Nitrogen-Doped Carbon Dots Modified Fe-Co Sulfide Nanosheets as High-Efficiency Electrocatalysts toward Oxygen Evolution Reaction.

Developing high-efficiency and stable oxygen evolution reaction (OER) electrocatalysts is an imperative requirement to produce green and clean hydrogen energy. In this work, the FeCoSy /NCDs composite with nitrogen-doped carbon dots (NCDs) modified Fe-Co sulfide (FeCoSy ) nanosheets is prepared by using a facile and mild one-pot solvothermal method. Benefiting from the low crystallinity and the synergistic effect between FeCoSy and NCDs, the optimal FeCoSy /NCDs-3 composite exhibits an overpotential of only 284 mV at 10 mA cm-2 , a small Tafel value of 52.1 mV dec-1 , and excellent electrochemical durability in alkaline solution. Remarkably, unlike ordinary metal sulfide electrocatalysts, the morphology, components, and structure of the FeCoSy /NCDs composite can be well retained after OER test. The NCDs modified FeCoSy composite with excellent electrocatalytic performance provides an effective approach to boost metal sulfide electrocatalysts for practical application.

Rational Design of High-Performance Electrodes Based on Ferric Oxide Nanosheets Deposited on Reduced Graphene Oxide for Advanced Hybrid Supercapacitors.

The core strategy for constructing ultra-high-performance hybrid supercapacitors is the design of reasonable and effective electrode materials. Herein, a facile solvothermal-calcination strategy is developed to deposit the phosphate-functionalized Fe2O3 (P-Fe2O3) nanosheets on the reduced graphene oxide (rGO) framework. Benefiting from the superior conductivity of rGO and the high conductivity and fast charge storage dynamics of phosphate ions, the synthesized P-Fe2O3/rGO anode exhibits remarkable electrochemical performance with a high capacitance of 586.6 F g-1 at 1 A g-1 and only 4.0% capacitance loss within 10 000 cycles. In addition, the FeMoO4/Fe2O3/rGO nanosheets are fabricated by utilizing Fe2O3/rGO as the precursor. The introduction of molybdates successfully constructs open ion channels between rGO layers and provides abundant active sites, enabling the excellent electrochemical features of FeMoO4/Fe2O3/rGO cathode with a splendid capacity of 475.4 C g-1 at 1 A g-1. By matching P-Fe2O3/rGO with FeMoO4/Fe2O3/rGO, the constructed hybrid supercapacitor presents an admirable energy density of 82.0 Wh kg-1 and an extremely long working life of 95.0% after 20 000 cycles. Furthermore, the continuous operation of the red light-emitting diode for up to 30 min demonstrates the excellent energy storage properties of FeMoO4/Fe2O3/rGO//P-Fe2O3/rGO, which provides multiple possibilities for the follow-up energy storage applications of the iron-based composites.

Aspergillus fumigatus Elongator complex subunit 3 affects hyphal growth, adhesion and virulence through wobble uridine tRNA modification.

The eukaryotic multisubunit Elongator complex has been shown to perform multiple functions in transcriptional elongation, histone acetylation and tRNA modification. However, the Elongator complex plays different roles in different organisms, and the underlying mechanisms remain unexplored. Moreover, the biological functions of the Elongator complex in human fungal pathogens remain unknown. In this study, we verified that the Elongator complex of the opportunistic fungal pathogen Aspergillus fumigatus consists of six subunits (Elp1-6), and the loss of any subunit results in similarly defective colony phenotypes with impaired hyphal growth and reduced conidiation. The catalytic subunit-Elp3 of the Elongator complex includes a S-adenosyl methionine binding (rSAM) domain and a lysine acetyltransferase (KAT) domain, and it plays key roles in the hyphal growth, biofilm-associated exopolysaccharide galactosaminogalactan (GAG) production, adhesion and virulence of A. fumigatus; however, Elp3 does not affect H3K14 acetylation levels in vivo. LC-MS/MS chromatograms revealed that loss of Elp3 abolished the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification of tRNA wobble uridine (U34), and the overexpression of tRNAGlnUUG and tRNAGluUUC, which normally harbor mcm5s2U modifications, mainly rescues the defects of the Δelp3 mutant, suggesting that tRNA modification rather than lysine acetyltransferase is responsible for the primary function of Elp3 in A. fumigatus. Strikingly, global proteomic comparison analyses showed significantly upregulated expression of genes related to amino acid metabolism in the Δelp3 mutant strain compared to the wild-type strain. Western blotting showed that deletion of elp3 resulted in overexpression of the amino acid starvation-responsive transcription factor CpcA, and deletion of CpcA markedly reversed the defective phenotypes of the Δelp3 mutant, including attenuated virulence. Therefore, the findings of this study demonstrate that A. fumigatus Elp3 functions as a tRNA-modifying enzyme in the regulation of growth, GAG production, adhesion and virulence by maintaining intracellular amino acid homeostasis. More broadly, our study highlights the importance of U34 tRNA modification in regulating cellular metabolic states and virulence traits of fungal pathogens.

Mycolicibacterium arseniciresistens sp. nov., isolated from lead-zinc mine tailing, and reclassification of two Mycobacterium species as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov.

A Gram-positive, acid-fast, aerobic, rapidly growing and non-motile strain was isolated from lead-zinc mine tailing sampled in Lanping, Yunnan province, Southwest China. 16S rRNA gene sequence analysis showed that the most closely related species of strain KC 300T was Mycolicibacterium litorale CGMCC 4.5724T (98.47 %). Additionally, phylogenomic and specific conserved signature indel analysis revealed that strain KC 300T should be a member of genus Mycolicibacterium, and Mycobacterium palauense CECT 8779T and Mycobacterium grossiae DSM 104744T should also members of genus Mycolicibacterium. The genome size of strain KC 300T was 6.2 Mb with an in silico DNA G+C content of 69.2 mol%. Chemotaxonomic characteristics of strain KC 300T were also consistent with the genus Mycolicibacterium. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values, as well as phenotypic, physiological and biochemical characteristics, support that strain KC 300T represents a new species within the genus Mycolicibacterium, for which the name Mycolicibacterium arseniciresistens sp. nov. is proposed, with the type strain KC 300T (=CGMCC 1.19494T=JCM 35915T). In addition, we reclassified Mycobacterium palauense and Mycobacterium grossiae as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov., respectively.

Surface Reconstruction for Selective Oxidation of Tetrahydroisoquinoline.

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

Assessment of cognitive dysfunction and its influencing factors after acute ischemic stroke.

OBJECTIVE: In order to provide a more accurate and effective basis for clinical diagnosis and treatment, patients with cognitive dysfunction after acute ischemic stroke (AIS) were evaluated and their influencing factors were analyzed. METHODS: A rigorous and systematic logistic regression analysis was conducted to comprehensively investigate the various influencing factors that contribute to cognitive dysfunction. RESULTS: Among them, the sex granulocyte/lymphocyte ratio (NLR), low-density lipoprotein cholesterol (LDL-C) level, and C-reactive protein (CRP) were also higher than those in the control group (p < 0.05). The scores of memory, orientation, visual and spatial function, abstract thinking and language in the control group were higher than those in the experimental group (p < 0.05). The results of multivariate logistic regression analysis showed that history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking and temporal lobe infarction were risk factors for cognitive dysfunction after AIS, while elevated BMI and love of exercise were protective factors for cognitive dysfunction after AIS. CONCLUSION: Patients with cognitive dysfunction had the highest incidence of temporal lobe infarction, and they scored lower than the control group on memory, orientation, visual and spatial function, abstract thinking, and language function. Multivariate logistic regression analysis showed that a history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking, and temporal lobe infarction were independent risk factors for cognitive dysfunction after acute ischemic stroke, while elevated BMI and a love of exercise were protective factors for cognitive dysfunction after acute ischemic stroke.

Mitochondrial Membrane-Associated Protein Mba1 Confers Antifungal Resistance by Affecting the Production of Reactive Oxygen Species in Aspergillus fumigatus.

Azole resistance in the human fungal pathogen Aspergillus fumigatus is becoming a major threat to global health. To date, mutations in the azole target-encoding cyp51A gene have been implicated in conferring azole resistance, but a steady increase in the number of A. fumigatus isolates with azole resistance resulting from non-cyp51A mutations has been recognized. Previous studies have revealed that some isolates with non-cyp51A mutation-induced azole resistance are related to mitochondrial dysfunction. However, knowledge of the molecular mechanism underlying the involvement of non-cyp51A mutations is limited. In this study, using next-generation sequencing, we found that nine independent azole-resistant isolates without cyp51A mutations had normal mitochondrial membrane potential. Among these isolates, a mutation in a mitochondrial ribosome-binding protein, Mba1, conferred multidrug resistance to azoles, terbinafine, and amphotericin B but not caspofungin. Molecular characterization verified that the TIM44 domain of Mba1 was crucial for drug resistance and that the N terminus of Mba1 played a major role in growth. Deletion of mba1 had no effect on Cyp51A expression but decreased the fungal cellular reactive oxygen species (ROS) content, which contributed to mba1-mediated drug resistance. The findings in this study suggest that some non-cyp51A proteins drive drug resistance mechanisms that result from reduced ROS production induced by antifungals.

Chryseobacterium luquanense sp. nov., a casein-hydrolysing bacterium from the Jiaozi Mountain in Yunnan, PR China.

Strain KC 927T was isolated during an investigation of the soil bacteria diversity on Jiaozi Mountain, central Yunnan, Southwest China. The strain was Gram-stain-negative, rod-shaped, non-motile, oxidase-negative, catalase-positive and aerobic. Results of 16S rRNA gene alignment and phylogenetic analysis indicated that strain KC 927T was a member of the genus Chryseobacterium and closely related to Chryseobacterium caseinilyticum GCR10T (98.4%), Chryseobacterium piscicola DSM 21068T (98.3 %) and 'Chryseobacterium formosus' CCTCC AB 2015118T (97.9 %). With a genome size of 4 348 708 bp, strain KC 927T had 33.5 mol% DNA G+C content and contained 4012 protein-coding genes and 77 RNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain KC 927T and C. caseinilyticum GCR10T, C. piscicola DSM 21068T and 'C. formosus' CCTCC AB 2015118T were 80.1, 79.6 and 90.7 %, and 25.5, 23.6 and 42.0 %, respectively. The main polar lipid of strain KC 927T was phosphatidylethanolamine and the respiratory quinone was MK-6. The major fatty acids (≥10 %) were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 3-OH. Evidence from phenotypic, phylogenetic and chemotaxonomic analyses support that strain KC 927T represents a new species of the genus Chryseobacterium, for which the name Chryseobacterium luquanense sp. nov. is proposed. The type strain is KC 927T (=CGMCC 1.18760T=JCM 35707T).

Branched Porous Ni3N as a Catalytic Electrode for Selective Semidehydrogenation of Tetrahydroisoquinoline.

Oxygen evolution in electrochemical water splitting needs a high overpotential that significantly reduces the energy efficiency. To explore an alternative anodic reaction to promote the production of hydrogen at the other end of water splitting and at the same time to get high-value-added chemicals is highly desirable. Herein, we demonstrate a novel branched porous Ni3N catalyst that is prepared for dehydrogenation of tetrahydroisoquinoline, which acts as an anodic oxidation reaction to promote H2 formation on the other end. Interestingly, the Ni3N catalytic electrode can induce effective semidehydrogenation with the selective formation of dihydroisoquinoline, which is difficult to be obtained by the usual direct synthesis route. The catalytic electrode exhibits a low potential of 1.55 V (vs RHE) for a catalytic current density of 61 mA cm-2 with dehydrogenation of tetrahydroisoquinoline and hydrogen production. In situ Raman spectra studies suggest that NiOOH is formed on the electrode surface, which mediates the oxidation semidehydrogenation process. This work also provides a strategy to fabricate nitride materials for applications beyond selective semidehydrogenation of tetrahydroisoquinoline.

Streptomyces plumbidurans sp. nov., a Pb2+-tolerant actinomycete.

A novel actinobacterium, designated KC 17012T, was isolated from lead zinc tailings collected from Lanping, Yunnan, PR China. Comparative 16S rRNA gene sequencing showed that KC 17012T belonged to the genus Streptomyces and was most closely related to the type strains of Streptomyces neyagawaensis (98.34%), Streptomyces panaciradicis (98.34%) and Streptomyces heilongjiangensis (98.27%). Phylogenetic tree analysis revealed strain KC 17012T formed a distinct clade. The genome size was 8.64 Mbp with a DNA G+C content of 70.8%. Digital DNA-DNA hybridization and average nucleotide identity values between the genome sequence of strain KC 17012T and those of S. neyagawaensis JCM 4796T (25.3 and 81.5 %) and S. panaciradicis NBRC 109811T (30.1 and 85.7 %) were below the thresholds of 70 and 96% for prokaryotic conspecific assignation. The strain formed long straight aerial hyphae which generated regular short rod spores with spiny surfaces. Growth occurred at 10-45 °C, pH 6-8 and with 0-9 % NaCl (w/v). Strain KC 17012T contained ll-diaminopimelic acid and the major whole-cell hydrolysates included glucose, mannose and ribose. The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified lipid and one unidentified phospholipid. On the basis of the results of a polyphasic taxonomic study, it is concluded that KC 17012T represents a novel species of the genus Streptomyces, for which the name Streptomyces plumbidurans sp. nov., is proposed. The type strain is KC 17012T (CGMCC 4.7704T=JCM 35204T).

Morphology-Dependent Electrocatalytic Performance of a Two-Dimensional Nickel-Iron MOF for Oxygen Evolution Reaction.

Developing highly efficient, low-cost, and durable oxygen evolution reaction (OER) electrocatalysts is extraordinarily desirable for achieving clean and sustainable hydrogen energy. Metal-organic frameworks (MOFs) are emerging as attractive candidates for OER electrocatalysts. Herein, a two-dimensional Fe-Ni MOF of Fe(py)2Ni(CN)4 (py = pyridine) is synthesized controllably to generate various nanostructures, including nanoboxes, nanocubes, nanoplates, and nanosheets. Since different morphologies expose different active crystal planes and generate disparate intrinsic active sites, these nanostructures exhibit obviously different electrocatalytic activities. Particularly, the nanoboxes with a hollow structure display superior electrocatalytic activity and stability for OER due to greater active surface area and higher intrinsic activity of the exposed crystal planes, delivering a low overpotential of 285 mV at 10 mA cm-2 and a small Tafel value of 50.9 mV dec-1 in a 1.0 M KOH solution. The morphology-dependent electrocatalytic properties demonstrated in this work provide an efficient strategy to optimize MOF precatalysts for electrochemical energy storage and conversion.

N-Doped Carbon as a Promoted Substrate for Ir Nanoclusters toward Hydrogen Oxidation in Alkaline Electrolytes.

Development of effective electrocatalysts toward hydrogen oxidation with a low content of noble metals has attracted the attention of the catalytic community. In this work, a novel catalyst composed of nitrogen-doped carbon acting as the substrate and Ir nanoclusters as active species was prepared, which was then employed as an effective catalyst for the hydrogen oxidation reaction (HOR) in an alkaline electrolyte. In 0.1 M KOH, the optimized catalyst provides an exchange current density of 0.144 mA cmIr-2 for HOR that outperforms the catalytic activity of the commercial Pt/C catalyst with a Pt content of 20 wt %. The substrate induces highly active Ir sites that markedly boosted the electrocatalytic activity for HOR. The nitrogen-doped carbon substrate increases the stability of Ir nanoclusters and decreases the absorption energy of hydrogen on Ir sites; at the same time, the higher electrostatic potential around the adsorbed hydrogen on Ir/N-doped carbon also enables them to be easily attracted by OH- species, both of which enhanced the catalytic activity. The excellent catalytic activity and the understanding shown here will give some hints for the development of HOR catalysts used in alkaline electrolytes.

Effectiveness and safety of perampanel as adjunctive therapy among Chinese patients with focal-onset epilepsy: A real-world prospective observational study.

OBJECTIVE: Perampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year. METHODS: A prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency. RESULTS: One hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic-clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026). CONCLUSION: Perampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.

Siccirubricoccus soli sp. nov., a novel bacterial species isolated from Jiaozi Mountain soil.

An isolate of Gram-stain-negative and strictly aerobic bacterium, designated KC 17139T, was isolated from Jiaozi Mountain sample in Yunnan, China. Cells were non-motile cocci to oval, catalase-positive and oxidase-positive. Growth occurred at 0-7% NaCl (w/v; optimum, 0%), pH 6.0-8.0 (optimum, pH 7.0) and 15-45 °C (optimum, 28-37 °C). The polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and four unidentified aminolipids (UALs). Strain KC 17139T contained summed feature 8 (comprising C18:1 ω7c and/or C18:1 ω6c), C18:1 2OH and C16:0 as major cellular fatty acids (> 5%) and ubiquinone-10 as the sole isoprenoid quinone. The 16S rRNA gene sequence analysis indicated that strain KC 17139T shared highest similarities with Siccirubricoccus phaeus 1-3T (96.7%) and Siccirubricoccus deserti SYSU D8009T (95.0%). Strain KC 17139T clustered with the two Siccirubricoccus type strains, but formed a separate branch in both 16S rRNA gene and genome-scale phylogenetic dendrograms. The genomic DNA G + C content of strain KC 17139T was 71.2%. Genomic comparisons between strain KC 17139T and its close relatives showed the highest digital DNA-DNA hybridisation to S. phaeus (35.5%), highest average nucleotide identity to S. phaeus (88.2%), indicating that strain KC 17139T represents a novel species. On the basis of results of phenotypic, chemotaxonomic and molecular analysis, we report a new bacterium strain KC 17139T belonged to genus Siccirubricoccus, for which the name Siccirubricoccus soli sp. nov. is proposed. The type strain is KC 17139T (= CGMCC 1.18756T = JCM 35132T).

Molecular Precursor Route to CuCo2S4 Nanosheets: A High-Performance Pre-Catalyst for Oxygen Evolution and Its Application in Zn-Air Batteries.

Development of high-efficiency non-precious metal-based electrocatalysts to drive the complex four-electron process of the oxygen evolution reaction (OER) is crucial for production of hydrogen and energy storage components. Herein, bimetallic CuCo2S4 nanosheets were created by a new molecular precursor route. The optimal CuCo2S4 catalyst demonstrates superior performance to catalyze the OER with excellent stability, which was confirmed by the low overpotential of 290 mV at 10 mA cm-2 in 1 M KOH. The catalytic activity can be maintained for at least 40 h. The catalyst after the OER was then detected. The results indicate that S-doped CoOOH/CuO nanosheets formed on the catalyst surface during the OER may act as the catalytic active substance. Furthermore, when employed as an air cathode in a Zn-air battery, it reveals a high open-cycle potential of 1.38 V and a peak power density of 123.9 mW cm-2. The performance of the rechargeable Zn-air battery is close to that fabricated with commercial precious metal-based electrocatalysts. These findings would furnish some guidelines for the design, development, and applications of bimetallic sulfide electrocatalysts for the OER.

CgCmk1 Activates CgRds2 To Resist Low-pH Stress in Candida glabrata.

In Candida glabrata, the transcription factor CgRds2 has been previously characterized as a regulator of glycerophospholipid metabolism, playing a crucial role in the response to osmotic stress. Here, we report that CgRds2 is also involved in the response to pH 2.0 stress. At pH 2.0, the deletion of CgRDS2 led to reduced cell growth and survival, by 33% and 57%, respectively, compared with those of the wild-type strain. These adverse phenotypes resulted from the downregulation of genes related to energy metabolism in the Cgrds2Δ strain at pH 2.0, which led to a 34% reduction of the intracellular ATP content and a 24% decrease in membrane permeability. In contrast, the overexpression of CgRDS2 rescued the growth defect of the Cgrds2Δ strain and increased cell survival at pH 2.0 by 17% compared with that of the wild-type strain, and this effect was accompanied by significant increases in ATP content and membrane permeability, by 42% and 19%, respectively. Furthermore, we found that the calcium/calmodulin-dependent protein kinase (CaMK) CgCmk1 physically interacts with the PAS domain of CgRds2, and CgCmk1 is required for CgRds2 activation and translocation from the cytoplasm to the nucleus under pH 2.0 stress. Moreover, CgCmk1 is critical for CgRds2 function in resistance to pH 2.0 stress, because cells of the Cgrds2-pas strain with a disrupted CgCmk1-CgRds2 interaction exhibited impaired energy metabolism and membrane permeability at pH 2.0. Therefore, our results indicate that CgCmk1 positively regulates CgRds2 and suggest that they promote resistance to low-pH stress by enhancing energy metabolism and membrane permeability in C. glabrataIMPORTANCE An acidic environment is the main problem in the production of organic acids in C. glabrata The present study reports that the calcium/calmodulin-dependent protein kinase CgCmk1 positively regulates CgRds2 to increase intracellular ATP content, membrane permeability, and resistance to low-pH stress. Hence, the transcription factor CgRds2 may be a potential target for improving the acid stress tolerance of C. glabrata during the fermentation of organic acids. The present study also establishes a new link between the calcium signaling pathway and energy metabolism.

Enhancement of Sphingolipid Synthesis Improves Osmotic Tolerance of Saccharomyces cerevisiae.

To enhance the growth performance of Saccharomyces cerevisiae under osmotic stress, mutant XCG001, which tolerates up to 1.5 M NaCl, was isolated through adaptive laboratory evolution (ALE). Comparisons of the transcriptome data of mutant XCG001 and the wild-type strain identified ELO2 as being associated with osmotic tolerance. In the ELO2 overexpression strain (XCG010), the contents of inositol phosphorylceramide (IPC; t18:0/26:0), mannosylinositol phosphorylceramide [MIPC; t18:0/22:0(2OH)], MIPC (d18:0/22:0), MIPC (d20:0/24:0), mannosyldiinositol phosphorylceramide [M(IP)2C; d20:0/26:0], M(IP)2C [t18:0/26:0(2OH)], and M(IP)2C [d20:0/26:0(2OH)] increased by 88.3 times, 167 times, 63.3 times, 23.9 times, 27.9 times, 114 times, and 208 times at 1.0 M NaCl, respectively, compared with the corresponding values of the control strain XCG002. As a result, the membrane integrity, cell growth, and cell survival rate of strain XCG010 increased by 24.4% ± 1.0%, 21.9% ± 1.5%, and 22.1% ± 1.1% at 1.0 M NaCl, respectively, compared with the corresponding values of the control strain XCG002 (wild-type strain with a control plasmid). These findings provided a novel strategy for engineering complex sphingolipids to enhance osmotic tolerance.IMPORTANCE This study demonstrated a novel strategy for the manipulation of membrane complex sphingolipids to enhance S. cerevisiae tolerance to osmotic stress. Elo2, a sphingolipid acyl chain elongase, was related to osmotic tolerance through transcriptome analysis of the wild-type strain and an osmosis-tolerant strain generated from ALE. Overexpression of ELO2 increased the content of complex sphingolipid with longer acyl chain; thus, membrane integrity and osmotic tolerance improved.

Genetic variants in incident SUDEP cases from a community-based prospective cohort with epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy-related mortality in young adults. It has been suggested that SUDEP may kill over 20 000 people with epilepsy in China yearly. The aetiology of SUDEP is unclear. Little is known about candidate genes for SUDEP in people of Chinese origin as most studies have ascertained this in Caucasians. No candidate genes for SUDEP in Chinese people have been identified. METHODS: We performed whole exome sequencing (WES) in DNA samples collected from five incident cases of SUDEP identified in a large epilepsy cohort in rural China. We filtered rare variants identified from these cases as well as screened for SUDEP, epilepsy, heart disease or respiratory disease-related genes from previous published reports and compared them with publicly available data, living epilepsy controls and ethnicity-match non-epilepsy controls, to identify potential candidate genes for SUDEP. RESULTS: After the filtering process, the five cases carried 168 qualified mutations in 167 genes. Among these genetic anomalies, we identified rare variants in SCN5A (1/5:20% in our cases), KIF6 (1/5:20% in our cases) and TBX18 (1/5:20% in our cases) which were absent in 330 living epilepsy control alleles from the same original cohort and 320 ethnicity-match non-epilepsy control alleles. CONCLUSIONS: These three genes were previously related to heart disease, providing support to the hypothesis that underlying heart disorder may be a driver of SUDEP risk.

Engineering of membrane phospholipid component enhances salt stress tolerance in Saccharomyces cerevisiae.

To increase the growth of industrial strains under environmental stress, the Saccharomyces cerevisiae BY4741 salt-tolerant strain Y00 that tolerates 1.2 M NaCl was cultured through nitroguanidine mutagenesis. The metabolomics and transcription data of Y00 were compared with those of the wild-type strain BY4741. The comparison identified two genes related to salt stress tolerance, cds1 and cho1. Modular assembly of cds1 and cho1 redistributed the membrane phospholipid component and decreased the ratio of anionic-to-zwitterionic phospholipid in strain Y03 that showed the highest salt tolerance. Therefore, significantly increased membrane potential and membrane integrity helped strain Y03 to resist salt stress (1.2 M NaCl). This study provides an effective membrane engineering strategy to enhance salt stress tolerance.

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations.

OBJECTIVE: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. RESULTS: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. CONCLUSION: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.