N6-Methyladenine DNA Modification in the Human Genome.

DNA N6-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in the human genome, and we cataloged 881,240 6mA sites accounting for ∼0.051% of the total adenines. [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification. 6mA sites were enriched in the coding regions and mark actively transcribed genes in human cells. DNA 6mA and N6-demethyladenine modification in the human genome were mediated by methyltransferase N6AMT1 and demethylase ALKBH1, respectively. The abundance of 6mA was significantly lower in cancers, accompanied by decreased N6AMT1 and increased ALKBH1 levels, and downregulation of 6mA modification levels promoted tumorigenesis. Collectively, our results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis.

A pressure-induced superhard SiCN4 compound uncovered by first-principles calculations.

Silicon-carbon-nitride (Si-C-N) compounds are a family of potential superhard materials with many excellent chemical and physical properties; however, only SiCN, Si2CN4 and SiC2N4 were synthesized. Here, we theoretically report a new SiCN4 compound with P41212, Fdd2 and R3̄ structures by first-principles structural predictions based on the particle swarm optimization algorithm. Pressure-induced structural phase transitions from P41212 to Fdd2, and then to the R3̄ phase were determined at 2 GPa and 249 GPa. By comparing enthalpy differences with 1/3Si3N4 + C + 4/3N2, it was found that these structures tend to decompose at ambient pressure. However, with the increase of pressure, the enthalpy differences of Fdd2 and R3̄ structures turn to be negative and they can be stabilized at a pressure of more than 41 GPa. They are also dynamically stable as no imaginary frequencies were found in their stabilized pressure ranges. The calculated band gap is 4.37 eV for P41212, 3.72 eV for Fdd2 and 3.81 eV for the R3̄ phase by using the Heyd-Scuseria-Ernzerhof (HSE06) method and the estimated Vickers hardness values are higher than 40 GPa by adopting the elastic modulus based hardness formula, which confirmed their superhard characteristics. These results provide significant insights into Si-C-N systems and will inevitably promote the future experimental works.

A Wide-Band Magnetoelectric Sensor Based on a Negative-Feedback Compensated Readout Circuit.

Magnetoelectric (ME) sensors cannot effectively detect broadband magnetic field signals due to their narrow bandwidth, and existing readout circuits are unable to vary the bandwidth of the sensors. To expand the bandwidth, this paper introduces a negative-feedback readout circuit, fabricated by introducing a negative-feedback compensation circuit based on the direct readout circuit of the ME sensor. The negative-feedback compensation circuit contains a current amplifier, a feedback resistor, and a feedback coil. For this purpose, a Metglas/PVDF/Metglas ME sensor was prepared. Experimental measurements show that there is a six-fold difference between the maximum and minimum values of the ME voltage coefficients in the 6-39 kHz frequency band for the ME sensor without the negative-feedback compensation circuit when the sensor operates at the optimal bias magnetic field. However, the ME voltage coefficient in this band remains stable, at 900 V/T, after the charge amplification of the direct-reading circuit and the negative-feedback circuit. In addition, experimental results show that this negative-feedback readout circuit does not increase the equivalent magnetic noise of the sensor, with a noise level of 240 pT/√Hz in the frequency band lower than 25 kHz, 63 pT/√Hz around the resonance frequency of 30 kHz, and 620 pT/√Hz at 39 kHz. This paper proposes a negative-feedback readout circuit based on the direct readout circuit, which greatly increases the bandwidth of ME sensors and promotes the widespread application of ME sensors in the fields of broadband weak magnetic signal detection and DBS electrode positioning.

Testing the Associations Between Attachment Anxiety, Relational Aggression and Depressive Symptoms in Romantic Relationships: Actor-Partner Interdependence Model and Actor-Partner Interdependence Mediator Model.

Emerging adulthood is a pivotal period for romantic relationships, yet the specific mechanisms through which attachment anxiety influences relationship dynamics and psychological outcomes in this phase are poorly understood. Particularly, in the context of romantic dyads, understanding how partners' behaviors and emotional patterns reciprocally influence each other remains underexplored. This study utilizes the Actor-Partner Interdependence Model and Actor-Partner Interdependence Mediator Model to explore the relationship between attachment anxiety,relational aggression (both perpetration and victimization), and depressive symptoms among emerging adults. A sample of 138 mixed-sex emerging adulthood couples from China, was recruited (Mage = 21.40, SD = 2.54; 50% female, 62.6% reporting that this relationship was ongoing for more than a year). Attachment anxiety significantly predicted relational aggression in both partners, with male attachment anxiety also significantly predicted female relational aggression. Significant indirect effects of both partners' relational aggression perpetration and victimization on their own and each other's relationship between attachment anxiety and depressive symptoms. These findings contribute to understanding the intricate dynamics of attachment anxiety and relational aggression in romantic relationships during emerging adulthood, emphasizing the need for targeted interventions to mitigate these risks.

General Theory for Bilayer Stacking Ferroelectricity.

Two-dimensional (2D) ferroelectrics, which are rare in nature, enable high-density nonvolatile memory with low energy consumption. Here, we propose a theory of bilayer stacking ferroelectricity (BSF), in which two stacked layers of the same 2D material, with different rotation and translation, exhibit ferroelectricity. By performing systematic group theory analysis, we find all the possible BSF in all 80 layer groups (LGs) and discover the rules about the creation and annihilation of symmetries in the bilayer. Our general theory can not only explain all the previous findings (including sliding ferroelectricity), but also provide a new perspective. Interestingly, the direction of the electric polarization of the bilayer could be totally different from that of the single layer. In particular, the bilayer could become ferroelectric after properly stacking two centrosymmetric nonpolar monolayers. By means of first-principles simulations, we predict that the ferroelectricity and thus multiferroicity can be introduced to the prototypical 2D ferromagnetic centrosymmetric material CrI_{3} by stacking. Furthermore, we find that the out-of-plane electric polarization in bilayer CrI_{3} is interlocked with the in-plane electric polarization, suggesting that the out-of-plane polarization can be manipulated in a deterministic way through the application of an in-plane electric field. The present BSF theory lays a solid foundation for designing a large number of bilayer ferroelectrics and thus colorful platforms for fundamental studies and applications.

Longitudinal relationships among career adaptability, resilience, and career commitment in chinese nursing undergraduates: testing differences in career interest between cross-lagged models.

PURPOSE: Various physiological and psychological negative situations experienced by nurses as a result of COVID-19 pandemic have been shown to increase their perception of organizational difficulty and decrease their career commitment, thereby accelerating the turnover rate of nurses. Resilience and career adaptability have important influences on career commitment, so there is a need to evaluate the relationships between them and the underlying mechanisms. PATIENTS AND METHODS: Using a cross-lagged design, the Career Adaptability Scale, the Chinese version of career commitment, and Davidson's Resilience Scale as research methods, we studied 692 nursing students for two consecutive years to evaluate the relationship among career adaptability, resilience, and career commitment. RESULTS: Career adaptability at T1 substantially and positively predicts the career commitment at T2. Career adaptability and resilience are mutually predictive. No interaction is found between resilience and career commitment over time. There is a substantial difference in the cross-lagged relationship among career adaptability, resilience, and career commitment for low- and high-career interest. CONCLUSION: Our results show the importance of developing career commitment early on. Developing career adaptability, enhancing resilience, and increasing career interest in nursing students might help to increase career commitment.

A cross-lagged study of the associations among problematic smartphone use, depressive symptoms, and suicidal ideation in chinese university students.

The present study aimed to investigate the longitudinal and reciprocal relationships among problematic smartphone use (PSU), depressive symptoms (DS), and suicidal ideation (SI) in Chinese university students. Using a cross-lagged design, the Mobile Phone Addiction Inventory Scale, the Center for Epidemiologic Studies Depression Scale, and the Self-Rating Idea of Suicide Scale as research instruments, 194 university students completed a questionnaire four consecutive times. June of Year 1, December of Year 2, June of Year 2, and December of Year 3 of their college study. We refer to these as the Time 1 (T1), Time 2 (T2), Time 3 (T3), and Time 4 (T4) assessments, respectively. The levels of PSU and DS fluctuated significantly over time. DS at T1 was significantly predicted to influence SI at T2 (ß = 0.17, p < .05); DS at T3 was significantly predicted by PSU and by SI at T2 (respectively, ß = 0.30, p < .05; ß = 0.21, p < .05); DS at T2 significantly predicted PSU at T3 (ß = 0.14, p < .05); and DS at T3 significantly predicted SI at T4 (ß = 0.14, p < .05) in the cross-lagged pathway. DS at T3 fully mediated the relationship between PSU at T2 and SI at T4 (indirect effect: ß = 0.133, 95% CI = [0.063, 0.213]). The results suggest that there is a reciprocal relationship between PSU and DS and, furthermore, that DS plays an important mediating role between PSU and SI. Our results suggest the importance of early identification and treatment of SI. Timely reduction of PSU and improvement of DS among university students may help prevent SI.

Dynamic Change of Endocannabinoid Signaling in the Medial Prefrontal Cortex Controls the Development of Depression After Neuropathic Pain.

Many patients with chronic pain conditions suffer from depression. The mechanisms underlying pain-induced depression are still unclear. There are critical links of medial prefrontal cortex (mPFC) synaptic function to depression, with signaling through the endocannabinoid (eCB) system as an important contributor. We hypothesized that afferent noxious inputs after injury compromise activity-dependent eCB signaling in the mPFC, resulting in depression. Depression-like behaviors were tested in male and female rats with traumatic neuropathy [spared nerve injury (SNI)], and neuronal activity in the mPFC was monitored using the immediate early gene c-fos and in vivo electrophysiological recordings. mPFC eCB Concentrations were determined using mass spectrometry, and behavioral and electrophysiological experiments were used to evaluate the role of alterations in eCB signaling in depression after pain. SNI-induced pain induced the development of depression phenotypes in both male and female rats. Pyramidal neurons in mPFC showed increased excitability followed by reduced excitability in the onset and prolonged phases of pain, respectively. Concentrations of the eCBs, 2-arachidonoylglycerol (2-AG) in the mPFC, were elevated initially after SNI, and our results indicate that this resulted in a loss of CB1R function on GABAergic interneurons in the mPFC. These data suggest that excessive release of 2-AG as a result of noxious stimuli triggers use-dependent loss of function of eCB signaling leading to excessive GABA release in the mPFC, with the final result being behavioral depression.SIGNIFICANCE STATEMENT Pain has both somatosensory and affective components, so the complexity of mechanisms underlying chronic pain is best represented by a biopsychosocial model that includes widespread CNS dysfunction. Many patients with chronic pain conditions develop depression. The mechanism by which pain causes depression is unclear. Although manipulation of the eCB signaling system as an avenue for providing analgesia per se has not shown much promise in previous studies. An important limitation of past research has been inadequate consideration of the dynamic nature of the connection between pain and depression as they develop. Here, we show that activity-dependent synthesis of eCBs during the initial onset of persistent pain is the critical link leading to depression when pain is persistent.

The mechanisms underlying the negative effect of depression on life satisfaction among the elderly: the roles of ostracism and economic income.

OBJECTIVES: Depression is prevalent among older persons, which seriously threatens their life satisfaction. This study aimed to explore the internal mechanisms by which depression influences life satisfaction among the elderly, as well as the mediating and moderating effects of ostracism and economic income, respectively, in a sample of rural older adults across China. DESIGN: This was a cross-sectional survey conducted as part of the project "Thousands of People and Hundreds of Villages (2019)." SETTING: Participants were rural older adults from 31 provincial-level administrative units across China. PARTICIPANTS: The sample composed of 1,754 participants aged 60 years and over. MEASUREMENTS: Depression was assessed with the depression subscale of the Depression Anxiety Stress Scales, life satisfaction with the Satisfaction with Life Scale, ostracism with the Ostracism Experience Scale (OES), and economic income and other control variables with related demographic scales. Moderation and mediation analyses were performed using the regression-based approach as conducted by Hayes (). RESULTS: Depression negatively predicted life satisfaction among the elderly. Ostracism played a partially mediating role between depression and life satisfaction. Economic income moderated the effect of depression and ostracism on life satisfaction: High economic income weakened the negative effect of depression on life satisfaction and enhanced the negative effect of ostracism on life satisfaction. CONCLUSION: Improving depressed elderly people's interpersonal relationships and financial support could improve their life satisfaction.

Analgesic Effects of Tonic and Burst Dorsal Root Ganglion Stimulation in Rats With Painful Tibial Nerve Injury.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is effective in treating chronic pain. While burst stimulation has been proven to enhance the therapeutic efficacy in spinal cord stimulation, currently only a tonic stimulation waveform is clinically used in DRG stimulation. We hypothesized that burst DRG stimulation might also produce analgesic effect in a preclinical neuropathic pain model. We evaluated both the therapeutic effects of burst DRG stimulation and the possible effects of DRG stimulation upon inflammation within the DRG in a preclinical neuropathic pain model. MATERIALS AND METHODS: Rats received either a painful tibial nerve injury or sham surgery. Analgesic effects of DRG stimulation were evaluated by testing a battery of evoked pain-related behaviors as well as measuring the positive affective state associated with relief of spontaneous pain using conditioned place preference. Histological evidence for neuronal trauma or neuroinflammation was evaluated. RESULTS: All of the waveforms tested (20 Hz-tonic, 20 Hz-burst, and 40 Hz-burst) have similar analgesic effects in sensory tests and conditioned place preference. Long-term DRG stimulation for two weeks does not change DRG expression of markers for nerve injury and neuroinflammation. CONCLUSIONS: DRG stimulation using burst waveform might be also suitable for treating neuropathic pain.

Electron deficiency but semiconductive diamond-like B2CN originated from three-center bonds.

B2CN was one of the synthesized light element compounds, which was expected to be superhard material with a metallic character due to its electron deficienct nature. However, in this work, we discovered two novel semiconducting superhard B2CN phases using particle swarm intelligence technique and first-principles calculations, which were reported to have three-dimensional and four coordinated covalent diamond-like structures. These two new phases were calculated to be dynamically stable at zero and high pressures, and can be deduced from the previously reported Pmma phase by pressure-induced structural phase transitions. More importantly, unlike the previously proposed metallic B2CN structures, these two new phases combine superhard (the calculated Vickers hardness reached ∼55 GPa) and semiconducting character. The semiconducting behavior of the newly predicted B2CN phases breaks the traditional view of the metallic character of the electron deficient diamond-like B-C-N ternary compounds. By a detail analyzation of the electron localization functions of these two new phases, three-center bonds were reported between some B, C and B atoms, which were suggested to be the primary mechanism that helps the compound overcome its electron-deficient nature and finally exhibit a semiconducting behavior.

Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis.

BACKGROUND: Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models. METHODS: The authors provided ganglion stimulation or spinal cord stimulation to rats with traumatic neuropathy (tibial nerve injury), or osteoarthritis induced by intraarticular knee monosodium iodoacetate, or without injury (naïve). Analgesia was evaluated by testing a battery of pain-related reflexive, functional, and affective behaviors. RESULTS: In rats with nerve injury, multilevel L4 and L5 ganglion stimulation decreased hypersensitivity to noxious mechanical stimulation more (area under curve, -1,447 ± 423 min × % response; n = 12) than single level ganglion stimulation at L4 ([-960 ± 251 min × % response; n = 8; P = 0.012] vs. L4 and L5), and L5 ([-676 ± 295 min × % response; n = 8; P < 0.0001] vs. L4 and L5). Spontaneous pain-like behavior, evaluated by conditioned place preference, responded to single L4 (Pretest [-93 ± 65 s] vs. Test [87 ± 82 s]; P = 0.002; n = 9), L5 (Pretest [-57 ± 36 s] vs. Test [137 ± 73 s]; P = 0.001; n = 8), and multilevel L4 and L5 (Pretest: -81 ± 68 s vs. Test: 90 ± 76 s; P = 0.003; n = 8) ganglion stimulation. In rats with osteoarthritis, multilevel L3 and L4 ganglion stimulation reduced sensitivity to knee motion more (-156 ± 28 min × points; n = 8) than L3 ([-94 ± 19 min × points in knee bend test; n = 7; P = 0.002] vs. L3 and L4) or L4 ([-71 ± 22 min × points; n = 7; P < 0.0001] vs. L3 and L4). Conditioned place preference during osteoarthritis revealed analgesic effectiveness for ganglion stimulation when delivered at L3 (Pretest [-78 ± 77 s] vs. Test [68 ± 136 s]; P = 0.048; n = 9), L4 (Pretest [-96 ± 51 s] vs. Test [73 ± 111 s]; P = 0.004; n = 9), and L3 and L4 (Pretest [-69 ± 52 s; n = 7] vs. Test [55 ± 140 s]; P = 0.022; n = 7). CONCLUSIONS: Dorsal root ganglion stimulation is effective in neuropathic and osteoarthritic preclinical rat pain models with peripheral pathologic origins, demonstrating effectiveness of ganglion stimulation in a placebo-free setting and justifying this model as a suitable platform for mechanistic studies.

Rapid prenatal diagnosis of Facioscapulohumeral Muscular Dystrophy 1 by combined Bionano optical mapping and karyomapping.

PURPOSE: To explore the feasibility of performing rapid prenatal diagnoses of FSHD1 using a combination of Bianano optical mapping and linkage-based karyomapping. METHODS: DNA specimens from a family that had been previously diagnosed with FSHD1 using Southern Blot analysis were used for this study. Genetic diagnosis of the proband, fetus chorionic amniotic fluid, and aborted fetal tissue was performed using Bianano optical mapping (BOM) together with linkage-based karyomapping. RESULTS: BOM analysis showed that the proband's 4q35.2 region contained four D4Z4 repeats and the 4qA permissible allele, consistent with the previous FSHD1 diagnosis obtained by Southern Blotting. BOM analysis of the fetus' 4q35.2 region was consistent with that of the proband. Karyomap analysis revealed that the fetus inherited the affected chromosome segment from the proband. After genetic counseling, the couple choose termination of pregnancy, and we performed gene diagnosis of the abortus tissue by BOM. CONCLUSIONS: Bianano optical mapping can determine the number of D4Z4 repeats and exclude interference of the 10q26.3 homologous region, and in combination with karyomapping, can be used for rapid and accurate prenatal diagnosis of FSHD1.

Long-read sequencing and haplotype linkage analysis enabled preimplantation genetic testing for patients carrying pathogenic inversions.

BACKGROUND: Preimplantation genetic testing (PGT) has already been applied in patients known to carry chromosomal structural variants to improve the clinical outcome of assisted reproduction. However, conventional molecular techniques are not capable of reliably distinguishing embryos that carry balanced inversion from those with a normal karyotype. We aim to evaluate the use of long-read sequencing in combination with haplotype linkage analysis to address this challenge. METHODS: Long-read sequencing on Oxford Nanopore platform was employed to identify the precise positions of inversion break points in four patients. Comprehensive chromosomal screening and genome-wide haplotype linkage analysis were performed based on SNP microarray. The haplotypes, including the break point regions, the whole chromosomes involved in the inversion and the corresponding homologous chromosomes, were established using informative SNPs. RESULTS: All the inversion break points were successfully identified by long-read sequencing and validated by Sanger sequencing, and on average only 13 bp differences were observed between break points inferred by long-read sequencing and Sanger sequencing. Eighteen blastocysts were biopsied and tested, in which 10 were aneuploid or unbalanced and eight were diploid with normal or balanced inversion karyotypes. Diploid embryos were transferred back to patients, the predictive results of the current methodology were consistent with fetal karyotypes of amniotic fluid or cord blood. CONCLUSIONS: Nanopore long-read sequencing is a powerful method to assay chromosomal inversions and identify exact break points. Identification of inversion break points combined with haplotype linkage analysis is an efficient strategy to distinguish embryos with normal or balanced inversion karyotypes, facilitating PGT applications.

Molecularly imprinted mesoporous silica incorporating C3N4 dots and CdTe quantum dots as ratiometric fluorescent probe for determination of Malachite Green.

A new dual-emission ratiometric fluorescent probe was synthesized and successfully used for the determination of Malachite Green (MG) in fish farming water. The ratiometric fluorescent probe was successfully composited by sol-gel method using C3N4 and CdTe quantum dots as fluorescent materials combined with mesoporous molecularly imprinted polymers. MG quenches the red fluorescence of the CdTe QDs (with excitation/emission wavelengths at 350/680 nm) while the blue fluorescence of C3N4 (with excitation/emission wavelengths at 350/458 nm) remains unchanged. The change of fluorescence color and fluorescence intensity ratio can be successfully used for quantification of malachite green. In addition, the mesoporous structure has a large surface and good adsorption capacity for malachite green. The normalized intensity of fluorescence increases linearly in the 50-1000 ng·mL-1 MG concentration range, and the detection limit is 10 ng·mL-1. The imprinting factor is 3.2. The nanoprobe was applied to the determination of MG in fish farming water samples. Recoveries and relative standard deviations were 92.5-97.8% and 2.5-6.2%, respectively. Graphical abstract Schematic representation of synthesis of molecularly imprinted mesoporous silica ratiometric fluorescent probes incorporating C3N4 dots and CdTe quantum dots for determination of malachite green.

Inhibition of Myeloperoxidase by N-Acetyl Lysyltyrosylcysteine Amide Reduces Oxidative Stress-Mediated Inflammation, Neuronal Damage, and Neural Stem Cell Injury in a Murine Model of Stroke.

Recent studies suggest that myeloperoxidase (MPO)-dependent oxidative stress plays a significant role in brain injury in stroke patients. We previously showed that N-acetyl lysyltyrosylcysteine amide (KYC), a novel MPO inhibitor, significantly decreased infarct size, blood-brain barrier leakage, infiltration of myeloid cells, loss of neurons, and apoptosis in the brains of middle cerebral artery occlusion (MCAO) mice. Inhibition of MPO also noticeably reduced neurologic severity scores of MCAO mice. Thus, our data support the idea that MPO-dependent oxidative stress plays a detrimental role in tissue injury in ischemic stroke. However, the mechanisms of MPO-induced injury in stroke are still largely unknown. Here, we present new evidence showing that KYC treatment greatly reduced inflammation by decreasing the number of proinflammatory M1 microglial cells and N1 neutrophils in the brains of MCAO mice. KYC also markedly reduced the expression of high-mobility group box 1, receptor for advanced glycation end products, and nuclear factor-κB in the brains of MCAO mice. Both neurons and neural stem cells (NSCs) were oxidatively injured by MPO-dependent oxidative stress in MCAO mice. Inhibiting MPO-dependent oxidative stress with KYC significantly reduced oxidative injury and apoptosis in neurons and NSCs. KYC treatment also protected transplanted exogenous NSCs in the brains of MCAO mice. Thus, our studies suggest that MPO-dependent oxidative stress directly injures brain tissues by oxidizing neurons and NSCs and increasing inflammation during stroke. Inhibition of MPO activity with KYC preserves neuronal function and helps the brain recover from injury after stroke.

Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke.

BACKGROUND: Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. METHODS: To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. RESULTS: Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. CONCLUSIONS: MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.

Childhood environmental risk and youth bedtime procrastination: A path model with life history strategy and sense of control as mediators.

BACKGROUND: Bedtime procrastination is a serious threat to youths' sleep quality and physical and mental health. It is affected by various psychological and physiological factors, but few studies focused on the impact and internal mechanism of childhood experience on bedtime procrastination in adulthood from the evolutionary and developmental perspective. OBJECTIVE: This study aims to explore the distal factors of bedtime procrastination among young people, that is, the association between childhood environmental risk (harshness and unpredictability) and bedtime procrastination, as well as the mediating roles of life history (LH) strategy and sense of control. PARTICIPANTS AND SETTING: By convenience sampling, 453 Chinese college students aged 16 to 24 (55.2 % males, Mage = 21.21 years) completed questionnaires regarding demographics, childhood environmental harshness (from neighborhood, school, and family), and unpredictability (parental divorce, household moves, and parental employment changes), LH strategy, sense of control, and bedtime procrastination. METHODS: Structural equation modeling was used to test the hypothesis model. RESULTS: The results showed that childhood environmental harshness and unpredictability were both positively associated with bedtime procrastination. Sense of control had a partial mediating role between harshness and bedtime procrastination (B = 0.02, 95%CI = [0.004, 0.042]), and between unpredictability and bedtime procrastination (B = 0.01, 95%CI = [0.002, 0.031]), respectively. LH strategy and sense of control had a serial mediating role between harshness and bedtime procrastination (B = 0.04, 95%CI = [0.010, 0.074]), and between unpredictability and bedtime procrastination (B = 0.01, 95%CI = [0.003, 0.029]), respectively. CONCLUSIONS: The findings suggest that childhood environmental harshness and unpredictability are potential predictors of youths' bedtime procrastination. Young people can reduce bedtime procrastination problems by slowing LH strategies and improving their sense of control.

The Long-Term Effect of Early-Life Uncertainty on Mental Health in Adolescence and Adulthood: A Meta-Analysis.

Turbulent changes in early life are a hidden source of childhood trauma, increasing potential risks for mental illness. Many studies have identified the link between childhood uncertainty and mental health. However, research on the long-term effect of early-life uncertainty (EU) on mental health has not been systematically synthesized. This meta-analysis aims to provide a quantitative estimate of the association between EU and subsequent mental health outcomes. Eight electronic databases and gray literature were searched. Twenty-eight studies met our inclusion criteria: samples of non-clinical adolescents or adults and clear and valid assessments. Random-effect models were used to calculate the pooled effect sizes of EU on internalizing problems, externalizing problems, and well-being. Meta-regression and subgroup analysis were used to explore potential moderators. Results indicated small to moderate associations involving EU and internalizing problem (r = .28; 95% confidence interval [CI] [0.228, 0.326]) and externalizing problem (r = .16; 95% CI [0.102, 0.220]). EU was not significantly associated with well-being (r = -.41; 95% CI [-0.738, 0.071]). Furthermore, moderator analyses found that composite uncertain experiences in childhood had a stronger negative effect than single experiences. EU was a stronger predictor of mental health problems in adults than in adolescents. Cross-sectional studies would amplify the correlation between EU and mental illness compared to longitudinal studies. In the future, childhood uncertain and unpredictable risks should receive more attention. More research needs to focus on positive psychological indicators and samples from non-Western countries.

Fractional quantum ferroelectricity.

For an ordinary ferroelectric, the magnitude of the spontaneous electric polarization is at least one order of magnitude smaller than that resulting from the ionic displacement of the lattice vectors, and the direction of the spontaneous electric polarization is determined by the point group of the ferroelectric. Here, we introduce a new class of ferroelectricity termed Fractional Quantum Ferroelectricity. Unlike ordinary ferroelectrics, the polarization of Fractional Quantum Ferroelectricity arises from substantial atomic displacements that are comparable to lattice constants. Applying group theory analysis, we identify 28 potential point groups that can realize Fractional Quantum Ferroelectricity, including both polar and non-polar groups. The direction of polarization in Fractional Quantum Ferroelectricity is found to always contradict with the symmetry of the "polar" phase, which violates Neumann's principle, challenging conventional symmetry-based knowledge. Through the Fractional Quantum Ferroelectricity theory and density functional calculations, we not only explain the puzzling experimentally observed in-plane polarization of monolayer α-In2Se3, but also predict polarization in a cubic compound of AgBr. Our findings unveil a new realm of ferroelectric behavior, expanding the understanding and application of these materials beyond the limits of traditional ferroelectrics.