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1.
Proc Natl Acad Sci U S A ; 120(35): e2309062120, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37603744

RESUMEN

Identifying efficient and accurate optimization algorithms is a long-desired goal for the scientific community. At present, a combination of evolutionary and deep-learning methods is widely used for optimization. In this paper, we demonstrate three cases involving different physics and conclude that no matter how accurate a deep-learning model is for a single, specific problem, a simple combination of evolutionary and deep-learning methods cannot achieve the desired optimization because of the intrinsic nature of the evolutionary method. We begin by using a physics-supervised deep-learning optimization algorithm (PSDLO) to supervise the results from the deep-learning model. We then intervene in the evolutionary process to eventually achieve simultaneous accuracy and efficiency. PSDLO is successfully demonstrated using both sufficient and insufficient datasets. PSDLO offers a perspective for solving optimization problems and can tackle complex science and engineering problems having many features. This approach to optimization algorithms holds tremendous potential for application in real-world engineering domains.

2.
J Neurosci ; 44(29)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886059

RESUMEN

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.


Asunto(s)
Ansiedad , Vías Nerviosas , Corteza Prefrontal , Estrés Psicológico , Animales , Ansiedad/psicología , Ansiedad/fisiopatología , Masculino , Estrés Psicológico/psicología , Estrés Psicológico/fisiopatología , Corteza Prefrontal/fisiopatología , Vías Nerviosas/fisiopatología , Vías Nerviosas/fisiología , Ratones , Miedo/fisiología , Miedo/psicología , Ratones Endogámicos C57BL , Área Tegmental Ventral/fisiopatología , Tálamo/fisiopatología , Núcleo Talámico Mediodorsal/fisiología , Núcleo Talámico Mediodorsal/fisiopatología
3.
J Virol ; : e0045824, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814067

RESUMEN

Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-ß, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.

4.
Glia ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801194

RESUMEN

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.

5.
Planta ; 259(6): 125, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634979

RESUMEN

MAIN CONCLUSION: Overexpression of MdLBD3 in Arabidopsis reduced sensitivity to salt and drought stresses and was instrumental in promoting early flowering. Salt and drought stresses have serious effects on plant growth. LATERAL ORGAN BOUNDARY DOMAIN (LBD) proteins are a plant-specific transcription factors (TFs) family and play important roles in plants in resisting to abiotic stress. However, about the function of LBDs in apple and other woody plants is little known. In this study, protein sequences of the LBD family TFs in apples were identified which contained conserved LOB domains. The qRT-PCR analysis showed that the MdLBD3 gene was widely expressed in various tissues and organs. The subcellular localization assay showed that the MdLBD3 protein was localized in the nucleus. Ectopic expression of MdLBD3 in Arabidopsis positively regulated its salt and drought resistance, and promoted early flowering. Collectively, these results showed that MdLBD3 improved the abiotic stress resistance, plant growth and development. Overall, this study provided a new gene for breeding that can increase the abiotic stress tolerance in apple.


Asunto(s)
Arabidopsis , Malus , Factores de Transcripción , Sequías , Fitomejoramiento , Estrés Salino , Clonación Molecular
6.
Opt Lett ; 49(13): 3733-3736, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950254

RESUMEN

The restriction of the field of view (FOV) enlargement and spatial resolution increase during optical monitoring was investigated. Traditional optical instruments usually have a fixed FOV in one test; thus, they have low accuracy for small samples under large motions/deformations. To improve the spatial resolution in a relatively large FOV of an optical instrument, a multiple-view 3D digital image correlation (3D-DIC) method based on pseudo-overlapped imaging is proposed. Using a set of optical components, pseudo-overlapped imaging can image two FOVs with the same camera, which converts one pair of cameras to four virtual cameras. Each virtual camera has the same whole pixels. Therefore, compared with the conventional 3D-DIC system, the proposed method simultaneously enlarges FOVs and increases spatial resolutions by two times. The efficiency, accuracy, and feasibility of the technique were validated through experiments.

7.
FASEB J ; 37(12): e23281, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37933920

RESUMEN

Signaling desensitization is key to limiting signal transduction duration and intensity. Signal transducer and activator of transcription 1 (STAT1) can mediate type II interferon (IFNγ)-induced immune responses, which are enhanced and inhibited by STAT1 phosphorylation and sumoylation, respectively. Here, we identified an N-MYC interacting protein, NMI, which can enhance STAT1 phosphorylation and STAT1-mediated IFNγ immune responses by binding and sequestering the E2 SUMO conjugation enzyme, UBC9, and blocking STAT1 sumoylation. NMI facilitates UBC9 nucleus-to-cytoplasm translocation in response to IFNγ, thereby inhibiting STAT1 sumoylation. STAT1 phosphorylation at Y701 and sumoylation at K703 are mutually exclusive modifications that regulate IFNγ-dependent transcriptional responses. NMI could not alter the phosphorylation level of sumoylation-deficient STAT1 after IFNγ treatment. Thus, IFNγ signaling is modulated by NMI through sequestration of UBC9 in the cytoplasm, leading to inhibition of STAT1 sumoylation. Hence, NMI functions as a switch for STAT1 activation/inactivation cycles by modulating an IFNγ-induced desensitization mechanism.


Asunto(s)
Interferón gamma , Sumoilación , Interferón gamma/metabolismo , Transducción de Señal , Fosforilación , Factor de Transcripción STAT1/genética
8.
Pharmacol Res ; 199: 107042, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38142878

RESUMEN

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.


Asunto(s)
Células Piramidales , Receptores de Dopamina D2 , Ratones , Masculino , Animales , Receptores de Dopamina D2/metabolismo , Células Piramidales/fisiología , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Núcleo Accumbens/fisiología , Conducta Social
9.
Eur J Pediatr ; 183(1): 435-444, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37924349

RESUMEN

The aim of the present study was to define an initial angle called ß and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14 years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle ß was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle ß, and other spirometric parameters were compared among groups. The diagnostic values of angle ß, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle ß. The poor-quality group exhibited a significantly smaller angle ß (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle ß among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle ß and FET values indicated poor-quality MEFV curves. The combination of angle ß < 74.58° and FET < 4.91 s had a significantly larger area under the curve than either one alone. The normal value of angle ß of children aged 4-14 years was 78.40 ± 0.12°.   Conclusions: Angle ß contributes to the quality control evaluation of spirometry in children. Both angle ß < 74.58° and FET < 4.91 s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6 years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle ß, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle ß < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91 s offers a higher diagnostic value.


Asunto(s)
Curvas de Flujo-Volumen Espiratorio Máximo , Niño , Humanos , Espirometría , Capacidad Vital , Pruebas de Función Respiratoria , Curva ROC , Volumen Espiratorio Forzado , Pirina
10.
Appl Opt ; 63(9): 2340-2351, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38568590

RESUMEN

The storage and transmission of videos at high spatial resolution remain a great challenge in image-based optical techniques. The uncertainty of digital image correlation (DIC) was assessed following speckle video compression under High Efficiency Video Coding (HEVC/H.265). First, the evaluation criterion for the DIC accuracy affected by compression was provided. The stability of H.265 video compression in DIC was studied considering different compressed frames under different target quantization parameters (QPs) and compression ratios (CRs). The deformation uncertainty of the DIC itself as affected by H.265 video compression was further investigated through uniform translation and non-uniform sinusoidal deformation performance. Moreover, the optimized digital speckle pattern (DSP) was re-evaluated considering video compression-induced uncertainty. DSPs with parameters of different diameters and randomness were compressed using various QPs and CRs. In addition, DSP evaluation was performed under both translation and non-homogeneous deformation conditions. The feasibility of the re-optimized DSP under H.265 video compression was validated using a defective bending beam, and DSP videos with a speckle size of 8 pixels reached a high CR within an acceptable margin of error.

11.
BMC Pediatr ; 24(1): 314, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714985

RESUMEN

Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.


Asunto(s)
Tratamiento Conservador , Displasia Ectodérmica , Humanos , Masculino , Displasia Ectodérmica/terapia , Recién Nacido , Vendajes
12.
PLoS Genet ; 17(12): e1009947, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34860835

RESUMEN

Efferocytosis is the process by which phagocytes recognize, engulf, and digest (or clear) apoptotic cells during development. Impaired efferocytosis is associated with developmental defects and autoimmune diseases. In Drosophila melanogaster, recognition of apoptotic cells requires phagocyte surface receptors, including the scavenger receptor CD36-related protein, Croquemort (Crq, encoded by crq). In fact, Crq expression is upregulated in the presence of apoptotic cells, as well as in response to excessive apoptosis. Here, we identified a novel gene bfc (booster for croquemort), which plays a role in efferocytosis, specifically the regulation of the crq expression. We found that Bfc protein interacts with the zinc finger domain of the GATA transcription factor Serpent (Srp), to enhance its direct binding to the crq promoter; thus, they function together in regulating crq expression and efferocytosis. Overall, we show that Bfc serves as a Srp co-factor to upregulate the transcription of the crq encoded receptor, and consequently boosts macrophage efferocytosis in response to excessive apoptosis. Therefore, this study clarifies how phagocytes integrate apoptotic cell signals to mediate efferocytosis.


Asunto(s)
Proteínas de Drosophila , Factores de Transcripción GATA , Fagocitos , Fagocitosis , Receptores Depuradores , Animales , Apoptosis/genética , Antígenos CD36/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Factores de Transcripción GATA/genética , Regulación del Desarrollo de la Expresión Génica/genética , Macrófagos/metabolismo , Fagocitos/metabolismo , Fagocitosis/genética , Receptores de Superficie Celular/genética , Receptores Depuradores/genética
13.
Molecules ; 29(2)2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38257230

RESUMEN

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.


Asunto(s)
Corylus , Hiperuricemia , Animales , Polifenoles/farmacología , Ácido Clorogénico/farmacología , Simulación del Acoplamiento Molecular , Pez Cebra , Farmacología en Red , Quempferoles , Hiperuricemia/tratamiento farmacológico , Xantina Oxidasa , Extractos Vegetales/farmacología
14.
J Neurosci ; 42(11): 2356-2370, 2022 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-35105676

RESUMEN

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeA neurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeA neurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeA neurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA-BNST). Optogenetic activation and inhibition of the sEHCeA-BNST pathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeA neurons underlying anxiety.SIGNIFICANCE STATEMENT Soluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeA neurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeA neurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.


Asunto(s)
Núcleo Amigdalino Central , Núcleos Septales , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/psicología , Núcleo Amigdalino Central/metabolismo , Núcleos Cerebelosos/metabolismo , Epóxido Hidrolasas , Humanos , Masculino , Ratones , Núcleos Septales/fisiología
15.
Anal Chem ; 95(4): 2452-2459, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36657472

RESUMEN

For the early diagnosis and effective evaluation of treatment effects of inflammation, a de novo bioanalytical method is urgently needed to monitor the metabolite nitric oxide (NO) associated with inflammatory diseases. However, developing a reliable detection method with excellent water solubility, biocompatibility, long retention time, and blood circulation is still challenging. In this work, we reported for the first time a de novo host-guest self-assembled nanosensor CTA for the quantitative detection and visualization of NO levels in inflammatory models. CTA mainly consists of two parts: (i) an adamantyl-labeled guest small-molecule RN-adH containing a classical response moiety o-phenylenediamine for a chemical-specific response toward NO and fluorophore rhodamine B with excellent optical properties as an internal reference for self-calibration and (ii) a remarkable water-soluble and biocompatible supramolecular ß-cyclodextrin polymer (Poly-ß-CD) host. In the presence of NO, the o-phenylenediamine unit was reacted with NO at a low pH value of ∼7.0, accompanied by changes in the intensity of the two emission peaks corrected for each other and the change in fluorescence color of the CTA solution from fuchsia to pink. Furthermore, CTA was an effective tool for NO detection with a fast response time (∼60 s), high selectivity, and sensitivity (LOD: 22.3 nM). Impressively, the CTA nanosensor has successfully achieved the targeted imaging of NO in living inflammatory RAW 264.7 cells and mice models with satisfactory results, which can provide a powerful molecular tool for the visualization and assessment of the occurrence and development of NO-related inflammatory diseases in complex biosystems.


Asunto(s)
Colorantes Fluorescentes , Óxido Nítrico , Animales , Ratones , Colorantes Fluorescentes/química , Fenilendiaminas , Agua/química
16.
Opt Express ; 31(12): 19958-19967, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37381400

RESUMEN

Micro bunched electron beams with periodic longitudinal density modulation at optical wavelengths give rise to coherent light emission. In this paper, we show attosecond micro bunched beam generation and acceleration in laser-plasma wakefield via particle-in-cell simulations. Due to the near-threshold ionization with the drive laser, the electrons with phase-dependent distributions are non-linearly mapped to discrete final phase spaces. Electrons can preserve this initial bunching structure during the acceleration, leading to an attosecond electron bunch train after leaving the plasma with separations of the same time scale. The modulation of the comb-like current density profile is about 2k0 ∼ 3k0, where k0 is the wavenumber of the laser pulse. Such pre-bunched electrons with low relative energy spread may have potential in applications related to future coherent light sources driven by laser-plasma accelerators and broad application prospects in attosecond science and ultrafast dynamical detection.

17.
Mol Psychiatry ; 27(2): 873-885, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34642458

RESUMEN

Long-term potentiation (LTP) in the hippocampus is the most studied form of synaptic plasticity. Temporal integration of synaptic inputs is essential in synaptic plasticity and is assumed to be achieved through Ca2+ signaling in neurons and astroglia. However, whether these two cell types play different roles in LTP remain unknown. Here, we found that through the integration of synaptic inputs, astrocyte inositol triphosphate (IP3) receptor type 2 (IP3R2)-dependent Ca2+ signaling was critical for late-phase LTP (L-LTP) but not early-phase LTP (E-LTP). Moreover, this process was mediated by astrocyte-derived brain-derived neurotrophic factor (BDNF). In contrast, neuron-derived BDNF was critical for both E-LTP and L-LTP. Importantly, the dynamic differences in BDNF secretion play a role in modulating distinct forms of LTP. Moreover, astrocyte- and neuron-derived BDNF exhibited different roles in memory. These observations enriched our knowledge of LTP and memory at the cellular level and implied distinct roles of astrocytes and neurons in information integration.


Asunto(s)
Astrocitos , Factor Neurotrófico Derivado del Encéfalo , Astrocitos/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Plasticidad Neuronal/fisiología , Neuronas/metabolismo
18.
Mol Psychiatry ; 27(2): 896-906, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34697452

RESUMEN

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.


Asunto(s)
Extinción Psicológica , Miedo , Animales , Extinción Psicológica/fisiología , Miedo/fisiología , Masculino , Ratones , Neurregulina-1 , Plasticidad Neuronal/fisiología , Parvalbúminas , Corteza Prefrontal/fisiología , Receptor ErbB-4
19.
BMC Gastroenterol ; 23(1): 54, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36879203

RESUMEN

BACKGROUND: The purpose of this research was to construct a novel predictive nomogram to identify specific stage IB gastric adenocarcinoma (GAC) populations who could benefit from postoperative adjuvant chemotherapy (ACT). METHOD: Between 2004 and 2015, 1889 stage IB GAC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) program database. Then Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were implemented. Finally, the predictive nomograms were constructed. The methods of area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to validate the clinical effectiveness of the models. RESULTS: Of these patients, 708 cases underwent ACT, while the other 1181 patients didn't receive ACT. After PSM, the patients in the ACT group presented a longer median overall survival (133 vs. 85 months, p = 0.0087). Among the ACT group, 194 (36.0%) patients achieving more prolonged overall survival than 85 months were regarded as the beneficiary population. Then the logistic regression analyses were performed, and age, gender, marital status, primary site, tumor size, and regional nodes examined were included as predicting factors to construct the nomogram. The AUC value was 0.725 in the training cohort and 0.739 in the validation cohort, which demonstrated good discrimination. And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. Furthermore, the prognostic nomogram predicting 1-, 3-, and 5-year cancer-specific survival presented good predictive ability. CONCLUSION: The benefit nomogram could guide clinicians in decision-making and selecting optimal candidates for ACT among stage IB GAC patients. And the prognostic nomogram presented great prediction ability for these patients.


Asunto(s)
Adenocarcinoma , Nomogramas , Humanos , Quimioterapia Adyuvante , Adenocarcinoma/tratamiento farmacológico , Área Bajo la Curva , Bases de Datos Factuales
20.
Avian Pathol ; 52(1): 12-24, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35980124

RESUMEN

The aim of this study was to evaluate the effects of anti-stress agents on the growth performance and immune function of broilers under immune stress conditions induced by vaccination. A total of 128, 1-day-old Arbor Acres broilers were randomly divided into four groups. Group normal control (NC) was the control group. Group vaccination control (VC), T 0.5%, and T 1% were the treatment groups, which were nasally vaccinated with two doses of the Newcastle disease virus (NDV) vaccine. The chicks in groups T 0.5% and T 1% were fed conventional diets containing 0.5% and 1% anti-stress agents. Thereafter, these broilers were slaughtered on 1, 7, 14, and 21 days post-vaccination. The results indicated that anti-stress agents could significantly reduce serum adrenocorticotropic hormone (ACTH) (P < 0.01) and cortisol (CORT) (P < 0.05) levels, and improve the growth performance (P < 0.05) and immune function of broilers (P < 0.05); However, the levels of malondialdehyde (MDA) (P < 0.05) were decreased, and the decreased total antioxidant capacity (T-AOC) (P < 0.01) levels mediated by vaccination were markedly improved. In addition, anti-stress agents could attenuate apoptosis in spleen lymphocytes (P < 0.01) by upregulating the ratio of Bcl-2 to BAX (P < 0.01) and downregulating the expression of caspase-3 and -9 (P < 0.01), which might be attributed to the inhibition of the enzymatic activities of caspase-3 and -9 (P < 0.05). In conclusion, anti-stress agents may improve growth performance and immune function in broilers under immune-stress conditions.RESEARCH HIGHLIGHTS Investigation of effects and mechanism of immune stress induced by vaccination.Beneficial effect of anti-stress agents on growth performance, immune function, oxidative stress, and regulation of lymphocyte apoptosis.Demonstration of the effects of apoptosis on immune function in the organism.


Asunto(s)
Antioxidantes , Pollos , Animales , Caspasa 3/metabolismo , Antioxidantes/metabolismo , Dieta/veterinaria , Vacunación/veterinaria , Inmunidad , Alimentación Animal/análisis , Suplementos Dietéticos
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