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Background The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. Methods Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. Results Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%–1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%–57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. Limitations The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. Conclusions Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

N6-methyladenosine (m6A) modification plays a critical role in mammalian development. However, the role of m6A in the skeletal muscle development remains largely unknown. Here, we report a global m6A modification pattern of goat skeletal muscle at two key development stages and identified that the m6A modification regulated the expression of the growth arrest and DNA damage-inducible 45B (GADD45B) gene, which is involved in myogenic differentiation. We showed that GADD45B expression increased during myoblast differentiation, whereas the downregulation of GADD45B inhibits myogenic differentiation and mitochondrial biogenesis. Moreover, the expression of GADD45B regulates the expression of myogenic regulatory factors and peroxisome proliferator-activated receptor gamma coactivator 1 alpha by activating the p38 mitogen-activated protein kinase (MAPK) pathway. Conversely, the inactivation of p38 MAPK abolished the GADD45B-mediated myogenic differentiation. Furthermore, we found that the knockdown of fat mass and obesity-associated protein (FTO) increases GADD45B m6A modification and decreases the stability of GADD45B mRNA, which impairs myogenic differentiation. Our results indicate that the FTO-mediated m6A modification in GADD45B mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation., Graphical abstract, Deng et al. provide the transcriptome-wide m6A map of goat skeletal muscle and demonstrate that FTO-mediated m6A modification in GADD45B mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation.

Summary Background In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012–15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age–sex–residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20–1·72] and 12-month prevalence OR 1·41 [1·12–1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68–3·38] and 12-month OR 2·80 [95% CI 1·88–4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39–2·51] and 12-month OR 1·85 [95% CI 1·40–2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Backlash-induced variations may lead to teeth separation and back-side tooth mesh in lightly loaded geared drive. Effects of teeth separation and back-side tooth mesh are considered. The dynamic model of a spur gear pair under multi-state meshing conditions such as teeth separation, drive- and back-side tooth mesh is established based on the gear transmission principle and forces acting on teeth. Time-varying meshing stiffness, time-varying friction, load distribution, comprehensive transmission error and backlash are included in the model. Variations of the dynamic meshing force of the system under different meshing states are analyzed numerically. The dynamic meshing force affects the meshing state of the system significantly. Furthermore, the effects of load, backlash and comprehensive transmission error on meshing states and vibro-impact properties of the system are studied by defining three different Poincare maps, where bifurcation diagrams, top Lyapunov exponent diagrams (TLE), phase portraits are used. Results indicate that the complicated phenomena such as drive-side impact, teeth separation and back-side impact gradually occur with the decrease of the load or the increase of the comprehensive error. However, these phenomena always exist with the increase in backlash. This study provides a theoretical reference for the optimization of gears.

The present work investigated the efficacy of social cognition and interaction training (SCIT) for patients with major depression. Thirty first-episode patients with major depression who received the SCIT plus the treatment-as-usual (i.e., SCIT + TAU group) were compared with twenty-nine patients who only received treatment-as-usual (i.e., TAU group). Patients received SCIT showed a significantly greater improvement on emotion perception, theory of mind, and attributional styles from baseline to follow-up assessments, with a significant reduction of severity of depressive symptoms, compared to those in TAU group. The preliminary findings indicate that SCIT is a feasible and promising method to improve social cognition for patients with major depression.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability (YLDs). However, nationally representative epidemiological data for depressive disorders, in particular depressed adults’ mental health services use, are still unavailable in China. The present study is a part of the Chinese National Mental Health Survey (CMHS), 2012–15, which reported the prevalence, treatment, and associated disability of depressive disorders in the Chinese general population. Methods: The CMHS recruited a representative sample of 28140 Chinese residents (≥ 18 years) by using multistage proportional-to-population-size sampling method. Trained investigators interviewed participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder (MDD), dysthymic disorder (DD), and depressive disorder not otherwise specified (DD-NOS). Participants with 12-month depressive disorders were asked whether they ever received any 12-month treatment for their emotional problems and the specific types of treatment providers. The Quick Inventory of Depressive Symptomatology and Sheehan Disability Scale (SDS) were used to evaluate the severity of and role impairments associated with 12-month depressive symptoms. Findings: The weighted lifetime and 12-month prevalence rates of any depressive disorder were 6.8% (95%CI: 5.8-7.8%) and 3.6% (95%CI: 3.0-4.2%), respectively; the corresponding figures were 3.4% (95%CI: 2.0-3.9%) and 2.1% (95%CI: 1.8-2.4%) for MDD, 1.4% (95%CI: 1.1-1.7%) and 1.0% (95%CI: 0.8-1.3%) for DD, and 3.2% (95%CI: 2.6-3.9%) and 1.4% (95%CI: 1.1-1.7%) for DD-NOS. Overall, 77.2% of persons with 12-month depressive disorders had role impairment of any SDS domain: 82.2% for MDD, 81.5% for DD, and 64.6% for DD-NOS. Depressed participants reported an average of 41.0 days out of role in the past year due to depression; the corresponding figures were 49.7 days for MDD, 54.9 days for DD, and 12.2 days for DD-NOS. In total, 88.9% of individuals with 12-month depressive disorders had clinically significant depressive symptoms: 93.7% for MDD, 91.7% for DD, and 77.5% for DD-NOS. MDD and DD had similar proportions of “severe” or “very severe” depressive symptoms (43.0% and 42.1%), which were higher than DD-NOS (13.9%). 9.5% of participants with 12-month depressive disorders were treated in any treatment sector: 3.6% in the specialty mental health (SMH), 1.5% in the general medical (GM), 0.3% in the human services (HS), and 3.3% in the complementary-alternative medical (CAM) sector. Respondents with MDD and DYS had the highest proportion of seeking treatment in SMH sector (4.7% and 3.0%) while those with DD-NOS had the highest proportion of seeking treatment in CAM sector (most treatments were Traditional Chinese Medicine) (3.3%). Only 0.5% of participants with depressive disorders were treated adequately. Rates of treatment adequacy of MDD and DYS in SMH sector were 9.2% and 2.4%, respectively. Both rates in GM sector were 0%. Interpretation: Compared to western countries, our data show a relatively low prevalence of depressive disorders in China. Nevertheless, their associated role impairments, symptom severities, and disabilities are severe. Importantly, the treatment rates are rather low, let alone adequate treatment. Nationwide programs aiming at removing barriers in availability, accessibility, and acceptability to mental healthcare are needed in China. Funding: The study was funded by the Special Research Project for Non-profit Public Service of the Chinese Ministry of Health (grant number 201202022), the National Twelfth Five-Year Plan for Science and Technology Support of the Chinese Ministry of Science and Technology (grant numbers 2012BAI01B01 & 2015BAI13B00) and the National Key R&D Program of China (grant numbers 2017YFC0907800, 2017YFC0907801). Declaration of Interests: The authors have no conflicts of interest to declare Ethical Approval: The study protocol of CMHS was approved by the Ethics Committee of the Sixth Hospital of Peking University (No.: IMH-IRB-2013-13-1).

The Yangtze River delta white goat is the only goat breed that produces high-quality brush hair, which is specifically used in top-grade writing brushes. Previous studies have indicated that the CMTM3 and DUSP1 genes are involved in the growth and cycle of high-quality brush hair, and these genes are thought to be involved in the formation of high-quality brush hair traits. In this study, we investigated the relationship between methylation of CMTM3 and DUSP1 and such traits. The results indicated that the relative expression levels of the CMTM3 and DUSP1 genes were higher in non-high-quality brush hair than in high-quality brush hair. Furthermore, the CpG sites of the DUSP1 gene were not methylated, and the methylation level of CMTM3 was negatively correlated with the gene expression level. We believe that the DUSP1 gene regulates the formation of high-quality brush hair by non-methylated, and that methylation of the CMTM3 gene results in a decrease in its expression, causing an increase in the activity of the androgen receptor and the level of androgen. This high androgen level promotes the growth of high-quality brush hair. These study results provide a theoretical basis for further elucidating the molecular mechanism of the formation of high-quality brush hair characteristics, and provide scientific reference for the molecular breeding of high-quality brush hair.

The pitch deviation caused by machining error affects the transmission stationarity of the spur gear pair. It results in time-variation of the contact ratio for the system by corner contact. Meshing characteristics of the spur gear pair with the pitch deviation are studied in order to analyze the time-varying contact ratio and motion characteristics of the system. The mathematical model of time-varying contact ratio is established to explore its time-varying characteristics. Dynamics model of the spur gear pair with the pitch deviation considering time-varying contact ratio under multi-state meshing is proposed. The transmission stationarity of the spur gear pair are explored by dynamic meshing forces. The influence of system parameters and operating parameters on dynamics characteristics of the spur gear pair with the pitch deviation considering time-varying contact ratio is studied by bifurcation diagrams, phase portraits and Poincare maps. Results show that the pitch deviation as a short-period error in the spur gear pair leads to complex periodic motions. The possibility of the tooth disengagement, back-side teeth contacting and chaotic motion for the spur gear pair increases with the increase of complexity of pitch deviation values. The transmission accuracy and stationarity for the spur gear pair decrease when pitch deviation values are complex. This study provides a theoretical basis for dynamics modeling and stationarity analysis of the spur gear transmission system and other gear transmission systems.

The pitch deviation of gears caused by machining leads to corner contact in actual meshing process. In order to study the influence of the pitch deviation on motion characteristics of the spur gear pair, meshing state functions are constructed to reflect multi-state meshing including mesh-in at corner contact, mesh-out at corner contact, single and double pair drive-side teeth mesh, single and double pair back-side teeth contact and tooth disengagement. The nonlinear dynamics model of spur gear pair with pitch deviations under multi-state meshing is established. Variation laws of dynamic meshing forces and meshing states for the spur gear pair are analyzed. The influence of main parameters on nonlinear dynamics of the spur gear pair with pitch deviations is investigated. Results indicate that the pitch deviation results in complex periodic motion as a short-period error in spur gear pair. It mainly affects transmission stability of the spur gear pair by changing meshing states. This investigation provides a theoretical basis for the parameter design of the spur gear transmission system and the influence of pitch deviation in other gear transmission systems.

The safe operation of gear pairs is the basic safety guarantee of the machine. The safety of the gear pair may be destroyed due to transfinite of kinematic variables and system parameters. In order to reveal its evolutionary mechanism, the safety characteristics of the spur gear pair are researched under the established safety domain. A nonlinear dynamics model of the spur gear pair considered multi-state meshing is introduced. The comprehensive teeth contact safety domain of the spur gear pair to prevent tooth surface contact fatigue, tooth surface plastic deformation and tooth root bending fatigue is established. A method of judging safety characteristics of the system is given. The safety basins, phase portraits and Poincare mappings are computed to reveal the distribution of the coexistence attractors and judge the safety characteristics of the system motions under the established safety domain in the state space. Multi-initial values bifurcation diagrams and the corresponding top Lypunov exponents (TLE) via the change of the backlash, the fluctuation coefficient of the comprehensive transmission error and the external load are used to catch the motions in the studied state space and study their transition. Bifurcation & safety dendrograms are constructed to study the evolutionary processes of the system safety characteristics. System parameters are divided into two types according to their influence on the erosion and bifurcation of the system safety basins. Two patterns to change the system safety characteristics from safe to unsafe are found. The sensitive parameters of meshing state change the safety characteristics by one-to-two bifurcation. The sensitive parameters of dynamic characteristics mainly affect the safety characteristics by changing the amplitude of kinematic variables and the dynamic response of the tooth disengagement or back-side teeth contacting state. The study is helpful in the selection of system parameters for mitigation and design against fatigue.

Olanzapine is an atypical antipsychotic drug that has been increasingly used for treatment in schizophrenia. It has been observed that olanzapine responses in schizophrenia patients vary individually, but the reason has not been elucidated. In the study, we aimed to comprehensively explore the relationships between olanzapine responses and genetic polymorphisms of drug metabolizing enzymes, transporters and target receptors, and so as to interpret the reason of good and poor responses of olanzapine. A total of 241 Chinese Han paranoid schizophrenia who treated with olanzapine alone for 4 weeks were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of olanzapine. The genetic polymorphisms were detected by improved multiple ligase detection reaction (iMLDR). Multivariate logistic regression analysis suggested that the genetic polymorphisms of CYP1A2 rs762551, UGT1A4 rs2011425, ABCB1 rs1045642, DRD2 rs1799732 and rs1799978, 5-HTR2A rs6311 were significantly associated with olanzapine response. Multifactor dimensionality reduction (MDR) analysis showed that there was a negative interaction between CYP1A2 rs762551, ABCB1 rs1045642, DRD2 rs1799978, 5-HTR2A rs6311 and the interaction model was the optimal model. Our findings could partially explain the different olanzapine outcome and provided evidence for clarifying the predictive indicators of olanzapine response in further.

Backlash plays a significant role in gear design and geared dynamics analysis. This study aims to establish a model of the time-varying backlash for a standard involute spur gear pair. The elastic deformations, thermal deformations and film thickness deformation at the meshing point are considered in this model. Asperity and fluid loads are included in film thickness. A time-varying backlash model with contact ratio is developed according to the force analysis at the meshing point. The contributions and effects of the various deformations on the backlash are analyzed. The effects of rotation speed, torque load and tooth surface temperature on the time-varying backlash are studied. Results show that the influence of various parameters on the backlash cannot be ignored. The time-varying backlash is less affected by elastic deformation and oil film thickness deformation, and is greatly affected by the thermal deformation. The time-varying backlash increases with the increase of torque load and the decreases of rotation speed and tooth surface temperature. Tooth surface temperature is validated experimentally due to its importance in the established model.

A face-gear drive system has been extensively used in important transmission devices with strict requirements for size and weight such as helicopter reducer and so on. Its dynamic characteristics directly affect the stability and reliability of the equipment. A piecewise torsional-bending-pendular nonlinear dynamics model of the face-gear drive system is established to study its nonlinear dynamics and dynamic characteristics. The multi-state engagements including drive-side teeth engaging, teeth disengagement, back-side teeth engaging, and alternate engaging between single-teeth pair and double-teeth pairs caused by the couple of the backlash and the contact ratio being greater than 1.0 is considered. The change of the dynamic engaging force and load distribution ratio for the system is analyzed by numerical results under three different states engagement. The effects of the load coefficient, meshing frequency and the comprehensive transmission error on the dynamic characteristics and nonlinear dynamics of the system are studied based on three different Poincare mappings defined by bifurcation diagrams, top Lyapunov exponent diagrams, phase portraits and variation curve of the dynamic engaging force. Results show that the complex phenomena such as teeth disengagement, drive-side and back-side impact occur with alternating meshing of the single and double pair teeth via the change of studied parameters. The research is helpful for the optimization of the face-gear drives.