reduced by administration of HGT,respectively. The disturbed metabolic state associated with CCl4-induced acute hepatic injury in rat urine and feces could be re-stored by HGT. Meanwhile,five potential biomarkers (2-oxoglutarate,citrate,creatinine,trimethylamine N-oxide,hippurate)in rat urine and three potential bio-markers(butyrate,glucose,uracil)in rat feces related to acute hepatic injury were reversed by administration of HGT,respectively. Conclusion HGT exerts pro-tective effects against CCl4-induced acute hepatic inju-ry in rats,which is probably mediated by regulation of tricarboxylic acid cycle and gut microbiota metabolism.

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Objective To investigate the value of using gonadotropin-releasing hormone agonist (GnRH-a) pretreatment in adenomyosis patients before adenomyomectomy. Methods From May 2012 to September 2015, 87 patients with adenomyosis who were non-effective to conservative therapy in Renmin Hospital of Wuhan University were enrolled in this study. According to the principle of randomized control, 41 patients were in the treatment group who were treated with GnRH-a 2-3 cycles before adenomyomectomy, while 46 patients in the control group. The control group paients were operated without any pretreatments. The blood loss, the number of penetrating into uterine cavity, duration of operation, duation of peritoneal drainage and the amount of drainage fluid, the difference of hemoglobin value before and after operation, total white blood cell count, duration of hospitalization, the maximum diameter of uterus and other indicators between the two groups were compared. Results In the treatment group, before and after treatment with GnRH-a, the uterus size, blood hemoglobinand CA125 value were statistically different (all P<0.05);between the treatment group of GnRH-a treated for 2 cycles and for 3 cycles, there were statistical differences of blood hemoglobin value [(108 ± 20) versus (118 ± 24) g/L], CA125 value [(26 ± 11) versus(19 ± 4) kU/L; all P<0.05]. There were statistical differences of blood loss in operation [(113 ± 32) versus (194 ± 42) ml], ratio of penetrating into uterine cavity [12%(5/41) versus 12%(8/46)], duration of operation[(79±23) versus (91±25) minutes], duration of peritoneal drainage after operation [(2.1±0.9) versus (3.0±1.2) days] and the amount of drainage fluid [(152±43) versus (232±32) ml], the difference of hemoglobin value before and after surgery [(-15.6±2.9) versus (-23.7±3.5) g/L], white blood cell count after 2-3 days of operation [(11.4±4.2)×109/L versus (13.5 ± 3.2) × 109/L], ratio of peri-operative blood transfusion [5% (2/41) versus 20% (9/46)] and duration of hospitalization [(11.2±1.9) versus (13.6±3.1) days] between the treatment group and the control group (all P<0.05). Conclusion The pretreatment of using GnRH-a before adenomyomectomy in adenomyosis patients has benefits for implementation of surgery and reducing peri-operative and postoperative complications.

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The first metatarsophalangeal joint bending plays an important role in the foot movement. However, the existing researches mainly focused on the movement scope of the joint and the clinical treatments of related foot diseases. In order to investigate the effects of the first metatarsophalangeal joint bending on human walking gait stability, the present researchers recruited 6 healthy young men to perform the first metatarsophalangeal joint constraint (FMJC) and barefoot (BF) walking tests. Data of the temporal and spatial parameters, the joint angles of lower limbs, the ground reaction forces (GRF) and utilized coefficients of friction (UCOF) were collected and analyzed. The results showed that, since hip and knee could produce compensation motions, the FMJC had no significant effects on waking gait, but the slip and fall probability increased significantly.

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