Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.

Fabrication of carboxymethyl cellulose-based thermo-sensitive hydrogels and inhibition of corneal neovascularization.

Corneal neovascularization (CNV) is a common multifactorial sequela of anterior corneal segment inflammation, which could lead to visual impairment and even blindness. The main treatments available are surgical sutures and invasive drug injections, which could cause serious ocular complications. To solve this problem, a thermo-sensitive drug-loaded hydrogel with high transparency was prepared in this study, which could achieve the sustained-release of drugs without affecting normal vision. In briefly, the thermo-sensitive hydrogel (PFNOCMC) was prepared from oxidized carboxymethyl cellulose (OCMC) and aminated poloxamer 407 (PF127-NH2). The results proved the PFNOCMC hydrogels possess high transparency, suitable gel temperature and time. In the CNV model, the PFNOCMC hydrogel loading bone morphogenetic protein 4 (BMP4) showed significant inhibition of CNV, this is due to the hydrogel allowed the drug to stay longer in the target area. The animal experiments on the ocular surface were carried out, which proved the hydrogel had excellent biocompatibility, and could realize the sustained-release of loaded drugs, and had a significant inhibitory effect on the neovascularization after ocular surface surgery. In conclusion, PFNOCMC hydrogels have great potential as sustained-release drug carriers in the biomedical field and provide a new minimally invasive option for the treatment of neovascular ocular diseases.

An Investigation of Cerebral Vascular Functional Properties in Middle-to-Old Age Community People With High Vascular Risk Profiles.

BACKGROUND: Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention. PURPOSE: To investigate the relationships between potential vascular functional markers and vascular risks, brain parenchymal damage, and cognition. STUDY TYPE: Retrospective. SUBJECTS: Two hundred two general community subjects (42-80 years, males/females: 127/75). FIELD STRENGTH/SEQUENCE: 3 T, spin echo T1W/T2W/FLAIR, resting-state functional MRI with an echo-planar sequence (rsfMRI), pseudo-continuous arterial spin labeling (pCASL) with a three-dimensional gradient-spin echo sequence. ASSESSMENT: Cerebral blood flow (CBF) in gray matter calculated using pCASL, blood transit times calculated using rsfMRI, and the SD of internal carotid arteries signal (ICAstd ) calculated using rsfMRI; visual assessment for lacunes; quantification of white matter hyperintensity volume; permutation test for quality control; collection of demographic and clinical data, Montreal Cognitive Assessment, Mini-Mental State Examination. STATISTICAL TESTS: Kolmogorov-Smirnov test; Spearman rank correlation analysis; Multivariable linear regression analysis controlling for covariates; The level of statistical significance was set at P < 0.05. RESULTS: Age was negatively associated with ICAstd (ß = -0.180). Diabetes was associated with longer blood transit time from large arteries to capillary bed (ß = 0.185, adjusted for age, sex, and intracranial volume). Larger ICAstd was associated with less presence of lacunes (odds ratio: 0.418, adjusted for age and sex). Higher gray matter CBF (ß = 0.154) and larger ICAstd (ß = 0.136) were associated with better MoCA scores (adjusted for age, sex, and education). DATA CONCLUSION: Prolonged blood transit time, decreased ICAstd , and diminished CBF were associated with vascular dysfunction and cognitive impairment. They may serve as vascular functional markers in future studies. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Oxygen Vacancies-Induced Antifouling Photoelectrochemical Aptasensor for Highly Sensitive and Selective Determination of α-Fetoprotein.

Accurate measurement of cancer markers in urine is a convenient method for tumor monitoring. However, the concentration of cancer markers in urine is so low that it is difficult to achieve their measurement. Photoelectrochemical (PEC) sensors are a promising technology to realize the detection of trace cancer markers due to their high sensitivity. Currently, the interference of nonspecific biomolecules in urine is the main reason affecting the high sensitivity and selectivity of PEC sensors in detecting cancer markers. In this work, a strategy of oxygen vacancy (OV) modulation is proposed to construct a fouling-resistant PEC aptamer sensing platform for the detection of α-fetoprotein (AFP), a liver cancer marker. The introduction of OVs induces the formation of intermediate localized states in the photoelectric material, which not only facilitates the separation of photogenerated carriers but also leads to the redshift of the light absorption edge. More importantly, OVs with positive electrical properties can be employed to modify the antifouling layer (C-PEG) with negatively charged groups through an electrostatic interaction. The synergistic effect of OVs, antifouling layer, and aptamer resulted in a TiO2/OVs/C-PEG-based PEC sensor achieves a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.3 pg/mL for AFP. In addition, the sensor successfully realized the determination of AFP in urine samples and accurately differentiated between normal people and liver cancer patients in the early and advanced stages. This project is of great significance in advancing the application of photoelectrochemical bioanalytical technology to achieve the detection of cancer markers in urine by investigating the construction of an OVs-regulated fouling-resistant sensing interface.

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants.

BACKGROUND: Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer's disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment. METHOD: Participants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess Aß aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden/Aß aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden/Aß aggregation and cognition. RESULTS: One hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN - , 48 CN + , 26 MCI + , and 19 AD + participants. Our findings revealed that there were negative associations between whole-brain Aß aggregation (r = - 0.249, p = 0.022) and WMH burden (r = - 0.458, p < 0.001) with DTI-ALPS. Additionally, Aß aggregation (r = 0.223, p = 0.041) and WMH burden (r = 0.294, p = 0.006) were both positively associated with choroid plexus volume. However, we did not observe significant correlations with PVS enlargement severity. DTI-ALPS was positively associated with memory (r = 0.470, FDR-p < 0.001), executive function (r = 0.358, FDR-p = 0.001), visual-spatial (r = 0.223, FDR-p < 0.040), and language (r = 0.419, FDR-p < 0.001). Conversely, choroid plexus volume showed negative correlations with memory (r = - 0.315, FDR-p = 0.007), executive function (r = - 0.321, FDR-p = 0.007), visual-spatial (r = - 0.233, FDR-p = 0.031), and language (r = - 0.261, FDR-p = 0.021). There were no significant correlations between PVS enlargement severity and cognitive performance. In the mediation analysis, we found that DTI-ALPS acted as a mediator in the relationship between WMH burden/Aß accumulation and memory and language performances. CONCLUSION: Our study provided evidence that both AD pathology (Aß) and CSVD were associated with glymphatic dysfunction, which is further related to cognitive impairment. These results may provide a theoretical basis for new targets for treating AD.

Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes.

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

Synthesis, Thermal Stability and Antifungal Evaluation of Two New Pyrrole Esters.

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.

Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study.

BACKGROUND: Arterial pulsation has been suggested as a key driver of paravascular cerebrospinal fluid flow, which is the foundation of glymphatic clearance. However, whether intracranial arterial pulsatility is associated with glymphatic markers in humans has not yet been studied. METHODS: Seventy-three community participants were enrolled in the study. 4D phase-contrast magnetic resonance imaging (MRI) was used to quantify the hemodynamic parameters including flow pulsatility index (PIflow) and area pulsatility index (PIarea) from 13 major intracerebral arterial segments. Three presumed neuroimaging markers of the glymphatic system were measured: including dilation of perivascular space (PVS), diffusivity along the perivascular space (ALPS), and volume fraction of free water (FW) in white matter. We explored the relationships between PIarea, PIflow, and the presumed glymphatic markers, controlling for related covariates. RESULTS: PIflow in the internal carotid artery (ICA) C2 segment (OR, 1.05; 95 % CI, 1.01-1.10, per 0.01 increase in PI) and C4 segment (OR, 1.05; 95 % CI, 1.01-1.09) was positively associated with the dilation of basal ganglia PVS, and PIflow in the ICA C4 segment (OR, 1.06, 95 % CI, 1.02-1.10) was correlated with the dilation of PVS in the white matter. ALPS was associated with PIflow in the basilar artery (ß, -0.273, p, 0.046) and PIarea in the ICA C2 (ß, -0.239, p, 0.041) and C7 segments (ß, -0.238, p, 0.037). CONCLUSIONS: Intracranial arterial pulsatility was associated with presumed neuroimaging markers of the glymphatic system, but the results were not consistent across different markers. Further studies are warranted to confirm these findings.

Building nonenhanced CT based radiomics model in discriminating arteriovenous malformation related hematomas from hypertensive intracerebral hematomas.

Objective: To develop and validate radiomics models on non-enhanced CT for discrimination of arteriovenous malformation (AVM) related hematomas from hypertensive intracerebral hematomas. Materials and methods: A total of 571 patients with acute intraparenchymal hematomas and baseline non-enhanced CT scans were retrospectively analyzed, including 297 cases of AVM related hematomas and 274 cases of hypertensive intracerebral hematomas. The patients were divided into training and validation cohorts in a 7:3 ratio with a random seed. A total of 1,688 radiomics features of hematomas were extracted from non-enhanced CT. Then, the least absolute shrinkage and selection operator (LASSO) regression was applied to select features and construct the radiomics models. In this study, a radiomics-based model was constructed that based on the radiomics features only. Furthermore, a combined model was constructed using radiomics features, clinical characteristics and radiological signs by radiologists' evaluation. In addition, we compared predictive performance of the two models for discrimination of AVM related hematomas from hypertensive intracerebral hematomas. Results: A total of 67 radiomics features were selected to establish radiomics signature via LASSO regression. The radiomics-based model was constructed with 2 classifiers, support vector machine (SVM) and logistic regression (LR). AUCs of the radiomics-based model in the training set were 0.894 and 0.904, in validation set were 0.774 and 0.782 in SVM classifier and LR classifier, respectively. AUCs of the combined model (combined with radiomics, age and calcification) in the training set were 0.976 and 0.981, in validation set were 0.896 and 0.907 in SVM classifier and LR classifier, respectively. The combined model showed greater AUCs than radiomics-based model in both training set and validation set. Conclusion: The combined model using radiomics, age and calcification showed a satisfactory predictive performance for discrimination of AVM related hematomas from hypertensive intracerebral hematomas and hold great potential for personalized clinical decision.

Development of a clinical automatic calculation of hypoglycemia during hemodialysis risk in patients with diabetic nephropathy.

BACKGROUND: Hypoglycemia is one of the most common complications in patients with DN during hemodialysis. The purpose of the study is to construct a clinical automatic calculation to predict risk of hypoglycemia during hemodialysis for patients with diabetic nephropathy. METHODS: In this cross-sectional study, patients provided information for the questionnaire and received blood glucose tests during hemodialysis. The data were analyzed with logistic regression and then an automated calculator for risk prediction was constructed based on the results. From May to November 2022, 207 hemodialysis patients with diabetes nephropathy were recruited. Patients were recruited at blood purifying facilities at two hospitals in Beijing and Inner Mongolia province, China. Hypoglycemia is defined according to the standards of medical care in diabetes issued by ADA (2021). The blood glucose meter was used uniformly for blood glucose tests 15 minutes before the end of hemodialysis or when the patient did not feel well during hemodialysis. RESULTS: The incidence of hypoglycemia during hemodialysis was 50.2% (104/207). The risk prediction model included 6 predictors, and was constructed as follows: Logit (P) = 1.505×hemodialysis duration 8~15 years (OR = 4.506, 3 points) + 1.616×hemodialysis duration 16~21 years (OR = 5.032, 3 points) + 1.504×having hypotension during last hemodialysis (OR = 4.501, 3 points) + 0.788×having hyperglycemia during the latest hemodialysis night (OR = 2.199, 2 points) + 0.91×disturbance of potassium metabolism (OR = 2.484, 2 points) + 2.636×serum albumin<35 g/L (OR = 13.963, 5 points)-4.314. The AUC of the prediction model was 0.866, with Matthews correlation coefficient (MCC) of 0.633, and Hosmer-Lemeshow χ2 of 4.447(P = 0.815). The automatic calculation has a total of 18 points and four risk levels. CONCLUSIONS: The incidence of hypoglycemia during hemodialysis is high in patients with DN. The risk prediction model in this study had a good prediction outcome. The hypoglycemia prediction automatic calculation that was developed using this model can be used to predict the risk of hypoglycemia in DN patients during hemodialysis and also help identify those with a high risk of hypoglycemia during hemodialysis.

Associations of Alzheimer's Disease Pathology and Small Vessel Disease With Cerebral White Matter Degeneration: A Tract-Based MR Diffusion Imaging Study.

BACKGROUND: White matter (WM) degeneration is a key feature of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. PURPOSE: To investigate how amyloid-ß (Aß), tau, and small vascular disease (SVD) jointly affect WM degeneration in subjects along AD continuum. STUDY TYPE: Retrospective. SUBJECTS: 152 non-demented participants (age: 55.8-91.6, male/female: 66/86) from the ADNI database were included, classified into three groups using the A (Aß)/T (tau)/N pathological scheme (Group 1: A-T-; Group 2: A+T-; Group 3: A+T+) based on positron emission tomography data. FIELD STRENGTH/SEQUENCE: 3T; T1-weighted images, T2-weighted fluid-attenuated inversion recovery images, T2*-weighted images, diffusion-weighted spin-echo echo-planar imaging sequence (54 diffusion directions). ASSESSMENT: Free-water diffusion model (generated parameters: free water, FW; tissue fractional anisotropy, FAt; tissue mean diffusivity, MDt); SVD total score; Neuropsychological tests. STATISTICAL TESTS: Linear regression analysis was performed to investigate the independent contribution of AD (Aß and tau) and SVD pathologies to diffusion parameters in each fiber tract, first in the entire population and then in each subgroup. We also investigated associations between diffusion parameters and cognitive functions. The level of statistical significance was set at p < 0.05 (false discovery rate corrected). RESULTS: In the entire population, we found that: 1) Increased FW was significantly associated with SVD and tau, while FAt and MDt were significantly associated with Aß and tau; 2) The spatial pattern of fiber tracts related to a certain pathological marker is consistent with the known distribution of that pathology; 3) Subgroup analysis showed that Group 2 and 3 had more alterations of FAt and MDt associated with Aß and tau; 4) Diffusion imaging indices showed significant associations with cognitive score in all domains except memory. DATA CONCLUSION: WM microstructural injury was associated with both AD and SVD pathologies, showing compartment-specific, tract-specific, and stage-specific WM patterns. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

The CADA-MRIT: An MRI Inventory Tool for Evaluating Cerebral Lesions in CADASIL Across Cohorts.

BACKGROUND AND OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on MRI vary widely not only within families but also between different cohorts reported worldwide. Many limitations prevent comparison of imaging data obtained with different scanners and sequences in different patient cohorts. We aimed to develop and validate a simple tool to inventory quickly the key MRI features in CADASIL to compare imaging data across different populations. METHODS: The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consists of 11 imaging items to assess periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (dPVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance, and time-effectiveness of CADA-MRIT were assessed using data from 3 independent patient cohorts. RESULTS: Imaging data from 671 patients with CADASIL (440 from France, 119 from Germany, and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, whereas CMB occurred in 83% of patients from the Asian cohort and in only 35% of European patients. CADA-MRIT scores obtained for WMH, CMB, and dPVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were from good to very good (weighted κ > 0.60). Global WMH and atrophy scores correlated strongly with accurate volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating 1 patient was approximately 2-3 minutes. DISCUSSION: The CADA-MRIT is an easy-to-use tool for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This instrument is reliable. It can be used with different imaging sequences or scanners. It also provides clinically relevant scores in a very short time for completion.

Rapid chiral purity identification of mandelic acid by Raman spectra in the O-H stretching region.

Chiral molecules play a very important role in biological systems, and more and more chiral drugs are used in the treatment of diseases. Mandelic acid (MA) is an important chiral starting substance or the key intermediate of some chiral drugs, and the rapid detection of its chiral purity is very important in the synthesis, separation and detection of drugs. In this study, we developed a method for rapid determination of chiral purity of MA by Raman spectroscopy, and measured a series of Raman spectra of different chiral MA. Through the analysis, it is found that the OH stretching vibration peak can be used to identify the components of chiral molecules, and the enantiomeric excess (ee value) obtained is in good agreement with the real value, and the error is about 5%. The experimental detection speed is fast and the efficiency is high. Our work firstly provides a new idea for the purity detection of chiral molecules by the original Raman spectrum.

Presumed periventricular venous infarction on magnetic resonance imaging and its association with increased white matter edema in CADASIL.

OBJECTIVES: Venous pathology could contribute to the development of parenchymal lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aim to identify presumed periventricular venous infarction (PPVI) in CADASIL and analyze the associations between PPVI, white matter edema, and microstructural integrity within white matter hyperintensities (WMHs) regions. METHODS: We included forty-nine patients with CADASIL from a prospectively enrolled cohort. PPVI was identified according to previously established MRI criteria. White matter edema was evaluated using the free water (FW) index derived from diffusion tensor imaging (DTI), and microstructural integrity was evaluated using FW-corrected DTI parameters. We compared the mean FW values and regional volumes with different levels of FW (ranging from 0.3 to 0.8) in WMHs regions between the PPVI and non-PPVI groups. We used intracranial volume to normalize each volume. We also analyzed the association between FW and microstructural integrity in fiber tracts connected with PPVI. RESULTS: We found 16 PPVIs in 10 of 49 CADASIL patients (20.4%). The PPVI group had larger WMHs volume (0.068 versus 0.046, p = 0.036) and higher FW in WMHs (0.55 versus 0.52, p = 0.032) than the non-PPVI group. Larger areas with high FW content were also found in the PPVI group (threshold: 0.7, 0.47 versus 0.37, p = 0.015; threshold: 0.8, 0.33 versus 0.25, p = 0.003). Furthermore, higher FW correlated with decreased microstructural integrity (p = 0.009) in fiber tracts connected with PPVI. CONCLUSIONS: PPVI was associated with increased FW content and white matter degeneration in CADASIL patients. CLINICAL RELEVANCE STATEMENT: PPVI is an important factor related with WMHs, and therefore, preventing the occurrence of PPVI would be beneficial for patients with CADASIL. KEY POINTS: •Presumed periventricular venous infarction is important and occurs in about 20% of patients with CADASIL. •Presumed periventricular venous infarction was associated with increased free water content in the regions of white matter hyperintensities. •Free water correlated with microstructural degenerations in white matter tracts connected with the presumed periventricular venous infarction.

Chitosan-based mussel-inspired hydrogel for rapid self-healing and high adhesion of tissue adhesion and wound dressings.

The hydrogel wound dressing with self-healing and adhesive property can provide better protection to the wound and prolong the service life of the material. Inspired by mussels, a high-adhesion, injectable, self-healing and antibacterial hydrogel was designed in this study. The lysine (Lys) and the catechol compound 3,4-dihydroxyphenylacetic acid (DOPAC) were grafted onto chitosan (CS). The presence of catechol group endows the hydrogel strong adhesion and antioxidation. In the experiment of wound healing in vitro, the hydrogel can adhere to the wound surface and promote wound heal. In addition, it has been proved the hydrogel has good antibacterial properties against S. aureus and E. coli. The treatment of CLD hydrogel, the degree of wound inflammation was significantly alleviated. The levels of TNF-α, IL-1ß, IL-6 and TGF-ß1 were reduced from 39.8379 %, 31.6768 %, 32.1015 % and 38.4911 % to 18.5931 %, 12.2275 %, 13.0524 % and 16.9959 %, respectively. And the levels of PDGFD and CD31 were increased from 35.6054 %, 21.7394 % to 51.8555 %, 43.9326 %, respectively. These results indicated that the CLD hydrogel has a good ability to promote angiogenesis, thickening of skin and epithelial structures.

Prospection deficits in patients with first-episode schizophrenia: a cross-sectional comparative study.

Prospection refers to the ability to simulate and pre-experience future events. Schizophrenia patients have difficulty in anticipating pleasure in future events, but previous studies examined prospection deficits in chronic schizophrenia patients. This study aimed to investigate prospection deficits in first-episode schizophrenia patients. Thirty first-episode schizophrenia patients and 31 healthy controls completed the Affective Prospection Task, which utilized pictorial cues to involve positive, neutral and negative prospection. Participants' ratings regarding the phenomenal characteristics of their prospected events were collected, and their prospected narratives were coded using a valid scoring manual. We also assessed intelligence, working memory and logical memory. The results showed, in all participants, valence of the cues significantly influenced participants' sense of pre-experience, temporal distance, emotion experience, vividness and participation of the prospected events, as well as the richness of sensory details. The two groups did not differ in self-report phenomenal characteristics of their prospected events. For coded characteristics, schizophrenia patients' prospected narratives were less rich in thought/emotion than controls, even after controlling for intelligence and memory deficits. We extended empirical evidence for prospection deficits from chronic schizophrenia samples to first-episode schizophrenia patients.

Identification of FCER1G as a key gene in multiple myeloma based on weighted gene co-expression network analysis.

PURPOSE: Although the prognosis of multiple myeloma (MM) has remarkably improved with the emerge of novel agents, it remains incurable and relapses inevitably. The molecular mechanisms of MM have not been well-studied. Herein, this study aimed to identify key genes in MM. MATERIALS AND METHODS: The GSE39754 dataset was used to screen differentially expressed genes (DEGs) and construct a co-expression network. Hub nodes were identified in the protein and protein interaction (PPI) network. Datasets GSE13591 and GSE2658 were used to validate hub genes. Moreover, function and gene set enrichment analyses were performed to elucidate the molecular pathogenesis of MM. RESULTS: In this study, 11 genes were found to be hub genes in the co-expression network, among which four genes (CD68, FCER1G, PLAUR and LCP2) were also identified as hub nodes. In the test dataset GSE13591, CD68 and FCER1G were significantly downregulated in MM. Besides, the areas under the curve (AUCs) of CD68 and FCER1G were greater than 0.8 in both the training dataset and the test dataset. Our results also confirmed that FCER1G highly expressed patients had remarkably longer survival times in MM. Function and pathway enrichment analyses suggested that hub genes were associated with epithelial mesenchymal transition, TNF-α signaling via NF-κB and inflammatory response. GSEA in our study indicated that FCER1G participated in NK cell mediated cytotoxicity and the NOD-like receptor signaling pathway. CONCLUSION: Our study identified FCER1G as a key gene in MM, providing a novel biomarker and potential molecular mechanisms of MM for further studies.

Visualizing Cerebral Small Vessel Degeneration During Aging and Diseases Using Magnetic Resonance Imaging.

Cerebral small vessel disease is a major contributor to brain disorders in older adults. It is associated with a much higher risk of stroke and dementia. Due to a lack of clinical and fluid biomarkers, diagnosing and grading small vessel disease are highly dependent on magnetic resonance imaging. In the past, researchers mostly used brain parenchymal imaging markers to represent small vessel damage, but the relationships between these surrogate markers and small vessel pathologies are complex. Recent progress in high-resolution magnetic resonance imaging methods, including time-of-flight MR angiography, phase-contrast MR angiography, black blood vessel wall imaging, susceptibility-weighted imaging, and contrast-enhanced methods, allow for direct visualization of cerebral small vessel structures. They could be powerful tools for understanding aging-related small vessel degeneration and improving disease diagnosis and treatment. This article will review progress in these imaging techniques and their application in aging and disease studies. Some challenges and future directions are also discussed. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 3.

Segmentation of incident lacunes during the course of ischemic cerebral small vessel diseases.

Background: Lacunes represent key imaging markers of cerebral small vessel diseases (cSVDs). During their progression, incident lacunes are related to stroke manifestations and contribute to progressive cognitive and/or motor decline. Assessing new lesions has become crucial but remains time-consuming and error-prone, even for an expert. We, thus, sought to develop and validate an automatic segmentation method of incident lacunes in CADASIL caused by cysteine mutation in the EGFr domains of the NOTCH3 gene, a severe and progressive monogenic form of cSVD. Methods: Incident lacunes were identified based on difference maps of 3D T1-weighted MRIs obtained at the baseline and 2 years later. These maps were thresholded using clustering analysis and compared with results obtained by expert visual analysis, which is considered the gold standard approach. Results: The median number of lacunes at the baseline in 30 randomly selected patients was 7 (IQR = [2, 11]). The median number of incident lacunes was 2 (IQR = [0, 3]) using the automatic method (mean time-processing: 25 s/patient) and 0.5 (IQR = [0, 2]) using the standard visual approach (mean time-processing: 8 min/patient). The complementary analysis of segmentation results is enabled to quickly remove false positives detected in specific locations and to identify true incident lesions not previously detected by the standard analysis (2 min/case). A combined approach based on automatic segmentation of incident lacunes followed by quick corrections of false positives allowed to reach high individual sensitivity (median at 0.66, IQR = [0.21, 1.00]) and global specificity scores (0.80). Conclusion: The automatic segmentation of incident lacunes followed by quick corrections of false positives appears promising for properly and rapidly quantifying incident lacunes in large cohorts of cSVDs.

Inferior Frontal Sulcal Hyperintensity on FLAIR is Associated with Small Vessel Disease but not Alzheimer's Pathology.

BACKGROUND: The inferior frontal sulci are essential sites on the route of cerebrospinal fluid outflow. A recent study suggests that inferior frontal sulcal hyperintensities (IFSH) on FLAIR images might be related to glymphatic dysfunction. OBJECTIVE: To investigate whether IFSH is associated with Alzheimer's disease (AD) pathology and cerebral small vessel disease (SVD) burden. METHODS: We retrospectively collected data from 272 non-demented subjects in the ADNI3 database. The IFSH was assessed on 3D fluid-attenuated inversion recovery images. The standardized uptake value ratios of amyloid and tau PET were used to reflect the AD pathology burden. To measure the SVD burden, we assessed white matter hyperintensities (WMH), dilation of perivascular spaces, microbleeds, and lacunes. Finally, we performed ordinal logistic regression analyses to investigate the associations between the IFSH score and AD pathology and SVD burden. RESULTS: The IFSH score was associated with the deep WMH score (OR, 1.79; 95% CI, 1.24 - 2.59) controlling for age and sex. The association remained significant in the multivariable regression models. There was no association between the IFSH score and AD pathology burden. CONCLUSION: This study suggests that the IFSH sign is associated with SVD but not AD pathology. Further studies are needed to confirm the findings.