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Compared with the nucleic acid amplification test (NATT), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid antigen self-testing (RAST) has advantages in speed and convenience. However, little is known about people's acceptance and influencing factors for SARS-CoV-2 RAST. A cross-sectional study was conducted from April 21 to 30, 2022 in China. The χ2 test and multivariate logistic regressions were used to identify the influencing factors. The structural equation model was used to test the extended protective motivation theory (PMT) model hypotheses. Among the total of 5107 participants, 62.5% were willing to accept the SARS-CoV-2 RAST. There were significant differences in acceptance among different residences (p < 0.001), educational level (p < 0.001), occupation (p < 0.001), monthly income (p < 0.001), travel frequency (p < 0.05), and feelings about NATT (p < 0.001). Response efficacy (ß = 0.05; p = 0.025) and self-efficacy (ß = 0.84; p < 0.001) had a positive effect, while response cost showed a negative effect (ß = -0.07; p < 0.001). The public's major concerns about SARS-CoV-2 RAST are its reliability, testing method, price, and authority. Overall, a moderate intention to use SARS-CoV-2 RAST was found among the Chinese population. The extended PMT can be used for the prediction of intention to accept the RAST. We need to take measures to increase people's acceptance of SARS-CoV-2 RAST.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Estudios Transversales , Reproducibilidad de los Resultados , ChinaRESUMEN
We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality ß of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.
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Deeply understanding virus-host interactions is a prerequisite for developing effective strategies to control frequently emerging infectious diseases, which have become a serious challenge for global public health. The type I interferon (IFN)-mediated JAK/STAT pathway is well known for playing an essential role in host antiviral immunity, but the exact regulatory mechanisms of various IFN-stimulated genes (ISGs) are not yet fully understood. We herein reported that SerpinA5, as a novel ISG, played a previously unrecognized role in antiviral activity. Mechanistically, SerpinA5 can upregulate the phosphorylation of STAT1 and promote its nuclear translocation, thus effectively activating the transcription of IFN-related signaling pathways to impair viral infections. Our data provide insights into SerpinA5-mediated innate immune signaling during virus-host interactions.
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Antivirales , Quinasas Janus , Antivirales/farmacología , Inmunidad Innata , Quinasas Janus/metabolismo , Fosforilación , Transducción de Señal , Factores de Transcripción STAT/metabolismo , Factor de Transcripción STAT1/metabolismo , Interferón Tipo I/metabolismo , Transporte Activo de Núcleo CelularRESUMEN
Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signalling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on primary differentiated and glioma stem cell (GSCs) migration, finding opposing preferences for anodal and cathodal migration, respectively. We next sought to determine whether chemically disrupting Akt through PTEN upregulation with the PPARγ agonist, pioglitazone, would modulate electrotaxis of these cells. We found that directed cell migration was significantly inhibited with the addition of pioglitazone in both differentiated GBM and GSCs subtypes. Western blot analysis did not demonstrate any change in PPARγ expression with and without exposure to EF. In summary we demonstrate opposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.
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Movimiento Celular/genética , Células Madre Neoplásicas/metabolismo , Neuroglía/metabolismo , PPAR gamma/genética , Taxia , Anilidas/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Electricidad , Electrodos , Campos Electromagnéticos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Neuroglía/efectos de los fármacos , Neuroglía/patología , PPAR gamma/agonistas , PPAR gamma/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Pioglitazona/farmacología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Objective: To determine the neuroprotective effects and underpinning mechanisms of thrombopoietin (TPO), Matrix Metalloproteinase-9(MMP-9) and Nuclear Factor-κB (NF-κB) after focal cerebral ischemia-reperfusion in rats. Methods: Male rats underwent 2 hours of right middle cerebral artery occlusion (MCAO) followed by 22 hours of reperfusion. PBS or TPO (0.1ug/kg) was administered from caudal vein before reperfusion. Neurologic deficits, brain edema, Evans blue (EB) extravasation, NF-κB and MMP-9 expression were subsequently examined. Results: Ischemia-reperfusion injury produced a large area of edema. TPO significantly reduced edema and alleviated neurologic deficits after ischemia-reperfusion. Ischemia-induced increases of NF-κB, MMP-9 and Evans blue extravasation were reduced by TPO intervention. Conclusion: TPO improved neurological function and ameliorated brain edema after stroke, partly by reducing the ischemia-induced increase of NF-κB and MMP-9.
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Edema Encefálico , Isquemia Encefálica/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/metabolismo , Daño por Reperfusión , Trombopoyetina/farmacología , Animales , Barrera Hematoencefálica , Edema Encefálico/complicaciones , Isquemia Encefálica/etiología , Masculino , Fármacos Neuroprotectores , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/complicacionesRESUMEN
Although many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21-34 of ULK4 were present in 4 out of 3391 schizophrenia patients from the International Schizophrenia Consortium, but absent in 3181 controls. Deletions removing exons 33 and 34 of the large splice variant of ULK4 also were enriched in Icelandic schizophrenia and bipolar patients compared with 98,022 controls (Pâ=â0.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts gives a P-value less than 0.0001 for schizophrenia, or for schizophrenia plus bipolar disorder. The expression of ULK4 is neuron-specific and developmentally regulated. ULK4 modulates multiple signalling pathways that include ERK, p38, PKC and JNK, which are involved in stress responses and implicated in schizophrenia. Knockdown of ULK4 disrupts the composition of microtubules and compromises neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia.
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Variaciones en el Número de Copia de ADN/genética , Neuritas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Esquizofrenia/genética , Animales , Movimiento Celular/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Ratones , Neuritas/patología , Neuronas/metabolismo , Neuronas/patología , Esquizofrenia/etiología , Esquizofrenia/patología , Eliminación de SecuenciaRESUMEN
BACKGROUND: Phosphate ester prodrugs of propofol (fospropofol, HX0969W) were designed to avoid the unsatisfactory water solubility of the parent drug. However, in previous clinical trials, there were reported prodrug side effects such as paresthesia and pruritus. The accumulation of a phosphate ester component was found to be the main culprit. To exclude this potential risk, we designed 2 amino acid propofol prodrugs (HX0969-Gly-F3, HX0969-Ala-HCl) based on the lead compound (HX0969) by introducing the amino acid group into the structures of the propofol prodrugs. We hypothesized that the improved propofol prodrugs could not only eliminate those adverse effects but also retain their rapid action and good water solubility. METHODS: The lead compound HX0969 was synthesized by the sodium borohydride-iodine system. HX0969W, HX0969-Gly-F3, and HX0969-Ala-HCl were synthesized from HX0969. The solubility of fospropofol, HX0969W, HX0969-Gly-F3, and HX0969-Ala-HCl in normal saline was tested. The bioconversions from those prodrugs to propofol in different physiological media (rat plasma, rhesus monkey plasma, and rat hepatic microsomes) were determined in vitro. An in vivo test in the rats was performed to measure the 50% effective dose (ED50) of the 4 propofol prodrugs. Their action onset time and duration time were also measured after their equipotent doses were given. RESULTS: (1) The water solubility of fospropofol, HX0969W, HX0969-Gly-F3, and HX0969-Ala-HCl was 461.46 ± 26.40 mg/mL, 189.45 ± 5.02 mg/mL, 49.88 ± 0.58 mg/mL, and 245.99 ± 4.83 mg/mL, respectively; (2) The hydrolysis tests in both the rat plasma and the rhesus monkey plasma revealed that the 2 amino acid prodrugs released propofol to a greater extent at a more rapid rate than the 2 phosphate prodrugs during the testing period of 5 hours. All 4 prodrugs released propofol rapidly in the presence of rat hepatic enzymes; (3) Compared with the previous prodrugs (fospropofol, HX0969W), the 2 novel compounds (HX0969-Gly-F3, HX0969-Ala-HCl) had a much shorter onset time when a much lower dose was given. CONCLUSIONS: Application of the amino acid group to the propofol prodrug can make the prodrug have good water solubility and a more rapid onset of action. In rat plasma, the 2 improved amino acid prodrugs (HX0969-Ala-HCl, HX0969-Gly-F3) had a more rapid rate of propofol release than the 2 phosphate ester prodrugs (fospropofol, HX0969W). The in vivo tests showed that HX0969-Ala-HCl and HX0969-Gly-F3 given IV could have a more rapid onset of action in a smaller dose than fospropofol and HX0969W. This novel design can enhance the efficiency of prodrugs converting to propofol.
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Anestésicos Intravenosos/farmacología , Compuestos Organofosforados/farmacología , Profármacos/farmacología , Propofol/análogos & derivados , Animales , Biotransformación , Diseño de Fármacos , Estabilidad de Medicamentos , Formaldehído/metabolismo , Hidrólisis , Técnicas In Vitro , Macaca mulatta , Microsomas Hepáticos/metabolismo , Compuestos Organofosforados/farmacocinética , Fosfatos/metabolismo , Profármacos/farmacocinética , Propofol/farmacocinética , Propofol/farmacología , Ratas , Ratas Sprague-Dawley , Oxibato de Sodio/farmacología , Solubilidad , AguaRESUMEN
Background: Sleep disturbance is a common comorbidity of major depressive disorder (MDD). However, network homogeneity (NH) changes of the default mode network (DMN) in MDD with sleep disturbances are unclear. Aims: The purpose of this study was to probe the abnormal NH in the DMN in MDD with sleep disturbances and to reveal the differences between MDD with or without sleep disturbances. Methods: Twenty-four patients with MDD and sleep disturbances (Pa_s), 33 patients with MDD without sleep disturbances (Pa_ns) and 32 healthy controls (HCs) were recruited in this study. Resting-state functional imaging data were analysed using NH. Results: Compared with Pa_ns and HCs, Pa_s showed decreased NH in the left superior medial prefrontal cortex and increased NH in the right precuneus. There was a negative correlation between NH in the left superior medial prefrontal cortex and sleep disturbances (r=-0.42, p=0.001) as well as a positive correlation between NH in the right precuneus and sleep disturbances (r=0.41, p=0.002) in patients with MDD. Conclusions: MDD with sleep disturbances is associated with abnormal NH in the DMN, which could differentiate pa_s from pa_ns. The DMN may play a crucial role in the neurobiological mechanisms of MDD with sleep disturbances.
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Bipolar disorder (BD) across different clinical stages may present shared and distinct changes in brain activity. We aimed to reveal the neuroimaging homogeneity and heterogeneity of BD and its relationship with clinical variables and genetic variations. In present study, we conducted fractional amplitude of low-frequency fluctuations (fALFF), functional connectivity (FC) and genetic neuroimaging association analyses with 32 depressed, 26 manic, 35 euthymic BD patients and 87 healthy controls (HCs). Significant differences were found in the bilateral pre/subgenual anterior cingulate cortex (ACC) across the four groups, and all bipolar patients exhibited decreased fALFF values in the ACC when compared to HCs. Furthermore, positive associations were significantly observed between fALFF values in the pre/subgenual ACC and participants' cognitive functioning. No significant changes were found in ACC-based FC. We identified fALFF-alteration-related genes in BD, with enrichment in biological progress including synaptic and ion transmission. Taken together, abnormal activity in ACC is a characteristic change associated with BD, regardless of specific mood stages, serving as a potential neuroimaging feature in BD patients. Our genetic neuroimaging association analysis highlights possible heterogeneity in biological processes that could be responsible for different clinical stages in BD.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/genética , Perfil Genético , Imagen por Resonancia Magnética/métodos , Neuroimagen , Giro del Cíngulo/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.
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Dopamina , Esquizofrenia , Ratones , Humanos , Animales , Dopamina/metabolismo , Esquizofrenia/metabolismo , Área Tegmental Ventral/metabolismo , Ratones Transgénicos , Corteza Prefrontal/metabolismo , Glucosa/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.
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Ratones Noqueados , Netrina-1 , Tractos Piramidales , Animales , Netrina-1/metabolismo , Netrina-1/genética , Ratones , Tractos Piramidales/metabolismo , Tractos Piramidales/patología , Axones/metabolismo , Axones/patologíaRESUMEN
BACKGROUND: The olfactory ensheathing cells (OECs) derived from olfactory bulb (OB) may improve motor function after transplantation in injured spinal cord. However, the effects of OEC transplantation on sensory function have not been reported yet. The purpose of this study is to investigate whether OEC transplantation could affect the sensory function and to analyze the underlying mechanism. RESULTS: OEC transplantation into the hemisected spinal cords can result in hyperalgesia, indicated by radiant and mechanical stimuli towards the plantar surface in rats. This could be associated with upregulation of Brain Derived Neurotrophic Factor (BDNF), indicated by RT-PCR. Immunofluorecent staining showed that BDNF was mainly located in the neurons of the laminas I and II of the dorsal horn. Moreover, a notable upregulation on the level of p-ERK (phosphorylation of extracellular signal-regulated kinase), the downstream molecule of BDNF, was detected by using Western Blot. These findings indicate that the increased BDNF level associated with the p-ERK was possibly involved in neuropathic pain in hemisected spinal cord subjected to OEC transplantation. CONCLUSIONS: The transplantation of OECs may induce the noticeable pain hypersensitivity in rats after hemisected spinal cord injury, and the possible mechanism may be associated with the phosphorylation of ERK and the activated BDNF overexpression.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trasplante de Células/efectos adversos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neuralgia/etiología , Neuroglía/fisiología , Bulbo Olfatorio/citología , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Supervivencia Celular , Células Cultivadas , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/genética , Regulación de la Expresión Génica/fisiología , Hiperalgesia/etiología , Neuronas/metabolismo , Dimensión del Dolor , Umbral del Dolor/fisiología , Estimulación Física/efectos adversos , ARN Mensajero/metabolismo , Ratas , Transducción de Señal/fisiología , Traumatismos de la Médula Espinal/cirugíaRESUMEN
Objective: Sleep disturbances (SD) are commonly found in patients with major depressive disorder (MDD). This study aims to explore the influence of SD symptoms on clinical characteristics in patients with MDD and to investigate the shared and distinct fractional amplitude of low-frequency fluctuation (fALFF) patterns in these patients with or without SD symptoms. Methods: Twenty-four MDD patients with SD symptoms (Pa_s), 33 MDD patients without SD symptoms (Pa_ns) and 32 healthy controls (HCs) were included in this study. The fALFF and correlation analyses were applied to analyze the features of imaging and clinical data. Results: Pa_s showed more severe anxiety and depression than Pa_ns. Compared with Pa_ns, Pa_s exhibited increased fALFF value in the left precuneus. Patients shared abnormal fALFF in the frontal-occipital brain regions. There was a positive correlation between fALFF values of the left precuneus and sleep disturbance scores (r = 0.607, p = 0.0000056734) in all patients in addition to a negative correlation between fALFF values of the left MOG/cuneus and HAMD-17 total scores (r = -0.595, p = 0.002141) in Pa_s. The receiver operating characteristic (ROC) results of the fALFF could be used to discriminate Pa_s from Pa_ns with a specificity of 72.73% and a sensitivity of 70.83%. Conclusion: Pa_s displayed more serious anxiety and depression symptoms. Patients shared abnormal fALFF in the frontal-occipital brain regions, which may be a common characteristic for MDD. And increased fALFF value in the left precuneus might be a specific neuroimaging feature of MDD patients with SD symptoms.
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Food foraging behavior requires higher cognitive function like investing efforts in decision making. Hoarding food for the future consumption in adverse climatic conditions or to avoid predatory threats needs precise perception and potential of decision making to overcome challenges in the time of need. The brain areas and neural circuitry responsible for such cognitive skills are poorly understood. Previously available animal models are trained prior to test, which makes it difficult to understand the true nature of animals, and hoard the food from external source into the cage. The new food foraging behavior test, recently developed and evidenced by Li et al., relies on untrained rats and test the competitive ability and hoarding from source within the test box. It can be used to study decision making potentials and underlying neural bases in laboratory settings. Multiple aspects like food quality/flavor preference, competitive nature can be assessed within the test box and the paradigm is conveniently customizable according the hypothesis. However, a detailed protocol guide, to be followed in the laboratory setting, for food foraging behavior test is not available. Therefore, it is urged to produce an elaborated guide for scientists to conduct food foraging behavior test in convenient and precise manner.
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Cilium is a highly conserved antenna-like structure protruding from the surface of the cell membrane, which is widely distributed on most mammalian cells. Two types of cilia have been described so far which include motile cilia and immotile cilia and the latter are also known as primary cilia. Dysfunctional primary cilia are commonly associated with a variety of congenital diseases called ciliopathies with multifaceted presentations such as retinopathy, congenital kidney disease, intellectual disability, cancer, polycystic kidney, obesity, Bardet Biedl syndrome (BBS), etc. Intraflagellar transport (IFT) is a bi-directional transportation process that helps maintain a balanced flow of proteins or signaling molecules essential for the communication between cilia and cytoplasm. Disrupted IFT contributes to the abnormal structure or function of cilia and frequently promotes the occurrence of ciliopathies. Intraflagellar transport 172 (IFT172) is a newly identified member of IFT proteins closely involved in some rare ciliopathies such as Mainzer-Saldino syndrome (MZSDS) and BBS, though the underpinning causal mechanisms remain largely elusive. In this review, we summarize the key findings on the genetic and protein characteristic of IFT172, as well as its function in intraflagellar transport, to provide comprehensive insights to understand IFT172-related ciliopathies.
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Most existing vaccines, delivered by intramuscular injection (IM), are typically associated with stringent storage requirements under cold-chain distribution and professional administration by medical personnel and often result in the induction of weak mucosal immunity. In this context, we reported a microneedle (MN) patch to deliver chitosan oligosaccharide (COS)-encapsulated DNA vaccines (DNA@COS) encoding spike and nucleocapsid proteins of SARS-CoV-2 as a vaccination technology. Compared with IM immunization, intradermal administration via the MN-mediated DNA vaccine effectively induces a comparable level of neutralizing antibody against SARS-CoV-2 variants. Surprisingly, we found that MN-mediated intradermal immunization elicited superior systemic and mucosal T cell immunity with enhanced magnitude, polyfunctionality, and persistence. Importantly, the DNA@COS nanoparticle vaccine loaded in an MN patch can be stored at room temperature for at least 1 month without a significant decrease of its immunogenicity. Mechanically, our strategy enhanced dendritic cell maturation and antiviral immunity by activating the cGAS-STING-mediated IFN signaling pathway. In conclusion, this work provides valuable insights for the rapid development of an easy-to-administer and thermostable technology for mucosal vaccines.
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Quitosano , Nanopartículas , Vacunas , Inmunidad Mucosa , Oligosacáridos , Anticuerpos AntiviralesRESUMEN
Background: Pre-existing cross-reactive immunity among different coronaviruses, also termed immune imprinting, may have a comprehensive impact on subsequent SARS-CoV-2 infection and COVID-19 vaccination effectiveness. Here, we aim to explore the interplay between pre-existing seasonal coronaviruses (sCoVs) antibodies and the humoral immunity induced by COVID-19 vaccination. Methods: We first collected serum samples from healthy donors prior to COVID-19 pandemic and individuals who had received COVID-19 vaccination post-pandemic in China, and the levels of IgG antibodies against sCoVs and SARS-CoV-2 were detected by ELISA. Wilcoxon rank sum test and chi-square test were used to compare the difference in magnitude and seropositivity rate between two groups. Then, we recruited a longitudinal cohort to collect serum samples before and after COVID-19 vaccination. The levels of IgG antibodies against SARS-CoV-2 S, S1, S2 and N antigen were monitored. Association between pre-existing sCoVs antibody and COVID-19 vaccination-induced antibodies were analyzed by Spearman rank correlation. Results: 96.0% samples (339/353) showed the presence of IgG antibodies against at least one subtype of sCoVs. 229E and OC43 exhibited the highest seroprevalence rates at 78.5% and 72.0%, respectively, followed by NL63 (60.9%) and HKU1 (52.4%). The levels of IgG antibodies against two ß coronaviruses (OC43 and HKU1) were significantly higher in these donors who had inoculated with COVID-19 vaccines compared to pre-pandemic healthy donors. However, we found that COVID-19 vaccine-induced antibody levels were not significant different between two groups with high levelor low level of pre-existing sCoVs antibody among the longitudinal cohort. Conclusion: We found a high prevalence of antibodies against sCoVs in Chinese population. The immune imprinting by sCoVs could be reactivated by COVID-19 vaccination, but it did not appear to be a major factor affecting the immunogenicity of COVID-19 vaccine. These findings will provide insights into understanding the impact of immune imprinting on subsequent multiple shots of COVID-19 vaccines.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Pandemias , Estaciones del Año , Estudios Seroepidemiológicos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Inmunoglobulina GRESUMEN
The gene Unc51-like kinase 4 (ULK4) belongs to the Unc-51-like serine/threonine kinase family and is assumed to encode a pseudokinase with unclear function. Recently, emerging evidence has suggested that ULK4 may be etiologically involved in a spectrum of neuropsychiatric disorders including schizophrenia, but the underlying mechanism remains unaddressed. Here, we summarize the key findings of the structure and function of the ULK4 protein to provide comprehensive insights to better understand ULK4-related neurodevelopmental and neuropsychiatric disorders and to aid in the development of a ULK4-based therapeutic strategy.
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Objectives: Schizophrenia (SCZ) patients display higher incidence of metabolic syndrome (MetS) and comorbidity of type II diabetes. Both atypical antipsychotics and genetic variants are believed to predispose the patients with the risk, but their interplay remains largely unknown. TCF7L2 is one of the most common genes strongly associated with glucose homeostasis which also participates in the pathogenesis of schizophrenia. In this study, we aimed to explore the regulatory roles of TCF7L2 in atypical antipsychotics-induced MetS. Methods: Mice with pancreatic ß-cell-specific Tcf7l2 deletion (CKO) were generated. The CKO mice and control littermates were subjected to olanzapine (4 mg/kg/day) or saline gavage for 6 weeks. Metabolic indices, ß cell mass, and the expressing levels of TCF7L2 and GLP-1R in the pancreatic tissue were closely monitored. Results: Tcf7l2 CKO mice displayed a spectrum of core features of MetS, which included remarkably increased rate of weight gain, higher fasting insulin, higher values of blood lipids (cholesterol, triglyceride, and low-density lipoprotein), impaired glucose tolerance, and hypertrophy of adipocytes. Notably, these effects could be further exacerbated by olanzapine. In addition, Tcf7l2 CKO mice with the olanzapine group showed significantly decreased expressions of GLP-1R protein and a trend of reduced pancreatic ß-cell mass. RT-qPCR revealed that the CKO mice presented a significantly less transcription of Sp5, an important element of the Wnt signaling pathway. Conclusion: Our study illustrates that mice with pancreatic ß-cell-targeted Tcf7l2 deletion were more vulnerable to suffer metabolic abnormalities after olanzapine administration. This impairment may be mediated by the reduced expression of GLP-1R.
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The long interspersed nuclear elements 1 (LINE-1/L1s) are the only active autonomous retrotransposons found in humans which can integrate anywhere in the human genome. They can expand the genome and thus bring good or bad effects to the host cells which really depends on their integration site and associated polymorphism. LINE-1 retrotransposition has been found participating in various neurological disorders such as autism spectrum disorder, Alzheimer's disease, major depression disorder, post-traumatic stress disorder and schizophrenia. Despite the recent progress, the roles and pathological mechanism of LINE-1 retrotransposition in schizophrenia and its heritable risks, particularly, contribution to "missing heritability" are yet to be determined. Therefore, this review focuses on the potentially etiological roles of L1s in the development of schizophrenia, possible therapeutic choices and unaddressed questions in order to shed lights on the future research.