Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.

Exploring the release mechanism of micro/nanoplastics from different layers of masks in water: towards reduction of plastic contamination in masks.

During the COVID-19 pandemic, a substantial quantity of disposable face masks was discarded, consisting of three layers of nonwoven fabric. However, their improper disposal led to the release of microplastics (MPs) and nanoplastics (NPs) when they ended up in aquatic environments. To analyze the release kinetics and size characteristics of these masks, release experiments were performed on commercially available disposable masks over a period of 7 days and micro- and nanoplastic releases were detected using fiber counting and nanoparticle tracking analysis. The study's findings revealed that there was no significant difference (p > 0.05) in the quantity of MPs released among the layers of the masks. However, the quantity of NPs released from the middle layer of the mask was 25.9 ± 1.3 × 108 to 81.3 ± 5.3 × 108 particles/piece, significantly higher than the inner and outer layers (p < 0.05). The release process of micro/nanoplastics (M/NPs) from each layer of the mask followed the Elovich equation and the power function equation, indicating that the release was divided into two stages. MPs in the range of 1-500 µm and NPs in the range of 100-300 nm dominated the release from each layer of the mask, accounting for an average of 93.81% and 67.52%, respectively. Based on these findings, recommendations are proposed to reduce the release of M/NPs from masks during subsequent use.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Introduction: Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. Methods: In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Results: Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). Conclusion: The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Room-Temperature Anisotropic Actuation Driven by a Synergistic Order-Disorder and Displacive Phase Transition in a Ferroelectric Crystal.

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

Tuning ferroelectric phase transition temperature by enantiomer fraction.

Tuning phase transition temperature is one of the central issues in phase transition materials. Herein, we report a case study of using enantiomer fraction engineering as a promising strategy to tune the Curie temperature (TC) and related properties of ferroelectrics. A series of metal-halide perovskite ferroelectrics (S-3AMP)x(R-3AMP)1-xPbBr4 was synthesized where 3AMP is the 3-(aminomethyl)piperidine divalent cation and enantiomer fraction x varies between 0 and 1 (0 and 1 = enantiomers; 0.5 = racemate). With the change of the enantiomer fraction, the TC, second-harmonic generation intensity, degree of circular polarization of photoluminescence, and photoluminescence intensity of the materials have been tuned. Particularly, when x = 0.70 - 1, a continuously linear tuning of the TC is achieved, showing a tunable temperature range of about 73 K. This strategy provides an effective means and insights for regulating the phase transition temperature and chiroptical properties of functional materials.

Halogen Substitution Regulates High Temperature Dielectric Switch in Lead-Free Chiral Hybrid Perovskites.

Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead-free HMHs (R-3FP)2 SbCl5 (1; 3FP=3-fluoropyrrolidinium) and (R-3FP)2 SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.

Study on Low-Temperature Performance Decay of Composite-Modified Porous Asphalt Mixture under Medium- and High-Temperature Water Erosion.

This paper studies the decay law of low-temperature crack resistance performance of rubber powder basalt fiber composite-modified porous asphalt concrete (CM-PAC) under medium- and high-temperature water erosion. Firstly, the prepared Marshall specimens were subjected to water erosion treatment at different temperatures of 20 °C, 40 °C, and 60 °C for 0-15 days. Then, the processed specimens were subjected to low-temperature splitting tests, and acoustic emission data during the splitting test process were collected using an acoustic emission device. It can be seen that the low-temperature splitting strength and low-temperature splitting stiffness modulus of CM-PAC gradually decrease with the increase in water erosion time. The maximum reduction rates of the two compared to the control group reached 72.63% and 91.60%, respectively. The low-temperature splitting failure strain gradually increases. Under the same erosion time, the higher the temperature of water, the more significant the amplitude of changes in the above parameters. In addition, it is shown that as the water erosion time increases, the first stage of loading on the specimen gradually shortens, and the second and third stages gradually advance. As the water temperature increases and the water erosion time prolongs, the acoustic emission energy released by the CM-PAC specimen during the splitting process slightly decreases. The application of acoustic emission technology in the splitting process can clarify the changes in the failure pattern of CM-PAC specimens during the entire loading stage, which can better reveal the impact of medium- to high-temperature water on the performance degradation of CM-PAC.

Photocatalytic degradation of polyethylene and polystyrene microplastics by α-Fe2O3/g-C3N4.

This study investigated the photodegradation of microplastics (MPs) by α-Fe2O3/g-C3N4. The effects of α-Fe2O3/g-C3N4 on MPs' surface were investigated through various techniques. With the addition of α-Fe2O3/g-C3N4 and under visible light irradiation, cracks and folds were observed on the MP films and particles. Compared to the treatment without photocatalyst addition, the mass loss of MPs increased with irradiation time when α-Fe2O3/g-C3N4 was added. Specifically, polystyrene films and particles in water showed 9.94% and 7.81% increased mass loss, respectively. The degradation of MPs using α-Fe2O3/g-C3N4 demonstrated the behavior consistent with the pseudo-first-order kinetic model. The presence of α-Fe2O3/g-C3N4 led to an increase in surface oxygen-containing functional groups and crystallinity while decreasing the average molecular weight of MPs. After 30 days of irradiation, the characteristic tensile bands of MPs with α-Fe2O3/g-C3N4 significantly increased, and the detection of carboxyl bands indicated the formation of carboxylic acid, ketones, and lactones as degradation products.

Kaolinite reduced Cd accumulation in peanut and remediate soil contaminated with both microplastics and cadmium.

Microplastics (MPs) increase the effective state of heavy metals (HMs) in soil and seriously threaten the yield and quality of peanuts (Arachis Hypogea L.). Kaolinite (KL) has the potential to ameliorate MP- and HM- contaminated soils, but the mechanism of action between them is not well understood. Therefore, 60-day experiments were conducted, where KL (1 %, 2 %) and MPs (0.1 %, 1 %) were individually or jointly mixed into soils with different cadmium (Cd) concentrations (0.5, 2.5, and 5.0 mg·kg-1) to cultivate peanuts in a greenhouse. Finally, soil-bioavailable Cd, peanut dry weight, peanut Cd concentrations, the pH, cation exchange capacity (CEC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were determined. It was shown that MPs negatively affected the peanut dry weight and increased the content of soil-bioavailable Cd and Cd concentration in peanut. In the MP- and Cd-contaminated soils, KL mitigated the negative influence of MPs by increasing the dry weight of peanuts by 8.40 %-40.59 %, decreasing the soil-bioavailable Cd by 23.70-35.74 %, and significantly decreasing peanut Cd concentrations by 9.65-30.86 %. The presence of MPs decreased soil pH (7.69-7.87) and the CEC (20.96-23.95 cmol·L-1) and increased the soil DOC (1.84-2.26 mg·kg-1). KL significantly increased soil pH (7.79-8.03) and the CEC (24.96-28.28 cmol·L-1) and mitigated the adverse influence of MPs on the pH and CEC of Cd-contaminated soils. A regression path analysis (RPA) evidenced that KL decreased Cd accumulation in plants by changing the properties of soil contaminated with MPs and Cd. The research results revealed the mechanism of KL on peanut growth and Cd absorption in MP- and Cd-contaminated soil. The results of this study provide a foundation to improve the quality of MP- and HM-contaminated soils and realize safe peanut production.

Unveiling Chiral Perovskite CD Signal Scaling: Discerning Authentic and Counterfeit Signals through Sample-State Analysis.

Circular dichroism (CD) spectroscopy is a well-known and powerful technique widely used for distinguishing chiral enantiomers based on their differential absorbance of the right and left circularly polarized light. With the increasing demand for solid-state chiral optics, CD spectroscopy has been extended to elucidate the chirality of solid-state samples beyond the traditional solution state. However, due to the sample preparation differential, the CD spectra of the same compound measured by different researchers may not be mutually consistent. In this study, we employ solution, powder, thin-film, and single-crystal samples to explore the challenges associated with CD measurements and distinguish between genuine and fake signals. Rational fabrication of the solid-state samples can effectively minimize the macroscopic anisotropic nature of the samples and thereby mitigate the influence of linear dichroism (LD) and linear birefringence (LB) effects, which arise from anisotropy-induced differences in the absorbances and refractive indices. The local anisotropic and overall isotropic features of the high-quality thin-film sample achieve an optically isotropic state, which exhibits superior CD signal repeatability at the front and back sides at different angles by rotating the sample along the light path. In addition, sample thickness-induced CD signal overload and absorption saturation pose more severe challenges than the LBLD-induced amplified CD signal but are rarely focused on. The CD signal overload in the deep UV region leads to the presence of fake signals, while absorption saturation results in a complete loss of the CD signal. These findings help obtain accurate CD signals by a well-fabricated optically isotropic sample to avoid LDLB and optimize the sample thickness to avoid fake signals and no signals.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

Dissociation between neuroanatomical and symptomatic subtypes in schizophrenia.

BACKGROUND: Schizophrenia is a complex and heterogeneous syndrome with high clinical and biological stratification. Identifying distinctive subtypes can improve diagnostic accuracy and help precise therapy. A key challenge for schizophrenia subtyping is understanding the subtype-specific biological underpinnings of clinical heterogeneity. This study aimed to investigate if the machine learning (ML)-based neuroanatomical and symptomatic subtypes of schizophrenia are associated. METHODS: A total of 314 schizophrenia patients and 257 healthy controls from four sites were recruited. Gray matter volume (GMV) and Positive and Negative Syndrome Scale (PANSS) scores were employed to recognize schizophrenia neuroanatomical and symptomatic subtypes using K-means and hierarchical methods, respectively. RESULTS: Patients with ML-based neuroanatomical subtype-1 had focally increased GMV, and subtype-2 had widespread reduced GMV than the healthy controls based on either K-means or Hierarchical methods. In contrast, patients with symptomatic subtype-1 had severe PANSS scores than subtype-2. No differences in PANSS scores were shown between the two neuroanatomical subtypes; similarly, no GMV differences were found between the two symptomatic subtypes. Cohen's Kappa test further demonstrated an apparent dissociation between the ML-based neuroanatomical and symptomatic subtypes (P > 0.05). The dissociation patterns were validated in four independent sites with diverse disease progressions (chronic vs. first episodes) and ancestors (Chinese vs. Western). CONCLUSIONS: These findings revealed a replicable dissociation between ML-based neuroanatomical and symptomatic subtypes of schizophrenia, which provides a new viewpoint toward understanding the heterogeneity of schizophrenia.

Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs.

We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.

A Two-Dimensional Hybrid Lead Bromide Ferroelectric Semiconductor with an Out-of-Plane Polarization.

A two-dimensional (2D) organic-inorganic hybrid perovskite (OIHP) material with out-of-plane ferroelectricity is the key to the miniaturization of vertical-sandwich-type ferroelectric optoelectronic devices. However, 2D OIHP ferroelectrics with out-of-plane polarization are still scarce, and effective design strategies are lacking. Herein, we report a novel 2D Dion-Jacobson perovskite ferroelectric semiconductor synthesized by a rigid-to-flexible cationic tailoring strategy, achieving an out-of-plane polarization of 1.7 µC/cm2 and high photoresponse. Integrating out-of-plane ferroelectricity with excellent photoelectric properties affords a promising platform to investigate ferroelectricity-related effects in vertical optoelectronic devices.

The behavior of microplastics and nanoplastics release from UV-aged masks in the water.

In this study, three types of disposable masks were exposed to ultraviolet (UV) irradiation to determine the effect of UV irradiation on the release of microplastics (MPs) and nanoplastic (NPs) from the masks. A kinetic model was used to investigate the mechanisms of M/NP release from the masks under UV irradiation. Results showed that UV irradiation exacerbated the damage to the structure of the mask over time. As the irradiation time increased, the middle layer of the mask was damaged first (15 d) and subsequently all layers of the mask were damaged (30 d). There was no significant difference in the quantity of M/NPs released from the treatment groups at different irradiance during a 5-d irradiation period. When the UV time reached 15 and 30 d, the highest quantity of M/NPs was released at 8.5 W/m2 followed by 4.9 W/m2, 15.4 W/m2, and 17.1 W/m2. Exponential equations fitted the release curve of M/NPs. The release quantity of M/NPs increases exponentially with increasing UV irradiation time, and the longer the irradiation time, the faster the rate of increase. Estimated release of 1.78 × 1017-3.66 × 1019 particles/piece of MPs and 8.23 × 1019-2.18 × 1022 particles/piece of NPs into the water when the masks are exposed to the real environment for 1-3 years.

Circularly Polarized Luminescence in Zero-Dimensional Antimony Halides: Structural Distortion Controlled Luminescence Thermometer.

Materials emitting circularly polarized luminescence (CPL) have been intensively studied for their promising applications in various fields. However, developing tunable and responsive CPL materials in a wide wavelength range remains a great challenge. Here, a pair of chiral (R,R/S,S-DCDA)3Sb2Cl12 (DCDA = dimethyl-1,2-cyclohexanediamine divalent cation) shows efficient broadband yellow emission with a photoluminescence (PL) quantum yield of 27.6% with a CPL asymmetry factor of 3 × 10-3. The associated chiroptical activity is attributed to the efficient chiral transfer as well as the self-trapped exciton emission originating from the large distortion of the inorganic blocks. Notably, (R,R/S,S-DCDA)3Sb2Cl12 exhibits a large red-shift emission exceeding 100 nm upon lowering temperature. An excellent linear correlation of the PL wavelength on temperature indicates that the compounds can be used as PL thermometers, which originates from a temperature-dependent linear structural distortion of the [SbCl6] emitter. This work inspires the potential utilization of CPL-emitting materials as responsive light sources.

The incomplete circle of Willis is associated with vulnerable intracranial plaque features and acute ischemic stroke.

BACKGROUND: The circle of Willis (CoW) plays a significant role in intracranial atherosclerosis (ICAS). This study investigated the relationship between different types of CoW, atherosclerosis plaque features, and acute ischemic stroke (AIS). METHODS: We investigated 97 participants with AIS or transient ischemic attacks (TIA) underwent pre- and post-contrast 3T vessel wall cardiovascular magnetic resonance within 7 days of the onset of symptoms. The culprit plaque characteristics (including enhancement grade, enhancement ratio, high signal in T1, irregularity of plaque surface, and normalized wall index), and vessel remodeling (including arterial remodeling ratio and positive remodeling) for lesions were evaluated. The anatomic structures of the anterior and the posterior sections of the CoW (A-CoW and P-CoW) were also evaluated. The plaque features were compared among them. The plaque features were also compared between AIS and TIA patients. Finally, univariate and multivariate regression analysis was performed to evaluate the independent risk factors for AIS. RESULT: Patients with incomplete A-CoW showed a higher plaque enhancement ratio (P = 0.002), enhancement grade (P = 0.01), and normalized wall index (NWI) (P = 0.018) compared with the patients with complete A-CoW. A higher proportion of patients with incomplete symptomatic P-CoW demonstrated more culprit plaques with high T1 signals (HT1S) compared with those with complete P-CoW (P = 0.013). Incomplete A-CoW was associated with a higher enhancement grade of the culprit plaques [odds ratio (OR):3.84; 95% CI: 1.36-10.88, P = 0.011], after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Incomplete symptomatic P-CoW was associated with a higher probability of HT1S (OR:3.88; 95% CI: 1.12-13.47, P = 0.033), after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Furthermore, an irregularity of the plaque surface (OR: 6.24; 95% CI: 2.25-17.37, P < 0.001), and incomplete symptomatic P-CoW (OR: 8.03, 95% CI: 2.43-26.55, P = 0.001) were independently associated with AIS. CONCLUSIONS: This study demonstrated that incomplete A-CoW was associated with enhancement grade of the culprit plaque, and incomplete symptomatic side P-CoW was associated with the presence of HT1S of culprit plaque. Furthermore, an irregularity of plaque surface and incomplete symptomatic side P-CoW were associated with AIS.

Unraveling schizophrenia replicable functional connectivity disruption patterns across sites.

Functional connectivity (FC) disruption is a remarkable characteristic of schizophrenia. However, heterogeneous patterns reported across sites severely hindered its clinical generalization. Based on qualified nodal-based FC of 340 schizophrenia patients (SZ) and 348 normal controls (NC) acquired from seven different scanners, this study compared four commonly used site-effect correction methods in removing the site-related heterogeneities, and then tried to cluster the abnormal FCs into several replicable and independent disrupted subnets across sites, related them to clinical symptoms, and evaluated their potentials in schizophrenia classification. Among the four site-related heterogeneity correction methods, ComBat harmonization (F1 score: 0.806 ± 0.145) achieved the overall best balance between sensitivity and false discovery rate in unraveling the aberrant FCs of schizophrenia in the local and public data sets. Hierarchical clustering analysis identified three replicable FC disruption subnets across the local and public data sets: hypo-connectivity within sensory areas (Net1), hypo-connectivity within thalamus, striatum, and ventral attention network (Net2), and hyper-connectivity between thalamus and sensory processing system (Net3). Notably, the derived composite FC within Net1 was negatively correlated with hostility and disorientation in the public validation set (p < .05). Finally, the three subnet-specific composite FCs (Best area under the receiver operating characteristic curve [AUC] = 0.728) can robustly and meaningfully discriminate the SZ from NC with comparable performance with the full identified FCs features (best AUC = 0.765) in the out-of-sample public data set (Z = -1.583, p = .114). In conclusion, ComBat harmonization was most robust in detecting aberrant connectivity for schizophrenia. Besides, the three subnet-specific composite FC measures might be replicable neuroimaging markers for schizophrenia.

Cerebral blood flow regulates iron overload in the cerebral nuclei of hemodialysis patients with anemia.

Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia.

Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.

Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.