The subgenomic flaviviral RNA suppresses RNA interference through competing with siRNAs for binding RISC components.

During the life cycle of mosquito-borne flaviviruses, substantial subgenomic flaviviral RNA (sfRNA) is produced via incomplete degradation of viral genomic RNA by host XRN1. Zika virus (ZIKV) sfRNA has been detected in mosquito and mammalian somatic cells. Human neural progenitor cells (hNPCs) in the developing brain are the major target cells of ZIKV, and antiviral RNA interference (RNAi) plays a critical role in hNPCs. However, whether ZIKV sfRNA was produced in ZIKV-infected hNPCs as well as its function remains not known. In this study, we demonstrate that abundant sfRNA was produced in ZIKV-infected hNPCs. RNA pulldown and mass spectrum assays showed ZIKV sfRNA interacted with host proteins RHA and PACT, both of which are RNA-induced silencing complex (RISC) components. Functionally, ZIKV sfRNA can antagonize RNAi by outcompeting small interfering RNAs (siRNAs) in binding to RHA and PACT. Furthermore, the 3' stem loop (3'SL) of sfRNA was responsible for RISC components binding and RNAi inhibition, and 3'SL can enhance the replication of a viral suppressor of RNAi (VSR)-deficient virus in a RHA- and PACT-dependent manner. More importantly, the ability of binding to RISC components is conversed among multiple flaviviral 3'SLs. Together, our results identified flavivirus 3'SL as a potent VSR in RNA format, highlighting the complexity in virus-host interaction during flavivirus infection.IMPORTANCEZika virus (ZIKV) infection mainly targets human neural progenitor cells (hNPCs) and induces cell death and dysregulated cell-cycle progression, leading to microcephaly and other central nervous system abnormalities. RNA interference (RNAi) plays critical roles during ZIKV infections in hNPCs, and ZIKV has evolved to encode specific viral proteins to antagonize RNAi. Herein, we first show that abundant sfRNA was produced in ZIKV-infected hNPCs in a similar pattern to that in other cells. Importantly, ZIKV sfRNA acts as a potent viral suppressor of RNAi (VSR) by competing with siRNAs for binding RISC components, RHA and PACT. The 3'SL of sfRNA is responsible for binding RISC components, which is a conserved feature among mosquito-borne flaviviruses. As most known VSRs are viral proteins, our findings highlight the importance of viral non-coding RNAs during the antagonism of host RNAi-based antiviral innate immunity.

Key Residue in the Precursor Region of M Protein Contributes to the Neurovirulence and Neuroinvasiveness of the African Lineage of Zika Virus.

The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.

Collision Localization and Classification on the End-Effector of a Cable-Driven Manipulator Applied to EV Auto-Charging Based on DCNN-SVM.

With the increasing popularity of electric vehicles, cable-driven serial manipulators have been applied in auto-charging processes for electric vehicles. To ensure the safety of the physical vehicle-robot interaction in this scenario, this paper presents a model-independent collision localization and classification method for cable-driven serial manipulators. First, based on the dynamic characteristics of the manipulator, data sets of terminal collision are constructed. In contrast to utilizing signals based on torque sensors, our data sets comprise the vibration signals of a specific compensator. Then, the collected data sets are applied to construct and train our collision localization and classification model, which consists of a double-layer CNN and an SVM. Compared to previous works, the proposed method can extract features without manual intervention and can deal with collision when the contact surface is irregular. Furthermore, the proposed method is able to generate the location and classification of the collision at the same time. The simulated experiment results show the validity of the proposed collision localization and classification method, with promising prediction accuracy.

Research on Fast Recognition and Localization of an Electric Vehicle Charging Port Based on a Cluster Template Matching Algorithm.

With the gradual maturity of driverless and automatic parking technologies, electric vehicle charging has been gradually developing in the direction of automation. However, the pose calculation of the charging port (CP) is an important part of realizing automatic charging, and it represents a problem that needs to be solved urgently. To address this problem, this paper proposes a set of efficient and accurate methods for determining the pose of an electric vehicle CP, which mainly includes the search and aiming phases. In the search phase, the feature circle algorithm is used to fit the ellipse information to obtain the pixel coordinates of the feature point. In the aiming phase, contour matching and logarithmic evaluation indicators are used in the cluster template matching algorithm (CTMA) proposed in this paper to obtain the matching position. Based on the image deformation rate and zoom rates, a matching template is established to realize the fast and accurate matching of textureless circular features and complex light fields. The EPnP algorithm is employed to obtain the pose information, and an AUBO-i5 robot is used to complete the charging gun insertion. The results show that the average CP positioning errors (x, y, z, Rx, Ry, and Rz) of the proposed algorithm are 0.65 mm, 0.84 mm, 1.24 mm, 1.11 degrees, 0.95 degrees, and 0.55 degrees. Further, the efficiency of the positioning method is improved by 510.4% and the comprehensive plug-in success rate is 95%. Therefore, the proposed CTMA in this paper can efficiently and accurately identify the CP while meeting the actual plug-in requirements.

Robust Adaptive Control of Fully Constrained Cable-Driven Serial Manipulator with Multi-Segment Cables Using Cable Tension Sensor Measurements.

The structure of the cable-driven serial manipulator (CDSM) is more complex than that of the cable-driven parallel manipulator (CDPM), resulting in higher model complexity and stronger structural and parametric uncertainties. These drawbacks challenge the stable trajectory-tracking control of a CDSM. To circumvent these drawbacks, this paper proposes a robust adaptive controller for an n-degree-of-freedom (DOF) CDSM actuated by m cables. First, two high-level controllers are designed to track the joint trajectory under two scenarios, namely known and unknown upper bounds of uncertainties. The controllers include an adaptive feedforward term based on inverse dynamics and a robust control term compensating for the uncertainties. Second, the independence of control gains from the upper bound of uncertainties and the inclusion of the joint viscous friction coefficient into the dynamic parameter vector are realised. Then, a low-level controller is designed for the task of tracking the cable tension trajectory. The system stability is analysed using the Lyapunov method. Finally, the validity and effectiveness of the proposed controllers are verified by experimenting with a three-DOF six-cable CDSM. In addition, a comparative experiment with the classical proportional-integral-derivative (PID) controller is carried out.

Development and validation of an LC-MS/MS method for the determination of a novel thienoquinolin urea transporter inhibitor PU-48 in rat plasma and its application to a pharmacokinetic study.

A specific, sensitive and stable high-performance liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of methyl 3-amino-6-methoxythieno [2,3-b]quinoline-2-carboxylate (PU-48), a novel diuretic thienoquinolin urea transporter inhibitor in rat plasma. In this method, the chromatographic separation of PU-48 was achieved with a reversed-phase C18 column (100 × 2.1 mm, 3 µm) at 35°C. The mobile phase consisted of acetonitrile and water with 0.05% formic acid added with a gradient elution at flow rate of 0.3 mL/min. Samples were detected with the triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via electrospray ionization source in positive mode. The retention time were 6.2 min for PU-48 and 7.2 min for megestrol acetate (internal standard, IS). The monitored ion transitions were mass-to-charge ratio (m/z) 289.1 → 229.2 for PU-48 and m/z 385.3 → 267.1 for the internal standard. The calibration curve for PU-48 was linear over the concentration range of 0.1-1000 ng/mL (r2 > 0.99), and the lower limit of quantitation was 0.1 ng/mL. The precision, accuracy and stability of the method were validated adequately. The developed and validated method was successfully applied to the pharmacokinetic study of PU-48 in rats.

Effects of crystalline state and self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of the novel anti-HIV compound 6-benzyl-1-benzyloxymethyl-5-iodouracil in rats.

The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size. The plasma concentrations of W-1 were measured by high performance liquid chromatography (HPLC). The results indicated that W-1 compound were presented as crystalline forms, A and B, the degree of crystallization in form B was higher than that in form A. The SNEDDS of W-1 displayed a significant increase in the dissolution rate than W-1 powder. Furthermore, after oral administration of W-1 (100 mg/kg), the pharmacokinetic parameters of form A, form B, and W-1 SNEDDS were as follows: AUC0-t 526.4 ± 123.5, 305.1 ± 58.5 and 2297 ± 451 ng h/mL (p < .05, when W-1 SNEDDS were compared with either form A or form B), respectively. With SNEDDS formulation, the relative bioavailabilities were enhanced by 4.36-fold and 7.53-fold over the form A and form B of W-1, respectively. In conclusion, the present results suggested that the crystalline states of W-1 might lead to the lower oral bioavailability, and SNEDDS formulation is a promising strategy of improving bioavailability, in spite of that crystalline states usually carry small lot-to-lot variability.

Effects of functional CYP2C8,CYP2C9,CYP3A5,and ABCB1 genetic variants on the pharmacokinetics of insulin sensitizer pioglitazone in Chinese Han individuals.

BACKGROUND AND OBJECTIVES: Pioglitazone is a thiazolidinedione antihyperglycemic drug with insulin-sensitizing properties. We investigated whether the variant genotypes of cytochrome P450 2C8 (CYP2C8), CYP2C9, CYP3A5 and transporter ABCB1 influence the pharmacokinetic phenotype of the substrate pioglitazone in Chinese individuals. PARTICIPANTS AND METHODS: Single-nucleotide polymorphisms were determined by the PCR-restriction fragment length polymorphism method in 244 (CYP2C8 and CYP2C9) healthy Chinese Han individuals. After a single oral dose of 30 mg pioglitazone, the plasma concentrations of the parent drug and of two major active metabolites M-III and M-IV were measured using a validated LC-MS/MS in 21 (genotyping CYP3A5 and ABCB1) of these 244 volunteers. RESULTS: The results confirmed that the unique frequencies of CYP2C8*2 (0.0%), CYP2C8*3 (0.0%), and CYP2C9*2 (0.0%) alleles were significantly different from those reported in Whites and Africans, and there were only 10 variant CYP2C9*1/*3 heterozygous (CYP2C9*3 carriers) among 244 Chinese individuals. These results were similar to those reported in Asian ethnic populations, including the Chinese. Unexpectedly, the pioglitazone AUC0-48 in CYP2C9*3 carriers was lower (50.8%), whereas the AUC0-48 ratios of metabolites M-III/pioglitazone and M-IV/pioglitazone increased to 134.3 and 155.8%, respectively, compared with the wild-type CYP2C9*1/*1 homozygous. Moreover, this phenomenon was not observed in individuals with genetic variants of CYP3A5*3 and ABCB1 (C1236T). CONCLUSION: The present research suggests that the CYP2C8, CYP3A5, and ABCB1 genes play no significant role in the interindividual variation of pioglitazone pharmacokinetics, whereas CYP2C9*3 carriers are likely to accelerate the metabolism of this antidiabetic drug in the Chinese Han ethnic population.

Identification of cytochrome P450s involved in the metabolism of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1) using human recombinant enzymes and rat liver microsomes in vitro.

1. The aim of this study was to identify the hepatic metabolic enzymes, which involved in the biotransformation of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) in rat and human in vitro. 2. The parent drug of W-1 was incubated with rat liver microsomes (RLMs) or recombinant CYPs (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5, respectively) in the presence or absence of nicotinamide adeninedinucleotide phosphate (NADPH)-regenerating system. The metabolites of W-1 were analyzed with liquid chromatography-ion trap-time of flight-mass spectrometry (LC-IT-TOF-MS). 3. The parent drug of W-1 was metabolized in a NADPH-dependent manner in RLMs. The kinetic parameters of prototype W-1 including Km, Vmax, and CLint were 2.3 µM, 3.3 nmol/min/mg protein, and 1.4 mL/min/mg protein, respectively. Two metabolites M1 and M2 were observed in shorter retention times (2.988 and 3.188 min) with a higher molecular ion at m/z 463.0160 (both M1 and M2) than that of the W-1 parent drug (6.158 min with m/z 447.0218). The CYP selective inhibition and recombinant enzymes also showed that two hydroxyl metabolites M1 and M2 are mainly mediated by CYP2C19 and CYP3A4. 4. The identification of CYPs involved in W-1 biotransformation is important to understand and minimize, if possible, the potential of drug-drug interactions.

Using support vector machines to identify literacy skills: Evidence from eye movements.

Is inferring readers' literacy skills possible by analyzing their eye movements during text reading? This study used Support Vector Machines (SVM) to analyze eye movement data from 61 undergraduate students who read a multiple-paragraph, multiple-topic expository text. Forward fixation time, first-pass rereading time, second-pass fixation time, and regression path reading time on different regions of the text were provided as features. The SVM classification algorithm assisted in distinguishing high-literacy-skilled readers from low-literacy-skilled readers with 80.3 % accuracy. Results demonstrate the effectiveness of combining eye tracking and machine learning techniques to detect readers with low literacy skills, and suggest that such approaches can be potentially used in predicting other cognitive abilities.

Development and validation of a high performance liquid chromatography method for determination of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor and its application to a pharmacokinetic study in rats.

A sensitive and selective high-performance liquid chromatographic (HPLC) method for determination of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor in rat plasma, was developed and validated. Chromatographic separation of W-1 and megestrol acetate (internal standard) was achieved on a reversed-phase C18 column at 25°C. The mobile phase was consisted of acetonitrile-water (60:40, v/v) and pumped at a flow rate of 1.0 mL/min. The ultraviolet (UV) detector was set at the absorption wavelength of 284 nm. The calibration curve for W-1 was linear over the concentration range of 0.01-8 µg/mL and the lower limit of quantification was 10 ng/mL. The intra- and inter-day precision and accuracy were <8.9 and 5.3%, respectively. The extraction recoveries ranged from 97.9 to 101.6%. The validated HPLC method was successfully applied to a pharmacokinetic study of W-1 in rats.

[Identification of Sun-dried and Sulfur-fumigated Chuanxiong Rhizoma by FTIR].

OBJECTIVE: To evaluate the sulfur-fumigation effects on the chemical constituents of Chuanxiong Rhizoma. METHODS: Alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples were analyzed by FIIR. FTIR spectra were acquired and disposed by software Omnic 8. 0, second derivative IR spectra were analyzed by software OPUS 6. 5 through smoothing and differentiation treatment to FTIR spectra, and the absorption frequencies of alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples were assessed by using principal component analysis with software SPSS. RESULTS: There were significant differences between sun-dried and sulfur-fumigated Chuanxiong Rhizoma samples in the region ranging from 2 000 cm-1 to 750 cm-1. Some absorption peaks weakened or disappeared, and some newly emerged after the processing of sulfur-fumigation. CONCLUSION: The processing of sulfur-fumigation can influence the effective constituents of Chuanxiong Rhizoma. The established method of FTIR combined with second derivative and principal component analysis has been proved to be an effective, intuitional and rapid approach to distinguish sun-dried and sulfur-fumigated Chuanxiong Rhizoma.

Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats.

In an anti-glomerular basement membrane (GBM) glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα+CD11c+MHC-II+CD3- (GIL CD8αα+ cells) were responsible for recovery through induction of T-cell apoptosis. Now, we identified peripheral blood CD8αα+CD11c+MHC-II+CD3- cells (PBMC CD8αα+CD3- cells), which shared 9 markers with GIL CD8αα+ cells. Upon incubation, PBMC CD8αα+CD3- cells displayed a morphology resembling that of dendritic cells. Similar to GIL CD8αα+ cells, PBMC CD8αα+CD3- cells were capable of inducing T-cell apoptosis in vitro. Hence, PBMC CD8αα+CD3- cells were likely the precursor of GIL CD8αα+ cells. We next tested their potential in vivo function. PBMC CD8αα+CD3- cells were able to infiltrate inflamed but not normal glomeruli. Isolated PBMC CD8αα+CD3- cells of Lewis rats were transferred into GN-prone Wistar-Kyoto rats at early inflammatory stage (days 17-25). When examined at day 45, both histopathology and blood urea nitrogen/serum creatinine level showed significantly attenuated GN in 80% of cell recipient Wistar-Kyoto rats. Separate experiments verified infiltration of transferred Lewis PBMC CD8αα+CD3- into the glomeruli, accompanied with apoptotic CD4+ T cells in the glomeruli of the recipient Wistar-Kyoto rats. Thus, PBMC CD8αα+CD3- cells of Lewis rats were able to terminate ongoing autoimmune inflammation in the glomeruli.

[Influence of sulfur-fumigated Paeoniae Radix Alba on contents of ten indicative components in Guizhi Decoction].

OBJECTIVE: To investigate the influence of sulfur-fumigated Paeoniae Radix Alba on the contents of main constituents in Guizhi Decoction. METHODS: HPLC was applied to the simultaneous determination and comparative analysis of ten main indicative components in Guizhi Decoction contained sun-dried and sulfur-fumigated Paeoniae Radix Alba. The analysis was performed on a Kromasil C18 column (250 mm x 4.6 mm, 5 µm) with the mobile phase consisting of acetonitrile-0.1% aqueous formic acid. The flow rate was 1.0 mL/min and the column temperature was 30 °C. The detection wavelengths were set at 254 nm and 280 nm, respectively. 20 µL was injected for analysis with gradient elution. RESULTS: There were obvious differences existed between the concentrations of ten main indicative components in Guizhi Decoction contained sun-dried and sulfur-fumigated Paeoniae Radix Alba. CONCLUSION: Sulfur-fumigated Paeoniae Radix Alba can influence the main effective constituents contained in Guizhi Decoction in quantity. The absence in the study of prescriptions affected by sulfur-fumigation is filled up through the investigation of the chemical basis of Guizhi Decoction influenced by sulfur-fumigated Paeoniae Radix Alba, and also strong evidences are offered to the further regulation and supervision of sulfur-fumigation in herbal medicines.

Profiling and characterization of volatile components from non-fumigated and sulfur-fumigated Flos Lonicerae Japonicae using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry coupled with chemical group separation.

Flos Lonicerae Japonicae (FLJ) is a popular herb used for many centuries in Traditional Chinese Medicine as a treatment of fever and inflammation. Non-fumigated processing of FLJ has been the traditional approach used in post-harvest preparation of the commodity for commercial use. However, in recent years, natural drying processing of FLJ has been replaced by sulfur-fumigation for efficiency and pest control. Sulfur-fumigation can induce changes in the volatile compounds of the herb, altering its medicinal properties. A comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF/MS) method was established for the resolution and determination of volatile components in non-fumigated and sulfur-fumigated FLJ. In this paper, analysis of the volatile oils in non-fumigated and sulfur-fumigated (including lab-prepared sulfur-fumigated and industrial sulfur-fumigated) FLJ was performed using GC×GC-TOF/MS. Seventy-three representative volatile components were identified, including furans, alkalies, acids, aldehydes, ketones, alcohols, terpenes, esters, and others, as the main components of FLJ volatile oils. The proposed method was successfully applied for rapid and accurate quality evaluation of FLJ and its related medicinal materials and preparations.

[Sulfur-fumigation, maintenance method of Chinese herbal medicine-discard or inheritance].

Sulfur-fumigation processing technology is an ancient maintenance method, which plays a certain role in storage and preservation for Chinese herbal medicine. But in recent years, with the further explanation of sulfur-fumigation processing mechanism and more attention to the safety of drugs, such traditional maintenance method of Chinese herbal medicine is now being questioned by more and more people. The authors think we should have selective inheritance rather than abslute discard to this ancient processing technology after reviewing the literatures published in recent 20 years, and some suggestions are also put forward, which can supply some references for related drug supervision departments.

[Quick identification and discrimination of sun-dried and sulfur-fumigated cimicifugae rhizoma by Fourier transform infrared spectroscopy].

OBJECTIVE: To develop a method for quick identification of sun-dried and sulfur-fumigated Cimicifugae Rhizoma by Fourier transform infrared spectroscopy (FTIR). METHODS: The alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma were analyzed and compared by FTIR combined with second derivative infrared spectroscopy. RESULTS: FTIR spectra showed that there were some differences in the positions of infrared absorption peaks and the relative intensities in the alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma, and the second derivative IR spectra clearly enhanced the spectral resolution of their differences. FTIR spectra showed that the new absorption peaks of Cimicifugae Rhizoma appeared and a part of original absorption peaks disappeared after sulfur-fumigation in aqueous extracts, while a lot of new absorption peaks appeared and the intensities of almost all absorption peaks significantly decreased after sulfur-fumigation in alcoholic extracts. Second derivative IR spectra showed that both sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by water differed significantly from each other ranging from about 3 950 to 3 940 cm(-1), 3 850 to 3 800 cm(-1), 1 800 to 1 750 cm(-1), as well as from 1 400 to 1 350 cm(-1); Differences also existed between sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by ethanol ranging from about 3 980 to 3 960 cm(-1), 3 850 to 3 800 cm(-1), and 1 500 to 1 460 cm(-1). CONCLUSION: The FTIR method combined with the second derivative IR spectrum can be used to analyze and distinguish sun-dried and sulfur-fumigated Cimicifugae Rhizoma quickly and accurately. The developed method provides an efficient approach for the quality control of Chinese herbal medicines with its simplicity and strong specificity.

The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation.

Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.

Moxibustion plus Acupuncture for the Treatment of Poststroke Shoulder Pain: A Randomized Controlled Pilot Study.

BACKGROUND: In China, 45% of stroke patients suffer from poststroke shoulder pain, which brings about many obstacles to further rehabilitation. To date, there have been a few studies evaluating the effects of acupuncture or massage in treating poststroke shoulder pain, and good effects have been shown. However, better clinical treatments are still needed. OBJECTIVE: To explore a more effective treatment for poststroke shoulder pain, the clinical effects of moxibustion plus acupuncture were assessed. METHODS: Sixty patients were randomly divided into the control and intervention groups. The control group received a standard stroke treatment protocol including acupuncture, and the intervention group was given moxibustion combined with acupuncture. The visual analogue scale (VAS), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer motor assessment, Barthel Index, and 17-item Hamilton Rating Scale for Depression (HAMD-17) were applied, and differences were analyzed. RESULTS: After 4 weeks of treatment, compared with the control group, the intervention group demonstrated significant improvement in Fugl-Meyer motor assessment and HAMD-17 (both p < 0.01) as well as in the VAS, NIHSS, and Barthel Index (all p < 0.05). CONCLUSION: Moxibustion plus acupuncture treatment can alleviate poststroke shoulder pain, improve upper limb motor function and the ability to perform activities of daily living, and relieve patients' depression.

The database of eye-movement measures on words in Chinese reading.

Eye movements are one of the most fundamental behaviors during reading. A growing number of Chinese reading studies have used eye-tracking techniques in the last two decades. The accumulated data provide a rich resource that can reflect the complex cognitive mechanisms underlying Chinese reading. This article reports a database of eye-movement measures of words during Chinese sentence reading. The database contains nine eye-movement measures of 8,551 Chinese words obtained from 1,718 participants across 57 Chinese sentence reading experiments. All data were collected in the same experimental environment and from homogenous participants, using the same protocols and parameters. This database enables researchers to test their theoretical or computational hypotheses concerning Chinese reading efficiently using a large number of words. The database can also indicate the processing difficulty of Chinese words during text reading, thus providing a way to control or manipulate the difficulty level of Chinese texts.