Postnatal nighttime light exposure and infant temperament at age 12 months: mediating role of genus Akkermansia.

The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.

Short-term exposures to PM2.5, PM2.5 chemical components, and antenatal depression: Exploring the mediating roles of gut microbiota and fecal short-chain fatty acids.

BACKGROUND: PM2.5 and its chemical components increase health risks and are associated with depression and gut microbiota. However, there is still limited evidence on whether gut microbiota and short-chain fatty acids (SCFAs) mediate the association between PM2.5, PM2.5 chemical components, and antenatal depression. The purpose of this study was to investigate the mediating role of maternal gut microbiota in correlations between short-term exposure to PM2.5, short-term exposure to PM2.5 chemical components, and antenatal depression. METHODS: Demographic information and stool samples were collected from 75 pregnant women in their third trimester. Their exposure to PM2.5 and PM2.5 chemical components was measured. Participants were divided into the non-antenatal depression group or the antenatal depression group according to the cut-off of 10 points on the Edinburgh Postnatal Depression Scale (EPDS). The gut microbiota were analyzed using the 16 S rRNA-V3/V4 gene sequence, and the concentration of PM2.5 and its chemical components was calculated using the Tracking Air Pollution in China (TAP) database. Gas chromatography-mass spectrometry was used to analyze SCFAs in stool samples. In order to assess the mediating effects of gut microbiota and SCFAs, mediation models were utilized. RESULTS: There were significant differences between gut microbial composition and SCFAs concentrations between the non-antenatal depression group and the antenatal depression group. PM2.5 and its chemical components were positively associated with EPDS scores and negatively associated with genera Enterococcus and Enterobacter. Genera Candidatus_Soleaferrea (ß = -7.21, 95%CI -11.00 to -3.43, q = 0.01) and Enterococcus (ß = -2.37, 95%CI -3.87 to -0.87, q = 0.02) were negatively associated with EPDS scores, indicating their potential protective effects against antenatal depression. There was no significant association between SCFAs and EPDS scores. The mediating role of Enterococcus between different lagged periods of PM2.5, PM2.5 chemical component exposure, and antenatal depression was revealed. For instance, Enterococcus explained 29.23% (95%CI 2.16-87.13%, p = 0.04) of associations between PM2.5 exposure level at the day of sampling (lag 0) and EPDS scores. CONCLUSION: Our study highlights that Enterococcus may mediate the associations between PM2.5, PM2.5 chemical components, and antenatal depression. The mediating mechanism through which the gut microbiota influences PM2.5-induced depression in pregnant women still needs to be further studied.

Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis.

The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

Perinatal depression and infant and toddler neurodevelopment: A systematic review and meta-analysis.

Many studies have focused on the effect of perinatal depression on neurodevelopment among children and adolescents. However, only a few studies have explored this relationship in infants and toddlers with inconsistent results. We performed a systematic review and meta-analysis to evaluate the association between perinatal depression and infant and toddler neurodevelopment during the first two postnatal years. Twenty-three studies were included in this meta-analysis. Perinatal depression was associated with poorer cognitive (Cohen's d = -0.19, SE= 0.06, 95% CI = -0.30 to -0.08), language (Cohen's d = -0.24, SE = 0.09, 95% CI = -0.40 to -0.07), and motor (Cohen's d = -0.15, SE = 0.05, 95% CI = -0.26 to -0.05) development. Subgroup analyses showed that the types of maternal depression (prenatal depression vs. postnatal depression), the method of measuring maternal depression (rating scale vs. diagnostic interview), and the time interval between assessment of exposure and outcome had an impact on the observed effect about neurodevelopment of infants and toddlers. In addition, the results of our study pointed to a stronger significant association between prenatal depression and cognitive, language, and motor delays in infants and toddlers, whereas the association between postnatal depression and cognitive, language, and motor delays in infants and toddlers was not statistically significant. In conclusion, this study provided convincing evidence that the perinatal window is a sensitive period for offspring neurodevelopment.

Combined impact of Hepatitis B virus and gestational diabetes mellitus on ultrasound-measured fetal growth and adverse perinatal outcomes: A seven-year retrospective study.

AIMS: To investigate the impact of pregnancy with combined hepatitis B virus (HBV) infection and Gestational diabetes mellitus (GDM) on fetal growth and adverse perinatal outcomes. METHODS: All the pregnant women with HBV infection and/or GDM who delivered at Women's Hospital, Zhejiang University between January 2015, and September 2022 were included. A total of 1633 pregnant women were recruited in the final analysis, including 409 women with HBV infection and GDM, 396 with HBV infection only, 430 with GDM only, and 398 without HBV infection and GDM. Linear and logistic regression models were used to study the impact of pregnancy with combined HBV infection and GDM on fetal growth and adverse perinatal outcomes. RESULTS: Pregnancy with combined HBV infection and GDM was associated with increased Z-scores on primary fetal ultrasound parameters and significantly increased the risk of fetal femur length overgrowth (OR: 2.88, 95 % CI: 1.13 âˆ¼ 7.35), placental abruption (OR: 3.64, 95 % CI: 1.18 âˆ¼ 11.22), and macrosomia (OR: 4.19, 95 % CI: 1.66 âˆ¼ 10.56) compared to pregnancy without HBV infection and GDM. CONCLUSIONS: Both maternal HBV infection and GDM are independently associated with adverse perinatal outcomes. Their combination further increases the risk of adverse perinatal outcomes.

O-GlcNAcylation of melanophilin enhances radiation resistance in glioblastoma via suppressing TRIM21 mediated ubiquitination.

The molecular mechanism of glioblastoma (GBM) radiation resistance remains poorly understood. The aim of this study was to elucidate the potential role of Melanophilin (MLPH) O-GlcNAcylation and the specific mechanism through which it regulates GBM radiotherapy resistance. We found that MLPH was significantly upregulated in recurrent GBM tumor tissues after ionizing radiation (IR). MLPH induced radiotherapy resistance in GBM cells and xenotransplanted human tumors through regulating the NF-κB pathway. MLPH was O-GlcNAcylated at the conserved serine 510, and radiation-resistant GBM cells showed higher levels of O-GlcNAcylation of MLPH. O-GlcNAcylation of MLPH protected its protein stability and tripartite motif containing 21(TRIM21) was identified as an E3 ubiquitin ligase promoting MLPH degradation whose interaction with MLPH was affected by O-GlcNAcylation. Our data demonstrate that MLPH exerts regulatory functions in GBM radiation resistance by promoting the NF-κB signaling pathway and that O-GlcNAcylation of MLPH both stabilizes and protects it from TRIM21-mediated ubiquitination. These results identify a potential mechanism of GBM radiation resistance and suggest a potential therapeutic strategy for GBM treatment.

Cumulative and lagged effects of varying-sized particulate matter exposure associates with toddlers' gut microbiota.

Particulate matter (PM) is an important component of air pollutants and is associated with various health risks. However, the impact of PM on toddlers' gut microbiota is rarely investigated. This study aimed to assess the cumulative and lagged effects of varying-sized PMs on toddlers' gut microbiota. We collected demographic information, stool samples, and exposure to PM from 36 toddlers aged 2-3 years. The toddlers were divided into warm season group and cooler season group according to the collection time of stool samples. The gut microbiota was processed and analyzed using 16S rRNA V3-V4 gene regions. The concentration of PM was calculated using China High Air Pollutants (CHAP) database. To assess the mixed effects of varying-sized PM, multiple-PM models were utilized. There were significant differences between the community composition, α- and ß-diversity between two groups. In multiple-PM models, there was a significant effect of weight quantile sum (PM1, PM2.5, and PM10) on α-diversity indices. In weight quantile sum models, after adjusting for a priori confounders, we found a negative effect of weight quantile sum on Enterococcus (ß = -0.134, 95% CI -0.263 to -0.006), positive effects of weight quantile sum on unclassified_f__Ruminococcaceae (ß = 0.247, 95% CI 0.102 to 0.393), Ruminococcus_1 (ß = 0.444, 95% CI 0.238 to 0.650), unclassified_f__Lachnospiraceae (ß = 0.278, 95% CI 0.099 to 0.458), and Family_XIII_AD_3011_group (ß = 0.254, 95% CI 0.086 to 0.422) in WSG and CSG. In lagged weight quantile sum models, the correlation between lag time PM levels and the gut microbiota showed seasonal trends, and weights of PM changed with lag periods. This is the first study to highlight that cumulative and lagged effects of PMs synergistically affect the diversities (α- and ß-diversity) and abundance of the gut microbiota in toddlers. Further research is needed to explore the mediating mechanism of varying-sized PMs exposure on the gut microbiota in toddlers.

Single-cell sequencing analysis of peripheral blood in patients with moyamoya disease.

BACKGROUND: At present, the etiology of moyamoya disease is not clear, and it is necessary to explore the mechanism of its occurrence and development. Although some bulk sequencing data have previously revealed transcriptomic changes in Moyamoya disease, single-cell sequencing data has been lacking. METHODS: Two DSA(Digital Subtraction Angiography)-diagnosed patients with moyamoya disease were recruited between January 2021 and December 2021. Their peripheral blood samples were single-cell sequenced. CellRanger(10 x Genomics, version 3.0.1) was used to process the raw data, demultiplex cellular barcodes, map reads to the transcriptome, and dowm-sample reads(as required to generate normalized aggregate data across samples). There were 4 normal control samples, including two normal samples GSM5160432 and GSM5160434 of GSE168732, and two normal samples of GSE155698, namely GSM4710726 and GSM4710727. Weighted co-expression network analysis was used to explore the gene sets associated with moyamoya disease. GO analysis and KEGG analysis were used to explore gene enrichment pathways. Pseudo-time series analysis and cell interaction analysis were used to explore cell differentiation and cell interaction. RESULTS: For the first time, we present a peripheral blood single cell sequencing landscape of Moyamoya disease, revealing cellular heterogeneity and gene expression heterogeneity. In addition, by combining with WGCNA analysis in public database and taking intersection, the key genes in moyamoya disease were obtained. namely PTP4A1, SPINT2, CSTB, PLA2G16, GPX1, HN1, LGALS3BP, IFI6, NDRG1, GOLGA2, LGALS3. Moreover, pseudo-time series analysis and cell interaction analysis revealed the differentiation of immune cells and the relationship between immune cells in Moyamoya disease. CONCLUSIONS: Our study can provide information for the diagnosis and treatment of moyamoya disease.

Inflammatory cytokines and prenatal depression: Is there a mediating role of maternal gut microbiota?

OBJECTIVE: The mechanism of levels of inflammatory cytokines that affects brain function and mood through gut microbiota has not been fully elucidated. This study aimed to investigate the potential mediating role of gut microbiota between maternal inflammatory cytokines levels and prenatal depression. DESIGN: There were 29 women in the prenatal depression group and 27 women in the control group enrolled in this study. The Edinburgh Postnatal Depression Scale (EPDS) score of 10 was considered the cut-off value for prenatal depression. We collected demographic information, stool and blood samples. The gut microbiota was profiled using V3-V4 gene sequence of 16S rRNA, and the concentration of inflammatory cytokines were analyzed. The mediation model was analyzed by using the model 4 in the process procedure for SPSS. RESULTS: There were significance differences in the concentration of interleukin-1beta (IL-1ß)(Z = -2.383, P = 0.017) and IL-17A (Z = -2.439, P = 0.015) between the prenatal depression group and control group. There was no significant difference in α- diversity and ß-diversity between the two groups. Intestinibacter (OR: 0.012; 95% CI, 0.001-0.195) and Escherichia_Shigella (OR: 0.103; 95% CI, 0.014-0.763) were protective factors for prenatal depression, while Tyzzerella (OR: 17.941; 95% CI, 1.764-182.445) and Unclassified_f_Ruminococcaceae (OR: 22.607; 95% CI, 1.242-411.389) were risk factors. And Intestinibacter play a mediation effect between IL-17A and prenatal depression. CONCLUSION: Maternal gut microbiota is a significant mediator of the relationship between inflammatory cytokines and prenatal depression. Further research is still needed in exploring the mediating mechanisms of gut microbiota between inflammatory cytokines and depression.

Characterization of transverse mode instability with a 4-quadrant photodiode.

Transverse mode instability (TMI) represents the main limitation for the power scaling of fiber laser systems with a diffraction-limited beam quality. In this context, it has become increasingly important to find a cheap and reliable way to monitor and characterize TMI and distinguish this effect from other dynamic perturbations. In this work, with the help of a position-sensitive detector, a novel method is developed to characterize the TMI dynamics even in the presence of power fluctuations. The position information of the fluctuating beam is recorded in the X- and Y-axis of the detector, which are used to track the temporal evolution of the center of gravity of the beam. The trajectories described by the beam within a specific time window contain rich information about TMI, which can be used to gain further insight into this phenomenon.

Liquid-liquid phase separation-related gene in gliomas: FABP5 is a potential prognostic marker.

BACKGROUND: The glioma is the most malignant human brain tumor. Early glioma detection and treatment are still difficult. New biomarkers are desperately required to aid in the evaluation of diagnosis and prognosis. METHODS: The single cell sequencing dataset scRNA-6148 for glioblastoma was obtained from the Chinese Glioma Genome Atlas database. Data were gathered for the transcriptome sequencing project. Genes involved in liquid-liquid phase separation (LLPS) were taken out of the DrLLPS database. To find the modules connected to LLPS, the weighted co-expression network was analyzed. Differential expression analysis was used to identify the differentially expressed genes (DEGs) in gliomas. Pseudo-time series analysis, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were used to investigate the role of important genes in the immunological microenvironment. We examined the function of key glioma genes using polymerase chain reaction (PCR) testing, CCK-8 assays, clone generation assays, transwell assays and wound healing assays. RESULTS: FABP5 was identified as a key gene in glioblastoma by multiomics research. Pseudo-time series analysis showed that FABP5 was highly linked with the differentiation of many different types of cells. GSEA revealed that FABP5 was strongly linked to several hallmark pathways in glioblastoma. We looked at immune cell infiltration and discovered a significant link between FABP5, macrophages and T cell follicular helpers. The PCR experiment results demonstrated that FABP5 expression was elevated in glioma samples. Cell experiments showed that FABP5 knockdown dramatically decreased the viability, proliferation, invasion and migration of the LN229 and U87 glioma cell lines. CONCLUSIONS: Our study provides a new biomarker, FABP5, for glioma diagnosis and treatment.

The landscape of micron-scale particles including microplastics in human enclosed body fluids.

Exogenous microparticles including microplastics are novel pollutants that could persist in the environment with potential health effects, while crucial data on their exposure in humans are still lacking. To understand the panorama of microparticles including microplastics exposure and distribution characteristics in different kinds of body fluids. A non-targeted microparticle internal exposure landscape analysis was done in thirteen kinds of human enclosed body fluids covering eight body systems. Totally 104 patients aged 24-96 years with an average age of 56 years were included in this study. After sample digestion, non-soluble microparticles were detected and identified with one Raman Microspectroscope under a strict quality control-particle detection system. Totally 702 microparticles with size ranging from 2.15 to 103.27 µm were detected in samples. Microparticles were identified into 84 substances or 66 molecules, most of which were firstly reported inside human body. Nine kinds of microplastics were originally reported in human body fluids with their size ranging from 19.66 to 103.27 µm. Microparticles exposure was unexpectedly high inside the human body despite the protection of biological barriers and membranes, raising awareness of the impact of particle pollution on sustainable development.

Fetuin-A alleviates neuroinflammation against traumatic brain injury-induced microglial necroptosis by regulating Nrf-2/HO-1 pathway.

BACKGROUND: The microglia-mediated inflammatory response is a vital mechanism of secondary damage following traumatic brain injury (TBI), but the underlying mechanism of microglial activation is unclear. METHODS: Controlled cortical impact (CCI) was induced in adult male C57BL/6J mice, and glutamate was used to construct a classical in vitro injury model in the primary microglia. Microglial activation was determined by western blot and immunostaining. The inflammatory factors were measured by enzyme-linked immunosorbent assay. The oxidative stress marker and mitochondrial reactive oxygen species (ROS) were measured by immunoblotting and MitoSox Red staining. Transmission electron microscopy was used to observe the typical morphology of necroptotic cells. RESULTS: Our quantitative proteomics identified 2499 proteins; 157 were significantly differentially expressed in brain tissue between the 6 h after CCI (CCI6h) group and sham group, and 109 were significantly differentially expressed between the CCI24h and sham groups. Moreover, compared with the sham group, the terms "acute-phase response", "inflammation", and "protein binding" were significantly enriched in CCI groups. Fetuin-A, a liver-secreted acute-phase glycoprotein, was involved in these biological processes. Using an experimental TBI model, we found that the Fetuin-A level peaked at 6 h and then decreased gradually. Importantly, we showed that administration of Fetuin-A reduced the cortical lesion volume and edema area and inhibited the inflammatory response, which was associated with suppressing microglial necroptosis, thus decreasing microglial activation. Furthermore, administration of Fetuin-A attenuated mitochondrial oxidative stress in glutamate-treated microglial cells, which is a critical mechanism of necroptosis suppression. In addition, we demonstrated that Fetuin-A treatment promoted translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus in vivo; however, the Nrf-2 inhibitor ML385 and si-heme oxygenase-1 (si-HO-1) disrupted the regulation of oxidative stress by Fetuin-A and induced increased ROS levels and necroptosis in glutamate-treated microglial cells. Fetuin-A also protected neurons from adverse factors in vivo and in vitro. CONCLUSIONS: Our results demonstrated that Fetuin-A activated Nrf-2/HO-1, suppressed oxidative stress and necroptosis levels, and thereby attenuates the abnormal inflammatory response following TBI. The findings suggest a potential therapeutic strategy for TBI treatment.

Hsp90 induces Acsl4-dependent glioma ferroptosis via dephosphorylating Ser637 at Drp1.

Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by the iron-dependent lipid reactive oxygen species (ROS) accumulation, but its mechanism in gliomas remains elusive. Acyl-coenzyme A (CoA) synthetase long-chain family member 4 (Acsl4), a pivotal enzyme in the regulation of lipid biosynthesis, benefits the initiation of ferroptosis, but its role in gliomas needs further clarification. Erastin, a classic inducer of ferroptosis, has recently been found to regulate lipid peroxidation by regulating Acsl4 other than glutathione peroxidase 4 (GPX4) in ferroptosis. In this study, we demonstrated that heat shock protein 90 (Hsp90) and dynamin-related protein 1 (Drp1) actively regulated and stabilized Acsl4 expression in erastin-induced ferroptosis in gliomas. Hsp90 overexpression and calcineurin (CN)-mediated Drp1 dephosphorylation at serine 637 (Ser637) promoted ferroptosis by altering mitochondrial morphology and increasing Acsl4-mediated lipid peroxidation. Importantly, promotion of the Hsp90-Acsl4 pathway augmented anticancer activity of erastin in vitro and in vivo. Our discovery reveals a novel and efficient approach to ferroptosis-mediated glioma therapy.

Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-ß signaling.

Glioblastoma (GBM) is the most aggressive primary brain tumor as one of the deadliest cancers. The TGF-ß signaling acts as an oncogenic factor in GBM, and plays vital roles in development of GBM. SMAD7 is a major inhibitor of TGF-ß signaling, while the deubiquitination of SMAD7 has been poorly studied in GBM. Here, we found USP2 as a new prominent candidate that could regulate SMAD7 stability. USP2 was lost in GBM, leading to the poor prognosis in patients. Moreover, aberrant DNA methylation mediated by DNMT3A induced the low expression of USP2 in GBM. USP2 depletion induced TGF-ß signaling and progression of GBM. In contrast, overexpressed USP2 suppressed TGF-ß signaling and GBM development. Specifically, USP2 interacted with SMAD7 and prevented SMAD7 ubiquitination. USP2 directly cleaved Lys27- and Lys48-linked poly-ubiquitin chains of SMAD7, and Lys27-linked poly-ubiquitin chains of SMAD7 K185 mediated the recruitment of SMAD7 to HERC3, which regulated Lys63-linked poly-ubiquitination of SMAD7. Moreover, we demonstrated that the DNMT3A inhibitor SGI-1027 induced USP2, suppressed TGF-ß signaling and GBM development. Thus, USP2 repressed development of GBM by inhibition TGF-ß signaling pathway via the deubiquitination of SMAD7.

Control and stabilization of the modal content of fiber amplifiers using traveling waves.

In this work we present a novel way to manipulate the effect of transverse mode instability by inducing traveling waves in a high-power fiber system. What sets this technique apart is the fact that it allows controlling the direction of the modal energy flow, for the first time to the best of our knowledge. Thus, using the method proposed in this work it will be possible to transfer energy from the higher-order mode into the fundamental mode of the fiber, which mitigates the effect of transverse mode instability, but also to transfer energy from the fundamental mode into the higher-order mode. Our simulations indicate that this approach will work both below and above the threshold of transverse mode instability. In fact, our model reveals that it can be used to force a nearly pure fundamental mode output in the fiber laser system almost independently of the input coupling conditions. In this context, this technique represents the first attempt to exploit the physics behind the effect of transverse mode instability to increase the performance of fiber laser systems.

Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury.

Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.

Psychosocial Characteristics, Perceived Neighborhood Environment, and Physical Activity Among Chinese Adolescents.

This study examined the independent associations between psychosocial factors, perceived neighborhood characteristics, and physical activity (PA) in Chinese adolescents. A cross-sectional study using a convenience sample was conducted in fall 2019 at a high school in Wuhan, China. Sociodemographic data, body weight, height, psychosocial factors, perceptions of neighborhood environment, and PA were collected using questionnaires. Hierarchical linear regression analyses were performed in 4 steps, where step 1 included demographic covariates, step 2 added psychosocial factors into the model, step 3 added perceived neighborhood environmental factors, and step 4 added interaction terms between significant psychosocial and environmental factors. A total of 4027 adolescents were included in analysis. The results of the third model indicated that friends' support (b = 4.58), friends' norms (b = 7.16), barriers to PA (b = -10.19), autonomous motivation (b = 4.75), self-efficacy (b = 8.86), the presence of shops/stores nearby (b = 5.79), and the availability of PA resources (b = 6.02) were significant predictors (P < .05) of moderate to vigorous PA. None of the interaction terms were significant in the fourth model. Our results suggest that interventions targeting the PA of Chinese adolescents should take into account the attitudes toward PA, perceived barriers to PA, controlled motivation, perceptions of neighborhood PA resource availability, and perceived neighborhood safety to maximize effectiveness.

Cryo-shocked cancer cells for targeted drug delivery and vaccination.

Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing "dead cells" by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen-treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge.

Up-regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury.

Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro-inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT-III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.