Exploring the neuroprotective role of artesunate in mouse models of anti-NMDAR encephalitis: insights from molecular mechanisms and transmission electron microscopy.

BACKGROUND: The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. METHODS: Adult female mice aged 8-10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. RESULTS: In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART's therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. CONCLUSIONS: At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

Different metal (Mn, Fe, Co, Ni, and Zr) decorated Cu/CeO2 catalysts for efficient CO oxidation in a rich CO2/H2 atmosphere.

In this work, CuM/CeO2 (M = Mn, Fe, Co, Ni, and Zr) catalysts with a low Cu content of 1 wt% were purposely designed and prepared using the co-impregnation method. The samples were characterized using various techniques (TG-DTA, XRD, N2-adsorption/desorption measurements, H2-TPR, XPS and Raman spectroscopy) and CO preferential oxidation (CO-Prox) under H2/CO2-rich conditions was performed. The results have shown that enhanced catalytic performance was achieved upon the introduction of Mn, Co and Ni, and little impact was observed with Zr doping, but Fe showed a negative effect, as compared with the Cu/CeO2 catalyst. Characterization data revealed that the M doping strongly changed the surface composition, revealing the decreased Cu/Ce ratios on the surface, which could be accounted for by the formation of more M/Cu-O-Ce solid solution, or strong Cu-M interactions. When Mn was used, the obtained CuMn/CeO2 catalyst revealed the highest concentration of the oxygen vacancies and Ce3+ ions, which could be correlated well with its superior catalytic performance. Compared with the Cu/CeO2 catalyst, the CO conversion rate increased by 24.7% at a low temperature of 90 °C over the CuMn/CeO2 catalyst. At 130 °C, the maximum CO conversion was 94.7% and the CO2 selectivity was 78.9%. Conversely, the Fe doped Cu/CeO2 catalyst demonstrated the poorest catalytic activity, which was due to the blockage effect of Fe species on Cu showing a high Fe/Cu ratio of 1.9 on the surface.

Effect of a Thermosensitive Hydroxybutyl Chitosan Hydrogel on Postoperative Sequalae and Quality of Life After Impacted Mandibular Third Molar Extraction.

BACKGROUND: Third molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PURPOSE: The study purpose was to measure and compare differences in pain, swelling, trismus, wound healing, and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. STUDY DESIGN, SETTING, SAMPLE: This study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. PREDICTOR VARIABLE: The predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiological saline) side. MAIN OUTCOME VARIABLE: The primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening, were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. COVARIATES: The covariates included age, sex, and operation time. ANALYSES: The Shapiro‒Wilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P < .05. RESULTS: The study included 60 patients (mean age: 25.81 ± 4.91; 23 (38%) males, 37 (62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < .001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < .001), maximal incisional opening (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P < .001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P < .001), and swelling (6.86 ± 0.70 mm, 7.15 ± 0.80 mm, day 3, P = .006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ± 2.14, day 3, P < .001). CONCLUSION AND RELEVANCE: The application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative QOL.

Chemical Mineralization of AMD into Schwertmannite Fixing Iron and Sulfate Ions by Structure and Adsorption: Paving the Way for Enhanced Mineralization Capacity.

Abundant iron and sulfate resources are present in acid mine drainage. The synthesis of schwertmannite from AMD rich in iron and sulfate could achieve the dual objectives of resource recovery and wastewater purification. However, schwertmannite cannot emerge spontaneously due to the Gibbs free energy greater than 0. This results in the iron and sulfate in AMD only being able to use the energy generated by oxidation in the coupling reaction to promote the formation of minerals, but this only achieved partial mineralization, which limited the remediation of AMD through mineralization. In order to clarify the mechanism of iron and sulfate removal by the formation of schwertmannite in AMD, kinetic and thermodynamic parameters were crucial. This work used H2O2 oxidation of Fe2+ as a coupling reaction to promote the formation of schwertmannite from 64.4% of iron and 15.7% of sulfate in AMD, and determined that 99.7% of the iron and 89.9% of sulfate were immobilized in the schwertmannite structural, and only a small fraction was immobilized by the adsorption of schwertmannite, both of which were consistent with second-order kinetics models. The thermodynamic data suggested that reducing the concentration of excess sulfate ions or increasing the energy of the system may allow more iron and sulfate to be immobilized by forming schwertmannite. Experimental verification using the reaction of potassium bicarbonate with the acidity in solution to increase the energy in the system showed that the addition of potassium bicarbonate effectively promoted the formation of schwertmannite from Fe3+ and SO42-. It provided a theoretical and research basis for the direct synthesis of schwertmannite from Fe3+ and SO42- rich AMD for the removal of contaminants from water and the recovery of valuable resources.

Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

Formation of superoxide and ozone-like species on Cu doped CeO2(111) and their CO oxidation reactivity: a DFT study.

The adsorption of O2 on Cu/CeO2(111) and the CO oxidation reactivity of the formed oxygen species were studied using the DFT method. The results showed that superoxide species (O2δ-), which directly interacted with Cu, formed when O2 adsorbed on the surface oxygen vacancies, while O2 adsorbed on the subsurface oxygen vacancies gave rise to ozone-like O3δ- species by combining with the nearest surface lattice oxygen (O1). PDOS showed that hybridization of the 2p orbitals between O2 and O1 formed a delocalized π bond, confirming the formation of O3δ-. For O2δ-, electrons on Cu and O1 transferred to O2 while the charge of Ce remained unchanged. However, for O3δ-, the transferred electrons were mainly from O1, and partially from O2, Ce1 and Ce2. It was very interesting that Cu also received a few electrons in the latter case. Compared with CO directly adsorbed on lattice oxygen, the two oxygen species were active for CO oxidation, forming CO2 or carbonates, and higher absolute adsorption energy was obtained with the interaction between CO and O3δ-. The findings of this study provide new insight on the CO oxidation reaction mechanism, facilitating an in-depth understanding of Cu-doped CeO2 catalysts.

Racial disparities in conditional survival of patients with bladder cancer: a population-based study.

BACKGROUND: Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. RESULTS: The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. CONCLUSIONS: While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Stochastic Propagation of Fatigue Cracks in Welded Joints of Steel Bridge Decks under Simulated Traffic Loading.

The fatigue cracking of orthotropic steel bridge decks (OSDs) is a difficult problem that hinders the development of steel structures. The most important reasons for the occurrence of fatigue cracking are steadily growing traffic loads and unavoidable truck overloading. Stochastic traffic loading leads to the random propagation behavior of fatigue cracks, which increases the difficulty of the fatigue life evaluations of OSDs. This study developed a computational framework for the fatigue crack propagation of OSDs under stochastic traffic loads based on traffic data and finite element methods. Stochastic traffic load models were established based on site-specific, weigh-in-motion measurements to simulate fatigue stress spectra of welded joints. The influence of the transverse loading positions of the wheel tracks on the stress intensity factor of the crack tip was investigated. The random propagation paths of the crack under stochastic traffic loads were evaluated. Both ascending and descending load spectra were considered in the traffic loading pattern. The numerical results indicated that the maximum value of KI was 568.18 (MPa·mm1/2) under the most critical transversal condition of the wheel load. However, the maximum value decreased by 66.4% under the condition of transversal moving by 450 mm. In addition, the propagation angle of the crack tip increased from 0.24° to 0.34°-an increase ratio of 42%. Under the three stochastic load spectra and the simulated wheel loading distributions, the crack propagation range was almost limited to within 10 mm. The migration effect was the most obvious under the descending load spectrum. The research results of this study can provide theoretical and technical support for the fatigue and fatigue reliability evaluation of existing steel bridge decks.

CXCL7 aggravates the pathological manifestations of neuromyelitis optica spectrum disorder by enhancing the inflammatory infiltration of neutrophils, macrophages and microglia.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). Our previous study indicated that neutrophil-related chemokine CXCL7 is elevated in the cerebrospinal fluid (CSF) of NMOSD patients. To study the potential function of CXCL7 during NMOSD, we measured the chemokines level in CSF of follow-up patients, and established three NMOSD mouse models by injecting aquaporin4 (AQP4)-IgG. Astrocytes loss, inflammatory infiltration, and myelin sheath damage were detected by western blot or immunofluorescence analysis. We found CXCL7 was significantly increased in the serum and CSF of model mice, and exogenous CXCL7 caused serious astrocyte injury, obvious microglia activation, and increased infiltration of neutrophils and macrophages, resulting in secondary demyelination. Consistently, knocking down the CXCL7 reversed the loss of AQP4, and attenuated the inflammatory response. Collectively, our data indicates that CXCL7 aggravates NMOSD-like pathological damage to astrocytes and myelin sheath mainly via promoting neuroinflammatory response.

Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models.

Currently, there is increasing attention on the regulatory effects of cannabidiol (CBD) on the inflammatory response and the immune system. However, the mechanisms have not yet been completely revealed. Mitofusin 2 (Mfn2) is a mitochondrial fusion protein involved in the inflammatory response. Here, we investigated whether Mfn2 confers the anti-inflammatory effects of CBD. We found that treatment with CBD decreased the levels of tumor necrosis factor α, interleukin 6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and ionized calcium-binding adaptor molecule-1 (Iba1) in lipopolysaccharide (LPS)-challenged microglia. CBD also significantly suppressed the increase in reactive oxygen species (ROS) and the decline of mitochondrial membrane potential in BV-2 cells subjected to LPS. Interestingly, CBD treatment increased the expression of Mfn2, while knockdown of Mfn2 blocked the effect of CBD. By contrast, overexpression of Mfn2 reversed the increase in the levels of iNOS, COX-2, and Iba1 induced by Mfn2 small interfering RNA. In mice challenged with LPS, we found that CBD ameliorated the anxiety responses and cognitive deficits, increased the level of Mfn2, and decreased the expression of Iba1. Since neuro-inflammation and microglial activation are the common events that are observed in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we treated EAE mice with CBD. Mice that received CBD showed amelioration of clinical signs, reduced inflammatory response, and increased myelin basic protein level. Most importantly, the adeno-associated virus delivery of short hairpin RNA against Mfn2 reversed the protective effects of CBD. Altogether, these results indicate that Mfn2 is an essential immunomodulator conferring the anti-inflammatory effects of CBD. Our results also shed new light on the mechanisms underlying the protective effects of CBD against inflammatory diseases including multiple sclerosis.

A stable and highly luminescent 3D Eu(III)-organic framework for the detection of colchicine in aqueous environment.

The metal-organic framework materials have an important application as sensors. In this work, a microporous three-dimensional (3D) Eu(III)-organic framework (Eu-MOF), [Eu2(3,5-bct)(phen)2(ox)2(H2O)]·H2O, was constructed from 3,5-bis(3'-carboxyphenyl)-1,2,4-triazole (3,5-H2bct), oxalate (ox) and 1,10-phenanthroline (phen) as a luminescent sensor. The free volume was found to be 15.7% per unit volume ignoring the free water molecules. The Eu-MOF showed bright red light due to the emission at 622 nm (5D0 → 7F2 transition) of the Eu(III) with high quantum yield (QY, 52.51%). The Eu-MOF exerted high luminescence stability in common organic solvents as well as aqueous solutions within a wide pH range from 4 to 11. Based on the luminescent Eu-MOF, the sensing behavior for colchicine in the aqueous environment was studied. Highly selective and sensitive detection (LOD = 2.43 × 10-5 mol L-1) of colchicine was observed by the Eu-MOF even in the presence of potential interfering components. The sensing mechanism for colchicine was investigated by experimental and theoretical results. It is worth noting that a film (Film@Eu-MOF) prepared by loading Eu-MOF showed intense characteristic red light emission under UV light. The luminescence color changed immediately from red to colorless when the Film@Eu-MOF came in contact with colchicine. Highly sensitive and rapid detection of colchicine in wastewater was achieved using this Film@Eu-MOF, which could be identified by the naked eye. The experimental results suggest that the synthesized Eu-MOF has potential application as a luminescent sensing material for pollutants in the environmental system.

Static and dynamic disturbance compensation for optical misalignment of large ground-based wide field survey telescope.

For large ground-based telescopes, static and dynamic disturbances would greatly degrade the optical performance. This is especially true for wide field survey telescopes with prime focus optics. The estimation of disturbance effects on large telescopes is becoming increasingly important during the design phase. Therefore, a wide field survey telescope with 2.5 m aperture and 3.5 deg field of view is studied in this research. This telescope is under construction now, and its first light is expected at the beginning of 2023. The estimation method for the optical performance under static and dynamic disturbances in the temporal domain and the active compensation method to improve the optical alignment, are investigated, which is a supplement for the simulation in the frequency domain. First, based on the mechanical model, the optical misalignment is established, where the deviation of the primary mirror is obtained from the length gauges and the deviation of the corrector is computed using the fitting method. Second, a method for compensating the static and dynamic disturbances is proposed, improving the optical performance. This method uses the disturbed primary mirror as the reference, and the corrector is actively controlled to align with it. Finally, a series of experimental tests and numerical simulations is conducted. The results show that the mechanical modeling error is within 10% and the maximum optical misalignment is reduced from 12''/0.27 to 0.2''/0.006mm for static disturbance and from 1.3''/0.03 to 0.4''/0.01mm for dynamic disturbance. Through active compensation, the telescope optical property is greatly improved. The modeling method and the simulation process mentioned in this research can also be used in the other relevant fields.

Digitized Construction of Iontronic Pressure Sensor with Self-Defined Configuration and Widely Regulated Performance.

Flexible pressure sensors are essential components for wearable smart devices and intelligent systems. Significant progress has been made in this area, reporting on excellent sensor performance and fascinating sensor functionalities. Nevertheless, geometrical and morphological engineering of pressure sensors is usually neglected, which, however, is significant for practical application. Here, we present a digitized manufacturing methodology to construct a new class of iontronic pressure sensors with optionally defined configurations and widely modulated performance. These pressure sensors are composed of self-defined electrode patterns prepared by a screen printing method and highly tunable pressure-sensitive microstructures fabricated using 3D printed templates. Importantly, the iontronic pressure sensors employ an iontronic capacitive sensing mechanism based on mechanically regulating the electrical double layer at the electrolyte/electrode interfaces. The resultant pressure sensors exhibit high sensitivity (58 kPa-1), fast response/recovery time (45 ms/75 ms), low detectability (6.64 Pa), and good repeatability (2000 cycles). Moreover, our pressure sensors show remarkable tunability and adaptability in device configuration and performance, which is challenging to achieve via conventional manufacturing processes. The promising applications of these iontronic pressure sensors in monitoring various human physiological activities, fabricating flexible electronic skin, and resolving the force variation during manipulation of an object with a robotic hand are successfully demonstrated.

Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from the amino-terminal domain of the GluN1 subunit.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models. METHODS: This study describes a novel female C57BL/6 mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using an amino terminal domain (ATD) peptide from the GluN1 subunit (GluN1356-385). RESULTS: Twelve weeks after immunization, the immunized mice showed significant memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice decreased the surface NMDAR cluster density in hippocampal neurons which was similar to the effect induced by the anti-NMDAR encephalitis patients' antibodies. Immunization also impaired long-term potentiation at Schaffer collateral-CA1 synapses and reduced NMDAR-induced calcium influx. CONCLUSION: We established a novel anti-NMDAR encephalitis model using active immunization with peptide GluN1356-385 targeting the ATD of GluN1. This novel model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.

Sensitivity and specificity of single and combined clouds analyses compared with quantitative motor unit potential analysis.

INTRODUCTION: Turns-amplitude, number of small segments (NSS)-activity, and envelope-activity clouds are three methods of electromyography (EMG) interference pattern analysis. Our objective was to evaluate the sensitivity and specificity of each individual cloud analysis and combined clouds analysis to compare with that of quantitative motor unit potential (QMUP) analysis. METHODS: A total of 379 muscles from 100 patients were analyzed by both QMUP and clouds analyses. Calculation of sensitivity and specificity was based on the clinical diagnosis as the "gold standard." RESULTS: For discrimination of abnormal vs normal and neuropathic vs non-neuropathic, combined clouds analysis had greater sensitivity than QMUP analysis and any single cloud analysis, but there were no differences in specificity. For discrimination of myopathic vs non-myopathic, combined clouds analysis and single cloud analysis had greater sensitivity than QMUP analysis, but there were no differences in specificity. DISCUSSION: Combined clouds analysis was superior to QMUP and each single cloud analysis for distinguishing normal, myopathic, and neuropathic muscles.

[Portable Pulse Detection System Based on IoT].

Aiming at the current situation of high cost, huge volume, complex operation and difficulty in real application of pulse analyzer, this study designs and implements a portable pulse detection system based on IoT. The design utilizes Raspberry Pi 3B+, STM32 series MCU and cloud server to collect, store, display and recognize pulse signals at CUN, GUAN and CHI. The system is small in size and low in cost, which can be connected with cloud server through network to make full use of resources. The experimental results show that the recognition accuracy of the main feature points of the pulse signal by the portable pulse analyzer is higher than 97%, which has a broad prospect of development and application.

Developing normal number of small segments-activity clouds of the electromyography interference pattern.

BACKGROUND: Number of small segments (NSS) and activity analysis is a mature method for electromyographic automatic interference pattern analysis (IPA), but there are few reports on the application of this technique. Our objective was to establish normal reference values of NSS-activity clouds. METHODS: The NSS and activity data of the sternocleidomastoid, deltoid, biceps brachii (long head), extensor digitorum communis, abductor digiti minimi, vastus medialis, tibialis anterior, and gastrocnemius (lateral head) muscles were obtained from 34 men and 25 women, aged 15-80 years, using concentric needle electrodes. A linear regression of log(NSS) vs log(activity) was performed and the slope, intercept and standard deviation were calculated for each muscle. These variables were transformed back to the original parameters to yield clouds. RESULTS: Normal NSS-activity clouds for the above eight muscles were obtained. CONCLUSIONS: Normal reference values of NSS-activity may facilitate detection of early and mild neurogenic and myogenic abnormalities.

Interleukin-1 receptor associated kinase (IRAK)-M -mediated type 2 microglia polarization ameliorates the severity of experimental autoimmune encephalomyelitis (EAE).

Toll-like receptor 4 (TLR4) play a key role in activating the innate immune system during pathogen recognition. In the pathogenesis of multiple sclerosis (MS), activated TLR4 together with myeloid differentiation primary response gene 88 (MyD88) produce an inflammatory microenvironment that promotes the differentiation of microglia into the M1 phenotype, who plays a key role in the pathogenesis of MS. Interleukin-1 receptor-associated kinase (IRAK)-M is specifically expressed in microglia in central nervous system (CNS) and act as a negative regulator of TLR4-MyD88 signaling pathway. Moreover, previous studies have shown that IRAK-M promotes the differentiation of type 2 microglia; however, its role in MS has not been explored. In the present study, we demonstrated that IRAK-M expression is elevated during EAE, and IRAK-M-/- mice significantly accelerated course and increased severity of disease, accompanied by a visible increase of the M1 microglia infiltrated. In conclusion, these data indicates that IRAK-M significantly improves EAE onset through down-regulation of the TLR4-MyD88 signaling pathway, which finally leads to differentiation of M2 phenotype in the microglia. Our study suggests that IRAK-M may be a potential therapeutic target for the treatment of MS.

Synthesis, microwave spectra, x-ray structure, and high-level theoretical calculations for formamidinium formate.

An efficient synthesis of formamidinium formate is described. The experimental x-ray structure shows both internal and external H-bonding to surrounding molecules. However, in the gas phase, this compound occurs as a doubly hydrogen bonded dimer between formamidine and formic acid. This doubly hydrogen-bonded structure is quite different from the solid state structure. Microwave spectra were measured in the 6-14 GHz range using a pulsed-beam Fourier transform microwave (MW) spectrometer. The two nonequivalent N-atoms exhibit distinct quadrupole coupling. The rotational, centrifugal distortion, and quadrupole coupling constants determined from the spectra have the following values: A = 5880.05(2), B = 2148.7710(2), C = 1575.23473(13), 1.5 χaa (N1) = 1.715(3), 0.5(χbb-χcc) (N1) = -1.333(4), 1.5 χaa (N2) = 0.381(2), 0.25(χbb-χcc) (N2) = -0.0324(2), and DJ = 0.002145(5) MHz. The experimental inertial defect, Δ = -0.243 amu Å2, is consistent with a planar structure. Accurate and precise rotational constants (A, B, and C), obtained from the MW measurements, were closely reproduced, within 1%-2% of the measured values, with the M11 DFT theoretical calculations. Detailed comparison of the measured and calculated A, B, and C rotational constants confirms the planar doubly hydrogen bonded structure. The calculated nitrogen quadrupole coupling strengths of the monomer are quite different from either of the two nitrogen sites of the dimer. The poor agreement between measured and calculated quadrupole coupling strengths shows that the dimer is not locked in the equilibrium structure but is likely undergoing large amplitude vibrational motion of the hydrogen atoms moving between the N and O atoms involved in the hydrogen bonding.

Elevated soluble syndecan-1 levels in neuromyelitis optica are associated with disease severity.

Syndecan-1 (SDC-1) is a transmembrane member that has a profound influence on the resolution of inflammation. Soluble syndecan-1 (sSDC-1) levels have been shown to increase in many inflammatory diseases. However, it remains unknown whether sSDC-1 concentration is elevated in neuromyelitis optica (NMO) and multiple sclerosis (MS) patients. The aims of this pilot study were to investigate the relationship between sSDC-1 and disease severity in NMO and MS and whether sSDC-1 has potential as an effective marker for disease severity. We measured sSDC-1 concentrations by using an enzyme-linked immunosorbent assay (ELISA). NMO patients had significantly higher CSF sSDC-1 levels than MS patients or controls. We also found a positive correlation between the increased CSF sSDC-1 levels and increased severity in NMO disease, but not in MS. In NMO, CSF sSDC-1 concentrations were positively correlated with CSF interleukin (IL)-6, IL-8 and IL-17. Overall, we showed levels of CSF sSDC-1 were higher in NMO patients and had a positive relationship with disease severity of NMO but not with MS. CSF sSDC-1 may be an effective marker of NMO disease severity.