Impacts of difficulties with emotion regulation on the longitudinal relationship between peer victimization and changes in adolescent nonsuicidal self-injury.

INTRODUCTION: Research has found that peer victimization is associated with adolescent nonsuicidal self-injury (NSSI) behavior; however, most of these studies ignored the association between these constructs at the within-person level. Additionally, the association between peer victimization and NSSI may vary among adolescents with different personal characteristics. With a longitudinal design, this study investigated whether and how emotion regulation (ER) difficulties moderate the relationship between peer victimization and changes in NSSI, with particular attention given to the unique moderating role of different dimensions of ER difficulties. METHODS: The study sample comprised 3,561 adolescents aged between 10 and 17 years old (Mage = 13.22, SD = 0.85; 56.9% males). Self-report assessments were administered in December 2021 and June 2022 in Shanxi province, China. RESULTS: The latent change score model showed that the adolescent NSSI increased during our assessments, with peer victimization as a significant predictor. ER difficulties moderated the association between peer victimization and NSSI changes, but interestingly, in an unexpected pattern. Specifically, peer victimization significantly predicted NSSI changes among adolescents with low ER difficulties but not for those with high ER difficulties. Moreover, among the multiple dimensions of ER difficulties, only nonacceptance of emotional responses and limited access to emotion regulation strategies interacted with peer victimization to predict NSSI changes and showed interaction patterns similar to those at the overall level of ER difficulties. CONCLUSIONS: The current study revealed the moderating role of ER difficulties in the relationship between peer victimization and changes in NSSI. These findings provide intervention implications for adolescents who engage in NSSI.

Outbreak of Septoria leaf spot caused by Sphaerulina musiva on Populus × euramericana in China.

In June 2023, severe leaf spots were noted in Populus × euramericana cv 'Nanlin95' plantations located in the Nanjing Baguazhou Wetland Park (32°09'16.97″N, 118°48'16.74″E) of Jiangsu Province and Populus × canadensis cv 'Sacrau 79' and Populus × canadensis cv 'Guariento' in the Liyuan Village in Nanyang City (32°53'43.70″N, 112°17'29.12″E) of Henan Province, respectively. The disease incidence in both locations could reach 97.9% (556 out of 568 trees) and 98.9% (2409 out of 2436 trees), respectively. The initial symptoms appear as numerous small and circular spots (1.59 to 3.18 mm in diameter) with gray or tan centers and dark-brown margins on the leaves. As the spots age, they sometimes enlarge, often coalesce, and may extend down the petioles. Diseased leaves and petioles were both surface sterilized with 75% ethanol for 30 seconds. With the aid of a hand lens, pycnidia (brown to black, spherical in profile, 90 to 250 µm diam) were easily picked out in the center of the spots and subsequently transferred into 1 mL sterilized water for preparing the spore suspension plated on KV8 medium amended with 100 mg/liter streptomycin sulfate and 50 mg/liter chloramphenicol. After 12 days of incubation, 86 single-spore isolates were obtained and identified as typical Septoria-like fungi according to morphological features, including slow-growing, gray or black colonies with pink mucilaginous matrix and hyaline, straight or curved conidia (size = 25 to 59 × 3.5 to 4 µm; septa = 1 to 6). Species identification was further validated by PCR amplification and sequencing of the internal transcribed spacer (ITS) region with ITS1/ITS4 primer pairs. Multiple sequence alignments with ClustalW revealed that the obtained ITS sequences of 86 isolates were 100% identical to each other. A BLAST search in GenBank indicated that the selfsame sequences of two representative isolates (isolate BGZ11 of Jiangsu Province, accession no. OR660379; isolate KZB22 of Henan Province, accession no. OR711499) shared 99.8% identity (494 of 495 bp) and 100% identity (504 of 504 bp) with related sequences of Sphaerulina musiva (Peck) Quaedvlieg, Verkley, and Crous (syn. = Septoria musiva Peck) in GenBank (MN275187; KF251619), respectively. Furthermore, we used a S. musiva-specific PCR assay (Abraham et al. 2018) on symptomatic leaf samples collected from the plantation. Each sample consisted of 20 cut-out leaf spots per leaf. Eight of the 10 samples were positive for S. musiva DNA. To confirm pathogenicity, six sterile tissue culture of poplar plants (Populus trichocarpa and Populus × euramericana cv 'Nanlin895') were respectively transplanted into pots and grown in a greenhouse for a week and for a month with an 18-h photoperiod augmented with sodium lamps and a 20°C (day)/16°C (night) temperature regime. Inoculations were conducted by spraying the plants with conidia suspension (106 conidia/mL) (LeBoldus et al. 2010). Control plants were sprayed with distilled water. Leaf spots were developed on the inoculated P. trichocarpa leaves at one week and P. × euramericana cv 'Nanlin895' leaves at 10 days after inoculation while no symptoms were observed on the control plants. The fungus S. musiva was successfully reisolated from all symptomatic leaves fulfilling Koch's postulates. Sphaerulina musiva only causes an endemic leaf spot disease on its natural North American host Populus. deltoides (Feau et al. 2010; Ostry 1987). However, on susceptible Populus species (e.g., P. balsamifera, P. trichocarpa, P. maximowiczii) and hybrids, S. musiva causes not only leaf spots but also severely damaging stem and branch cankers (Jeger et al. 2018; LeBoldus et al. 2009; Sondreli et al. 2020). To our knowledge, this is the first report of S. musiva causing leaf spots on poplar in China. Large-scale timber imports (e.g., cut branches, isolated bark, wood with and without bark) potentially lead to anthropogenic-facilitated transport of this pathogen. This outbreak of Septoria leaf spot underscores the potential threat of this pathogen to P. × euramericana in China, where it is widely planted as a keystone forestry species.

Differential Response of MYB Transcription Factor Gene Transcripts to Circadian Rhythm in Tea Plants (Camellia sinensis).

The circadian clock refers to the formation of a certain rule in the long-term evolution of an organism, which is an invisible 'clock' in the body of an organism. As one of the largest TF families in higher plants, the MYB transcription factor is involved in plant growth and development. MYB is also inextricably correlated with the circadian rhythm. In this study, the transcriptome data of the tea plant 'Baiyeyihao' were measured at a photoperiod interval of 4 h (24 h). A total of 25,306 unigenes were obtained, including 14,615 unigenes that were annotated across 20 functional categories within the GO classification. Additionally, 10,443 single-gene clusters were annotated to 11 sublevels of metabolic pathways using KEGG. Based on the results of gene annotation and differential gene transcript analysis, 22 genes encoding MYB transcription factors were identified. The G10 group in the phylogenetic tree had 13 members, of which 5 were related to the circadian rhythm, accounting for 39%. The G1, G2, G8, G9, G15, G16, G18, G19, G20, G21 and G23 groups had no members associated with the circadian rhythm. Among the 22 differentially expressed MYB transcription factors, 3 members of LHY, RVE1 and RVE8 were core circadian rhythm genes belonging to the G10, G12 and G10 groups, respectively. Real-time fluorescence quantitative PCR was used to detect and validate the expression of the gene transcripts encoding MYB transcription factors associated with the circadian rhythm.

Significant Promotion of Light Absorption Ability and Formation of Triplet Organics and Reactive Oxygen Species in Atmospheric HULIS by Fe(III) Ions.

Metal ions are key components in atmosphere that potentially affect the optical properties and photochemical reactivity of atmospheric humic-like substances (HULIS), while this mechanism is still unclear. In this study, we demonstrated that atmospheric HULIS coupled with Fe3+, Cu2+, Zn2+, and Al3+ exhibited distinct optical properties and reactive intermediates from that of HULIS utilizing three-dimensional fluorescence spectroscopy and electron paramagnetic resonance spectroscopy. The HULIS components showed light absorption that increased by 56% for the HULIS-Fe3+ system, fluorescence blue shift, and fluorescence quenching, showing a certain dose-effect relationship. These are mainly attributed to the fact that the highly oxidative HULIS chromophores have a stronger complexing ability with Fe3+ ions than the other metal ions. In addition, triplet organics (promoting ratio: 53%) and reactive oxygen species (promoting ratio: 82.6%) in the HULIS-Fe3+ system showed obvious generation promotion. Therefore, the main assumption of the photochemical mechanisms of atmospheric HULIS in the HULIS-Fe3+ system is that Fe3+ ions can form 3HULIS*-Fe3+ complexation with photoexcited 3HULIS* and then transition to the ground state through energy transfer, electron transfer, or nonradiative transition, accompanied by the formation of singlet oxygen and hydroxyl radicals. Our results provide references for evaluating the radiative forcing and aging effect of metal ions on atmospheric aerosols.

Structural characterisation of a full-length mitochondrial outer membrane TOM40 preprotein translocase: implications for its interaction with presequence peptides.

Tom40, the central component of the preprotein translocase of the mitochondrial outer membrane (TOM complex), forms the import pore that facilitates the translocation of preproteins across the outer membrane. Though the function of Tom40 has been intensively studied, the details of the interactions between presequence peptides and Tom40 remain unclear. In this study, we expressed rat Tom40 in Escherichia coli and purified it from inclusion bodies before investigating the refolded protein by fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The far-UV CD spectra of the refolded Tom40 in various concentrations of urea revealed that the refolded protein has a well-defined structure consisting mainly of ß-sheet. Moreover, the specific binding of presequence peptides to Tom40, which was demonstrated by fluorescence quenching, showed that the refolded purified protein is functional and that the interaction between Tom40 and presequence peptides is mainly electrostatic in nature.

In-hospital Medical Costs of Infections Caused by Carbapenem-resistant Klebsiella pneumoniae.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major health threat, but the economic impact of carbapenem resistance in K. pneumoniae infections remains largely uninvestigated. Methods: We constructed a retrospective cohort of all patients hospitalized at West China Hospital in 2017 who had CRKP- or carbapenem-susceptible K. pneumoniae (CSKP)-positive clinical samples. Propensity score matching (PSM) was used to control the impact of potential confounding variables, including demographics, comorbidities, and treatment, and to observe the impact of factors other than length of stay (LOS). Patients who survived were subjected to subgroup analyses stratified by infection type. Results: There were 267 patients with CRKP and 1328 with CSKP. Patients with CRKP had a higher crude in-hospital mortality rate (14.61% vs 5.65%, P < .05) and longer LOS (median, 31 vs 19 days; P < .05). PSM for demographics, comorbidities, and treatment generated 237 pairs. Patients with CRKP had higher medical costs than those with CSKP during the entire hospitalization (median, in US dollars, $22962 vs $11755, respectively; P < .05) and during the period after infection (median, $9215 vs $6904, respectively; P < .05). When LOS was matched, patients with CRKP still had high excess costs compared to those with CSKP (median, $22917 vs $13851, respectively, for the entire hospitalization, P < .05; $9101 vs $7001, respectively, after infection, P < .05). For infection type, the sample size generated sufficient power to compare only the patients with pneumonia. For surviving patients, high excess costs were observed in those with pneumonia caused by CRKP as compared to CSKP ($21890 vs $11698, respectively, for the entire hospitalization, P < .05; $9773 vs $5298, respectively, after infection, P < .05). Medicines other than antibacterial agents and nonmedicinal therapies contributed most (57.8%) of the excess costs associated with CRKP. Conclusions: Carbapenem resistance in K. pneumoniae was associated with increased medical costs not accounted for by the cost of antimicrobial therapy.

Poly(2-ethyl-2-oxazoline)-doxorubicin conjugate-based dual endosomal pH-sensitive micelles with enhanced antitumor efficacy.

Dual endosomal pH-sensitive micelles were designed and fabricated to deliver doxorubicin (DOX) for treating breast cancer based on a poly(2-ethyl-2-oxazoline) (PEOz)-DOX (PEOz-hyd-DOX) conjugate. PEOz-hyd-DOX was successfully synthesized by connecting DOX to PEOz via an acid cleavable hydrazone linker and self-assembled into nanosized micelles, which further physically encapsulated DOX. The conjugate and DOX-loaded conjugate micelles displayed faster release of DOX at pH 5.0 than at pH 7.4. This pH-dependent release behavior might assist the quick diffusion of DOX from acidic endosomes or lysosomes and the intracellular transfer into the nucleus after internalization, which was confirmed by confocal laser scanning microscopy images. As expected, PEOz-hyd-DOX conjugate and DOX-loaded conjugate micelles maintained cytotoxicity of DOX. In addition, the dual endosomal pH-sensitive micelles were found to substantially enhance antitumor efficacy and reduce side effects compared with free DOX. Therefore, PEOz-hyd-DOX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.

Endosomal pH-Responsive Polymer-Based Dual-Ligand-Modified Micellar Nanoparticles for Tumor Targeted Delivery and Facilitated Intracellular Release of Paclitaxel.

PURPOSE: The purpose of the present study was to design and fabricate endosomal pH-sensitive dual-ligand-modified micellar nanoparticles to achieve enhanced drug delivery to tumor cells and facilitated intracellular drug release. METHODS: End-group-carboxylated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) and cyclic Arg-Gly-Asp-Tyr-Lys- and anti-prostate specific membrane antigen antibody-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) were synthesized and characterized by (1)H NMR and gel permeation chromatography, and self-assembled into micelles. Paclitaxel-loaded dual-ligand-modified micelles were prepared by thin-film hydration method, and characterized by dynamic light scattering, transmission electron microscope, pH-dependent in vitro release and stability. Intracellular paclitaxel delivery was measured by flow cytometry and imaged by confocal microscopy. In vitro cytotoxicity was studied in the 22Rv1 xenograft prostate tumor cell lines. RESULTS: The prepared dual-ligand-modified micelles with about 30 nm in diameter and rapid intracellular drug release behavior at endo/lysosomal pH were very effective in enhancing the cytotoxicity of paclitaxel against 22Rv1 cells by increasing the cellular uptake, which was verified the correlation with the expression of integrin αvß3 and prostate specific membrane antigen in tumor cells by flow cytometric analysis and confocal microscopy, compared with single ligand-modified micelles. CONCLUSION: These findings provided valuable information that the application of combining of dual-ligand modifications with pH-sensitivity to polymeric micelles may be a promising approach in the efficient delivery of anticancer drugs for treatment of integrin αvß3 and prostate specific membrane antigen expressing prostate cancers.

Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity.

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

Bounded rationality in healthcare: unraveling the psychological factors behind patient satisfaction in China.

Introduction: Patient satisfaction is a crucial metric to gauge the quality of medical services, but the psychological factors influencing patient satisfaction remain insufficiently explored. Methods: This study examines these psychological factors by applying the theory of bounded rationality to 1,442 inpatients in Hangzhou, China, whose data were collected using a questionnaire. One-way ANOVA, correlation analysis, and hierarchical regression were used to analyze patient satisfaction and its associated factors. Additionally, the path analysis of the structural equation model revealed the mechanisms behind the key psychological factors that influenced patient satisfaction. Results: Medical risk perception, the social cognition of the medical environment, and social desirability bias had significant positive impacts on patient satisfaction. By contrast, negative emotions had a significant negative impact on patient satisfaction. Notably, patients' negative emotions had both a suppressive effect and a positive moderating effect on the relationship between medical risk perception and patient satisfaction. Similarly, social desirability bias had a suppressive effect on the correlation between the social cognition of the medical environment and patient satisfaction, albeit with a negative moderating effect. Discussion: These results suggest that when evaluating and improving patient satisfaction, accounting only for the factors that directly influence medical service quality is insufficient, as the indirect and moderating effects of patients' negative emotions and the social cognition of the medical environment must also be considered. Medical service providers should thus address patients' negative emotions, establish good doctor-patient relationships, optimize service environments, provide managers with medical risk education and training on negative emotions, and prioritize patient-centered care. Additionally, the government and relevant health departments should optimize medical policies, enhance fairness and accessibility, and create a positive social cognitive environment through public education and awareness campaigns.

Key drivers of the oxidative potential of PM2.5 in Beijing in the context of air quality improvement from 2018 to 2022.

The mass concentration of atmospheric particulate matter (PM) has been continuously decreasing in the Beijing-Tianjin-Hebei region. However, health endpoints do not exhibit a linear correlation with PM mass concentrations. Thus, it is urgent to clarify the prior toxicological components of PM to further improve air quality. In this study, we analyzed the long-term oxidative potential (OP) of water-soluble PM2.5, which is generally considered more effective in assessing hazardous exposure to PM in Beijing from 2018 to 2022 based on the dithiothreitol assay and identified the crucial drivers of the OP of PM2.5 based on online monitoring of air pollutants, receptor model, and random forest (RF) model. Our results indicate that dust, traffic, and biomass combustion are the main sources of the OP of PM2.5 in Beijing. The complex interactions of dust particles, black carbon, and gaseous pollutants (nitrogen dioxide and sulfur dioxide) are the main factors driving the OP evolution, in particular, leading to the abnormal rise of OP in Beijing in 2022. Our data shows that a higher OP is observed in winter and spring compared to summer and autumn. The diurnal variation of the OP is characterized by a declining trend from 0:00 to 14:00 and an increasing trend from 14:00 to 23:00. The spatial variation in OP of PM2.5 was observed as the OP in Beijing is lower than that in Shijiazhuang, while it is higher than that in Zhenjiang and Haikou, which is primarily influenced by the distribution of black carbon. Our results are of significance in identifying the key drivers influencing the OP of PM2.5 and provide new insights for advancing air quality improvement efforts with a focus on safeguarding human health in Beijing.

Experiencing stress impact on adolescent repetitive nonsuicidal self-injury: The Mediating role of emotion dysregulation and maladaptive cognitive schemas.

BACKGROUND: Repetitive nonsuicidal self-injury (R-NSSI) is a growing concern in adolescents and is associated with various mental health problems. However, little is known about the potential psychology and addiction mechanisms of R-NSSI in adolescents. This study aimed to examine the mediating effects of emotion dysregulation and maladaptive cognitive schemas based on the Interaction of Person-Affect-Cognition-Execution (I-PACE) model and the integrated model of NSSI among adolescents who repeatedly engage in NSSI. METHODS: This longitudinal study was conducted in two waves with 6-month lags. A total of 3925 adolescents (Mage = 13.22 ± 0.86 years, 42 % female) were recruited from three middle schools. Relevant questionnaires were used to evaluate stressful life events, emotion dysregulation, maladaptive cognitive schemas, NSSI, and NSSI addictive features. The structural equation modeling approach was conducted separately for adolescents who engaged in occasional NSSI (O-NSSI) and those who engaged in R-NSSI. RESULTS: Results showed that emotion dysregulation played a significant mediating role in the associations between stressful life events and NSSI frequency, and both maladaptive cognitive schemas and emotion dysregulation played a significant mediating role in the associations between stressful life events and NSSI addictive features in adolescents who engaged in R-NSSI but not in those who engaged in O-NSSI. LIMITATIONS: The main limiting factor is self-reported data. CONCLUSIONS: These findings contribute to the understanding of the psychological and addictive mechanisms involved in R-NSSI. Both emotion dysregulation and maladaptive cognitive schemas could be a suitable therapeutic target to reduce R-NSSI in the context of stress during adolescence.

[Influence of Ammonium Sulfate and Ammonium Nitrate on the Properties of Ambient PM2.5 in Zhenjiang].

Recently, the contribution of inorganic salts (nitrates in particular) to the mass concentration of particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) has been increasing across China. However, it is urgent to understand how the increased inorganic salts affect the crucial properties of PM2.5. Here, we conducted continuous field observations at Zhenjiang Ecology and Environment Protection Bureau from January 1 to December 31, 2021. The mass concentrations of ammonium sulfate[(NH4)2SO4] and ammonium nitrate (NH4NO3) were calculated using different methods. The contributions of (NH4)2SO4 and NH4NO3 to the extinction coefficient, hygroscopic growth, and acidity of PM2.5 were discussed in detail. Our results demonstrated that the mean mass concentrations of (NH4)2SO4 and NH4NO3 during the study period were (6.5±4.5) and (15.0±13.3) µg·m-3, which contributed (20.5±18.2)% and (34.5±18.4)% to the mass concentration of PM2.5, respectively. The total extinction coefficient of PM2.5 was (224.5±194.2) Mm-1, in which NH4NO3 was the largest contributor[(40.1±20.9)%] followed by (NH4)2SO4[(19.1±10.8)%]. (NH4)2SO4 and NH4NO3 were also the dominant contributors to the hygroscopic growth of PM2.5. In particular, NH4NO3contributed from (53.8±13.4)% to (61.6±14.6)% to the aerosol water content of PM2.5 under pollution conditions. Thus, NH4NO3 was a key air pollutant to be targeted for further improving the visibility and air quality in Zhenjiang in the future. However, the reduction in the precursors of NH4NO3 would lead to an increase in aerosol acidity, particularly in the spring and winter seasons. Our results help us understand the evolution of air quality and the related impacts and also provide important information on air quality improvement in Zhenjiang in the future.

Role of the voltage-gated proton channel Hv1 in insulin secretion, glucose homeostasis, and obesity.

Diabetes is characterized by an absolutely inadequate insulin secretion (type 1 diabetes mellitus) or a relative deficit in insulin secretion due to insulin resistance (type 2 diabetes mellitus), both of which result in elevated blood glucose. Understanding the molecular mechanisms underlying the pathophysiology of diabetes could lead to the development of new therapeutic approaches. The voltage-gated proton channel Hv1 is an ion channel with specific selectivity for protons, which is regulated by membrane potential and intracellular pH. Recently, our studies showed that Hv1 is expressed in ß cells of the endocrine pancreas. Knockout of Hv1 reduces insulin secretion and results in hyperglycemia and glucose intolerance, but not insulin resistance. Furthermore, knockout of Hv1 leads to diet-induced obesity due to inflammation and hepatic steatosis. Increasing evidence suggests that Hv1 plays a pivotal role in glucose homeostasis and lipid metabolism. This review aims to summarize advances made so far in our understanding of the roles of Hv1 in the regulation of insulin secretion in ß cells, glucose homeostasis, and obesity.

Adverse childhood experiences, recent negative life events, and non-suicidal self-injury among Chinese college students: the protective role of self-efficacy.

BACKGROUND: Non-suicidal self-injury (NSSI) is a severe health problem closely related to adverse childhood experiences (ACEs). However, the underlying mechanisms by which ACEs may affect NSSI are largely unknown. Self-efficacy (NSSI-SE) and recent negative life events (RNLEs) may play important roles in this relationship. This study aimed to clarify the relationship between ACEs and NSSI among college students by examining the role of self-efficacy (NSSI-SE) and RNLEs in this process. METHOD: Relevant self-report questionnaires were used to evaluate ACEs, RNLEs, NSSI-SE, and NSSI. A questionnaire of 1036 Chinese undergraduates (Mage = 19.65, 28.9% males, 71.1% females) was collected in a cross-sectional manner. The associations between ACEs, RNLEs, NSSI-SE and NSSI were assessed using Pearson correlation analyses. Then, hierarchical multiple linear regressions were used to analyze the effects of ACEs and RNLEs on NSSI, as well as the protective effect of NSSI-SE on the above relations. RESULTS: NSSI was associated with both ACEs and RNLEs. ACEs and RNLEs could directly increase the risks of participating in NSSI, and the effects of ACEs and RNLEs on NSSI were independent without an interactive effect. NSSI-SE buffered the relationship between ACEs and NSSI, as well as between RNLEs and NSSI. Compared to individuals with a low level of NSSI-SE, ACEs and RNLEs were not significantly associated with NSSI in persons with a high level of NSSI-SE. CONCLUSION: NSSI-SE may buffer the effect of ACEs and RNLEs on NSSI, indicating that future interventions can be enhanced by targeting NSSI-SE among college students with ACEs or RNLEs to prevent their engagement in NSSI.

Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity.

The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (Mpro, also called 3CLpro) that cut the viral precursor polyproteins and is a major target for antiviral drug design. Here, we showed that heparin interacts with the Mpro of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the Mpro protein with dissociation constants KD of 16.66 and 31.60 µM at 25 and 35 °C, respectively. From thermodynamic parameters of the interaction, there are hydrophobic and hydrogen bond interactions between them. Fluorescence resonance energy transfer (FRET) assay demonstrated that heparin inhibits the proteolytic activity of Mpro with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC50) of 7.8 ± 2.6 nM. Furthermore, molecular docking analysis revealed that the recognition and binding groups of heparin within the active site of SARS-CoV-2 Mpro provide important new information for the characteristics of the interactions of heparin with the protease. Our finding suggested that heparin might have a potential role in inhibiting SARS-CoV-2 infection through inhibiting Mpro activity of SARS-CoV-2.

Automated quantification of brain connectivity in Alzheimer's disease using ClusterMetric.

Diffusion magnetic resonance imaging tractography allows investigating brain structural connections in a noninvasive way and has been widely used for understanding neurological disease. Quantification of brain connectivity along with its length by dividing a fiber bundle into multiple segments (node) is a powerful approach to assess biological properties, which is termed as tractometry. However, current tractometry methods face challenges in node identification along with the length of complex bundles whose morphology is difficult to summarize. In addition, the anatomic measure reflecting the macroscopic fiber cross-section has not been followed in previous tractometry. In this paper, we propose an automated fiber bundle quantification, which we refer to as ClusterMetric. The ClusterMetric uses a data-driven approach to identify fiber clusters corresponding to subdivisions of the white matter anatomy and identify consistent space nodes along the length of clusters across individuals. The proposed method is demonstrated by applicating to our collected dataset including 23 Alzheimer's disease (AD) patients and 22 healthy controls (HCs) and a public dataset of ADNI including 53 AD patients and 85 HCs. The altered white matter tracts in AD group are observed using both datasets, which involve several major fiber tracts including the corpus callosum, corona-radiata-frontal, arcuate fasciculus, inferior occipito-frontal fasciculus, uncinate fasciculus, thalamo-frontal, superior longitudinal fasciculus, inferior cerebellar peduncle, cingulum bundle, and extreme capsule. These fiber clusters represent the white matter connections that could be most affected in AD, suggesting the ability of our method in identifying potential abnormalities specific to local regions within a fiber cluster.

The Effects of Different Anesthesia Methods on the Treatment of Parkinson's Disease by Bilateral Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) surgery for Parkinson's disease (PD) is routinely performed at medical centers worldwide. However, it is debated whether general anesthesia (GA) or traditional local anesthetic (LA) is superior. Purpose: This study aims to compare the effects of LA and GA operation methods on clinical improvement in patients with PD, such as motor and non-motor symptoms, after STN-DBS surgery at our center. Method: A total of 157 patients with PD were retrospectively identified as having undergone surgery under LA (n = 81) or GA (n = 76) states. In this study, the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III) in three states, levodopa-equivalent-daily-dose (LEDD), surgical duration, intraoperative microelectrode recording (iMER) signal length, postoperative intracranial volume, electrode implantation error, neuropsychological function, quality of life scores, and complication rates were collected and compared. All patients with PD were routinely followed up at 6, 12, 18, and 24 months postoperatively. Result: Overall improvement in UPDRS-III was demonstrated at postoperative follow-up, and there was no significant difference between the two groups in medication-off, stimulation-off state and medication-off, stimulation-on state. However, UPDRS-III scores in medication-on, stimulation-on state under GA was significantly lower than that in the LA group. During postoperative follow-up, LEDD in the LA group (6, 12, 18, and 24 months, postoperatively) was significantly lower than in the GA group. However, there were no significant differences at baseline or 1-month between the two groups. The GA group had a shorter surgical duration, lower intracranial volume, and longer iMER signal length than the LA group. However, there was no significant group difference in electrode implantation accuracy and complication rates. Additionally, the Hamilton Anxiety Scale (HAMA) was significantly lower in the GA group than the LA group at 1-month follow-up, but this difference disappeared at longer follow-up. Besides, there was no significant group difference in the 39-item Parkinson's Disease Questionnaire (PDQ-39) scale scores. Conclusion: Although both groups showed overall motor function improvement without a significant postoperative difference, the GA group seemed superior in surgical duration, intracranial volume, and iMER signal length. As the accuracy of electrode implantation can be ensured by iMER monitoring, DBS with GA will become more widely accepted.

Examining how and why polygenic dopamine composite levels moderate adolescents' vulnerability to peer victimization.

Extensive literature documents that dopaminergic genes play an important role in the link between adverse environments and adolescents' problem behavior. However, little is known about the potential mechanism underlying adolescents' vulnerability to peer victimization. The current study examined the effect of the interplay between a polygenic dopamine composite (i.e., COMT Val158Met and DRD2-141C Ins/Del polymorphisms) and peer victimization on adolescents' externalizing problems as well as the mediating role of emotion dysregulation in the interactive effects in a sample of 393 Chinese adolescents (Mean age = 14.71 years; 50.1% girls). A significant moderation of dopaminergic genetic composite was observed in girls but not in boys. In addition, emotion dysregulation partially explained the moderating effect of dopaminergic genes. Specifically, girls with genic composite indexing low dopamine activity reported a higher level of emotion dysregulation when faced with more peer victimization. More difficulties with emotion regulation, in turn, predicted more pronounced externalizing problems in girls. This study underscores polygenic underpinnings of adolescent vulnerability to negative peer experiences and suggests the importance of considering sex differences when investigating genic influence on the relationship between adverse environments and externalizing problems.

Paeonol triggers apoptosis in HeLa cervical cancer cells: the role of mitochondria-related caspase pathway.

Paeonol is a biologically active component purified from the root bark of Cortex Moutan that exerts pharmacological effects on the cervical cancer. In this study, we aim to evaluate the anti-cervical cancer capacity of paeonol and to investigate the mechanism driving its anti-cervical cancer effect. Paeonol administration markedly restrained the proliferation and caused apoptosis in HeLa cells. Furthermore, paeonol treatment resulted in a mitochondrial dysfunction in HeLa cells, including the inducing of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and the release of cytochrome c. Moreover, the Bcl-2/Bax proportion was obviously downregulated and cleaved caspase-3 expression was evaluated through paeonol treatment. Additionally, the expression of p-PI3K and p-Akt was noticeably reduced in response to paeonol treatment in HeLa cells. Our findings indicated that paeonol exerts an anticancer potential in HeLa cells, at least in a manner, via triggering the mitochondrial pathway of cellular apoptosis by inhibiting PI3K/Akt signaling. Thus, paeonol has great potential as a promising therapeutic compound to resist human cervical cancer.