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.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Regulation of depressive-like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala.

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.

Spectacle-wearing compliance and its associated determinants among infants with bilateral corrective refractive errors: An observational study.

This study aimed to evaluate spectacle-wearing compliance and identify the determinants associated with it in infants with bilateral corrective refractive errors. Infants aged < 3 years with bilateral corrective refractive errors who were supplied with spectacles for > 1 month were enrolled at the pediatric comprehensive clinic of Zhongshan Ophthalmic Center. Spectacle-wearing compliance was evaluated by calculating the percentage of spectacle-wearing time in the awake time (STIT), and its potential determinants were identified based on interviews with the infants' caregivers using univariate and multivariate logistic regression analysis. Pearson correlation analysis was performed to further determine the degree of correlation between spectacle-wearing compliance and weight of spectacles. A total of 366 infants (age: 20.85 ±â€…9.06 months, male: 54.92%) were included. The mean percentage of STIT was 64.00%±41.69%. The communication between caregivers of different infants regarding spectacle-wearing experience (P = .004, OR = 2.290, 95% confidence interval [CI] for OR = 1.301-4.029), perceptions of spectacle-wearing importance (P = .000, OR = 6.337, 95% CI for OR = 3.664-10.961), and weight of spectacles (P = .000, OR = 7.271, 95% CI for OR = 4.141-12.769) were significantly associated with spectacle-wearing compliance. Besides, spectacle-wearing compliance was positively correlated with the weight of spectacles (P < .01), exhibiting a decreasing trend with the weight of spectacles. Overall, spectacle-wearing compliance requires improvement. Moreover, efficient strategies aimed at improving spectacle-wearing compliance, such as enhancing communication between caregivers of different infants regarding spectacle-wearing experience, raising awareness about the importance of wearing spectacles, and reducing the weight of spectacles, are urgently needed.

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Surgical approach to and morphology of visually significant persistent pupillary membranes.

PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: 31 eyes from 19 patients were included with the mean age of 7.2 years. 3 morphological variants of PPMs were observed: type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The corrected distance visual acuity was significantly improved from 0.34 ± 0.18 logMAR preoperatively to 0.17 ± 0.09 logMAR postoperatively ( P < .001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSIONS: PPMs were categorized into 3 types according to their different morphologies, which helped to determine the best surgical strategy.

Modulation Effects of the CEP128 Gene on Radiotherapy-Related Brain Injury: A Longitudinal Structural Study Using Multi-Parametric Brain MR Images.

BACKGROUND: The promoter variant rs17111237 in the CEP128 closely relates to radiotherapy (RT)-related brain necrosis in nasopharyngeal carcinoma (NPC) patients. PURPOSE: To explore RT-related dynamic alterations in brain morphology and their potential genetic mechanism, and to explore the modulatory effects of CEP128 genetic variants on RT-related brain morphological alterations in NPC patients. STUDY TYPE: Prospective, longitudinal. POPULATION: One hundred one patients with histopathologic ally-proven NPC (age 41.64 ± 9.63, 46 male), analyzed at baseline (pre-RT), 3-months post-RT and 6 months post-RT, and 19 sex-, age- and education-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3D gradient echo brain volume (3D-BRAVO) and diffusion-weighted single-shot spin-echo echo-planar sequences at 3.0 T. ASSESSMENT: rs17111237 in CEP128 was detected by Sanger sequencing. Structural and diffusion images were processed with FreeSurfer and FSL. Morphometric similarity network (MSN) was constructed with nine cortical indices derived from structural and diffusion images. STATISTICAL TESTS: One-way ANOVA, chi-square test. Pearson's correlation analysis was conducted to measure the relationship between CEP128 gene-expression level in human brain and MSN alterations. Repeated analysis of variance performed to assess group differences in MSN and the modulatory effects of the CEP128 gene within patients. Significance level: P < 0.05, false-discovery rate correction. RESULTS: RT-related significant widespread MSN alterations were observed in the cortices of NPC patients. Notably, regional MSN alterations had a weak but significant negative correlation with the cortical pattern of CEP128 gene expression (r = -0.152). Furthermore, rs17111237 in the CEP128 had significant modulatory effects on the observed MSN alterations in NPC patients, with the modulatory effects being most obvious at 3 months post-RT. CONCLUSIONS: MSN has potential to serve as a sensitive biomarker to detect RT-related brain injury. Inter-brain regional and inter-patient variability of RT-related brain injuries may be attributed to the cortical expression of the CEP128 gene and the modulatory effects of the promoter variant rs17111237 in CEP128. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Pretreatment MRI-Based Radiomics for Prediction of Rectal Cancer Outcome: A Discovery and Validation Study.

RATIONALE AND OBJECTIVES: Accurate prediction of local recurrence or distant metastasis is critical for developing individualized therapies for locally advanced rectal cancer (LARC) patients after standard therapy. This study aims to develop and validate a multiparameter MRI-based radiomics signature (RS) for prognostic prediction in LARC patients receiving neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) and to explore the ability of RS for personalized survival risk stratification. MATERIALS AND METHODS: In this multi-center study, 454 patients who received nCRT and TME and completed 3 years of follow-up participated. RS was constructed for prognostic prediction based on features extracted from pretreatment multiparameter MRI in a training cohort (TC; n = 298), which was tested in an internal validation cohort (IVC; n = 75) and further validated in an independent external validation cohort (EVC; n = 81). Furthermore, the ability of RS for personalized survival risk stratification was explored using the Kaplan-Meier survival curves. RESULTS: The RS model showed satisfactory accuracy for prognostic prediction with AUCs of 0.83, 0.81 and 0.82 in the TC, IVC and EVC, respectively. In addition, RS helped to refine risk stratification for LARC patients on the basis of significantly different 3-year disease-free survival rates, independent of their pathological stage, pre-surgery CEA, and even treatment modality. CONCLUSIONS: The proposed RS can be used not only to predict local recurrence or distant metastasis but also to serve as an effective postoperative survival risk stratification tool for clinicians to facilitate decision-making for LARC patients receiving standard treatment.

Multiphase and multiparameter MRI-based radiomics for prediction of tumor response to neoadjuvant therapy in locally advanced rectal cancer.

BACKGROUND: To develop and validate radiomics models for prediction of tumor response to neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC) using both pre-NAT and post-NAT multiparameter magnetic resonance imaging (mpMRI). METHODS: In this multicenter study, a total of 563 patients were included from two independent centers. 453 patients from center 1 were split into training and testing cohorts, the remaining 110 from center 2 served as an external validation cohort. Pre-NAT and post-NAT mpMRI was collected for feature extraction. The radiomics models were constructed using machine learning from a training cohort. The accuracy of the models was verified in a testing cohort and an independent external validation cohort. Model performance was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The model constructed with pre-NAT mpMRI had favorable accuracy for prediction of non-response to NAT in the training cohort (AUC = 0.84), testing cohort (AUC = 0.81), and external validation cohort (AUC = 0.79). The model constructed with both pre-NAT and post-NAT mpMRI had powerful diagnostic value for pathologic complete response in the training cohort (AUC = 0.86), testing cohort (AUC = 0.87), and external validation cohort (AUC = 0.87). CONCLUSIONS: Models constructed with multiphase and multiparameter MRI were able to predict tumor response to NAT with high accuracy and robustness, which may assist in individualized management of LARC.

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients.

BACKGROUND: Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). METHODS: We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. RESULTS: Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. CONCLUSION: This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

Shared and specific neurobiology in bipolar disorder and unipolar disorder: Evidence based on the connectome gradient and a transcriptome-connectome association study.

BACKGROUND: Distinguishing bipolar disorder (BD) and unipolar disorder (UD) remains challenging. To identify the common and diagnosis-specific neuropathological alterations and their potential molecular mechanisms in patients with UD and BD (with a current depressive episode). METHODS: Resting-state functional magnetic resonance imaging was obtained from 279 participants (95 BD patients, 107 UD patients and 77 health controls). Connectome gradients analysis was performed to explore the shared and diagnosis-specific gradient alterations in BD and UD. The Allen Human Brain Atlas data was used to explore the potential gene mechanisms of the gradient alterations. RESULTS: BD and UD had shared hierarchical disorganisation, including downgrading and contraction from the unimodal sensory networks (vision and sensorimotor) to the transmodal cognitive networks (limbic, frontoparietal, dorsal attention, and default) (all P < 0.05, FDR corrected) in gradient 1 and gradient 2. The BD patients had specific connectome gradient dysfunction in the subcortical network. Moreover, the hierarchical disorganisation was closely correlated with profiles of gene expression specific to the neuroglial cells in the prefrontal cortex in BD and UD, while the most correlated gene ontology biological processes and function were concentrated in synaptic signalling, calcium ion binding, and transmembrane transporter activity. CONCLUSION: These findings reveal the shared and diagnosis-specific neurobiological mechanism underlying BD and UD patients, which advances our understanding of the neuromechanisms of these disorders.

DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus.

Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling.

The s-oph enzyme for efficient degradation of polyvinyl alcohol: soluble expression and catalytic properties.

BACKGROUND: Polyvinyl alcohol (PVA) is one of the most widely used water-soluble polymers with remarkable mechanical properties. However, water-soluble polymers are among the major organic pollutants of streams, river, and marine ecosystems. Once dispersed in aqueous systems, they can directly interfere with the life cycle of aquatic organisms via direct toxic effects. There is thus an urgent need for microorganisms or enzymes that can efficiently degrade them. Oxidized PVA hydrolase plays an important role in the pathway of PVA biodegradation. It is the key enzyme in the second step of the pathway for complete degradation of PVA. METHODS AND RESULTS: The s-oph gene was cloned from the laboratory-isolated strain Sphingopyxis sp. M19. This gene was expressed in the Escherichia coli system pET32a/s-oph expression vector, with the products forming an inclusion body. By binding with a molecular chaperone, pET32a/s-oph/BL21 (DE3)/pGro7 was successfully constructed, which enabled the s-oph gene to be solubly expressed in E. coli. The protein encoded by the s-oph gene was purified at a yield of 16.8 mg L-1, and its catalytic activity reached 852.71 U mg-1. In the s-oph enzyme reaction system, the efficiency of PVA degradation was increased to 233.5% compared with that of controls. CONCLUSIONS: The s-oph enzyme exhibited the characteristics of being able to degrade PVA with high efficiency, specificity, and stability. This enzyme has good potential for practical application in ameliorating plastic pollution and protecting the environment.

Transcriptional expression of radiation-induced early cortical morphological alterations and its association with radiation necrosis in patients with nasopharyngeal carcinoma.

PURPOSE: To explore the effects of standard radiotherapy on cortical morphology and its potential transcriptional expression, and to determine the predictive power of cortical morphological measurement at the early stage for radiation necrosis (RN) occurrence within 3 years post-radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: 185 NPC patients participated. Pre-treatment and post-radiotherapy (1-3 months) structural MRI were collected longitudinally and prospectively. Multiple cortical morphological indices were compared between pre-treatment and post-radiotherapy. Brain-wide gene expression was used to assess the transcriptional profiles associated with radiation-induced cortical morphological changes. Machine learning was used to construct predictive models for RN with cortical morphological alterations at the early stage. RESULTS: Relative to pre-treatment, NPC patients exhibited a widespread reduction in cortical volume (CV) and cortical thickness (CT) post-radiotherapy (p < 0.001). Partial least squares regression analysis revealed that radiotherapy-related cortical atrophy was closely related to transcriptional profiles (p < 0.001), with the most correlated genes enriched in ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Furthermore, models constructed with cortical morphological features at 1-3 months post-radiotherapy had favorable predictive power for RN occurrence in NPC patients within 3-year follow-up, the area under the curve was 0.854 and 0.843 for CV and CT, respectively. CONCLUSIONS: NPC patients exhibited widespread cortical atrophy at 1-3 months post-radiotherapy, which was closely correlated with dysfunction of the ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Cortical morphology at 1-3 months post-radiotherapy may serve as an early biomarker for identifying RN.

Association Between MRI-Assessed Patterns of Connectome Gradient and Gene-Expression Profiles in Two Independent Patient Cohorts With Hepatitis B Virus-Related Cirrhosis.

BACKGROUND: Patients with hepatitis B virus-related cirrhosis (HBV-RC) exhibit progressive neurologic dysfunction from primary sensorimotor to high-order cognition, as their disease advances. However, the exact neurobiologic mechanisms and the potential association with gene-expression profiles are not fully understood. PURPOSE: To explore the hierarchical disorganization in the large-scale functional connectomes in HBV-RC patients and to investigate its potential underlying molecular basis. STUDY TYPE: Prospective. POPULATION: Fifty HBV-RC patients and 40 controls (Cohort 1) and 30 HBV-RC patients and 38 controls (Cohort 2). FIELD STRENGTH/SEQUENCE: Gradient-echo echo-planar and fast field echo sequences at 3.0 T (Cohort 1) and 1.5 T (Cohort 2). ASSESSMENT: Data were processed with Dpabi and the BrainSpace package. Gradient scores were evaluated from global to voxel level. Cognitive measurement and patients grouping were based on psychometric hepatic encephalopathy scores. The whole-brain microarray-based gene-expression data were obtained from the AIBS website. STATISTICAL TESTS: One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, Spearman's correlation coefficient (r), the gaussian random field correction, false discovery rate (FDR) correction and the Bonferroni correction. Significance level: P < 0.05. RESULTS: HBV-RC patients exhibited a robust and replicable connectome gradient dysfunction, which was significantly associated with the gene-expression profiles in both cohorts (r = 0.52 and r = 0.56, respectively). The most correlated genes were enriched in γ-aminobutyric acid (GABA) and GABA-related receptor genes (FDR q value <0.05). Moreover, the connectome gradient dysfunction at network level observed in HBV-RC patients correlated with their poor cognitive performance (Cohort 2: visual network, r = -0.56; subcortical network, r = 0.66; frontoparietal network, r = 0.51). DATA CONCLUSION: HBV-RC patients had hierarchical disorganization in the large-scale functional connectomes, which may underly their cognitive impairment. In addition, we showed the potential molecular mechanism of the connectome gradient dysfunction, which suggested the importance of GABA and GABA-related receptor genes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A Selective Oxidation Strategy towards the Yolk-Shell Structured ZnS@C Material for Ultra-Stable Li-Ion Storage.

Metal chalcogenides are attractive anode materials for lithium-ion batteries (LIBs) due to their high theoretical capacities. With the advantages of low cost and abundance reserves, ZnS is regarded as the prime candidate anode material for future generations, but its practical application is hindered by the large volume expansion during repeated cycling processes and inherent poor conductivity. Rational design of the microstructure with large pore volume and high specific surface area is of great significance to solve these problems. Here, a carbon-coated ZnS yolk-shell structure (YS-ZnS@C) has been prepared by selective partial oxidation of a core-shell structured ZnS@C precursor in air and subsequent acid etching. Studies show that the carbon wrapping and proper etching to bring cavities can not only improve the material's electrical conductivity, but can also effectively alleviate the volume expansion problem of ZnS during its cycles. As a LIB anode material, the YS-ZnS@C exhibits an obvious superiority in capacity and cycle life compared to ZnS@C. The YS-ZnS@C composite shows a discharge capacity of 910 mA h g-1 at the current density of 100 mA g-1 after 65 cycles, compared to only 604 mA h g-1 for ZnS@C after 65 cycles. Notably, at a large current density of 3000 mA g-1, a capacity of 206 mA h g-1 can still be maintained after 1000 cycles (over three times of the capacity for ZnS@C). It is expected that the synthetic strategy developed here is applicable to designing various high-performance metal chalcogenide-based anode materials for LIBs.

Embedding Lanthanide Organic Polyhedra into Mesoporous Silica Nanoparticles for the Photocatalytic Degradation of Organic Dyes.

Organic pollutants cause severe environmental problems because of their damage to human health and ecological systems. Photocatalytic degradation of persistent organic pollutants is of great importance to address these hazards. Herein, we report a lanthanide organic polyhedra-based hybrid material Gd8 L12 ⊂MSN with the capability of photocatalytic dye degradation. Gd8 L12 ⊂MSN was prepared by embedding the Gd8 L12 complex into mesoporous silica nanoparticles (MSNs) using a "ship-in-a-bottle" strategy. Photocurrent response tests revealed that this hybrid material is a potential semiconductor and could generate a rapid and steady photocurrent upon irradiation. Further dye degradation experiments indicated that it could photocatalyze the degradation of familiar organic dyes. Thereinto, compared with the critical Gd8 L12 complex, the hybrid material exhibited an acceleration of 2.4 times and realized reusability. This not only offers a potential advanced photocatalyst for degrading persistent organic pollutants, but also provides a strategy for the application of supramolecular materials in environmental science.

Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome.

Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.

Two Polysaccharides from Liupao Tea Exert Beneficial Effects in Simulated Digestion and Fermentation Model In Vitro.

Liupao tea is an important dark tea, but few studies on purified Liupao tea polysaccharide (TPS) are reported in the literature. In this study, two TPSs, named TPS2 and TPS5, with molecular weights of 70.5 and 133.9 kDa, respectively, were purified from Liupao tea. TPS2 contained total sugar content (53.73% ± 1.55%) and uronic acid content (35.18% ± 0.96%), while TPS5 was made up of total sugar (51.71% ± 1.1%), uronic acid (40.95% ± 3.12%), polyphenols (0.43% ± 0.03%), and proteins (0.11% ± 0.07%). TPS2 and TPS5 were composed of Man, Rha, GlcA, Glc, Gal, and Ara in the molar ratios of 0.12:0.69:0.20:0.088:1.60:0.37 and 0.090:0.36:0.42:0.07:1.10:0.16, respectively. The effects of TPS2 and TPS5 on digestion and regulation of gut microbiota in hyperlipidemic rats were compared. In simulated digestion, TPS5 was degraded and had good antioxidant effect, whereas TPS2 was not affected. The bile acids binding capacities of TPS2 and TPS5 were 42.79% ± 1.56% and 33.78% ± 0.45%, respectively. During in vitro fermentation, TPS2 could more effectively reduce pH, promote the production of acetic acid and propionic acid, and reduce the ratio of Firmicutes to Bacteroidetes. TPS5 could more effectively promote the production of butyric acid and increase the abundance of genus Bacteroides. Results indicate that polysaccharides without polyphenols and proteins have better antidigestibility and bile acid binding. Meanwhile, polysaccharides with polyphenols and proteins have a better antioxidant property. Both have different effects on the gut microbiota.