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Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
The fall armyworm (Spodoptera frugiperda), a destructive pest that originated in South and North America, spread to China in early 2019. Controlling this invasive pest requires an understanding of its population structure and migration patterns, yet the invasion genetics of Chinese S. frugiperda is not clear. Here, using the mitochondrial cytochrome oxidase subunit I (COI) gene, triose phosphate isomerase (Tpi) gene and eight microsatellite loci, we investigated genetic structure and genetic diversity of 16 S. frugiperda populations in China. The Tpi locus identified most S. frugiperda populations as the corn-strains, and a few were heterozygous strains. The microsatellite loci revealed that the genetic diversity of this pest in China was lower than that in South America. Furthermore, we found moderate differentiation among the populations, distinct genetic structures between adjacent populations and abundant genetic resources in the S. frugiperda populations from China sampled across 2 years. The survival rate of S. frugiperda was significantly higher when it was fed on corn leaves than on rice leaves, and the larval stage mortality rate was the highest under both treatments. Our results showed that S. frugiperda probably invaded China via multiple independent introductions and careful pesticide control, continuous monitoring and further studies will be needed to minimize its potential future outbreak.
Globalization in clinical trials for Alzheimer’s disease (AD) drug development has increased rapidly. It would substantially support persons with dementia to access novel therapeutics in a coordinated and efficient manner. In this chapter, we overview the significant drives of globalization in AD drug development: the growth of the world’s AD population, the need for a larger sample in trials to secure enrollment in the required timeframe, and the ethnographic and ethnobiological contributors. We also discuss the major issues relevant to global trials: the geographic variation across trial sites, the differences in study participants, and the lack of harmonized global regulatory mechanisms. In the end, this chapter recommends that improving site performance, enhancing infrastructure development, and promoting universal regulatory mechanism should be prioritized to maximize the contribution of globalization to the AD drug development ecosystem.
This study presents a novel context awareness multihuman–robot interaction (MHRI) system that allows multiple operators to interact with a robot. In the system, a monocular multihuman 3D pose estimator is first developed with the convolutional neural network. The estimator first regresses a set of 2D joints representations of body parts and then restores the 3D joints positions based on these 2D representations. Further, the 3D joints are assigned to the corresponding individual with a priority–redundancy association algorithm. The whole 3D pose of each person is reconstructed in real time, even in crowded scenes containing both self-occlusion of the body and inter-person occlusion. Then, the identities of multiple persons are recognized with action context and 3D skeleton tracking to improve interactive efficiency. For context-awareness multitask interaction, the robot control strategy is designed based on target goal generation and correction. The generated goal is taken as a reference to the model predictive controller (MPC) to generate motion trajectory. Different interactive requirements are adapted by adjusting the weight parameters of the energy function of the MPC controller. Multihuman–robot interactive experiments, including dynamic obstacle avoidance (human–robot safety) and cooperative handling, demonstrate the feasibility and effectiveness of the MHRI, and the safety and collaborative efficiency of the system are evaluated with HRI metrics.
This retrospective study investigated the predictive value of the Controlling Nutritional Status (CONUT) score in patients with intermediate-stage hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). Nomograms were developed to predict progression-free and overall survival (PFS, OS). The medical data of 228 patients with HCC and treated with TACE were collected. The patients were apportioned to 2 groups according to CONUT score: low or high (<4, ≥4). Univariate and multivariate analyses were performed using Cox regression for OS and PFS. OS and PFS were estimated by the Kaplan-Meier curve and compared with the log-rank test. Nomograms were constructed to predict patient OS and PFS. The nomograms were evaluated for accuracy, discrimination, and efficiency. The cut-off value of CONUT score was 4. The higher the CONUT score, the worse the survival; Kaplan-Meier curves showed significant differences in OS and PFS between the low and high CONUT score groups (P = 0·033, 0·047). The nomograms including CONUT, based on the prognostic factors determined by the univariate and multivariate analyses, to predict survival in HCC after TACE were generated. The CONUT score is an important prognostic factor for both OS and PFS for patients with intermediate HCC who underwent TACE. The cut-off value of the CONUT score was 4. A high CONUT score suggests poor survival outcomes. Nomograms generated based on the CONUT score were good models to predict patient OS and PFS.
Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor, belonging to the tyrosine kinase receptor superfamily. IGF1R plays a role not only in normal cell development but also in malignant transformation, which has become a candidate therapeutic target for the treatment of human cancer. This study aimed to explore insertions and deletions (indels) in IGF1R gene and investigate their association with growth traits in four Chinese cattle breeds (Xianan cattle, Jinnan cattle, Qinchuan cattle and Nanyang cattle). The current paper identified a 28-bp indel by polymerase chain reaction within IGF1R gene. The analysis showed that there was a significant correlation between the locus and the hucklebone width of Nanyang cattle in four periods, in which it was highly correlated at 6, 12 and 18 months. At the age of 6 months, it was also significantly correlated with body height, body weight and body length. Association analysis showed that the locus in Jinnan cattle was extremely significantly correlated with body slanting length and body weight, and significantly correlated with chest circumference. There was no significant correlation between this locus and growth traits of Xianan cattle and Qinchuan cattle. The detected indel in the IGF1R gene was significantly associated with growth traits in Jinnan and Nanyang cattle, and could be used as a molecular marker for growth trait selection.
Empirical research is largely supportive of the assertion of instrumental stakeholder theory that a positive relationship exists between “managing for stakeholders” and firm performance. However, despite considerable debate on the subject, the amount of variation across firm investments in stakeholders (stakeholder management performance) has not been adequately investigated. We address this gap using a sample of more than eighteen thousand firm-level observations over ten years. We find evidence to support an inverted U–shaped relationship between variation in stakeholder management performance and Tobin’s q, suggesting that firms that have some imbalance in their stakeholder management, but not too much, perform best. We discuss the implications of our study for instrumental stakeholder theory and managerial practice.
This paper presents a method to solve the kinematics of a rigid-flexible and variable-diameter continuous manipulator. The multi-segment underwater manipulator is driven by McKibben water hydraulic artificial muscle (WHAM). Considering the effect of elasticity and friction, we optimized the static mathematical model of WHAM. The kinematic model of the manipulator with load is established based on the hypothesis of piecewise constant curvature (PCC). We developed an optimization algorithm to calculate the length of the WHAMs according to the principle of minimum strain energy and obtain the configuration space parameters of the kinematic model. Based on the infinitesimal method, the homogeneous transformation matrices of the variable-diameter bending sections are computed, and the terminal position and attitude are obtained. In this paper, we studied the working space of the manipulator by quantitative analysis of the impact factors including pressure and load. A deep neural network (DNN) with six hidden layers is designed to solve inverse kinematics. The forward kinematic results are used to train and test the DNN, and the correlation coefficient between the output and target samples reaches 0.945. We carried out an underwater experiment and verified the effectiveness of the kinematic modeling and solution method.
China accounts for 17% of the global disease burden attributable to mental, neurological and substance use disorders. As a country undergoing profound societal change, China faces growing challenges to reduce the disease burden caused by psychiatric disorders. In this review, we aim to present an overview of progress in neuroscience research and clinical services for psychiatric disorders in China during the past three decades, analysing contributing factors and potential challenges to the field development. We first review studies in the epidemiological, genetic and neuroimaging fields as examples to illustrate a growing contribution of studies from China to the neuroscience research. Next, we introduce large-scale, open-access imaging genetic cohorts and recently initiated brain banks in China as platforms to study healthy brain functions and brain disorders. Then, we show progress in clinical services, including an integration of hospital and community-based healthcare systems and early intervention schemes. We finally discuss opportunities and existing challenges: achievements in research and clinical services are indispensable to the growing funding investment and continued engagement in international collaborations. The unique aspect of traditional Chinese medicine may provide insights to develop a novel treatment for psychiatric disorders. Yet obstacles still remain to promote research quality and to provide ubiquitous clinical services to vulnerable populations. Taken together, we expect to see a sustained advancement in psychiatric research and healthcare system in China. These achievements will contribute to the global efforts to realize good physical, mental and social well-being for all individuals.
The late Palaeozoic Yong’an–Meizhou depression belt is an important iron (Fe) and polymetallic metallogenic belt in southern China. It has undergone a transformation from Tethys to the circum-Pacific tectonic domain. The Luoyang deposit is one of the typical Fe skarn deposits in the Yong’an–Meizhou depression belt of eastern China. Garnet is a characteristic mineral in the deposit. Two generations of garnets are detected in the deposit based on their textural characteristics and trace-element contents, and are represented by Fe-enriched andradite. The first generation of garnets (Grt1) have two types of garnets (Grt1-A and Grt1-B). Type A garnets of the first generation (Grt1-A) (Adr80-88) replaced by massive diopside-magnetite assemblage exhibit distinct oscillatory zonings and display patterns of enriched light rare earth elements (LREE) to weak heavy rare earth elements (HREE), with weak negative to positive Eu anomalies, and highest U, ΣREE and Sn contents. Type B garnets of the first generation (Grt1-B) are irregular zones (Adr94-96) coexisting with magnetite, in which Grt1-A is generally dissolved, and have obviously LREE-enriched and HREE-depleted patterns, with weak negative to positive Eu anomalies, and moderate U, ΣREE and Zn contents. Garnets of the second generation (Grt2) (Adr96-99) that replaced massive magnetite together with sphalerite show unzoned patterns, with a flat REE pattern and pronounced negative Eu anomalies as well as contents of lowest U and ΣREE, and highest W. The substitution of REEs in garnets occurs as [X2+]VIII –1[REE3+]VIII +1[Si4+]IV –1[Z3+]IV +1in an Al-enriched environment. Luoyang hydrothermal fluids shifted from reducing conditions with relatively high-U and -ΣREE characteristics to oxidizing conditions with relatively low-U and -ΣREE characteristics. The reduced siderophile elements and increased fO2 in fluid during Grt1-B formation caused magnetite mineralization and reduced Zn contents during Grt2 formation, causing the deposition of sphalerite. All garnets formed from magmatic fluid and were controlled by infiltrative metasomatism in an opened system.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.
This study compared dementia knowledge between older Chinese adults in Melbourne, Australia, and Beijing, China, and explored factors associated with dementia knowledge between these two groups. Ultimately, this study aimed to inform the development of tailored dementia education programs for older Chinese adults.
A cross-sectional design was employed in this study.
Participants were recruited from 5 Chinese community senior groups in Melbourne and 10 community health centers in Beijing from March to May 2019.
A total of 379 older Chinese adults aged 50 and over completed the questionnaire, including 153 from Melbourne and 226 from Beijing.
Dementia knowledge was assessed using the Alzheimer’s Disease Knowledge Scale (ADKS). Demographic characteristics, dementia-related experience, and the mental health status of participants were collected. Stepwise linear regression was used to analyze the factors associated with dementia knowledge.
In general, older Chinese adults in Melbourne and Beijing reported similar levels of dementia knowledge for both the overall ADKS scale (mean ± SD: 17.2 ± 2.9 in Melbourne vs. 17.5 ± 2.9 in Beijing, p > 0.05) and the seven subdomains. Of the subdomains, the highest correct response rates were observed in the life impact of the dementia subdomain, and the lowest rates were observed in the caregiving subdomain. Stepwise linear regression analysis revealed that younger age and self-reported dementia worry were significantly associated with higher levels of dementia knowledge in the Melbourne group, whereas a positive family history of dementia was significantly associated with higher levels of dementia knowledge in the Beijing group.
Older Chinese adults living in Melbourne and Beijing share similar levels of dementia knowledge, but factors associated with their knowledge are different. These findings will inform the development of culturally and socially appropriate dementia education programs for older Chinese populations in different countries.
Based on a cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aimed to evaluate the relationship between sleep duration and the incidence of cognitive impairment among older Chinese adults.
We conducted a prospective analysis based on 3692 participants from the CLHLS at baseline (in 2011), and as a 3-year follow-up (till 2014), 531 participants (14.4%) had cognitive impairment, which was defined as a Mini-Mental State Examination score <24. Sleep duration was classified into three groups: short (≤5 hours/day), normal (>5 but <10 hours), and long (≥10 hours/day). A logistic regression model was used to examine the association between baseline sleep duration and cognitive impairment after adjusting for sociodemographic data, living habits, and health conditions.
Five hundred sixty-two participants (15.2%) were in the short-duration group, and 608 participants (16.5%) were in the long-duration group. After adjusting for multiple potential confounders, compared with normal sleep duration, long sleep duration was associated with the incidence of cognitive impairment (OR = 1.309, 95% CI: 1.019–1.683), especially among men (OR = 1.527, 95% CI: 1.041–2.240) and those having a primary and above education level (OR = 1.559, 95% CI: 1.029–2.361). No significant association was observed between short sleep duration and cognitive impairment (OR = 0.860, 95% CI: 0.646–1.145).
Excessive sleep may increase the risk of cognitive impairment in older individuals. It may be a suggestive sign of early neurodegeneration and may be a useful clinical tool to identify those at a higher risk of progressing to cognitive impairment.
The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women.
Case–control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk.
A case-control study of women at three major hospitals in Guangzhou, China.
From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited.
In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer.
Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.
The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case–control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future.
Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.