Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

On practicing magicine, from wonder to care: A systematic review of studies that apply magic in healthcare.

RATIONALE: Magic, traditionally perceived as entertainment, has been increasingly employed in healthcare to enhance health and well-being. Despite its potential benefits across various dimensions of health, including biological, psychological, and social, a comprehensive review highlighting its broad applications in healthcare remains unexplored. OBJECTIVE: This study aims to explore the diverse uses of magic within healthcare, progressing from entertainment to integral medical care, termed "magicine." METHODS: This systematic review adopted a narrative synthesis approach, and an extensive database search was conducted including Embase Classic & Embase, MEDLINE (Ovid), Scopus, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and CINAHL (EBSCOhost), from the earliest records to 22 June 2023. Potential applications of magic in healthcare were explored with an unrestricted search strategy. A quality assessment was conducted using the Mixed Methods Appraisal Tool. (Registration: PROSPERO number CRD42023417122.) RESULTS: This review identified 82 journal articles, including 11 randomized controlled trials, four quasi-experimental designs, 10 pre-experimental designs, five qualitative studies, three mixed methods studies, two observational studies, five review articles, and 42 commentaries. The review resulted in the conception of "magicine ennead" - nine diverse areas where magic can be applied in healthcare including physical rehabilitation, cognitive training, psychotherapy, humor therapy, distraction therapy, social skills, health education, doctor-patient relationships, and surgical techniques. These applications demonstrate the potential of magic to enhance health outcomes for the general population and improve the clinical practice of healthcare professionals. CONCLUSIONS: Magic in healthcare shows potential for varied applications, and a deeper understanding of these applications could lead to optimized and cost-efficient intervention programs. Given the heterogeneity and varied methodological quality of the current research, future studies necessitate the adoption of rigorous designs with active controls.

Identification of KU-55933 as an anti-atherosclerosis compound by using a hemodynamic-based high-throughput drug screening platform.

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 (Id-1) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 µM), Apicidin (10 µM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations.

Characterization of genes involved in micronutrients and toxic metals detoxification in Brassica napus by genome-wide cDNA library screening.

Stresses caused by deficiency/excess of mineral nutrients or of pollution of toxic metals have already become a primary factor in limiting crop production worldwide. Genes involved in minerals and toxic metals accumulation/tolerance could be potential candidates for improving crop plants with enhanced nutritional efficiency and environmental adaptability. In this study, we first generated a high-quality yeast expression cDNA library of Brassica napus (Westar), and 46 genes mediating excess micronutrients and toxic metals detoxification were screened using the yeast genetic complementation system, including 11, 5, 6, 14, 6, and 5 genes involved in cadmium (Cd), zinc (Zn), iron (Fe), manganese (Mn), boron (B), and copper (Cu) tolerance, respectively. Characterization of genes mediating excess ions stress resistance in this study is beneficial for us to further understand ions homeostasis in B. napus.

Asymmetric conformations of cleaved HIV-1 envelope glycoprotein trimers in styrene-maleic acid lipid nanoparticles.

During virus entry, the pretriggered human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer initially transits into a default intermediate state (DIS) that remains structurally uncharacterized. Here, we present cryo-EM structures at near-atomic resolution of two cleaved full-length HIV-1 Env trimers purified from cell membranes in styrene-maleic acid lipid nanoparticles without antibodies or receptors. The cleaved Env trimers exhibited tighter subunit packing than uncleaved trimers. Cleaved and uncleaved Env trimers assumed remarkably consistent yet distinct asymmetric conformations, with one smaller and two larger opening angles. Breaking conformational symmetry is allosterically coupled with dynamic helical transformations of the gp41 N-terminal heptad repeat (HR1N) regions in two protomers and with trimer tilting in the membrane. The broken symmetry of the DIS potentially assists Env binding to two CD4 receptors-while resisting antibody binding-and promotes extension of the gp41 HR1 helical coiled-coil, which relocates the fusion peptide closer to the target cell membrane.

The effects of a magic-based intervention on self-esteem, depressive symptoms, and quality of life among community-dwelling older adults: a randomised controlled trial.

BACKGROUND: Magic-based programs have been utilised to enhance well-being across various health aspects. However, there is a lack of studies on whether performing magic tricks can provide mental health benefits for older adults living in the community. Therefore, this study aims to investigate the effects of a magic-based intervention program on self-esteem, depressive symptoms, and quality of life (QOL), and to examine the relationship between these factors in older adults. METHODS: Thirty-eight participants, aged 60-90 years, were randomly assigned to either a magic intervention group or a control group. The magic intervention program, tailored for older adults, was conducted for 90 min, twice weekly, over 6 weeks. The Rosenberg Self-Esteem Scale (RSE), the 15-item Geriatric Depression Scale (GDS-15), and the World Health Organization Quality of Life-BREF scores were measured and analyzed in both groups before and after the intervention. RESULTS: The magic-based intervention significantly increased self-esteem and reduced depressive symptoms in older adults, with large effect sizes. However, no significant impact on QOL was observed. Additionally, no significant correlation was found between the improvement in self-esteem and the reduction in depressive levels. Despite this, a moderate but significant negative correlation was detected between the post-intervention scores of RSE and GDS-15 in the magic intervention group. CONCLUSIONS: The study demonstrated that the magic intervention program was beneficial in promoting mental health in community-dwelling older adults. Implementing magic programs in communities appears to be an effective approach to enhance self-esteem and alleviate depressive symptoms in the older population.

Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated. METHODS: Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs). RESULTS: A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE-/-) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE-/- mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis. CONCLUSIONS: The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.

Effectiveness of online and offline health education myopia intervention on primary school students / 中国学校卫生

Objective@#To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices.@*Methods@#From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools.@*Results@#The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93，10.37，2.29， P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05).@*Conclusions@#Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.

Impact of a magic recreation program on older adults with minor depressive symptoms in a long-term care facility: A pilot randomized controlled trial.

OBJECTIVES: To evaluate a magic recreation program to reduce depressive symptoms in institutionalized older adults. METHODS: We conducted a pilot randomized controlled trial in which participants were assigned to either a magic group (n = 6) or a control group with usual activities (n = 6). The magic group received a 6-week magic recreation program. The data were analyzed by generalized estimating equations in terms of intention-to-treat analysis. A sensitivity analysis was conducted by examining the complete case analysis. RESULTS: The magic recreation program significantly improved the scores of Patient Health Questionnaire-9 in the magic group (Wald χ 2 = 8.816, p = 0.004, Cohen's  d  = 1.51, power = 0.9968). The results of the sensitivity analysis were consistent with the results of primary analysis. CONCLUSIONS: The 6-week magic recreation program reduced depressive symptoms among institutionalized older adults with minor depressive symptoms.

Corrigendum: The Effects of a Magic Intervention Program on Cognitive Function and Neurocognitive Performance in Elderly Individuals With Mild Cognitive Impairment.

[This corrects the article DOI: 10.3389/fnagi.2022.854984.].

Manganese(III)-promoted highly stereoselective phosphorylation of acyclic tertiary enamides to synthesize E-selective ß-phosphoryl enamides.

A concise manganese(III)-promoted stereoselective ß-phosphorylation of acyclic tertiary enamides and diverse H-phosphine oxides was achieved. This reaction proceeds with absolute E-selectivity in contrast to Z-selectivity obtained in other previous works and affords various E-selective ß-phosphorylated tertiary enamides in high efficiency. To the best of our knowledge, this is the first case of E-selective ß-phosphorylation of tertiary enamides through C-H functionalization. In addition, the method features broad substrate scope, good functional group compatibility and efficient scale-up.

Visualization of a Machine Learning Framework toward Highly Sensitive Qualitative Analysis by SERS.

Surface-enhanced Raman spectroscopy (SERS), providing near-single-molecule-level fingerprint information, is a powerful tool for the trace analysis of a target in a complicated matrix and is especially facilitated by the development of modern machine learning algorithms. However, both the high demand of mass data and the low interpretability of the mysterious black-box operation significantly limit the well-trained model to real systems in practical applications. Aiming at these two issues, we constructed a novel machine learning algorithm-based framework (Vis-CAD), integrating visual random forest, characteristic amplifier, and data augmentation. The introduction of data augmentation significantly reduced the requirement of mass data, and the visualization of the random forest clearly presented the captured features, by which one was able to determine the reliability of the algorithm. Taking the trace analysis of individual polycyclic aromatic hydrocarbons in a mixture as an example, a trustworthy accuracy no less than 99% was realized under the optimized condition. The visualization of the algorithm framework distinctly demonstrated that the captured feature was well correlated to the characteristic Raman peaks of each individual. Furthermore, the sensitivity toward the trace individual could be improved by least 1 order of magnitude as compared to that with the naked eye. The proposed algorithm distinguished by the lesser demand of mass data and the visualization of the operation process offers a new way for the indestructible application of machine learning algorithms, which would bring push-to-the-limit sensitivity toward the qualitative and quantitative analysis of trace targets, not only in the field of SERS, but also in the much wider spectroscopy world. It is implemented in the Python programming language and is open-source at https://github.com/3331822w/Vis-CAD.

The Effects of a Magic Intervention Program on Cognitive Function and Neurocognitive Performance in Elderly Individuals With Mild Cognitive Impairment.

Objectives: Cognitive training is one of the management options for elderly individuals who suffer from mild cognitive impairment (MCI) and an effective way to improve executive function. This study aimed to evaluate the effectiveness of a magic intervention program as a method of cognitive training in improving cognitive function and neurocognitive performance in this group. Methods: Twenty-four participants aged 60-80 years with MCI were recruited and randomly assigned to a magic intervention group or a control group. The magic intervention group received a 6-week magic intervention program. The primary endpoints were the scores for the cognitive assessment tests [e.g., Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)] for general cognitive function. The secondary endpoints were the behavioral [e.g., accuracy and reaction times] and the electroencephalographic [e.g., event-related potential (ERP) P3 amplitudes] performance during the Flanker task to assess attention and inhibitory control. All variables were measured before and after the magic intervention. Results: The results showed that the 6-week magic intervention significantly improved the MoCA scores in the cognitive assessment tests although no significant pre-post intervention difference was observed in the MMSE scores. In terms of neurocognitive performance, the magic intervention had significantly positive effects on the accuracy, reaction times, and P3 amplitudes when performing the Flanker task. Conclusion: The results of the present study showed that the 6-week magic intervention had beneficial effects on the cognitive and electrophysiological performance in the elderly subjects with MCI. For such a group, lifestyle intervention programs that encourage participation such as the magic practice and performance may be a viable suggestion to prevent the progression of MCI to Alzheimer's disease.

Rapid qualitative and quantitative analysis of trace aconitum phytotoxin by SERS.

The dual functions of phytotoxin, such as aconitine, with biological activity and toxicity ignited the related food poisoning intentionally or accidentally from time to time. The fast and accurate qualitative analysis is a prerequisite for tracking the source of poisoning and taking correct treatments. Taking the single molecule level sensitivity and molecular fingerprinting of Surface-enhanced Raman spectroscopy (SERS), we developed a highly sensitive and accurate strategy for the trace detection of three structurally similar aconitines (ATs) (aconitine, mesaconitine and hypoaconitine) by employing the 100 nm Ag NPs colloid as the SERS substrate. It was figured out that the lowest detectable concentration is in the level of 5.0 µg/L for these three ATs with the linear range of 5.0-100.0 µg/L. The qualitative and quantitative analysis of trace ATs spiked in various food samples was realized in 3 mins, which demonstrated the SERS based strategy is very promising towards the fast and on-site detection of ATs in the field of food safety or criminal identification.

Qualitative analysis of trace quinolone antibiotics by SERS with fine structure dependent sensitivity.

Antibiotics are widely used in daily life, which has created a global scenario where many pathogenic organisms have become effectively resistant to antibiotics. The abuse or overuse of antibiotics causes significant environmental pollution and even endangers human health. It is well-known that antibiotics' efficacy (toxicity) is determined by molecular structure. Therefore, structure-level qualitative analysis with high sensitivity and accuracy is vitally important. Characterized by fingerprinting recognition, Raman spectroscopy, especially surface-enhanced Raman spectroscopy (SERS), has become an essential qualitative analysis tool in various fields, such as environmental monitoring and food safety. With the exception of chirality, this study completed the qualitative trace analysis of 16 quinolone antibiotics (QNs) with fine molecular structure differences using SERS. The sensitivity was tuned in by one order of magnitude through the different electronegativity and steric hindrances of the slightly changed functional groups in the specific antibiotics. The fine structure dependent sensitivity enables SERS to be a powerful on-site monitoring tool to control the abuse of antibiotics with high toxicity; thus, decreasing the subsequent risk to the environmental ecology and human society.

Microstructures of FeCoNiMo and CrFeCoNiMo Alloys, and the Corrosion Properties in 1 M Nitric Acid and 1 M Sodium Chloride Solutions.

FeCoNiMo and CrFeCoNiMo equimolar alloys were prepared by arc-melting. The microstructures of the as-cast alloys were examined by SEM, HREM and XRD; and a potentiodynamic polarization test of the as-cast alloys was undertaken to evaluate the corrosion resistance in the solutions. Results showed that both of FeCoNiMo and CrFeCoNiMo equimolar alloys had a dendritic structure. The dendrites of these two alloys were a single phase which was a simple cubic (SC) structure with large lattice constant; and the interdendrities of these two alloys had a dual-phased eutectic structure in which the phases were face-centered cubic (FCC) and simple cubic (SC). The hardness of CrFeCoNiMo alloy was higher than that of FeCoNiMo alloy. Additionally, the potentiodynamic polarization test showed that CrFeCoNiMo alloy was better than FeCoNiMo alloy in 1 M nitric acid and 1 M sodium chloride solutions. Adding chromium into FeCoNiMo alloy could increase corrosion resistance in these two solutions. All of the results indicated that the CrFeCoNiMo alloy surpassed FeCoNiMo alloy.

Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: To study the safety and patients' tolerance of transcranial magnetic stimulation (TMS), we conducted a systematic review and meta-analysis of the major depressive disorder population. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature published before April 30th, 2021 and performed a random-effects meta-analyses which included drop-out due to adverse events, serious adverse events and other non-serious adverse events as primary and secondary outcomes. RESULTS: A total of 53 randomized sham-controlled trials with 3,273 participants were included. There was no increased risk of drop-out due to an adverse event (active TMS intervention group=3.3%, sham TMS intervention group=2.3%, odds ratio = 1.30, 95% CI= 0.78-2.16, P = 0.31) or a serious adverse event (active TMS intervention group=0.9%, sham TMS intervention group=1.5%, odds ratio = 0.67, 95% CI= 0.29-1.55, P = 0.35). Our findings suggest that TMS intervention may significantly increase the risk of non-serious adverse events including: headaches (active TMS intervention group=22.6%, sham TMS intervention group=16.2%, odds ratio = 1.48, 95% CI= 1.15-1.91, P = 0.002), discomfort (active TMS intervention group=10.9%, sham TMS intervention group=5.0%, odds ratio 1.98, 95% CI= 1.22-3.21, P = 0.006) and pain (active TMS intervention group=23.8%, sham TMS intervention group=5.2%, odds ratio= 8.09, 95% CI= 4.71-13.90, P < 0.001) at the stimulation site, but these non-serious events were mostly mild and transient after TMS treatment. CONCLUSIONS: These findings provide evidence for the safety and patients' tolerance of transcranial magnetic stimulation technique as an alternative monotherapy or as an add-on treatment for major depressive disorder.

Sperm flagellar 2 (SPEF2) is essential for sperm flagellar assembly in humans.

Spermiogenesis is a complex and tightly regulated process, consisting of acrosomal biogenesis, condensation of chromatin, flagellar assembly, and disposal of extra cytoplasm. Previous studies have reported that sperm flagellar 2 (SPEF2) deficiency causes severe asthenoteratozoospermia owing to spermiogenesis failure, but the underlying molecular mechanism in humans remains unclear. Here, we performed proteomic analysis on spermatozoa from three SPEF2 mutant patients to study the functional role of SPEF2 during sperm tail development. A total of 1262 differentially expressed proteins were detected, including 486 upregulated and 776 downregulated. The constructed heat map of the differentially expressed proteins showed similar trends. Among these, the expression of proteins related to flagellar assembly, including SPEF2, sperm associated antigen 6 (SPAG6), dynein light chain tctex-type 1 (DYNLT1), radial spoke head component 1 (RSPH1), translocase of outer mitochondrial membrane 20 (TOM20), EF-hand domain containing 1 (EFHC1), meiosis-specific nuclear structural 1 (MNS1) and intraflagellar transport 20 (IFT20), was verified by western blot. Functional clustering analysis indicated that these differentially expressed proteins were specifically enriched for terms such as spermatid development and flagellar assembly. Furthermore, we showed that SPEF2 interacts with radial spoke head component 9 (RSPH9) and IFT20 in vitro, which are well-studied components of radial spokes or intra-flagellar transport and are essential for flagellar assembly. These results provide a rich resource for further investigation into the molecular mechanism underlying the role that SPEF2 plays in sperm tail development and could provide a theoretical basis for gene therapy in SPEF2 mutant patients in the future.

Risk of Personality disorders among childhood maltreatment victims: A nation-wide population-based study in Taiwan.

BACKGROUND: To date, numerous cohort studies and meta-analyses have shown that childhood maltreatment is associated with a wide range of adverse physiological and psychological symptoms. Although childhood maltreatment has been linked to an increased risk of personality disorders, the direction and magnitude of the association remain uncertain. Therefore, this cohort study aimed to evaluate whether children who have suffered childhood maltreatment have a higher incidence of subsequent personality disorders, using a nationwide database in Taiwan. METHODS: We conducted a large retrospective cohort study using data drawn from Taiwan's National Health Insurance Research Database between 2000 and 2015. A total of 10,345 children who experienced childhood maltreatment were identified using International Classification of Disease codes. They were then compared with 41,380 children who never experienced childhood maltreatment in terms of the prevalence rates of personality disorders. RESULTS: Childhood maltreatment was associated with an increased risk of personality disorders (considering the control as reference: adjusted hazard ratio, 2.12; 95% confidence interval, 1.90-2.36; p < 0.001). The Kaplan-Meier analysis revealed a significantly higher 15-year cumulative incidence of personality disorders among childhood maltreatment victims than among controls (log-rank test, p < 0.001). CONCLUSIONS: The present population-based study showed a positive association between prior childhood maltreatment and subsequent personality disorders in the general Taiwanese population. In order to reduce the risk of personality disorders, interventions should be implemented, identifying and supporting economically disadvantaged families and vulnerable children as early as possible.

Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow.

RATIONALE: Disturbed flow occurring in arterial branches and curvatures induces vascular endothelial cell (EC) dysfunction and atherosclerosis. We postulated that disturbed flow plays important role in modulating phosphoprotein expression profiles to regulate endothelial functions and atherogenesis. OBJECTIVE: The goal of this study is to discover novel site-specific phosphorylation alterations induced by disturbed flow in ECs to contribute to atherosclerosis. METHODS AND RESULTS: Quantitative phosphoproteomics analysis of ECs exposed to disturbed flow with low and oscillatory shear stress (0.5±4 dynes/cm2) versus pulsatile shear stress (12±4 dynes/cm2) revealed that oscillatory shear stress induces phospho-YY1S118 (serine [S]118 phosphorylation of Yin Yang 1) in ECs. Elevated phospho-YY1S118 level in ECs was further confirmed to be present in the disturbed flow regions in experimental animals and human atherosclerotic arteries. This disturbed flow-induced EC phospho-YY1S118 is mediated by CK2α (casein kinase 2α) through its direct interaction with YY1. Yeast 2-hybrid library screening and in situ proximity ligation assays demonstrate that phospho-YY1S118 directly binds ZKSCAN4 (zinc finger with KRAB [krüppel-associated box] and SCAN [SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA] domains 4) to induce promoter activity and gene expression of HDM2 (human double minute 2), which consequently induces EC proliferation through downregulation of p53 and p21CIP1. Administration of apoE-deficient (ApoE-/-) mice with CK2-specific inhibitor tetrabromocinnamic acid or atorvastatin inhibits atherosclerosis formation through downregulations of EC phospho-YY1S118 and HDM2. Generation of novel transgenic mice bearing EC-specific overexpression of S118-nonphosphorylatable mutant of YY1 in ApoE-/- mice confirms the critical role of phospho-YY1S118 in promoting atherosclerosis through EC HDM2. CONCLUSIONS: Our findings provide new insights into the mechanisms by which disturbed flow induces endothelial phospho-YY1S118 to promote atherosclerosis, thus indicating phospho-YY1S118 as a potential molecular target for atherosclerosis treatment.