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Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.
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Canales Iónicos Sensibles al Ácido , Isquemia Encefálica , Ácido Glutámico , Animales , Femenino , Humanos , Masculino , Ratones , 2-Amino-5-fosfonovalerato/efectos adversos , 2-Amino-5-fosfonovalerato/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , Canales Iónicos Sensibles al Ácido/química , Canales Iónicos Sensibles al Ácido/deficiencia , Canales Iónicos Sensibles al Ácido/efectos de los fármacos , Canales Iónicos Sensibles al Ácido/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Regulación Alostérica/efectos de los fármacos , Sitios de Unión/genética , Isquemia Encefálica/inducido químicamente , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ácido Glutámico/análogos & derivados , Ácido Glutámico/metabolismo , Ácido Glutámico/farmacología , Ácido Glutámico/toxicidad , Ratones Noqueados , Mutagénesis Sitio-Dirigida , Protones , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
The tongue is a highly specialized muscular organ with diverse cellular origins, which provides an excellent model for understanding mechanisms controlling tissue-tissue interactions during organogenesis. Previous studies showed that SHH signaling is required for tongue morphogenesis and tongue muscle organization, but little is known about the underlying mechanisms. Here we demonstrate that the Foxf1/Foxf2 transcription factors act in the cranial neural crest cell (CNCC)-derived mandibular mesenchyme to control myoblast migration into the tongue primordium during tongue initiation, and thereafter continue to regulate intrinsic tongue muscle assembly and lingual tendon formation. We performed chromatin immunoprecipitation sequencing analysis and identified Hgf, Tgfb2 and Tgfb3 among the target genes of Foxf2 in the embryonic tongue. Through genetic analyses of mice with CNCC-specific inactivation of Smo or both Foxf1 and Foxf2, we show that Foxf1 and Foxf2 mediate hedgehog signaling-mediated regulation of myoblast migration during tongue initiation and intrinsic tongue muscle formation by regulating the activation of the HGF and TGFß signaling pathways. These data uncover the molecular network integrating the SHH, HGF and TGFß signaling pathways in regulating tongue organogenesis.
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Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog , Ratones , Animales , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Organogénesis/genética , Lengua , Transducción de Señal/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismoRESUMEN
Hybrid plants are found extensively in the wild, and they often demonstrate superior performance of complex traits over their parents and other selfing plants. This phenomenon, known as heterosis, has been extensively applied in plant breeding for decades. However, the process of decoding hybrid plant genomes has seriously lagged due to the challenges associated with genome assembly and the lack of appropriate methodologies for their subsequent representation and analysis. Here, we present the assembly and analysis of two hybrids, an intraspecific hybrid between two maize (Zea may ssp. mays) inbred lines and an interspecific hybrid between maize and its wild relative teosinte (Zea may ssp. parviglumis), utilizing a combination of PacBio High Fidelity (HiFi) sequencing and chromatin conformation capture sequencing data. The haplotypic assemblies are well-phased at chromosomal scale, successfully resolving the complex loci with extensive parental structural variations (SVs). By integrating into a bi-parental genome graph, the haplotypic assemblies can facilitate downstream short-reads-based SV calling and allele-specific gene expression analysis, demonstrating outstanding advantages over a single linear genome. Our work offers a comprehensive workflow that aims to facilitate the decoding of numerous hybrid plant genomes, particularly those with unknown or inaccessible parentage, thereby enhancing our understanding of genome evolution and heterosis.
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In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.
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Envejecimiento Prematuro , Linfocitos T , Animales , Ratones , Envejecimiento/genética , Envejecimiento Prematuro/genética , Apoptosis , Inflamación , MamíferosRESUMEN
T1 image is a widely collected imaging sequence in various neuroimaging datasets, but it is rarely used to construct an individual-level brain network. In this study, a novel individualized radiomics-based structural similarity network was proposed from T1 images. In detail, it used voxel-based morphometry to obtain the preprocessed gray matter images, and radiomic features were then extracted on each region of interest in Brainnetome atlas, and an individualized radiomics-based structural similarity network was finally built using the correlational values of radiomic features between any pair of regions of interest. After that, the network characteristics of individualized radiomics-based structural similarity network were assessed, including graph theory attributes, test-retest reliability, and individual identification ability (fingerprinting). At last, two representative applications for individualized radiomics-based structural similarity network, namely mild cognitive impairment subtype discrimination and fluid intelligence prediction, were exemplified and compared with some other networks on large open-source datasets. The results revealed that the individualized radiomics-based structural similarity network displays remarkable network characteristics and exhibits advantageous performances in mild cognitive impairment subtype discrimination and fluid intelligence prediction. In summary, the individualized radiomics-based structural similarity network provides a distinctive, reliable, and informative individualized structural brain network, which can be combined with other networks such as resting-state functional connectivity for various phenotypic and clinical applications.
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Encéfalo , Radiómica , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , NeuroimagenRESUMEN
Neurodegeneration arising from aging, injury, or diseases has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration affects dendrites, in part due to the limited assay systems available. To develop an assay for dendrite degeneration and repair, we used photo-switchable caspase-3 (caspase-Light-Oxygen-Voltage-sensing [caspase-LOV]) in peripheral class 4 dendrite arborization (c4da) neurons to induce graded neurodegeneration by adjusting illumination duration during development and adulthood in Drosophila melanogaster. We found that both developing and mature c4da neurons were able to survive while sustaining mild neurodegeneration induced by moderate caspase-LOV activation. Further, we observed active dendrite addition and dendrite regeneration in developing and mature c4da neurons, respectively. Using this assay, we found that the mouse Wallerian degeneration slow (WldS) protein can protect c4da neurons from caspase-LOV-induced dendrite degeneration and cell death. Furthermore, our data show that WldS can reduce dendrite elimination without affecting dendrite addition. In summary, we successfully established a photo-switchable assay system in both developing and mature neurons and used WldS as a test case to study the mechanisms underlying dendrite regeneration and repair.
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Dendritas/metabolismo , Drosophila melanogaster , Animales , Caspasas/metabolismo , Técnicas Citológicas/métodos , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ratones , Neuronas/metabolismo , Degeneración Walleriana/metabolismoRESUMEN
The effects of surface roughness on the performance of the Zn metal anode in aqueous electrolytes are investigated by experiments and computational simulations. Smooth surfaces can homogenize the nucleation and growth of Zn, which helps to form a flat Zn anode under high current density. In spite of these advantages, the whole surface of the smooth electrode serves as the reactive contact area for parasitic reactions, generating severe hydrogen evolution, corrosion, and byproduct formation, which seriously hinder the long-term cycle stability of the Zn anode. To trade off this double-sided effect, we identify a medium degree of surface roughness that could stabilize the Zn anode for 1000 h cycling at 1.0 mAh cm-2. The electrode also enabled stable cycling for 800 h at a high current density of 5.0 mAh cm-2. This naked Zn metal anode with optimized surface roughness holds great promise for direct use in aqueous zinc ion batteries.
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BACKGROUND: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis. RESULTS: We report generation of Alx4f/f conditional mice and show that tissue-specific Cre-mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4-null mice but without affecting postnatal survival. While Alx4-null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development. CONCLUSION: The Alx4f/f mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.
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The significance of iron in myocardial mitochondria function cannot be underestimated, because deviations in iron levels within cardiomyocytes may have profound detrimental effects on cardiac function. In this study, we investigated the effects of ferroportin 1 (FPN1) on cardiac iron levels and pathological alterations in mice subjected to chronic intermittent hypoxia (CIH). The cTNT-FPN1 plasmid was administered via tail vein injection to induce the mouse with FPN1 overexpression in the cardiomyocytes. CIH was established by exposing the mice to cycles of 21%-5% FiO2 for 3 min, 8 h per day. Subsequently, the introduction of hepcidin resulted in a reduction in FPN1 expression, and H9C2 cells were used to establish an IH model to further elucidate the role of FPN1. First, FPN1 overexpression ameliorated CIH-induced cardiac dysfunction, myocardial hypertrophy, mitochondrial damage and apoptosis. Second, FPN1 overexpression attenuated ROS levels during CIH. In addition, FPN1 overexpression mitigated CIH-induced cardiac iron accumulation. Moreover, the administration of hepcidin resulted in a reduction in FPN1 levels, further accelerating the CIH-induced levels of ROS, LIP and apoptosis in H9C2 cells. These findings indicate that the overexpression of FPN1 in cardiomyocytes inhibits CIH-induced cardiac iron accumulation, subsequently reducing ROS levels and mitigating mitochondrial damage. Conversely, the administration of hepcidin suppressed FPN1 expression and worsened cardiomyocyte iron toxicity injury.
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Apoptosis , Cardiomegalia , Proteínas de Transporte de Catión , Hipoxia , Hierro , Miocitos Cardíacos , Especies Reactivas de Oxígeno , Animales , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Cardiomegalia/metabolismo , Cardiomegalia/genética , Cardiomegalia/patología , Cardiomegalia/etiología , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Hipoxia/metabolismo , Hipoxia/complicaciones , Ratones , Especies Reactivas de Oxígeno/metabolismo , Hierro/metabolismo , Masculino , Hepcidinas/metabolismo , Hepcidinas/genética , Línea Celular , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , RatasRESUMEN
The evolution of jaws has played a major role in the success of vertebrate expansion into a wide variety of ecological niches. A fundamental, yet unresolved, question in craniofacial biology is about the origin of the premaxilla, the most distal bone present in the upper jaw of all amniotes. Recent reports have suggested that the mammalian premaxilla is derived from embryonic maxillary prominences rather than the frontonasal ectomesenchyme as previously shown in studies of chicken embryos. However, whether mammalian embryonic frontonasal ectomesenchyme contributes to the premaxillary bone has not been investigated and a tool to trace the contributions of the frontonasal ectomesenchyme to facial structures in mammals is lacking. The expression of the Alx3 gene is activated highly specifically in the frontonasal ectomesenchyme, but not in the maxillary mesenchyme, from the beginning of facial morphogenesis in mice. Here, we report the generation and characterization of a novel Alx3CreERT2 knock-in mouse line that express tamoxifen-inducible Cre DNA recombinase from the Alx3 locus. Tamoxifen treatment of Alx3CreERT2/+;Rosa26mTmG/+ embryos at E7.5, E8.5, E9.5, and E10.5, each induced specific labeling of the embryonic medial nasal and lateral nasal mesenchyme but not the maxillary mesenchyme. Lineage tracing of Alx3CreERT2-labeled frontonasal mesenchyme from E9.5 to E16.5 clearly showed that the frontonasal mesenchyme cells give rise to the osteoblasts generating the premaxillary bone. Furthermore, we characterize a Dlx1-Cre BAC transgenic mouse line that expresses Cre activity in the embryonic maxillary but not the frontonasal mesenchyme and show that the Dlx1-Cre labeled embryonic maxillary mesenchyme cells contribute to the maxillary bone as well as the soft tissues lateral to both the premaxillary and maxillary bones but not to the premaxillary bone. These results clearly demonstrate the developmental origin of the premaxillary bone from embryonic frontonasal ectomesenchyme cells in mice and confirm the evolutionary homology of the premaxilla across amniotes.
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Cabeza , Factores de Transcripción , Embrión de Pollo , Ratones , Animales , Factores de Transcripción/genética , Cara , Huesos Faciales , Ratones Transgénicos , MamíferosRESUMEN
All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.
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Currently, the desired research focus in energy storage technique innovation has been gradually shifted to next-generation aqueous batteries holding both high performance and sustainability. However, aqueous Zn-I2 batteries have been deemed to have great sustainable potential, owing to the merits of cost-effective and eco-friendly nature. However, their commercial application is hindered by the serious shuttle effect of polyiodides during reversible operations. In this work, a Janus functional binder based on chitosan (CTS) molecules was designed and prepared; the polar terminational groups impart excellent mechanical robustness to hybrid binders; meanwhile, it can also deliver isochronous enhancement on physical adsorption and redox kinetics toward I2 species. By feat of highly effective remission to shuttle effect, the CTS cell exhibits superb electrochemical storage capacities with long-term robustness, specifically, 144.1 mAh g-1, at a current density of 0.2 mA g-1 after 1500 cycles. Simultaneously, the undesired self-discharging issue could be also well-addressed; the Coulombic efficiency could remain at 98.8 % after resting for 24 h. More importantly, CTS molecules endow good biodegradability and reusable properties; after iodine species were reloaded, the recycled devices could also deliver specific capacities of 73.3 mAh g-1, over 1000 cycles. This Janus binder provides a potential synchronous solution to realize high comprehensive performance with high iodine utilization and further make it possible for sustainable Zn-I2 batteries.
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Repeated use of opioid analgesics may cause a paradoxically exacerbated pain known as opioid-induced hyperalgesia (OIH), which hinders effective clinical intervention for severe pain. Currently, little is known about the neural circuits underlying OIH modulation. Previous studies suggest that laterocapsular division of the central nucleus of amygdala (CeLC) is critically involved in the regulation of OIH. Our purpose is to clarify the role of the projections from infralimbic medial prefrontal cortex (IL) to CeLC in OIH. We first produced an OIH model by repeated fentanyl subcutaneous injection in male rats. Immunofluorescence staining revealed that c-Fos-positive neurons were significantly increased in the right CeLC in OIH rats than the saline controls. Then, we used calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) labeling and the patch-clamp recordings with ex vivo optogenetics to detect the functional projections from glutamate pyramidal neurons in IL to the CeLC. The synaptic transmission from IL to CeLC, shown in the excitatory postsynaptic currents (eEPSCs), inhibitory postsynaptic currents (eIPSCs) and paired-pulse ratio (PPR), was observably enhanced after fentanyl administration. Moreover, optogenetic activation of this IL-CeLC pathway decreased c-Fos expression in CeLC and ameliorated mechanical and thermal pain in OIH. On the contrary, silencing this pathway by chemogenetics exacerbated OIH by activating the CeLC. Combined with the electrophysiology results, the enhanced synaptic transmission from IL to CeLC might be a cortical gain of IL to relieve OIH rather than a reason for OIH generation. Scaling up IL outputs to CeLC may be an effective neuromodulation strategy to treat OIH.
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Analgésicos Opioides , Hiperalgesia , Ratas , Masculino , Animales , Hiperalgesia/metabolismo , Analgésicos Opioides/metabolismo , Ratas Sprague-Dawley , Amígdala del Cerebelo/metabolismo , Dolor/metabolismo , Fentanilo , Corteza Prefrontal/metabolismoRESUMEN
Microplastics, such as polylactic acid (PLA), are ubiquitous environmental pollutants with unclear implications for health impact. This study aims to elucidate the mechanisms of PLA-induced inflammatory liver injury, focusing on disturbance of bile acid metabolism. The in vitro PLA exposure experiment was conducted using HepG2 cells to assess cell viability, cytokine secretion, and effects on bile acid metabolism. In vivo, male C57BL/6 J mice were exposed to PLA for ten days continuously, liver function and histopathological assessment were evaluated after the mice sacrificed. Molecular analyses including quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, were applied to evaluate the expression of bile acid metabolizing enzymes and transporters. PLA exposure resulted in decreased cell viability in HepG2 cells, increased inflammation and altered bile acid metabolism. In mice, PLA exposure resulted in decreased body weight and food intake, impaired liver function, increased hepatic inflammation, altered bile acid profiles, and dysregulated expression of bile acid metabolic pathways. PLA exposure disrupts bile acid metabolism through inhibition of the CYP7A1 enzyme and activation of the FGF-JNK/ERK signaling pathway, contributing to liver injury. These findings highlight the potential hepatotoxic effects of environmentally friendly plastics PLA and underscore the need for further research on their biological impact.
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Ferroptosis is an iron-dependent cell death mechanism involving the accumulation of lipid peroxides. As a critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be downregulated in epilepsy. However, the mechanism of ferroptosis in epilepsy remains unclear. In this study, bioinformatics analysis, analysis of epilepsy patient blood samples and cell and mouse experiments revealed strong associations among epilepsy, ferroptosis, microRNA-211-5p and purinergic receptor P2X 7 (P2RX7). P2RX7 is a nonselective ligand-gated homotrimeric cation channel, and its activation mainly increases neuronal activity during epileptic seizures. In our study, the upregulation of P2RX7 in epilepsy was attributed to the downregulation of microRNA (miR)-211-5p. Furthermore, P2RX7 has been found to regulate GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of the MAPK/ERK signaling pathway in murine models. The dynamic decrease in miR-211-5p expression induces hypersynchronization and both nonconvulsive and convulsive seizures, and forebrain miR-211-5p suppression exacerbates long-lasting pentylenetetrazole-induced seizures. Additionally, in this study, induction of miR-211-5p expression or genetic-silencing of P2RX7 significantly reduced the seizure score and duration in murine models through the abovementioned pathways. These results suggest that the miR-211-5p/P2RX7 axis is a novel target for suppressing both ferroptosis and epilepsy.
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Epilepsia , Ferroptosis , MicroARNs , Humanos , Animales , Ratones , Epilepsia/genética , Estrés Oxidativo , Convulsiones , MicroARNs/genética , Receptores Purinérgicos P2X7/genéticaRESUMEN
Sodium-ion batteries (SIBs) have gradually become one of the most promising energy storage techniques in the current era of post-lithium-ion batteries. For anodes, transitional metal selenides (TMSe) based materials are welcomed choices , owing to relatively higher specific capacities and enriched redox active sites. Nevertheless, current bottlenecks are blamed for their poor intrinsic electronic conductivities, and uncontrollable volume expansion during redox reactions. Given that, an interfacial-confined isochronous conversion strategy is proposed, to prepare orthorhombic/cubic biphasic TMSe heterostructure, namely CuSe/Cu3 VSe4 , through using MXene as the precursor, followed by Cu/Se dual anchorage. As-designed biphasic TMSe heterostructure endows unique hierarchical structure, which contains adequate insertion sites and diffusion spacing for Na ions, besides, the surficial pseudocapacitive storage behaviors can be also proceeded like 2D MXene. By further investigation on electronic structure, the theoretical calculations indicate that biphasic CuSe/Cu3 VSe4 anode exhibits well-enhanced properties, with smaller bandgap and thus greatly improves intrinsic poor conductivities. In addition, the dual redox centers can enhance the electrochemical Na ions storage abilities. As a result, the as-designed biphasic TMSe anode can deliver a reversible specific capacity of 576.8 mAh g-1 at 0.1 A g-1 , favorable Na affinity, and reduced diffusion barriers. This work discloses a synchronous solution toward demerits in conductivities and lifespan, which is inspiring for TMSe-based anode development in SIBs systems.
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Common purslane (Portulaca oleracea) integrates both C4 and crassulacean acid metabolism (CAM) photosynthesis pathways and is a promising model plant to explore C4-CAM plasticity. Here, we report a high-quality chromosome-level genome of nicotinamide adenine dinucleotide (NAD)-malic enzyme (ME) subtype common purslane that provides evidence for 2 rounds of whole-genome duplication (WGD) with an ancient WGD (P-ß) in the common ancestor to Portulacaceae and Cactaceae around 66.30 million years ago (Mya) and another (Po-α) specific to common purslane lineage around 7.74 Mya. A larger number of gene copies encoding key enzymes/transporters involved in C4 and CAM pathways were detected in common purslane than in related species. Phylogeny, conserved functional site, and collinearity analyses revealed that the Po-α WGD produced the phosphoenolpyruvate carboxylase-encoded gene copies used for photosynthesis in common purslane, while the P-ß WGD event produced 2 ancestral genes of functionally differentiated (C4- and CAM-specific) beta carbonic anhydrases involved in the C4 + CAM pathways. Additionally, cis-element enrichment analysis in the promoters showed that CAM-specific genes have recruited both evening and midnight circadian elements as well as the Abscisic acid (ABA)-independent regulatory module mediated by ethylene-response factor cis-elements. Overall, this study provides insights into the origin and evolutionary process of C4 and CAM pathways in common purslane, as well as potential targets for engineering crops by integrating C4 or CAM metabolism.
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Portulaca , Portulaca/genética , Portulaca/metabolismo , Duplicación de Gen , Metabolismo Ácido de las Crasuláceas , Evolución Biológica , Filogenia , Fotosíntesis/genéticaRESUMEN
Cameras, LiDAR, and radars are indispensable for accurate perception of the surrounding environment and autonomous driving. Failure mechanisms of silicon-based CMOS image sensor (CIS) irradiated by 1550â nm nanosecond laser were investigated systematically in this paper. The damages of CIS were divided into point damage, line damage, and cross damage according to different damage performances. The damage thresholds under different irradiation conditions (different repetition rates, pulse widths, and irradiation times) were explored. Large repetition rates and long irradiation times would induce more heat accumulation, more temperature increase, and a low point damage threshold. The damage threshold for a pulse with a narrow pulse width is lower than that for a pulse with a long pulse width. The damaged CIS was analyzed further by focused ion beam (FIB) and scanning electron microscope (SEM). The damage location in the internal CIS structure was analyzed and the overall failure process was summarized. The results we get could enrich the database of laser damage mechanisms and laser damage thresholds of CIS, which will provide meaningful guidance for the camera design technology and anti-laser reinforcement technology of optoelectronic devices.
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A visible-light-induced cascade reaction is described for the one-pot synthesis of 6-hydroxyindoloquinazolinones using isatins (or isatins and isatoic anhydrides) and aliphatic carboxylic acids. The method provides 36 desired products in 33-96% yield, exhibiting broad substrate scope and good functional group tolerance. This approach utilizes inexpensive and commercially available starting materials, enabling the direct construction of high-value complex structures under mild conditions without the need for photocatalyst, showcasing significant applicability and environmental friendliness.
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The pathogenesis of Parkinson's disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-ß levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.