DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis.

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.

Antigen-specific NK cell memory in rhesus macaques.

Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exists in primates. We found that splenic and hepatic NK cells from SHIV(SF162P3)-infected and SIV(mac251)-infected macaques specifically lysed Gag- and Env-pulsed dendritic cells in an NKG2-dependent fashion, in contrast to NK cells from uninfected macaques. Moreover, splenic and hepatic NK cells from Ad26-vaccinated macaques efficiently lysed antigen-matched but not antigen-mismatched targets 5 years after vaccination. These data demonstrate that robust, durable, antigen-specific NK cell memory can be induced in primates after both infection and vaccination, and this finding could be important for the development of vaccines against HIV-1 and other pathogens.

GluA1 Degradation by Autophagy Contributes to Circadian Rhythm Effects on Cerebral Ischemia Injury.

The mechanisms of many diseases, including central nervous system disorders, are regulated by circadian rhythms. The development of brain disorders such as depression, autism, and stroke is strongly associated with circadian cycles. Previous studies have shown that cerebral infarct volume is smaller at night (active phase) than during the day (inactive phase) in ischemic stroke rodent models. However, the underlying mechanisms remain unclear. Increasing evidence suggests that glutamate systems and autophagy play important roles in the pathogenesis of stroke. Here, we report that GluA1 expression was decreased and autophagic activity was increased in active-phase male mouse models of stroke compared with the inactive-phase models. In the active-phase model, induction of autophagy decreased the infarct volume, whereas inhibition of autophagy increased the infarct volume. Meanwhile, GluA1 expression was decreased following activation of autophagy and increased following inhibition of autophagy. We used Tat-GluA1 to uncouple p62, an autophagic adapter, from GluA1 and found that this blocked the degradation of GluA1, an effect similar to that of inhibition of autophagy in the active-phase model. We also demonstrated that knock-out of the circadian rhythm gene Per1 abolished the circadian rhythmicity of the volume of infarction and also abolished GluA1 expression and autophagic activity in wild-type (WT) mice. Our results suggest an underlying mechanism by which the circadian rhythm participates in the autophagy-dependent regulation of GluA1 expression, which influences the volume of infarction in stroke.SIGNIFICANCE STATEMENT Circadian rhythms affect the pathophysiological mechanisms of disease. Previous studies suggested that circadian rhythms affect the infarct volume in stroke, but the underlying mechanisms remain largely unknown. Here, we demonstrate that the smaller infarct volume after middle cerebral artery occlusion/reperfusion (MCAO/R) during the active phase is related to lower GluA1 expression and activation of autophagy. The decrease in GluA1 expression during the active phase is mediated by the p62-GluA1 interaction, followed by direct autophagic degradation. In short, GluA1 is the substrate of autophagic degradation, which mainly occurs after MCAO/R during the active phase but not the inactive phase.

Application of Proteomics and Machine Learning Methods to Study the Pathogenesis of Diabetic Nephropathy and Screen Urinary Biomarkers.

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide, causing significant health problems. Early diagnosis of the disease is quite inadequate. To screen urine biomarkers of DN and explore its potential mechanism, this study collected urine from 87 patients with type 2 diabetes mellitus (which will be classified into normal albuminuria, microalbuminuria, and macroalbuminuria groups) and 38 healthy subjects. Twelve individuals from each group were then randomly selected as the screening cohort for proteomics analysis and the rest as the validation cohort. The results showed that humoral immune response, complement activation, complement and coagulation cascades, renin-angiotensin system, and cell adhesion molecules were closely related to the progression of DN. Five overlapping proteins (KLK1, CSPG4, PLAU, SERPINA3, and ALB) were identified as potential biomarkers by machine learning methods. Among them, KLK1 and CSPG4 were positively correlated with the urinary albumin to creatinine ratio (UACR), and SERPINA3 was negatively correlated with the UACR, which were validated by enzyme-linked immunosorbent assay (ELISA). This study provides new insights into disease mechanisms and biomarkers for early diagnosis of DN.

Cathepsin B as a key regulator of ferroptosis in microglia following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke marked by elevated mortality and disability rates. Recently, mounting evidence suggests a significant role of ferroptosis in the pathogenesis of ICH. Through a combination of bioinformatics analysis and basic experiments, our goal is to identify the primary cell types and key molecules implicated in ferroptosis post-ICH. This aims to propel the advancement of ferroptosis research, offering potential therapeutic targets for ICH treatment. Our study reveals pronounced ferroptosis in microglia and identifies the target gene, cathepsin B (Ctsb), by analyzing differentially expressed genes following ICH. Ctsb, a cysteine protease primarily located in lysosomes, becomes a focal point in our investigation. Utilizing in vitro and in vivo models, we explore the correlation between Ctsb and ferroptosis in microglia post-ICH. Results demonstrate that ICH and hemin-induced ferroptosis in microglia coincide with elevated levels and activity of Ctsb protein. Effective alleviation of ferroptosis in microglia after ICH is achieved through the inhibition of Ctsb protease activity and protein levels using inhibitors and shRNA. Additionally, a notable increase in m6A methylation levels of Ctsb mRNA post-ICH is observed, suggesting a pivotal role of m6A methylation in regulating Ctsb translation. These research insights deepen our comprehension of the molecular pathways involved in ferroptosis after ICH, underscoring the potential of Ctsb as a promising target for mitigating brain damage resulting from ICH.

Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia.

OBJECTIVE: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema. METHODS: A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation. RESULTS: During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level. CONCLUSION: AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.

Risk factors and predictors of recurrence of febrile seizures in children in Nantong, China: a retrospective cohort study.

BACKGROUND: Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model. METHODS: This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence. RESULTS: Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717. CONCLUSION: Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil-lymphocyte ratio (NLR) as a predictor of FS recurrence.

[Analysis of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferinemia cataract syndrome].

OBJECTIVE: To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferritinemia cataract syndrome (HHCS). METHODS: A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification. RESULTS: The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2417.70 ng/mL, reference range: 30 ~ 400 ng/ml). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c.280A>C and c.124-124+3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c.-160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS. CONCLUSION: The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.

Picturing immediate echolalia within the context of autism: Examining its formats, actions and patterns under conversation analysis.

Echolalia, a prevalent feature of Autism Spectrum Disorders (ASD), has been extensively debated among behaviourists and developmental researchers for decades, long segmenting clinical work within the context of autism. This qualitative study aimed to explore the interactive underpinnings of immediate echolalia naturally occurring in dyadic conversation between autistic individuals and clinicians, employing turn-by-turn and sequence-by-sequence analysis within the framework of Conversation Analysis (CA). The results revealed that varying the complete-incomplete-transformed format, echolalia helped participants a) express their emotions, b) automatically associate conversation, c) organise their response, d) maintain conversational reciprocity, and e) assist with request initiation. Within the context of echolalia, the dynamics of conversation exhibited blocking, diverting, or affiliating patterns. The current study provides insights into the interactive traits of immediate echolalia and underscores the potential utility for clinical therapists to employ the echoic sources in clinical intervention.

Unbalanced regulation of Sec22b and Ykt6 blocks autophagosome axonal retrograde flux in neuronal ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury in ischemic penumbra is accountable for poor outcome of ischemic stroke patients receiving recanalization therapy. Compelling evidence previously demonstrated a dual role of autophagy in stroke. This study aimed to understand the traits of autophagy in the ischemic penumbra and the potential mechanism that switches the dual role of autophagy. We found that autophagy induction by rapamycin and lithium carbonate performed before ischemia reduced neurological deficits and infarction, while autophagy induction after reperfusion had the opposite effect in the male murine middle cerebral artery occlusion/reperfusion model, both of which were eliminated in mice lacking autophagy (Atg7flox/flox; Nestin-Cre). Autophagic flux determination showed that reperfusion led to a blockage of axonal autophagosome retrograde transport in neurons, which then led to autophagic flux damage. Then, we found that ischemia-reperfusion induced changes in the protein levels of Sec22b and Ykt6 in neurons, two autophagosome transport-related factors, in which Sec22b significantly increased and Ykt6 significantly decreased. In the absence of exogenous autophagy induction, Sec22b knockdown and Ykt6 overexpression significantly alleviated autophagic flux damage, infarction, and neurological deficits in neurons or murine exposed to cerebral ischemia-reperfusion in an autophagy-dependent manner. Furthermore, Sec22b knockdown and Ykt6 overexpression switched the outcome of rapamycin post-treatment from deterioration to neuroprotection. Thus, Sec22b and Ykt6 play key roles in neuronal autophagic flux, and modest regulation of Sec22b and Ykt6 may help to reverse the failure of targeting autophagy induction to improve the prognosis of ischemic stroke.Significance Statement:The highly polarized architecture of neurons with neurites presents challenges for material transport, such as autophagosomes, which form at the neurite tip and need to be transported to the cell soma for degradation. Here, we demonstrate that Sec22b and Ykt6 act as autophagosome porters and play an important role in maintaining the integrity of neuronal autophagic flux. Ischemia-reperfusion-induced excess Sec22b and loss of Ykt6 in neurons lead to axonal autophagosome retrograde trafficking failure, autophagic flux damage, and finally neuronal injury. Facilitated axonal autophagosome retrograde transport by Sec22b knockdown and Ykt6 overexpression may reduce ischemia-reperfusion-induced neuron injury and extend the therapeutic window of pharmacological autophagy induction for neuroprotection.

Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Patterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19). METHODS: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using viral culture and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical and epidemiologic metadata were reviewed. RESULTS: We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset and in 1 of 67 (1.5%) immunocompetent patients 10 days after symptom onset (P = .001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients. CONCLUSIONS: Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.

Association between Yili goose sperm motility and expression profiles of mRNA and miRNA in testis.

BACKGROUND: The study was conducted to find out the candidate microRNA (miRNA) and genes that associated with sperm motility of Yili goose through small RNA sequencing of testicular tissue of Yili goose, and provide a theoretical basis for the study of the regulation mechanism of sperm motility of Yili goose gander. RESULTS: In this study, five male geese with high sperm motility and five male geese with low sperm motility were slaughtered to obtain their testis tissues for small RNA sequencing, and biological information methods were used for data analysis. The results showed that a total of 1575 known miRNAs and 68 novel miRNAs were identified in the testis tissue of Yili goose, and 71 differentially expressed miRNAs and 660 differentially expressed genes were screened. GO functional analysis showed that miRNAs target genes were mainly involved in the binding, kinase activity, structural constituent of cytoskeleton and intermediate filament cytoskeleton. KEGG functional analysis showed that miRNAs target genes were significantly enriched in arginine and proline metabolism, glycolysis / gluconeogenesis, fructose and mannose metabolism and beta-Alanine metabolism and other pathways. miRNAs-mRNAs interaction network suggests miR-140/miR-140-3p/miR-140-3p-NKAIN3, let-7d-BTG1 and miR-145-5p/miR -145a-5p-CLEC2E may play an important role in testis development and spermatogenesis. CONCLUSIONS: The results of this study suggest that the sperm motility of Yili goose may be regulated by different miRNAs, and the target genes are significantly enriched in pathways related to sperm metabolism, indicating that miRNAs affect the sperm motility of Yili goose by regulating the metabolic process of sperm and the expression of related genes. This study can provide a reference for revealing the regulation mechanism of Yili goose sperm motility at the molecular level.

Genome-wide association study exploring the genetic architecture of eggshell speckles in laying hens.

BACKGROUND: Eggshell speckle phenotype is an important trait in poultry production because they affect eggshell quality. However, the genetic architecture of speckled eggshells remains unclear. In this study, we determined the heritability of eggshell speckles and conducted a genome-wide association study (GWAS) on purebred Rhode Island Red (RIR) hens at 28 weeks to detect potential genomic loci and candidate genes associated with eggshell speckles. RESULTS: The heritability of eggshell speckles was 0.35 at 28 weeks, and the speckle level is not related to other eggshell quality traits in terms of phenotypic correlation. We detected 311 SNPs (6 significantly, and 305 suggestively associated) and 39 candidate genes associated with eggshell speckles. Based on the pathway analysis, the 39 candidate genes were mainly involved in alpha-linolenic acid metabolism, linoleic acid metabolism, ether lipid metabolism, GnRH signaling pathway, vascular smooth muscle contraction, and MAPK signaling pathway. Ultimately, ten genes, LOC423226, SPTBN5, EHD4, LOC77155, TYRO3, ITPKA, DLL4, PLA2G4B, PLA2G4EL5, and PLA2G4EL6 were considered the most promising genes associated with eggshell speckles that were implicated in immunoregulation, calcium transport, and phospholipid metabolism, while its function in laying hens requires further studies. CONCLUSIONS: This study provides new insights into understanding the genetic basis of eggshell speckles and has practical application value for the genetic improvement of eggshell quality.

Receptor-interacting protein 3-phosphorylated Ca2+ /calmodulin-dependent protein kinase II and mixed lineage kinase domain-like protein mediate intracerebral hemorrhage-induced neuronal necroptosis.

Necroptosis-mediated cell death is an important mechanism in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Our previous study has demonstrated that receptor-interacting protein 1 (RIP1) mediated necroptosis in SBI after ICH. However, further mechanisms, such as the roles of receptor-interacting protein 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), and Ca2+ /calmodulin-dependent protein kinase II (CaMK II), remain unclear. We hypothesized that RIP3, MLKL, and CaMK II might participate in necroptosis after ICH, including their phosphorylation. The ICH model was induced by autologous blood injection. First, we found the activation of necroptosis after ICH in brain tissues surrounding the hematoma (propidium iodide staining). Meanwhile, the phosphorylation and expression of RIP3, MLKL, and CaMK II were differently up-regulated (western blotting and immunofluorescent staining). The specific inhibitors could suppress RIP3, MLKL, and CaMK II (GSK'872 for RIP3, necrosulfonamide for MLKL, and KN-93 for CaMK II). We found the necroptosis surrounding the hematoma and the concrete interactions in RIP3-MLKL/RIP3-CaMK II also both decreased after the specific intervention (co-immunoprecipitation). Then we conducted the short-/long-term neurobehavioral tests, and the rats with specific inhibition mostly had better performance. We also found less blood-brain barrier (BBB) injury, and less neuron loss (Nissl staining) in intervention groups, which supported the neurobehavioral tests. Besides, oxidative stress and inflammation were also alleviated with intervention, which had significant less reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, lactate dehydrogenase (LDH), Iba1, and GFAP surrounding the hematoma. These results confirmed that RIP3-phosphorylated MLKL and CaMK II participate in ICH-induced necroptosis and could provide potential targets for the treatment of ICH patients.

IL-1ß/IL-1R1 signaling is involved in the propagation of α-synuclein pathology of the gastrointestinal tract to the brain.

The pathological hallmark of Parkinson's disease (PD) is the intraneuronal accumulation of misfolded alpha-synuclein (termed Lewy bodies) in dopaminergic neurons of substantia nigra par compacta (SNc). It is assumed that the α-syn pathology is induced by gastrointestinal inflammation and then transfers to the brain by the gut-brain axis. Therefore, the relationship between gastrointestinal inflammation and α-syn pathology leading to PD remains to be investigated. In our study, rotenone (ROT) oral administration induces gastrointestinal tract (GIT) inflammation in mice. In addition, we used pseudorabies virus (PRV) for tracing studies and performed behavioral testing. We observed that ROT treatments enhance macrophage activation, inflammatory mediator expression, and α-syn pathology in the GIT 6-week post-treatment (P6). Moreover, pathological α-syn was localized with IL-1R1 positive neural cells in GIT. In line with these findings, we also find pS129-α-syn signals in the dorsal motor nucleus of the vagus (DMV) and tyrosine hydroxylase in the nigral-striatum dynamically change from 3-week post-treatment (P3) to P6. Following that, pS129-α-syn was dominant in the enteric neural cell, DMV, and SNc, accompanied by microglial activation, and these phenotypes were absent in IL-1R1r/r mice. These data suggest that IL-1ß/IL-1R1-dependent inflammation of GIT can induce α-syn pathology, which then propagates to the DMV and SNc, resulting in PD.

Circadian Rhythm Regulator REV-ERBα Attenuates Neuroapoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) is associated with circadian rhythm abnormalities, in which REV-ERBα plays a major regulatory role. Our ambition was to investigate the capacity of REV-ERBα to inhibit neuronal neuroapoptosis induced by early brain injury (EBI) after SAH. The endovascular perforation model was used to produce experimental SAH in Sprague-Dawley rats. Specific small-interfering RNA was used to downregulate the expression REV-ERBα while SR9009 was used to upregulate the expression before assessments. Short- and long-term neurobehavior assessments, immunofluorescence staining, TUNEL staining, Nissl staining, brain water content, and Western blot were performed. The expression level of endogenous REVERBα tended to increase and then decrease after SAH and peaked at 48 h. REV-ERBα upregulation diminished neuronal apoptosis and enhanced neurological function deficits. Meanwhile, REV-ERBα downregulation aggravated the damage. Furthermore, the levels of downstream proteins of REV-ERBα (i.e., brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK)) changed accordingly with REV-ERBα regulation. REV-ERBα may attenuate neuronal apoptosis in EBI after SAH through the BMAL1/CLOCK pathway.

Educational Psychology Is Evolving to Accommodate Technology, Multiple Disciplines, and Twenty-First-Century Skills.

This article covers recent research activities in educational psychology that have an interdisciplinary emphasis and that accommodate twenty-first-century skills in addition to the traditional foundations of literacy, numeracy, science, reasoning (problem-solving), and academic subject matter. We emphasize digital technologies because they are capable of tracking learning data in rich detail and reliably delivering interventions that are tailored to individual learners in particular sociocultural contexts. This is a departure from inflexible pedagogical approaches that previously have been routinely adopted in most classrooms and other contexts of instruction with no precise record of learning and instructional activities. A good design of educational technology embraces the principles of learning science, identifies the basic types of learning that are needed, implements relevant technological affordances, and accommodates feedback from different stakeholders. This article covers research in literacy, collaborative problem-solving, motivation, emotion, and science, technology, engineering, and mathematics (STEM) areas.

Scattering characteristics of a terahertz Bessel vortex beam by 3D dielectric-coated targets.

In order to explore the application of terahertz (THz) vortex beams in 3D dielectric-coated target detection and imaging, scattering characteristics of a THz Bessel vortex beam by 3D dielectric-coated conducting targets are investigated in terms of the combination of planewave angular spectrum expansion and a physics optics method in this paper. The accuracy of the proposed method is verified by comparing with the results of FEKO software. The scattering characteristics of a THz Bessel vortex beam by several typical 3D dielectric-coated targets are analyzed in detail. The effects of the beam parameters (topological charge, half-cone angle, incident angle and frequency) are discussed. The results show that with an increase of topological charge, the magnitude of the radar cross section (RCS) decreases, and the maximum value moves away from the incident direction gradually; the distribution of the RCS does not keep symmetry as the incident angle increases, and the corresponding orbital angular momentum state distribution of the far-scattered field is distorted remarkably.

Genomic signatures reveal selection in Chinese and European domesticated geese.

The Swan goose and Greylag goose are species of geese native to East Asia and Europe, respectively, and are widely believed to be the ancestors of Chinese and European domesticated geese. The Yili goose (YL) and European domestic geese originated from the Greylag goose, but the history of domestication is unclear. In this study, we sequenced and analyzed the genome of the YL goose and the Hortobagy goose to combine with other previously sequenced goose populations for in-depth analysis. The population genetic variations in Stone geese, East Zhejiang White Geese, Taihu geese and Zi geese were also identified and compared. The results showed that admixture gene flow existed in the YL geese population, which was introgressed by Chinese geese, suggesting that gene flow events were frequent and widespread among domesticated geese. Further selected sweep analysis identified candidate genes and metabolic pathways that may be related to the differences in morphology. Several genes such as TGFBR3L, CMYA5, FOXD1, ARHGEF28 and SUCLG2 are associated with growth, reproduction and fertility traits. The results of this study will help to understand the genetic characteristics of domestic geese and the genes affecting important traits and provide a basis for the improved breed of domestic geese.

Possible Mechanism of Dysphania ambrosioides (L.) Mosyakin & Clemants Seed Extract Suppresses the Migration and Invasion of Human Hepatocellular Carcinoma Cells SMMC-7721.

Mexican tea (Dysphania ambrosioides (L.) Mosyakin & Clemants) is rich in phenolic acids and flavonoids and could be a potential medicinal herb that can be used for prevention of human hepatocellular carcinoma. The objective of this study was to elaborate the possible mechanism for the prevention or treatment of hepatocellular carcinoma using Mexican tea, and to provide new avenues for the utilization of the invasive plant. In this study, the D. ambrosioides seed extracts (CSE) were analyzed by gas chromatography-mass spectrometry, and the effects of CSE on proliferation, migration, invasion, and gene expression of SMMC-7721 cells were investigated. Eight compounds were identified in CSE, and the compound with the highest content was ascaridole (25.82 %). The proliferation was significantly inhibited by CSE (p<0.05), and IC50 values were 0.587 g/L, 0.360 g/L, and 0.361 g/L at 24 h, 36 h, and 48 h, respectively. Migration and invasion were significantly inhibited (p<0.05). The network pharmacology and transcriptome analysis indicated that 2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-one, cis-11-eicosenoic acid and 2-ethylcyclohexanone might be the active compounds. Transcriptome analysis indicated that the Wnt signaling pathway, which is related to migration and invasion, was significantly altered; this was verified by western blot assay. The expression of wnt11, lef1 and mmp7 genes in SMMC-7721 cells was significantly down-regulated (p<0.05), while gsk-3ß was significantly up-regulated (p<0.05). These results indicate that CSE inhibits the invasion and migration of SMMC-7721 cells in hepatocellular carcinoma through the Wnt signaling pathway.