Focal cortical dysplasia II caused by brain somatic mutation of IRS-1 is associated with ERK signaling pathway activation.

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.

Modulation of Nucleation and Growth Kinetics of Perovskite Nanocrystals Enables Efficient and Spectrally Stable Pure-Red Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.

Imparting Chemiresistor with Humidity-Independent Sensitivity toward Trace-Level Formaldehyde via Substitutional Doping Platinum Single Atom.

The modification of metal oxides with noble metals is one of the most effective means of improving gas-sensing performance of chemiresistors, but it is often accompanied by unintended side effects such as sensor resistance increases up to unmeasurable levels. Herein, a carbonization-oxidation method is demonstrated using ultrasonic spray pyrolysis technique to realize platinum (Pt) single atom (SA) substitutional doping into SnO2 (named PtSA-SnO2). The substitutional doping strategy can obviously enhance gas-sensing properties, and meanwhile decrease sensor resistance by two orders of magnitude (decreased from ≈850 to ≈2 MΩ), which are attributed to the tuning of band gap and fermi-level position, efficient single atom catalysis, and the raising of adsorption capability of formaldehyde, as validated by the state-of-the-art characterizations, such as spherical aberration-corrected scanning transmission electron microscopy (Cs-corrected STEM), in situ diffuse reflectance infrared Fourier transformed spectra (in situ DRIFT), CO temperature-programmed reduction (CO-TPR), and theoretical calculations. As a proof of concept, the developed PtSA-SnO2 sensor shows humidity-independent (30-70% relative humidity) gas-sensing performance in the selective detection of formaldehyde with high response, distinguishable selectivity (8< Sformaldehyde/Sinterferant <14), and ultra-low detection limit (10 ppb). This work presents a generalized and facile method to design high-performance metal oxides for chemical sensing of volatile organic compounds (VOCs).

Zeolites as a Class of Semiconductors for High-Performance Electrically Transduced Sensing.

Zeolites are widely used as catalysts and adsorbents in the chemical industry, but their potential for electronic devices has been stunted to date, as they are commonly recognized as electronic insulators. Here, we have for the first time demonstrated that Na-type ZSM-5 zeolites are ultrawide-direct-band-gap semiconductors based on optical spectroscopy, variable-temperature current-voltage characteristics, and photoelectric effect as well as electronic structure theoretical calculations and further unraveled the band-like charge transport mechanism in electrically conductive zeolites. The increase in charge-compensating Na+ cations in Na-ZSM-5 decreases the band gap and affects its density of states, shifting the Fermi level close to the conduction band. Remarkably, the semiconducting Na-ZSM-5 zeolites have been first applied for constructing electrically transduced sensors that can sense trace-level (77 ppb) ammonia with unprecedentedly high sensitivity, negligible cross-sensitivity, and high stability under moisture ambient conditions compared with conventional semiconducting materials and conductive metal-organic frameworks (MOFs). The charge density difference shows that the massive electron transfer between NH3 molecules and Na+ cations ascribed to Lewis acid sites enables electrically transduced chemical sensing. This work opens a new era of zeolites in applications of sensing, optics, and electronics.

Impacts of meteorological parameters on the occurrence of air pollution episodes in the Sichuan basin.

Episodes of fine-particulate matter (PM2.5) pollution are a widespread and common occurrence in China, and have potentially serious implications for human health. Meteorological conditions play an important role in air quality and influence the formation of regional air pollution episodes. This study applied a new classification method and daily PM2.5 concentration data to (a) evaluate different levels of air pollution in the Sichuan-Chongqing region between 2015 and 2017, and (b) investigate their relationships with meteorological parameters including atmospheric boundary layer height, wind speed, temperature inversion, weather type, and atmospheric transport. We identified a total of 40 air pollution episodes, the most severe of which occurred in winter when the atmospheric layer height was low. These heavy pollution events also coincided with low surface (10 m) wind speeds and temperature inversions, weather conditions that generally result from low pressure over the northwestern Sichuan Basin (90-102° E, 28-36° N) and southerly atmospheric transport.

Somatic variants in new candidate genes identified in focal cortical dysplasia type II.

OBJECTIVE: Focal cortical dysplasia type II (FCDII) is a malformation of cortex development commonly found in children with drug-resistant epilepsy. FCDII has been associated with somatic mutations in mammalian target of rapamycin (mTOR)-related pathway genes and an upregulation of mTOR. Somatic mutations were found in 10%-63% of FCDII samples; the frequency of the mutant allele was 0.93%-33.5%. This study aimed to find new candidate genes involved in FCDII. METHODS: We collected resected FCD lesions, perilesional brain tissues, and peripheral blood from 17 children with pathologically confirmed FCDII. We performed whole exome sequencing and followed a set of screening and analysis strategies to identify potentially deleterious somatic variants (PDSVs) in brain-expressed genes. We performed site-specific amplicon sequencing to validate the results. We also performed an in vitro functional study on an IRS1 variant. RESULTS: In six of 17 samples, we identified seven PDSVs in seven genes, including two frameshift variants and five missense variants. The frequencies of the variant allele were 1.29%-5.50%. The genes were MTOR, TSC2, IRS1, RAB6B, RALA, HTR6, and ZNF337. PDSVs in IRS1, RAB6B, ZNF337, RALA, and HTR6 had not been previously associated with FCD. In one lesion, two PDSVs were found in two genes. In a transfected cell line, we demonstrated that the c.1791dupG (identified in FCDII from Patient 1) led to a truncated IRS1 and significant mTOR hyperactivation compared to cells that carried wild-type IRS1. mTOR was also activated in FCDII tissue from Patient 1. SIGNIFICANCE: Seven PDSVs were identified in FCDII lesions in six of 17 children. Five variant genes had not been previously associated with cortical malformations. We demonstrated that the IRS1 variant led to mTOR hyperactivation in vitro. Although functional experiments are needed, the results provide evidence for novel candidate genes in the pathogenesis of FCDII.

[Focal zone integral and multiple axial scanning based acoustic resolution photoacoustic microscopy with high lateral resolution in-depth].

Acoustic resolution photoacoustic microscopy (ARPAM) combines the advantages of high optical contrast, and high ultrasonic spatial resolution and penetration. However, in photoacoustic microscopy (PAM), the information from deep regions can be greatly affected by the shallow targets, and most importantly, the irreconcilable conflict between the lateral resolution and depth of fields has always be a major factor that limits the imaging quality. In this work, an ARPAM system was developed, in which a non-coaxial arrangement of light illumination and acoustic detection was adopted to alleviate the influence of the tissue surface on the deep targets, and a novel focal zone integral algorithm was applied with multiple axial scanning to improve the lateral resolution. Phantom experiment results show that, the build system can maintain a consistent high lateral resolution of 0.6 mm over a large range in axial direction, which is close to the theoretical calculations. The following tumor imaging results on nude mice indicate that, the proposed method can provide more in-depth information compared with the conventional back detection ARPAM method. With the development of fast repetition lasers and image scanning technologies, the proposed method may play an important role in cerebral vascular imaging, cervical cancer photoacoustic endoscopic detection, and superficial tumor imaging.

Regional differences in molecular characteristics of atmospheric water-soluble organic carbon over northern China: Comparison of remote, rural, and urban environments.

Atmospheric water-soluble organic carbon (WSOC) is a critical component of airborne particulates. It significantly affects the Earth's energy balance, air quality, and human health. Despite its importance, the molecular composition and sources of WSOC remain unclear, particularly in non-urban areas. In this study, we collected total suspended particulate (TSP) samples from three sites in northern China: Erenhot (remote site), Zhangbei (rural site), and Jinan (urban site). The WSOC components were analyzed using high-performance liquid chromatography coupled with high-resolution mass spectrometry. The results showed that the formula numbers of identified compounds exhibited a decreasing trend of Jinan (2647) > Zhangbei (2046) > Erenhot (1399). Among the assigned formulas, CHO compounds were the most abundant category for all three sites, accounting for 33 %-38 % of the identified compounds, followed by the CHON compounds with contributions of 27 %-30 %. In the remote site of Erenhot, CHO compounds were dominated by oxidized unsaturated organic compounds, and CHON compounds were mainly low-oxygenated aliphatic compounds, suggesting a significant influence of primary emissions. In contrast, the urban site of Jinan showed higher contributions of CHO and CHON compounds with elevated oxidation degrees, indicating the influence of more extensive secondary oxidation processes. Atmospheric WSOC in Erenhot and Zhangbei had abundant reduced sulfur-containing species, likely from coal or diesel combustion, while that in Jinan was characterized by aliphatic organosulfates and nitrooxy-organosulfates, which are mainly associated with traffic emissions and biogenetic sources, respectively. These findings reveal significant differences in the molecular composition of WSOC in different atmospheric environments and improve our understanding of the chemical properties, potential sources, and transformations of organic aerosols.

Portable and Hand-Held Ammonia Gas Sensor Enables Noninvasive Prediagnosis of Helicobacter pylori Infection.

Disease diagnosis of Helicobacter pylori (Hp) through human exhaled breath analysis has attracted considerable attention. However, conventional methods, such as carbon 13 (13C) breath test and infrared spectrometers, are facing the challenge of achieving portability and reliability synchronously. Herein, we report a portable and hand-held Hp analyzer using a bimetallic PtRu@SnO2-based gas sensor for the prediagnosis of Hp infection, which is based on detecting ammonia (NH3) as a potential biomarker in exhaled breath. Owing to the surface functionalization through highly catalytically active bimetallic PtRu nanoparticles (NPs) prepared by a photochemical reduction strategy, the PtRu@SnO2-based sensor exhibits high sensitivity and selectivity toward trace-level (200 ppb) NH3 even at high-humidity surroundings (80% RH). Consequently, the designed portable and hand-held Hp analyzer makes the accurate determination of NH3 at 800 ppb in exhaled breath. The tuning of energy band structure and electrical characteristics and the catalytic modulation of NH3 oxidation by PtRu NPs are proposed to be the reasons behind the enhanced NH3 gas-sensing performance, as confirmed by in situ analysis using an online MKS MultiGas 2030 FTIR gas analyzer. This work paves the way for the prediagnosis of Hp infection using a metal oxide gas sensor.

Reply to the Comment on "Understanding the Increasing Trend of Sensor Signal with Decreasing Oxygen Partial Pressure by a Sensing-Reaction Model Based on O2- Species".

In our recent work (ACS Sens.2022, 7, 1095-1104), Mirabella et al. provided comments on our publication, mainly focusing on the controversy between the oxygen vacancy model and the ionosorbed model and the related derivation based on the law of mass action. Herein we explain the correlation between the ionosorption model and the oxygen vacancy model and provide a brief introduction of our view on these two models. Moreover, a more detailed derivation about the law of mass action is provided to explain the relationship between surface electron concentration, oxygen partial pressure, adsorbed oxygen density, and oxygen vacancy density.

All-Nanofiber Network Structure for Ultrasensitive Piezoresistive Pressure Sensors.

Sensing materials with fiber structures are excellent candidates for the fabrication of flexible pressure sensors due to their large specific surface area and abundant contact points. Here, an ultrathin, flexible piezoresistive pressure sensor that consists of a multilayer nanofiber network structure prepared via a simple electrospinning technique is reported. The ultrathin sensitive layer is composite nanofiber films composed of poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) and polyamide 6 (PEDOT:PSS/PA6) prepared by simultaneous electrospinning. PEDOT:PSS conductive fibers and PA6 elastic fibers are interwoven to form a multilayer network structure that can achieve ultrahigh sensitivity by forming a wealth of contact points during loading. In particular, gold-deposited PA6 fibers as upper and lower flexible electrodes can effectively increase the initial resistance. Due to this special fiber electrode structure, the sensor is able to generate a large electrical signal variability when subjected to a weak external force. The devices with different sensing properties can be obtained by controlling the electrospinning time. The sensor based on the PEDOT:PSS/PA6 nanofiber network has high sensitivity (6554.6 kPa-1 at 0-1.4 kPa), fast response time (53 ms), and wide detection range (0-60 kPa). Significantly, the device maintains ultrahigh sensitivity when cyclically loaded over 10,000 cycles at 5 kPa, which makes it have great prospects for applications in human health monitoring and motion monitoring.

Brain Somatic Variant in Ras-Like Small GTPase RALA Causes Focal Cortical Dysplasia Type II.

Purpose: In our group's previous study, we performed deep whole-exome sequencing and targeted amplicon sequencing in the postoperative brain tissue of epilepsy patients with focal cortical dysplasia type II (FCD II). We identified the first somatic variant of RALA in the brain tissue of a child with FCD type IIb. RALA encodes a small GTPase of the Ras superfamily. To date, the role of RALA in brain development is not yet known. In this study, we reported that the RALA somatic variant led to FCD type II through activation of the mammalian target of rapamycin (mTOR) pathways. Materials and Methods: HEK293T cells were transfected in vitro to analyze the expression of the RalA protein, as well as phosphorylated S6 (P-S6), one of the major markers of mTOR pathway activation, RalA GTPase activity, and the interaction between RalA and its downstream binding effectors. In vivo, wild-type, and mutant RALA plasmids were transfected into the local cortex of mice using in utero electroporation to evaluate the effect of RALA c.G482A on neuronal migration. Results: The RALA c.G482A mutation increased RalA protein expression, the abnormal activation of the mTOR pathways, RalA GTPase activity, and binding to downstream effectors. RALA c.G482A local transfection in the embryonic brain in utero induced abnormal cortical neuron migration in mice. Conclusion: This study demonstrated for the first time that the somatic gain-of-function variant of RALA activates the mTOR pathway and leads to neuronal migration disorders in the brain, facilitating the development of FCD II. Therefore, RALA brain somatic mutation may be one of the pathogenic mechanisms leading to FCD II, which is always related to drug-resistant epilepsy in children. However, more somatic variations of this gene are required to be confirmed in more FCD II patient brain samples.

Cadmium sulfide in-situ derived heterostructure hybrids with tunable component ratio for highly sensitive and selective detection of ppb-level H2S.

Herein, we reported cadmium sulfide derivatives pine needles-like CdS/CdO heterostructure hybrids synthesized by hydrothermal treatment and subsequent self-template oxidation approach. The component ratio of the CdS/CdO hybrids can be controlled specifically via tuning the annealing treatment protocol, and thereby giving rise to the optimization of morphology, electrical characteristics, and gas sensing properties of derived hybrids. As proof of concept, the pine needles-like CdS/CdO, which obtained after different annealing temperatures and durations, as sensitive material was employed to manufacture H2S gas sensors. The sensor based on CdS/CdO hybrids (400 °C & 1 h) exhibited high sensitivity (73.5 to 5 ppm), ppb-level limit of detection (10 ppb), and excellent selectivity regardless of the interference of other gases at optimal working temperature of 200 °C. Due to the abnormal resistance variation of n-type cadmium sulfide derived hybrids while contacting with H2S, the sensing mechanism mainly depends on the surface chemical conversion from oxide to sulfide. The pine needles-like hierarchical morphology provided an excellent scaffold for the carriers transportation and the growth of the CdO, which played a key role in resistance modulation both in air and target gas, resulting in the enhanced H2S sensing performance ultimately.

Multifunctional Flexible Ionic Skin with Dual-Modal Output Based on Fibrous Structure.

Flexible wearable electronic devices with multiple sensing functions that simulate human skin in all aspects have become a popular research topic. However, the current expensive and time-consuming means of integration and the complex decoupling process are hampering the further development of multifunctional sensors. Here, an ultraflexible ionic fiber membrane (IFM) prepared by a simple electrospinning technique is reported, which exhibits pressure and humidity sensing properties. With the help of different electrode structures, the IFM-based multifunctional sensor achieved pressure and humidity detection with different sensing mechanisms. Pressure sensing with high sensitivity (49.7 kPa-1 at 0-30 kPa) and wide detection range (0-220 kPa) was indicated by the capacitive signal. Humidity sensing with high linearity (1.086% per percent relative humidity (RH)) in the range 15%-90% RH was indicated by the resistance signal. In particular, the multimodal output of capacitance/resistance corresponding to pressure/humidity in this study directly addresses the problem of accurately distinguishing the two stimuli. Furthermore, we have demonstrated that the impact between pressure and humidity is negligible when measured simultaneously and independently. Because of the excellent pressure/humidity sensing performance, we have fabricated a smart bracelet and mask for pulse, skin moisture, and breathe monitoring, which indicates the promising future of multifunctional flexible sensors based on IFM in the healthcare field.

Understanding the Increasing Trend of Sensor Signal with Decreasing Oxygen Partial Pressure by a Sensing-Reaction Model Based on O2- Species.

Although the increasing trend of sensor signal with decreasing oxygen partial pressure was observed quite early, the underlying mechanism is still elusive, which is a hindrance to accurate gas detection under varying oxygen partial pressure. In this work, a sensing model based on previous experimental and theoretical results is proposed, in which the O2- species is determined to be the main oxygen species because O- species has not been observed by direct spectroscopic studies. On this basis, combined with the band bending of SnO2 at different oxygen partial pressures, the functional relationship between the surface electron concentration, oxygen partial pressure, and reducing gas concentration is established, which includes three forms corresponding to the depletion layer, accumulation layer, and flat band. In the depletion layer case, the variation of the sensor resistance to different concentrations of CO and oxygen can be well fitted with our function model. Besides, this model predicts that the response of sensors will no longer maintain the increasing trend in an extremely hypoxic atmosphere but will decrease and approach 1 with the background oxygen content further going down to 0.

Interannual variability of dust height and the dynamics of its formation over East Asia.

The vertical structure of dust layers is rarely investigated, despite its critical role in exploring the radiative and microphysical effects of dust aerosols. In this study, we primarily investigate the temporal variability of most probable dust height (MPDH) over dust source regions in East Asia and its interactions with climate parameters using CALIPSO lidar measurements under cloud-free conditions in spring from 2007 to 2018. The vertical profile of dust aerosols exhibits significant interannual variability over this time; dust is mainly concentrated below 7 km and associated with a dust occurrence frequency (DOF) of 0.6, and the DOF is much higher than that over the Sahara and West Asia. We also found that high Indian Ocean sea surface temperature (SST) significantly contributes to the transport of dust aerosols to downstream areas by changing the circulation field near the equator and in the mid-low latitudes of the Northern Hemisphere, which results in low MPDH over northern China. MPDH is significantly negatively correlated with 500-hPa westerly wind and precipitation, and is positively correlated with surface air temperature (SAT) and normalized difference vegetation index (NDVI). Furthermore, MPDH is positively correlated with the Arctic Oscillation (AO) and the Atlantic Multidecadal Oscillation (AMO), but negatively correlated with the El Niño-Southern Oscillation (ENSO). The correlation coefficient between AMO and MPDH is 0.71 after detrending, which indicates that the AMO also plays an important role in the interannual variability of MPDH over East Asia. Furthermore, the Indian Ocean SST is the main influencing factor of the interannual variability of MPDH over northern China, but zonal wind is probably only the intermediate mechanism.

MOF-Derived Mesoporous and Hierarchical Hollow-Structured In2O3-NiO Composites for Enhanced Triethylamine Sensing.

It remains a challenge to design and fabricate high-performance gas sensors using metal-organic framework (MOF)-derived metal oxide semiconductors (MOS) as sensing materials due to the structural damage during the annealing process. In this study, the mesoporous In2O3-NiO hollow spheres consisting of nanosheets were prepared via a solvothermal reaction and subsequent cation exchange. More importantly, the transformation of Ni-MOF into In/Ni-MOF through exchanging the Ni2+ ion with In3+ ion can prevent the destruction of the porous reticular skeleton and hierarchical structure of Ni-MOF during calcination. Thus, the mesoporous In2O3-NiO hollow composites possess high porosity and large specific surface area (55.5 m2 g-1), which can produce sufficient permeability pathways for volatile organic compound (VOCs) molecules, maximize the active sites, and enhance the capacity of VOC capture. The mesoporous In2O3-NiO-based sensors exhibit enhanced triethylamine (TEA) sensing performance (S = 33.9-100 ppm) with distinct selectivity, good long-term stability, and lower detection limit (500 ppb) at 200 °C. These results can be attributed to the mesoporous hollow hierarchical structure and p-n junction of In2O3-NiO. The preparation concept mentioned in this work may provide a versatile platform applicable to various mesoporous composite sensing material-based hollow structures.

Water-soluble brown carbon in atmospheric aerosols along the transport pathway of Asian dust: Optical properties, chemical compositions, and potential sources.

As an important type of light-absorbing aerosol, brown carbon (BrC) has the potential to affect the atmospheric photochemistry and Earth's energy budget. A comprehensive field campaign was carried out along the transport pathway of Asian dust during the spring of 2016, including a desert site (Erenhot), a rural site (Zhangbei), and an urban site (Jinan), in northern China. Optical properties, bulk chemical compositions, and potential sources of water-soluble brown carbon (WS-BrC) were investigated in atmospheric total suspended particulate (TSP) samples. Samples from Zhangbei had higher mass absorption efficiency at 365 nm (MAE365, 1.32 ± 0.34 m2 g-1) than those from Jinan (1.00 ± 0.23 m2 g-1) and Erenhot (0.84 ± 0.30 m2 g-1). Compere to the non-dust samples, elevated water-soluble organic carbon (WSOC) concentrations and MAE365 values of dust samples from Erenhot are related to the input of high molecular weight organic compounds and biogenic matter from the Gobi Desert, while lower values from Zhangbei and Jinan are attributed to the dilution effect caused by strong northwesterly winds. Based on fluorescence excitation-emission matrix spectra and parallel factor analysis, two humic-like (C1 and C2) and two protein-like (C3 and C4) substances were identified. Together, C1 and C2 accounted for ~64% of total fluorescence intensity at the highly polluted urban Jinan site; C3 represented ~45% at the rural Zhangbei site where local biomass burning affects; and C4 contributed ~24% in the desert region (Erenhot) due to dust-sourced biogenic substances. The relative absorptive forcing of WS-BrC compared to black carbon at 300-400 nm was about 31.3%, 13.9%, and 9.2% during non-dust periods at Erenhot, Zhangbei, and Jinan, respectively, highlighting that WS-BrC may significantly affect the radiative balance of Earth's climate system and should be included in radiative forcing models.

A Patient With CAD Deficiency Responsive to Uridine and Literature Review.

CAD encodes a multifunctional enzyme involved in de novo pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing identified CAD compound heterozygous mutations in a new male patient with global developmental delay (DD), refractory epilepsy, and anemia with anisopoikilocytosis. We further reviewed all published cases with CAD deficiency. Five patients were collected from two publications, including three males and two females, and all presented with DD, drug-resistant epilepsy, and anemia with anisopoikilocytosis. Four out of six patients (including the present case) were supplemented with uridine, which led to immediate cessation of seizures, resolved anemia with anisopoikilocytosis, and progress in global development. The other two patients, who were not treated with uridine, died at the ages of 4 and 5 years. In summary, CAD deficiency is probably a treatable neurometabolic disorder.

Clinical features and surgical outcomes in young children with focal cortical dysplasia type II.

AIMS: To investigate clinical characteristics and surgery outcomes of young children with focal cortical dysplasia (FCD) type II. METHODS: Young children (onset age ≤6 years) with FCDII who underwent epileptic surgery in Children Epilepsy Center of Peking University First Hospital in 2014-2018 were followed up for at least 6 months after surgery. RESULTS: One hundred and twelve children with FCDII were included, with median age of onset 0.9 years (0.01-5.9), who underwent surgery at 4.1 years old (0.8-16.2). Focal seizures were most frequent (90.2%) and epileptic spasms presented in 23 (20.5%) cases. Epileptic encephalopathy was not uncommon (12.5%), associated with earlier epilepsy onset and higher rate of bilateral onset on ictal EEG (OR = 0.213, 9.059; P = .041, .004). At the last follow-up, 88.4% achieved seizure-free. Before surgery, 49.1% showed moderate/severe developmental delay, associated with earlier seizure onset and higher rate of history of epileptic encephalopathy (OR = 0.740, 5.160, P = .023, .042). For 48 children with preoperatively moderate/severe developmental delay, DQ rank at 6 months postsurgery was improved in only four cases. CONCLUSION: For young children with FCDII, they tend to present with epileptic encephalopathies and show moderate/severe developmental delay before surgery. The seizure outcome was favorable after surgery. For children with preoperatively moderate/severe developmental delay, developmental outcome at 6 months after surgery was not satisfactory.