Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

A Detection and Tracking Method Based on Heterogeneous Multi-Sensor Fusion for Unmanned Mining Trucks.

There exist many difficulties in environmental perception in transportation at open-pit mines, such as unpaved roads, dusty environments, and high requirements for the detection and tracking stability of small irregular obstacles. In order to solve the above problems, a new multi-target detection and tracking method is proposed based on the fusion of Lidar and millimeter-wave radar. It advances a secondary segmentation algorithm suitable for open-pit mine production scenarios to improve the detection distance and accuracy of small irregular obstacles on unpaved roads. In addition, the paper also proposes an adaptive heterogeneous multi-source fusion strategy of filtering dust, which can significantly improve the detection and tracking ability of the perception system for various targets in the dust environment by adaptively adjusting the confidence of the output target. Finally, the test results in the open-pit mine show that the method can stably detect obstacles with a size of 30-40 cm at 60 m in front of the mining truck, and effectively filter out false alarms of concentration dust, which proves the reliability of the method.

Maternal urban particulate matter exposure and signaling pathways in fetal brains and neurobehavioral development in offspring.

It is well understood that exposure to particulate matter (PM) can have adverse effects on the nervous system. When pregnant women are exposed to PM, their fetuses are also affected through the placenta. However, the mechanisms by which fetal brain development is regulated between mother and fetus remain unclear. C57BL/6J pregnant mice were exposed to PM at embryonic day (E) 2.5, 5.5, 8.5, 11.5, 14.5, and 17.5 via nasal drip at three doses (3, 6, 12 mg/kg of body weight) or PBS control. Neurobehavioral changes in the offspring were examined at 5-6-week-old by open field test (OFT) and elevated plus maze (EPM). The maternal and fetal brain and placenta were collected at E18.5, and molecular signal changes were explored using transcriptome analysis. We found that both male and female low-dose pups and male middle-dose pups traveled a significantly longer distance than controls in EPM tests. Both male and female low-dose pups showed a higher frequency of entering the center area and female low-dose pups exhibited a higher percentage of distance moved in the center area than controls in OFT tests. Gene expression in the maternal brain, fetal brain, and placenta at E18.5 was altered. Differentially expressed genes were enriched in the neuroactive ligand-receptor interaction pathway in all three tissue types. Pathway analysis revealed that the PI3K-Akt and PKC signaling was dysregulated in the fetal brain in the high-dose group compared with the control group. The pathways play a role in neuronal survival and apoptosis. Furthermore, there is a dose-dependent increase in Caspase-6, neuronal apoptosis and neurodegeneration biomarker, levels in E18.5 fetal brain (P = 0.06). In conclusion, our study demonstrated that prenatal PM exposure enhanced exploration and locomotor activity in adolescent offspring and altered molecular events in maternal brain, fetal brain, and placenta. The connections of these changes warrant further investigations.

Negative air ion exposure ameliorates depression-like behaviors induced by chronic mild stress in mice.

The presence of negative air ions (NAI) is suggested to be a beneficial factor in improving psychological status and used in treating depression as an alternative approach. However, more biological evidence from animal models is needed to ensure the effects of NAI on the mood regulation, through which can facilitate identification of possible underlying mechanisms. In this study, the chronic mild stress (CMS) protocol was used to induce depressive-like behaviors in mice, and the effects of NAI exposure on CMS-induced depression-like behaviors were examined. Thirty-day NAI exposure prevented the CMS-induced depression-like behaviors as shown by the restoration of sucrose preference and reduced immobility time in the tail suspension test. In addition, the elevation of serous corticosterone was present in CMS-treated mice but not existed in those with the NAI exposure. Furthermore, we observed altered ratios of some cytokines secreted by type 1 T helper (Th1) cells and Th2 cells in CMS-treated mice, but it could be restored after NAI exposure. In conclusion, NAI intervention is able to ameliorate CMS-induced depression-like behaviors in mice, and this effect is associated with the alteration of corticosterone and functional rebalance between Th1 and Th2 cells.

Salicylic acid carboxyl glucosyltransferase UGT87E7 regulates disease resistance in Camellia sinensis.

Plant immune response following pathogenic infection is regulated by plant hormones, and salicylic acid (SA) and its sugar conjugates play important roles in establishing basal resistance. Here, the important pathogen Pseudopestalotiopsis camelliae-sinensis (Pcs) was isolated from tea gray blight, one of the most destructive diseases in tea plantations. Transcriptomic analysis led to the discovery of the putative Camellia sinensis UDP-glucosyltransferase CsUGT87E7 whose expression was significantly induced by SA application and Pcs infection. Recombinant CsUGT87E7 glucosylates SA with a Km value of 12 µM to form SA glucose ester (SGE). Downregulation reduced the accumulation of SGE, and CsUGT87E7-silenced tea plants exhibited greater susceptibility to pathogen infection than control plants. Similarly, CsUGT87E7-silenced tea leaves accumulated significantly less SA after infection and showed reduced expression of pathogenesis-related genes. These results suggest that CsUGT87E7 is an SA carboxyl glucosyltransferase that plays a positive role in plant disease resistance by modulating SA homeostasis through a mechanism distinct from that described in Arabidopsis (Arabidopsis thaliana). This study provides insight into the mechanisms of SA metabolism and highlights the role of SGE in the modulation of plant disease resistance.

A Vibration Control Method for Hybrid-Structured Flexible Manipulator Based on Sliding Mode Control and Reinforcement Learning.

The hybrid-structured flexible manipulator has a complex structure and strong coupling between state variables. Meanwhile, the natural frequency of the hybrid-structured flexible manipulator varies with the motion of the telescopic joint, so it is difficult to suppress the vibration quickly. In this article, the tip state signal of the hybrid-structured flexible manipulator is decomposed into elastic vibration signal and tip vibration equilibrium position signal, and a combined control method is proposed to improve tip positioning accuracy and trajectory tracking accuracy. In the proposed combined control method, an improved nominal model-based sliding mode controller (NMBSMC) is used as the main controller to output the driving torque, and an actor-critic-based reinforcement learning controller (ACBRLC) is used as an auxiliary controller to output small compensation torque. The improved NMBSMC can be divided into a nominal model-based sliding mode robust controller and a practical model-based integral sliding mode controller. Two sliding mode controllers with different structures make full use of the mathematical model and the measured data of the actual system to improve the vibration equilibrium position tracking accuracy. The ACBRLC uses the tip elastic vibration signal and the prioritized experience replay method to obtain the small reverse compensation torque, which is superimposed with the output of the NMBSMC to suppress tip vibration and improve the positioning accuracy of the hybrid-structured flexible manipulator. Finally, several groups of experiments are designed to verify the effectiveness and robustness of the proposed combined control method.

ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors.

Genome-wide association studies uncovered the association of ZNF804A (Zinc-finger protein 804A) with schizophrenia (SZ). In vitro data have indicated that ZNF804A might exert its biological roles by regulating spine and neurite morphogenesis. However, no in vivo data are available for the role of ZNF804A in psychiatric disorders in general, SZ in particular. We generated ZFP804A mutant mice, and they showed deficits in contextual fear and spatial memory. We also observed the sensorimotor gating impairment, as revealed by the prepulse inhibition test, but only in female ZFP804A mutant mice from the age of 6 months. Notably, the PPI difference between the female mutant and control mice was no longer existed with the administration of Clozapine or after the ovariectomy. Hippocampal long-term potentiation was normal in both genders of the mutant mice. Long-term depression was absent in male mutants, but facilitated in the female mutants. Protein levels of hippocampal serotonin-6 receptor and GABAB1 receptor were increased, while those of cortical dopamine 2 receptor were decreased in the female mutants with no obvious changes in the male mutants. Moreover, the spine density was reduced in the cerebral cortex and hippocampus of the mutant mice. Knockdown of ZFP804A impaired the neurite morphogenesis of cortical and hippocampal neurons, while its overexpression enhanced neurite morphogenesis only in the cortical neurons in vitro. Our data collectively support the idea that ZFP804A/ZNF804A plays important roles in the cognitive functions and sensorimotor gating, and its dysfunction may contribute to SZ, particularly in the female patients.

The unreasonable use of high beam at nighttime among motor vehicle drivers / 预防医学

Objective@#To observe the incidence of unreasonable use of high beam at nighttime among motor vehicle drivers, so as to provide the evidence for the prevention and control of road traffic injury. @*Methods@#Four roads into city and five urban roads were selected in Yongkang of Zhejiang Province. An automatic recording system was used to collect the unreasonable use of high beam among motor vehicle drivers on the selected roads from 19:00 to 5:00 on Monday, Wednesday, Friday and Sunday during a week in July 2020. The regression tree model was used to analyze the relationship of the unreasonable use of high beam with road, time and traffic flow. @*Results@# A total of 89 989 motor vehicles were observed, and 2 419 motor vehicle drivers had unreasonable use of high beam, with an incidence rate of 2.69%. The incidence rate of the unreasonable use of high beam was 3.14% in the roads into city, which was higher than 2.30% in the urban roads ( P<0.05 ). The incidence rates of the unreasonable use of high beam in the roads into city and in the urban roads were 5.15% and 2.90% on Wednesday, which were higher than those on Monday ( 2.89% and 2.34% ), Friday ( 2.90% and 1.92% ) and Sunday (2.06% and 2.12%). The highest incidence rate of the unreasonable use of high beam in the roads into city was 6.07% between 4:00 and 5:00, and in the urban roads was 4.50% between 2:00 and 3:00. The results of regression tree classification analysis showed that the highest incidence rate was 8.13% on the roads into city in the east, west and south directions, and on the urban roads in the east and north directions with less than 317 vehicles per hour on Wednesday. @*Conclusion@#It is more likely for motor vehicle drivers to use high beams unreasonably at nighttime on the roads into city with less traffic flow.

Dehydration-Induced Carotenoid Cleavage Dioxygenase 1 Reveals a Novel Route for ß-Ionone Formation during Tea (Camellia sinensis) Withering.

ß-Ionone is a carotenoid-derived flavor and fragrance compound with a complex fruity and woody scent, known for its violet aroma. Due to the low odor threshold, ß-ionone dramatically affects the aroma and quality of tea. Previous studies have shown that ß-ionone increases during tea withering; however, its formation and regulation during the withering process are far from being understood. As dehydration is the most important stress during the withering of the tea leaves, we isolated a dehydration-induced gene belonging to the subfamily of carotenoid cleavage dioxygenases called carotenoid cleavage dioxygenase 1a (CsCCD1a) from Camellia sinensis and expressed it in Escherichia coli. The recombinant protein could generate volatile ß-ionone and pseudoionone from carotenoids. CsCCD1a was induced by dehydration stress, and its expression was related to the ß-ionone accumulation during tea withering. Overall, this study elucidated that CsCCD1a catalyzes the formation of ß-ionone in C. sinensis and enhanced the understanding of the ß-ionone formation under multiple stresses during the processing of tea.

Induction of priming by cold stress via inducible volatile cues in neighboring tea plants.

Plants have evolved sophisticated defense mechanisms to overcome their sessile nature. However, if and how volatiles from cold-stressed plants can trigger interplant communication is still unknown. Here, we provide the first evidence for interplant communication via inducible volatiles in cold stress. The volatiles, including nerolidol, geraniol, linalool, and methyl salicylate, emitted from cold-stressed tea plants play key role(s) in priming cold tolerance of their neighbors via a C-repeat-binding factors-dependent pathway. The knowledge will help us to understand how plants respond to volatile cues in cold stress and agricultural ecosystems.

Behavioral abnormalities and phosphorylation deficits of extracellular signal-regulated kinases 1 and 2 in rat offspring of the maternal immune activation model.

Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia.

Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation.

BACKGROUND: Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. METHODS: Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague-Dawley rats prenatally challenged with polyriboinosinic-polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1ß, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. RESULTS: Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. CONCLUSIONS: Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.

Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial.

Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18-45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 µg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile.

A novel SNP in promoter region of RP11-3N2.1 is associated with reduced risk of colorectal cancer.

Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic non-coding RNAs (lincRNAs) could play a regulatory role in its expression level and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage case-control study to investigate the associations of Tag SNPs within the promoter region of selected lincRNAs from microarray data with risk of CRC. A total of 320 cases and 319 controls were recruited in the test set to explore the associations between 16 SNPs with no deviations from Hardy-Weinberg equilibrium (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as the validation set to confirm the significant associations. RP11-3N2.1 rs13230517 polymorphism was found to be negatively associated with CRC in both test set (AA vs. GG, OR = 0.68, 95% CI = 0.48-0.96) and validation set (AA vs. GG, OR = 0.76, 95% CI = 0.59-0.98). Pooled analysis showed that individuals with GA/AA genotypes had a significantly decreased risk of CRC when compared with those carrying GG genotype (OR = 0.74, 95% CI = 0.60-0.90) in the combined set. The crossover analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than GG carriers among non-drinkers in both test and combined set. However, no gene-environment multiplicative interactions were found on risk of CRC. Our findings suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC and have the potential to be a biomarker for predicting the risk of CRC.

Sex disparities in cancer incidence in Jiashan County, China, 1995-2014.

PURPOSE: To describe the sex-specific incidence rates and the male-to-female incidence-rate ratios (IRRs) of different cancer types, and to explore the corresponding sex disparities in an area of Eastern China. METHODS: We used data from the Cancer Registry in Jiashan County, and calculated the sex-specific age-standardized (2010 China standard population) incidence rates and the male-to-female IRRs for different cancer types during the period 1995-2014. RESULTS: The age-standardized incidence rates of all cancers for the whole period 1995-2014 were 151.48 per 100,000 person-years for males and 83.75 per 100,000 person-years for females, and the corresponding male-to-female IRR was 1.81 (95% confidence interval: 1.77-1.85). Specifically, males presented higher incidences in most types of cancer with the exceptions of cancers of connective and other soft tissues, gallbladder (including extrahepatic bile ducts), and thyroid gland. In addition, the age-specific incidences of the ten most common cancers in males were higher than those in females in most age groups. CONCLUSIONS: Our results reveal a male predominance in incidence for a majority of cancers in Jiashan County, Eastern China. Possible explanations for these sex disparities in cancer incidence may include lifestyle factors, particularly smoking.

ELISA analysis of urinary nephrin and podocalyxin standardized by aquaporin-2 in adult patients with nephrotic syndrome.

OBJECTIVE: To investigate urinary nephrin and podocalyxin standardized by aquaporin (AQP)-2 using the enzyme-linked immunosorbent assay (ELISA) method in adult nephrotic syndrome (NS) patients. METHODS: In 107 adult NS patients (27 proliferative nephritis, 77 non-proliferative, and 3 amyloidosis) undergoing renal biopsy, urinary nephrin, podocalyxin and AQP2 were measured by ELISA. Urinary nephrin and podocalyxin were standardized by AQP2 (neph/AQP and PCX/AQP) and values were compared with 11 healthy controls. RESULTS: Urinary neph/AQP correlated positively to PCX/AQP (r = 0.51, p < 0.001). Urinary neph/AQP and PCX/AQP were lower in controls than NS patients. Both proliferative and non-proliferative NS patients excreted high urinary neph/AQP and PCX/AQP without a significant difference between them (p > 0.05). Patients with focal segmental glomerular sclerosis (FSGS) excreted higher urinary neph/AQP (p = 0.09) and PCX/AQP (p < 0.05) compared to the other patients. Urinary neph/AQP and PCX/AQP were increased in the immunoglobulin M nephropathy patients. Amyloidosis patients excreted lower neph/AQP and PCX/AQP. The sensitivity was 0.87 and specificity 0.37 when the neph/AQP borderline value of 0.16 was adopted [area under the curve (AUC) = 0.61]. The sensitivity was 0.74 and specificity 0.61 when the PCX/AQP borderline value was 3.06 (AUC = 0.69). CONCLUSIONS: Urinary neph/AQP and PCX/AQP are increased in NS patients, with FSGS patients showing the highest levels. To distinguish FSGS from other NS forms, the measurement of urinary PCX/AQP may be a practical method, and superior to neph/AQP.