Association of MRI Indexes of the Perivascular Space Network and Cognitive Impairment in Patients with Obstructive Sleep Apnea.

Background The role of perivascular space (PVS) dysfunction in obstructive sleep apnea (OSA) requires further study. Purpose To compare MRI indexes of PVS across patients with differing severities of OSA and relate them with disease characteristics and treatment. Materials and Methods This single-center prospective study included healthy controls (HCs) and patients with complaints of snoring who underwent MRI and cognitive evaluation between June 2021 and December 2022. Participants with complaints of snoring were classified into four groups (snoring, mild OSA, moderate OSA, and severe OSA). PVS networks were assessed at MRI using PVS volume fraction, extracellular free water (FW), and diffusion tensor imaging analysis along the PVS (DTI-ALPS). One-way analysis of variance and Pearson correlation were used for analysis. Alterations in PVS indexes and cognitive performance after treatment were assessed in 15 participants with moderate OSA. Results A total of 105 participants (mean age, 33.4 years ± 8.9 [SD]; 80 males) and 50 HCs (mean age, 37.0 years ± 8.6; 33 males) were included. Higher mean PVS volume fraction was observed in participants with severe OSA (n = 23) than in patients with mild OSA (n = 36) (0.11 vs 0.10; P = .03). Participants with severe OSA exhibited higher mean FW index (0.11) than both HCs (0.10; P < .001) and patients with mild OSA (0.10; P = .003). All patient groups had lower DTI-ALPS than HCs (range, 1.5-1.9 vs 2.1; all P < .001). DTI-ALPS correlated with cognitive performance on the Stroop Color and Word Test (r range, -0.23 to -0.24; P value range, .003-.005). After treatment, PVS indexes changed (P value range, <.001 to .01) and cognitive performance improved (P value range, <.001 to .03). Conclusion Differences in PVS indexes were observed among participants with differing severities of OSA and HCs. Indexes correlated with measures of cognitive function, and changes in indexes and improvement in cognitive performance were observed after treatment in participants with moderate OSA. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Port in this issue.

Non-Abelian Topological Bound States in the Continuum.

Bound states in the continuum (BICs), which are spatially localized states with energies lying in the continuum of extended modes, have been widely investigated in both quantum and classical systems. Recently, the combination of topological band theory with BICs has led to the creation of topological BICs that exhibit extraordinary robustness against disorder. However, the previously proposed topological BICs are only limited in systems with Abelian gauge fields. Whether non-Abelian gauge fields can induce topological BICs and how to experimentally explore these phenomena remains unresolved. Here, we report the theoretical and experimental realization of non-Abelian topological BICs, which are generated by the interplay between two inseparable pseudospins and can coexist in each pseudospin subspace. This unique characteristic necessitates non-Abelian couplings that lack any Abelian counterparts. Furthermore, the non-Abelian couplings can also offer a new avenue for constructing topological subspace-induced BICs at bulk dislocations. Those exotic phenomena are observed by non-Abelian topolectrical circuits. Our results establish the connection between topological BICs and non-Abelian gauge fields, and serve as the catalyst for future investigations on non-Abelian topological BICs across different platforms.

The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT.

INTRODUCTION: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs. METHODS: This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic; CVD- and transplant-related variables; medications; urine albumin-to-creatinine ratio; and randomization status. We calculated areas under the curves (AUCs) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables. RESULTS: Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF, and death (aHR 1.85 [1.25-2.73], p < 0.01; 2.24 [1.36-3.70)], p < 0.01; 2.30 [1.48-3.58], p < 0.01, respectively) as compared to quartile 1. Adding angiopoietins to preexisting clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, p = 0.005) and GF or death (AUC improved from 0.68 to 0.70, p = 0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs. CONCLUSION: Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Knowledge-guided data mining on the standardized architecture of NRPS: Subtypes, novel motifs, and sequence entanglements.

Non-ribosomal peptide synthetase (NRPS) is a diverse family of biosynthetic enzymes for the assembly of bioactive peptides. Despite advances in microbial sequencing, the lack of a consistent standard for annotating NRPS domains and modules has made data-driven discoveries challenging. To address this, we introduced a standardized architecture for NRPS, by using known conserved motifs to partition typical domains. This motif-and-intermotif standardization allowed for systematic evaluations of sequence properties from a large number of NRPS pathways, resulting in the most comprehensive cross-kingdom C domain subtype classifications to date, as well as the discovery and experimental validation of novel conserved motifs with functional significance. Furthermore, our coevolution analysis revealed important barriers associated with re-engineering NRPSs and uncovered the entanglement between phylogeny and substrate specificity in NRPS sequences. Our findings provide a comprehensive and statistically insightful analysis of NRPS sequences, opening avenues for future data-driven discoveries.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Interface Engineering with the Coupling of a 3D Porous Structure Enables MoP2-NiCoP Heterostructure Nanosheets for Enhanced Alkaline Hydrogen Evolution Reaction.

One of the crucial parts of the electrochemically focused energy conversion and storage system is the hydrogen evolution reaction. The further exploration of electrocatalysts made of nonprecious metals could help to bring the technology closer to industrialization. Here, we present an effective hydrogen evolution reaction (HER) electrocatalyst that employs hydrothermal and phosphorization steps to create three-dimensional (3D) porous MoP2-NiCoP heterostructure nanosheets on nickel foam (MoP2-NiCoP/NF). H2O-dissociation and H-adsorption were effectively achieved due to the distinctive interface engineering between NiCoP and MoP2, which functions as a channel for immediate electron transfer. Compared to the single-component MoP2 and NiCoP, the synergistic interaction between the heterogeneous components coupling and the 3D porous structure enables MoP2-NiCoP/NF to exhibit satisfactory catalytic activity with an ultralow overpotential of 50 mV at 10 mA cm-2, which is close to the commercial Pt/C catalyst in alkaline media. More importantly, it exhibits good stability, with the ability to be electrolyzed in 1.0 M KOH electrolyte for 24 h without a significant change in overpotential. This study offers directions for the design of low-cost, high-activity, transition metal phosphides (TMPs)-based HER catalyst alternatives for future practical applications.

Integrated Heterogeneous Engineering with the Vacancy Defect of Porous CoPv-MoxPv Nanosheets for an Accelerated Hydrogen Evolution Reaction.

Electrochemical water splitting is a possible way of realizing sustainable and clean hydrogen production but is challenging, because a highly active and durable electrocatalyst is essential. In this work, we integrated heterogeneous engineering and vacancy defect strategies to design and fabricate a heterostructure electrocatalyst (CoPv-MoxPv/CNT) with abundant phosphorus vacancies attached to carbon nanotubes (CNTs). The vacancy defects enabled the optimization of the electronic structure; thereby, the electron-rich low-valent metal sites enhanced the ability of nonmetallic P to capture proton H. Meanwhile, the heterogeneous interface between bimetallic phosphides and CNTs realized rapid electron transfer. In addition, the Co, Mo, and P active species in the electrocatalytic process exposed increased amounts of active sites featuring porous nanosheet structures, which facilitated the adsorption of reaction intermediates and thus enhanced the hydrogen evolution reaction performance. In particular, the optimized CoPv-MoxPv/CNT catalyst possesses an overpotential of 138 mV at a current density of 10 mA cm-2 and long-term stability for 24 h. This work offers insights and possibilities for the engineering and exploration of transition metal-based electrocatalysts through combining multiple synergistic strategies.

Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

Altered neurovascular coupling in the children with attention-deficit/hyperactivity disorder: a comprehensive fMRI analysis.

The coupling between resting-state cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signals reflects the mechanism of neurovascular coupling (NVC), which have not been illustrated in attention-deficit/hyperactivity disorder (ADHD). Fifty ADHD and 42 age- and gender-matched typically developing controls (TDs) were enrolled. The NVC imaging metrics were investigated by exploring the Pearson correlation coefficients between CBF and BOLD-derived quantitative maps (ALFF, fALFF, DCP maps). Three types of NVC metrics (CBF-ALFF, CBF-fALFF, CBF-DCP coupling) were compared between ADHD and TDs group, and the inner association between altered NVC metrics and clinical variables in ADHD group was further analyzed. Compared to TDs, ADHD showed significantly reduced whole-brain CBF-ALFF coupling (P < 0.001). Among regional level (all PFDR < 0.05), ADHD showed significantly lower CBF-ALFF coupling in bilateral thalamus, default-mode network (DMN) involving left anterior cingulate (ACG.L) and right parahippocampal gyrus (PHG.R), execution control network (ECN) involving right middle orbital frontal gyrus (ORBmid.R) and right inferior frontal triangular gyrus (IFGtriang.R), and increased CBF-ALFF coupling in attention network (AN)-related left superior temporal gyrus (STG.L) and somatosensory network (SSN))-related left rolandic operculum (ROL.L). Furthermore, increased CBF-fALFF coupling was found in the visual network (VN)-related left cuneus and negatively correlated with the concentration index of ADHD (R = - 0.299, PFDR = 0.035). Abnormal regional NVC metrics were at widespread neural networks in ADHD, mainly involved in DMN, ECN, SSN, AN, VN and bilateral thalamus. Notably, this study reinforced the insights into the neural basis and pathophysiological mechanism underlying ADHD.

Mixed Reality Surgical Navigation System; Positional Accuracy Based on Food and Drug Administration Standard.

BACKGROUND: Computer assisted surgical navigation systems are designed to improve outcomes by providing clinicians with procedural guidance information. The use of new technologies, such as mixed reality, offers the potential for more intuitive, efficient, and accurate procedural guidance. The goal of this study is to assess the positional accuracy and consistency of a clinical mixed reality system that utilizes commercially available wireless head-mounted displays (HMDs), custom software, and localization instruments. METHODS: Independent teams using the second-generation Microsoft HoloLens© hardware, Medivis SurgicalAR© software, and localization instruments, tested the accuracy of the combined system at different institutions, times, and locations. The ASTM F2554-18 consensus standard for computer-assisted surgical systems, as recognized by the U.S. FDA, was utilized to measure the performance. 288 tests were performed. RESULTS: The system demonstrated consistent results, with an average accuracy performance that was better than one millimeter (.75 ± SD .37 mm). CONCLUSION: Independently acquired positional tracking accuracies exceed conventional in-market surgical navigation tracking systems and FDA standards. Importantly, the performance was achieved at two different institutions, using an international testing standard, and with a system that included a commercially available off-the-shelf wireless head mounted display and software.

Newly discovered mechanisms that mediate tumorigenesis and tumour progression: circRNA-encoded proteins.

Proteins produced by cap-independent translation mediated by an internal ribosome entry site (IRES) in circular RNAs (circRNAs) play important roles in tumour progression. To date, numerous studies have been performed on circRNAs and the proteins they encode. In this review, we summarize the biogenesis of circRNAs and the mechanisms regulating circRNA-encoded proteins expression. We also describe relevant research methods and their applications to biological processes such as tumour cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), apoptosis, autophagy and chemoresistance. This paper offers deeper insights into the roles that circRNA-encoded proteins play in tumours. It also provides a theoretical basis for the use of circRNA-encoded proteins as biomarkers of tumorigenesis and for the development of new targets for tumour therapy.

Disrupted small-world networks in children with drug-naïve atten-tion-deficit/hyperactivity disorder: a DTI-based network analysis.

OBJECTIVES: To explore the alterations in the white matter (WM) structural connectome in children with drug-naïve attention-deficit/hyperactivity disorder (ADHD). METHODS: Forty-nine pediatric ADHD and 51 age- and gender-matched typically developing (TD) children aged 6-14 years old were enrolled. This cross-sectional study applied graph theoretical analysis to assess the white matter organization based on deterministic diffusion tensor imaging (DTI). WM structural connectivity was constructed in 90 cortical and subcor-tical regions, and topological parameters of the resulting graphs were calculated. Networks were compared between two groups. The digit cancellation test (DCT) was taken to evaluate clinical symptom severity in pediatric ADHD, using the concentration index and the total cancellation test scores. Then, a partial correlation analysis was performed to explore the re-lationship between significant topologic metrics and clinical symptom severity. RESULTS: Compared to TDs, ADHD showed an increase in the characteristic path length (Lp), normalized clustering coefficient (γ), small-worldness (σ), and a decrease in the global effi-ciency (Eglob) (all P <0.05). Furthermore, ADHD showed reduced nodal centralities mainly in the regions of default mode (DMN), central executive network (CEN), basal ganglia, and bilateral thalamus (all P <0.05). After performing Benjamini-Hochberg's procedure, only left orbital part of superior frontal gyrus (ORBsup.L) and left caudate (CAU) were statistically significant (P < 0.05, FDR-corrected). In addition, the concentration index of ADHD was negatively correlated with the nodal betweenness of the left orbital part of the middle frontal gyrus (ORBmid.L) (r = -0.302, P = 0.042). CONCLUSIONS: Our findings revealed an ADHD-related shift of WM network topology toward "regularization" pattern, characterized by decreased global network integration, which is also reflected by changed nodal centralities involving DMN, CEN, basal ganglia, and bilateral thalamus. ADHD could be understood by examining the dysfunction of large-scale spatially distributed neural networks.

Breast Amide Proton Transfer Imaging at 3 T: Diagnostic Performance and Association With Pathologic Characteristics.

BACKGROUND: Amide proton transfer (APT) imaging has been increasingly applied in tumor characterization. However, its value in evaluating breast cancer remains undetermined. PURPOSE: To assess the diagnostic performance of APT imaging in breast cancer and its association with prognostic histopathologic characteristics. STUDY TYPE: Prospective. SUBJECTS: Eighty-four patients with breast lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/single-shot fast spin echo APT imaging. ASSESSMENT: APTw signal in breast lesion was quantified. Lesion malignancy, T stage, grades, Ki-67 index, molecular biomarkers (estrogen receptor [ER] expression, progesterone receptor [PR] expression, human epidermal growth factor receptor [HER-2] expression), molecular subtypes (luminal A, luminal B, triple negative, and HER-2 enriched) were determined. STATISTICAL TESTS: Student t-test, one-way analysis of variance, receiver operating characteristic analysis, and Pearson's correlation with P < 0.05 as statistical significance. RESULTS: APTw signal was significantly higher in malignant lesions (1.55% ± 1.24%) than in benign lesions (0.54% ± 1.13%), and in grade III lesions than in grade II lesions (1.65% ± 0.84% vs. 0.96% ± 0.96%), and in T2- (1.57% ± 0.64%) and T3-stage lesions (1.54% ± 0.63%) than in T1-stage lesions (0.81% ± 0.64%) for invasive breast carcinoma of no special type. APTw signal significantly correlated with Ki-67 index (r = 0.364) but showed no significant difference in groups of ER (P = 0.069), PR (P = 0.069), HER-2 (P = 0.961), and among molecular subtypes (P = 0.073). DATA CONCLUSION: APT imaging shows potential in differentiating breast lesion malignancy and associates with prognosis-related tumor grade, T stage, and proliferative activity. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Glymphatic system dysfunction in pediatric acute lymphoblastic leukemia without clinically diagnosed central nervous system infiltration: a novel DTI-ALPS method.

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) infiltration commonly occurs in children with acute lymphoblastic leukemia (ALL). Nevertheless, CNS infiltration is rarely detected at the initial diagnosis. The glymphatic system, which regulates cerebrospinal fluid (CSF) and interstitial fluid transport, is considered one of the possible routes of CNS infiltration by leukemia cells. In this study, we used diffusion tensor image analysis along the perivascular space (DTI-ALPS) method to investigate glymphatic system function and obtained CSF volume using synthetic magnetic resonance imaging (SyMRI) in pediatric ALL without clinically diagnosed CNS infiltration. MATERIALS AND METHODS: Twenty-nine ALL and 29 typically developing (TD) children were prospectively recruited (age 4-16 years) in the present study. Group differences in brain volumetric parameters, brain water diffusivities, and the ALPS index were evaluated after controlling for age, gender, and handedness. Furthermore, significant group-different parameters were correlated with clinical information using partial correlations analysis. RESULTS: Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). Moreover, the ALPS index was negatively associated with the risk classification (r = - 0.59, pFDR-corrected = 0.04) in pediatric ALL. CONCLUSIONS: Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration. These novel findings suggested that the glymphatic system might be essential in the early-stage process of ALL CNS infiltration, which provides a new direction for exploring underlying mechanisms and early detection of pediatric ALL CNS infiltration. KEY POINTS: • Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). • The ALPS index was negatively associated with the risk classification (r = -0.59, pFDR-corrected = 0.04) in pediatric ALL. • Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggested that the ALPS index and CSF volume might be promising imaging markers for early detection of pediatric ALL CNS infiltration.

Constructing a Functionalized Electrocatalyst of a Transition Metal Chalcogenide on Accordion-Like MXene to Boost the Hydrogen Evolution Reaction.

MXenes exhibit unique layered structures and excellent electrical conductivity, and their multiple surface termination groups are favorable for hosting impressive performance for electrochemical reactions. Therefore, a two-dimensional (2D) layered MXene-based catalyst may become a novel high-efficiency electrocatalyst to replace traditional noble metal electrocatalysts. In this work, a transition metal chalcogenide (MoS2/CuS) and MXene are combined to prepare a 2D electrocatalyst (MoS2/CuS/MXene) for the hydrogen evolution reaction (HER). MXene exhibited a large specific surface area in the shape of an accordion, which was very beneficial for the growth of nanomaterials. CuS/MXene promoted electron transfer and improved the exposed active site for HER. The exposed MoS2 edges exhibited a high chemical adsorption capacity, which is conducive to HER. Electrochemical tests reveal that the MoS2/CuS/MXene electrocatalyst can reduce the charge transfer resistance toward the HER and increase active sites for HER, leading to enhancing the catalytic performance. The MoS2/CuS/MXene electrocatalyst affords an efficient HER with a low overpotential (115 mV@10 mA cm-2). This work offers a new idea to create layered transition metal chalcogenide- and MXene-based electrocatalysts for HER.

Paired dCas9 design as a nucleic acid detection platform for pathogenic strains.

The wide application of molecular beacon probes in specific DNA detection, especially in the fast prototyping of pathogen DNA detection kits in point-of-care diagnostics, has been hindered by the nonflexible choice of target sequences and the unstable fluorophore output. We developed an in vitro DNA detection system consisting of a pair of dCas9 proteins linked to split halves of luciferase, named the Paired dCas9 (PC) reporter. Co-localization of the reporter pair to a ~46 bp target sequence defined by two single guide RNAs (sgRNAs) activated luciferase which subsequently generated highly intensified luminescent signals. Combined with an array design and statistical analyses, the PC reporter system could be programmed to access sequence information across the entire genome of the pathogenic Mycobacterium tuberculosis H37Rv strain. These findings suggest great potential for the PC reporter in effective and affordable in vitro nucleic acid detection technologies. In this article we highlighted the systems design from our previous researchworkon the PC reporter (Zhang et al, 2015)with a focuson methodology.

The Relationship Between Cortical Morphological and Functional Topological Properties and Clinical Manifestations in Patients with Posttraumatic Diffuse Axonal Injury: An Individual Brain Network Study.

To evaluate the altered network topological properties and their clinical relevance in patients with posttraumatic diffuse axonal injury (DAI). Forty-seven participants were recruited in this study, underwent 3D T1-weighted and resting-state functional MRI, and had single-subject morphological brain networks (MBNs) constructed by Kullback-Leibler divergence and functional brain networks (FBNs) constructed by Pearson correlation measurement interregional similarity. The global and regional properties were analyzed and compared using graph theory and network-based statistics (NBS), and the relationship with clinical manifestations was assessed. Compared with those of the healthy subjects, MBNs of patients with DAI showed a higher path length ([Formula: see text]: P = 0.021, [Formula: see text]: P = 0.011), lower clustering ([Formula: see text]: P = 0.002) and less small-worldness ([Formula: see text]: P = 0.002), but there was no significant difference in the global properties of FBNs (P: 0.161-0.216). For nodal properties of MBNs and FBNs, several regions showed significant differences between patients with DAI and healthy controls (HCs) (P < 0.05, FDR corrected). NBS analysis revealed that MBNs have more altered morphological connections in the frontal parietal control network and interhemispheric connections (P < 0.05). DAI-related global or nodal properties of MBNs were correlated with physical disability or dyscognition (P < 0.05/7, with Bonferroni correction), and the alteration of functional topology properties mediates this relationship. Our results suggested that disrupted morphological topology properties, which are mediated by FBNs and correlated with clinical manifestations of DAI, play a critical role in the short-term and medium-term phases after trauma.

Dexmedetomidine provides type-specific tumour suppression without tumour-enhancing effects in syngeneic murine models.

BACKGROUND: Dexmedetomidine is a widely used anaesthetic adjuvant for cancer resection surgeries. However, recent reports suggest that it may promote tumour growth or metastasis, so it is essential to clarify its tumour-related effects. METHODS: Seven syngeneic murine tumour models were used to assess the impact of dexmedetomidine on primary tumour growth, spontaneous tumour metastasis, and surgical resection-associated metastasis. Cancer cell proliferation and apoptosis experiments, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays, immune cell analysis, specific T-cell depletion experiments, and gene transcription analysis were conducted to identify the underlying mechanisms. RESULTS: Dexmedetomidine did not affect growth of EO771 or 4T1 breast tumours, LAP0297 or LLC lung tumours, MCA205 fibrosarcoma, or their spontaneous lung metastases. It did not promote lung metastasis after breast cancer resection. Dexmedetomidine significantly suppressed MCA38 and CT26 colorectal tumour growth (P<0.01) and promoted apoptosis in MCA38 tumour tissues (P<0.05) without affecting proliferation and apoptosis of MCA38 tumour cells in vitro, suggesting indirect anti-tumour effects. Dexmedetomidine increased the proportions of intratumour CD4+ T (P<0.01), CD8+ T (P<0.001), and natural killer cells (P<0.01), and it upregulated transcription of the cytotoxicity-related genes Infg, Tnfa, and Cxcl9 (P<0.05) in MCA38 tumours. Either CD8+ or CD4+ T-cell depletion reversed the anti-tumour effects of dexmedetomidine on MCA38 tumours (P<0.05). CONCLUSIONS: Dexmedetomidine conferred colorectal tumour-type specific suppression by modulation of tumour CD4+ and CD8+ T cells without tumour-enhancing effects.