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This paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD. Twenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample -test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain. Compared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC). OCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD.

Obsessive-compulsive disorder (OCD) is thought to arise from dysconnectivity among interlinked brain regions resulting in a wide spectrum of clinical manifestations. Cortical gyrification, a key morphological feature of human cerebral cortex, has been considered associated with developmental connectivity in early life. Monitoring cortical gyrification alterations may provide new insights into the developmental pathogenesis of OCD. Sixty-two medication-naive patients with OCD and 59 healthy controls (HCs) were included in this study. Local gyrification index (LGI) was extracted from T1-weighted MRI data to identify the gyrification changes in OCD. Total distortion (splay, bend, or twist of fibers) was calculated using diffusion-weighted MRI data to examine the changes in white matter microstructure in patients with OCD. Compared with HCs, patients with OCD showed significantly increased LGI in bilateral medial frontal gyrus and the right precuneus, where the mean LGI was positively correlated with anxiety score. Patients with OCD also showed significantly decreased total distortion in the body, genu, and splenium of the corpus callosum (CC), where the average distortion was negatively correlated with anxiety scores. Intriguingly, the mean LGI of the affected cortical regions was significantly correlated with the mean distortion of the affected white matter tracts in patients with OCD. We demonstrated associations among increased LGI, aberrant white matter geometry, and higher anxiety in patients with OCD. Our findings indicate that developmental dysconnectivity-driven alterations in cortical folding are one of the neural substrates underlying the clinical manifestations of OCD.

Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene. Genetic risk factors for depression This genomic analysis of more than 5,000 Chinese women with recurrent major depressive disorder (MDD) has identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10. One is near the sirtuin1 ( SIRT1 ) gene, and the other is in an intron of the phospholysine phosphohistidine inorganic pyrophosphate phosphatase ( LHPP ) gene. The authors suggest that the association close to SIRT1 may implicate abnormalities in mitochondria as risk factors for the disease. Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide 1 , poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified 2 , despite analysis of more than 9,000 cases 3 . Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene ( P  = 2.53 × 10 −10 ), the other in an intron of the LHPP gene ( P = 6.45 × 10 −12 ). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2.53 × 10^sup -10^), the other in an intron of the LHPP gene (P = 6.45 × 10^sup -12^). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants. The SARS-CoV-2 spike (S) protein mediates viral entry by binding of its receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor and mutations of the S protein may have a great impact on virus transmissibility. Here, the authors characterize the interactions of six different SARS-CoV-2 RBD variants among them Alpha, Beta and Gamma and present crystal structures of these ACE2-RBD complexes.

This work investigated the mechanistic role of chloride ions (Cl−) in the Belousov–Zhabotinsky (B-Z) oscillating reaction. We conducted a multivariate statistical analysis of the B-Z response, established a quadratic polynomial regression model, and determined the contributions of the experimental parameters to the induction time. The results indicate that the relationship between the experimental parameters and the induction time is often nonmonotonic, exhibiting secondary dependence. Then, we studied the influence mechanism by which Cl− affects the B-Z reaction system. Both experimental and theoretical studies indicate that as the concentration of Cl− increases, the system becomes more active as the activation energy increases. When the Cl− concentration is less than 1 mmol/L, the induced apparent activation energy remains relatively constant. However, as the Cl− concentration increases from 1.00 mmol/L to 2.00 mmol/L, the induced apparent activation energy increases rapidly from 50 kJ/mol to 120 kJ/mol, which severely hinders the induction period and then increases the induction time.

Hydraulic active suspension has the coupling characteristics of integrated mechanical-hydraulic-control system, and its performance is also affected by external interference, noise interference, and other factors. Therefore, a novel controller is presented to achieve system-level optimal performances by using the collaborative control method. The proposed collaborative method is provided an implementation framework, and includes outer loop control of Linear Quadratic Regulator (LQR), inside loop control of modified linearized active disturbance rejection control (M-LADRC) and Kalman filter, and so on. In addition, the semi-physical simulation method is used to the simulation and test, and the force tracking control test for hydraulic servo system and Kalman filter test are carried out. Finally, the performance of semi-physical active suspension is compared with that of the ideal active suspension and passive suspension under the different road profile excitation. The superiority and effectiveness are verified for the collaborative control method. The collaborative controller has improved the suspension system performance and is more practical, which is beneficial for the application of the achievements.

Introduction Anxiety and depression often co-occur in adolescents, with factors from family and school playing a significant role in the comorbidity. However, network analysis has not examined and clarified the detailed bridge and central symptoms of this comorbidity caused by online learning and perceived parental relationships across different COVID-19 times. Methods Over four months, 2,356 secondary school students completed the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7. Participants were divided into harmonious and disharmonious groups based on their answers to a question about parental conflicts. Results The results indicated that adolescents perceiving more parental conflicts showed a denser comorbidity network after four months of online learning. Significant bridge symptoms decreased from three to two across two waves in the harmonious group, while in the disharmonious group, they increased from two to three. The number of central symptoms increased from one in wave 1 to three in wave 2 for the harmonious group, while four in wave 1 decreased to two in wave 2 for the disharmonious group. Furthermore, the CLPN analysis revealed that the strongest positive cross-lagged edge intensity between symptoms was anhedonia—energy in the harmonious group, with anhedonia being the most trigger symptom. In contrast, for the disharmonious group, guilt—suicide and trouble relaxing—excessive worry were the strongest cross-lagged edge, and trouble relaxing was the most trigger symptom. Conclusion These findings may have implications for interventions designed to promote adolescent mental health in the context of online learning and parental conflicts.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2–related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.