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Research in environmental education adopts a broad concept of environmental literacy, recognizing the multifaceted nature that encompasses cognitive, affective, and behavioral components. However, minimal research has examined how these components interact with each other across various cities. The present study aims to fill this gap by investigating the interplay between the components of environmental literacy, such as affiliation with nature, environmental knowledge, and environmental behavior. More importantly, the study explores how these relationships vary across different cities that differ in sustainable development levels. Children (N = 979, M[subscript age] = 11.13) from 29 cities in China completed measures of affiliation with nature, environmental literacy, and pro-environmental behavior (PEB). We classified the cities into high versus low sustainable development levels using the Low-Carbon and Green Index--a comprehensive measure of sustainable development, including energy consumption, carbon emissions, and public policy. A moderated mediation analysis revealed that environmental knowledge mediated the relation between affiliation with nature and PEB only in cities with higher sustainable levels. As a result, environmental education should be tailored to a city's sustainable development level to better encourage pro-environmental behavior.

Abstract Heteroaromatic N‐oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N‐oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic N‐oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu‐catalyzed atroposelective method for synthesizing biaryl N‐oxides via de novo heteroaromatic N‐oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of N‐oxides with novel heteroaromatic scaffolds. The axially chiral N‐oxide product 3f demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product 3e exhibits promising therapeutic efficacy against triple‐negative breast cancer, with IC50 values of 4.8 and 5.2 µm in MDA‐MB‐231 and MDA‐MB‐468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic N‐oxides but also encourages further exploration of N‐oxide entities in the discovery of bioactive small molecules.

BackgroundAirway mucus hypersecretion (AMH) can occur in children with acute respiratory diseases, but its underlying mechanisms and relationship with the lower respiratory tract microbiota (LRTM) are not yet fully understood. This study investigates the characteristics of LRTM in children with Mycoplasma pneumoniae pneumonia (MPP) and its impact on AMH.MethodsWe collected bronchoalveolar lavage fluid and related clinical indicators from 202 children with MPP. 16S rRNA gene amplicon sequencing was used for detection and identification. Microbial diversity and characteristic genera were compared, and their abundance was analyzed for correlations with clinical factors.ResultsAs the disease course (days from onset to bronchoscopy, grouped into T1, T2, T3) extended, α-diversity of the LRTM gradually increased, particularly in the T3 hypersecretion group. Moreover, significant differences were observed in the incidence of AMH, co-infection rates, peripheral white blood cell (WBC) count, and C-reactive protein levels. In AMH, Mycoplasmoides and Veillonella abundance and peripheral neutrophils were risk factors for increased secretions. In addition, in the T3 co-infection group, Streptococcus and Prevotella increased, replacing Stenotrophomonas as the dominant genus, possibly due to β-lactam antibiotic use. Prevotella abundance was strongly correlated with WBC.ConclusionThe composition and structure of LRTM in children with MPP played a crucial role in AMH and disease progression.

Abstract We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day “0”) or repeated mild (1.5 atm on days “0” and “2”) traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1–9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

African swine fever virus (ASFV) is a large double-stranded DNA virus with a complex structural architecture and encodes more than 150 proteins, where many are with unknown functions. E184L has been reported as one of the immunogenic ASFV proteins that may contribute to ASFV pathogenesis and immune evasion. However, the antigenic epitopes of E184L are not yet characterized. In this study, recombinant E184L protein was expressed in prokaryotic expression system and four monoclonal antibodies (mAbs), designated as 1A10, 2D2, 3H6, and 4C10 were generated. All four mAbs reacted specifically with ASFV infected cells. To identify the epitopes of the mAbs, a series of overlapped peptides of E184L were designed and expressed as maltose binding fusion proteins. Accordingly, the expressed fusion proteins were probed with each E184L mAb separately by using Western blot. Following a fine mapping, the minimal linear epitope recognized by mAb 1A10 was identified as 119IQRQGFL125, and mAbs 2D2, 3H6, and 4C10 recognized a region located between 153DPTEFF158. Alignment of amino acids of E184L revealed that the two linear epitopes are highly conserved among different ASFV isolates. Furthermore, the potential application of the two epitopes in ASFV diagnosis was assessed through epitope-based ELISA using 24 ASFV positive and 18 negative pig serum and the method were able to distinguish positive and negative samples, indicating the two epitopes are dominant antigenic sites. To our knowledge, this is the first study to characterize the B cell epitopes of the antigenic E184L protein of ASFV, offering valuable tools for future research, as well as laying a foundation for serological diagnosis and epitope-based marker vaccine development.

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

African swine fever (ASF) continues to cause enormous economic loss to the global pig industry. Since there is no safe and effective vaccine, accurate and timely diagnosis of ASF is essential to implement control measures. Indirect immunofluorescence assay (IFA) is a gold standard serological method recommended by the World Organization for Animal Health (WOAH). In this study, we used primary fetal kidney cells to establish a wild boar cell line (BK2258) that supported the efficient replication of ASF virus (ASFV) SD/DY-I/21 and showed visible cytopathic effect (CPE). Moreover, using BK2258, we established a sensitive and specific IFA for ASFV antibody detection. To standardize and evaluate the performance of this assay, we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20, and immunized with the vaccine candidate HLJ/18-7GD, field samples, and negative serum samples. The IFA reacted with the ASFV-positive sera and displayed bright fluorescence foci. There was no non-specific green fluorescence due to cellular senescence or other cell damage-causing factors. Compared to a commercial indirect enzyme-linked immunosorbent assay (iELISA), ASFV antibodies were detected 1–4 days earlier using our IFA. The detection limits of the IFA and iELISA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400, respectively, indicating that the IFA is more sensitive than iELISA. The newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens (i.e., Classical swine fever virus (CSFV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcme circovirus type 2 (PCV2), Pseudorabies virus (PRV), Foot-and-Mouth disease virus type O (FMDV/O), and Porcine epidemic diarrhea virus (PEDV)). This study thus provides a sensitive, specific, and reliable detection method that is suitable for the serological diagnosis of ASF.

IntroductionSleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation.MethodsRats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed.ResultsCompared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1–7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation.DiscussionIn conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

Hemorrhagic transformation (HT) and restrictive therapeutic time window are significant limitations of delayed t-PA (tissue-type plasminogen activator) thrombolytic therapy in ischemic stroke patients. Plant Momordica charantia-derived exosome-like nanovesicles (MC-ELNs) can protect the blood–brain barrier (BBB) and inhibit neuronal apoptosis in stroke rats by inhibiting matrix metalloproteinase 9(MMP-9) expression. This study explored the therapeutic function and underlying mechanisms of MC-ELNs in treating HT. In delayed t-PA-treated ischemia-reperfusion rats, MC-ELNs significantly reduced mortality, HT, and cell apoptosis; MC-ELNs improved neurological function and BBB's integrity. MC-ELNs reduced ONOO− and MMP-9 expression and inhibited the release of HMGB1 from intracellular to extracellular in vivo and in vitro. ONOO− donor SIN-1 directly induced extracellular secretion of HMGB1, MC-ELNs and FeTmPyP (ONOO− decomposition catalyst, PDC) significantly reduced the expression of HMGB1 and inhibited MMP-9 activation in vitro. These findings indicate that MC-ELNs could protect BBB integrity and improve t-PA-induced HT by inhibiting the ONOO−/HMGB1/MMP-9 pathway.

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 μM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 μM) promoted nuclear translocation of β-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the β-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Background: The role home-schooling of children in parental mental health during the COVID-19 pandemic in Taiwan remains unknown. This study aimed to assess the association between parental psychological distress and home-schooling in a socio-ecological context during the peak of the first wave of the COVID-19 pandemic in Taiwan. Methods: This was a prospective cohort study. In total, 902 parents (father: n = 206, mother: n = 696) who home-schooled children under 18 years of age were recruited by purposive sampling from 17 cities in Taiwan. Data were collected between 19 July and 30 September 2021 through a survey. Multilevel regression models were used to examine the association between parents’ psychological distress and home-schooling considering the characteristics at the person and city levels. Results: Parental psychological distress was positively associated with difficulty in setting up electronic devices and increased disputes between parents and children, and it was negatively associated with time management and increased time spent bonding with their children during home-schooling (Ps

Background: Infants and children with feeding difficulties have swallowing dysfunction and high risk of aspiration, which could be silent without choking, resulting in recurrent pneumonia and long-term respiratory morbidity. Videofluoroscopic swallow study (VFSS) is a useful tool for real-time visualization of the swallowing process and airway aspiration. This study reported a single-institutional 10-year experience of VFSS in pediatric patients with feeding difficulties and the efficacy of swallowing therapy. Methods: From 2011 to 2020, 30 infants and children with feeding difficulties received VFSS examinations in a medical center at a median age of 19 months (range 7 days–8 years). The images of the swallowing process (oral phase, triggering of pharyngeal swallowing, and pharyngeal phase) under videofluoroscopy were analyzed by a radiologist and a speech-language pathologist. Aspiration severity was assessed from VFSS observations and rated by an eight-point Penetration-Aspiration-Scale (PAS), with higher scores indicating increased severity. Swallowing therapy was performed by experienced speech-language therapists, and follow-up of oral feeding tolerance and risk of aspiration pneumonia was done. Results: Of the 30 patients, 24 (80%) had neurological deficits. High PAS scores (6–8) were observed in 25 (83.4%) patients, and 22 had a PAS score of 8, indicating silent aspiration. Of the 25 patients with high PAS scores, 19 (76%) had neurological deficits, and 18 (72%) depended on tube feeding at a median age of 20 months. Swallowing problems occurred most frequently during the pharyngeal phase in the patients with high PAS scores. VFSS-based swallowing therapy improved oral feeding ability and reduced aspiration episodes. Conclusion: Infants and children with swallowing dysfunction and neurological deficits had high risk of severe aspiration. Swallowing problems in the pharyngeal phase were the most common VFSS findings in patients with severe aspiration. VFSS may help guide problem-oriented swallowing therapy to reduce the risk of recurrent aspiration.

Utilizing a longitudinal dataset encompassing 30 Chinese provinces and municipalities (with the exception of Tibet, Hong Kong, Macao, and Taiwan) that spans the years 2011 through to 2021, this study adopts the spatial Durbin model to study the path and mechanism behind the promotion of carbon emission reductions through intelligent manufacturing. The results show the following: ① Intelligent manufacturing plays a crucial role in promoting the reduction of carbon emissions. ② Government interventions can amplify the positive influence of intelligent manufacturing in reducing carbon emissions, and intelligent manufacturing promotes carbon emission reductions by accelerating scientific and technological innovation. ③ There is temporal heterogeneity: upgrading intelligent manufacturing exerted a substantial influence in advancing the reduction of carbon emissions during the timeframe from 2011 to 2019, while it exerted a notable impeding impact on the reduction of carbon emissions during the timeframe from 2011 to 2019. ④ There is spatial heterogeneity: in the eastern region, upgrading intelligent manufacturing promoted carbon emission reductions in 2011–2015, but it inhibited carbon emission reductions in 2016–2021. Consequently, here are the insights we have distilled: ① Enhancing the overall advancement level of intelligent manufacturing can effectively promote carbon emission reductions in China; ② It can also play an important role in guiding governments in making these upgrades and actively promoting them in conjunction with technological innovations.

Background: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. Methods: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. Results: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. Conclusions: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Abstract Children of mothers with hypertensive disorders of pregnancy (HDP) have high rates of preterm-birth (gestational age

Blood-brain barrier (BBB) dysfunction plays a pivotal role in the pathology of chronic cerebral hypoperfusion (CCH)-related neurodegenerative diseases. Continuous endothelial cells (EC) that line the blood vessels of the brain are important components of the BBB to strictly control the flow of substances and maintain the homeostatic environment of the brain. However, the molecular mechanisms from the perspective of EC-induced BBB dysfunction after CCH are largely unknown. In this study, the BBB function was assessed using immunostaining and transmission electron microscopy. The EC dysfunction profile was screened by using EC enrichment followed by RNA sequencing. After identified the key EC dysfunction factor, C-kit, we used the C-kit inhibition drug (imatinib) and C-kit down-regulation method (AAV-BR1-C-kit shRNA) to verify the role of C-kit on BBB integrity and EC transcytosis after CCH. Furthermore, we also activated C-kit with stem cell factor (SCF) to observe the effects of C-kit on BBB following CCH. We explored that macromolecular proteins entered the brain mainly through EC transcytosis after CCH and caused neuronal loss. Additionally, we identified receptor tyrosine kinase C-kit as a key EC dysfunction molecule. Furthermore, the pharmacological inhibition of C-kit with imatinib counteracted BBB leakage by reducing caveolae-mediated transcytosis. Moreover, treatment with AAV-BR1-C-kit shRNA, which targets brain EC to inhibit C-kit expression, also ameliorated BBB leakage by reducing caveolae-mediated transcytosis. Furthermore, the SCF increased the permeability of the BBB by actively increasing caveolae-mediated transcytosis. This study provides evidence that C-kit is a key BBB permeability regulator through caveolae-mediated transcytosis in EC after CCH.

Abstract African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry.

Safety resilient city is a frontier concept of urban safety development and a hot topic in the field of urban safety research. In this paper, the relevant research results of domestic and foreign scholars are reviewed from the perspectives of concepts and models, the evaluation indicator system of urban safety resilience is compared in terms of risk types, evaluation objects, evaluation dimensions and quantitative methods, and the development of international standards for resilient cities is discussed. Based on the literature review, the connotation of the triangular theoretical model of urban safety resilience is explained, and an urban safety resilience evaluation index system applicable to Chinese cities is proposed, which provides support for the development of the national standard “Guide for safety resilient city evaluation” (GB/T 40947-2021). It is applied to six representative cities as examples for evaluation to explore the direction of Chinese urban safety resilience improvement. The pathway for improving the safety resilience of Chinese cities is discussed.

Although existing studies have proved that autistic traits (AT) may have relations to non-suicidal self-injury (NSSI) behaviors, its associations with anxiety, rumination and experiential avoidance (EA) are still unclear. The current study, based on a sample of 1317 Chinese college students, explored the associations between AT, anxiety and NSSI, and the possible modulating roles of rumination and EA in these associations. The results shows that 1) a total of 334 (25.36%) students reported a history of NSSI and 30 (2.28%) students were categorized as high AT; 2) Students with high AT reported higher rates of NSSI than those with low AT (36.67% vs. 25.10%); 3) AT, anxiety, rumination and EA have positive relations with NSSI; 4) AT predicted NSSI indirectly through anxiety; 5) Rumination and EA significantly moderated the effects of AT on NSSI via anxiety. In conclusion, this study confirms the indirect effect of AT on NSSI through anxiety in Chinese college students, and further clarifies the reinforcing effects of rumination and EA on the associations between AT, anxiety and NSSI. These findings suggest that developing adaptive emotion-regulating strategies and positive coping styles might promote the prevention and treatment of NSSI behaviors among autistic individuals.

Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue (cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.

Abstract Background Myxomycetes are a group of eukaryotes belonging to Amoebozoa, which are characterized by a distinctive life cycle, including the plasmodium stage and fruit body stage. Plasmodia are all found to be associated with bacteria. However, the information about bacteria diversity and composition in different plasmodia was limited. Therefore, this study aimed to investigate the bacterial diversity of plasmodia from different myxomycetes species and reveal the potential function of plasmodia-associated bacterial communities. Results The bacterial communities associated with the plasmodia of six myxomycetes (Didymium iridis, Didymium squamulosum, Diderma hemisphaericum, Lepidoderma tigrinum, Fuligo leviderma, and Physarum melleum) were identified by 16S rRNA amplicon sequencing. The six plasmodia harbored 38 to 52 bacterial operational taxonomic units (OTUs) that belonged to 7 phyla, 16 classes, 23 orders, 40 families, and 53 genera. The dominant phyla were Bacteroidetes, Firmicutes, and Proteobacteria. Most OTUs were shared among the six myxomycetes, while unique bacteria in each species only accounted for a tiny proportion of the total OTUs. Conclusions Although each of the six myxomycetes plasmodia had different bacterial community compositions, a high similarity was observed in the plasmodia-associated bacterial communities' functional composition. The high enrichment for gram-negative (> 90%) and aerobic (> 99%) bacteria in plasmodia suggest that myxomycetes may positively recruit certain kinds of bacteria from the surrounding environment.

Abstract The interrelationships between neuronal viability, synaptic integrity, and microglial responses remain in infancy. In dealing with the question, we induced a stretch injury to evaluate the mechanical effects of trauma on rat primary cortical neurons and BV2 microglial cells in a transwell culture system. The viability of primary neurons and BV2 cells was determined by MTT. Synaptic integrity was evaluated by determining the expression of beta-secretase 1 (BACE1), amyloid-beta (Aβ), microtubule-associated protein 2 (MAP2), and synaptophysin (vehicle protein). Both CD16/32-positive (CD16/32+) and CD206-positive (CD206+) microglia cells were detected by immunofluorescence staining. The phagocytic ability of the BV2 cells was determined using pHrodo E. coli BioParticles conjugates and flow cytometry. We found that stretch injury BV2 cells caused reduced viability and synaptic abnormalities characterized by Aβ accumulation and reductions of BACE1, MAP2, and synaptophysin in primary neurons. Intact BV2 cells exhibited normal phagocytic ability and were predominantly CD206+ microglia cells, whereas the injured BV2 cells exhibited reduced phagocytic ability and were predominantly CD16/32+ microglial cells. Like a stretch injury, the injured BV2 cells can cause both reduced viability and synaptic abnormalities in primary neurons; intact BV2 cells, when cocultured with primary neurons, can protect against the stretch-injured-induced reduced viability and synaptic abnormalities in primary neurons. We conclude that CD206+ and CD16/32+ BV-2 cells can produce neuroprotective and cytotoxic effects on primary cortical neurons.

Abstract Depression is a common and debilitating condition for which effective treatments are needed. Lepidium meyenii Walp (Maca) is a plant with potential medicinal effects in treating depression. Recently, there has been growing interest in plant‐derived extracellular vesicles (EVs) due to their low toxicity and ability to transport to human cells. Targeting the gut–brain axis, a novel strategy for depression management, may be achieved through the use of Maca‐derived EVs (Maca‐EVs). In this study, we successfully isolated Maca‐EVs using gradient ultracentrifugation and characterized their shape, size, and markers (CD63 and TSG101). The in vivo imaging showed that the Dil‐labeled Maca‐EVs crossed the brain–blood barrier and accumulated in the brain. The behavioral tests revealed that Maca‐EVs dramatically recovered the depression‐like behaviors of unpredictable chronic mild stress (UCMS) mice. UCMS mice fecal were characterized by an elevated abundance of g_Enterococcus, g_Lactobacillus, and g_Escherichia_Shigella, which were significantly restored by administration of Maca‐EVs. The effects of Maca‐EVs on the altered microbial and fecal metabolites in UCMS mice were mapped to biotin, pyrimidine, and amino acid (tyrosine, alanine, aspartate, and glutamate) metabolisms, which were closely associated with the serotonin (5‐HT) production. Maca‐EVs were able to increase serum monoamine neurotransmitter levels in UCMS mice, with 5‐HT showing the most significant changes. We further demonstrated that 5‐HT improved the expression of brain‐derived neurotrophic factor, a key regulator of neuronal plasticity, and its subsequent activation of TrkB/p‐AKT signaling by regulating the GTP‐Cdc42/ERK pathway. These findings suggest that Maca‐EVs enhance 5‐HT release, possibly by modulating the gut–brain axis, to improve depression behavior. Our study sheds light on a novel approach to depression treatment using plant‐derived EVs.

BackgroundPrior studies have proved the relationships between childhood emotional abuse (CEA) histories and suicidal thoughts or behaviors in adulthood, however, how emotion regulation strategies work as the mediating mechanism is necessary to be investigated. This study aimed to further verify the impacts of rumination, experiential avoidance (EA) and depression on the associations between CEA and non-suicidal self-injury (NSSI) and suicidal ideation (SI) on a sample of Chinese college students.MethodsThe Childhood Emotional Abuse Questionnaire, the Non-Suicidal Self-Injury Questionnaire, the Symptom Checklist, the Ruminative Response Scale, the Acceptance and Action Questionnaire-II and the Zung Self-Rating Depression Scale were completed by 1,317 college students.ResultsThe rates of NSSI and SI of students with CEA experiences were 31.70 and 7.90% respectively, both higher than those without such experiences. The mediating roles of rumination, EA and depression between CEA and NSSI and SI were significant (p

Abstract The distinctive layered crystal structures and diverse properties of 2D layered materials (2DLMs) have established them as prospective building blocks for implementing next‐generation optoelectronics. One critical predicament in terms of light sensing is the weak absorption caused by the atomic‐scale thickness, as well as the limited effective wavelength range/low spectral selectivity constrained by the intrinsic band structures. Despite the fact that numerous noble metal antennas are harnessed for enhancing the light–matter coupling, they suffer from exorbitant cost and narrow resonant optical windows. To this end, a number of non‐noble plasmonic optical antennas have been developed to improve the light‐sensing properties of 2DLM photodetectors, and tremendous advances have been accomplished. Herein, a comprehensive overview of this subject is provided based on four aspects; namely, non‐noble metal antenna promoted 2DLM photodetectors, heteroatom doped semiconductor antenna promoted 2DLM photodetectors, non‐stoichiometric semiconductor antenna promoted 2DLM photodetectors, and MXene antenna promoted 2DLM photodetectors. The focus is on the device structures, preparation, and underlying mechanisms. In the end, the challenges are highlighted, and potential strategies addressing them are proposed, which aim to navigate the upcoming exploration in the related domains and fully exert the pivotal role of non‐noble plasmonic optical antennas toward advancing 2DLM photodetectors.

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against S. aureus. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on S. aureus cells, which would eventually cause the cellular autolysis.

World trade networks are exhaustively described by pairwise interactions, and overlook higher-order structure from the outcome of collective interactions at the level of groups of nodes like multilateral trade agreements. To address this limitation, we collect multiplex world trade networks, including the bilateral regional trade agreement network, which represents pairwise interactions; the multilateral regional trade agreement network, which naturally represents a higher-order network structure; and the import and export trade network, which represents pairwise interactions and additional complexities. The analysis of simplicial centrality, including degree, closeness, and subgraph at 0, 1, and 2-simplex levels, reveals that intra-level correlations are high, while inter-levels may exhibit significant disparities. Nodes with low centrality at higher-order levels could influence network robustness due to the diversity of interactions and higher-order dependencies. Simplicial centrality on robustness of multiplex world trade networks under random and targeted attacks reveals that the complex connectivity of higher-order levels renders them more vulnerable post-attack. An optimization strategy of the rebalancing of network centrality is proposed to enhance the robustness, and the simulation shows risks posed to central nodes are minimized and opportunities for peripheral nodes to partake in global trade are broadened.

Detecting light from a wealth of physical degrees of freedom (e.g. wavelength, intensity, polarization state, phase, etc) enables the acquirement of more comprehensive information. In the past two decades, low-dimensional van der Waals materials (vdWMs) have established themselves as transformative building blocks toward lensless polarization optoelectronics, which is highly beneficial for optoelectronic system miniaturization. This review provides a comprehensive overview on the recent development of low-dimensional vdWM polarized photodetectors. To begin with, the exploitation of pristine 1D/2D vdWMs with immanent in-plane anisotropy and related heterostructures for filterless polarization-sensitive photodetectors is introduced. Then, we have systematically epitomized the various strategies to induce polarization photosensitivity and enhance the degree of anisotropy for low-dimensional vdWM photodetectors, including quantum tailoring, construction of core–shell structures, rolling engineering, ferroelectric regulation, strain engineering, etc, with emphasis on the fundamental physical principles. Following that, the ingenious optoelectronic applications based on the low-dimensional vdWM polarized photodetectors, including multiplexing optical communications and enhanced-contrast imaging, have been presented. In the end, the current challenges along with the future prospects of this burgeoning research field have been underscored. On the whole, the review depicts a fascinating landscape for the next-generation high-integration multifunctional optoelectronic systems.

African swine fever (ASF) is a highly infectious, transboundary viral disease of domestic and wild pigs, and is currently the most serious threat to world swine production, resulting in significant economic loss. In the absence of vaccines and treatments, the control of the disease entirely depends on accurate and early diagnosis accompanied by the culling of infected pigs. Thus, a highly specific and sensitive diagnostic assay is required during an outbreak and surveillance of the disease. In this study, a highly sensitive, specific, rapid and repeatable P22-monoclonal antibody-based blocking enzyme-linked immunosorbent assay (bELISA) assay was developed for the detection of antibodies against genotype I and II African swine fever viruses(ASFVs). A total of 806 pig serum samples were tested to evaluate the performance of the diagnostic assay. To determine the PI (percent Inhibition) cut-off value, receiver-operating characteristic (ROC) analysis was applied. According to the ROC analysis of the data, 98.10% specificity and 100% sensitivity were recorded when the threshold cut-off value of PI was established at 47%. In addition, the assay was able to detect ASFV antibodies as early as 9 days post-infection when serum samples from experimentally infected pigs were used. Taking all together, the results of the present study indicated that the P22-mAb based bELISA assay can be used for rapid and accurate detection of antibodies against ASFV, which could play a valuable role in the containment and prevention of ASFV as an alternative to other serological diagnostic methods. Also, this study will assist researchers to further investigate the immunogenic importance of P22 protein in ASFV infection.

Abstract Aims To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after cerebral ischemic/reperfusion (I/R). Methods The apoptosis and proliferation of C17.2 cells transfected with the p-KAP1-expression plasmids and the expression of proliferation cell nuclear antigen (PCNA) and p-KAP1 were detected by immunofluorescence and Western blotting after the Oxygen Glucose deprivation/reperfusion model (OGD/R). The interaction of p-KAP1 and CUL4A with PCNA was analyzed by immunoprecipitation. In the rats MCAO model, we performed the adeno-associated virus (AAV) 2/9 gene delivery of p-KAP1 mutants to verify the proliferation of endogenous NSCs and the colocalization of PCNA and CUL4A by immunofluorescence. Results The level of p-KAP1 was significantly down-regulated in the stroke model in vivo and in vitro. Simulated p-KAP1(S824) significantly increased the proliferation of C17.2 cells and the expression of PCNA after OGD/R. Simulated p-KAP1(S824) enhanced the binding of p-KAP1 and PCNA and decreased the interaction between PCNA and CUL4A in C17.2 cells subjected to OGD/R. The AAV2/9-mediated p-KAP1(S824) increased endogenous NSCs proliferation, PCNA expression, p-KAP1 binding to PCNA, and improved neurological function in the rat MCAO model. Conclusions Our findings confirmed that simulated p-KAP1(S824) improved the survival and proliferation of endogenous NSCs. The underlying mechanism is that highly expressed p-KAP1(S824) promotes binding to PCNA, and inhibits the binding of CUL4A to PCNA. This reduced CUL4A-mediated ubiquitination degradation to increase the stability of PCNA and promote the survival and proliferation of NSCs.

Polyurea is widely used in marine anti-corrosion engineering because it has the physical advantages of high tensile strength, strong adhesion, excellent waterproof and anti-corrosion performance as well as mature construction technology. In this paper, the origin, characteristics and development direction of polyurea coating technology were first introduced, and then the applications of polyurea coating in the fields of concrete protection and metal protection in marine atmospheric environment and seawater environment in recent years were summarized, respectively. Aiming at the problems of coating performance degradation and failure caused by complex environmental factors such as temperature, corrosive medium erosion and collision during service, the research progress of new polyurea coatings was discussed, including the research on improving the performance of coatings such as corrosion resistance, wetting and hardness with organic and inorganic nanoparticles as fillers, and the research on new polyurea microcapsule coatings that could respond intelligently and repair microcracks independently, and the research on the processing and preparation technology of new self-healing materials such as electrospinning. Finally, the shortcomings and challenges of the current research on polyurea coating were pointed out, and the future research trend of polyurea coating in marine environment was prospected.

Objective To explore the mechanism of two-partner secretion with an in vitro reconstitution system. Methods Spheroplasts were used to construct FhaB mutants with different molecular weights, and then combined with FhaC containing proteoliposomes to perform the translocation experiments followed by digestion with proteinase K to test the transportation of substrates with different sizes in vitro by this recombinant system. Results After successful construction of the mutant, 37 ku, 60 ku and 80 ku bands secreted by spheroplasts were detected, and FhaC-containing protein liposomes could transport these three substrates with molecular weight as high as 80 ku. Conclusions The recombinant transport system constructed in vitro may transport substrates with large molecular weight and the mechanism of the two-partner secretion can be studied by this system.

Emergencies in gas pipeline networks can lead to significant loss of life and property, necessitating extensive professional knowledge for effective response and management. Effective emergency response depends on specialized knowledge, which can be captured efficiently through domain-specific lexicons. The goal of this research is to develop a specialized lexicon that integrates domain-specific knowledge to improve emergency management in gas pipeline networks. The process starts with an enhanced version of Term Frequency–Inverse Document Frequency (TF-IDF), a statistical method used in information retrieval, combined with filtering logic to extract candidate words from investigation reports. Simultaneously, we fine tune the Chinese Bidirectional Encoder Representations from Transformers (BERT) model, a state-of-the-art language model, with domain-specific data to enhance semantic capture and integrate domain knowledge. Next, words with similar meanings are identified through word similarity analysis based on standard terminology and risk inventories, facilitating lexicon expansion. Finally, the domain-specific lexicon is formed by amalgamating these words. Validation shows that this method, which integrates domain knowledge, outperforms models that lack such integration. The resulting lexicon not only assigns domain-specific weights to terms but also deeply embeds domain knowledge, offering robust support for cause analysis and emergency management in gas pipeline networks. [ABSTRACT FROM AUTHOR]

Background Paroxysmal sympathetic hyperactivity (PSH) has been linked to a worse clinical prognosis in patients with traumatic brain injury. We aimed to identify the risk factors and clinical features associated with basilar artery occlusion (BAO) presenting with PSH as the first clinical presentation. Methods This study recruited patients with acute BAO who received endovascular therapy (EVT) at two stroke centers in China. PSH Assessment Measure ≥8 was included in the PSH+ group, while those with a score below 8 were classified as the PSH-group. Clinical data and radiological findings were compared between the two groups. A binary logistic regression model was employed to identify independent risk factors for PSH. Results 101 participants were enrolled, of whom 19 (18.8%) presented with PSH as the initial manifestation of BAO. Worse prognosis (modified Rankin Scale score of 4-6) at day 90 occurred in 14 (73.7%) of the PSH+ patients and 42 (51.2%) of the PSH-patients (P=0.076). The 90-day mortality rate was higher in the PSH+ group with 12 (63.2%) participants, compared with 31 (37.8%) participants in the PSH-group (P=0.044). A significantly increased risk of PSH was found in patients with midbrain involvement (OR 6.53, 95% CI 1.56 to 27.30, P=0.01) and a high baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 1.15, 95% CI 1.01 to 1.31, P=0.037). Conclusions Patients with BAO presenting with PSH as the initial clinical manifestation experience a higher risk of 90-day mortality, despite undergoing EVT. Midbrain infarction and baseline NIHSS score may be significant risk factors for PSH following BAO. [ABSTRACT FROM AUTHOR]