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To solve the constant contact force control problem between the end tool of a 5 degrees of freedom hybrid optical mirror processing robot and a workpiece, an adaptive impedance control method for the pneumatic servo-polishing system of the robot is designed. Firstly, the pneumatic servo-polishing control system at the end of the robot is set up. Secondly, the impedance control method for contact force is investigated based on the mathematical model of the pneumatic servo-polishing control system. Additionally, the causes of steady-state error of impedance control are analyzed theoretically, and the calculation method for steady-state error of impedance control is deduced. Finally, an indirect adaptive impedance controller based on Lyapunov Stability Principle is developed to estimate the environmental stiffness and position online, so as to reduce steady-state error and realize the tracking of polishing contact force. The simulation and experimental results suggest that the adaptive impedance control method not only recognizes that the contact force of the robot is relatively constant during the polishing process but also has high control accuracy for the force, fast-tracking response for the abrupt force, and considerable adaptability to the variable environmental stiffness.
Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homoeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterisation of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-dehydrocholesterol reductase, which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in the regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.
Purple nutsedge (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 proven to be crucial for tuberization in tuberous plants. Therefore, understanding the relationship between GA3 and tuber development and propagation of C. rotundus will provide valuable information for controlling this weed. This study shows that the GA3 content decreases with tuber development, which corresponds to lower expression of bioactive GA3 synthesis genes (CrGA20ox, two CrGA3ox genes) and two upregulated GA3 catabolism genes (CrGA2ox genes), indicating that GA3 is involved in tuber development. Simultaneously, the expression of two CrDELLA genes and CrGID1 declines with tuber growth and decreased GA3, and yeast two-hybrid assays confirm that the GA3 signaling is DELLA-dependent. Furthermore, exogenous application of GA3 markedly reduces the number and the width of tubers and represses the growth of the 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.
Smoking contributes to a variety of neurodegenerative diseases and neurobiological abnormalities, suggesting that smoking is associated with accelerated brain aging. However, the neurobiological mechanisms affected by smoking, and whether they are genetically influenced, remain to be investigated.
Using structural magnetic resonance imaging data from the UK Biobank (n = 33 293), a brain age predictor was trained on non-smoking healthy groups and tested on smokers to obtain the BrainAge Gap (BAG). The cumulative effect of multiple common genetic variants associated with smoking was then calculated to acquire a polygenic risk score (PRS). The relationship between PRS, BAG, total gray matter volume (tGMV), and smoking parameters was explored and further genes included in the PRS were annotated to identify potential molecular mechanisms affected by smoking.
The BrainAge in smokers was predicted with very high accuracy (r = 0.725, MAE = 4.16). Smokers had a greater BAG (Cohen's d = 0.074, p < 0.0001) and higher PRS (Cohen's d = 0.63, p < 0.0001) than non-smokers. A higher PRS was associated with increased amount of smoking, mediated by BAG and tGMV. Several neurotransmitters and ion channel pathways were enriched in the group of smoking-related genes involved in addiction, brain synaptic plasticity, and some neurological disorders.
By using a simplified single indicator of the entire brain (BAG) in combination with the PRS, this study highlights the greater BAG in smokers and its linkage with genes and smoking behavior, providing insight into the neurobiological underpinnings and potential features of smoking-related aging.
Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure.
We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled.
Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure.
These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.
The relationship between magmatism and gold mineralization has been a topic of interest in understanding the formation of ore deposits. The Baizhangzi gold deposit, located in the northern margin of the North China Craton, is hosted by the Baizhangzi granite (BZG) and provides a case to evaluate the relation between granite and gold mineralization in Late Triassic. In this study, we present petrography, bulk geochemistry, zircon U-Pb isotope and trace elements data, as well as major elements of biotite and plagioclase for the BZG to evaluate the petrogenesis and link with gold mineralization. The BZG comprises biotite monzogranite, biotite-bearing monzogranite and monzogranite (BZGs). Zircon U-Pb geochronology shows that all the granitoids of BZGs were coeval with a formation age of 232 Ma. The granitoids, with high SiO2, Al2O3 and Sr, while low Y and Yb, show adakitic affinity. They are enriched in LILFs (e.g., Rb, Ba, Th, U and Sr) and LREEs, while depletion in HFSEs (e.g., Nb, Ta, P and Ti). The geochemical and mineral chemical data suggest that the granitoids have experienced the fractional crystallization of biotite + plagioclase + K- feldspar + apatite. Crystallization temperature is estimated as ca. 700°C, and pressure is between 0.71 kbar and 1.60 kbar. The monzogranite shows higher values of logfO2, △FMQ and △NNO than the biotite-bearing monzogranite, ranging from −19.76 to −11.71, −4.93 to +3.67 and −5.48 to +3.11, respectively. The fractional crystallization, together with high fO2, K-metasomatism and low evolution degree, provided favourable conditions for gold mineralization.
The advent of immersive and interactive technologies has facilitated the growth of the museum and gallery sector by offering a variety of new experiences. In the UK and China, in particular, the museum and gallery sector lies at the heart of the creative industries and makes a significant contribution to cultural growth. Both countries have recognised the impact of such technologies on the growth of the sector and have actively sought opportunities to use them for bilateral collaboration. However, the interest in immersive and interactive technologies among museum and gallery audiences remains underexplored, as do their preferences and behavioural patterns with respect to such technologies. This study discusses the key findings of user research, exploring the awareness, experiences and preferences of current museum and gallery audiences regarding (i) immersive and interactive museum and gallery experiences and (ii) the cultural exchange between the UK and China.
A blunted hypothalamic–pituitary–adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated.
Seventy-seven participants (17–22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17–22 years old, 24 women).
Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response.
This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.
There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.
Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
Pumilio3 (Pum3), an evolutionarily distant homologue of the classical RNA-binding protein PUF (PUMILIO and FBF) family member, is also involved in the process of RNA metabolism through post-transcriptional regulation. However, the functions of Pum3 in mouse oocyte maturation and preimplantation embryonic development have not been elucidated. By comparing RNA levels in different tissues, we found that Pum3 was widely expressed in multiple tissues, but moderately predominant in the ovary. Histochemical staining suggested that the PUM3 protein exhibits positive signals in oocytes, granulosa cells and theca cells of different follicle stages. Oocyte immunofluorescence results showed a slightly higher level of PUM3 protein in metaphase II compared with the germinal vesicle (GV) stage. After knockdown of Pum3 in GV oocytes using siRNA injection (siPUM3), no obvious defect was observed in the processes of GV breakdown and polar body extrusion during in vitro maturation (IVM) for the siPum3 oocytes. Compared with the control group, the siPUM3 group displayed no significant abnormality in the cleavage and blastocyst formation rate of these fertilized oocytes. Therefore, we can conclude that depletion of Pum3 does not affect mouse oocyte maturation and early embryonic development in vitro.
To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).
We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.
TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.
Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets.
TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS.
In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (PPWAS-ROS/MAP = 4.15 × 10−2 and PPWAS-Banner = 3.38 × 10−3) and APOL2 (PPWAS-ROS/MAP = 4.49 × 10−3 and PPWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05).
Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
About a fourth of Chinese adolescents developed clinically significant depressive symptoms following a disaster. However, little is known about whether and how post-trauma negative life events and a sense of security are associated with depressive symptoms in this population. This study examined the psychological experiences of Chinese young people who had experienced the 2013 Ya’an earthquake in Sichuan, China.
This cross-sectional study was conducted in 2019. A total of 693 Chinese middle school students completed a questionnaire that measured their level of depressive symptoms, trauma exposure, stressful life events, and sense of security.
Results of hierarchical multiple-regression analyses showed that the level of life stress from stressful life events was positively associated with the level of depressive symptoms (β = 0.416, P < 0.001) and the level of the sense of security was negatively associated with the level of depressive symptoms (β = −0.352, P < 0.001) when analysis controlled for age, gender, and trauma exposure.
These findings highlight the importance of considering the influence of life stressors and the sense of security in devising measures and strategies for the prevention of the manifestation of depression among young people, particularly those who were exposed to disasters.
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
Characteristic changes in the asymmetric nature of the human brain are associated with neurodevelopmental differences related to autism. In people with autism, these differences are thought to affect brain structure and function, although the structural and functional bases of these defects are yet to be fully characterized.
We applied a comprehensive meta-analysis to resting-state functional and structural magnetic resonance imaging datasets from 370 people with autism and 498 non-autistic controls using seven datasets of the Autism Brain Imaging Data Exchange Project. We studied the meta-effect sizes based on standardized mean differences and standard deviations (s.d.) for lateralization of gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo). We examined the functional correlates of atypical laterality through an indirect annotation approach followed by a direct correlation analysis with symptom scores.
In people with autism, 85, 51, and 51% of brain regions showed a significant diagnostic effect for lateralization in GMV, fALFF, and ReHo, respectively. Among these regions, 35.7% showed overlapping differences in lateralization in GMV, fALFF, and ReHo, particularly in regions with functional annotations for language, motor, and perceptual functions. These differences were associated with clinical measures of reciprocal social interaction, communication, and repetitive behaviors. A meta-analysis based on s.d. showed that people with autism had lower variability in structural lateralization but higher variability in functional lateralization.
These findings highlight that atypical hemispheric lateralization is a consistent feature in autism across different sites and may be used as a neurobiological marker for autism.
In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.