Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

The associations of peripheral interleukin alterations and hippocampal subfield volume deficits in schizophrenia.

The hippocampus is one of the brain regions most vulnerable to inflammatory insults, and the relationships between peripheral inflammation and hippocampal subfields in patients with schizophrenia remain unclear. In this study, forty-six stably medicated patients with schizophrenia and 48 demographically matched healthy controls (HCs) were recruited. The serum levels of IL - 1ß, IL-6, IL-10, and IL-12p70 were measured, and 3D high-resolution T1-weighted magnetic resonance imaging was performed. The IL levels and hippocampal subfield volumes were both compared between patients and HCs. The associations of altered IL levels with hippocampal subfield volumes were assessed in patients. Patients with schizophrenia demonstrated higher serum levels of IL-6 and IL-10 but lower levels of IL-12p70 than HCs. In patients, the levels of IL-6 were positively correlated with the volumes of the left granule cell layer of the dentate gyrus (GCL) and cornu Ammonis (CA) 4, while the levels of IL-10 were negatively correlated with the volumes of those subfields. IL-6 and IL-10 might have antagonistic roles in atrophy of the left GCL and CA4. This suggests a complexity of peripheral cytokine dysregulation and the potential for its selective effects on hippocampal substructures, which might be related to the pathophysiology of schizophrenia.

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.

Facile Synthesis of Rigid Binuclear Manganese Complexes for Magnetic Resonance Angiography and SLC39A14-Mediated Hepatic Imaging.

Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.

A subtype of schizophrenia patients with altered methylation level of genes related to immune cell activity.

BACKGROUND: Epigenetic changes are plausible molecular sources of clinical heterogeneity in schizophrenia. A subgroup of schizophrenia patients with elevated inflammatory or immune-dysregulation has been reported by previous studies. However, little is known about epigenetic changes in genes related to immune activation in never-treated first-episode patients with schizophrenia (FES) and its consistency with that in treated long-term ill (LTS) patients. METHODS: In this study, epigenome-wide profiling with a DNA methylation array was applied using blood samples of both FES and LTS patients, as well as their corresponding healthy controls. Non-negative matrix factorization (NMF) and k -means clustering were performed to parse heterogeneity of schizophrenia, and the consistency of subtyping results from two cohorts. was tested. RESULTS: This study identified a subtype of patients in FES participants (47.5%) that exhibited widespread methylation level alterations of genes enriched in immune cell activity and a significantly higher proportion of neutrophils. This clustering of FES patients was validated in LTS patients, with high correspondence in epigenetic and clinical features across two cohorts. CONCLUSIONS: In summary, this study demonstrated a subtype of schizophrenia patients across both FES and LTS cohorts, defined by widespread alterations in methylation profile of genes related to immune function and distinguishing clinical features. This finding illustrates the promise of novel treatment strategies targeting immune dysregulation for a subpopulation of schizophrenia patients.

Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility.

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Free water alterations in different inflammatory subgroups in schizophrenia.

BACKGROUND: Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia. METHODS: Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1ß), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water. RESULTS: We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1ß (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1ß level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1ß levels, peripheral IL-1ß was significantly associated with free water values in white matter while no such association was detected in the patient group. CONCLUSIONS: Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.

Medical image foundation models in assisting diagnosis of brain tumors: a pilot study.

OBJECTIVES: To build self-supervised foundation models for multicontrast MRI of the whole brain and evaluate their efficacy in assisting diagnosis of brain tumors. METHODS: In this retrospective study, foundation models were developed using 57,621 enhanced head MRI scans through self-supervised learning with a pretext task of cross-contrast context restoration with two different content dropout schemes. Downstream classifiers were constructed based on the pretrained foundation models and fine-tuned for brain tumor detection, discrimination, and molecular status prediction. Metrics including accuracy, sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the performance. Convolutional neural networks trained exclusively on downstream task data were employed for comparative analysis. RESULTS: The pretrained foundation models demonstrated their ability to extract effective representations from multicontrast whole-brain volumes. The best classifiers, endowed with pretrained weights, showed remarkable performance with accuracies of 94.9, 92.3, and 80.4%, and corresponding AUC values of 0.981, 0.972, and 0.852 on independent test datasets in brain tumor detection, discrimination, and molecular status prediction, respectively. The classifiers with pretrained weights outperformed the convolutional classifiers trained from scratch by approximately 10% in terms of accuracy and AUC across all tasks. The saliency regions in the correctly predicted cases are mainly clustered around the tumors. Classifiers derived from the two dropout schemes differed significantly only in the detection of brain tumors. CONCLUSIONS: Foundation models obtained from self-supervised learning have demonstrated encouraging potential for scalability and interpretability in downstream brain tumor-related tasks and hold promise for extension to neurological diseases with diffusely distributed lesions. CLINICAL RELEVANCE STATEMENT: The application of our proposed method to the prediction of key molecular status in gliomas is expected to improve treatment planning and patient outcomes. Additionally, the foundation model we developed could serve as a cornerstone for advancing AI applications in the diagnosis of brain-related diseases.

Altered cerebellar effective connectivity in first-episode schizophrenia and long-term changes after treatment.

AIM: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ. METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom. RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission. CONCLUSION: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.

Altered temporal lobe connectivity is associated with psychotic symptoms in drug-naïve adolescent patients with first-episode schizophrenia.

Research on individuals with a younger onset age of schizophrenia is important for identifying neurobiological processes derived from the interaction of genes and the environment that lead to the manifestation of schizophrenia. Schizophrenia has long been recognized as a disorder of dysconnectivity, but it is largely unknown how brain connectivity changes are associated with psychotic symptoms. Twenty-one adolescent-onset schizophrenia (AOS) patients and 21 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) was used to investigate local brain connectivity alterations in AOS. Regions with significant ReHo changes in patients were selected as "seeds" for further functional connectivity (FC) analysis and Granger causality analysis (GCA), and associations of the obtained functional brain measures with psychotic symptoms in patients with AOS were examined. Compared with HCs, AOS patients showed significantly increased ReHo in the right middle temporal gyrus (MTG), which was positively correlated with PANSS-positive scores, PSYRATS-delusion scores and auditory hallucination scores. With the MTG as the seed, lower connectivity with the bilateral postcentral gyrus (PCG) and higher connectivity with the right precuneus were observed in patients. The reduced FC between the right MTG and bilateral PCG was significantly and positively correlated with hallucination scores. GCA indicated decreased Granger causality from the right MTG to the left middle frontal gyrus (MFG) and from the right MFG to the right MTG in AOS patients, but such effects did not significantly associate with psychotic symptoms. Abnormalities in the connectivity within the MTG and its connectivity with other networks were identified and were significantly correlated with hallucination and delusion ratings. This region may be a key neural substrate of psychotic symptoms in AOS.

Rutin-coated ultrasmall manganese oxide nanoparticles for targeted magnetic resonance imaging and photothermal therapy of malignant tumors.

Manganese oxide nanoparticles (MONs)-based contrast agents have attracted increasing attention for magnetic resonance imaging (MRI), attributed to their good biocompatibility and advantageous paramagnetism. However, conventional MONs have poor imaging performance due to low T1 relaxivity. Additionally, their lack of tumor-targeting theranostics capabilities and complex synthesis pathways have impeded clinical applications. Rutin (Ru) is an ideal tumor-targeted ligand that targets glucose transporters (GLUTs) overexpressed in various malignant tumors, and exhibits photothermal effects upon chelation with metal ions. Herein, a series of Ru-coated MONs (Ru/MnO2) were synthesized using a straightforward, rapid one-step process. Specifically, Ru/MnO2-5, with the smallest crystal size of approximately 4 nm, exhibits the highest T1 relaxivity (33.3 mM-1s-1 at 1.5 T, surpassing prior MONs) along with notable stability, photothermal efficacy, and tumor-targeting ability. Furthermore, Ru/MnO2-5 shows promise in MRI and photothermal therapy of H22 tumors owing to its superior GLUTs-mediated tumor-targeting capability.

The difference in volumetric alternations of the orbitofrontal-limbic-striatal system between major depressive disorder and anxiety disorders: A systematic review and voxel-based meta-analysis.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders (ANX) are psychiatric disorders with high mutual comorbidity rates that might indicate some shared neurobiological pathways between them, but they retain diverse phenotypes that characterize themselves specifically. However, no consistent evidence exists for common and disorder-specific gray matter volume (GMV) alternations between them. METHODS: A systematic review and meta-analysis on voxel-based morphometry studies of patients with MDD and ANX were performed. The effect of comorbidity was explicitly controlled during disorder-specific analysis and particularly investigated in patient with comorbidity. RESULTS: A total of 45 studies with 54 datasets comprising 2196 patients and 2055 healthy participants met the inclusion criteria. Deficits in the orbitofrontal cortex, striatum, and limbic regions were found in MDD and ANX. The disorder-specific analyses showed decreased GMV in the bilateral anterior cingulate cortex, right striatum, hippocampus, and cerebellum in MDD, while decreased GMV in the left striatum, amygdala, insula, and increased cerebellar volume in ANX. A totally different GMV alternation pattern was shown involving bilateral temporal and parietal gyri and left fusiform gyrus in patients with comorbidity. LIMITATIONS: Owing to the design of included studies, only partial patients in the comorbid group had a secondary comorbidity diagnosis. CONCLUSION: Patients with MDD and ANX shared a structural disruption in the orbitofrontal-limbic-striatal system. The disorder-specific effects manifested their greatest severity in distinct lateralization and directionality of these changes that differentiate MDD from ANX. The comorbid group showed a totally different GMV alternation pattern, possibly suggesting another illness subtype that requires further investigation.

The biological impact of deuterium and therapeutic potential of deuterium-depleted water.

Since its discovery by Harold Urey in 1932, deuterium has attracted increased amounts of attention from the scientific community, with many previous works aimed to uncover its biological effects on living organisms. Existing studies indicate that deuterium, as a relatively rare isotope, is indispensable for maintaining normal cellular function, while its enrichment and depletion can affect living systems at multiple levels, including but not limited to molecules, organelles, cells, organs, and organisms. As an important compound of deuterium, deuterium-depleted water (DDW) possess various special effects, including but not limited to altering cellular metabolism and potentially inhibiting the growth of cancer cells, demonstrating anxiolytic-like behavior, enhancing long-term memory in rats, reducing free radical oxidation, regulating lipid metabolism, harmonizing indices related to diabetes and metabolic syndrome, and alleviating toxic effects caused by cadmium, manganese, and other harmful substances, implying its tremendous potential in anticancer, neuroprotective, antiaging, antioxidant, obesity alleviation, diabetes and metabolic syndrome treatment, anti-inflammatory, and detoxification, thereby drawing extensive attention from researchers. This review comprehensively summarizes the latest progress in deuterium acting on living organisms. We start by providing a snapshot of the distribution of deuterium in nature and the tolerance of various organisms to it. Then, we discussed the impact of deuterium excess and deprivation, in the form of deuterium-enriched water (DEW) and deuterium-depleted water (DDW), on living organisms at different levels. Finally, we focused on the potential of DDW as an adjuvant therapeutic agent for various diseases and disorders.

Multivariate associations between neuroanatomy and cognition in unmedicated and medicated individuals with schizophrenia.

Previous studies that focused on univariate correlations between neuroanatomy and cognition in schizophrenia identified some inconsistent findings. Moreover, antipsychotic medication may impact the brain-behavior profiles in affected individuals. It remains unclear whether unmedicated and medicated individuals with schizophrenia would share common neuroanatomy-cognition associations. Therefore, we aimed to investigate multivariate neuroanatomy-cognition relationships in both groups. A sample of 59 drug-naïve individuals with first-episode schizophrenia (FES) and a sample of 115 antipsychotic-treated individuals with schizophrenia were finally included. Multivariate modeling was conducted in the two patient samples between multiple cognitive domains and neuroanatomic features, such as cortical thickness (CT), cortical surface area (CSA), and subcortical volume (SV). We observed distinct multivariate correlational patterns between the two samples of individuals with schizophrenia. In the FES sample, better performance in token motor, symbol coding, and verbal fluency tests was associated with greater thalamic volumes but lower CT in the prefrontal and anterior cingulate cortices. Two significant multivariate correlations were identified in antipsychotic-treated individuals: 1) worse verbal memory performance was related to smaller volumes for the most subcortical structures and smaller CSA mainly in the temporal regions and inferior parietal lobule; 2) a lower symbol coding test score was correlated with smaller CSA in the right parahippocampal gyrus but greater volume in the right caudate. These multivariate patterns were sample-specific and not confounded by imaging quality, illness duration, antipsychotic dose, or psychopathological symptoms. Our findings may help to understand the neurobiological basis of cognitive impairments and the development of cognition-targeted interventions.

Porphyrin-Based Self-Assembled Nanoparticles for PET/MR Imaging of Sentinel Lymph Node Metastasis.

Diagnosing of lymph node metastasis is challenging sometimes, and multimodal imaging offers a promising method to improve the accuracy. This work developed porphyrin-based nanoparticles (68Ga-F127-TAPP/TCPP(Mn) NPs) as PET/MR dual-modal probes for lymph node metastasis imaging by a simple self-assembly method. Compared with F127-TCPP(Mn) NPs, F127-TAPP/TCPP(Mn) NPs synthesized by amino-porphyrins (TAPP) doping can not only construct PET/MR bimodal probes but also improve the T1 relaxivity (up to 456%). Moreover, T1 relaxivity can be adjusted by altering the molar ratio of TAPP/TCPP(Mn) and the concentration of F127. However, a similar increase in T1 relaxivity was not observed in the F127-TCPP/TCPP(Mn) NPs, which were synthesized using carboxy-porphyrins (TCPP) doping. In a breast cancer lymph node metastasis mice model, subcutaneous injection of 68Ga-F127-TAPP/TCPP(Mn) NPs through the hind foot pad, the normal lymph nodes and metastatic lymph nodes were successfully distinguished based on the difference of PET standard uptake values and MR signal intensities. Furthermore, the dark brown F127-TAPP/TCPP(Mn) NPs demonstrated the potential for staining and mapping lymph nodes. This study provides valuable insights into developing and applying PET/MR probes for lymph node metastasis imaging.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Altered cerebral white matter network topology and cognition in children with obstructive sleep apnea.

OBJECTIVES: The study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA. METHODS: Graph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition. RESULTS: Children with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus. CONCLUSIONS: OSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.

Glucosylation endows nanoparticles with TLR4 agonist capability to trigger macrophage polarization and augment antitumor immunity.

Carbohydrates have emerged as promising candidates for immunomodulation, however, how to present them to immune cells and achieve potent immunostimulatory efficacy remains challenging. Here, we proposed and established an effective way of designing unique glyconanoparticles that can amplify macrophage-mediated immune responses through structural mimicry and multiple stimulation. We demonstrate that surface modification with glucose can greatly augment the immunostimulatory efficacy of nanoparticles, comparing to mannose and galactose. In vitro studies show that glucosylation improved the pro-inflammatory efficacy of iron oxide nanoparticles (IONPs) by up to 300-fold, with the immunostimulatory activity of glucosylated IONPs even surpassing that of LPS under certain conditions. In vivo investigation show that glucosylated IONPs elicited increased antitumor immunity and achieved favorable therapeutic outcomes in multiple murine tumor models. Mechanistically, we proposed that glucosylation potentiated the immunostimulatory effect of IONPs by amplifying toll-like receptors 4 (TLR4) activation. Specifically, glucosylated IONPs directly interacted with the TLR4-MD2 complex, resulting in M1 macrophage polarization and enhanced antitumor immunity via activation of NF-κB, MAPK, and STAT1 signaling pathways. Our work provides a simple modification strategy to endow nanoparticles with potent TLR4 agonist effects, which may shed new light on the development of artificial immune modulators for cancer immunotherapy.

Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia.

Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role in the interaction between neuroinflammation and brain dysfunction. Most previous studies included treated and long-term ill patients, while antipsychotics and illness course might both affect the choroid plexus. Here, we recruited first-episode antipsychotic-naïve schizophrenia patients, performed high-resolution structural brain scan and manually extracted choroid plexus volume. Choroid plexus volume was compared between patients and healthy controls after controlling for age, sex and intracranial volume. Age and sex effects were examined on choroid plexus volume in patient and healthy control groups respectively. In patients, we also examined the correlation of choroid plexus volume with volume measures of cortical and subcortical gray matter, white matter, lateral ventricular as well as symptom severity and cognitive function. Schizophrenia patients showed significantly enlarged choroid plexus volume compared with healthy controls. Choroid plexus volume was positively correlated with age in only patient group and we found significantly larger choroid plexus volumes in males than females in both patient and healthy control groups, while the sex effects did not differ between groups. Choroid plexus volume was only found correlated with lateral ventricular volume among the brain volume measures. No significant correlation between choroid plexus volume and clinical ratings or cognitive performance was observed. Without potential confounding effects of pharmacotherapy or illness course, our findings indicated the enlargement of choroid plexus in schizophrenia might be an enduring trait for schizophrenia.

Ultrasound-guided photoacoustic (US-PA) tomography of the breast: Biochemical differentiation using intrinsic tissue markers-lipids, collagen and hemoglobin with histopathologic correlation.

In this pilot study, we investigated the utility of handheld ultrasound-guided photoacoustic (US-PA) imaging probe for analyzing ex-vivo breast specimens obtained from female patients who underwent breast-conserving surgery (BCS). We aimed to assess the potential of US-PA in detecting biochemical markers such as collagen, lipids, and hemoglobin, and compare these findings with routine imaging modalities (mammography, ultrasound) and histopathology results, particularly across various breast densities. Twelve ex-vivo breast specimens were obtained from female patients with a mean age of 59.7 ± 9.5 years who underwent BCS. The tissues were illuminated using handheld US-PA probe between 700 and 1100 nm across all margins and analyzed for collagen, lipids, and hemoglobin distribution. The obtained results were compared with routine imaging and histopathological assessments. Our findings revealed that lipid intensity and distribution decreased with increasing breast density, while collagen exhibited an opposite trend. These observations were consistent with routine imaging and histopathological analyses. Moreover, collagen intensity significantly differed (P < 0.001) between cancerous and normal breast tissue, indicating its potential as an additional biomarker for risk stratification across various breast conditions. The study results suggest that a combined assessment of PA biochemical information, such as collagen and lipid content, superimposed on grey-scale ultrasound findings could aid in distinguishing between normal and malignant breast conditions, as well as assist in BCS margin assessment. This underscores the potential of US-PA imaging as a valuable tool for enhancing breast cancer diagnosis and management, offering complementary information to existing imaging modalities and histopathology.