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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated primary inflammatory myelinopathy of the central nervous system that primarily affects the optic nerve and spinal cord. The aquaporin 4 antibody (AQP4-Ab) is a specific autoantibody marker for NMOSD. Most patients with NMOSD are seropositive for AQP4-Ab, thus aiding physicians in identifying ways to treat NMOSD. AQP4-Ab has been tested in many clinical and laboratory studies, demonstrating effectiveness in diagnosing NMOSD. Recently, novel assays have been developed for the rapid and accurate detection of AQP4-Ab, providing further guidance for the diagnosis and treatment of NMOSD. This article summarizes the importance of rapid and accurate diagnosis for treating NMOSD based on a review of the latest relevant literature. We discussed current challenges and methods for improvement to offer new ideas for exploring rapid and accurate AQP4-Ab detection methods, aiming for early diagnosis of NMOSD.
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Based on a typical ozone ï¼O3ï¼ pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds ï¼VOCsï¼ during different pollution periods ï¼clean period ï¼CPï¼, pollution rise period ï¼PRPï¼, heavy pollution period ï¼HPPï¼, and pollution decline period ï¼PDPï¼ï¼ in the urban area were analyzed. Both positive matrix factorization ï¼PMFï¼ and an observation-based model ï¼OBMï¼ were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρï¼O3-8hï¼ during the HPP period in the urban area was ï¼246.67±11.24ï¼ µg·m-3, and ρï¼O3-1hï¼ had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds ï¼OVOCsï¼, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential ï¼OFPï¼. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals ï¼HO2·ï¼ and methyl peroxide radicals ï¼CH3O2·ï¼ with NO, and the net ozone generation rate during the HPP phase [Pï¼O3ï¼net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.
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Mineral resource bases have dual properties, e.g., mineral resources and environmental pollution. The latter could be classified into natural and anthropogenic pollution based on identifying the spatial distribution characteristics and sources of heavy metals in the soil. The Hongqi vanadium titano-magnetite mineral resources base in Luanping County, Luanhe watershed, was taken as the research object. The geo-accumulation index (Igeo), Nemerow comprehensive pollution index (PN), and potential ecological risk (Ei) were utilized to assess the soil heavy metal pollution characteristics, and redundancy analysis (RDA) and positive determinate matrix factorization (PMF) were employed to identify sources of the soil heavy metals. The results revealed that the mean contents of Cr, Cu, and Ni in the parent material of medium-basic hornblende metamorphic rock and medium-basic gneisses metamorphic rock were 1-2 times that in other parent materials in the concentrated area of mineral resources. However, the mean contents of Pb and As were lower. Fluvial alluvial-proluvial parent materials had the highest mean content of Hg, and the mean content of Cd was higher in the parent materials of medium-basic gneisses metamorphic rocks, acid rhyolite volcanic rocks, and fluvial alluvial-proluvial facies. The Igeodecreased in the following order:Cd>Cu>Pb>Ni>Zn>Cr>Hg>As. PN ranged from 0.61 to 18.99, and the sample proportion of moderate and severe pollution reached 10.00% and 8.08% respectively. Pishowed that the contents of Cu, Cd, Cr, and Ni were relatively higher in the parent material of intermediate-basic hornblende metamorphic rocks and intermediate-basic gneiss metamorphic rocks. Ei decreased in the order of Hg(58.06)>Cd(39.72)>As(10.98)>Cu(6.56) >Pb(5.60)>Ni(5.43)>Cr(2.01)>Zn(1.10). Samples whose RI was lower than 150 accounted for 84.27%, showing that the research area was predominantly at a slight potential ecological risk level. The sources of soil heavy metals were dominated by parent material weathering, followed by the mixed sources of agricultural activities and transportation, the exploitation of mining, and fossil burning, which accounted for 41.44%, 31.83%, 22.01%, and 4.73%, respectively. The risks of heavy metal pollution in the mineral resource base were characterized as multi-source instead of the single source from the mining industry. These research results provide the scientific basis for regional green mining development and eco-environmental protection.
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The development and utilization of saline-alkaline water, an important backup resource, has received widespread attention. However, the underuse of saline-alkaline water, threatened by the single species of saline-alkaline aquaculture, seriously affects the development of the fishery economy. In this work, a 30-day NaHCO3 stress experimental study combined with analyses of untargeted metabolomics, transcriptome, and biochemical approaches was conducted on crucian carp to provide a better understanding of the saline-alkaline stress response mechanism in freshwater fish. This work revealed the relationships among the biochemical parameters, endogenous differentially expressed metabolites (DEMs), and differentially expressed genes (DEGs) in the crucian carp livers. The biochemical analysis showed that NaHCO3 exposure changed the levels of several physiological parameters associated with the liver, including antioxidant enzymes (SOD, CAT, GSH-Px), MDA, AKP, and CPS. According to the metabolomics study, 90 DEMs are involved in various metabolic pathways such as ketone synthesis and degradation metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. In addition, transcriptomics data analysis showed that a total of 301 DEGs were screened between the control group and the high NaHCO3 concentration group, of which 129 up-regulated genes and 172 down-regulated genes. Overall, NaHCO3 exposure could cause lipid metabolism disorders and induce energy metabolism imbalance in the crucian carp liver. Simultaneously, crucian carp might regulate its saline-alkaline resistance mechanism by enhancing the synthesis of glycerophospholipid metabolism, ketone bodies, and degradation metabolism, at the same time increasing the vitality of antioxidant enzymes (SOD, CAT, GSH-Px) and nonspecific immune enzyme (AKP). Herein, all results will provide new insights into the molecular mechanisms underlying the stress responses and tolerance to saline-alkaline exposure in crucian carp.
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Carpas , Carpa Dorada , Animales , Carpa Dorada/metabolismo , Carpas/genética , Multiómica , Antioxidantes/metabolismo , Hígado , Superóxido Dismutasa/metabolismo , Glicerofosfolípidos/metabolismo , Agua/metabolismoRESUMEN
Alkaline pectate lyase has developmental prospects in the textile, pulp, paper, and food industries. In this study, we selected BacPelA, the pectin lyase with the highest expression activity from Bacillus clausii, modified and expressed in Escherichia coli BL21(DE3). Through fragment replacement, the catalytic activity of the enzyme was significantly improved. The optimum pH and temperature of the modified pectin lyase (PGLA-rep4) were 11.0 and 70 °C, respectively. It also exhibited a superior ability to cleave methylated pectin. The enzyme activity of PGLA-rep4, measured at 235 nm with 0.2% apple pectin as the substrate, was 554.0 U/mL, and the specific enzyme activity after purification using a nickel column was 822.9 U/mg. After approximately 20 ns of molecular dynamics simulation, the structure of the pectin lyase PGLA-rep4 tended to be stable. The root mean square fluctuation (RMSF) values at the key catalytically active site, LYS168, were higher than those of the wildtype PGLA. In addition, PGLA-rep4 was relatively stable in the presence of metal ions. PGLA-rep4 has good enzymatic properties and activities and maintains a high pH and temperature. This study provides a successful strategy for enhancing the catalytic activity of PGLA-rep4, making it the ultimate candidate for degumming and various uses in the pulp, paper, and textile industries.
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Geochemical differentiation of soils has a series of consequences on plant and places pressure on the ecological environment. The quantitative evaluation of element migration in the Earth's critical zone is a challenging task. In this study, two demonstration study areas of Scutellaria baicalensis Georgi were selected, and multiple chemical weathering indexes, chemical loss fraction, mass migration coefficients and biological enrichment coefficient method were used to assess the ecological and geochemical suitability. The results show that for the element of Fe, Zn, Se, Cu, Co, Ni, Mo and Ge, the degree of weathering and soil maturation, were greater in the rhyolitic tuff area than in the Plagioclase gneiss area. In both research sites, the heavy metal level of samples in Scutellaria baicalensis Georgi did not exceed the standard limits. The plagioclase gneiss region's surface soil environment was more alkaline, and the content of soil organic matter was lower, resulting in a higher bioenrichment intensity of Ge, Co, Cu, and Se elements in Scutellaria baicalensis Georgi than in the rhyolite-tuff area. The elements of Cd, Nb, Mo, Pb and As are considerably enriched in the soil of the plagioclase gneiss area but lost by leaching in the soil of the rhyolite tuff area, which is connected to the interplay of elemental abundance and human impact in the parent materials. This study provides a good example of how to assess growth suitability of Chinese medicinal materials in the Earth's critical zone.
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An efficient strategy that can guide the synthesis of materials with superior mechanical properties is important for advanced material/device design. Here, we report a feasible way to enhance hardness in transition-metal monocarbides (TMCs) by optimally filling the bonding orbitals of valence electrons. We demonstrate that the intrinsic hardness of the NaCl- and WC-type TMCs maximizes at valence electron concentrations of about 9 and 10.25 electrons per cell, respectively; any deviation from such optimal values will reduce the hardness. Using the spark plasma sintering technique, a number of W1-xRexC (x = 0-0.5) have been successfully synthesized, and powder X-ray diffractions show that they adopt the hexagonal WC-type structure. Subsequent nanoindentation and Vickers hardness measurements corroborate that the newly developed W1-xRexC samples (x = 0.1-0.3) are much harder than their parent phase (i.e., WC), marking them as the hardest TMCs for practical applications. Furthermore, the hardness enhancement can be well rationalized by the balanced occupancy of bonding and antibonding states. Our findings not only elucidate the unique hardening mechanism in a large class of TMCs but also offer a guide for the design of other hard and superhard compounds such as borides and nitrides.
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A total of 86 soil samples, 86 corn kernel samples, 50 tailings samples, and 33 ore rock samples were collected in reclaimed land and surrounding areas of typical vanadium-titanium magnetite tailings located in the Chengde Central Region and analyzed for 14 elements (P, Fe, Cu, Ni, Cd, Cr, Pb, Zn, Hg, Ti, Mn, and Mo) and speciation of heavy metals. This study investigated the bioaccumulation and translocation characteristics of heavy metals in a soil-maize system based on a descriptive statistical analysis, a geological accumulative index, bioconcentration factors, and a redundancy analysis. The results showed that the average accumulation index of surface soil followed an order of P > Cu > Fe2O3 > Cr > Ti > V > Ni > Mn > Cd > Zn > Mo > As > Pb > Hg, while the accumulation level of heavy metals was generally categorized as either no accumulation or moderate accumulation. Compared to China's soil environmental quality standard risk screening values (GB15618-2018), the over-standard rates of Cr and Cu were 2.32% and 1.16%, respectively. The content of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and surrounding areas was relatively high, and the content of Mo, Ni, Cu, Zn, Cd, and Cr in the control area was relatively high. The over-standard rates of Ni, Zn, and Cu in the corn kernels were 13.61%, 13.23%, and 5.17% respectively, according to China's national food safety standard limits for contaminants in food (GB 2762-2017). The bioconcentration factors of Fe, Ti, As, Pb, and Mn in the corn kernels of the tailings and the surrounding areas were relatively higher, while the bioconcentration factors of Mo, Ni, Cu, Zn, Cd, and Cr were lower than in control area. The bioactive components of Cd accounted for 50.17%, which was the highest, followed by Ni, Zn, and Cu with average ratios of 13.61%, 13.23%, and 5.17%, respectively. Compared to the control area, the Pb, As and Hg elements in the soil samples of the reclaimed land showed a lower total amount but a higher bioavailability content and soil pH value, while the Cu and Hg elements showed a higher total amount but lower bioavailability content and soil pH value. These differences in total heavy metal concentrations, bioavailability amounts, and soil pH values made the bioconcentration intensity of As and Pb in the tailings reservoir and surrounding area relatively higher. When studying the ecological risk of heavy metal pollution or determining the remediation target value of reclaimed land in a mine tailings reservoir and the soil around the mine area, the bioavailable state limit of heavy metals should be should be taken into account as the evaluation standard.
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Metales Pesados , Contaminantes del Suelo , Bioacumulación , China , Monitoreo del Ambiente , Óxido Ferrosoférrico , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , Titanio , Vanadio , Zea maysRESUMEN
OBJECTIVE: To investigate the sineoculis homeobox homolog 1 (SIX1) affect the epithelial mesenchymal transition (EMT) in papillary thyroid carcinoma (PTC) through regulating TGF-ß/Smad2/3 signaling pathway. METHODS: The SIX1 expression in cytological specimens, tissues or PTC cell lines was detected by qRT-PCR, western blotting or immunohistochemistry. A series of vitro experiments including flow cytometry, CCK-8, wound-healing and Transwell were used to evaluate the biological characteristics in a PTC cell line (NPA cells), which were divided into Blank, Negative control (NC), SIX1, SIX1-siRNA, LY-364947 (TGF-ß/Smad2/3 pathway inhibitor) and SIX1 + LY-364947 groups. TGF-ß/Smad2/3 pathway and EMT related protein expression were measured by qRT-PCR and western blotting. RESULTS: SIX1 mRNA expression was increased in cytological specimens from PTC patients as compared with the non-toxic nodular goitre (NTG) patients. Moreover, compared with adjacent normal tissues, expressions of SIX1, N-cadherin and Vimentin were higher while E-cadherin was lower in PTC tissues; and SIX1 was positively correlated with N-cadherin and Vimentin but was negatively correlated with E-cadherin. Furthermore, the SIX1 expression was associated with histopathology, extrathyroidal extension (ETE), lymph node metastasis (LNM), pT stage, TNM stage, and distant metastasis. In addition, the expressions of TGFß1, p-SMAD2/3, N-cadherin and Vimentin were downregulated in NPA cells after LY-364947 treatment with upregulated E-cadherin, decreased cell proliferation and metastasis, and enhanced cell apoptosis, which was reversed by SIX1 overexpression. CONCLUSION: Silencing SIX1 can inhibit TGF-ß/Smad2/3 pathway, thereby suppressing EMT in PTC, which may be a novel avenue for the treatment of PTC.
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Transición Epitelial-Mesenquimal/genética , Proteínas de Homeodominio/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Apoptosis , Cadherinas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Silenciador del Gen , Humanos , Metástasis Linfática , ARN Mensajero/metabolismo , Transducción de Señal , Proteína Smad2/genética , Proteína smad3/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/metabolismo , Factor de Crecimiento Transformador beta/genética , Regulación hacia Arriba , Vimentina/metabolismoRESUMEN
The multi-environment media of water, surface soil and vadose zone soil samples were collected in the upstream of Miyun Reservoir, in the Luanping Basin of Chengde City, Hebei Province. The aim was to identify the pollution source, ratio, spatial distribution, migration, and transformation characteristics of nitrogen in groundwater. Hydrogeochemistry, soil total nitrogen, and dissolved nitrate nitrogen of vadose zone soil analysis and a multi isotope tracer technique of δ15 N-NO3 and δ18O-NO3, δ34S-SO4 and δ18O-SO4, δ14 C, combined with land-use type analysis and geostatistics, were used in the study. The results showed that nitrate was the main form of nitrogen in the groundwater of the Luanping Basin. The NO3- concentration of groundwater was significantly correlated with the land-use types of residential land and cultivated land where the nitrate pollution of shallow groundwater was mainly distributed. Of the groundwater samples, 13.79% exceeded the National Standard ⠢ for Groundwater (GB/T 14848-2017) of NO3- concentration value, while the excess multiple was 1.04-3.86, and 37.93% of the groundwater samples exceeded the World Health Organization NO3- concentration standard value. The excess multiple was 1.08-6.83. The spatial variation of groundwater NO3- concentration, soil total nitrogen and surface soil dissolved nitrate nitrogen of vadose zone was affected by the combination of natural structural factors and anthropogenic factors. The source of groundwater nitrate was mainly from livestock manure and domestic sewage, followed by chemical fertilizer leaching. The nitrogen cycle in the aeration zone-groundwater-dominated nitrogen circulation in the groundwater runoff area of the piedmont basin was nitrification. These findings are highly significant for the prevention and remediation of groundwater pollution when viewing the basin system as an independent unit, and for studying the sources and fate of nitrate pollution in the water environment.
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Agua Subterránea , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Nitratos/análisis , Isótopos de Nitrógeno/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
China National GeneBank DataBase (CNGBdb) is a data platform aiming to systematically archiving and sharing of multi-omics data in life science. As the service portal of Bio-informatics Data Center of the core structure, namely, "Three Banks and Two Platforms" of China National GeneBank (CNGB), CNGBdb has the advantages of rich sample resources, data resources, cooperation projects, powerful data computation and analysis capabilities. With the advent of high throughput sequencing technologies, research in life science has entered the big data era, which is in the need of closer international cooperation and data sharing. With the development of China's economy and the increase of investment in life science research, we need to establish a national public platform for data archiving and sharing in life science to promote the systematic management, application and industrial utilization. Currently, CNGBdb can provide genomic data archiving, information search engines, data management and data analysis services. The data schema of CNGBdb has covered projects, samples, experiments, runs, assemblies, variations and sequences. Until May 22, 2020, CNGBdb has archived 2176 research projects and more than 2221 TB sequencing data submitted by researchers globally. In the future, CNGBdb will continue to be dedicated to promoting data sharing in life science research and improving the service capability. CNGBdb website is: https://db.cngb.org/.
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Bases de Datos Genéticas , Macrodatos , China , Genómica , Difusión de la InformaciónRESUMEN
Fabricating electron transport layers at low temperatures is challenging but highly desired in the field of flexible perovskite solar cells (f-PSCs). In this study, highly uniform cerium oxide (CeO x ) films prepared by the UV-O3 treatment have been successfully applied as the electron transport layer (ETL) in methylammonium lead halide (CH3NH3PbI3) perovskite-based f-PSCs. Under AM 1.5 G sunlight with 100 mW cm-2, these cells exhibited an open-circuit voltage (V oc) of 0.98 V, a short-circuit current density (J sc) of 19.42 mA cm-2, a fill factor (FF) of 0.72 and power conversion efficiency (PCE) of 14.63%. The PCE was much higher than that of the control planar CeO x ETL (PCE â¼ 9.08%) prepared at a low temperature (80 °C) without the UV-O3 treatment, and this was ascribed to the improved CeO x film, enhanced light absorption and suppressed charge recombination. The cells that bend at 15 mm of radius showed excellent stability with less than 10% reduction in PCE after 500 cycles of repeated bending at ambient temperature. The charge-transmission kinetic parameters and long-term stability of the CeO x -based f-PSCs were analyzed as well.
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A total of 351 surface soil samples (0-20 cm) were collected from the Luanhe River Basin in Chengde City (a typical area of concentrated mineral resources) and analyzed for 12 heavy metals (Cu, Ni, Cd, Cr, Pb, Zn, Hg, V, Ti, Mn, As, and Co). The geochemical baseline values of the heavy metals were determined using the reference element method and the cumulative frequency curve method. Furthermore, the spatial structure and distribution characteristics of the heavy metals were assessed based on PCA and geostatistical analysis. The accumulation of heavy metal pollution in different types of soil and in association with different land use patterns was also evaluated using a geological accumulative index. The results showed that the geochemical baseline values of V, Ti, Cd, Pb, Mn, and Co in the surface soils of the Luanhe River Basin were higher than their background values for Hebei Province. In contrast, the geochemical baseline values of As, Zn, Cr, Cu, Ni, and Hg were lower than their background values. The average accumulation index of the surface soils followed the order of Cd > Pb > Cu > Ti > Mn > Zn > Cr > Ni > Co > V > Hg > As. More than 80% of the soil samples were categorized as having no accumulation or moderate accumulation of Pb, Ti, V, As, and Co, while over 70% of the soil samples were categorized as having no accumulation or moderate accumulation of Hg, Mn, Ni, Cu, As, Cd, and Cr. With respect to different soil types, the average accumulation index of heavy metals followed the order of fluvo-aquic soil>cinnamon soil>brown soil. With respect to land use types, the accumulation index of heavy metals followed the order of industrial and mining land > shrub forest land > agricultural land > woodland and grassland. The accumulation of Pb and Cd in the surface soils of agricultural land was relatively high in comparison to the other elements, with 27.69% and 25.38% of the samples being above the moderate accumulation level, respectively. The iron group elements Ti, V, Co, Ni, and Cr are likely to derive from naturally high geological background sources, while the spatial patterns of Cd, Pb, Zn, Mn, Cu, and As were associated with the combination of parent material and anthropogenic inputs. The accumulation of Hg was mainly influenced by human activities.
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Copper(I)-catalyzed stereodivergent nucleophilic propargylation at the anomeric carbon of unprotected N-acetyl mannosamine was developed using 3-substituted allenylboronates as a nucleophile. The homopropargylic alcohol products contained two contiguous stereocenters, and two stereoisomers out of the four possible isomers were selectively obtained in a catalyst-controlled manner by applying either basic conditions: a MesCu/(R,R,R)-Ph-SKP catalyst with a B(OiPr)3 additive or acidic conditions: a CuBF4/(S,S,S)-Ph-SKP catalyst with an MeB(OiPr)2 additive. Mechanistic studies suggested the presence of distinct active nucleophilic species depending on the conditions: an allenylcopper species under the basic conditions or an allenylboronate activated by the Lewis acidic copper catalyst under the acidic conditions. The propargylation products were concisely transformed into C3-substituted sialic acids in two steps without the use of protecting groups.
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Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.
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Enfermedad de Charcot-Marie-Tooth/genética , Animales , Calcio/metabolismo , Técnicas de Sustitución del Gen , Humanos , Ratones , Ratones Transgénicos , Mutación Missense , LinajeRESUMEN
A copper(I)-catalyzed enantioselective addition of enynes to ketones was developed. The method allows facile construction of enantiomerically enriched tertiary alcohols using skipped enynes as stable hydrocarbon pronucleophiles. The combination of a soft copper(I)-conjugated Brønsted base catalyst with a chiral diphosphine ligand, (S,S)-Ph-BPE, enabled chemoselective deprotonation of the skipped enynes in the presence of ketones bearing intrinsically more acidic α-protons. The catalytically generated chiral allylcopper species enantio-, diastereo-, regio-, and chemoselectively reacted with ketones, thereby demonstrating excellent substrate generality with functional group tolerance. The skipped enyne moieties of the pronucleophiles were exclusively converted to cis-conjugated enynes, which will eventually allow for further versatile transformations.
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We developed a copper(I)-catalyzed stereodivergent anomeric propargylation of unprotected aldoses as a facile synthetic pathway to a broad variety of sialic acid derivatives. The soft allenylcopper(I) species, catalytically generated from stable allenylboronic acid pinacolate (2), is unusually inert to protonolysis by the multiple hydroxy groups of the substrates and thereby functions as a carbon nucleophile. The key additive B(OMe)3 facilitated ring-opening of the nonelectrophilic cyclic hemiacetal forms of aldoses to the reactive aldehyde forms. The chirality of the catalyst, and not the internal stereogenic centers of substrates, predominantly controlled the stereochemistry of the propargylation step; i.e., the diastereoselectivity was switched simply by changing the catalyst chirality. This is the first nonenzyme catalyst-controlled stereodivergent C-C bond elongation at the anomeric center of unprotected aldoses, which contain multiple protic functional groups and stereogenic centers. The propargylation products can be expeditiously transformed into naturally occurring and synthetic sialic acid derivatives in a simple three-step sequence. This synthetic method, which requires no protecting groups, can be performed on a gram-scale and thus offers general and practical access to various sialic acid derivatives from unprotected aldoses.
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La-Co-O mixed oxides (LCO) were prepared by co-precipitation method with the presence of polyethylene glycol (PEG) as dispersant. The influence of adding different molecular weight of PEG (0, 2 000, 6 000, 20 000 g·mol-1) on the physicochemical and catalytic properties of La-Co-O mixed oxides for total oxidation of benzene was investigated. The samples were characterized by means of N2 physical adsorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), temperature-programmed reduction by H2 (H2-TPR), temperature-programmed desorption of O2 (O2-TPD), and X-ray photoelectron spectroscopy (XPS). The order of catalytic activity was found to be LCO-PEG6000>LCO>LCO-PG20000>LCO-PG2000. Particularly, LCO-PEG6000 exhibited benzene conversion of 99% at temperature as low as 383 â, which was 126 â lower than that of LCO. The characterization result reveals that all samples had a BET surface area of about 9ï½10 m2·g-1. The XRD result shows that on all samples LaCoO3 perovskite was mainly formed together with a small amount of La2O3 and Co3O4. The addition of PEG was favorable for the formation of LaCoO3 perovskite. Particularly, the addition of PEG-6000 effectively suppressed the agglomeration of LaCoO3 perovskite, giving rise to small and uniform particles as observed by SEM. Moreover, the results of H2-TPR and O2-TPD indicate that the obtained La-Co-O mixed oxides showed higher reducibility and lattice oxygen mobility, and the Co 2p XPS analysis suggests that more surface Co3+ active species were presented by the addition of PEG-6000. These properties are thought to contribute to the high activity in benzene total oxidation.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations. Women heterozygous for G6PD mutations exhibit variation in the loss of enzyme activity but the cause of this phenotypic variation is unclear. We determined DNA methylation and X-inactivation patterns in 71 G6PD-deficient female heterozygotes and 68 G6PD non-deficient controls with the same missense mutations (G6PD Canton c.1376G>T or Kaiping c.1388G>A) to correlate determinants with variable phenotypes. Specific CpG methylations within the G6PD promoter were significantly higher in G6PD-deficient heterozygotes than in controls. Preferential X-inactivation of the G6PD wild-type allele was determined in heterozygotes. The incidence of preferential X-inactivation was 86.2% in the deficient heterozygote group and 31.7% in the non-deficient heterozygote group. A significant negative correlation was observed between X-inactivation ratios of the wild-type allele and G6PD/6-phosphogluconate dehydrogenase (6PGD) ratios in heterozygous G6PD Canton (r=-0.657, p<0.001) or Kaiping (r=-0.668, p<0.001). Multivariate logistic regression indicated that heterozygotes with hypermethylation of specific CpG sites in the G6PD promoter and preferential X-inactivation of the wild-type allele were at risk of enzyme deficiency.
Asunto(s)
Metilación de ADN , Variación Genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/genética , Mutación Missense , Inactivación del Cromosoma X , Adulto , Secuencia de Bases , Islas de CpG , Femenino , Genotipo , Deficiencia de Glucosafosfato Deshidrogenasa/patología , Heterocigoto , Humanos , Modelos Logísticos , Anotación de Secuencia Molecular , Fenotipo , Fosfogluconato Deshidrogenasa/genética , Regiones Promotoras Genéticas , Factores de RiesgoRESUMEN
Genetic recombination has been implicated as a mechanism that drives mutagenesis in the human globin gene clusters, either as a result of unequal crossover or gene conversion. In this paper, a novel fusion gene was identified in a Chinese girl with hemoglobin H disease. The proband's father was a compound heterozygote for the common -α(4.2) deletion and this fusion gene, and her mother was heterozygous for the common --(SEA) deletion (--(SEA)/αα). Both her parents had a hypochromic and microcytic red cell phenotype and a normal hemoglobin level. Molecular studies revealed a compound heterozygote for the --(SEA) deletion and this novel fusion gene and the patient had the clinical features of classic hemoglobin H disease. Sequence analysis revealed that the mutant gene was the result of a fusion between the α2 and ψα1 genes. The recombination began at exon 3 of α2 gene, crossing with exon 3 of the ψα1 gene. With this recombination, the conservative 3'UTR of the α2 gene was changed, and an extensive transcript with a new signal 1048bp 3' to the terminating codon was found. The abnormal transcripts of the fusion gene read through the intergenic sequence.