A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells.

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

Dhx38 is required for the maintenance and differentiation of erythro-myeloid progenitors and hematopoietic stem cells by alternative splicing.

Mutations that occur in RNA-splicing machinery may contribute to hematopoiesis-related diseases. How splicing factor mutations perturb hematopoiesis, especially in the differentiation of erythro-myeloid progenitors (EMPs), remains elusive. Dhx38 is a pre-mRNA splicing-related DEAH box RNA helicase, for which the physiological functions and splicing mechanisms during hematopoiesis currently remain unclear. Here, we report that Dhx38 exerts a broad effect on definitive EMPs as well as the differentiation and maintenance of hematopoietic stem and progenitor cells (HSPCs). In dhx38 knockout zebrafish, EMPs and HSPCs were found to be arrested in mitotic prometaphase, accompanied by a 'grape' karyotype, owing to the defects in chromosome alignment. Abnormal alternatively spliced genes related to chromosome segregation, the microtubule cytoskeleton, cell cycle kinases and DNA damage were present in the dhx38 mutants. Subsequently, EMPs and HSPCs in dhx38 mutants underwent P53-dependent apoptosis. This study provides novel insights into alternative splicing regulated by Dhx38, a process that plays a crucial role in the proliferation and differentiation of fetal EMPs and HSPCs.

Efficacy of physical exercise intervention on children with acute lymphoblastic leukemia during treatment and rehabilitation: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the impact of physical exercise intervention on children with acute lymphoblastic leukemia (ALL) during the treatment and rehabilitation consolidation periods. METHOD: Randomized controlled trials (RCTs) were retrieved from PubMed, Scopus, Web of Science, CNKI, and Cochrane databases, with a search time range from database establishment to September 1, 2023. The quality of the included RCTs was evaluated using the Cochrane risk assessment tool, and a systematic evaluation was conducted using RevMan 5.4. The study has been registered with INPLASY (registration number: 202390100). RESULT: A total of 12 RCTs including 423 subjects was included. The meta-analysis results showed that long-term exercise intervention can effectively improve the endurance performance (SMD = 1.37, 95% CI 0.45 to 2.29, p = 0.004), functional mobility (MD = - 1.17, 95% CI - 1.85 to - 0.49, p = 0.0008), cancer-related fatigue (CRF) (MD = - 1.25, 95% CI - 1.69 to - 0.80, p < 0.00001), and quality of life (QOL) (MD = 4.93, 95% CI 1.80 to 8.05, p = 0.002) of ALL children during the treatment and rehabilitation consolidation periods. Its promoting effect on the muscle strength (SMD = 0.53, 95% CI - 0.33 to 1.39, p = 0.23) and bone mineral density (BMD) (SMD = 0.48, 95% CI 0.20 to 0.77, p = 0.05) of the subjects was not significant. Further meta-analysis showed that exercise intervention with a duration of less than 1 year (SMD = 0.91, 95% CI 0.55 to 1.28, p < 0.00001) rather than more than 1 year (SMD = - 0.16, 95% CI - 0.61 to 0.29, p = 0.49) can effectively reduce subject BMD, while in terms of strength, exercise intervention can effectively improve strength during the treatment period (SMD = 0.97, 95% CI 0.40 to 1.54, p = 0.0008) rather than the consolidation period (SMD = - 0.27, 95% CI - 1.08 to 0.53, p = 0.51). CONCLUSION: Long-term regular exercise can effectively improve the endurance, functional mobility, CRF, and QOL of children with ALL in the rehabilitation and treatment consolidation stages. Their strength and BMD may be influenced by the timing of treatment and the intervention cycle, respectively. Considering the limited number of included literature and the instability of some outcome indicators, it is necessary to design more comprehensive and rigorous high-quality RCTs in the future to test the exercise efficacy of ALL children.

A study on the impact of acute exercise on cognitive function in Alzheimer's disease or mild cognitive impairment patients: A narrative review.

This narrative review follows the JBI approach and comprehensively explores the effects and mechanisms of acute exercise on cognitive function in Alzheimer's disease (AD) and Mild cognitive impairment (MCI) patients. The results showed that the combination of acute exercise and cognitive training improved the cognitive function of AD patients better than aerobic exercise or resistance training alone. For patients with MCI, moderate intensity acute aerobic exercise and resistance exercise were beneficial to enhance Inhibitory control (IC), but high-intensity acute exercise was adverse to improve IC; Brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor 1 (IGF-1) may assume the potential mediating mechanism of acute exercise on cognitive function in AD and MCI patients, but more research is needed to further confirm this mechanism.

Relationship between pistol players' psychophysiological state and shot performance: Activation effect of EEG and HRV.

OBJECTIVE: To understand the mechanism of dual activation of the brain and heart in pistol athletes during shooting performances, through synchronized monitoring of electroencephalogram (EEG) and electrocardiogram (ECG). METHODS: Eighteen adolescents air pistol athletes were placed in a simulated competition environment and performed 40 self-paced shooting tasks, and simultaneously monitored the athletes' EEG, ECG, and shooting performance during the preparation period. RESULTS: (1) In the successful performance, the power values of the alpha wave of the athlete's T7 area showed a significant upward trend 6 s before the shot, but there was no significant change in the alpha wave in the T8 area. In the failure performance, the alpha wave in the T7 and T8 areas did not change significantly 6 s before the shot. (2) The Fz theta wave power value of athletes in successful performance showed a significant upward trend in the 6 s before firing, and in the failure performance, it showed an "inverted U-shaped" characteristic of rising first and then decreasing. (3) Regardless of whether it was a success or a failure, the SMR wave power value of the athlete's central area has no significant change before the shot. (4) At 6 s before the shot, the athlete's heart rate and R-R interval (RRI) in the successful performance showed a significant decline and rise, respectively, but there was no significant change in the failure performance. (5) Approaching the firing time, the athletes' EEG and ECG have a more significant correlation in successful performance and a more synchronized trend, while the correlation was lower in failure performance. CONCLUSIONS: The psychophysiological state of young air pistol athletes was closely related to shooting performance. If the brain-cardiac system maintains a benign dual activation level during the aiming and firing period, it will be beneficial to the improvement of shooting performance, otherwise, it was easy to reduce shooting performance.

The role of loneliness and learning burnout in the regulation of physical exercise on internet addiction in Chinese college students.

OBJECTIVE: To explore the mediating effects of physical exercise on internet addiction in Chinese college students and to reveal the mediating effects of loneliness and learning burnout on physical exercise and internet addiction. METHODS: 1238 Chinese college students were investigated by physical exercise scale, loneliness scale, learning burnout scale, and internet addiction scale. The SPSS 27.0 was used to conduct a correlation analysis of the data and AMOS21.0 was used to establish a structural equation model to investigate the mediation effect. RESULTS: Physical exercise could directly negatively predict the internet addiction of college students. Loneliness and learning burnout partially mediate the relationship between physical exercise and internet addiction, and the mediating pathways included "physical exercise-loneliness-internet addiction", "physical exercise-learning burnout-internet addiction", and "physical exercise-loneliness-learning burnout-internet addiction", accounting for 9.38%, 15.63% and 21.88% of the total effect, respectively. In the chain mediation effect, it was mainly the loneliness and sub-dimensions of learning burnout (low mood, misbehavior) that were at play. CONCLUSION: Physical exercise not only directly affects internet addiction of college students but also indirectly affects internet addiction through the independent mediating effect of loneliness and learning burnout and the chain mediating effect of "loneliness-learning burnout".

Efficacy, Safety, and Tolerability of Ansofaxine (LY03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial.

BACKGROUND: Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). METHODS: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6. RESULTS: A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (-12.46; χ2 = -9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group. CONCLUSION: Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.

Cardiovascular Effects of High-Frequency Magnetic Seizure Therapy Compared With Electroconvulsive Therapy.

BACKGROUND: Magnetic seizure therapy (MST) is a novel convulsive therapy that has been shown to have antidepressant efficacy comparable to electroconvulsive therapy (ECT) with fewer cognitive side effects. However, the cardiovascular (CVS) effects of high frequency MST in comparison to ECT have not been investigated. MATERIALS AND METHODS: Forty-five patients with depression received 6 treatment sessions of 100 Hz MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on CVS function including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate pressure product (RPP) were collected at baseline (T0), after the induction of anesthesia but before the electrical stimulation (T1), during convulsion (T2), 2 minutes after cessation of motor seizure (T3), 5 minutes after cessation of motor seizure (T4), and 10 minutes after cessation of motor seizure (T5). Comparisons were made with baseline data and between MST and ECT groups. RESULTS: There were statistically significant elevations in the maximum HR, SBP, DBP, and RPP in patients receiving ECT compared with MST both in the initial and sixth treatments (all P < 0.05). Particularly, at T2, the ECT group had significantly higher HR, SBP, DBP, and RPP than those in MST group both in initial and sixth treatment (all P < 0.001). At the sixth treatment, the ECT group had significantly higher SBP, DBP, and RPP during the treatment than in the MST group (all P < 0.001). LIMITATIONS: The anesthetic choices for this study may limit the generalizability of our findings. The sample size was relatively small. CONCLUSIONS: Compared with ECT, high-frequency MST has fewer CVS side effects and may be a safer option for depression patients with CVS disorders.

Psychoeducation for psychiatric inpatients following remission of a manic episode in bipolar I disorder: A randomized controlled trial.

OBJECTIVE: The aim of the present study was to evaluate the effectiveness of psychoeducation for bipolar I inpatients following remission of a manic episode in a Chinese population. METHOD: The study recruited currently medicated bipolar I patients, aged 18-60 years, who were in remission from a manic episode, as determined using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). Patients were randomized (1:1) to either eight sessions of group-based psychoeducation (active treatment group) or regular free discussions (control group). The primary outcomes were the rates of any type of recurrence and rehospitalization following treatment. The secondary outcomes were changes in mood symptoms, medication adherence, global functioning, as well as treatment response (as measured using the Clinical Global Impression scale). Subjects were assessed at baseline and then at 2 weeks, and 1, 2, 3, 5, 7, 9, and 12 months following treatment. RESULTS: At 1 year, patients receiving the psychoeducation treatment demonstrated significantly less recurrence. Those in the treatment group also showed a significant reduction in mania recurrence but not depressive recurrence, and psychoeducation increased time to remission. Notably, lower rates of rehospitalization were found in the active treatment group. Those receiving the psychoeducation treatment also revealed higher change from baseline on measures of depression (17-item Hamilton Rating Scale for Depression), mania (Young Mania Rating Scale), global functioning (Clinical Global Impression-severity scale and World Health Organization Disability Assessment Schedule) (P<.05). However, there were no significant group differences for the medication adherence scores. CONCLUSION: This preliminary evidence suggests that short, group-based psychoeducation benefits currently medicated inpatients following the remission of mania in bipolar I disorder. This intervention warrants further investigation, especially in other Chinese populations. If future studies confirm its benefits, group-based psychoeducation could be incorporated into routine psychiatric inpatient care for bipolar patients in China.

Perception of inpatients following remission of a manic episode in bipolar I disorder on a group-based Psychoeducation program: a qualitative study.

BACKGROUND: This forms the first study of a group-based psychoeducation program for inpatients following remission of a manic episode in patients suffering from bipolar I disorder in a Chinese population. The aim was to explore the patient's perspectives of the program and their suggestions regarding ways to improve the intervention in the future. METHODS: Semi-structured and in-depth interviews were conducted with 15 participants who had participated in 8 sessions of a group psychoeducation program over 2 weeks. The verbatim transcripts of those interviews were analysed using thematic analysis. RESULTS: Five themes emerged from the data, including the patients' perception of participating in the program, their perception of the setting, perception of participating in a group program, perception of the learning content and of the outcome of participating in the program. CONCLUSIONS: The results presented here describe how the short-term group psychoeducation program was experienced by the patients. Recommendations are also offered to improve the setting, content, and delivery. Our findings provide evidence that the program is beneficial for manic patients with bipolar I disorder, and this intervention warrants further research especially in a Chinese population. If these benefits are confirmed in future studies, this program could be incorporated into routine psychiatric inpatient care in China.

Can physical activity counteract the negative effects of sedentary behavior on the physical and mental health of children and adolescents? A narrative review.

Background: The increase in sedentary behavior (SB) in children and adolescents is one of the major threats to global public health, and the relationship between physical activity (PA) and SB has always been a key topic. Methods: The literature search was conducted through PubMed, Web of Science, CNKI, Wanfang, and Scopus, and 121 pieces of literature were included in this study after screening and evaluation. Results: (1) SB caused by screen time such as mobile phones and TVs has varying degrees of negative impact on obesity, cardiovascular metabolism, skeletal muscle development, and cognitive, and psychological disorders in children and adolescents. (2) Regular physical activity could effectively prevent, offset, or improve the harm of SB to the physical and mental health of children and adolescents, mainly by reducing the incidence of obesity, and cardiovascular and metabolic risks, promoting skeletal muscle development, and improving cognitive function and mental health. (3) The mechanism of physical activity to prevent or ameliorate the harm of SB was relatively complex, mainly involving the inhibition or activation of neurobiomolecules, the improvement of blood and cell metabolic factors, and the enhancement of brain functional connectivity. Conclusions: Children and adolescents should avoid excessive SB, and through a variety of moderate to vigorous physical activity (MVPA) to replace or intermittent SB, which could effectively prevent or improve the harm of SB to physical and mental health.

Can an intervention integrating sports and medicine improve children's health more effectively? Monitoring based on sleep, body mass index, and heart rate variability.

Background: Theoretical studies have suggested that the integration of sports and medicine with one another could positively affect children's health. By monitoring the variation characteristics of children's sleep, body mass index (BMI), and heart rate variability (HRV), we explored and compared the influences of and differences between two interventions - physical exercise and an intervention integrating sports and medicine - on improving children's health. Methods: We conducted a randomised controlled study, where we randomly divided 136 children into the physical exercise group (PEG), the integration of sports and medicine group (ISMG), and the control group. We measured sleep, BMI, and HRV at baseline and week eight. Results: After the eight-week intervention, the sleep scores in the PEG and the ISMG were significantly lower than in the control group, while the scores in the ISMG were significantly lower than in the PEG. After the eight-week intervention, the BMI of both the PEG and the ISMG was significantly lower than that of the control group, without a significand difference between the two intervention groups. After the eight-week intervention, the standard deviation of normal-to-normal intervals (SDNN), root mean square differences of the standard deviation (RMSSD), low-frequency of normal (LFn), and high-frequency of normal (HFn) in the PEG and the ISMG were significantly higher than those in the control group, again without a significant difference between the two intervention groups. After intervention, sleep, BMI, and HRV of the three groups were correlated with one another to different degrees, but the correlation coefficient of the two exercise groups was higher. Conclusions: Based on the interventions, we observed a significant correlation between sleep, BMI, and HRV in children. Regular physical exercise or an intervention integrating sports and medicine could synergistically improve sleep, BMI, and HRV in this population, with the latter having a better effect on improving sleep quality.

Cross-species single-cell landscapes identify the pathogenic gene characteristics of inherited retinal diseases.

Introduction: Inherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs. Methods: Single-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell-cell communication analysis, and trajectory inference analysis. Results: The cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs. Conclusion: We identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

Mood Status Response to Physical Activity and Its Influence on Performance: Are Chronotype and Exercise Timing Affect?

PURPOSE: It is well known that there is an obvious 24 h diurnal variation in the individual's mood state and physiological activity, and training at different times of the day may lead to different exercise performance and metabolic outcomes; however, the time-dependent effect of emotional state on physical activity and the influence of its circadian rhythm on exercise performance are still not comprehensively understood. Based on this, this study summarizes the rhythmic experimental research in the field of sport psychology, and it aims to provide the basis for coaches to optimize sports training scientifically and to improve the mental health of the related crowd to the greatest extent. METHODS: The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Web of Science, Medline, and CNKI databases for relevant literature; the search scope was research before September 2022. RESULTS: 13 studies comprising 382 subjects examined the effects of exercise timing on mood responses to exercise or the effects of circadian rhythms of mood on exercise performance, which included 3 RCTs and 10 Non-RCTs. The subjects included athletes (both training or retired), college students, and healthy adults. Two studies were designed for long-term exercise intervention (aerobic training and RISE) and the rest for acute intervention (CrossFit training, HIIT, aerobic combined with muscle conditioning training, constant power exhaustion training, and cycling) or physical function tests (RSA + BTV tests, 30 s Wingate test, muscle strength + CMJ + swimming performance test, RSSJA, shooting accuracy tests + 10 × 20 m dribbling sprint, 200 m time trials). All trials reported specific exercise timing; of these, 10 studies reported subjects' chronotypes, most commonly using the MEQ scale, while 1 recorded with the CSM. Mood responses were assessed with the POMS scale in 10 studies, while 3 other studies used the UMACL, PANAS, and GAS scales, respectively. CONCLUSION: There was much inconsistency between the results, with subjects likely to be exposed to more sunlight (the main timing factor of the circadian rhythm) during early morning exercise, resulting in feeling more positive emotions; however, following a night's rest, delayed responses and poor functioning of the various organ systems of the human body may also lead to higher feelings of fatigue and negative emotions indirectly. Conversely, for athletes, their physical function tests are also more susceptible to the circadian rhythm of emotions, suggesting the importance of synchronizing them. In addition, night owls' emotional state during physical activity seems to be more susceptible to exercise timing than that of early birds. In order to achieve the best emotional state, it is suggested that night owls arrange courses in the afternoon or evening in future training.

Exergames improve cognitive function in older adults and their possible mechanisms: A systematic review.

Objective: The degree of aging in China is deepening, leading to cognitive decline and seriously affecting the health status of the elderly. This article explores the benefits of exergames in improving cognitive function in older adults through a literature review, with aim of contributing to the development of healthy aging. Methods: Using PubMed, Web of Science, CNKI, dimensional spectrum, search for research papers from 2005 to April 2023 by using keywords such as a somatosensory game, cognitive function, execute function, working memory, aged and suppression control. PEDro Scale was used to check the quality of the literature. Results: A total of 16 papers were included in the review. Exergames improve the executive function of the elderly and support the relationship between exergames and cognitive performance in older adults. From a mechanistic perspective, somatosensory play promotes signal transduction of brain neurotrophin, thereby protecting the structure and function of neurons in specific brain regions and delays the decline of executive function in older adults as much as possible. Conclusions: It is recommended to use exergames as an intervention measure for the physical and mental health preservation of older adults. Suggest adopting personalised exergames in the future to explore the impact of cognitive and physical functions in elderly people, as well as measurable changes in brain structure.

Chan-Chuang and resistance exercise for drug rehabilitation: a randomized controlled trial among Chinese male methamphetamine users.

Objective: To examine the health benefits of Chan-Chuang and resistance exercise. Methods: We deployed an 8-week randomized controlled trial, in which 76 male methamphetamine users were allocated to control (n = 25), Chan-Chuang (n = 26), and residence exercise groups (n = 25). Our primary outcomes were drug craving, mental wellbeing, sleep quality, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). Our secondary outcomes were body mass index (BMI), vital capacity, grip strength, balance, and vertical jump. Results: Chan-Chuang exercise resulted in reduced HR, DBP, and MAP, along with improvements in vital capacity, grip strength, and balance compared to the control group. Resistance exercise reduced SBP and MAP, and also improved vital capacity, grip strength, balance, and vertical jump. Conclusion: These findings may support the role of Chan-Chuang and resistance exercise in maintaining the physical fitness of methamphetamine users at mandatory detention centers.

Reduced suicidality after electroconvulsive therapy is linked to increased frontal brain activity in depressed patients: a resting-state fMRI study.

Objective: Suicidality is commonly observed in patients with depressive episodes, and electroconvulsive therapy (ECT) has been found to be effective in treating these patients. However, the role of ECT in suicidality remains unclear. This study used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the changes in brain function before and after ECT in depressed patients with suicidality. Methods: In total, 26 depressed patients with suicidality underwent rs-fMRI at baseline and after 8-12 sessions of ECT. In addition, 32 healthy controls (HCs) matched for age, gender, and educational level underwent rs-fMRI once. The amplitude of low-frequency fluctuations (ALFF), the fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were measured to evaluate whole brain function. Differences between the groups and time points (before and after ECT) were compared. Clinical symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17) and Beck Scale for Suicide Ideation (BSSI). Results: At baseline, patients exhibited decreased ALFF in the right postcentral and precentral gyrus and decreased fALFF in the right supramarginal and postcentral gyrus, left superior frontal gyrus (SFG), as well as the superior and middle temporal gyrus compared to HCs. Patients also had lower ReHo in the left amygdala, anterior cingulate, and postcentral gyrus, and in the right thalamus, insula, and postcentral gyrus. They also exhibited higher ALFF in the bilateral temporal gyrus and insula as well as higher fALFF in the cerebellum. Following ECT, fALFF in the left SFG and orbital frontal cortex (OFC) significantly increased and was inversely correlated with the reduction of BSSI scores (r = -0.416, p = 0.048), whereas no correlation was found with changes in HAMD-17scores. Conclusion: Our findings suggest that the left SFG and OFC may play a key role in the mechanism of ECT for suicidality. The decrease of fALFF in the left SFG and OFC may represent a potential mechanism through which ECT effectively treats suicidality in depressed patients.

The splicing factor DHX38 enables retinal development through safeguarding genome integrity.

DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder.

Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, -20.0; 160 mg, -19.9) vs. placebo (-14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.