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Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety–impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear.
The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety–impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures.
We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety–impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years.
We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety–impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up.
Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety–impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted.
Cyperus rotundus L. is a globally distributed noxious weed that poses a significant challenge for control due to its fast and efficient propagation through the tuber, which is the primary reproductive organ. Gibberellic acid (GA3) has proved to be crucial for tuberization in tuberous plants. Therefore, understanding the relationship between GA3 and tuber development and propagation of C.roundus will provide valuable information for controlling this weed. This study shows that the content of GA3 decreases with tuber development, which corresponds to lower expression of bioactive GA3 synthesis genes (CrGA20ox, two CrGA3oxs) and two up-regulated GA3 catabolism genes (CrGA2oxs), indicating that GA3 is involved in tuber development. Simultaneously, the expressions of CrDELLAs and CrGID1 decline with tuber growth and GA3 decreasing, and Yeast two-hybrid (Y2H) assays confirm that the GA3 signaling is DELLA-dependent. Furthermore, exogenous application of GA3 markedly reduces the number and the width of tuber, and represses the growth of tuber chain, further confirming the negative impact that GA3 has on tuber development and propagation. Taken together, these results demonstrate that GA3 is involved in tuber development and regulated by the DELLA-dependent pathway in C. rotundus, and plays a negative role in tuber development and propagation.
We tested the ability of our natural language processing (NLP) algorithm to identify delirium episodes in a large-scale study using real-world clinical notes.
We used the Rochester Epidemiology Project to identify persons ≥ 65 years who were hospitalized between 2011 and 2017. We identified all persons with an International Classification of Diseases code for delirium within ±14 days of a hospitalization. We independently applied our NLP algorithm to all clinical notes for this same population. We calculated rates using number of delirium episodes as the numerator and number of hospitalizations as the denominator. Rates were estimated overall, by demographic characteristics, and by year of episode, and differences were tested using Poisson regression.
In total, 14,255 persons had 37,554 hospitalizations between 2011 and 2017. The code-based delirium rate was 3.02 per 100 hospitalizations (95% CI: 2.85, 3.20). The NLP-based rate was 7.36 per 100 (95% CI: 7.09, 7.64). Rates increased with age (both p < 0.0001). Code-based rates were higher in men compared to women (p = 0.03), but NLP-based rates were similar by sex (p = 0.89). Code-based rates were similar by race and ethnicity, but NLP-based rates were higher in the White population compared to the Black and Asian populations (p = 0.001). Both types of rates increased significantly over time (both p values < 0.001).
The NLP algorithm identified more delirium episodes compared to the ICD code method. However, NLP may still underestimate delirium cases because of limitations in real-world clinical notes, including incomplete documentation, practice changes over time, and missing clinical notes in some time periods.
Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene–environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.
Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
In the Late Neoarchaean, the lithosphere of the North China Craton (NCC) experienced a strong extensional event, which is of great significance for understanding the evolution of the continental crust in the Precambrian. In this study, a suite of mafic dykes from Shandong province in the northeastern NCC were investigated to determine the nature, timing and source of rift-related magma activities using zircon U–Pb data, whole-rock geochemistry and Nd–Hf isotopes. Zircon U–Pb dating of four dolerites by laser ablation – inductively coupled plasma – mass spectrometry (LA-ICP-MS) yielded weighted mean 207Pb/206Pb ages in the range 2509 ± 6.1 to 2537 ± 6.2 Ma (2σ, 95 % confidence interval). The mafic dykes are classified as alkaline rocks based on their K2O + Na2O contents (6.78–7.21 wt %) and belong to the shoshonitic series according to their K2O contents (3.23–3.36 wt %). The dolerites show low concentrations of light rare earth elements ((La/Yb)N between 7.17 and 8.55), positive Eu anomalies (Eu/Eu* between 1.12 and 1.27), positive Ba, K, Pb, Sr, Eu, Dy and Lu anomalies, and depleted U, Nb, Pr, Ta, P, Nd and Ti anomalies. The dykes are characterized by low initial (87Sr/86Sr)i (∼0.6969), positive εNd(t) values (0.2–0.8) and εHf(t) values (0.5–8.6) and relatively old mean Nd and Hf model age (2.73 Ga). Collectively, the data suggest that the mafic dykes were derived from the partial melting (10–20 %) of an isotope-depleted garnet–lherzolite mantle source that was hybridized through interaction with subducted lower crustal material. The parental magmas of these dykes underwent a certain number of crustal contaminations during magma ascent. The mafic magmatism represented in the form of the dyke swarms is considered to be a response to widespread lithospheric extension which affected the NCC at c. 2.5 Ga during the Neoarchaean.
The frog-inspired robots with amphibious locomotion ability have greatest application prospects and practical value in the fields of resource exploration and environmental reconnaissance. Although frog-inspired robots have been of interest over many years, research on frog-inspired amphibious robots is still in its infancy. Since the locomotion mechanism is the basis for the research of frog-inspired amphibious robots, the research methods of the single motion mechanism of frogs are firstly inductive analyzed, and a reference scheme is proposed to inspire the research on the amphibious motion mechanism. Then, we collect and introduce a systematic discussion of the research status of frog-inspired robots according to the locomotion mode. The characteristics of the robots are analyzed from the aspects of design concept, structural characteristics, driving method, and motion performance. Finally, the technical challenges faced by the research on the frog-inspired robots are analyzed, and the development trend is predicted. The authors hope that this study can provide an informative reference for future research in the direction of frog-inspired amphibious robot.
Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.
Coronavirus disease (COVID-19) has spread worldwide due to high infectivity. The social sexual environment in rural areas of China and the weak basic medical facilities may affect the treatment and transmission of the disease. The aim of this study was to understand the knowledge, attitudes, and practices (KAP) related to COVID-19 among residents in rural areas experiencing the epidemic and the factors, to provide a basis for further epidemic prevention and control.
The COVID-19 KAP of rural residents in Hebei Province was collected by the snowball sampling method. The COVID-19 KAP questionnaire was distributed on social platforms such as WeChat and QQ through a network questionnaire.
The overall level of COVID-19 KAP in rural residents was good, but in terms of knowledge, the correct rate of isolation was 73.2%, the correct rates of 2 disinfection items were 72.3% and 77.4%, and the correct rate of hand-washing was 70.7%; 54.5% residents felt panic; 81.0% disinfected household items; and 84.9% washed their hands correctly. Residents still needed to strengthen these aspects. A binary logistic analysis showed that age, education, and participation in training were factors affecting the level of COVID-19 KAP.
This study found that rural residents had good levels of COVID-19 KAP, but there were gaps in specific issues that warrant attention. We advocate training on COVID-19 for rural residents.
Childhood trauma influences the clinical features of schizophrenia. In this study, we examined how childhood trauma and perceived stress are associated with clinical manifestations and subcortical gray matter volumes (GMVs) in patients with schizophrenia.
We recruited 127 patients with schizophrenia and 83 healthy controls for assessment of early childhood trauma, perceived stress, and clinical symptoms. With structural brain imaging, we identified the GMVs of subcortical structures and examined the relationships between childhood trauma, perceived stress, clinical symptoms, and subcortical GMVs.
Compared to controls, patients with schizophrenia showed higher levels of childhood trauma and perceived stress. Patients with schizophrenia showed significantly smaller amygdala and hippocampus GMVs as well as total cortical GMVs than age-matched controls. Childhood trauma score was significantly correlated with the severity of clinical symptoms, depression, perceived stress, and amygdala GMVs. Perceived stress was significantly correlated with clinical symptoms, depression, and hippocampus and amygdala GMVs. Further, the association between childhood trauma (emotional neglect) and stress coping ability was mediated by right amygdala GMV in patients with schizophrenia.
Patients with schizophrenia had more exposure to early-life trauma and poorer stress coping. Both childhood trauma and perceived stress were associated with smaller amygdala volumes. The relationship between early-life trauma and perceived stress was mediated by right amygdala GMV in patients with schizophrenia. These findings together suggest the long-term effects of childhood trauma on perceived stress and the subcortical volumetric correlates of the effects in schizophrenia.
Obsessive-compulsive personality disorder (OCPD) is a high-prevalence personality disorder characterized by subtle but stable interpersonal dysfunction. There have been only limited studies addressing the behavioral patterns and cognitive features of OCPD in interpersonal contexts. The purpose of this study was to investigate how behaviors differ between OCPD individuals and healthy controls (HCs) in the context of guilt-related interpersonal responses.
A total of 113 participants were recruited, including 46 who were identified as having OCPD and 67 HCs. Guilt-related interpersonal responses were manipulated and measured with two social interactive tasks: the Guilt Aversion Task, to assess how anticipatory guilt motivates cooperation; and the Guilt Compensation Task, to assess how experienced guilt induces compensation behaviors. The guilt aversion model and Fehr–Schmidt inequity aversion model were adopted to analyze decision-making in the Guilt Aversion Task and the Guilt Compensation Task, respectively.
Computational model-based results demonstrated that, compared with HCs, the OCPD group exhibited less guilt aversion when making cooperative decisions as well as less guilt-induced compensation after harming others.
Our findings indicate that individuals with OCPD tend to be less affected by guilt than HCs. These impairments in guilt-related responses may prevent adjustments in behaviors toward compliance with social norms and thus result in interpersonal dysfunctions.
Family functioning is associated with anxiety and depression. Perinatal depression and anxiety are common and influence the well-being of women, partners and their offspring. However, little is known about differences in associations between family functioning and mood symptoms in women and their partners in early pregnancy.
Investigating differences in associations between family functioning and anxious and depressive symptoms in women and their partners in early pregnancy.
In total, 171 woman–partner pairs were enrolled. The Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item scale (GAD-7) and Family Assessment Device (FAD) were performed. Correlation analysis and multiple linear regression analysis were applied to investigate the associations.
In pregnant women, all the subscale scores on the FAD were correlated with total scores on the EPDS and GAD-7 (all P < 0.05), whereas only the Roles subscale showed a predicting effect in regression models (P < 0.01). In partners, all the subscale scores on the FAD were related to total scores on the PHQ-9 (all P < 0.05), whereas only the Problem Solving subscale showed a predicting effect (P = 0.029).
Our findings indicate that family functioning in the domain of roles is associated with anxious and depressive symptoms in pregnant women and functioning in the domain of problem solving is associated with depressive symptoms in partners. Clinicians should pay special attention to roles and problem solving when assessing mood symptoms in pregnant women and their partners. This study also provides a basis for family health education in early pregnancy.
Complex fault patterns associated with rift development in the Hailar Basin were largely influenced by the Mongolia–Okhotsk Ocean and Palaeo-Pacific tectonic regimes during the Late Jurassic to Early Cretaceous periods. Based on 3D seismic data from the Beier Depression in the Hailar Basin, we characterized the reactivation history of multi-trend major faults and examined the evolution of the Beier Depression during the Early Cretaceous period. NE–SW-, NW–SE- and ENE–WSW-oriented major faults originated from strike-slip-associated structures that were pre-existing fabrics and then were reactivated and propagated upward under extensional regimes in the Late Jurassic. During the syn-rift stage (K1t–K1n), the Hailar Basin was in a NNW–SSE- to NW–SE-oriented extensional setting, and major faults of all orientations were active. There was tectonic quiescence (K1n1L) between the syn-rift stages (a rifting transition stage). The short compression stage after the syn-rift stage caused regional compressional deformation. During the post-rift stage (K1d–K1y), the extension direction rotated to an E–W orientation, and a new population of N–S-trending faults formed together with the reactivation of NE–SW- and ENE–WSW-trending major faults. Structural analysis shows that the major ENE–WSW-trending major faults were polycyclic growth faults reactivated via an upward propagation mode and that the NE–SW-trending faults were dip linkage faults reactivated via a dip linkage mode. The reactivation intensity of the NE–SW-trending major faults was stronger than that of the ENE–WSW-trending major faults. These results demonstrate the differences in the evolution of the different trending faults in the same tectonic regime, and the complexity of the final fault patterns in the Beier Depression was produced by differences in the reactivation of major faults. The originate interpretation of the multi-trend major faults in the Hailar Basin provides new insights into fault generation, and the classification of fault growth also has useful implications for future research on multiphase rifts.
The sequential occurrence of three layers of smooth muscle layers (SML) in human embryos and fetus is not known. Here, we investigated the process of gut SML development in human embryos and fetuses and compared the morphology of SML in fetuses and neonates. The H&E, Masson trichrome staining, and Immunohistochemistry were conducted on 6–12 gestation week human embryos and fetuses and on normal neonatal intestine. We showed that no lumen was seen in 6–7th gestation week embryonic gut, neither gut wall nor SML was developed in this period. In 8–9th gestation week embryonic and fetal gut, primitive inner circular SML (IC-SML) was identified in a narrow and discontinuous gut lumen with some vacuoles. In 10th gestation week fetal gut, the outer longitudinal SML (OL-SML) in gut wall was clearly identifiable, both the inner and outer SML expressed α-SMA. In 11–12th gestation week fetal gut, in addition to the IC-SML and OL-SML, the muscularis mucosae started to develop as revealed by α-SMA immune-reactivity beneath the developing mucosal epithelial layer. Comparing with the gut of fetuses of 11–12th week of gestation, the muscularis mucosae, IC-SML, and OL-SML of neonatal intestine displayed different morphology, including branching into glands of lamina propria in mucosa and increased thickness. In conclusions, in the human developing gut between week-8 to week-12 of gestation, the IC-SML develops and forms at week-8, followed by the formation of OL-SML at week-10, and the muscularis mucosae develops and forms last at week-12.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case–control study of 260 AMD cases and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95 % confidence interval (CI) of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs (95 % CI) were 0·30 (0·10, 0·88) for lutein and 0·28 (0·11, 0·74) for β-cryptoxanthin. The associations for other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD. ORs (95% CIs) comparing extreme categories were 0·42 (0·20, 0·88) for spinach and 0·52 (95% CI: 0·27, 0·98) for egg. Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0·23; 95% CI: 0·08, 0·71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.
The aim of this study was to explore the status of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in three areas with differing water iodine concentrations; and to discuss the relationships between these two thyroid antibodies and thyroid diseases in the three areas. We investigated 2503 adults from three areas. Urinary iodine concentrations, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), TPOAb, TGAb and thyroid volume (TV) were measured, and thyroid ultrasonography was performed. The positivity rates of TGAb(+), TPOAb(+) and TGAb(+) and TPOAb(+) or TGAb(+) were significantly higher in iodine fortification (IF) areas than iodine adequate (IA) areas (all P < 0·05). In IF and iodine excess areas, the positivity rates of TPOAb(+), TGAb(+) and TPOAb(+) or TGAb(+) significantly increased with age (all P for trend < 0·05). The levels of TSH, TV and the prevalence of overt hypothyroidism, subclinical hypothyroidism and goitre were significantly elevated in the thyroid antibody-positive groups in the three areas, but the FT3 was diminished (all P < 0·010). Positivity for TPOAb and TGAb was associated with an increased risk of subclinical hypothyroidism in the three areas. In areas with different median water iodine, positivity for both TPOAb and TGAb was associated with elevated TSH values. Notably, with the increased levels of TPOAb, the frequency of abnormally elevated TSH increased dramatically in the three areas.