Chronotoxici-Plate Containing Droplet-Engineered Rhythmic Liver Organoids for Drug Toxicity Evaluation.

The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi-timepoint drug administration strategies across a wide range of drugs. Here, droplet-engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici-plate as an in vitro high-throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time-dependent variations are demonstrated in toxicity on the Chronotoxici-plate, highlighting the importance of considering time-dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing.

Circadian modulation of glucose utilization via CRY1-mediated repression of Pdk1 expression.

Life adapts to daily environmental changes through circadian rhythms, exhibiting spontaneous oscillations of biological processes. These daily functional oscillations must match the metabolic requirements responding to the time of the day. We focus on the molecular mechanism of how the circadian clock regulates glucose, the primary resource for energy production and other biosynthetic pathways. The complex regulation of the circadian rhythm includes many proteins that control this process at the transcriptional and translational levels and by protein-protein interactions. We have investigated the action of one of these proteins, cryptochrome (CRY), whose elevated mRNA and protein levels repress the function of an activator in the transcription-translation feedback loop, and this activator causes elevated Cry1 mRNA. We used a genome-edited cell line model to investigate downstream genes affected explicitly by the repressor CRY. We found that CRY can repress glycolytic genes, particularly that of the gatekeeper, pyruvate dehydrogenase kinase 1 (Pdk1), decreasing lactate accumulation and glucose utilization. CRY1-mediated decrease of Pdk1 expression can also be observed in a breast cancer cell line MDA-MB-231, whose glycolysis is associated with Pdk1 expression. We also found that exogenous expression of CRY1 in the MDA-MB-231 decreases glucose usage and growth rate. Furthermore, reduced CRY1 levels and the increased phosphorylation of PDK1 substrate were observed when cells were grown in suspension compared to cells grown in adhesion. Our data supports a model that the transcription-translation feedback loop can regulate the glucose metabolic pathway through Pdk1 gene expression according to the time of the day.

Versatile Multi-Wavelength Light-Responsive Metal-Organic Frameworks Micromotor through Porphyrin Metalation for Water Sterilization.

Traditional metal-organic frameworks (MOFs) based micro/nanomotors (MOFtors) can achieve three-dimensional (3D) motion mainly depending on noble metal (e.g., Pt), toxic fuels (e.g., hydrogen peroxide), and surfactants, or under external magnetic fields. In this study, light-driven MOFtors are constructed based on PCN-224(H) and regulated their photothermal and photochemical properties responding to the light of different wavelengths through porphyrin metalation. The resulting PCN-224(Fe) MOFtors presented a strong 3D motion at a maximum speed of 1234.9 ± 367.5 µm s-1 under visible light due to the various gradient fields by the photothermal and photochemical effects. Such MOFtors exhibit excellent water sterilization performance. Under optimal conditions, the PCN-224(Cu) MOFtors presented the best antibacterial performance of 99.4%, which improved by 23.4% compared to its static counterpart and 43.7% compared to static PCN-224(H). The underlying mechanism demonstrates that metal doping could increase the production of reactive oxygen species (ROS) and result in a more positive surface charge under light, which are short-distance effective sterilizing ingredients. Furthermore, the motion of MOFtors appears very important to extend the short-distance effective sterilization and thus synergistically improve the antibacterial performance. This work provides a new idea for preparing and developing light-driven MOFtors with multi-responsive properties.

Synthetic Biohybrids of Red Blood Cells and Cascaded-Enzymes@ Metal-Organic Frameworks for Hyperuricemia Treatment.

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H2 O2 . In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half-life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.

Surfactant-Mediated Crystalline Structure Evolution Enabling the Ultrafast Green Synthesis of Bismuth-MOF in Aqueous Condition.

Green synthesis of stable metal-organic frameworks (MOFs) with permanent and highly ordered porosity at room temperature without needing toxic and harmful solvents and long-term high-temperature reactions is crucial for sustainable production. Herein, a rapid and environmentally friendly synthesis strategy is reported to synthesize the complex topological bismuth-based-MOFs (Bi-MOFs), [Bi9(C9H3O6)9(H2O)9] (denoted CAU-17), in water under ambient conditions by surfactant-mediated sonochemical approach, which could also be applicable to other MOFs. This strategy explores using cetyltrimethylammonium bromide (CTAB) amphiphilic molecules as structure-inducing agents to control the removal of non-coordinated water (dehydration) and enhance the degree of deprotonation of the ligands, thereby regulating the coordination and crystallization in aqueous solutions. In addition, another two new strategies for synthesizing CAU-17 by crystal reconstruction and one-step synthesis in binary solvents are provided, and the solvent-induced synthesis mechanism of CAU-17 is studied. The as-prepared CAU-17 presents a competitive iodine capture capability and effective delivery of the antiarrhythmic drug procainamide (PA) for enteropatia due to the broad pH tolerance and the unique phosphate-responsive destruction in the intestine. The findings will provide valuable ideas for the follow-up study of surfactant-assisted aqueous synthesis of MOFs and their potential applications.

Light-driven MOF-based micromotors with self-floating characteristics for water sterilization.

Three-dimensional motion (especially in the Z-axis direction) of metal-organic frameworks (MOFs)-based micromotors (MOFtors) is essential but still in its infancy. Herein, we propose a simple strategy for designing light-driven MOFtors that move in the Z-axis direction and efficiently kill Staphylococcus aureus (S. aureus). The as-prepared polypyrrole nanoparticles (PPy NPs) with excellent photothermal properties are combined with ZIF-8 through a simple in situ encapsulation method, resulting in multi-wavelength photothermally-responsive MOFtors (PPy/ZIF-8). Under the irradiation of near-infrared (NIR)/ultraviolet (UV)/blue light, the MOFtors all exhibited negative phototaxis and high-speed motion behaviour with the highest speed of 2215 ± 338 µm s-1. In addition, it is proved that these MOFtors can slowly self-float up in an aqueous environment. The light irradiation will accelerate the upward movement of the MOFtors, and the time required for the MOFtors to move to the top is negatively correlated with the light intensity. Finally, efficient antibacterial performances (up to 98.89% against S. aureus) are achieved with these light-driven MOFtors owing to the boosted Zn2+ release by vigorous stirring motion and physical entrapment by the upward motion under light irradiation.

The uncovered biases and errors in clinical determination of bone age by using deep learning models.

OBJECTIVES: To evaluate AI biases and errors in estimating bone age (BA) by comparing AI and radiologists' clinical determinations of BA. METHODS: We established three deep learning models from a Chinese private dataset (CHNm), an American public dataset (USAm), and a joint dataset combining the above two datasets (JOIm). The test data CHNt (n = 1246) were labeled by ten senior pediatric radiologists. The effects of data site differences, interpretation bias, and interobserver variability on BA assessment were evaluated. The differences between the AI models' and radiologists' clinical determinations of BA (normal, advanced, and delayed BA groups by using the Brush data) were evaluated by the chi-square test and Kappa values. The heatmaps of CHNm-CHNt were generated by using Grad-CAM. RESULTS: We obtained an MAD value of 0.42 years on CHNm-CHNt; this result indicated an appropriate accuracy for the whole group but did not indicate an accurate estimation of individual BA because with a kappa value of 0.714, the agreement between AI and human clinical determinations of BA was significantly different. The features of the heatmaps were not fully consistent with the human vision on the X-ray films. Variable performance in BA estimation by different AI models and the disagreement between AI and radiologists' clinical determinations of BA may be caused by data biases, including patients' sex and age, institutions, and radiologists. CONCLUSIONS: The deep learning models outperform external validation in predicting BA on both internal and joint datasets. However, the biases and errors in the models' clinical determinations of child development should be carefully considered. KEY POINTS: • With a kappa value of 0.714, clinical determinations of bone age by using AI did not accord well with clinical determinations by radiologists. • Several biases, including patients' sex and age, institutions, and radiologists, may cause variable performance by AI bone age models and disagreement between AI and radiologists' clinical determinations of bone age. • AI heatmaps of bone age were not fully consistent with human vision on X-ray films.

Large-Scale Self-Assembly of MOFs Colloidosomes for Bubble-Propelled Micromotors and Stirring-Free Environmental Remediation.

The design of MOF-based micromotors (MOFtors) is still challenging and with limited approaches, especially for the MOF nanoparticles (NPs). Herein, we report a universal and straightforward strategy to efficiently self-assembly MOF NPs into robust MOFtors for enhanced organic- or heavy-metal-ion-contaminants remediation without mechanical stirring. Based on the transient Pickering emulsion method, Fe3 O4 @NH2 -UiO-66 (Fe-UiO) NPs are rapidly self-assembled into Fe3 O4 @NH2 -UiO-66 colloidosomes (Fe-UiOSomes) on a large scale, and the formation mechanism is systematically studied. The Fe-UiOSomes-Pt micromotors through chemical reduction (Micromotor-C) presented a higher motility of 450±180 µm s-1 in a 5 wt% H2 O2 aqueous solution. Finally, the bubble-propelled Micromotor-C was employed to efficiently remove dyes and heavy metal ions (94 % for MO and 91 % for CrVI ).

Laser-based bioprinting for multilayer cell patterning in tissue engineering and cancer research.

3D printing, or additive manufacturing, is a process for patterning functional materials based on the digital 3D model. A bioink that contains cells, growth factors, and biomaterials are utilized for assisting cells to develop into tissues and organs. As a promising technique in regenerative medicine, many kinds of bioprinting platforms have been utilized, including extrusion-based bioprinting, inkjet bioprinting, and laser-based bioprinting. Laser-based bioprinting, a kind of bioprinting technology using the laser as the energy source, has advantages over other methods. Compared with inkjet bioprinting and extrusion-based bioprinting, laser-based bioprinting is nozzle-free, which makes it a valid tool that can adapt to the viscosity of the bioink; the cell viability is also improved because of elimination of nozzle, which could cause cell damage when the bioinks flow through a nozzle. Accurate tuning of the laser source and bioink may provide a higher resolution for reconstruction of tissue that may be transplanted used as an in vitro disease model. Here, we introduce the mechanism of this technology and the essential factors in the process of laser-based bioprinting. Then, the most potential applications are listed, including tissue engineering and cancer models. Finally, we present the challenges and opportunities faced by laser-based bioprinting.

Amplitude of low-frequency fluctuation may be an early predictor of delayed motor development due to neonatal hyperbilirubinemia: a fMRI study.

BACKGROUND: Acute bilirubin encephalopathy or kernicterus is the worst consequence of brain damage caused by the elevation of total unbound serum bilirubin (TSB) in neonates. The present study aimed to visualize the characteristic brain regions of neonates with hyperbilirubinemia (HB) using functional magnetic resonance imaging (fMRI) and to measure the amplitude of low-frequency fluctuation (ALFF) values. METHODS: This was a prospective cohort study, which included newborns with HB who were hospitalized at the Children's Hospital of Fudan University. The control group included neonates admitted with neonatal simple wet lung or pneumonia without neurological disease or brain injury. Newborns were divided into a severe hyperbilirubinemia group (SHB), moderate HB group, and control group based on TSB levels. The newborns completed routine MRI combined with fMRI scans and brainstem auditory evoked potentials (BAEPs) during their hospitalization. RESULTS: A total of 251 newborns were included in this study. There were 45 patients in the SHB group, 65 in the HB group, and 141 in the control group. The average ALFF value in the basal ganglia region in the SHB group was the highest, which was greater than that in the HB and control groups (P<0.001). The ALFF increased with an increase in TSB concentration. Based on the results of the Bayley Scales of infant development assessment, we further found that the most significant difference in ALFF remained in the basal ganglia region between newborns with motor development scores above 70 (including 70) and below 70. Correlation analysis revealed a strong negative correlation between motor development scores and ALFF (r=-0.691, P<0.001). When ALFF alone was used to predict motor development, the sensitivity was 89%. When ALFF was combined with TSB and BEAP results, the area under the ROC curve was the largest (AUC =0.85). The sensitivity and specificity of the model were 67.86% and 90.77%, respectively. CONCLUSIONS: The ALFF value may be able to serve as an early imaging biomarker and has a greater sensitivity than TSB or BAEP results in predicting long-term motor development (18 m) in HB.

Altered striatum centered brain structures in SHANK3 deficient Chinese children with genotype and phenotype profiling.

SHANK3 deficiency represents one of the most replicated monogenic risk factors for autism spectrum disorder (ASD) and SHANK3 caused ASD presents a unique opportunity to understand the underlying neuropathological mechanisms of ASD. In this study, genetic tests, comprehensive clinical and neurobehavioral evaluations, as well as multimodal structural MRI using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were conducted in SHANK3 group (N = 14 with SHANK3 defects), ASD controls (N = 26 with idiopathic ASD without SHANK3 defects) and typically developing (TD) controls (N = 32). Phenotypically, we reported several new features in Chinese SHANK3 deficient children including anteverted nares, sensory stimulation seeking, dental abnormalities and hematological problems. In SHANK3 group, VBM revealed decreased grey matter volumes mainly in dorsal striatum, amygdala, hippocampus and parahippocampal gyrus; TBSS demonstrated decreased fractional anisotropy in multiple tracts involving projection, association and commissural fibers, including middle cerebral peduncle, corpus callosum, superior longitudinal fasciculus, corona radiata, external and internal capsule, and posterior thalamic radiation, etc. We report that the disrupted striatum centered brain structures are associated with SHANK3 deficient children. Study of subjects with monogenic cause offer specific insights into the neuroimaging studies of ASD. The discovery may support a path for future functional connectivity studies to allow for more in-depth understandings of the abnormal neural circuits and the underlying neuropathological mechanisms for ASD.

DeepVolume: Brain Structure and Spatial Connection-Aware Network for Brain MRI Super-Resolution.

Thin-section magnetic resonance imaging (MRI) can provide higher resolution anatomical structures and more precise clinical information than thick-section images. However, thin-section MRI is not always available due to the imaging cost issue. In multicenter retrospective studies, a large number of data are often in thick-section manner with different section thickness. The lack of thin-section data and the difference in section thickness bring considerable difficulties in the study based on the image big data. In this article, we introduce DeepVolume, a two-step deep learning architecture to address the challenge of accurate thin-section MR image reconstruction. The first stage is the brain structure-aware network, in which the thick-section MR images in axial and sagittal planes are fused by a multitask 3-D U-net with prior knowledge of brain volume segmentation, which encourages the reconstruction result to have correct brain structure. The second stage is the spatial connection-aware network, in which the preliminary reconstruction results are adjusted slice-by-slice by a recurrent convolutional network embedding convolutional long short-term memory (LSTM) block, which enhances the precision of the reconstruction by utilizing the previously unassessed sagittal information. We used 305 paired brain MRI samples with thickness of 1.0 mm and 6.5 mm in this article. Extensive experiments illustrate that DeepVolume can produce the state-of-the-art reconstruction results by embedding more anatomical knowledge. Furthermore, considering DeepVolume as an intermediate step, the practical and clinical value of our method is validated by applying the brain volume estimation and voxel-based morphometry. The results show that DeepVolume can provide much more reliable brain volume estimation in the normalized space based on the thick-section MR images compared with the traditional solutions.

Co3O4@CdS Hollow Spheres Derived from ZIF-67 with a High Phenol and Dye Photodegradation Activity.

The Co3O4@CdS double-layered hollow spheres were first prepared by the template-removal method with the assistance of the ZIF-67 material; the structure has been proved by transmission electron microscopy (TEM). The Co3O4@CdS hollow spheres calcinated at 400 °C exhibited the highest photodegradation activity. Nearly 90% phenol was degraded after 2 h of visible-light irradiation. More than 80% rhodamine-B (RhB) was degraded within the first 30 min and nearly eliminated after 1 h of irradiation. The mechanism of the photodegradation reaction was investigated. Based on the analysis of electron spin resonance (ESR) spectra and radical trapping test, it was found that superoxide radicals are the major oxidative species for dye degradation and holes and hydroxyl radicals are the major oxidative species for phenol degradation. These results may be used in industrial wastewater treatment. The reaction obeys first-order reaction kinetics, and the rate constant of the Co3O4@CdS hollow sphere in dye degradation is 0.05 min-1 and that in phenol degradation is 0.02 min-1, which is three times higher than that of CdS nanoparticles. These results indicated the high oxidizing ability of the samples.

Application of Robot-Assisted Frameless Stereoelectroencephalography Based on Multimodal Image Guidance in Pediatric Refractory Epilepsy: Experience of a Pediatric Center in a Developing Country.

OBJECTIVE: To introduce the application of robot-assisted frameless stereoelectroencephalography (SEEG) based on multimodal image fusion technology in pediatric refractory epilepsy in a pediatric center from a developing country. METHODS: We retrospectively evaluated pediatric patients with drug-resistant epilepsy who underwent SEEG monitoring at the Children's Hospital of Fudan University from July 2014 to August 2017. Application of multimodal image fusion technology in SEEG was described in detail. Seizure outcomes were assessed according to the International League Against Epilepsy classification. RESULTS: A total of 208 patients were initially eligible and underwent a rigorous phase I evaluation. SEEG explorations were performed in 20 patients who entered phase II assessment (11 male and 9 female patients) with a median age of 7.99 ± 4.07 years. In total, 181 electrodes were implanted (9 per implantation), among which 16 implantations were unilateral (6 left and 10 right) and 4 were bilateral. The mean operating time was 3 hours and no obvious hemorrhage occurred. Electrode displacement and pneumocephalus were observed in 1 and 2 patients, respectively. Thirteen and 7 patients underwent tailored resection and radiofrequency thermocoagulation, respectively. Among resection cases, focal cortical dysplasia was the predominant pathologic type. The overall seizure outcome after a mean follow-up of 2.65 years was International League Against Epilepsy class 1 in 13, class 2 in 2, class 3 in 3, class 4 in 1, and class 5 in 1 patient, respectively. CONCLUSIONS: The combination of multimodal image fusion and frameless robot-assisted SEEG is demonstrated to be safe and effective on children with refractory epilepsy in developing countries.

Clinical Features, Treatment, and Outcomes Among Chinese Children With Anti-methyl-D-aspartate Receptor (Anti-NMDAR) Encephalitis.

Objective: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common form of autoimmune encephalitis in pediatric patients. In this study, we aimed to investigate the clinical features and long-term outcomes of pediatric patients with anti-NMDAR encephalitis in China. Methods: We conducted a retrospective study of children (age range: 0-18 years) with anti-NMDAR encephalitis treated at Children's Hospital of Fudan University between July 2015 and November 2018. Demographic characteristics, clinical features, treatment, and outcomes were reviewed. Results: Thirty-four patients with anti-NMDAR encephalitis were enrolled (age range: 5 months to 14 years; median age: 7 years; female: 18). The median follow- up duration was 20 months (range: 6-39 months). Eighteen (52.9%) patients initially presented with seizures and 10 (29.4%) with abnormal (psychiatric) behaviors or cognitive dysfunction. Thirty (88.2%) patients exhibited more than two symptoms during the disease course. No neoplasms were detected. Twelve (35.2%) patients had abnormal cerebrospinal fluid (CSF) findings, including leukocytosis, and increased protein concentration. Eighteen (52.9%) patients exhibited normal brain MRI findings. Electroencephalography revealed abnormal background activity in 27 (79.4%) patients, and epileptiform discharges in 16 (47.0%) patients prior to immunotherapy. All patients received first-line immunotherapy, with 30 (88.2%) and four (11.8%) patients achieving good (Modified Rankin Scale [mRS] score of 0-2) and poor outcomes (mRS score of 3-5), respectively. Initial mRS scores differed significantly between the good and poor outcome groups. Fourteen out of 18 patients (77.7%) with seizures accepted anti-epileptic drug (AED) administration, and seizure freedom was achieved in 12 out of 14 (85.7%) patients at the last follow-up. Ten of these 12 (83.3%) patients withdrew from AED treatment within 1 year. Conclusions: Most patients achieved seizure freedom, so long-term use of AEDs may not be necessary for pediatric patients with anti-NMDAR encephalitis. Among our patients, 83.3% were sensitive to first-line immunotherapy and achieved good outcomes. Higher mRS scores before immunotherapy predicted poor outcomes, highlighting the need for a comprehensive assessment of patients with anti-NMDAR encephalitis.

Clinical features of postinfectious bronchiolitis obliterans in children undergoing long-term nebulization treatment.

BACKGROUND: Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treatment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to outline the features of clinical, high-resolution computed tomography (HRCT) and pulmonary function test (PFT) of PIBO, undergoing maintenance therapy utilizing a triple nebulization treatment and to determine the factors associated with prognosis. METHODS: Children diagnosed with PIBO were followed up between April 2014 and March 2017. The clinical features after maintenance nebulization treatment for 12 months were thereafter summarized. RESULTS: Thirty patients, 21 boys and 9 girls, were enrolled in the study. The median age of patients was 17.4 months, with a range between 3.0 and 33 months. Persistent coughing and wheezing were detected whilst wheezing and crackles were the common manifestations presented. HRCT scans revealed patchy ground and glass opacity, while PFT showed fixed airway obstruction in all patients. Four patients were lost during follow-up. After treatment, the clinical symptoms were improved greatly in all patients (P < 0.01). The mean increase in the percentage of TPEF%TE and VPEF%VE were improved greatly (P < 0.01). Images of the HRCT scan indicated marked improvements in 18 patients (81.8%) in comparison with scans obtained pre-treatment. CONCLUSIONS: Our data suggest a potential role of long-term nebulization treatment of budesonide, terbutaline, ipratropium bromide on PIBO, due to its efficacy as indicated in the improved clinical symptoms, pulmonary functions and CT manifestations identified in the children. New prospective and controlled studies are required to confirm this proposition.

Infantile Onset Intractable Inflammatory Bowel Disease Due to Novel Heterozygous Mutations in TNFAIP3 (A20).

Background: Mutations in tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a key player in the negative feedback regulation of nuclear factor-κB signaling, have recently been recognized as leading to early onset autoinflammatory and autoimmune syndrome. Here, we have reported the phenotypes of 3 infantile onset intractable inflammatory bowel disease (IBD) patients with TNFAIP3 mutations and reviewed previously reported cases to establish phenotypic features associated with TNFAIP3 monogenicity. Methods: From January 1, 2015, to December 31, 2017, we recruited 58 infantile-onset IBD patients. Targeted sequencing and whole-exome sequencing were performed. Sanger sequencing confirmed the variants and determined the parental origin. We followed all the patients with TNFAIP3 mutations in our cohort and analyzed their clinical data. Results: Genetic screening in all 58 patients with infantile-onset IBD revealed 44 (75.9%) cases of monogenic disorders, and 3 de novo TNFAIP3 mutations were identified, including 1 nonsense and 2 frame shift mutations. All the mutations resulted in premature stop codon. All 3 patients had multiple systemic involvements, with predominant gastrointestinal diseases. Conclusions: Most infantile-onset IBD was associated with monogenetic mutation, and in addition to the 50 reported genes, other rare genetic variants need to be determined. TNFAIP3 may be an important candidate gene. The treatment of TNFAIP3-associated infantile-onset-IBD was challenging. 10.1093/ibd/izy165_video1izy165.video15789607089001.

Facile fabrication of highly controllable gating systems based on the combination of inverse opal structure and dynamic covalent chemistry.

A three-dimensional (3D) inverse opal with periodic and porous structures has shown great potential for applications not only in optics and optoelectronics, but also in functional membranes. In this work, the benzaldehyde group was initially introduced into a 3D nanoporous inverse opal, serving as a platform for fabricating functional membranes. By employing the dynamic covalent approach, a highly controllable gating system was facilely fabricated to achieve modulable and reversible transport features. It was found that the physical/chemical properties and pore size of the gating system could easily be regulated through post-modification with amines. As a demonstration, the gated nanopores were modified with three kinds of amines to control the wettability, surface charge and nanopore size which in turn was exploited to achieve selective mass transport, including hydrophobic molecules, cations and anions, and the transport with respect to the physical steric hindrance. In particular, the gating system showed extraordinary reversibility and could recover to its pristine state by simply changing pH values. Due to the unlimited variety provided by the Schiff base reaction, the inverse opal described here exhibits a significant extendibility and could be easily post-modified with stimuli-responsive molecules for special purposes. Furthermore, this work can be extended to employ other dynamic covalent routes, for example Diels-Alder, ester exchange and disulfide exchange-based routes.

Endoscopic Third Ventriculostomy Instead of Shunt Revision in Children Younger Than 3 Years of Age.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) is a valuable option in the treatment of shunt failure, but no clinical data exist for young children. The aim of this study was to elucidate the role of ETV in patients younger than 3 years of age with shunt malfunction. METHODS: A cohort of 37 patients younger than 3 years of age with shunt malfunction underwent ETV instead of shunt revision. Patients' preoperative condition and medical history were studied to determine the impact of a number of variables on outcome. The Fisher exact test was used to assess differences among groups. RESULTS: Median age at ETV was 21.6 months (8-36 months). Diagnosis was obstructive hydrocephalus in 24 patients and communicating hydrocephalus in 13. Median age at initial shunt placement was 3.2 months (10 days to 30 months). The etiology of shunt malfunction was obstruction (n = 27) or infection (n = 10). Overall ETV failure rate was 40.5% (15/37). Patients whose age at initial shunt placement was <6 months and/or who had a preterm birth history had higher relative rates of ETV failure. Other variables, including type of hydrocephalus, interval between initial shunt placement and ETV, history of intraventricular bleeding and/or infection, and etiology of shunt malfunction, did not significantly affect the final outcome. CONCLUSIONS: Patients younger than 3 years with obstructive or communicating hydrocephalus may benefit from ETV in the event of shunt malfunction and have about a 60% probability of becoming shunt free.

Novel morphology changes from 3D ordered macroporous structure to V2O5 nanofiber grassland and its application in electrochromism.

Because vanadium pentoxide (V2O5) is the only oxide that shows both anodic and cathodic coloration electrochromism, the reversible lithium ion insertion/extraction processes in V2O5 lead to not only reversible optical parameter changes but also multicolor changes for esthetics. Because of the outstanding electrochemical properties of V2O5 nanofibers, they show great potential to enhance V2O5 electrochromism. However, the development and practical application of V2O5 nanofibers are still lacking, because traditional preparation approaches have several drawbacks, such as multiple processing steps, unsatisfactory electrical contact with the substrate, expensive equipment, and rigorous experimental conditions. Herein, we first report a novel and convenient strategy to prepare grass-like nanofiber-stacked V2O5 films by a simple annealing treatment of an amorphous, three-dimensionally ordered macroporous vanadia film. The V2O5 nanofiber grassland exhibits promising transmittance modulation, fast switching responses, and high color contrast because of the outstanding electrochemical properties of V2O5 nanofibers as well as the high Li-ion diffusion coefficients and good electrical contact with the substrate. Moreover, the morphology transformation mechanism is investigated in detail.