Dependency of mitochondrial quantity on blastocyst timeline obscures its actual effect to pregnancy outcomes.

Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.

Gender-Specific Trajectories of Non-Suicidal Self-Injury among Adolescents: Predictive Roles of Distal and Proximal Risk Factors.

Non-suicidal self-injury (NSSI) is considered a strong risk factor for suicide. Although NSSI is prevalent among adolescents and varies by gender, few studies have examined the gender-specific trajectory of NSSI and its predictors. This study examined the trajectory of NSSI among Chinese adolescent boys and girls separately, and the roles of distal (i.e., childhood maltreatment and its specific subtypes) and proximal risk factors (i.e., emotional dysregulation, peer victimization) on their trajectories. A total of 3290 Chinese adolescents (Mage = 13.08; SD = 0.84; 57.6% boys) participated in assessments at three time points. Latent class growth models identified three trajectories for boys: Low stable (92.5%), moderate increasing (5.0%) and high decreasing (2.5%). Four trajectories were identified for girls: Low stable (87.9%), moderate increasing (7.6%), high decreasing (3.0%) and high stable (1.5%). Multinomial logistic regression analyses revealed that both emotional dysregulation and emotional abuse predicted the trajectories of moderate increasing, high decreasing and high stable for girls, as well as predicted moderate increasing and high decreasing trajectories for boys. Peer victimization served as a significant risk factor predicting the moderate increasing and high decreasing trajectories only for girls, while overall childhood maltreatment was a remarkable predictor for the moderate increasing and high decreasing trajectories of boys. The findings highlighted the importance of gender differences in understanding the progression of NSSI and the key predictors, informing effective strategies for prevention and intervention.

Comorbidity of loneliness and social anxiety in adolescents: Bridge symptoms and peer relationships.

RATIONALE: Previous research investigating the comorbidity of loneliness and social anxiety symptoms in population samples has relied on latent variable modeling in which averaged scores representing dimensions were derived from observed symptoms. Studies have not examined how loneliness and social anxiety co-occur at the symptom level or their relations with peer relationships. OBJECTIVE: This study examined the comorbidity of loneliness and social anxiety and the role of peer relationships (i.e., the number of reciprocated friends, friendship quality, and bullying victimization) in adolescents' co-occurring network using a large sample of Chinese adolescents. METHODS: We performed a network analysis in a sample of Chinese adolescents (N = 2601, 51.6% male, M age = 13.9 years, SD = 0.60). Participants completed self-report measures of loneliness, social anxiety, bullying victimization, and friendship quality as well as peer nomination measures of the number of reciprocated friends. RESULTS: Network analysis revealed that feeling ridiculed, fear of being rejected, having difficulty asking others to do things together, and feeling left out at school were essential bridge symptoms in the co-occurrence of loneliness and social anxiety. Bullying victimization had more positive associations with symptoms of social anxiety, and friendship quality had more negative associations with symptoms of loneliness. CONCLUSIONS: The findings provide preliminary evidence for the comorbidity of loneliness and social anxiety symptoms in adolescents. The results also highlight the potential importance of targeting peer relationships in the prevention and intervention of loneliness and social anxiety symptoms. The combination of longitudinal networks and interventions on bridge symptoms may provide further insight into the development of the links between peer relationships, loneliness, and social anxiety symptoms.

Profiles and Transitions of Loneliness and Depressive Symptoms among Migrant Children: Predictive Role of Bullying Victimization.

Although loneliness and depressive symptoms are particularly prominent among migrant children and often occur simultaneously, little is known about the co-occurring and transitional nature of loneliness and depressive symptoms among migrant children, and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of loneliness and depressive symptoms among migrant children using latent profile analysis and latent transition analysis, as well as how bullying victimization predicted their profile memberships and transitions. A total of 692 migrant children (55.3% males, Mage = 9.41, SD = 0.55, range = 8 to 12 years old at T1) participated in both two waves of the study over six months. The results indicated that low profile (59.2%), moderate profile (22.0%), moderately high profile (14.3%), and high profile (4.5%) were identified at Time 1; low profile (69.4%), predominantly loneliness profile (16.8%), predominantly depressive symptoms profile (6.5%), and high profile (7.3%) were identified at Time 2. Migrant children in at-risk profiles displayed varying degrees of transition. Migrant children experiencing more bullying victimization were more likely to belong or transition to at-risk profiles. The findings highlight the importance of subgroup differences considerations in understanding the co-occurring and transitional nature of loneliness and depressive symptoms, as well as the predictive role of bullying victimization, informing effective strategies for prevention and intervention.

Bidirectional relationship between bullying victimization and functions of aggression in adolescents: The mediating effect of teacher justice.

INTRODUCTION: Bullying victimization and aggression are frequent phenomena among adolescents and have been linked to various mental health problems. Although the correlation between bullying victimization and aggression is well-documented, the direction between the two has been debated. Moreover, the underlying mechanism through which victimization influences aggression or vice versa has gained little attention. The current study used data across two-time points to address this gap and explore the reciprocal relationships between victimization and aggression. The mediating role of teacher justice and related gender differences were also examined. METHODS: A total of 2462 Chinese adolescents (50.9% boys; Mage = 13.95 years, SD = 0.60) completed measures on two occasions in 1 year with 6-month assessment intervals. Structural equation modeling was used to examine the longitudinal relations among the variables. RESULTS: Results found that bullying victimization significantly and positively predicted both reactive and proactive aggression over time among the total sample. Reactive aggression significantly positively predicted victimization, while proactive aggression negatively predicted victimization in boys. Furthermore, teacher justice mediated the relationships between victimization and both functions of aggression. Mediation was gender-specific, with a significant mediating effect on girls. CONCLUSIONS: The results reveal the violent cycle of bullying victimization and aggression and underscore the role of teacher justice in this process. These findings have important implications for targeted interventions.

Profiles and Transitions of Non-Suicidal Self-Injury and Depressive Symptoms among Adolescent Boys and Girls: Predictive Role of Bullying Victimization.

Although non-suicidal self-injury (NSSI) and depressive symptoms often co-occur, as well as display distinct profiles in different genders, few studies examined the gender-specific profiles and transitions of NSSI and depressive symptoms among adolescents and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of NSSI and depressive symptoms for Chinese adolescent boys and girls separately, along with the predictive role of bullying victimization in subgroup memberships and transitions. A total of 3510 adolescents (52.9% boy, M age = 13.36, SD = 0.50) participated in two waves of the study over six months. The results indicated that four and three profiles identified for girls and boys separately. Adolescents in at-risk profiles showed varying degrees of transition. Adolescents with more bullying victimization were more likely to belong or transition to at-risk profiles for both genders, and bullying victimization exacerbated girls transitioning into co-occurring high profile but not in boys. The findings indicate distinct profile and transition patterns of NSSI and depressive symptoms, as well as different risk role of bullying victimization on their profiles and transitions in boys and girls, highlighting the importance of gender differences in understanding co-occurring and transitional nature of NSSI and depressive symptoms and the risk role of bullying victimization, informing effective strategies for prevention and intervention.

Joint Developmental Trajectories of Likability and Popularity: Associations with Social Behavior among Chinese Adolescents.

The beginning of secondary school is a critical time point of adolescents' development as they entered a new peer context in which social status was re-established. As the key indicators of social status, likability and popularity co-occur but also display distinct developmental trajectories over time. Nevertheless, little is known about the joint developmental trajectories of likability and popularity among adolescents and how identified trajectories are associated with important social behavior. The current study examined the joint developmental trajectories of likability and popularity among Chinese adolescents and their associations with social behavior (prosocial behavior, aggression, and peer victimization) over time. A total of 1509 Chinese 7th grade students (53.6% male, Mage = 13.1, SD = 0.67) participated in self-report and peer nomination assessments on three occasions at 6-month intervals. Parallel process latent growth mixture models revealed four distinct trajectories of likability and popularity: social status decreasing, average, high social status, and social status increasing. The high social status group showed the highest levels of prosocial behavior, the lowest levels of peer victimization, and higher aggression than the average group. The social status decreasing group and social status increasing group exhibited the lower prosocial behavior as well as the higher aggression and peer victimization compared to the average group over time. The findings highlight the co-occurrence but diversity of developmental patterns of likability and popularity in adolescence.

Joint trajectories of loneliness, depressive symptoms, and social anxiety from middle childhood to early adolescence: associations with suicidal ideation.

This study examined the joint trajectories of loneliness, depressive symptoms, and social anxiety from middle childhood to early adolescence and their associations with suicidal ideation. A total of 643 Chinese elementary school students (55.2% male; Mage = 9.01; SD = 0.75; range = 7 to 11 years at T1) completed measures on six occasions at 6-month intervals. Parallel process latent class growth models revealed five distinct trajectories of loneliness, depressive symptoms, and social anxiety: "congruent-low" (45.1%), "moderately low with predominant loneliness and depressive symptoms" (15.7%), "moderate with predominant loneliness and depressive symptoms" (4.2%), "moderately low with predominant social anxiety" (24.9%), and "congruent-high" (10.1%). The highest suicidal ideation was observed among adolescents who persistently experienced two or three symptoms, followed by those who persistently experienced one predominant symptom, and finally, adolescents who persistently experienced low levels of all three symptoms. The findings highlight the importance of individual differences considerations in understanding the joint patterns of loneliness, depressive symptoms, and social anxiety among youth during the transition into adolescence and the need for more sophisticated intervention programs tailored to the unique characteristics of the relevant trajectories to reduce the risk of suicidal ideation.

Reduced mitochondrial DNA content correlate with poor clinical outcomes in cryotransfers with day 6 single euploid embryos.

Objective: To investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst. Methods: A retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for aneuploidy (PGT-A) from 1,305 individuals, and 1,383 embryos involved cryotransfers of single euploid embryo between January 2015 and December 2019. The studied cohort was divided for algorithm establishment on the NGS platform (n=40), correlation of biological features (n=1,635), and correlation of reproductive outcomes (n=1,340). Of the algorithm derived from the NGS platform, the reliability and repeatability were validated via qPCR assay and inter-run controls, respectively. Of the correlation across biological features, stratification analyses were applied to evaluate the effect from a single contributor. Eventually, the correlation between the mtDNA ratios and reproductive outcomes was adjusted according to the significant effector(s). Results: The mtDNA ratios showed statistically different between embryos with different days of blastocyst formation ([Day 5]: 1.06 vs. [Day 6]: 0.66, p=0.021), and between embryos with different expansion stages ([Expansion 5]: 1.05 vs. [Expansion 6]: 0.49, p=0.012). None or weakly correlated with the maternal age, morphology, ploidy, and gender. Analyzed by the different days of blastocyst formation with fixed expansion score as 5 in the euploid single embryo transfers (eSET), the day 6 eSET showed significantly lower reduced mtDNA ratio (n=139) in failure groups of fetal heartbeat (p=0.004), ongoing pregnancy (p=0.007), and live birth (p=0.01); however, no correlation between mtDNA ratios and pregnancy outcomes was observed in the day 5 eSET (n=1,201). Conclusions: The study first demonstrated that mtDNA ratio was dependent on the days of blastocyst formation while expansion stage was fixed. Lower mtDNA ratios were observed in the day 6 eSET with adverse outcomes. The present stratification analyses reveal that the timeline of embryo is an important covariate to the mtDNA content.

Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.

Constrained Parameter Estimation for a Mechanistic Kinetic Model of Cobalt-Hydrogen Electrochemical Competition during a Cobalt Removal Process.

A mechanistic kinetic model of cobalt-hydrogen electrochemical competition for the cobalt removal process in zinc hydrometallurgical was proposed. In addition, to overcome the parameter estimation difficulties arising from the model nonlinearities and the lack of information on the possible value ranges of parameters to be estimated, a constrained guided parameter estimation scheme was derived based on model equations and experimental data. The proposed model and the parameter estimation scheme have two advantages: (i) The model reflected for the first time the mechanism of the electrochemical competition between cobalt and hydrogen ions in the process of cobalt removal in zinc hydrometallurgy; (ii) The proposed constrained parameter estimation scheme did not depend on the information of the possible value ranges of parameters to be estimated; (iii) the constraint conditions provided in that scheme directly linked the experimental phenomenon metrics to the model parameters thereby providing deeper insights into the model parameters for model users. Numerical experiments showed that the proposed constrained parameter estimation algorithm significantly improved the estimation efficiency. Meanwhile, the proposed cobalt-hydrogen electrochemical competition model allowed for accurate simulation of the impact of hydrogen ions on cobalt removal rate as well as simulation of the trend of hydrogen ion concentration, which would be helpful for the actual cobalt removal process in zinc hydrometallurgy.

Mycobacterial species and their contribution to cholesterol degradation in wastewater treatment plants.

Mycobacterium often presents as an abundant bacterial genus in activated sludge in many wastewater treatment plants (WWTPs), but the species-level taxonomy and functions remain poorly understood. In this study, we profiled the mycobacterial communities in eleven WWTPs from five countries by pyrosequencing the rpoB amplicons and searching against a customized database of mycobacterial rpoB sequences. Results indicated that major mycobacterial species were related to M. brumae, M. crocinum, M. sphagni, etc., most of which belong to poorly characterized rapidly-growing group. A few opportunistic pathogenic species were detected, suggesting the potential risk of mycobacteria in WWTPs. Genomic analysis of four isolates from activated sludge indicated these genomes contained genes of degradations of alkane, aromatics, steroids and a variety of cytochrome P450 families. Additionally, a few key genes responsible for cholesterol degradation were detected in a full-scale activated sludge metatranscriptomic dataset reported previously and taxonomically assigned to mycobacteria. Evidence showed that all isolates can degrade cholesterol, a major composition of sewage. Relative abundance of mycobacteria in activated sludge was enriched by 4.7 folds after adding cholesterol into the influent for one week. Our results provided the insights into mycobacterial species and functions in WWTPs.

Optimal vaccination policies for an SIR model with limited resources.

The purpose of the paper is to use analytical method and optimization tool to suggest a vaccination program intensity for a basic SIR epidemic model with limited resources for vaccination. We show that there are two different scenarios for optimal vaccination strategies, and obtain analytical solutions for the optimal control problem that minimizes the total cost of disease under the assumption of daily vaccine supply being limited. These solutions and their corresponding optimal control policies are derived explicitly in terms of initial conditions, model parameters and resources for vaccination. With sufficient resources, the optimal control strategy is the normal Bang-Bang control. However, with limited resources, the optimal control strategy requires to switch to time-variant vaccination.

The community dynamics of major bioleaching microorganisms during chalcopyrite leaching under the effect of organics.

To determine the effect of organics (yeast extract) on microbial community during chalcopyrite bioleaching at different temperature, real-time polymerase chain reaction (PCR) was employed to analyze community dynamics of major bacteria applied in bioleaching. The results showed that yeast extract exerted great impact on microbial community, and therefore influencing bioleaching rate. To be specific, yeast extract was adverse to this bioleaching process at 30°C due to decreased proportion of important chemolithotrophs such as Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans. However, yeast extract could promote bioleaching rate at 40°C on account of the increased number and enhanced work of Ferroplasma thermophilum, a kind of facultative bacteria. Similarly, bioleaching rate was enhanced under the effect of yeast extract at 50°C owing to the work of Acidianus brierleyi. At 60°C, bioleaching rate was close to 100% and temperature was the dominant factor determining bioleaching rate. Interestingly, the existence of yeast extract greatly enhanced the relative competitiveness of Ferroplasma thermophilum in this complex bioleaching microbial community.