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Objective: Leukodystrophies are a diverse group of rare inherited disorders that affect the white matter of the central nervous system with a wide phenotypic spectrum. We aimed to characterize the clinical and genetic features of leukodystrophies in a central‐southern Chinese cohort. Methods: A cohort of 16 Chinese probands with leukodystrophy was recruited and performed genetic analysis by targeted panels or whole‐exome sequencing. Further functional analysis of identified mutations in the colony stimulating factor 1 receptor (CSF1R) gene was explored. Results: A total of eight pathogenic variants (3 novel, 5 documented) were identified in genes including AARS2, ABCD1, CSF1R, and GALC. Common symptoms of leukodystrophy such as cognitive decline, behavioral symptoms, bradykinesia, and spasticity were observed in mutation carriers as well as other rare features (e.g., seizure, dysarthric, and vision impairment). Overexpressing CSF1R mutants p.M875I and p.F971Sfs*7 in vitro showed pronounced cleavage CSF1R and suppressed protein expression, respectively, and reduced transcripts of both mutants were observed. CSF1 treatment revealed deficient and suppressed CSF1R phospho‐activation with the mutants. In contrast to the plasma membrane and endoplasmic reticulum (ER) localized wild‐type CSF1R, M875I mutant showed much less membrane association and greater detainment in the ER, whereas F971Sfs*7 mutation led to aberrant non‐ER localization. Both mutations caused suppressed cell viability, which was partially resulted from deficient/suppressed CSF1R‐ERK signaling. Interpretation: In summary, our findings expand the mutation spectrum of these genes in leukodystrophies. Supported by in vitro validation of the pathogenicity of heterozygous CSF1R mutations, our data also provide insights into the pathogenic mechanisms of CSF1R‐related leukodystrophy. [ABSTRACT FROM AUTHOR]

Classical molecular dynamics (MD) simulations were used to study the separation of carbon dioxide from methane by three formulations of the deep eutectic solvent (DES) ethaline (choline chloride: ethylene glycol at 1:2, 1:4, and 1:8 molar ratios), confined inside graphite and titania (rutile) slit pores of two different pore widths, 2 and 5 nm. In addition, equivalent DES systems in the bulk were studied, which can also be viewed as a model supported DES membrane with μm‐sized pores. Our results indicate that variations in the ratio of ethylene glycol, which in turn affect the interactions of all DES species with the gas molecules and the different pore walls, plus confinement effects resulting from varying the pore sizes, can affect the gas separation performance of these systems in complex ways. The highest permselectivities (~20), computed as the product of the diffusivity and solubility selectivities, are observed for 1:2 ethaline in a 5 nm graphite pore, followed by the 1:4 DES in a 5 nm graphite pore, 1:2 ethaline in a 2 nm graphite pore, and the 1:8 bulk DES. In bulk systems, all three selectivities reach their highest values for 1:8 ethaline. When the DESs are confined in the nanopores, the solubility selectivity for most systems improves compared to the equivalent bulk systems, with the graphite pores having the largest solubility selectivities for any given ethylene glycol ratio. In contrast, the diffusivity selectivities in confined systems tend to be similar to the values observed in the bulk DESs. Interaction energies and local density profiles were used to rationalize absorption and diffusivity of gases in our systems. Confining ethaline in graphite and rutile nanopores tends to weaken the CO2‐ethylene glycol and CO2‐cation interactions compared to the values observed in equivalent bulk ethaline systems, which also affect the local density profiles. Our results confirm that variations in ethylene glycol ratio, pore size, and pore wall material can lead to significant changes in gas separation performance. Other porous matrices, for example, nanoporous polymer formulations and graphene oxides, should be considered in follow‐up studies as they may lead to significant improvements in gas separation performance as compared to the bulk DES. [ABSTRACT FROM AUTHOR]

Surgical resection of lesions and closed‐loop suppression are the two main treatment options for patients with refractory epilepsy whose symptoms cannot be managed with medicines. Unfortunately, failures in foci localization and seizure prediction are constraining these treatments. Electrical impedance tomography (EIT), sensitive to impedance changes caused by blood flow or cell swelling, is a potential new way to locate epileptic foci and predict seizures. Animal validation is a necessary research process before EIT can be used in clinical practice, but it is unclear which among the many animal epilepsy models is most suited to this task. The selection of an animal model of epilepsy that is similar to human seizures and can be adapted to EIT is important for the accuracy and reliability of EIT research results. This study provides an overview of the animal models of epilepsy that have been used in research on the use of EIT to locate the foci or predict seizures; discusses the advantages and disadvantages of these models regarding inducement by chemical convulsant and electrical stimulation; and finally proposes optimal animal models of epilepsy to obtain more convincing research results for foci localization and seizure prediction by EIT. The ultimate goal of this study is to facilitate the development of new treatments for patients with refractory epilepsy. This article is categorized under:Neuroscience > Clinical NeurosciencePsychology > Brain Function and Dysfunction [ABSTRACT FROM AUTHOR]

Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug–drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh‐performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the Km values were 18.9 and 36.4 μM and the Vmax values were 0.02 and 0.20 μM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC50 values of 2.63, 3.03 and 6.51 μM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC50 values of 1.48, 11.87 and 14.16 μM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug–drug interactions by affecting the activities of CYP3A4 and 2D6. [ABSTRACT FROM AUTHOR]

Aspen Plus® simulations using the Peng‐Robinson (PR‐EOS) and the COSMO‐SAC models were performed to study absorption power cycles (APCs) using mixtures of R‐134a with two ionic liquids, [C2C1im][Tf2N] or [C6C1im][Tf2N], and compared against an R‐134a organic Rankine cycle (ORC) operating under similar conditions. The PR‐EOS results were in agreement with calculations from a PR model fitted to the R‐134a + IL experimental phase equilibrium data. The APCs have similar efficiencies and outperform the ORC by 3%–46%, with the largest differences observed when operating with lower grade (lower TH) heating sources, lower quality cooling (higher TL), and lower subcooling in the pump inlet stream. The PR‐EOS and the Conductor‐like Screening Model Segment Activity Coefficient (COSMO‐SAC) results follow similar trends, but numerical discrepancies are observed in the cycle efficiencies and stream flow rates and compositions due to differences in solubilities and enthalpy changes between both models, suggesting that improvements are needed to increase the accuracy of COSMO‐SAC for these systems. [ABSTRACT FROM AUTHOR]

Efficient optical coupling between nano‐ and macroscale areas is strongly suppressed by the diffraction limit. This work presents a possible solution to this fundamental problem via the experimental fabrication, characterization, and comprehensive theoretical analysis of structures referred to as "photonic funnels." The funnels represent a novel composite material platform that combines hyperbolic dielectric response with geometry‐assisted optical confinement. Experimentally, funneling of mid‐infrared light through openings with diameters as small as 1/25th of the free space wavelength (λ0) is demonstrated. By analyzing the optical response of the funnels, as fabricated, both confinement of mid‐infrared radiation to the λ0/25 areas and efficient outcoupling of light from deep subwavelength areas are confirmed. [ABSTRACT FROM AUTHOR]

We study a noisy graph isomorphism problem, where the goal is to perfectly recover the vertex correspondence between two edge‐correlated graphs, with an initial seed set of correctly matched vertex pairs revealed as side information. We show that it is possible to achieve the information‐theoretic limit of graph sparsity in time polynomial in the number of vertices n. Moreover, we show the number of seeds needed for perfect recovery in polynomial‐time can be as low as nϵ in the sparse graph regime (with the average degree smaller than nϵ) and Ω(logn) in the dense graph regime, for a small positive constant ϵ. Unlike previous work on graph matching, which used small neighborhoods or small subgraphs with a logarithmic number of vertices in order to match vertices, our algorithms match vertices if their large neighborhoods have a significant overlap in the number of seeds. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation. [ABSTRACT FROM AUTHOR]