Children's early signs and developmental trajectories of psychotic-like experiences.

INTRODUCTION: Children who experience persistent psychotic-like experiences (PLEs) are at a higher risk of developing psychotic disorder later in life. The developmental trajectories of PLEs are influenced by various factors. Therefore, it is important to identify early characteristics that can distinguish and predict between different developmental trajectories of PLEs. METHODS: Using PLEs scores from the Adolescent Brain Cognitive Development (ABCD) data across three waves, we categorized participants into five distinct PLEs trajectories groups: persistent group (n = 47), remitting group (n = 185), increasing group (n = 117), remittent group (n = 21), and no PLEs group (n = 4,476). We utilized linear mixed-effect models and generalized linear mixed-effect models to examine the differences in baseline characteristics, including psychological and behavioral problems, suicidality, trauma experiences, developmental milestones, cognitive function, physical health, family income, family history of mental illness, and brain structureamong these PLEs trajectory groups. RESULTS: We found that psychological and behavioral problems (such as DSM-oriented scales/externalizing/ADHD/social/attention/thought problems) assessed by the Child Behavior Checklist (CBCL) were associated with all PLEs groups. The persistent PLEs group had greater ADHD/social/thought problems and suicidal behavior compared to the remitting PLEs group. Comparing with the no PLEs group, poor cognitive function, abnormal brain structure (such as temporal lobe and supramarginal gyrus), more trauma experiences, and lower family income were found in only one of the PLEs groups, but not all PLEs groups. CONCLUSION: The development of PLEs is accompanied by changes in many domains, implying a dynamic and complex developmental process. Given that psychological and behavioral problems can predict the emergence of PLEs at any time and can be regarded as risk factors for persistent PLEs, thereby enabling early precisely interventions, it is important to place greater emphasis on assessing psychological and behavioral problems.

Can digital self-harm relate to suicidal thoughts and behaviors beyond physical self-harm?

BACKGROUND: Digital self-harm (DiSH) is a recently identified self-harm distinct from physical self-harm (PSH, also known as non-suicidal self-injury, NSSI). Although prior research has shown that DiSH was associated with suicidal thoughts and behaviors (STBs), it was still unclear whether DiSH has a unique association with STBs after controlling for PSH. METHOD: A cross-sectional survey was conducted on Chinese college students. The lifetime prevalence of DiSH and PSH, the functions of DiSH, recent suicide experiences (including suicide ideation, plans, and attempts), anxiety and depression were examined. A total of 5281 participants were analyzed. RESULTS: A total of 10.83% of participants had ever engaged in DiSH, and 1.59% of participants reported histories of both DiSH and PSH. Among participants with a history of PSH, 30.11% engaged in DiSH. Engagement in DiSH was significantly associated with suicide ideation (SI), suicide plans (SPs), and suicide attempts (SAs). More importantly, participants who engaged in both DiSH and PSH showed higher odds of SI and SPs compared to those who had only engaged in PSH. Regarding the functions of DiSH, using DiSH for self-punishment was associated with SI and SPs, and using DiSH for sensation seeking was associated with SPs and SAs. Similar results were found for the association between DiSH and anxiety and depression. CONCLUSIONS: Our findings suggest that DiSH has a unique association with the risks of STBs beyond PSH. Early identification and intervention for DiSH are crucial, even for individuals who already engage in PSH.

Inhibition of SOCS3 signaling in the nucleus tractus solitarii and retrotrapezoid nucleus alleviates hypoventilation in diet-induced obese male mice.

The central leptin signaling system has been found to facilitate breathing and is linked to obesity-related hypoventilation. Activation of leptin signaling in the nucleus tractus solitarii (NTS) and retrotrapezoid nucleus (RTN) enhances respiratory drive. In this study, we investigated how medullary leptin signaling contributes to hypoventilation and whether respective deletion of SOCS3 in the NTS and RTN could mitigate hypoventilation in diet-induced obesity (DIO) male mice. Our findings revealed a decrease in the number of CO2-activated NTS neurons and downregulation of acid-sensing ion channels in DIO mice compared to lean control mice. Moreover, NTS leptin signaling was disrupted, as evidenced by the downregulation of phosphorylated STAT3 and the upregulation of SOCS3 in DIO mice. Importantly, deleting SOCS3 in the NTS and RTN significantly improved the diminished hypercapnic ventilatory response in DIO mice. In conclusion, our study suggests that disrupted medullary leptin signaling contributes to obesity-related hypoventilation, and inhibiting the upregulated SOCS3 in the NTS and RTN can alleviate this condition.

Process model of emotion regulation-based digital intervention for emotional problems.

Background: To address the lack of mental health practitioners in developing countries, the current study explored the feasibility of a newly developed self-guided digital intervention program TEA (training for emotional adaptation) in alleviating depressive and anxiety symptoms, as one of a few studies which adapted from theoretical models with effective intervention techniques. Methods: The first part of this study involved 11 professional mental health practitioners giving feedback on the feasibility of the TEA; while the second part involved a mixed-method single-arm study with 32 participants recruited online, who went through the seven intervention sessions within 14 days. The questionnaires were collected before, after, 14 days after, and 30 days after intervention. Additionally, 10 participants were invited to semi-structured interviews regarding their suggestions. Results: Practitioners thought that the TEA showed high professionalism (8.91/10) and is suitable for treating emotional symptoms (8.09/10). The generalized estimating equation model showed that the TEA significantly reduced participants' depressive and anxiety symptoms, while the effects of the intervention remained 30 days post intervention (Cohen's d > 1). Thematic analysis revealed three main themes about future improvement, including content improvement, interaction improvement, and bug-fixing. Conclusions: To address the current needs for digital mental health intervention programs to account for the insufficient availability of mental health services in China, the current study provides preliminary evidence of the effectiveness of TEA, with the potential to address the urgent need for remote mental health services. Trial registration: The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2200065944].

Machine Learning Explains Long-Term Trend and Health Risk of Air Pollution during 2015-2022 in a Coastal City in Eastern China.

Exposure to air pollution is one of the greatest environmental risks for human health. Air pollution level is significantly driven by anthropogenic emissions and meteorological conditions. To protect people from air pollutants, China has implemented clean air actions to reduce anthropogenic emissions, which has led to rapid improvement in air quality over China. Here, we evaluated the impact of anthropogenic emissions and meteorological conditions on trends in air pollutants in a coastal city (Lianyungang) in eastern China from 2015 to 2022 based on a random forest model. The annual mean concentration of observed air pollutants, including fine particles, inhalable particles, sulfur dioxide, nitrogen dioxide, and carbon monoxide, presented significant decreasing trends during 2015-2022, with dominant contributions (55-75%) by anthropogenic emission reduction. An increasing trend in ozone was observed with an important contribution (28%) by anthropogenic emissions. The impact of meteorological conditions on air pollution showed significant seasonality. For instance, the negative impact on aerosol pollution occurred during cold months, while the positive impact was in warm months. Health-risk-based air quality decreased by approximately 40% in 8 years, for which anthropogenic emission made a major contribution (93%).

C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity.

Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 âˆ¼ 0.0966 µM, and their selectivity index was SI > 1415 âˆ¼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 µM and 9.23 µM, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 µM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.

An approach to determine solution properties in micro pipes by near-field microwave microscopy.

In this article, we propose a quantitative, non-destructive and noninvasive approach to obtain electromagnetic properties of liquid specimens utilizing a home-designed near-field microwave microscopy. The responses of aqueous solutions can be acquired with varying concentrations, types (CaCl2, MgCl2, KCl and NaCl) and tip-sample distances. An electromagnetic simulation model also successfully predicts the behaviors of saline samples. For a certain type of solutions with varying concentrations, the results are concaves with different bottoms, and the symmetric graphs of concave extractions can clearly identify different specimens. Moreover, we obtain electromagnetic images of capillaries with various saline solutions, as well as a Photinia × fraseri Dress leaf.

Disordered Leptin signaling in the retrotrapezoid nucleus is associated with the impaired hypercapnic ventilatory response in obesity.

Sleep-disordered breathing is characterized by disruptions of normal breathing patterns during sleep. Obesity is closely related to hypoventilation or apnea and becomes a primary risk factor for sleep-disordered breathing. Leptin, a peptide secreted by adipose tissue, has been implicated in central control of breathing. Activation of the retrotrapezoid nucleus (RTN) neurons, a critical central respiratory chemoreceptor candidate, potentiates a central drive to breathing. Here, we ask whether the disordered leptin signaling in the RTN is responsible for obesity-related hypoventilation. In a diet induced obesity (DIO) mouse model, the hypercapnic ventilatory response (HCVR) was assessed and the cellular leptin signaling in the RTN was examined. Our main findings demonstrate that DIO mice exhibit overweight, hypercapnia, high levels of serum and cerebrospinal leptin. During exposure to room air, DIO mice manifest basal hypoventilation with a rapid and shallow breathing pattern. Exposure to CO2 elicits the impaired HCVR in DIO mice. In addition, both the number of CO2-activated neurons and expression of TASK-2 channels in the RTN are dramatically reduced in DIO mice. Moreover, there is leptin signaling disorder in RTN neurons in DIO mice, including a significant decrease in leptin-activated RTN neurons, downregulation of phosphorylated STAT3 and upregulation of SOCS3. Altogether, we suggest that the disordered leptin/STAT3/SOCS3 signaling pathway in the RTN plays a role in obesity-related hypoventilation.

Activation of Phox2b-Expressing Neurons in the Nucleus Tractus Solitarii Drives Breathing in Mice.

The nucleus tractus solitarii (NTS) is implicated in the control of breathing, but the neuronal phenotype and circuit mechanism involved in such a physiological function remain incompletely understood. This study focused on the respiratory role of paired-like homeobox 2b gene (Phox2b)-expressing NTS neurons and sought to determine whether selective stimulation of this set of neurons activates breathing in male mice. A Cre-dependent vector encoding a Gq-coupled human M3 muscarinic receptor (hM3Dq) was microinjected into the NTS of Phox2b-Cre transgenic mice. The hM3Dq-transduced neurons were pharmacologically activated in conscious mice while respiratory effects were measured by plethysmography. We demonstrate that chemogenetic stimulation of Phox2b-expressing NTS neurons significantly increased baseline minute volume via an increase in respiratory frequency rather than tidal volume. Chemogenetic stimulation also synergized with moderate CO2 stimulation to enhance pulmonary ventilatory response. Selective ablation of Phox2b-expressing NTS neurons notably attenuated a hypercapnic ventilatory response. Moreover, histological evidence revealed that stimulation of Phox2b-expressing NTS neurons increased neuronal activity of the preBötzinger complex. Finally, we presented the neuroanatomical evidence of direct projection of Phox2b-expressing NTS neurons to putative respiratory central pattern generator. Overall, these findings suggest that selective activation of Phox2b-expressing NTS neurons potentiates baseline pulmonary ventilation via an excitatory drive to respiratory central pattern generator and this group of neurons is also required for the hypercapnic ventilatory response.SIGNIFICANCE STATEMENT The nucleus tractus solitarii (NTS) has been implicated in the control of breathing. The paired-like homeobox 2b gene (Phox2b) is the disease-defining gene for congenital central hypoventilation syndrome and is restrictively present in brainstem nucleus, including the NTS. Using a chemogenetic approach, we demonstrate herein that selective stimulation of Phox2b-expressing NTS neurons vigorously potentiates baseline pulmonary ventilation via an excitatory drive to respiratory central pattern generator in rodents. Genetic ablation of these neurons attenuates the hypercapnic ventilatory response. We also suggest that a fraction of Phox2b-expressing neurons exhibit CO2 sensitivity and presumably function as central respiratory chemoreceptors. The methodology is expected to provide a future applicability to the patients with sleep-related hypoventilation or apnea.

Leptin Signaling in the Carotid Body Regulates a Hypoxic Ventilatory Response Through Altering TASK Channel Expression.

Leptin is an adipose-derived hormone that plays an important role in the regulation of breathing. It has been demonstrated that obesity-related hypoventilation or apnea is closely associated with leptin signaling pathways. Perturbations of leptin signaling probably contribute to the reduced sensitivity of respiratory chemoreceptors to hypoxia/hypercapnia. However, the underlying mechanism remains incompletely understood. The present study is to test the hypothesis that leptin signaling contributes to modulating a hypoxic ventilatory response. The respiratory function was assessed in conscious obese Zucker rats or lean littermates treated with an injection of leptin. During exposure to hypoxia, the change in minute ventilation was lower in obese Zucker rats than chow-fed lean littermates or high fat diet-fed littermates. Such a change was abolished in all groups after carotid body denervation. In addition, the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT3), as well as putative O2-sensitive K+ channels including TASK-1, TASK-3 and TASK-2 in the carotid body, was significantly reduced in obese Zucker rats compared with the other two phenotype littermates. Chronic administration of leptin in chow-fed lean Zucker rats failed to alter basal ventilation but vigorously increased tidal volume, respiratory frequency, and therefore minute volume during exposure to hypoxia. Likewise, carotid body denervation abolished such an effect. In addition, systemic leptin elicited enhanced expression of pSTAT3 and TASK channels. In conclusion, these data demonstrate that leptin signaling facilitates hypoxic ventilatory responses probably through upregulation of pSTAT3 and TASK channels in the carotid body. These findings may help to better understand the pathogenic mechanism of obesity-related hypoventilation or apnea.