Plasma alpha-trypsin inhibitor heavy chain 4 as an age-specific biomarker in the diagnosis and treatment of major depressive disorder.

Background: The diagnosis of major depressive disorder (MDD) mainly depends on subjective clinical symptoms, without an acceptable objective biomarker for the clinical application of MDD. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) showed a high specificity as biomarker for the diagnosis and treatment of MDD. The present study aimed to investigate differences in plasma ITIH4 in two different aged MDD patients and underlying pathological mechanisms of plasma ITIH4 in the occurrence and development of MDD. Methods: Sixty-five adult MDD patients, 51 adolescent MDD patients, and 64 healthy controls (HCs) were included in the present study. A 14-days' antidepressive treatment was conducted in all MDD patients. Psychological assessments were performed and plasma ITIH4 and astrocyte-related markers were detected for all participants. Results: (1) Plasma levels of ITIH4 in adult MDD patients were significantly higher than adolescent MDD patients and HCs, and significantly increased plasma ITIH4 levels was observed in adolescent MDD patients compared with HCs (2). There were positive correlations between plasma ITIH4 levels and 24-item Hamilton Depression Scale (HAMD-24) scores and plasma glial fibrillary acidic protein (GFAP) levels in MDD patients, however, plasma ITIH4 levels were significantly correlated with age just in adult MDD patients (3). Plasma ITIH4 showed area under the curve values of 0.824 and 0.729 to differentiate adult MDD patients and adolescent MDD patients from HCs, respectively (4). There was significant decrease in plasma levels of ITIH4 between before and after antidepressive treatment in adult MDD patients, but not in adolescent MDD patients (5). Changed value of ITIH4 levels were correlated with the changed value of GFAP levels and changed rate of HAMD-24 scores in adult MDD patients following antidepressive treatment. Conclusion: Plasma ITIH4 may be potential plasma biomarkers of MDD with age-related specificity, which was associated with depressive symptoms astrocyte-related pathologic changes, and antidepressive treatment efficacy.

Uterine arteriovenous malformation: a case report with proposal for pathogenesis.

Uterine arteriovenous malformation (UAM) is a rare medical condition. Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients. Here, we present one elderly woman with uncommon UAM. We first discuss our experience regarding the diagnoses and treatments of UAM and then propose a hypothesis for the pathogenesis of UAM.

Association of Pain Intensity and Sensitivity with Suicidal Ideation in Adolescents with Depressive Disorder.

Purpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls. Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects' suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed. Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P<0.001), and the pain intensity in the MDD group (3.77±2.48) was significantly higher than the Control group (0.617±0.99) (P <0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation. Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.

Combinatorial targeting of glutamine metabolism and lysosomal-based lipid metabolism effectively suppresses glioblastoma.

Antipsychotic drugs have been shown to have antitumor effects but have had limited potency in the clinic. Here, we unveil that pimozide inhibits lysosome hydrolytic function to suppress fatty acid and cholesterol release in glioblastoma (GBM), the most lethal brain tumor. Unexpectedly, GBM develops resistance to pimozide by boosting glutamine consumption and lipogenesis. These elevations are driven by SREBP-1, which we find upregulates the expression of ASCT2, a key glutamine transporter. Glutamine, in turn, intensifies SREBP-1 activation through the release of ammonia, creating a feedforward loop that amplifies both glutamine metabolism and lipid synthesis, leading to drug resistance. Disrupting this loop via pharmacological targeting of ASCT2 or glutaminase, in combination with pimozide, induces remarkable mitochondrial damage and oxidative stress, leading to GBM cell death in vitro and in vivo. Our findings underscore the promising therapeutic potential of effectively targeting GBM by combining glutamine metabolism inhibition with lysosome suppression.

Effect of molecular weight of chitosan on quercetin-loaded chitosan nanoparticles.

BACKGROUND: The widespread use of quercetin is limited by its instability, low solubility and poor oral bioavailability. Encapsulation of quercetin using a nanoparticle delivery system is an effective way to overcome these drawbacks. RESULTS: The effect of the molecular weight (Mw) of chitosan (CS) (100, 200, 500 and 1000 kDa) on quercetin-loaded chitosan nanoparticles (QCNPs) was investigated. The structure, stability, release properties and antioxidant activities of the nanoparticles (QCNP-10, QCNP-20, QCNP-50 and QCNP-100) were assessed. Particle size of QCNPs decreased and polydispersity index increased with the increasing Mw of CS. The main forces involved in the formation of QCNPs were hydrogen bonding and hydrophobic interaction. X-ray diffraction verified that quercetin was loaded into CS nanoparticles. The photostability and thermal stability of QCNPs increased with increasing Mw of CS. QCNP-100 exhibited the lowest release rate in a mixture of water and anhydrous ethanol. The antioxidant activities of QCNPs were enhanced with increasing Mw of CS, and QCNP-100 possessed the highest antioxidant activities, which might be relevant to its smallest particle size. CONCLUSION: Overall, these results revealed that the Mw of CS affected the properties of QCNPs, and QCNP-100 possessed the smallest particle, best stability, lowest release rate and highest antioxidant activities. © 2024 Society of Chemical Industry.

Engineered probiotic cocktail with two cascade metabolic Escherichia coli for the treatment of hyperlysinemia.

Engineering probiotics have emerged as a potential strategy for the treatment of metabolic diseases. However, due to the exceptional complexity of these metabolic disorders and the intricate relationship between gut microbes, it is difficult to achieve an ideal therapeutic effect in a specific metabolic disorder using only a single engineered strain. In this work, we proposed a probiotic cocktail strategy by engineering two cascade metabolic bacteria to treat hyperlysinemia, an inherited lysine metabolic disorder with loss of α-aminoadipate semialdehyde synthase (AASS) activity. A probiotic E. coli Nissle 1917 strain EcNT (pTLS) with a heterologous enzyme pathway in Saccharomyces cerevisiae was engineered to metabolize the excess lysine. Another one EcNT (pK25) was engineered to consume the products of lysine metabolism. The bacterial cocktail enables the maintenance of a metabolic cascade with AASS-like functional activity to maintain the blood lysine concentrations and downstream metabolites. In vitro experimental results showed that the cocktail bacteria had a better metabolic capacity and metabolites balance at a ratio of EcNT (pTLS) and EcNT (pK25) of 1:2. Feeding of the cocktail bacteria to the mouse model effectively reduced the concentration of lysine and balanced saccharopine in the plasma of hyperlysinemia-like mice. These findings not only provide a promising strategy of probiotic stains for the treatment of hyperlysinemia but also highlight the potential of engineered cascade cocktails to intervene and even cure other inherited metabolic diseases.

The Association between Cyberbullying Victimization and Depression among Children: A Moderated Mediation Model.

Cyberbullying victimization is becoming more prevalent and adversely affects mental health. This research explores the relationship between the two variables and the underlying mechanism, especially for children, as the impact of mental health in childhood might last a lifetime. Primary school students (N = 344; Mage = 9.90; 43.90% girls) completed self-report questionnaires regarding cyberbullying victimization, self-perceived social competence, optimism, and depression at school. Gender and grade were controlled as covariates. Depression was positively predicted by cyberbullying victimization, while self-perceived social competence played a partially mediating role. In addition, optimism directly and indirectly moderated the effects of cyberbullying victimization on depression. Specifically, the effects were stronger for children with low levels of optimism. Therefore, efforts to enhance children's self-perceived social competence and optimism may reduce their depression resulting from cyberbullying victimization.

STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth.

SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis. Pharmacological inhibition of STAT3 significantly reduces the levels of unsaturated FAs and phospholipids bearing unsaturated FA chains by reducing the SCAP-SREBP-1 signaling axis and its downstream effector SCD1. Examination of clinical samples from patients with glioblastoma, the most lethal brain tumor, demonstrates a substantial co-expression of STAT3, SCAP, SREBP-1, and SCD1. These findings unveil STAT3 directly regulates the expression of SCAP and SREBP-1 to promote FA synthesis, ultimately fueling tumor progression.

Blue light-mediated gene expression as a promising strategy to reduce antibiotic resistance in Escherichia coli.

The discovery of antibiotics has noticeably promoted the development of human civilization; however, antibiotic resistance in bacteria caused by abusing and overusing greatly challenges human health and food safety. Considering the worsening situation, it is an urgent demand to develop emerging nontraditional technologies or methods to address this issue. With the expanding of synthetic biology, optogenetics exhibits a tempting prospect for precisely regulating gene expression in many fields. Consequently, it is attractive to employ optogenetics to reduce the risk of antibiotic resistance. Here, a blue light-controllable gene expression system was established in Escherichia coli based on a photosensitive DNA-binding protein (EL222). Further, this strategy was successfully applied to repress the expression of ß-lactamase gene (bla) using blue light illumination, resulting a dramatic reduction of ampicillin resistance in engineered E. coli. Moreover, blue light was utilized to induce the expression of the mechanosensitive channel of large conductance (MscL), triumphantly leading to the increase of streptomycin susceptibility in engineered E. coli. Finally, the increased susceptibility of ampicillin and streptomycin was simultaneously induced by blue light in the same E. coli cell, revealing the excellent potential of this strategy in controlling multidrug-resistant (MDR) bacteria. As a proof of concept, our work demonstrates that light can be used as an alternative tool to prolong the use period of common antibiotics without developing new antibiotics. And this novel strategy based on optogenetics shows a promising foreground to combat antibiotic resistance in the future.

Comparative analysis of biofilm characterization of probiotic Escherichia coli.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Enhancing the Cooling Efficiency of Aluminum-Filled Epoxy Resin Rapid Tool by Changing Inner Surface Roughness of Cooling Channels.

In low-pressure wax injection molding, cooling time refers to the period during which the molten plastic inside the mold solidifies and cools down to a temperature where it can be safely ejected without deformation. However, cooling efficiency for the mass production of injection-molded wax patterns is crucial. This work aims to investigate the impact of varying surface roughness on the inner walls of the cooling channel on the cooling efficiency of an aluminum-filled epoxy resin rapid tool. It was found that the cooling time for the injection-molded products can be determined by the surface roughness according to the proposed prediction equation. Employing fiber laser processing on high-speed steel rods allows for the creation of microstructures with different surface roughness levels. Results demonstrate a clear link between the surface roughness of cooling channel walls and cooling time for molded wax patterns. Employing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm for low-pressure wax injection molding can save time, with a cooling efficiency improvement of approximately 34%. Utilizing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm on the inner walls of the cooling channel can save the cooling time by up to approximately 60%. These findings underscore the significant role of cooling channel surface roughness in optimizing injection molding processes for enhanced efficiency.

Engineering a Lactobacillus Lysine Riboswitch to Dynamically Control Metabolic Pathways for Lysine Production in Corynebacterium glutamicum.

Knock-out of genes of metabolic pathways is conventionally used in the metabolic engineering of microorganisms, but it is not applicable for genes of essential pathways. In order to avoid undesirable effects caused by gene deletion, it is attractive to develop riboswitches to dynamically control the metabolic pathways of microbial cell factories. In this regard, the aim of this study is to utilize the lysine riboswitch to control gene expressions of the biosynthetic pathways and by-pathways and thus improve lysine production in Corynebacterium glutamicum. To achieve this, a natural lysine riboswitch from Lactobacillus plantarum (LPRS) was first detected and then fused with RFP to test its functionality. After that, engineered lysine-activated (Lys-A) and lysine-repressed (Lys-R) riboswitches were successfully screened by dual genetic selection. Furthermore, the optimized A263 and R152 were applied to control the expression of aspartate kinase III and homoserine dehydrogenase in the lysine-producing strain C. glutamicum QW45, respectively. In contrast with QW45, the growth of the resulting A263-lysC mutant QW48 was similar to that of QW45; however, the growth of the resulting R357-hom mutant QW54 was slightly inhibited, indicating an inhibition of threonine biosynthesis caused by the riboswitch upon binding of intracellular lysine. Importantly, the lysine production of QW48 and QW54 was, respectively, 35% and 43% higher than that of the parent strain QW45, implying more metabolic flux directed into the lysine synthesis pathway. Finally, the engineered A263 and R357 were simultaneously applied to the same mutant QW55, which greatly improved lysine production. Thus, the approach demonstrated in this work could be principally used as a powerful tool to dynamically control any other undesired metabolic pathways.

Prevalence and associated factors of depression, anxiety and stress among clinical therapists in China in the context of early COVID-19 pandemic.

Objectives: To study the socio-demographic characteristics and the prevalence of depression, anxiety, and stress among clinical therapists in China during the early Coronavirus disease 2019 (COVID-19) pandemic and to identify associated factors. Method: This cross-sectional study was part of a multicenter, nationally representative survey conducted through WeChat from January 2021 to March 2021. Data, including socio-demographics, health-related behaviors, and information on whether they participated in the frontline work of treating COVID-19, were collected anonymously. Respondents also completed the Depression Anxiety Stress Scales-21 (DASS-21). Results: In total, 396 clinical therapists in the selected hospitals completed the questionnaires, with a response rate of 89.0%. Respondents were predominantly female (77.3%). About 6.6% of the participants were current tobacco users, and 20.7% had participated in the frontline work of treating COVID-19. Overall, 22.0%, 17.9%, and 8.8% of participants were classified as having clinically meaningful depression, anxiety, and stress, respectively, based on DASS-21 scores. Multiple logistic regression in Model 1 and Model 2 showed that depression, anxiety, and stress were associated with regular physical activity and frequent insomnia (all, p < 0.05). In anxiety model 2, the associated factors for anxiety during the pandemic were identified as education (master's degree or more, OR=0.520; 95% CI=0.283-0.955), marital status (single, OR=2.064; 95% CI=1.022-4.168), tobacco use (OR=4.265; 95% CI=1.352-13.454), regular physical activity (OR=0.357; 95% CI=0.192-0.663), frequent insomnia (OR=6.298; 95% CI =2.522-15.729), and participation in the frontline work of treating COVID-19 (OR=3.179; 95% CI=1.697-5.954). The COVID-19 epidemic did not significantly increase the depression and stress levels among clinical therapists, but it did significantly increase anxiety levels. Conclusion: During the COVID-19 pandemic, depression, anxiety and stress were relatively common among clinical therapists in China. Regular physical activity and good sleep were important protective factors against emotional problems. Therefore, encouraging regular physical activity and actively addressing clinical therapists' sleep problems is beneficial to improving the ability to cope with negative emotions. The COVID-19 epidemic significantly increased anxiety, and awareness and interventions should be recommended to reduce anxiety among clinical therapists during the COVID-19 pandemic.

Ultrafast Process Characterization of Laser-Induced Damage in Fused Silica Using Pump-Probe Shadow Imaging Techniques.

This study delves into the intricate dynamics of laser-induced damage in fused silica using a time-resolved pump-probe (TRPP) shadowgraph. Three typical ultra-fast processes, laser-induced plasma evolution, shockwave propagation and material fracture splashing, were quantitatively investigated. The results indicate that the diameter of plasma is proportional to the pulse laser energy and increases linearly during the pulse laser duration with an expansion rate of approximately 6 km/s. The maximum shockwave velocity on the air side is 9 km/s, occurring at the end of the pulse duration, and then rapidly decreases due to air resistance, reaching approximately 1 km/s around a 300 ns delay. After hundreds of nanoseconds, there is a distinct particle splashing phenomenon, with the splashing particle speed distribution ranging from 0.15 km/s to 2.0 km/s. The particle sizes of the splashing particles range from 4 µm to 15 µm. Additionally, the smaller the delay, the faster the speed of the splashing particles. Overall, TRPP technology provides crucial insights into the temporal evolution of laser-induced damage in fused silica, contributing to a comprehensive understanding essential for optimizing the performance and safety of laser systems.

The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. METHODS: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). RESULTS: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. CONCLUSION: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.

The association between mental health symptoms and alcohol use among Chinese psychiatrists during the early stage of the COVID-19 pandemic.

AIM: To investigate the association between mental health symptoms, alcohol use, and alcohol misuse among psychiatrists in China during the early stage of the COVID-19 pandemic. METHODS: We conducted an online survey to collect data regarding mental health symptoms and alcohol use among psychiatrists in early 2020. The Depression Anxiety Stress Scale-Chinese Version (DASS-21) was used to assess depression, anxiety, and stress symptoms, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to assess alcohol use. RESULTS: In total, 3774 psychiatrists completed the survey. AUDIT-C scores were positively correlated with DASS total and depression, anxiety, and stress subscales (total: r = 0.015, depression: r = 0.121, anxiety: r = 0.103, and stress: r = 0.096, all p < 0.05). Alcohol misuse was associated with male sex (OR = 4.754), cigarette smoking (OR = 2.441), administrative position (OR = 1.811), depression (OR = 1.489), and stress (OR = 1.504). Those who reported increased alcohol use during the pandemic were more likely to be male (OR = 2.174), endorse anxiety symptoms (OR = 2.386), or increased stress (OR = 2.402). CONCLUSIONS: Mental health symptoms were common among psychiatrists during the COVID-19 pandemic. Depression and stress symptoms were significantly associated with alcohol misuse. Anxiety and stress symptoms were associated with reported increases in alcohol use. Though a causal relationship cannot be inferred, our findings suggest that strategies promoting healthcare professionals' mental well-being should include alcohol use.

Prenatal diagnosis of developmental and epileptic encephalopathy 9 with a 10.05-Mb microdeletion at Xq21.31q22.1 inherited from mother: A case report and literature review.

BACKGROUND: Developmental and epileptic encephalopathy 9 (DEE9) is characterized by early infantile seizures and mild-to-severe neuropsychiatric symptoms. Despite being an X-linked dominant disorder, DEE9 mainly affects heterozygous females or mosaic males, while hemizygous males are less affected. PCDH19 gene has been documented as the causative gene. METHODS: Karyotyping analysis and copy number variation sequencing (CNV-seq) were performed on a pregnant woman with epilepsy, together with her husband, son, and fetus. RESULTS: A disease-causing microdeletion, seq[GRCh37] del(X)(q21.31q22.1) (90310001-100360000), was identified in the pregnant woman and her female fetus. The microdeletion includes the entire PCDH19 gene and is classified as "pathogenic" according to the American College of Medical Genetics and Genomics guidelines. CONCLUSION: In this case study, we have not only identified the epilepsy type of the woman as DEE9 but have also made an unfavorable prognosis for her fetus. Our findings from this prenatal case provide valuable clinical resources for prenatal diagnosis and genetic counseling, while also implying the potential of CNV-seq as a viable method for uncovering PCDH19-related epilepsy.

Evolution of intrinsic defects and ring structures on the surface of fused silica optics after CO2 laser conditioning.

Recently and interestingly, experiments show that the CO2 laser conditioning can significantly increase the laser-induced damage threshold (LIDT) of fused silica optics, but its underlying mechanism has not been clearly revealed. This Letter reports the experimental studies on the evolution of the intrinsic point defects and intrinsic ring structures on the surface of fused silica optics under the CO2 laser irradiation. The laser conditioning can effectively reduce the intrinsic defect contents in the surface layer of mechanically processed fused silica. However, the suppression effect of defects can be affected by the initial surface state. If there are micro-cracks on the component surface, the effect of the laser conditioning would be limited. The evolution of the intrinsic ring structures indicate that most of the intrinsic defects tend to recombine as short (Si-O)n ring structures during the laser healing of the micro-fractures. The observed recombination behavior and suppression of the intrinsic defects can help find out the reason for the increase of the LIDT of the fused silica optics.

Phytochromes transmit photoperiod information via the evening complex in Brachypodium.

BACKGROUND: Daylength is a key seasonal cue for animals and plants. In cereals, photoperiodic responses are a major adaptive trait, and alleles of clock genes such as PHOTOPERIOD1 (PPD1) and EARLY FLOWERING3 (ELF3) have been selected for in adapting barley and wheat to northern latitudes. How monocot plants sense photoperiod and integrate this information into growth and development is not well understood. RESULTS: We find that phytochrome C (PHYC) is essential for flowering in Brachypodium distachyon. Conversely, ELF3 acts as a floral repressor and elf3 mutants display a constitutive long day phenotype and transcriptome. We find that ELF3 and PHYC occur in a common complex. ELF3 associates with the promoters of a number of conserved regulators of flowering, including PPD1 and VRN1. Consistent with observations in barley, we are able to show that PPD1 overexpression accelerates flowering in short days and is necessary for rapid flowering in response to long days. PHYC is in the active Pfr state at the end of the day, but we observe it undergoes dark reversion over the course of the night. CONCLUSIONS: We propose that PHYC acts as a molecular timer and communicates information on night-length to the circadian clock via ELF3.

Excessive Daytime Sleepiness and Insomnia Symptoms in Adolescents With Major Depressive Disorder: Prevalence, Clinical Correlates, and the Relationship With Psychiatric Medications Use.

OBJECTIVE: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD. METHODS: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12-18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma'anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity. RESULTS: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027-1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028-1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199-3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052-3.633), suicide attempts (OR=1.765, 95% CI=1.037-3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523-2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196-0.952). CONCLUSION: EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.