Analgesic Mechanism of Dexmedetomidine and Esketamine in Rats with Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) is usually caused by external direct or indirect factors, and with a high morbidity and mortality rate. The aim of this study was to observe the effects of Dexmedetomidine (DEX) combined with Esketamine (ESK) on pain behavior and potential analgesic mechanisms in rats with SCI. The goal was to provide a reliable multimodal analgesic medication regimen for SCI. METHODS: Thirty rats were divided into five groups with six rats in each group: Sham group, SCI group, DEX group, ESK group, and DEX+ESK group. The SCI model in rats was constructed, and the motor function of hind limbs of rats was measured using Basso Beattie Bresnahan (BBB) locomotor rating scale and inclined plate test. The levels of interleukin 18 (IL-18), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the spinal cord were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of substance P (SP), neurokinin-1 receptor (NK-1R), B cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) in the rats' spinal cord were measured by Western blot assay. The viability of spinal astrocytes was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: After 7 days, the BBB scores were significantly higher in the DEX, ESK, and DEX+ESK groups compared to the SCI group (p < 0.01). Additionally, the DEX+ESK group had significantly higher scores than both the DEX and ESK groups (p < 0.01). The maximum angle of the DEX (p < 0.05), ESK (p < 0.05), and DEX+ESK groups (p < 0.01) were higher than the SCI group, and the maximum angle of DEX+ESK group was higher than DEX and ESK groups (p < 0.05). The levels of IL-18, IL-1ß, and TNF-α in the DEX, ESK, and DEX+ESK groups were lower than the SCI group (p < 0.01), while the DEX+ESK group had significantly lower IL-18, IL-1ß, and TNF-α levels than the DEX and ESK groups (p < 0.01). The levels of SP (p < 0.01) and NK-1R (p < 0.05) were lower in the DEX, ESK, and DEX+ESK groups compared to the SCI group, and the levels of SP and NK-1R were lower in the DEX+ESK group compared to the DEX and ESK groups (p < 0.01). The DEX and ESK groups suppressed the activity of spinal astrocytes (p < 0.01), however, the DEX+ESK group had larger effects on spinal astrocytes than the ESK group (p < 0.05). CONCLUSIONS: Treatment using DEX combined with ESK improves the motor function, inhibits inflammation and astrocyte activity, and exerts analgesic effects on rats with SCI. These findings can serve as a reference for the selection of multi-modal analgesics.

"Brain age" predicts disability accumulation in multiple sclerosis.

OBJECTIVE: Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well-developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of "brain age" analysis on disability in MS using a large, real-world dataset. METHODS: Brain age analysis is predicated on the over-estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset (>13,000 imaging sessions from >6,000 individual MS patients). Effects of MS, MS disease course, disability, lesion burden, and DMT efficacy were assessed using linear mixed effects models. RESULTS: MS was associated with advanced predicted brain age cross-sectionally and accelerated brain aging longitudinally in all techniques. While MS disease course (relapsing vs. progressive) did contribute to advanced brain age, disability was the primary correlate of advanced brain age. We found that advanced brain age at study enrollment predicted more disability accumulation longitudinally. Lastly, a more youthful appearing brain (predicted brain age less than actual age) was associated with decreased disability. INTERPRETATION: Brain age is a technically tractable and clinically relevant biomarker of disease pathology that correlates with and predicts increasing disability in MS. Advanced brain age predicts future disability accumulation.

Spatiotemporal evolution of water ecological footprint based on the emergy-spatial autocorrelation method.

To quantify and analyze the human demand for water resources and the available supply of water resource systems, this study combined emergy analysis and spatial autocorrelation analysis to establish a quantification and analysis system for water ecological footprint (WEF). First, the emergy theory of ecological economics and WEF were combined to propose an emergy quantification method for WEF and water ecological carrying capacity (WEC). Based on the spatial autocorrelation method, three-dimensional ecological footprint indicators (footprint size and depth) were introduced to analyze the spatial correlation and spatial aggregation of capital flow occupation and capital stock consumption in the water resource system. Using the Yellow River Basin (YRB) as the study area to verify the applicability of the WEF quantification and analysis system based on the emergy-spatial autocorrelation method, the following results were obtained. (1) From 2003 to 2018, the per capita WEF of the YRB generally showed a slow growth trend. (2) Compared to the upper and lower reaches of the YRB, the middle reaches had a higher WEF, and the WEC of the YRB was generally high in the west and low in the east. (3) Utilization of the water resources capital in the basin was generally unsustainable. It is necessary to take measures to promote rational allocation and efficient utilization of water resources for the coordinated development of society, the economy, and the environment in the YRB. (4) The emergy-spatial autocorrelation method is applied to basin/region water sustainability studies for decision makers.

Cross-Sectional and Longitudinal Associations Among Children's Interpersonal Trust, Reputation for Trustworthiness, and Relationship Closeness.

Interpersonal trust plays a crucial role in the formation and maintenance of social relationships. The present cross-sectional and longitudinal research examines the development of interpersonal trust judgments with reference to (1) the trustee's reputation for trustworthiness, and (2) the nature of the trustor's relationship closeness with the trustee. There were 194 7- to 13-year-olds who participated in the first wave of the study, and 107 of those individuals also participated in two subsequent waves across a 2-year period. Both cross-sectional and longitudinal results showed that with age, reputation for trustworthiness becomes less important and relationship closeness become more important. We also found that relationship closeness played a greater role in interpersonal trust evaluations for girls than for boys. These findings indicate that the way children make trust evaluations becomes increasingly relationship-specific over time and is more relationship-specific for girls than for boys.

Spatially Graded Millimeter Sized Mo1-xWxS2 Monolayer Alloys: Synthesis and Memory Effect.

The band gap engineering of two-dimensional (2D) transition metal dichacogenides (TMDs) could significantly broaden their applications, especially in electronics and optoelectronics. Alloying is a more effective approach to synthesize 2D ternary TMD materials with tunable bandgaps by regulating the compositions. Whether the alloying could induce memory effects is of interest as a scientific problem and worthy to be studied. A thermal evaporation-assisted chemical vapor deposition (CVD) method was proposed to grow millimeter size gradient alloyed monolayer Mo1-xWxS2. This method reveals a promising and universal methodology for the development of gradient alloyed TMDs because of the precise controlling of each precursor. The synthesized Mo1-xWxS2 monolayer crystal has a gradient composition with x ranging from 0.1 to 1. The W and Mo atoms homogeneously alloyed with random distribution in the Mo1-xWxS2 monolayer. As reported, the deep energy levels induced by sulfur vacancies can be effectively suppressed to shallow energy levels by alloying TMDs. The series distribution of the shallow energy levels in the band of the graded alloy semiconductor can act as multiple charge trapping states, which leads to obvious memory effects in the device. These results present a new opportunity for memory devices and related applications.

Malyngamide F Possesses Anti-Inflammatory and Antinociceptive Activity in Rat Models of Inflammation.

Objective: Inflammation and pain are involved in the pathophysiology of various clinical conditions. This investigation aims to probe the analgesic and anti-inflammatory activity of Maltoamide F. Methods: The possible toxicity of Maltoamide F was evaluated by an acute toxicity test. To assess the anti-inflammatory and antinociceptive effects of Maltoamide F on rats, the models of carrageenan-caused paw edema, xylene-induced ear edema, arachidonic-acid- (AA-) induced ear edema, formalin-caused plantar edema, and cotton-pellet-induced granuloma were established. Levels of TNF-α, PGE-2, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Results: Maltoamide F was safe at oral doses of 1-10 mg/kg for rats. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) notably reduced carrageenan-induced edema percentage of paws in rats and decreased levels of PGE-2, IL-6, and TNF-α in homogenates of foot tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced levels of PGE-2, IL-6, and TNF-α in foot tissues of formalin-induced rats. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) repressed AA-induced increase of ear thickness in rats and reduced levels of PGE-2, IL-6, and TNF-α in homogenates of ear tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced xylene-induced weight of ear edema in rats and reduced levels of PGE-2, IL-6, and TNF-α in homogenates of ear tissues. Maltoamide F (1 mg/kg, 5 mg/kg, and 10 mg/kg) reduced levels of PGE-2, IL-6, and TNF-α in homogenates of cotton ball granuloma of cotton-pellet-induced rats. Conclusions: Maltoamide F possessed anti-inflammatory and analgesic activity in inflammatory models of rats.

Synthesis of large-area monolayer and few-layer MoSe2 continuous films by chemical vapor deposition without hydrogen assistance and formation mechanism.

Two dimensional (2D) MoSe2 with a layered structure has attracted extensive research due to its excellent electronic and optical properties. The controlled synthesis of large-scale and high-quality MoSe2 is highly desirable but still remains challenging. Ambient pressure chemical vapor deposition (APCVD) is an excellent method for the synthesis of 2D materials but the inevitable use of hydrogen during the growth and the easy formation of cracks in the ultrathin films still need to be solved. In the present work, we reported the synthesis of large-area continuous MoSe2 films with different layers by the APCVD method without the assistance of hydrogen on SiO2/Si substrates just by raising the reaction temperature of Se. The synthesized continuous MoSe2 films can reach several centimeters, which can be seen clearly by naked eyes, and, more importantly, the size of the monolayer film can reach up to 3 mm. The morphology, structural characteristics, and optical properties of the synthesized MoSe2 films have been investigated, demonstrating good performance and high crystallinity of the films. Raman spectra give the empirical expression of the frequency difference between E2g1 and A1g dependence of the layer number (N = 1-10 L) for CVD grown MoSe2, which is useful in layer number identification. Further, the formation mechanism of the MoSe2 continuous film is of interest as a fundamental scientific problem and needs to be studied. We proposed the wing model, boundary layer theory, and diffusion theory to account quantitatively for the formation behavior of the MoSe2 film. The presented facile growth method and theoretical model are useful to synthesize other ultrathin transition metal dichalcogenide films and understand the formation behaviors of the systems.

REGION SPECIFIC AUTOMATIC QUALITY ASSURANCE FOR MRI-DERIVED CORTICAL SEGMENTATIONS.

Quality control (QC) is a vital step for all scientific data analyses and is critically important in the biomedical sciences. Image segmentation is a common task in medical image analysis, and automated tools to segment many regions from human brain MRIs are now well established. However, these methods do not always give anatomically correct labels. Traditional methods for QC tend to reject statistical outliers, which may not necessarily be inaccurate. Here, we make use of a large database of over 12,000 brain images that contain 68 parcellations of the human cortex, each of which was assessed for anatomical accuracy by a human rater. We trained three machine learning models to determine if a region was anatomically accurate (as 'pass', or 'fail') and tested the performance on an independent dataset. We found good performance for the majority of labeled regions. This work will facilitate more anatomically accurate large-scale multi-site research.

Biocompatible and pH-Responsive Colloidal Surfactants with Tunable Shape for Controlled Interfacial Curvature.

Molecular-surfactant-stabilized emulsions are susceptible to coalescence and Ostwald ripening. Amphiphilic particles, which have a much stronger anchoring strength at the interface, could effectively alleviate these problems to form stable Pickering emulsions. Herein, we describe a versatile method to fabricate biocompatible amphiphilic dimer particles through controlled coprecipitation and phase separation. The dimer particles consist of a hydrophobic PLA bulb and a hydrophilic shellac-PEG bulb, thus resembling nonionic molecular surfactants. The size and diameter ratio of the dimer particles are readily tunable, providing flexible control over the water/oil interfacial curvature and thus the type of emulsion. The particle-stabilized emulsions were stable for a long period of time and could be destabilized through a pH-triggered response. The biocompatible amphiphilic dimer particles with tunable morphology and functionality are thus ideal colloidal surfactants for various applications.

Bivariate genomic analysis identifies a hidden locus associated with bacteria hypersensitive response in Arabidopsis thaliana.

Multi-phenotype analysis has drawn increasing attention to high-throughput genomic studies, whereas only a few applications have justified the use of multivariate techniques. We applied a recently developed multi-trait analysis method on a small set of bacteria hypersensitive response phenotypes and identified a single novel locus missed by conventional single-trait genome-wide association studies. The detected locus harbors a minor allele that elevates the risk of leaf collapse response to the injection of avrRpm1-modified Pseudomonas syringae (P = 1.66e-08). Candidate gene AT3G32930 with in the detected region and its co-expressed genes showed significantly reduced expression after P. syringae interference. Our results again emphasize that multi-trait analysis should not be neglected in association studies, as the power of specific multi-trait genotype-phenotype maps might only be tractable when jointly considering multiple phenotypes.

Overproduction of efflux pumps caused reduced susceptibility to carbapenem under consecutive imipenem-selected stress in Acinetobacter baumannii.

PURPOSE: Acinetobacter baumannii is an important pathogen in the nosocomial infections worldwide. Combining with carbapenemases, efflux pumps and outer membrane proteins (OMPs) have been thought to affect the development of carbapenem resistance in A. baumannii. This study aimed to investigate the contributions of different efflux pumps and OMPs in developing carbapenem resistance in a clinical isolate of A. baumannii and reveal the possible mechanism of overproduction of main efflux pumps. PATIENTS AND METHODS: In this study, an imipenem-susceptible clinical isolate was identified as A. baumannii and named SZE. Several common carbapenemases were detected by polymerase chain reaction (PCR). Imipenem-selected mutants were selected from SZE by serial subcultivations on Mueller-Hinton agar, and the minimum inhibitory concentration (MIC) was detected. Gene expressions of four families of efflux pumps, five OMPs, and blaOXA-51 were determined by reverse transcription quantitative PCR, and comparisons were made between SZE strain and the imipenem-selected mutants. The adeRS system in SZE and its mutant was sequenced and aligned. RESULTS: Under consecutive imipenem-selected stress, the MIC to imipenem increased gradually from 0.125 µg/mL to 8 µg/mL. The effect of resistance inducement was almost neutralized when treated with an efflux pump inhibitor. The expression of efflux pumps, adeB, adeG, and adeJ, was increased by 6.9-, 4.0-, and 2.1-fold in mutants, respectively, compared to SZE. A single mutation (G to A) at position 58 was detected in the regulatory adeRS system and possibly upregulated the adeB expression, and then affected the carbapenem resistance in A. baumannii strains. CONCLUSION: In conclusion, under consecutive imipenem-selected stress in vitro, A. baumannii strain evolved the ability to reduce susceptibility to a variety of antimicrobials by overproduction of efflux pumps. Especially, the resistance-nodulation-cell division super family and a nucleotide mutant in adeRS regulating system caused the overexpression of adeABC.