RESUMEN
The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration.
Asunto(s)
Células Endoteliales , Meninges , Pez Cebra , Animales , Meninges/citología , Meninges/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/citología , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Vasos Linfáticos/citología , Vasos Linfáticos/metabolismo , Animales Modificados Genéticamente , Linfangiogénesis/fisiología , Regeneración/fisiologíaRESUMEN
Parkinson's disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson's disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson's disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.
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A major cause of intestinal failure (IF) is intestinal epithelium necrosis and massive loss of enterocytes, especially in the jejunum, the major intestinal segment in charge of nutrient absorption. However, mechanisms underlying jejunal epithelial regeneration after extensive loss of enterocytes remain elusive. Here, we apply a genetic ablation system to induce extensive damage to jejunal enterocytes in zebrafish, mimicking the jejunal epithelium necrosis that causes IF. In response to injury, proliferation and filopodia/lamellipodia drive anterior migration of the ileal enterocytes into the injured jejunum. The migrated fabp6+ ileal enterocytes transdifferentiate into fabp2+ jejunal enterocytes to fulfill the regeneration, consisting of dedifferentiation to precursor status followed by redifferentiation. The dedifferentiation is activated by the IL1ß-NFκB axis, whose agonist promotes regeneration. Extensive jejunal epithelial damage is repaired by the migration and transdifferentiation of ileal enterocytes, revealing an intersegmental migration mechanism of intestinal regeneration and providing potential therapeutic targets for IF caused by jejunal epithelium necrosis.
Asunto(s)
Enterocitos , Yeyuno , Animales , Pez Cebra , Transdiferenciación Celular , Mucosa Intestinal , NecrosisRESUMEN
Unstable interface between highly reductive Li metal and a conventional liquid electrolyte leads to uncontrollable Li dendrites and Li pulverization, thus limiting the practical applications of Li metal batteries with high energy density. Herein, a fluorinated quasi-solid polymer electrolyte is synthesized to stabilize Li metal via the C-F/LiF enriched solid electrolyte interphase (SEI) derived from the fluorinated polymer skeleton. Benefiting from the homogenized ion plating/stripping process guided by lithophilic C-F and rapid Li+ transportation assisted by LiF, Li dendrites and Li pulverization are suppressed. As a result, the Li||Li symmetrical cell with the fluorinated quasi-solid polymer electrolyte remains stable over 1400â h at a current density of 0.3â mA cm-2 . LiNi0.8 Co0.1 Mn0.1 O2 ||Li battery delivers a long-term cycling performance, where the capacity retains 87.77 % of its initial state after 300 cycles at 0.5 C in the voltage range from 2.8 to 4.4â V.
RESUMEN
Good safety, high interfacial compatibility, low cost, and facile processability make polymer-based solid electrolytes promising materials for next-generation batteries. Key issues related to polymer-based solid electrolytes, such as synthesis methods, ionic conductivity, and battery architecture, are investigated in past decades. However, mechanistic understanding of the ionic conduction is still lacking, which impedes the design and optimization of polymer-based solid electrolytes. In this review, the ionic conduction mechanisms and optimization strategies of polymer-based solid electrolytes, including solvent-free polymer electrolytes, composite polymer electrolytes, and quasi-solid/gel polymer electrolytes, are summarized and evaluated. Challenges and strategies for enhancing the ionic conductivity are elaborated, while the ion-pair dissociation, ion mobility, polymer relaxation, and interactions at polymer/filler interfaces are highlighted. This comprehensive review is especially pertinent for the targeted enhancement of the Li-ion conductivity of polymer-based solid electrolytes.
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During coordinated development of two neighboring organs from the same germ layer, how precursors of one organ resist the inductive signals of the other to avoid being misinduced to wrong cell fate remains a general question in developmental biology. The liver and anterior intestinal precursors located in close proximity along the gut axis represent a typical example. Here we identify a zebrafish leberwurst (lbw) mutant with a unique hepatized intestine phenotype, exhibiting replacement of anterior intestinal cells by liver cells. lbw encodes the Cdx1b homeoprotein, which is specifically expressed in the intestine, and its precursor cells. Mechanistically, in the intestinal precursors, Cdx1b binds to genomic DNA at the regulatory region of secreted frizzled related protein 5 (sfrp5) to activate sfrp5 transcription. Sfrp5 blocks the mesoderm-derived, liver-inductive Wnt2bb signal, thus conferring intestinal precursor cells resistance to Wnt2bb. These results demonstrate that the intestinal precursors avoid being misinduced toward hepatic lineages through the activation of the Cdx1b-Sfrp5 cascade, implicating Cdx/Sfrp5 as a potential pharmacological target for the manipulation of intestinal-hepatic bifurcations, and shedding light on the general question of how precursor cells resist incorrect inductive signals during embryonic development.
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Hepatocitos , Pez Cebra , Animales , Pez Cebra/genética , Hepatocitos/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Hígado/metabolismoRESUMEN
Practical applications of polymer electrolytes in lithium (Li) metal batteries with high-voltage Ni-rich cathodes have been hindered by the dendrite growth and poor oxidative stability of electrolytes. Herein, a self-healing polymer electrolyte is developed by in situ copolymerization of 2-(3-(6-methyl4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA) and ethylene glycol methyl ether acrylate (EGMEA) monomers. With the electrolyte, the dendrite growth is inhibited by spontaneously repairing dendrite-induced defects, cracks, and voids at the Li/electrolyte interface; the suppressed dendrite growth and associated electro-chemo behaviors are visualized by the kinetic Mont-Carlo simulation. Benefitting from the high ionic conductivity, wide electrochemical window and good interfacial stability, the self-healing polymer electrolyte enables stable cycling of the LiNi0.8 Mn0.1 Co0.1 O2 (NMC811) cathode under 4.7 V, achieving a high specific capacity of ≈228.8 mAh g-1 and capacity retention of 80.4% over 500 cycles. The new electrolyte is very promising for developing highly safe and dendrite-free Li metal batteries with high energy density.
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A flexible and free-standing 3D reduced graphene oxide@polypyrrole-polyethylene glycol (RGO@PPy-PEG) foam was developed for wearable supercapacitors. The device was fabricated sequentially, beginning with the electrodeposition of PPy in the presence of a PEG-borate on a sacrificial Ni foam template, followed by a subsequent GO wrapping and chemical reduction process. The 3D RGO@PPy-PEG foam electrode showed excellent electrochemical properties with a large specific capacitance of 415 F g-1 and excellent long-term stability (96% capacitance retention after 8000 charge-discharge cycles) in a three electrode configuration. An assembled (two-electrode configuration) symmetric supercapacitor using RGO@PPy-PEG electrodes exhibited a remarkable specific capacitance of 1019 mF cm-2 at 2 mV s-1 and 95% capacitance retention over 4000 cycles. The device exhibits extraordinary mechanical flexibility and showed negligable capacitance loss during or after 1000 bending cycles, highlighting its great potential in wearable energy devices.