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A mediation analysis approach is proposed for multiple exposures, multiple mediators, and a continuous scalar outcome under the linear structural equation modeling framework. It assumes that there exist orthogonal components that demonstrate parallel mediation mechanisms on the outcome, and thus is named principal component mediation analysis (PCMA). Likelihood-based estimators are introduced for simultaneous estimation of the component projections and effect parameters. The asymptotic distribution of the estimators is derived for low-dimensional data. A bootstrap procedure is introduced for inference. Simulation studies illustrate the superior performance of the proposed approach. Applied to a proteomics-imaging dataset from the Alzheimer's disease neuroimaging initiative (ADNI), the proposed framework identifies protein deposition - brain atrophy - memory deficit mechanisms consistent with existing knowledge and suggests potential AD pathology by integrating data collected from different modalities.

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This study investigated the influence of Konjac Glucomannan (KGM) with varying degrees of polymerization (DKGMx) on the gelatinization and retrogradation characteristics of wheat starch, providing new insights into starch-polysaccharide interactions. This research uniquely focuses on the effects of DKGMx, utilizing multidisciplinary approaches including Rapid Visco Analysis (RVA), Differential Scanning Calorimetry (DSC), rheological testing, Low-Field Nuclear Magnetic Resonance (LF-NMR), and molecular simulations to assess the effects of DKGMx on gelatinization temperature, viscosity, structural changes post-retrogradation, and molecular interactions. Our findings revealed that higher degrees of polymerization (DP) of DKGMx significantly enhanced starch's pasting viscosity and stability, whereas lower DP reduced viscosity and interfered with retrogradation. High DP DKGMx promoted retrogradation by modifying moisture distribution. Molecular simulations revealed the interplay between low DP DKGMx and starch molecules. These interactions, characterized by increased hydrogen bonds and tighter binding to more starch chains, inhibited starch molecular rearrangement. Specifically, low DP DKGMx established a dense hydrogen bond network with starch, significantly restricting molecular mobility and rearrangement. This study provides new insights into the role of the DP of DKGMx in modulating wheat starch's properties, offering valuable implications for the functional improvement of starch-based foods and advancing starch science.

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BACKGROUND: The incidence of autoimmune diseases and breast cancer is significantly higher in women compared to men. Previous observational studies have not conclusively determined the relationship between these two conditions. This study utilizes the Mendelian randomization approach to investigate the genetic association between autoimmune diseases and breast cancer. METHOD: Two-sample Mendelian randomization was conducted on a European population using the GWAS database. The inverse variance-weighted method served as the primary analytical approach. The MR-PRESSO test was applied to detect horizontal pleiotropy. To ensure result robustness, the FDR correction method was used. RESULT: The study revealed that Sjögren's syndrome lowers the overall risk of breast cancer (OR 0.96, 95% CI [0.93-0.99], p = 0.011). Idiopathic inflammatory myopathy shows a protective effect against overall breast cancer (OR 0.98, 95% CI [0.97-0.99], p = 0.035). An association was identified between rheumatoid arthritis and overall breast cancer (OR 0.98, 95% CI [0.96-1.00], p = 0.050). No causal link was found between systemic lupus erythematosus, systemic sclerosis, and overall breast cancer. The study also suggests that Sjögren's syndrome, rheumatoid arthritis, and idiopathic inflammatory myopathy might reduce the risk of developing HER + breast cancer. Specifically, Sjögren's syndrome (OR = 0.90, 95% CI [0.83-0.98], p = 0.02), rheumatoid arthritis (OR = 0.94, 95% CI [0.91-0.98], p = 0.006), and idiopathic inflammatory myopathy (OR = 0.96, 95% CI [0.93-0.99], p = 0.036). Additionally, systemic lupus erythematosus was found to lower the risk of HER- breast cancer (OR = 0.95, 95% CI [0.91-0.99], p = 0.046). The study did not establish a causal relationship between these five autoimmune diseases and ER + or ER- breast cancer. CONCLUSION: This study found that autoimmune diseases may act as protective factors against breast cancer risk.

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The integration of visual simulation and biorehabilitation devices promises great applications for sustainable electronics, on-demand integration and neuroscience. However, achieving a multifunctional synergistic biomimetic system with tunable optoelectronic properties at the individual device level remains a challenge. Here, an electro-optically configurable transistor employing conjugated-polymer as semiconductor layer and an insulating polymer (poly(1,8-octanediol-co-citrate) (POC)) with clusterization-triggered photoactive properties as dielectric layer is shown. These devices realize adeptly transition from electrical to optical synapses, featuring multiwavelength and multilevel optical synaptic memory properties exceeding 3 bits. Utilizing enhanced optical memory, the images learning and memory function for visual simulation are achieved. Benefiting from rapid electrical response akin to biological muscle activation, increased actuation occurs under increased stimulus frequency of gate voltage. Additionally, the transistor on POC substrate can be effectively degraded in NaOH solution due to degradation of POC. Pioneeringly, the electro-optically configurability stems from light absorption and photoluminescence of the aggregation cluster in POC layer after 200 °C annealing. The enhancement of optical synaptic plasticity and integration of motion-activation functions within a single device opens new avenues at the intersection of optoelectronics, synaptic computing, and bioengineering.

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Pyridines and cyclopropanes are important structural units in chemistry. Herein, we introduce a photoredox-catalyzed approach for the ring opening and 1,3-oxypyridylation of aryl cyclopropanes using 4-cyanopyridines and carboxylic acids. This sequential process involves single-electron oxidation of the aryl cyclopropane, leading to nucleophilic ring opening and radical pyridylation at the benzylic position. The redox-neutral reaction exhibits high regioselectivity under mild reaction conditions, offering a broad substrate scope and wide applicability.

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Risk evaluation is ubiquitous in decisions. Deep brain stimulation of the subthalamic nucleus is effective for Parkinson's disease and obsessive-compulsive disorder, and can be associated with impulsivity and hypomania. Subthalamic stimulation has seemingly contrasting effects on impulsivity enhancing conflict-induced impulsivity but decreasing risk taking. Here, using a card gambling task paired with intracranial recordings (n = 25) and within-subject case control acute stimulation (n = 15) of the right subthalamic nucleus, we dissociated objective risk and uncertainty and subjective physiological markers of risk. Acute stimulation decreased risk taking (P = 0.010, Cohen's d = 0.72) and increased subthalamic theta activity (P < 0.001, Cohen's d = 0.72). Critically, stimulation negatively shifted the relationship between subthalamic physiology and a measure of evidence accumulation similar to observations with stimulation-induced conflict processing. This highlights the phenotypic and physiological heterogeneity of impulsivity, yet linking mechanisms underlying stimulation-induced conflict and risk. Finally, stimulation-induced risk seeking implicates the ventral subthalamic nucleus and dissociating anatomical and functional connectivity with the mesial prefrontal cortex. Our findings have implications for conceptualizations of impulsivity, and clinical relevance for neuropsychiatric disorders.

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BACKGROUND: This single-blind randomized controlled trial was aimed to evaluate the microbiological and clinical effects of Zeger therapy on gingival health. METHODS: Twenty-four adults with gingivitis were recruited and monitored micro-biologically and clinically at baseline (Day 0), 4 weeks (Day 29) after therapy. All volunteers received one-stage full-mouth supragingival scaling as basic oral health care for baseline, and then randomly divided into experimental (koumiss, n = 12) or control (none, n = 12) group. The koumiss was used once a day for 4 weeks. RESULTS: The microbial diversity of the experimental group increased significantly after drinking koumiss (p < 0.05), mainly owing to increasing of Gram-positive bacteria (p = 0.038) and oral health-related microbes (Rothia, Corynebacterium, Actinomyces, Saccharibacteria_TM7, etc.), decreasing of Gram-negative bacteria (p = 0.009) and periodontal disease-related microbes (Porphyromonas, Fusobacterium, Veillonella, etc.), while the microbial diversity of the control group had no significant change (p > 0.05). However, there was no significant difference between the two groups in the clinical parameters (p > 0.05). CONCLUSIONS: Zeger therapy promotes the diversity of supragingival microbiome in adults with gingivitis and increases the abundance of some beneficial flora while decreasing some harmful without clinical parameters marked changing, which holds promise for improving of gingivitis and may be a valuable oral health care approach in the future. TRIAL REGISTRATION: The clinical trial was approved by the Medical Ethics Committee of West China Hospital of Stomatology, Sichuan University, batch No. WCHSIRB-D-2021-428. Before patient registration began, the prospective clinical trial was registered in www. CLINICALTRIALS: gov public repository in China under the registration number ChiCTR2200060555 on 04/06/2022.

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Unmanned aerial vehicle (UAV)-assisted communication based on automatic modulation classification (AMC) technology is considered an effective solution to improve the transmission efficiency of wireless communication systems, as it can adaptively select the most suitable modulation method according to the current communication environment. However, many existing deep learning (DL)-based AMC methods cannot be directly applied to UAV platform with limited computing power and storage space, because of the contradiction between accuracy and efficiency. This paper mainly studies the lightweight of DL-based AMC networks to improve adaptability in resource-constrained scenarios. To address this challenge, we propose an ultra-lightweight neural network (ULNN). This network incorporates a lightweight convolutional structure, attention mechanism, and cross-channel feature fusion technique. Additionally, we introduce data augmentation (DA) based on signal phase offsets during the model training process, aimed at improving the model's generalization ability and preventing overfitting. Through experimental validation on the public dataset RML2016.10 A, the ULNN we proposed achieves an average precision of 62.83% with only 8815 parameters and reaches a peak classification accuracy of 92.11% at SNR = 10 dB. The experimental results show that ULNN can achieve high recognition accuracy while keeping the model lightweight, and is suitable for UAV platform with limited resources.

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Mesenchymal stem cells (MSCs) are heterogeneous in morphology and transcriptome, resulting in varying therapeutic outcomes. In this study, we found that 3D spheroid culture of heterogeneous MSCs, which have undergone conventional 2D monolayer culture for 5-6 passages, synchronized the cells into a uniform cell population with dramatically reduced cell size, and considerably increased levels of immunosuppressive genes and growth factors. Single-cell RNA sequencing (scRNA-seq) analysis of the cells revealed that 3D MSCs consisted of 2 major cell subpopulations and both expressed high levels of immunosuppressive factors, compared to 6 subpopulations in 2D MSCs. In addition, 3D MSCs showed a greater suppressive effect on T cells. Moreover, intravenous infusion of a large dose of 3D MSCs prior to imiquimod (IMQ) treatment significantly improved psoriatic lesion. Thus, our results indicate that 3D spheroid culture reprograms heterogeneous MSCs into a uniform immunosuppressive phenotype and promises a novel therapeutic potential for inflammatory diseases.

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Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥ 43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

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BACKGROUND: Associations of dietary sodium and potassium intake with fracture risk are inconsistent and the effects of salt substitute on fracture incidence are unknown. We assessed the effect of salt substitute compared to regular salt intake on fracture incidence using data from the Salt Substitute and Stroke Study (SSaSS). METHODS: SSaSS was a cluster-randomized controlled trial conducted in 600 villages in northern China. Villages were randomly allocated into intervention and control groups in a 1:1 ratio. Salt substitute was provided to intervention villages and control villages continued regular salt use for 5 years. The primary outcome for this secondary analysis was the incidence of all fractures. Secondary outcomes included incidence of vertebral fracture, non-vertebral fracture, and fracture of unknown or non-specific location. RESULTS: 20,995 participants were included in this study, and 821 fractures occurred during follow-up. Intention-to-treat analyses showed no differences between the salt substitute and regular salt groups in the incidence of all fractures (rate ratio (RR) 0.96; 95% CI 0.81 to 1.14), vertebral fracture (RR 0.82; 95% CI 0.53 to 1.26), non-vertebral fracture (RR 1.05; 95% CI 0.86 to 1.29), or fracture of unknown or non-specific location (RR 0.80; 95% CI 0.54 to 1.18). CONCLUSIONS: Use of salt substitute compared to regular salt had no detectable effect on the incidence of fracture in a population at high risk of cardiovascular disease and fracture. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02092090. Registered on March 12, 2014.

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Bovine viral diarrhea-mucosal disease (BVD-MD) is a contagious disease in cattle, caused by the bovine viral diarrhea virus (BVDV). This virus continues to spread globally, exerting pressure on both public health and the economy. Despite its impact, there are currently no effective drugs for treating BVDV. This study utilized Madin-Darby bovine kidney (MDBK) cells as a model to investigate the antiviral effects of melatonin against Bovine Viral Diarrhea Virus (BVDV) and its connection with endoplasmic reticulum (ER) stress. Our results show that melatonin can suppress BVDV proliferation in MDBK cells by modulating the endoplasmic reticulum (ER) stress-mediated NF-κB pathway and autophagy. Specifically, melatonin alleviated ER stress, inhibited the activation of IκBα and p65, regulated autophagy, and reduced the expression levels of pro-inflammatory cytokines. Further, when we treated BVDV-infected cells with the ER stress inducer thapsigargin, it led to significant activation of the NF-κB pathway and autophagy. Conversely, treating the cells with the ER stress inhibitor 4-phenylbutyric acid reversed these effects. These findings suggest that melatonin exerts its antiviral effects primarily through the PERK-eIF2α-ATF4 of ER stress-mediated NF-κB pathway and autophagy. Overall, our study underscores the potential of melatonin as an effective protective and therapeutic option against BVDV, offering insights into its anti-infective mechanisms.

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Background and aims: Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease characterized by chronic inflammation. The Inflammatory Burden Index (IBI) is a newly proposed comprehensive inflammation index used to assess systemic inflammation. The relationship between IBI and RA, as well as its all-cause mortality, remains unclear. The objective of this study was to examine the correlation between IBI and RA and to analyze the association between IBI and all-cause mortality in RA. Methods: The study comprehensively analyzes adult data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The participants' IBI was calculated using the formula IBI = CRP * neutrophils/lymphocytes. Three models were constructed to investigate the relationship between IBI and the prevalence of RA. Nonlinear relationships were determined using restricted cubic spline curves. Stratified analyses and interaction tests were used to explore the relationship between RA and IBI in different subgroups. The same data analyses were applied to investigate the association between IBI and RA all-cause mortality. Results: The data analyses revealed a stable positive and nonlinear correlation between IBI and the risk of RA, as well as a positive, nonlinear, J-shaped association between IBI and RA all-cause mortality. The correlation and association were consistent across most subgroups, and multiple covariates had no effect on the results. No significant effect of multiple covariates on the association was found through interaction tests. Conclusion: Our study has demonstrated a positive correlation between the prevalence of RA and all-cause mortality with the IBI index. This suggests that lower levels of inflammation in the body are associated with a reduced risk of RA prevalence and all-cause mortality. Further prospective studies are required to explore the mechanisms involved.

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PURPOSE: We aim to determine the effectiveness of adding electroacupuncture to standard triple antiemetic therapy for treating chemotherapy-induced nausea and vomiting (CINV). METHODS: From March 2022 to December 2023, a randomized, blind, sham-controlled trial conducted across six Chinese hospitals investigated patients with breast cancer undergoing highly emetogenic chemotherapy (HEC). Patients were randomly assigned to either true electroacupuncture (n = 120) or sham electroacupuncture (n = 119) groups, with both groups receiving standard triple antiemetic therapy. The primary end point was the proportion of complete protection (no vomiting, no need for rescue treatment, and no significant nausea, as evaluated using the visual analog scale [VAS]) within 120 hours after receiving HEC. RESULTS: Among 239 randomly assigned patients, 235 (98.3%) completed the trial. In the full analysis set, compared with the sham electroacupuncture group, the true electroacupuncture group demonstrated a significant increase in the complete protection rate from 34.5% to 52.9% (P = .004). Additionally, true electroacupuncture also showed enhanced total control (4.3% v 13.4%; P = .014), no significant nausea (37.9% v 58.8%; P = .001), no nausea (4.3% v 13.4%; P = .014), and nausea VAS score = 0 mm (4.3% v 12.6%; P = .023). However, the occurrence of no vomiting in the overall stage was similar (76.7% v 73.9%; P = .622) in both groups. Post hoc exploratory analysis showed a significantly higher rate of complete protection during the delayed stage in the true electroacupuncture group compared with the sham electroacupuncture group, with no significant difference observed during the acute stage. CONCLUSION: Adding true electroacupuncture to standard triple antiemetic therapy significantly enhances the efficacy of CINV treatment in patients with breast cancer receiving HEC.

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Conventional fluorescent materials frequently exhibit narrow-band emissions with a small full width at half-maximum (fwhm) due to localized-state characteristics, but electroluminescence is less efficient owing to the utilization of only singlet excitons. In this work, taking advantage of naphthalimide (NAI)-acetylide derivatives with a rigid planar structure and localized transition characteristics, we elaborately designed two mononuclear Pt(II) complexes with weak double emissions of fluorescence and phosphorescence. Taking them as synthetic precursors, we prepared three PtAu2 heteronuclear clusters and successfully attained highly efficient narrow-band red phosphorescence with the fwhm below 30 nm. Both theoretical and experimental results suggest that the phosphorescence of PtAu2 clusters mainly originates from the naphthalimide-localized 3IL (intraligand) triplet state. Solution-processed organic light-emitting diodes (OLEDs) achieved highly efficient narrow-band red electroluminescence with an external quantum efficiency (EQE) of 16.7%. The CIE coordinates of the electroluminescence (0.69, 0.31) closely match the standard red emission for ultrahigh-definition display.

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Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

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BACKGROUND: With the widespread use of CDK4/6 inhibitors, the number of discontinuations and reductions due to adverse events is increasing. Therefore, we examined the risk of dose reduction, discontinuation, and occurrence of serious adverse events and death due to adverse events when CDK4/6 inhibitors are combined with endocrine drugs. METHODS: We searched English-language articles published up to February 10, 2024, using RR values (risk ratio) to indicate the risk of discontinuation, dose reduction, death, and the risk of serious adverse events. RESULTS: When CDK4/6 inhibitors were used in combination with endocrine drugs, abemaciclib resulted in the highest risk of discontinuation, dose reduction, and serious adverse events. Ribociclib caused the highest risk of death. CONCLUSION: When using CDK4/6 inhibitors in the clinical setting, a comprehensive evaluation should be performed to avoid dosage reductions and discontinuations and to choose the most appropriate treatment regimen.

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The effect of dietary antioxidants on blood pressure (BP) regulation and hypertension risk remains largely unknown. This study aimed to comprehensively assess the impacts of dietary antioxidants on systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), and hypertension risk among Chinese adults. The cross-sectional study assessed data from 12,046 Chinese adults, evaluating dietary antioxidant quality scores (DAQS) and total antioxidant capacity (DTAC) via a validated food frequency questionnaire. MAP was derived using the formula DBP + (0.412 ×PP), with PP calculated as SBP - DBP. The relationship between DAQS, DTAC, and hypertension prevalence was analyzed using multivariable logistic regression. Among participants not taking antihypertensive medications, those in the highest groups of DTAC and DAQS had significantly lower SBP, DBP, MAP, and PP compared to those in the lowest groups (all p-trends <0.001). Relative to the lowest quintile (Q1) of DTAC (adjusted odds ratios (OR) for hypertension decreased in Q2 (OR 0.90, 95%CI 0.79-1.03), Q3 (OR 0.65, 95% CI 0.56-0.76), Q4 (OR 0.51, 95% CI 0.43-0.60), and Q5 (OR 0.38, 95% CI 0.31-0.46) (p trend <0.001). For DQAS, hypertension OR of category 5 was 0.38 (95% CI 0.32-0.46) compared to that of category 1. Increased vitamin A, Zinc, and selenium intake correlated with reduced hypertension risk. A significant non-linear DTAC and linear DAQS relationships were observed and hypertension risk. Antioxidant-rich diets markedly lowered SBP, DBP, MAP, PP, and hypertension risk.

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Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P < 5 × 10-8) associations, including five known (MAPT, MOBP, STX6, RUNX2, SLCO1A2) and one novel locus (C4A). Integration with cell type-specific epigenomic annotations reveal an oligodendrocytic signature that might distinguish PSP from AD and Parkinson's disease in subsequent studies. Candidate PSP risk gene prioritization using expression quantitative trait loci (eQTLs) identifies oligodendrocyte-specific effects on gene expression in half of the genome-wide significant loci, and an association with C4A expression in brain tissue, which may be driven by increased C4A copy number. Finally, histological studies demonstrate tau aggregates in oligodendrocytes that colocalize with C4 (complement) deposition. Integrating GWAS with functional studies, epigenomic and eQTL analyses, we identify potential causal roles for variation in MOBP, STX6, RUNX2, SLCO1A2, and C4A in PSP pathogenesis.

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Engineering of hollow particles with tunable internal structures often requires complicated processes and/or invasive cleavage. Halogen-bond driven 3D confined-assembly of block copolymers has shed light on the engineering of polymer organization along with the fabricating of unique nanostructures. Herein, a family of multilevel hollow-structured particles (e.g., fully porous, multi-chamber, multi-shell, and concentric multi-layer architectures) is reported via halogen-bond regulated 3D confined-assembly of amphiphilic polymer networks. To do so, polystyrene-b-poly(2-vinyl pyridine)-b-poly(ethylene oxide) (PS-b-P2VP-b-PEO) amphiphilic triblock copolymer is selected, where P2VP blocks act as halogen acceptor. Meanwhile, poly(3-(2,3,5,6-tetrafluoro-4-iodophenoxy) propyl acrylate) (PTFIPA) is employed as halogen donor. Halogen-bond driven donor-acceptor linking between PTFIPA and P2VP block presented in PS-b-P2VP-b-PEO, can lead to the formation of supramolecular polymeric networks, along with the increased P2VP domain and tunable hydrophobic volume. Therefore, an adjustable packing parameter (p) is thus anticipated, which can enable the morphology transformation sequence until an equilibrium state is reached. Moreover, computer simulations are further utilized as the tool to interpret such morphologies transition and identify the precise distribution of each component. Benefiting from the tunable hollow structure and a substantial surface for transporting purpose, these structurally novel particles open perspectives toward promising applications including encapsulation, nanoreactor, and catalyst support.