Enhanced interactions of interlayer excitons in free-standing heterobilayers.

Strong, long-range dipole-dipole interactions between interlayer excitons (IXs) can lead to new multiparticle correlation regimes1,2, which drive the system into distinct quantum and classical phases2-5, including dipolar liquids, crystals and superfluids. Both repulsive and attractive dipole-dipole interactions have been theoretically predicted between IXs in a semiconductor bilayer2,6-8, but only repulsive interactions have been reported experimentally so far3,9-16. This study investigated free-standing, twisted (51°, 53°, 45°) tungsten diselenide/tungsten disulfide (WSe2/WS2) heterobilayers, in which we observed a transition in the nature of dipolar interactions among IXs, from repulsive to attractive. This was caused by quantum-exchange-correlation effects, leading to the appearance of a robust interlayer biexciton phase (formed by two IXs), which has been theoretically predicted6-8 but never observed before in experiments. The reduced dielectric screening in a free-standing heterobilayer not only resulted in a much higher formation efficiency of IXs, but also led to strongly enhanced dipole-dipole interactions, which enabled us to observe the many-body correlations of pristine IXs at the two-dimensional quantum limit. In addition, we firstly observed several emission peaks from moiré-trapped IXs at room temperature in a well-aligned, free-standing WSe2/WS2 heterobilayer. Our findings open avenues for exploring new quantum phases with potential for applications in non-linear optics.

Low-intensity pulsed ultrasound activated the anti-tumor immunity by irradiating the spleen of mice in 4 T-1 breast cancer.

Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS.

Clinical features, disease progression, and nuclear imaging in ATXN2-related parkinsonism in a longitudinal cohort.

BACKGROUND: Spinocerebellar ataxia 2 (SCA2) with a low range of CAG repeat expansion of ATXN2 gene can present with predominant or isolated parkinsonism that closely resembles Parkinson's disease (PD). This study is aimed at comparing clinical features, disease progression, and nuclear imaging between ATXN2-related parkinsonism (ATXN2-P) and PD. METHODS: Three hundred and seventy-seven clinically diagnosed PD with family history were screened by multiplex ligation-dependent probe amplification, whole-exome sequencing or target sequencing, and dynamic mutation testing of 10 SCA subtypes. The baseline and longitudinal clinical features as well as the dual-tracer positron emission tomography (PET) imaging were compared between ATXN2-P and genetically undefined familial PD (GU-fPD). RESULTS: Fifteen ATXN2-P patients from 7 families and 50 randomly selected GU-fPD patients were evaluated. Significantly less resting tremor and more symmetric signs were observed in ATXN2-P than GU-fPD. No significant difference was found in motor progression and duration from onset to occurrence of fluctuation, dyskinesia, and recurrent falls between the two groups. Cognitive impairment and rapid-eye-movement sleep behavior disorder were more common in ATXN2-P. During follow-up, olfaction was relatively spared, and no obvious progression of cognition dysfunction evaluated by Mini-Mental State Examination scores was found in ATXN2-P. PET results of ATXN2-P demonstrated a symmetric, diffuse, and homogenous dopamine transporter loss of bilateral striatum and a glucose metabolism pattern inconsistent with that in PD. CONCLUSIONS: Symmetric motor signs and unique nuclear imaging might be the clues to distinguish ATXN2-P from GU-fPD.

Using a smartphone-based self-management platform to study sex differences in Parkinson's disease: multicenter, cross-sectional pilot study.

BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.

Control priority based on source-specific DALYs of PM2.5-bound heavy metals by PMF-PSCF-IsoSource model in urban and suburban Beijing.

To determine the priority control sources, an approach was proposed to evaluate the source-specific contribution to health risks from inhaling PM2.5-bound heavy metals (PBHMs). A total of 482 daily PM2.5 samples were collected from urban and suburban areas of Beijing, China, between 2018 and 2019. In addition to the PMF-PSCF model, a Pb isotopic IsoSource model was built for more reliable source apportionment. By using the comprehensive indicator of disability-adjusted life years (DALYs), carcinogenic and noncarcinogenic health risks could be compared on a unified scale. The study found that the annual average concentrations of the total PBHMs were significantly higher in suburban areas than in urban areas, with significantly higher concentrations during the heating season than during the nonheating season. Comprehensive dust accounted for the largest contribution to the concentration of PBHMs, while coal combustion contributed the most to the DALYs associated with PBHMs. These results suggest that prioritizing the control of coal combustion could effectively reduce the disease burden associated with PBHMs, leading to notable public health benefits.

In Vivo 18 F-Florzolotau Tau Positron Emission Tomography Imaging in Parkinson's Disease Dementia.

BACKGROUND: Tau pathology is observed during autopsy in many patients with Parkinson's disease dementia (PDD). Positron emission tomography (PET) imaging using the tracer 18 F-florzolotau has the potential to capture tau accumulation in the living brain. OBJECTIVE: The aim was to describe the results of 18 F-florzolotau PET/CT (computed tomography) imaging in patients with PDD. METHODS: Ten patients with PDD, 9 with Parkinson's disease with normal cognition (PD-NC), and 9 age-matched healthy controls (HCs) were enrolled. Clinical assessments and 18 F-florzolotau PET/CT imaging were performed. RESULTS: 18 F-Florzolotau uptake was significantly higher in the cortical regions of patients with PDD compared with both PD-NC and HCs, especially in the temporal lobe. Notably, 18 F-florzolotau uptake in the occipital lobe of patients with PDD showed a significant correlation with cognitive impairment as reflected by Mini-Mental State Examination (MMSE) scores. CONCLUSIONS: 18 F-Florzolotau PET imaging can effectively capture the occurrence of tau pathology in patients with PDD, which was also linked to MMSE scores. © 2022 International Parkinson and Movement Disorder Society.

Association between Respiratory Function and Motor Function in Different Stages of Parkinson's Disease.

INTRODUCTION: Respiratory dysfunction in patients with Parkinson's disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. METHODS: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson's disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey's post hoc test. RESULTS: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF25-75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = -0.248, p = 0.046), disease duration (r = -0.276, p = 0.026), H&Y scale (r = -0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = -0.277, p = 0.025), disease duration (r = -0.291, p = 0.019), H&Y scale (r = -0.434, p = 0.0001). FEF25-75% was negatively correlated with disease duration (r = -0.247, p = 0.047), H&Y scale (r = -0.278, p = 0.025). CONCLUSION: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.

In Vivo 18 F-APN-1607 Tau Positron Emission Tomography Imaging in MAPT Mutations: Cross-Sectional and Longitudinal Findings.

BACKGROUND: Frontotemporal lobar degeneration with tauopathy caused by MAPT (microtubule-associated protein tau) mutations is a highly heterogenous disorder. The ability to visualize and longitudinally monitor tau deposits may be beneficial to understand disease pathophysiology and predict clinical trajectories. OBJECTIVE: The aim of this study was to investigate the cross-sectional and longitudinal 18 F-APN-1607 positron emission tomography/computed tomography (PET/CT) imaging findings in MAPT mutation carriers. METHODS: Seven carriers of MAPT mutations (six within exon 10 and one outside of exon 10) and 15 healthy control subjects were included. All participants underwent 18 F-APN-1607 PET/CT at baseline. Three carriers of exon 10 mutations received follow-up 18 F-APN-1607 PET/CT scans. Standardized uptake value ratio (SUVR) maps were obtained using the cerebellar gray matter as the reference region. SUVR values observed in MAPT mutation carriers were normalized to data from healthy control subjects. A regional SUVR z score ≥ 2 was used as the criterion to define positive 18 F-APN-1607 PET/CT findings. RESULTS: Although the seven study patients had heterogenous clinical phenotypes, all showed a significant 18 F-APN-1607 uptake characterized by high-contrast signals. However, the anatomical localization of tau deposits differed in patients with distinct clinical symptoms. Follow-up imaging data, which were available for three patients, demonstrated worsening trends in patterns of tau accumulation over time, which were paralleled by a significant clinical deterioration. CONCLUSIONS: Our data represent a promising step in understanding the usefulness of 18 F-APN-1607 PET/CT imaging for detecting tau accumulation in MAPT mutation carriers. Our preliminary follow-up data also suggest the potential value of 18 F-APN-1607 PET/CT for monitoring the longitudinal trajectories of frontotemporal lobar degeneration caused by MAPT mutations. © 2021 International Parkinson and Movement Disorder Society.

Disease Progression in Patients with Parkin-Related Parkinson's Disease in a Longitudinal Cohort.

BACKGROUND: There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. METHODS: Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. RESULTS: At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). CONCLUSION: Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Propagated α-synucleinopathy recapitulates REM sleep behaviour disorder followed by parkinsonian phenotypes in mice.

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson's disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson's disease in this animal model.

Quasi-line Spectral Emissions from Highly Crystalline One-Dimensional Organic Nanowires.

Zero-phonon line (ZPL) emissions have key applications in single-photon emission sources, quantum information processing, and single-molecule spectroscopy. All recent attempts to realize ZPL emissions are based on the techniques of confining and doping molecules in matrixes or solutions in low-temperature Shpol'skii systems. The requirement of two-component systems reduces the light emission efficiency from the molecules and limits their applications in solid-state electronic applications and quantum computing devices. Here, we report the first experimental demonstration of the Shpol'skii effect in a one-component organic solid-state system at low temperature. We observe a ZPL emission with a width of ∼1 to 2 nm and a high value of the Debye-Waller factor (0.72) from our epitaxially grown highly crystalline and ordered 1D organic nanowire, which is attributed to a specific molecular configuration and a higher degree of molecular orientation as compared to that of the bulk thin film counterpart. Our results pave the way for organic 1D wires (with quasi-line spectra) for applications in lasing, nanosensors, and interconnects/functional units in next-generation miniaturized optoelectronics.

Clinical characteristics of cognitive impairment in patients with Parkinson's disease and its related pattern in 18 F-FDG PET imaging.

This study aimed to characterize the clinical features and the related cerebral glucose metabolism pattern of cognitive impairments in Parkinson's disease (PD) with positron emission tomography (PET) imaging. We recruited 168 PD patients and 100 age-matched healthy controls of similar education and gender distribution. All of those enrolled underwent clinical assessment including the unified Parkinson's disease rating scale motor score, Hoehn and Yahr scale, and comprehensive neuropsychological tests including domains of executive function, attention, memory, visuospatial function, and language. Demographics and the results of cognitive measures were compared between patients and healthy controls. Cognition status was classified as PD patients with dementia (PD-D), PD patients with mild cognitive impairment (PD-MCI), or PD patients with normal cognition (PD-NC). In 53 PD patients who underwent 18 F-fluorodeoxyglucose (18 F-FDG) PET imaging, correlations between Z-score values of the different cognitive domains and cerebral 18 F-FDG uptake were assessed using statistical parametric mapping (SPM8) corrected for age and motor severity. A total of 23.2% of PD patients were PD-MCI and 8.9% were PD-D. In the group of PD-MCI, 96.3% showed multiple-domain deficits, with executive function and attention impairment most predominantly involved. All the cognitive domain scores with the exception of language correlated with 18 F-FDG metabolisms, primarily in posterior temporo-parieto-occipital association cortical areas. This study found that cognitive impairment in PD particularly encompasses frontal/executive deficits. Posterior cortical areas, containing multiple neurotransmitters and neural circuits, may play an important role in the pathogenesis of cognitive impairment in PD.

Depressive Symptoms Are Associated With Color Vision but not Olfactory Function in Patients With Parkinson's Disease.

Depressive symptoms and sensory dysfunction, such as reduction in visual and olfactory function, are common in Parkinson's disease (PD). Previous studies have suggested that depressive symptoms are associated with visual impairments and potentially with hyposmia in several types of mood disorders. However, the relationship between depressive symptoms and sensory dysfunction remains unclear in PD. To examine the association of depressive symptoms with color vision and olfactory function in PD, the authors conducted a cross-sectional study in 159 patients with PD. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI-II) and the 30-item Geriatric Depression Scale (GDS-30); color vision was tested with the Farnsworth-Munsell 100 Hue Test (FMT); and olfactory function was tested with the Sniffin' Sticks Screening 12 Test. Results showed that the total error score (TES) for the FMT was significantly and independently correlated with scores on both the BDI-II and GDS-30 in a positive manner, suggesting that more severe depressive symptoms are associated with poorer color vision in PD. In addition, both somatic and effective subscores for the BDI-II were correlated with the TES on the FMT, while no significant correlation was observed between total scores on the Sniffin' Sticks Screening 12 Test and BDI-II or GDS-30. The decrease in color vision but not olfactory function was found to be associated with the severity of depressive symptoms in PD patients, supporting the idea that the occurrence of depressive symptoms in PD is linked with disruption of the visual system.

A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.

BACKGROUND: Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically. CASE PRESENTATION: We reported a consanguineous family (two affected sisters) with Perrault syndrome. The proband had the characteristics of Perrault syndrome: ovarian dysgenesis, bilateral hearing loss and obvious neurological signs. Target genetic sequencing and triplet repeat primed PCR (TP-PCR) plus capillary electrophoresis was conducted to detect causative mutations in the proband. The detected variant was further confirmed in the proband and tested in other family members by Sanger sequencing. Both the proband and her sister were found homozygous for the novel variant HSD17B4 c.298G > T (p.A100S) with their parents heterozygous. Detected by western blot, the protein expression of HSD17B4 mutant was much lower than that of the wild type in SH-SY5Y cells transfected by HSD17B4 wild type or mutant plasmid, which indicated the pathogenicity of the HSD17B4 mutation. CONCLUSIONS: Our findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome with the likely pathogenic variant c.298G > T (p.A100S). Special manifestations of cerebellar impairment were found in cases caused by HSD17B4 mutations. Besides, attention should be paid to distinguish Perrault syndrome from D-bifunctional protein deficiency and hereditary ataxia.

PEG-stabilized bilayer nanodisks as carriers for doxorubicin delivery.

Spherical nanoparticles as a classic delivery vehicle for anticancer drugs have been extensively investigated, but study on the shape of nanoparticles has received little attention until now. Here, a nonspherical poly(ethylene glycol) (PEG)-stabilized bilayer nanodisk consisting of 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC) and PEG5000-glyceryl distearate (PEG5K-GCDS) was prepared for doxorubicin delivery, called DOX-Disks. The prepared disks were open bilayer structures, with a hydrophobic discoid center built by DSPC and a hydrophilic PEG edge. Mean particle diameter of the disk was 80.14 nm, and the disk height was about 6 nm with aspect ratio about 12. Encapsulation efficiency of DOX-Disks was as high as 96.1%, and DOX release from DOX-Disks was pH-dependent (25.6% of total DOX released at 24 h in pH 7.4). The pharmacokinetic performances showed that DOX-Disks demonstrated long circulation time in blood and larger AUC (11.7-fold of t1/2 and 31.7-fold of AUC) in rats compared with DOX solutions (DOX-Sol). Tissue distribution in H22 tumor bearing mice demonstrated higher tumor accumulation (9.7-fold) and lower heart toxicities (25.7-fold) at 48 h after iv administration, in comparison with DOX-Sol. In addition, DOX-Disks exhibited much effectiveness in inhibiting tumor cell growth, and the IC50 values were 2.03, 0.85, and 0.86 µg/mL for DOX-Sol and 0.23, 0.24, and 0.20 µg/mL for DOX-Disks after treatment for 48, 72, and 96 h against MCF-7/Adr cells, respectively. DOX-Disks were taken up into MCF-7/Adr cells via energy-dependent endocytosis processes, involved in clathrin-mediated, macropinocytosis-mediated, and non-clathrin- and non-caveolae-mediated endocytosis pathways. In summary, such PEG-stabilized bilayer nanodisks could be one of the promising carriers for antitumor drugs via extended blood circulation and improved tumor distribution.

Prevalence of internet gaming disorder among Chinese adolescents: A systematic review and meta-analysis.

This study aimed to evaluate the prevalence of IGD among Chinese adolescents. Articles published up to April 11, 2024 were retrieved from PubMed, Wiley Online Library, Embase, Web of Science, Ebsco, CNKI, and WanFang. Random-effects models and univariate meta-regression analyses were used to calculate prevalence and heterogeneity estimates with the support of Stata17.0 software. The prevalence of IGD in Chinese adolescents was 10 % (95 %CI: 8 %-12 %). Univariate regression analyses revealed some significant moderators of IGD prevalence, including gender, sample size, and survey year. Spatiotemporal analysis showed the prevalence of IGD varied considerably across provinces in different survey years.

Striatum and globus pallidus structural abnormalities in schizophrenia: A retrospective study of the different stages of the disease.

BACKGROUND: The basal ganglia are important structures for the release of dopamine in the limbic circuits of the midbrain, and the striatum and globus pallidus are the major nuclei of the basal ganglia, and the dysfunction of these regions has been the basis of many models that have attempted to explain the underlying mechanisms of schizophrenia symptoms. The purpose of this study was to investigate the changes in the volume of the striatum subregion and globus pallidus in three different stages of schizophrenia, and to analyze whether these volume changes were related to antipsychotic drugs and schizophrenia symptoms. METHODS: In this study, we investigated the volume of the striatum and globus pallidus in patients with schizophrenia at three different stages. The study included 57 patients with first-episode schizophrenia (FSZ), 51 patients with early-stage schizophrenia (ESZ), 86 patients with chronic schizophrenia (CSZ), and 191 healthy controls (HC), all of whom underwent structured magnetic resonance imaging (MRI) scans. Covariance analysis was performed using SPSS 26.0 was used for covariance analysis to determine whether there were significant differences in striatal subregion and globus pallidus volume between groups, and stratified analysis was used to further eliminate the effect of age on brain volume. Finally, the correlation analysis between the region of interest and the cumulative dose of antipsychotic drugs and psychotic symptoms was performed. RESULTS: The comparison between the different stages of the illness showed significant volume differences in the left caudate nucleus (lCAU) (F = 2.665, adjusted p = 0.048), left putamen (lPUT) (F = 12.749, adjusted p < 0.001), left pallidum (lPAL) (F = 41.111, adjusted p < 0.001), and right pallidum (rPAL) (F = 14.479, adjusted p < 0.001). Post-hoc analysis with corrections showed that the volume differences in the lCAU subregion disappeared. Further stratified analysis controlling for age showed that compared with the HC, the lPAL (t = 4.347, p < 0.001) was initially significantly enlarged in the FSZ group, the lPUT (t = 4.493, p < 0.001), rPUT (t = 2.190, p = 0.031), lPAL (t = 7.894, p < 0.001), and rPAL (t = 4.983, p < 0.001) volumes were all significantly increased in the ESZ group, and the lPUT (t = 3.314, p = 0.002), lPAL (t = 6.334, p < 0.001), and rPAL (t = 3.604, p < 0.001) subregion volumes were also significantly increased in the CSZ group. Correlation analysis showed that lPUT and bilateral globus pallidus were associated with cumulative dose of antipsychotics, but were not associated with clinical symptoms in each subregion. CONCLUSION: The findings suggest that different subregions of the striatum and globus pallidus show significant volume differences at different stages of schizophrenia compared to HC. These volume differences may be strong radiographic evidence for schizophrenia. In addition, the lPAL was the only significantly different brain region observed in the FSZ group, suggesting that it may be a sensitive indicator of early brain structural changes in schizophrenia. Finally, our findings support the hypothesis that antipsychotic drugs have an effect on the volume of brain structures.

Recommendations for the reference concentration of cadmium exposure based on a physiologically based toxicokinetic model integrated with a human respiratory tract model.

Cadmium (Cd) poses a significant threat to human health. However, chronic toxicity parameters for inhalation exposure are lacking, especially for noncritical systemic toxic effects. A physiologically based toxicokinetic (PBTK) model can be used to extrapolate toxicity parameters across various exposure routes. We combined a PBTK model with a human respiratory tract (HRT) model, which is applicable to the general population and capable of simulating the deposition and clearance processes of various airborne Cd compounds in the respiratory tract. Monte Carlo analysis was used to simulate the distribution of sensitive parameters to reflect individual variability. Validation based on datasets from general and occupational populations showed that the improved model had acceptable or better predictive performance, outperforming the original model with a 14.45 % decrease in the root mean square error (RMSE). Using this PBTK-HRT model, we extrapolated toxicity parameters from oral exposure to inhalation exposure for four systemic toxic effects with doseresponse relationships but no known inhalation toxicity parameters, and ultimately recommended reference concentrations (RfCs) for four diseases (chronic kidney disease: 0.01 µg/m3, osteoporosis: 0.01 µg/m3, stroke: 0.04 µg/m3, diabetes mellitus: 0.13 µg/m3), contributing to a comprehensive assessment of the health risks of Cd inhalation exposure. ENVIRONMENTAL IMPLICATION: Cadmium (Cd), a heavy metal, can cause lung cancer, chronic kidney disease, and osteoporosis and pose a significant threat to human health. We combined a physiologically based toxicokinetic (PBTK) model with a human respiratory tract (HRT) model to achieve better predictive performance and wider applicability; this model was subsequently employed for route-to-route extrapolation of toxicity parameters. Additionally, for the first time, we focused on multiple subchronic and chronic systemic toxic effects in addition to critical effects and derived their reference concentrations (RfCs), which can be used to assess the health risk of Cd inhalation exposure more comprehensively and accurately.

Different structural connectivity patterns in the subregions of the thalamus, hippocampus, and cingulate cortex between schizophrenia and psychotic bipolar disorder.

OBJECTIVE: Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) are two major psychotic disorders with similar symptoms and tight associations on the psychopathological level, posing a clinical challenge for their differentiation. This study aimed to investigate and compare the structural connectivity patterns of the limbic system between SCZ and PBD, and to identify specific regional disruptions associated with psychiatric symptoms. METHODS: Using sMRI data from 146 SCZ, 160 PBD, and 145 healthy control (HC) participants, we employed a data-driven approach to segment the hippocampus, thalamus, hypothalamus, amygdala, and cingulate cortex into subregions. We then investigated the structural connectivity patterns between these subregions at the global and nodal levels. Additionally, we assessed psychotic symptoms by utilizing the subscales of the Brief Psychiatric Rating Scale (BPRS) to examine correlations between symptom severity and network metrics between groups. RESULTS: Patients with SCZ and PBD had decreased global efficiency (Eglob) (SCZ: adjusted P<0.001; PBD: adjusted P = 0.003), local efficiency (Eloc) (SCZ and PBD: adjusted P<0.001), and clustering coefficient (Cp) (SCZ and PBD: adjusted P<0.001), and increased path length (Lp) (SCZ: adjusted P<0.001; PBD: adjusted P = 0.004) compared to HC. Patients with SCZ showed more pronounced decreases in Eglob (adjusted P<0.001), Eloc (adjusted P<0.001), and Cp (adjusted P = 0.029), and increased Lp (adjusted P = 0.024) compared to patients with PBD. The most notable structural disruptions were observed in the hippocampus and thalamus, which correlated with different psychotic symptoms, respectively. CONCLUSION: This study provides evidence of distinct structural connectivity disruptions in the limbic system of patients with SCZ and PBD. These findings might contribute to our understanding of the neuropathological basis for distinguishing SCZ and PBD.

Disease progression in proposed brain-first and body-first Parkinson's disease subtypes.

A new Parkinson's disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PDpRBD-, representing the brain-first subtype), PD patients with possible premotor RBD (PDpRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.