Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer's disease.

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD-associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD-associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD.

Nanostructure-based orbital angular momentum encryption and multiplexing.

The orthogonality among the OAM modes provides a new degree of freedom for optical multiplexing communications. So far, traditional Dammann gratings and spatial light modulators (SLMs) have been widely used to generate OAM beams by modulating electromagnetic waves at each pixel. However, such architectures suffer from limitations in terms of having a resolution of only a few microns and the bulkiness of the entire optical system. With the rapid development of the electromagnetic theory and advanced nanofabrication methods, artificial nanostructures, especially optical metasurfaces, have been introduced which greatly shrink the size of OAM multiplexing devices while increasing the level of integration. This review focuses on the study of encryption, multiplexing and demultiplexing of OAM beams based on nanostructure platforms. After introducing the focusing characteristics of OAM beams, the interaction mechanism between OAM beams and nanostructures is discussed. The physical phenomena of helical dichroism response and spatial separation of OAM beams achieved through nanostructures, setting the stage for OAM encryption and multiplexing, are reviewed. Afterward, the further advancements and potential applications of nanophotonics-based OAM multiplexing are deliberated. Finally, the challenges of conventional design methods and dynamic tunable techniques for nanostructure-based OAM multiplexing technology are addressed.

Expression of human Ras-related protein Rab39B variant T168K in Caenorhabditis elegans leads to motor dysfunction and dopaminergic neuron degeneration.

Human RAB39B gene is related to familial early-onset Parkinson disease. In early adulthood, men with the RAB39B c.503C > A (Thr168Lys, p. T168K) mutation develop typical tremor, bradykinesia, and alpha-synuclein accumulation. We investigated the pathological mechanism of RAB39B T168K in a Caenorhabditis elegans model. In early adult C. elegans, RAB39B T168K led to dopaminergic neuron degeneration that presented as disrupted dendrites and blunt neuronal cells. Abnormal dopamine secretion was inferred from a decline in motor function and a positive basal slowing phenotype. Dopamine-associated tests confirmed that synthesis and recycling of dopamine were normal. The RAB39B T168K mutation might impair dopamine vesicular transmission from the presynaptic membrane to the synaptic gap in dopaminergic neurons. The release-dependent feedback mechanism in neurotransmitters regulates the balance of receptor activities. Protein-protein interactions network analysis revealed that RAB39B may also function in lysosomal degradation and autophagy. Impaired disposal of misfolded α-synuclein eventually leads to protein aggregation. Thus, like other members of the Rab family, RAB39B may be involved in vesicular transport associated with dopamine secretion and α-synuclein clearance.

Mental health disparities in young adults with arrest history: a survey-based, cross-sectional analysis.

BACKGROUND: Over 4.53 million arrests were made in 2021 in the United States. People under 26 years of age were more likely to be arrested than older people. Although mental health disparities are prominent in the incarcerated population, the subject has not been closely examined among young adults specifically. OBJECTIVES: This study examines how criminal justice involvement, specifically arrests, affects the mental health of adults between 18 and 25 years of age. METHODS: We analyzed secondary data using the 2021 National Survey on Drug Use and Health (NSDUH). The study used a subsample of 13,494 people aged 18 to 25 years, including 7,330 women and 6,164 men. History of arrest was the key independent variable. Depression, serious mental illness (SMI), substance use, suicidal ideation, and suicide attempt were the outcome variables. We performed five multivariate logistic regression models for each outcome variable, controlling for race/ethnicity, income, and education level for men and women separately. RESULTS: Of 13,494 respondents, 6.63% had a history of arrest. Among young women, a history of arrest was associated with significantly higher adjusted odds ratios for all mental health concerns. Most notably, a history of arrest increased the likelihood of substance use by a factor of 15.19, suicide attempts by 2.27, SMI by 1.79, suicidal ideation by 1.75, and depression by 1.52. Among young men, a history of arrest was associated with increased adjusted odds ratios (AORs) for substance use (AOR, 13.37; p < .001), suicidal ideation (AOR, 1.45; p = .011), and suicide attempt (AOR, 1.82; p = .044). CONCLUSIONS: We found a strong relationship between young people having an arrest history and mental health concerns. More specifically, a history of arrest was associated with all mental health concerns among young women, while it was associated with only substance use and suicide among young men. Providing arrestees with appropriate mental health care would benefit them and the criminal justice system by decreasing the odds of recidivism.

Case report: GCA like picture-preceding inaugural MOGAD presentation: A patient with a sudden-onset uniocular blindness.

RATIONALE: Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) represents a demyelinating neurological syndrome characterized by the presence of serum IgG antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG). Concurrently, giant cell arteritis (GCA) constitutes a systemic autoimmune vasculitis. PATIENT CONCERNS: In this case, we describe an elderly female patient who presented with the sudden onset of a severe headache, unilateral blindness, and clinical manifestations resembling those of GCA. DIAGNOSIS: Upon conducting a comprehensive analysis of serum antibodies, the diagnosis of MOGAD was established due to the presence of detectable serum MOG-IgG. INTERVENTIONS: Subsequently, the patient was administered intravenous methylprednisolone therapy, commencing 27 days after the initial onset of symptoms. OUTCOMES: It is noteworthy that patients afflicted by MOGAD typically manifest severe visual impairment, which, in many instances, exhibits significant improvement following immunotherapeutic interventions. However, this particular patient did not experience any amelioration in visual function despite glucocorticoid therapy. LESSONS: This unique case illustrates that the clinical presentation resembling GCA may precede the inaugural manifestation of MOGAD. This suggests the possibility of immune-mediated arterial involvement. The significance of glucocorticoid therapy in the context of immune-related diseases warrants further scrutiny, particularly in cases where MOG-IgG screening should be promptly considered.

Arbitrarily polarized bound states in the continuum with twisted photonic crystal slabs.

Arbitrary polarized vortex beam induced by polarization singularity offers a new platform for both classical optics and quantum entanglement applications. Bound states in the continuum (BICs) have been demonstrated to be associated with topological charge and vortex polarization singularities in momentum space. For conventional symmetric photonic crystal slabs (PhCSs), BIC is enclosed by linearly polarized far fields with winding angle of 2π, which is unfavorable for high-capacity and multi-functionality integration-optics applications. Here, we show that by breaking σz-symmetry of the PhCS, asymmetry in upward and downward directions and arbitrarily polarized BIC can be realized with a bilayer-twisted PhCS. It exhibits elliptical polarization states with constant ellipticity angle at every point in momentum space within the vicinity of BIC. The topological nature of BIC reflects on the orientation angle of polarization state, with a topological charge of 1 for any value of ellipticity angle. Full coverage of Poincaré sphere (i.e., [Formula: see text] and [Formula: see text]) and higher-order Poincaré sphere can be realized by tailoring the twist angles. Our findings may open up new avenues for applications in structured light, quantum optics, and twistronics for photons.

Neuromyelitis optica spectrum disease coexisting with subacute combined degeneration: a case report.

BACKGROUND: Subacute combined degeneration (SCD) is a demyelinating disease characterized by vitamin B12 deficiency related segmental degeneration of the dorsal or lateral columns of the spinal cord. However, few cases have been reported as a comorbidity of SCD and neuromyelitis optica spectrum disease (NMOSD). CASE PRESENTATION: Herein, we describe a female patient (61-year-old) who had sensory deficits, paresthesia, and weakness of the distal extremities for over 2 months. She then received an initial diagnosis of SCD with typical inverted "V-sigh" hyperintensities over the posterior aspect of the spinal cord in magnetic resonance imaging (MRI - T2-weighted imaging), as well as megaloblastic anaemia in blood examinations. From the past history, there was no evidence of a dietary deficiency or gastric abnormalities. However, traditional treatment with vitamin B12 supplementation was ineffective. Hence, a demyelinating antibody examination showed that she had antibodies targeting aquaporin 4 (AQP4) in both the cerebrospinal fluid and serum, leading to the diagnosis of NMOSD. Her clinical symptoms were obviously improved after treatment with intravenous glucocorticoids. CONCLUSION: People who have nutritional deficiency or altered gastrointestinal function are more likely to develop SCD. This case raises the awareness that the poor therapeutic effects of simple vitamin B12 supplementation could be explained by immunoreactions against AQP4. A better recognition will be of great importance for the correct diagnosis of the comorbidity, as well as for essential treatment and even a better prognosis.

Health behaviors and tooth retention among older adults in China: findings from the 4th Chinese national oral health survey.

BACKGROUND: This study aimed to examine the association between oral health behaviors and tooth retention among Chinese older adults. METHODS: Data were used from the 4th Chinese National Oral Health Survey, a nationally representative sample. The sample included 9054 older adults aged 55 to 74. Control variables and oral health behaviors were measured through a questionnaire interview, and the number of remaining teeth and periodontal health were obtained from an oral health examination. A chi-square test was used for univariate analysis. Multivariate Logistic regression was used to explore the association between health behaviors and the number of remaining teeth. RESULTS: The average number of remaining teeth in the sample was 24.4 ± 7.7. There was a higher proportion of older adults living in urban areas with 20 or more teeth than those living in rural areas (83.2% vs. 79.4%, P < 0.001); and a higher proportion of individuals with high education levels with 20 or more teeth compared to those with low education levels (P < 0.001). Logistic regression models showed that older adults who used toothpicks `(OR = 3.37, 95% CI 2.94-3.85), dental floss (OR = 1.93, 95% CI 1.05-3.53), toothpaste (OR = 3.89, 95% CI 3.14-4.83); and never smoked (OR = 1.43 95% CI 1.20-1.70) were more likely to retain 20 or more natural teeth; whereas older adults who had a dental visit were less likely to retain 20 or more natural teeth (OR = 0.45, 95% CI 0.39-052). CONCLUSION: Good oral hygiene practices, never smoking, and regular dental visits focusing on prevention are significantly associated with teeth retention. It is critical to promote a healthy lifestyle and improve prevention-oriented oral health care systems.

Planar chiral metasurfaces with maximal and tunable chiroptical response driven by bound states in the continuum.

Optical metasurfaces with high quality factors (Q-factors) of chiral resonances can boost substantially light-matter interaction for various applications of chiral response in ultrathin, active, and nonlinear metadevices. However, current approaches lack the flexibility to enhance and tune the chirality and Q-factor simultaneously. Here, we suggest a design of chiral metasurface supporting bound state in the continuum (BIC) and demonstrate experimentally chiroptical responses with ultra-high Q-factors and near-perfect circular dichroism (CD = 0.93) at optical frequencies. We employ the symmetry-reduced meta-atoms with high birefringence supporting winding elliptical eigenstate polarizations with opposite helicity. It provides a convenient way for achieving the maximal planar chirality tuned by either breaking in-plane structure symmetry or changing illumination angle. Beyond linear CD, we also achieved strong near-field enhancement CD and near-unitary nonlinear CD in the same planar chiral metasurface design with circular eigen-polarization. Sharply resonant chirality realized in planar metasurfaces promises various practical applications including chiral lasers and chiral nonlinear filters.

Mutant VPS35-D620N induces motor dysfunction and impairs DAT-mediated dopamine recycling pathway.

The D620N mutation in vacuolar protein sorting protein 35 (VPS35) gene has been identified to be linked to late onset familial Parkinson disease (PD). However, the pathophysiological roles of VPS35-D620N in PD remain unclear. Here, we generated the transgenic Caenorhabditis elegans overexpressing either human wild type or PD-linked mutant VPS35-D620N in neurons. C. elegans expressing VPS35-D620N, compared with non-transgenic controls, showed movement disorders and dopaminergic neuron loss. VPS35-D620N worms displayed more swimming induced paralysis but showed no defects in BSR assays, thus indicating the disruption of dopamine (DA) recycling back inside neurons. Moreover, VPS35 formed a protein interaction complex with DA transporter (DAT), RAB5, RAB11 and FAM21. In contrast, the VPS35-D620N mutant destabilized these interactions, thus disrupting DAT transport from early endosomes to recycling endosomes, and decreasing DAT at the cell surface. These effects together increased DA in synaptic clefts, and led to dopaminergic neuron degeneration and motor dysfunction. Treatment with reserpine significantly decreased the swimming induced paralysis in VPS35-D620N worms, as compared with vehicle treated VPS35-D620N worms. Our studies not only provide novel insights into the mechanisms of VPS35-D620N-induced dopaminergic neuron degeneration and motor dysfunction via disruption of DAT function and the DA signaling pathway but also indicate a potential strategy to treat VPS35-D620N-related PD and other disorders.

Magnetic modulation of topological polarization singularities in momentum space.

The polarization singularities in momentum space, rather than in real space, are capturing interest for active singular optics with exotic light scattering and various topological phenomena, which have potential applications in vortex nano-lasers, valley exciton emission, and others. Here, we propose to magnetically control the polarization singularities in momentum space in the photonic crystal slabs with inversion spatial symmetry (P symmetry). A pair of C points (circular polarization points) with the same topological charge is spawned from a V point (polarization vortex center), and they can be dynamically shifted in momentum space with the variation of the magnetic field. Moreover, the coupling between transverse electric (TE) and transverse magnetic (TM) modes induced by the magnetic field gives rise to a hybrid mode, which can close certain leaky channels to achieve an accidental V point. Such active manipulation of polarization singularities with magnetic field is promised for various applications in light-matter interactions and reveals novel phenomena and physics in singular optics and topological photonics.

Evaluation of Blood Glial Fibrillary Acidic Protein as a Potential Marker in Huntington's Disease.

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD. Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity. Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2. Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

Dynamics of Topological Polarization Singularity in Momentum Space.

The polarization singularity in momentum space has recently been discovered as a new class of topological signatures of Bloch modes in photonic crystal slabs concerning the far-field radiations, beyond its near-field description with widely explored topological band theory. Bound states in the continuum (BICs) in photonic crystal slabs are demonstrated as vortex eigenpolarization singularities in momentum space and the circular polarization points (C points) are also obtained based on BICs, opening up more possibilities for exotic light scattering and various topological phenomena of singular optics. Here, focusing on the nondegenerate bands, we report the generation to annihilation of two pairs of C points in momentum space in the photonic crystal slabs with inversion symmetry but broken up-down mirror symmetry. Interestingly, as the C points evolve with the structure parameter, we find two merging processes of C points, where an accidental at-Γ BIC and unidirectional radiative resonances with leaky channels of drastically different radiative lifetime emerge. The whole evolution is governed by the global charge conservation and the sum of topological charges equals to zero. Our findings suggest a novel recipe for dynamic generation and manipulation of various polarization singularities in momentum space and might shed new light to control the resonant and topological properties of light-matter interactions.

Adaptable Invisibility Management Using Kirigami-Inspired Transformable Metamaterials.

Many real-world applications, including adaptive radar scanning and smart stealth, require reconfigurable multifunctional devices to simultaneously manipulate multiple degrees of freedom of electromagnetic (EM) waves in an on-demand manner. Recently, kirigami technique, affording versatile and unconventional structural transformation, has been introduced to endow metamaterials with the capability of controlling EM waves in a reconfigurable manner. Here, we report for a kirigami-inspired sparse meta-architecture, with structural density of 1.5% in terms of the occupation space, for adaptive invisibility based on independent operations of frequency, bandwidth, and amplitude. Based on the general principle of dipolar management via structural reconstruction of kirigami-inspired meta-architectures, we demonstrate reconfigurable invisibility management with abundant EM functions and a wide tuning range using three enantiomers (A, B, and C) of different geometries characterized by the folding angle ß. Our strategy circumvents issues of limited abilities, narrow tuning range, extreme condition, and high cost raised by available reconfigurable metamaterials, providing a new avenue toward multifunctional smart devices.

Multimodal Neuroimaging Predictors of Learning Performance of Sensorimotor Rhythm Up-Regulation Neurofeedback.

Electroencephalographic (EEG) neurofeedback (NFB) is a popular neuromodulation method to help one selectively enhance or inhibit his/her brain activities by means of real-time visual or auditory feedback of EEG signals. Sensory motor rhythm (SMR) NFB protocol has been applied to improve cognitive performance, but a large proportion of participants failed to self-regulate their brain activities and could not benefit from NFB training. Therefore, it is important to identify the neural predictors of SMR up-regulation NFB training performance for a better understanding the mechanisms of individual difference in SMR NFB. Twenty-seven healthy participants (12 males, age: 23.1 ± 2.36) were enrolled to complete three sessions of SMR up-regulation NFB training and collection of multimodal neuroimaging data [resting-state EEG, structural magnetic resonance imaging (MRI), and resting-state functional MRI (fMRI)]. Correlation analyses were performed between within-session NFB learning index and anatomical and functional brain features extracted from multimodal neuroimaging data, in order to identify the neuroanatomical and neurophysiological predictors for NFB learning performance. Lastly, machine learning models were trained to predict NFB learning performance using features from each modality as well as multimodal features. According to our results, most participants were able to successfully increase the SMR power and the NFB learning performance was significantly correlated with a set of neuroimaging features, including resting-state EEG powers, gray/white matter volumes from MRI, regional and functional connectivity (FC) of resting-state fMRI. Importantly, results of prediction analysis indicate that NFB learning index can be better predicted using multimodal features compared with features of single modality. In conclusion, this study highlights the importance of multimodal neuroimaging technique as a tool to explain the individual difference in within-session NFB learning performance, and could provide a theoretical framework for early identification of individuals who cannot benefit from NFB training.