Whole brain morphologic features improve the predictive accuracy of IDH status and VEGF expression levels in gliomas.

Glioma is a systemic disease that can induce micro and macro alternations of whole brain. Isocitrate dehydrogenase and vascular endothelial growth factor are proven prognostic markers and antiangiogenic therapy targets in glioma. The aim of this study was to determine the ability of whole brain morphologic features and radiomics to predict isocitrate dehydrogenase status and vascular endothelial growth factor expression levels. This study recruited 80 glioma patients with isocitrate dehydrogenase wildtype and high vascular endothelial growth factor expression levels, and 102 patients with isocitrate dehydrogenase mutation and low vascular endothelial growth factor expression levels. Virtual brain grafting, combined with Freesurfer, was used to compute morphologic features including cortical thickness, LGI, and subcortical volume in glioma patient. Radiomics features were extracted from multiregional tumor. Pycaret was used to construct the machine learning pipeline. Among the radiomics models, the whole tumor model achieved the best performance (accuracy 0.80, Area Under the Curve 0.86), while, after incorporating whole brain morphologic features, the model had a superior predictive performance (accuracy 0.82, Area Under the Curve 0.88). The features contributed most in predicting model including the right caudate volume, left middle temporal cortical thickness, first-order statistics, shape, and gray-level cooccurrence matrix. Pycaret, based on morphologic features, combined with radiomics, yielded highest accuracy in predicting isocitrate dehydrogenase mutation and vascular endothelial growth factor levels, indicating that morphologic abnormalities induced by glioma were associated with tumor biology.

Cortical myelin and thickness mapping provide insights into whole-brain tumor burden in diffuse midline glioma.

Systemic infiltration is a hallmark of diffuse midline glioma pathogenesis, which can trigger distant disturbances in cortical structure. However, the existence and effects of these changes have been underexamined. This study aimed to investigate whole-brain cortical myelin and thickness alternations induced by diffuse midline glioma. High-resolution T1- and T2-weighted images were acquired from 90 patients with diffuse midline glioma with H3 K27-altered and 64 patients with wild-type and 86 healthy controls. Cortical thickness and myelin content was calculated using Human Connectome Project pipeline. Significant differences in cortical thickness and myelin content were detected among groups. Short-term survival prediction model was constructed using automated machine learning. Compared with healthy controls, diffuse midline glioma with H3 K27-altered patients showed significantly reduced cortical myelin in bilateral precentral gyrus, postcentral gyrus, insular, parahippocampal gyrus, fusiform gyrus, and cingulate gyrus, whereas diffuse midline glioma with H3 K27 wild-type patients exhibited well-preserved myelin content. Furtherly, when comparing diffuse midline glioma with H3 K27-altered and diffuse midline glioma with H3 K27 wild-type, the decreased cortical thickness in parietal and occipital regions along with demyelination in medial orbitofrontal cortex was observed in diffuse midline glioma with H3 K27-altered. Notably, a combination of cortical features and tumor radiomics allowed short-term survival prediction with accuracy 0.80 and AUC 0.84. These findings may aid clinicians in tailoring therapeutic approaches based on cortical characteristics, potentially enhancing the efficacy of current and future treatment modalities.

Machine learning-based identification and characterization of mast cells in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis. OBJECTIVES: Using machine learning, we localized and characterized esophageal mast cells (MCs) to decipher their potential role in disease pathology. METHODS: Esophageal biopsy samples (EoE, control) were stained for MCs by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled. Machine learning software was trained to identify, enumerate, and characterize MCs, designated Mast Cell-Artificial Intelligence (MC-AI). RESULTS: MC-AI enumerated cell counts with high accuracy. During active EoE, epithelial MCs increased and lamina propria (LP) MCs decreased. In controls and EoE remission patients, papillae had the highest MC density and negatively correlated with epithelial MC density. MC density in the epithelium and papillae correlated with the degree of epithelial eosinophilic inflammation, basal zone hyperplasia, and LP fibrosis. MC-AI detected greater MC degranulation in the epithelium, papillae, and LP in patients with EoE compared with control individuals. MCs were localized further from the basement membrane in active EoE than EoE remission and control individuals but were closer than eosinophils to the basement membrane in active EoE. CONCLUSIONS: Using MC-AI, we identified a distinct population of homeostatic esophageal papillae MCs; during active EoE, this population decreases, undergoes degranulation, negatively correlates with epithelial MC levels, and significantly correlates with distinct histologic features. Overall, MC-AI provides a means to understand the potential involvement of MCs in EoE and other disorders.

Phenotypic features, prevalence of KCNJ11-MODY in Chinese patients with early-onset diabetes and a literature review.

OBJECTIVE: Gain-of-function (GOF) variants of KCNJ11 cause neonate diabetes and maturity-onset diabetes of the young (KCNJ11-MODY), while loss-of-function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11-MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early-onset type 2 diabetes (EOD). DESIGN, PATIENTS AND MEASUREMENTS: We performed next-generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11-MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11-MODY. RESULTS: We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p = .268). Among 80 previously reported patients with KCNJ11-MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C-peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. CONCLUSIONS: Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11-MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11-MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments.

Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance.

AIMS: Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD). MATERIALS AND METHODS: ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants. RESULTS: Sixty-two rare ALMS1 variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of ALMS1 pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of ALMS1 according to ACMG were identified. Moreover, rare heterozygous pD variants of ALMS1 were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR. CONCLUSIONS: ALMS1 rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.

Evaluation of Key Molecular Markers in Adult Diffuse Gliomas Based on a Novel Combination of Diffusion and Perfusion MRI and MR Spectroscopy.

BACKGROUND: Preoperative identification of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status could help clinicians select the optimal therapy in patients with diffuse glioma. Although, the value of multimodal intersection was underutilized. PURPOSE: To evaluate the value of quantitative MRI biomarkers for the identification of IDH mutation and 1p/19q codeletion in adult patients with diffuse glioma. STUDY TYPE: Retrospective. POPULATION: Two hundred sixteen adult diffuse gliomas with known genetic test results, divided into training (N = 130), test (N = 43), and validation (N = 43) groups. SEQUENCE/FIELD STRENGTH: Diffusion/perfusion-weighted-imaging sequences and multivoxel MR spectroscopy (MRS), all 3.0 T using three different scanners. ASSESSMENT: The apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) of the core tumor were calculated to identify IDH-mutant and 1p/19q-codeleted statuses and to determine cut-off values. ADC models were built based on the 30th percentile and lower, CBV models were built based on the 75th centile and higher (both in five centile steps). The optimal tumor region was defined and the metabolite concentrations of MRS voxels that overlapped with the ADC/CBV optimal region were calculated and added to the best-performing diagnostic models. STATISTICAL TESTS: DeLong's test, diagnostic test, and decision curve analysis were performed. A P value <0.05 was considered to be statistically significant. RESULTS: Almost all ADC models achieved good performance in identifying IDH mutation status, among which ADC_15th was the most valuable parameter (threshold = 1.186; Youden index = 0.734; AUC_train = 0.896). The differential power of CBV histogram metrics for predicting 1p/19q codeletion outperformed ADC histogram metrics, and the CBV_80th-related model performed best (threshold = 1.435; Youden index = 0.458; AUC_train = 0.724). The AUCs of ADC_15th and CBV_80th models in the validation set were 0.857 and 0.733. These models tended to improve after incorporation of N-acetylaspartate/total_creatine and glutamate-plus-glutamine/total_creatine, respectively. DATA CONCLUSION: The intersection of ADC-, CBV-based histogram and MRS provide a reliable paradigm for identifying the key molecular markers in adult diffuse gliomas. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

A millimeter water-in-oil droplet as an alternative back exchange prevention strategy for hydrogen/deuterium exchange mass spectrometry of peptides/proteins.

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a versatile bioanalytical technique for protein analysis. Since the reliability of HDX-MS analysis considerably depends on the retention of deuterium labels in the post-labeling workflow, deuterium/hydrogen (D/H) back exchange prevention strategies, including decreasing the pH, temperature, and exposure time to protic sources of the deuterated samples, are widely adopted in the conventional HDX-MS protocol. Herein, an alternative and effective back exchange prevention strategy based on the encapsulation of a millimeter droplet of a labeled peptide solution in a water-immiscible organic solvent (cyclohexane) is proposed. Cyclohexane was used to prevent the undesirable uptake of water by the droplet from the atmospheric vapor through the air-water interface. Using the pepsin digest of deuterated myoglobin, our results show that back exchange kinetics of deuterated peptides is retarded in a millimeter droplet as compared to that in the bulk solution. Performing pepsin digestion directly in a water-in-oil droplet at room temperature (18-21 °C) was found to preserve more deuterium labels than that in the bulk digestion with an ice-water bath. Based on the present findings, it is proposed that keeping deuterated peptides in the form of water-in-oil droplets during the post-labelling workflow will facilitate the preservation of deuterium labels on the peptide backbone and thereby enhance the reliability of the H/D exchange data.

RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.

The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1-H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial-temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability.

Investigation of the genetic and clinical features of laterality disorders in prenatal diagnosis: discovery of a novel compound heterozygous mutation in the DNAH11 gene.

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.

Peptide Oxidation Induced by Liquid-Solid Contact Electrification as Revealed in Liquid Microjunction-Surface Sampling Probe Mass Spectrometry.

Reproducible peptide oxidation was observed using a homebuilt liquid microjunction-surface sampling probe (LMJ-SSP) platform for analyzing peptide standards. Although electrochemical oxidation and corona discharges have previously been associated with analyte oxidation in electrospray ionization (ESI) and ESI-related ambient ionization mass spectrometry (MS) methods, they were unlikely the causes for the peptide oxidation observed in the LMJ-SSP studies. A systematic investigation demonstrated that analyte oxidation was induced during the droplet drying on a solid surface through liquid-solid electrification processes. To minimize unwanted analyte oxidation, the water content in the sample solution should be decreased and the use of hydroxyl-functionalized substrates, such as glass slides, should be avoided. In addition, if water is an essential solvent component, adding an antioxidant, such as ascorbic acid, to the sample solution before droplet evaporation on the solid surface could lower the percentage of analyte oxidation. The present findings apply to all the MS methods that involve drying microliters of sample solution onto a suitable substrate in their sample preparation protocols.

Freestanding Block Copolymer Membranes with Tunable Pore Sizes Promoted by Subnanometer Nanowires.

Block copolymers (BCPs) have enduring appeal for its intriguing assembly behaviors. Nevertheless, the unsatisfactory mechanical properties of BCPs make it a problem to fabricate freestanding membranes and hindered practical applications. Herein, a freestanding membrane with tunable pore size is prepared simply by co-assembly of BCPs and subnanometer nanowires (SNWs), combining the abundant function of BCPs and prominent mechanical properties of SNWs. Benefited from synergy of the components and the hierarchical structure, the tensile strength of composite membrane is promoted by two orders of magnitude compared to that of BCPs. With the columnar pores aligning vertically to surfaces and the pore size regulated by processing conditions, the membranes exhibit precise size-selected effect in ultrafiltration of Au nanoparticles (Au NPs) and can distinct NPs with diameter difference as tiny as 5 nm, demonstrating the promising prospect in separation technology and even widespread fields.

Progressive structural damage in sleep-related hypermotor epilepsy.

This study aimed to explore the alterations in gray matter volume (GMV) based on high-resolution structural data and the temporal precedence of structural alterations in patients with sleep-related hypermotor epilepsy (SHE). After preprocessing of T1 structural images, the voxel-based morphometry and source-based morphometry (SBM) methods were applied in 60 SHE patients and 56 healthy controls to analyze the gray matter volumetric alterations. Furthermore, a causal network of structural covariance (CaSCN) was constructed using Granger causality analysis based on structural data of illness duration ordering to assess the causal impact of structural changes in abnormal gray matter regions. The GMVs of SHE patients were widely reduced, mainly in the bilateral cerebellums, fusiform gyri, the right angular gyrus, the right postcentral gyrus, and the left parahippocampal gyrus. In addition to those regions, the results of the SBM analysis also found decreased GMV in the bilateral frontal lobes, precuneus, and supramarginal gyri. The analysis of CaSCN showed that along with disease progression, the cerebellum was the prominent node that tended to affect other brain regions in SHE patients, while the frontal lobe was the transition node and the supramarginal gyrus was the prominent node that may be easily affected by other brain regions. Our study found widely affected regions of decreased GMVs in SHE patients; these regions underlie the morphological basis of epileptic networks, and there is a temporal precedence relationship between them.

Investigation on hybrid laser ablation and its application in fused silica damage mitigation.

We present and investigate a hybrid laser-based method of surface shaping for damage mitigation on fused silica surfaces. Damage sites were removed and precisely shaped into an optically-benign cone by a procedure of femtosecond laser ablation with a subsequent CO2 laser polishing process. The morphology of the cone rim was quantitatively predicted by a numerical model. Since the heat-affected zone (HAZ) of the laser polishing process was effectively confined by the optimization of ablation parameters, the dimensions of the raised rim were reduced by an order of magnitude. The intensity of the on-axis hotspot was positively related to the dimensions of the raised rim, and thus an inapparent downstream intensification was achieved by the rim reduction. Laser-induced damage threshold (LIDT) of the cone was tested to be ∼14 J/cm2 on the input surface. Therefore, the presented method is appropriate to mitigate damage and also provides a promising approach to manufacturing functional microstructures for high-power applications.

Influence of defects on the femtosecond laser damage resistance of multilayer dielectric gratings.

Multilayer dielectric (MLD) gratings with high diffraction efficiency and a high laser-induced damage (LID) threshold for pulse compressors are key to scaling the peak and average power of chirped pulse amplification lasers. However, surface defects introduced by manufacturing, storage, and handling processes can reduce the LID resistance of MLD gratings and impact the laser output. The underlying mechanisms of such defect-initiated LID remain unclear, especially in the femtosecond regime. In this Letter, we model dynamic processes in interactions of a 20-fs near-infrared (NIR) laser pulse and a MLD grating design in the presence of cylindrically symmetrical nodules and particle contaminants and cracks at the surface. Utilizing a dynamic model based on a 2D finite difference in time domain (FDTD) field solver coupled with photoionization, electron collision, and refractive index modification, we study the simulation results for the damage site distribution initiated by defects of various types and sizes and its impact on the LID threshold of the grating design.

Artificial Intelligence Applications in Glioma With 1p/19q Co-Deletion: A Systematic Review.

As an important genomic marker for oligodendrogliomas, early determination of 1p/19q co-deletion status is critical for guiding therapy and predicting prognosis in patients with glioma. The purpose of this study is to systematically review the literature concerning the magnetic resonance imaging (MRI) with artificial intelligence (AI) methods for predicting 1p/19q co-deletion status in glioma. PubMed, Scopus, Embase, and IEEE Xplore were searched in accordance with the Preferred Reporting Items for systematic reviews and meta-analyses guidelines. Methodological quality of studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2. Finally, 28 studies were included in the quantitative analysis. Diagnostic test accuracy reached an area under the ROC curve of 0.71-0.98 were reported in 24 studies. The remaining four studies with no available AUC provided an accuracy of 0.75-0. 89. The included studies varied widely in terms of imaging sequences, input features, and modeling methods. The current review highlighted that integrating MRI with AI technology is a potential tool for determination 1p/19q status pre-operatively and noninvasively, which can possibly help clinical decision-making. However, the reliability and feasibility of this approach still need to be further validated and improved in a real clinical setting. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 2.

An MRI Study Combining Virtual Brain Grafting and Surface-Based Morphometry Analysis to Investigate Contralateral Alterations in Cortical Morphology in Patients With Diffuse Low-Grade Glioma.

BACKGROUND: The human brain has ability to reorganize itself in response to glioma. However, the mechanism of cortical reorganization remains unclear. PURPOSE: To investigate alterations in cortical thickness and local gyration index (LGI) in patients with unilateral frontal lobe diffuse low-grade glioma (DLGG). STUDY TYPE: Retrospective. SUBJECTS: Ninety-nine patients with histopathologically proven DLGG invading the left frontal lobe (LF; N = 56) or the right frontal lobe (RF; N = 43), and healthy controls (HC; N = 53). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D T1-weighted images and gadolinium enhanced T1-weighted images using magnetization-prepared rapid gradient echo sequence, T2-weighted images, and fluid-attenuated inversion recovery using turbo spin echo sequence. ASSESSMENT: In patients with DLGG, virtual brain grafting combined with Freesurfer was utilized to enable automated cortical thickness and LGI calculation. In HC, standard FreeSurfer pipeline was applied to calculate these measures. Radiomic features were extracted from glioma using Pyradiomic software. STATISTICAL TESTS: General linear model and Pearson's correlation analysis. A P value <0.05 was considered statistically significant. RESULTS: For LF patients, there was significantly increased cortical thickness in the rostral middle frontal gyrus, significantly reduced cortical thickness in the precentral gyrus and hypogyrification in the lingual and medial orbitofrontal (MOF) gyrus in contralateral hemisphere. For RF patients, there was significantly increased cortical thickness in the middle temporal, lateral occipital extending to isthmus cingulate gyrus, significantly reduced cortical thickness in the precentral gyrus and hypogyrification in the lingual gyrus in the contralateral hemisphere. A negative association between four textural features of DLGG and LGI in the right MOF gyrus of LF group was found (r = -0.609, -0.442, -0.545, and -0.417, respectively). DATA CONCLUSION: Cortical thickness compensation was shown in contralateral homotopic location and some distant contralateral regions. Additionally, there was decreased cortical thickness in the contralateral precentral gyrus and hypogyrification in contralateral lingual gyrus. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Use of group IIB metal ions as charge carriers for collision-induced dissociation of glycopeptide and glycan.

RATIONALE: Dissociation of biomolecules by tandem mass spectrometry (MS/MS) generates a variety of fragment ions which provide useful information for the structural characterization of biomolecules. Different fragmentation strategies result in different mass spectra for the same molecule and thus provide distinct features. Charge carriers play important roles in determining the dissociation pathways of the target precursor ions. The use of various transition metals ions as charge carriers of glycopeptide and glycan might provide additional structural information and needs to be investigated. METHODS: A 9.4 T SolariX FTICR mass spectrometer was used for collision-induced dissociation (CID) of glycopeptide and glycan. Group IIB metal ions, including Zn2+ , Cd2+ and Hg2+ , were used as charge carriers. Glycopeptide NLTK-M5 G2 and glycan G1F were used as the model systems. RESULTS: For Zn2+ - and Cd2+ -adducted species, cross-ring cleavages, glycosidic cleavages and cleavages along the peptide backbone could be obtained. There is a high degree of similarity in their CID spectra with that of Mg2+ ion-adducted glycopeptide species. For Hg2+ -adducted species, only glycosidic cleavages were observed in high abundance. The formation of doubly-charged ions (M2+ ) and a series of [f-H]+ fragments indicated unique dissociation pathways for Hg2+ -adducted glycopeptide. CONCLUSIONS: Zn2+ and Cd2+ -adducted glycopeptide species produced similar dissociation CID spectra, whereas Hg2+ -adducted species produced significantly different CID spectra. Similar CID dissociation features were also observed for Group IIB metal ions adducted glycan species. These results demonstrated that different metal ions might be used to tune the dissociation behaviors of glycopeptides and glycans.

Ventral Tegmental Area Glutamatergic Neurons Facilitated Emergence From Isoflurane Anesthesia Involves Excitation of Lateral Septum γ-Aminobutyric Acid-ergic Neurons in Mice.

BACKGROUND: Ventral tegmental area (VTA) glutamatergic neurons promote wakefulness in the sleep-wake cycle; however, their roles and neural circuit mechanisms during isoflurane (ISO) anesthesia remain unclear. METHODS: Fiber photometry and in vivo electrophysiology were used to observe the changes in neuronal or terminal activity during ISO anesthesia and arousal processes. Optogenetic and anesthesia behaviors were used to investigate the effects of VTA glutamatergic neurons and their projections to the lateral septum (LS) during ISO anesthesia and arousal. Anterograde and retrograde tracings were performed to identify the connections between VTA glutamatergic neurons and the LS. RESULTS: Population activity and firing rates of VTA glutamatergic neurons decreased during ISO anesthesia (ISO: 95% confidence interval [CI], 0.83-2.06 Spikes.s-1 vs wake: 95% CI, 3.53-7.83 Spikes.s-1; P =.0001; n = 34 from 4 mice). Optogenetic activation of VTA glutamatergic neurons reduced the burst-suppression ratio in electroencephalography (laser: 95% CI, 13.09%-28.76% vs pre: 95% CI, 52.85%-71.59%; P =.0009; n = 6) and facilitated emergence (ChR2: 95% CI, 343.3-388.0 seconds vs mCherry: 95% CI, 447.6-509.8 seconds; P < .0001; n = 11/12) from ISO anesthesia. VTA glutamatergic neurons monosynaptically innervated LS γ-aminobutyric acid (GABA)-ergic neurons. The activity of VTA glutamatergic terminals in the LS decreased during ISO anesthesia, and optogenetic activation of the VTA glutamatergic terminals in the LS facilitated emergence from ISO anesthesia. Furthermore, optogenetic activation of VTA glutamatergic terminals increased the firing rates of LS γ-aminobutyric acid-ergic (GABAergic) neurons (laser: 95% CI, 0.85-4.03 Spikes.s-1 vs pre: 95% CI, 0.24-0.78 Spikes.s-1; P =.008; n = 23 from 4 mice) during ISO anesthesia. CONCLUSIONS: VTA glutamatergic neurons facilitated emergence from ISO anesthesia involving excitation of LS GABAergic neurons.

Prenatal ultrasound findings, genetic testing, and literature review of Isolated left subclavian artery.

BACKGROUND: The occurrence of Isolated left subclavian artery (ILSA) is relatively rare, ILSA is caused by the persistence of the dorsal segment of the sixth left arch, with regression of the fourth arch artery and interruption of the left dorsal aorta at the distal end of the seventh intersegmental artery on the left side during embryonic development. The left subclavian artery is connected to the pulmonary artery through an arterial duct, which can be closed or unobstructed. This abnormality can lead to congenital subclavian steal syndrome and vertebrobasilar artery insufficiency. CASE PRESENTATION: We reported three fetuses with ILSA and intracardiac malformation. Among them, one case was suspected to be diagnosed with ILSA by echocardiography, while the other two cases were not diagnosed, but were accidentally discovered during autopsy. We have also conducted a literature review of its prenatal screening, diagnosis, management, and outcomes. Our three cases were tested by WES-Trio (whole exome sequencing). Worldwide, the ILSA cases reported in English literature have not been detected by WES. And likely pathogenic results were found in our two cases. Although it could not explain the intracardiac malformation we found, it will help to explore the etiology in the future. CONCLUSIONS: Prenatal echocardiography detection and diagnosis of ILSA is a new challenge, which has different effects on the prognosis of the fetus. When finding intracardiac malformation with right aortic arch, we need to perform an unconventional view of ultrasound scanning and combine with CDFI to find the origin of the left subclavian artery. Although we cannot find the cause of the disease temporarily, but our genetic results can help prenatal genetic counseling.

Versatile Inorganic Subnanometer Nanowire Adhesive.

Adhesives are applied extensively in daily life and industries, and people have developed numerous commercial polymeric adhesives. However, in most cases, these adhesives work on dry surfaces in air and form permanent bonds with the substrates, limiting the applications of adhesives. Inspired by the innate adhesive functions of some animals, such as geckos, spiders, mussels, and clingfish, scientists have developed various adhesive compositions and structures to meet various conditions. Here, we show a versatile subnanometer nanowire (SNW) adhesive with high strength and great reversibility, which could be prepared at a large scale through a facile room-temperature reaction. The SNW adhesive contacts the substrates at multiple sites due to the ultrahigh flexibility, and meanwhile, the multilevel interactions among the SNWs endow them with strong cohesion, so they exhibit good adhesive performance. This adhesive is applicable to various substrates, such as metals, polymers, and glass, and not only possesses good stability at room temperature in air but also is suitable for underwater environments and ultralow temperatures. Moreover, this adhesive could be easily recycled and removed from the substrates without any residue and damage. The SNW adhesive not only inspires the design of hierarchical adhesive structures with new contact modes but also has potential for practical applications.