Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Routine Workflow of Spatial Proteomics on Micro-formalin-Fixed Paraffin-Embedded Tissues.

In the era of single-cell biology, spatial proteomics has emerged as an important frontier. However, it still faces several challenges in technology. Formalin-fixed paraffin-embedded (FFPE) tissues are an important material in spatial proteomics, in which fixed tissues are excised using laser capture microdissection (LCM), followed by protein identification with mass spectrometry. For a satisfied spatial proteomics upon FFPE tissues, the excision area is expected to be as small as possible, and the identified proteins are countered upon as much as possible. For a general laboratory for spatial proteomics, a routine workflow is required, not relying on any special device, and is easily operating. In view of these challenges in technology, we initiated a technology evaluation throughout the entire procedure of proteomic analysis with micro-FFPE tissues. In contrast to the protocols reported previously, several innovations in technology were proposed and conducted, such as removal of destaining, decross-linking with "hang-down", solution simplification for peptide generation and balancing to excision area, and capture rate of micro-FFPE tissues. After optimization of all the necessary steps, a routine workflow was established, in which the minimized area for protein identification was 0.002 mm2, while the excision area for a consistent proteomic analysis was 0.05 mm2. Using the developed workflow and collecting the micro-FFPE tissues continuously, for the first time, a spatial proteomic atlas of mouse brain was preliminarily constructed, which exhibited the typical characteristics of spatial-dependent protein abundance and functional enrichment.

Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.

BACKGROUND: Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD. METHODS: We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment. RESULTS: Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p < .05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD. CONCLUSIONS: Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.

Adverse childhood experiences in offspring living with parental mental illness: a controlled study from China.

BACKGROUND: Adverse childhood experiences (ACEs) affect children's development, and their harm to health is pervasive throughout the life course. AIMS: To identify ACEs and their risk factors in Chinese household with or without parental mental illness. METHODS: A controlled study was conducted among 181 young adults with parental mental illness (positive group) and 201 demographically matched individuals without parental mental illness (negative group). Univariate and multivariate analyses were performed to study the correlation between ACEs and their risk factors. RESULTS: The positive group suffered emotional abuse, domestic violence, bullying, and cumulative ACEs more frequently than the negative group. In the positive group, living in rural areas and having a low household economic status during childhood were identified as risk factors for cumulative ACEs, whereas a higher education level of the mother was a protective factor for cumulative ACEs in univariate analyses. Low household economic status remained an independent risk factor for cumulative ACEs in the positive group in multivariate analyses. CONCLUSIONS: Children living with parental mental illness are more vulnerable to ACEs, and our findings highlight the importance of socioeconomic factors in increasing the risk of ACEs. To alleviate the deleterious impact of parental mental illness on offspring, multidimensional supports are needed.

Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging.

Schwann cell (SC)-specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1 f/f mice with myelin protein zero (P0)-Cre mice. P0-Cre+/- , MCT1 f/f mice have no detectable early developmental defects, but develop hypomyelination and reduced conduction velocity in sensory, but not motor, peripheral nerves during maturation and aging. Furthermore, reduced mechanical sensitivity is evident in aged P0-Cre+/- , MCT1 f/f mice. MCT1 deletion in SCs impairs both their glycolytic and mitochondrial functions, leading to altered lipid metabolism of triacylglycerides, diacylglycerides, and sphingomyelin, decreased expression of myelin-associated glycoprotein, and increased expression of c-Jun and p75-neurotrophin receptor, suggesting a regression of SCs to a less mature developmental state. Taken together, our results define the contribution of SC MCT1 to both SC metabolism and peripheral nerve maturation and aging.

Robust expression of SIRT6 inhibits pulpitis via activation of the TRPV1 channel.

Invasion of dentinal tubules and pulp tissue by pathogenic bacteria may cause infection leading to pulpitis. Sirtuin 6 (SIRT6) is a NAD-dependent protein deacetylase encoded by the SIRT6 gene. The effect of SIRT6 on lipopolysaccharide (LPS)-induced pulpitis and its mechanism of action were discussed in this study. Dental pulp cells (DPCs) were extracted from human teeth and injected with LPS to induce inflammation. The cells injected with LPS showed substantially decreased expression of SIRT6. The overexpression of SIRT6, induced by plasmid-transfection of DPCs with SIRT6 overexpressing vector, led to a marked decrease in proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) and deactivation of NF kappa B pathway. Additionally, dentin matrix protein-1 (DMP1), a promoter of inflammation in dental pulp tissues, was downregulated. Further investigation revealed that SIRT6 promotes ubiquitination of the transient receptor potential vanilloid 1 (TRPV1) channel, leading to its degradation and deactivation. The role of TRPV1 in the anti-inflammatory effects of SIRT6 was determined through incubation of SIRT6-expressing dental pulp stem cells (DPSCs) with capsaicin. This incubation counteracted the effect of SIRT6 on cytokines and DMP1. The injection of lentivirus-SIRT6 attenuated LPS-induced pulpitis in vivo by suppressing TRPV1 activity. Thus, SIRT6 inhibits the TRPV1 channel during LPS-induced inflammation of dental pulp. SIGNIFICANCE OF THE STUDY: This study discussed the effect of sirtuin 6 (SIRT6) on lipopolysaccharide (LPS)-induced pulpitis as well as its mechanism of action and found that SIRT6 may be a negative regulator of pulpitis. Additionally, low expression of SIRT6 and high expression of transient receptor potential vanilloid 1 (TRPV1) in LPS-treated human dental pulp cells are closely associated with proinflammatory cytokines, dentin matrix protein 1 expression, and activation of the NF-κB pathway, which indicated that TRPV1 may be a biomarker for pulpitis and the SIRT6-TRPV1-CGRP axis maybe a clinical target due to their role regulating inflammation and neuropathic pain.

Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse.

BACKGROUND: Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive. RESULTS: In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions. CONCLUSIONS: This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data.

Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain.

Mitochondrial dynamics and mitophagy have been linked to cardiovascular and neurodegenerative diseases. Here, we demonstrate that the mitochondrial division dynamin Drp1 and the Parkinson's disease-associated E3 ubiquitin ligase parkin synergistically maintain the integrity of mitochondrial structure and function in mouse heart and brain. Mice lacking cardiac Drp1 exhibited lethal heart defects. In Drp1KO cardiomyocytes, mitochondria increased their connectivity, accumulated ubiquitinated proteins, and decreased their respiration. In contrast to the current views of the role of parkin in ubiquitination of mitochondrial proteins, mitochondrial ubiquitination was independent of parkin in Drp1KO hearts, and simultaneous loss of Drp1 and parkin worsened cardiac defects. Drp1 and parkin also play synergistic roles in neuronal mitochondrial homeostasis and survival. Mitochondrial degradation was further decreased by combination of Drp1 and parkin deficiency, compared with their single loss. Thus, the physiological importance of parkin in mitochondrial homeostasis is revealed in the absence of mitochondrial division in mammals.

Data Collection for Mobile Group Consumption: An Asynchronous Distributed Approach.

Mobile group consumption refers to consumption by a group of people, such as a couple, a family, colleagues and friends, based on mobile communications. It differs from consumption only involving individuals, because of the complex relations among group members. Existing data collection systems for mobile group consumption are centralized, which has the disadvantages of being a performance bottleneck, having single-point failure and increasing business and security risks. Moreover, these data collection systems are based on a synchronized clock, which is often unrealistic because of hardware constraints, privacy concerns or synchronization cost. In this paper, we propose the first asynchronous distributed approach to collecting data generated by mobile group consumption. We formally built a system model thereof based on asynchronous distributed communication. We then designed a simulation system for the model for which we propose a three-layer solution framework. After that, we describe how to detect the causality relation of two/three gathering events that happened in the system based on the collected data. Various definitions of causality relations based on asynchronous distributed communication are supported. Extensive simulation results show that the proposed approach is effective for data collection relating to mobile group consumption.

Ethoxyquin prevents chemotherapy-induced neurotoxicity via Hsp90 modulation.

OBJECTIVE: Peripheral neurotoxicity is a major dose-limiting side effect of many chemotherapeutic drugs. Currently there are no effective disease-modifying therapies for chemotherapy-induced peripheral neuropathies, but these side effects of chemotherapy are potentially ideal targets for development of neuroprotective therapies, because candidate drugs can be co- or preadministered before the injury to peripheral axons takes place. METHODS: We used a phenotypic drug screening approach to identify ethoxyquin as a potential neuroprotective drug and carried out additional biochemical experiments to identify its mechanism of action. RESULTS: We validated the screening results with ethoxyquin and its derivatives and showed that they prevented paclitaxel-induced peripheral neuropathy without blocking paclitaxel's ability to kill tumor cells. Furthermore, we demonstrated that ethoxyquin acts by modulating the chaperone activity of heat shock protein 90 (Hsp90) and blocking the binding of 2 of its client proteins, ataxin-2 and Sf3b2. Ethoxyquin-induced reduction in levels of both of these proteins resulted in prevention of axonal degeneration caused by paclitaxel. INTERPRETATION: Ethoxyquin and its novel derivatives as well as other classes of small molecules that act as Hsp90 modulators may offer a new opportunity for development of drugs to prevent chemotherapy-induced axonal degeneration.

Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits: Evidence from the Shanghai birth cohort.

The epidemiological evidence regarding prenatal PFAS exposure and its interaction with genetic factors on the autistic traits risk is unclear. This study included 1610 mother-child pairs from the Shanghai Birth Cohort (SBC). Ten PFAS were quantified in blood serum collected in the first trimester. Child autistic traits were evaluated at age 4 using a Chinese version of the social responsiveness scale-short form (SRS-SF). We calculated the polygenic risk score (PRS) to evaluate the cumulative genetic effects of autism. Additive interaction models were established to explore whether genetic susceptibility modified the effects of prenatal PFAS exposure. After adjusting for confounders, we found prenatal PFOA exposure was associated with an increased risk of autistic traits in children (OR, 3.05; 95 % CI, 1.14-7.58), and the increased risk associated with PFOA was mitigated among women who reported pre-pregnancy folic acid supplementation. Additionally, an increased risk of autistic traits was observed in children with higher levels of prenatal PFHxS exposure and a high PRS (p for interaction = 0.021). Our findings suggest prenatal PFAS exposure may increase the risk of autistic traits in children, especially in those with a high genetic risk. Further research is warranted to confirm this association and explore the underlying mechanisms.

Dissecting the long-term neurobehavioral impact of embryonic benz[a]anthracene exposure on zebrafish: Social dysfunction and molecular pathway activation.

Benz[a]anthracene (BaA), a prevalent environmental contaminant within the polycyclic aromatic hydrocarbon class, poses risks to both human health and aquatic ecosystems. The impact of BaA on neural development and subsequent social behavior patterns remains inadequately explored. In this investigation, we employed the zebrafish as a model to examine the persisting effects of BaA exposure on social behaviors across various developmental stages, from larvae, juveniles to adults, following embryonic exposure. Our findings indicate that BaA exposure during embryogenesis yields lasting neurobehavioral deficits into adulthood. Proteomic analysis highlights that BaA may impair neuro-immune crosstalk in zebrafish larvae. Remarkably, our proteomic data also hint at the activation of the aryl hydrocarbon receptor (AHR) and cytochrome P450 1A (CYP1A) pathway by BaA, leading to the hypothesis that this pathway may be implicated in the disruption of neuro-immune interactions, contributing to observable behavioral disruptions. In summary, our findings suggest that early exposure to BaA disrupts social behaviors, such as social ability and shoaling behaviors, from the larval stage through to maturity in zebrafish, potentially through the detrimental effects on neuro-immune processes mediated by the AHR-CYP1A pathway.

PfAgo-Based Zika Virus Detection.

As a mosquito-borne flavivirus, Zika virus (ZIKV) has been identified as a global health threat. The virus has been linked to severe congenital disabilities, including microcephaly and other congenital malformations, resulting in fatal intrauterine death. Therefore, developing sensitive and specific methods for the early detection and accurate diagnosis of the ZIKV is essential for controlling its spread and mitigating its impact on public health. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the non-structural protein 5 (NS5) region of the ZIKV genome (abbreviated ZIKV-PAND). Without preamplification with the polymerase chain reaction (PCR), the minimum detection concentration (MDC) of ZIKV-PAND was about 10 nM. When introducing an amplification step, the MDC can be dramatically decreased to the aM level (8.3 aM), which is comparable to qRT-PCR assay (1.6 aM). In addition, the diagnostic findings from the analysis of simulated clinical samples or Zika virus samples using ZIKV-PAND show a complete agreement of 100% with qRT-PCR assays. This correlation can aid in the implementation of molecular testing for clinical diagnoses and the investigation of ZIKV infection on an epidemiological scale.

The effect of weighted blankets on sleep and related disorders: a brief review.

Background: Sleep disorders such as insomnia can lead to a range of health problems. The high risk of side effects and drug abuse of traditional pharmacotherapy calls for a safer non-pharmacotherapy. Aims: To examine the use and efficacy of weighted blankets in improving sleep and related disorders in different populations and explore the possible mechanisms. Methods: A literature search was conducted using PubMed, Embase, Web of Science, MEDLINE, Cochrane Library and CNKI databases. Eligible studies included an intervention with weighted blankets and outcomes covering sleep and/or related disorders (behavioral disturbance, negative emotions and daytime symptoms). Studies using other deep pressure, compression, or exercise-related interventions were excluded. Conclusions: Most of the included studies showed that weighted blankets could effectively improve sleep quality and alleviate negative emotions and daytime symptoms in patients with sleep disorders, attention deficit hyperactivity disorder, autism spectrum disorder, and other related disorders, with a possible mechanism of deep pressure touch. Recommendations: Weighted blankets might be a promising tool for sleep interventions among individuals with sleep disorders in clinical settings. More high-quality and large-scale randomized controlled trials are needed to further validate the safety and efficacy of weighted blankets and explore precise mechanisms.

Heterogeneous associations of multiplexed environmental factors and multidimensional aging metrics.

Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Novel Nucleic Acid Detection for Human Parvovirus B19 Based on Pyrococcus furiosus Argonaute Protein.

Parvovirus B19 (B19V) is pathogenic to humans and causes various human diseases. However, no antiviral agents or vaccines currently exist for the treatment or prevention of B19V infection. Therefore, developing sensitive and specific methods for B19V infection diagnosis is essential for accurate diagnoses. Previously, a Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas12a (cpf1)-based electrochemical biosensor (E-CRISPR) with a picomole sensitivity for B19V detection was established. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the nonstructural protein 1 (NS1) region of the B19V viral genome (abbreviated B19-NS1 PAND). Benefiting from independent protospacer adjacent motif (PAM) sequences, PfAgo can recognize their target with guide DNA (gDNA) that is easy to design and synthesize at a low cost. In contrast to E-CRISPR, without preamplification with Polymerase Chain Reaction (PCR), the Minimum Detectable Concentration (MDC) of three guide- or single guide-mediated B19-NS1 PAND was about 4 nM, approximately 6-fold more than E-CRISPR. However, when introducing an amplification step, the MDC can be dramatically decreased to the aM level (54 aM). In addition, the diagnostic results from clinical samples with B19-NS1 PAND revealed 100% consistency with PCR assays and subsequent Sanger sequencing tests, which may assist in molecular testing for clinical diagnosis and epidemiological investigations of B19V.

Childhood experiences and needs of offspring living with paternal and maternal severe mental illness: A retrospective study in China.

OBJECTIVE: Parental mental illness is considered one of the strongest risk factors for the development of children. This study aimed to describe the adverse childhood experiences and needs of offspring living with parental severe mental illness (SMI) in China and to compare the differences in needs between offspring living with maternal SMI and those living with paternal SMI. METHOD: Overall, 381 participants, including 76 living with paternal SMI, 104 living with maternal SMI, and 201 living without parental mental illness, were enrolled. Data were collected using questionnaires from five sites in China. Differences among the three groups were compared using analysis of variance and chi-square test. Factors were extracted using exploratory factor analysis, and differences in factor scores between the paternal and maternal SMI groups were compared using the rank sum test. RESULTS: The percentages of poverty, family care, and housework were significantly higher in the paternal SMI group and maternal SMI group, compared with the control group, and those of school dropout and relationship with friends were significantly higher in the maternal SMI group (p < 0.0167). The need for stigma reduction in the maternal SMI group was significantly higher than that in the paternal SMI group (p = 0.015). CONCLUSION: Our findings highlight the importance of considering the impact of maternal and paternal SMI on child development. There is an urgent need to develop a national program to assist families with mentally ill parents to provide services for children living with parental SMI.

Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy.

OBJECTIVE: Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus-associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments, and that a spatial pattern of mitochondrial dysfunction contributes to the distal degeneration of sensory nerve fibers. METHODS: We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV)-infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. RESULTS: We identified increased levels of mtDNA common deletion mutation in postmortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. INTERPRETATION: Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies.

Flow Regulation Performance Analysis of Microfluidic Passive Valve for High Throughput Liquid Delivery.

A microfluidic passive valve (MPV) is important for precise flow control, and it determines the reliability of the microfluidic system. In this paper, a novel MPV capable of delivering a constant flow rate independently of inlet pressure changes is proposed. The flow rate of the MPV is adjusted by the difference between the fluid force on the upper surface of the valve core and the spring force. The constant flow rate of the MPV is maintained by automatically changing the size of the gap channel formed by the groove on the valve core and the baffle on the valve body. The nearly constant flow rate of the MPV is 6.26 mL/min, with a variation of 6.5% under the inlet pressure varied from 1.25 kPa to 3.5 kPa. In addition, the flow characteristics of the MPV are analyzed by numerical simulation. With the increase in the inlet pressure, the maximum velocity gradually increases, while the increment of the maximum velocity decreases. In the movement process of the valve core, the region of pressure drop becomes larger. This work has a certain reference value for the design and research of the MPVs with high throughput liquid delivery.

Effect of a contact-based education intervention on reducing stigma among community health and care staff in Beijing, China: Pilot randomized controlled study.

The aim was to assess the feasibility of an intervention to reduce stigma among primary care and community healthcare staff in Beijing, China through a contact-based education intervention. Participants were randomly assigned to: (i) "education only" group, a lecture-based education; or (ii) "education and contact" group, lectures plus contact with people with lived experience of mental illness. Each participant completed an assessment of mental health stigma related: knowledge (mental health knowledge schedule, MAKS); attitudes (mental illness: clinicians' attitudes scale, MICA-4); and behavior (reported and intended behavior scale, RIBS) before and after the intervention, with follow up at 1 month and 3 months after the intervention. A total of 121 healthcare staff were recruited. Both "education only" group and "education and contact" group showed improved knowledge after the intervention, MAKS scores increased by 1.77 ± 3.15 VS 2.46 ± 2.49 (both p < 0.001), respectively. There was no between-group difference in MAKS score. The "education and contact" group showed a significantly greater improvement for MICA and RIBS score than the "education only" group: the MICA score decreased by 4.43 ± 9.42 VS 8.41 ± 7.48 (p = 0.027), and the RIBS score increased by 2.28 ± 3.89 VS 4.57 ± 3.53 (p = 0.003), in the "education only" and the "education and contact" groups respectively, but the between group differences disappeared at 1 month and 3 months follow-up points. The positive effects on stigma levels (knowledge, attitudes and behaviours) in both groups were sustained at 3 months. The intervention to reduce stigma among the primary and community healthcare staff through a contact-based education intervention was feasible in Beijing.