Pancreatic endocrine islets are vital for glucose homeostasis. However, the islet developmental trajectory and its regulatory network are not well understood. To define the features of these specification and differentiation processes, we isolated individual islet cells from TgBAC(neurod1:EGFP) transgenic zebrafish and analyzed islet developmental dynamics across four different embryonic stages using a single-cell RNA-seq strategy. We identified proliferative endocrine progenitors, which could be further categorized by different cell cycle phases with the G1/S subpopulation displaying a distinct differentiation potential. We identified endocrine precursors, a heterogeneous intermediate-state population consisting of lineage-primed alpha, beta and delta cells that were characterized by the expression of lineage-specific transcription factors and relatively low expression of terminally differentiation markers. The terminally differentiated alpha, beta, and delta cells displayed stage-dependent differentiation states, which were related to their functional maturation. Our data unveiled distinct states, events and molecular features during the islet developmental transition, and provided resources to comprehensively understand the lineage hierarchy of islet development at the single-cell level.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca 2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca 2+ ] i and faster increase in responding to blockage of Na + /Ca 2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca 2+ ] i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca 2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Using first-principles calculations, we have investigated the electronic and optical properties of MoSe2 with Se vacancies (SVSe, α-DVSe, and β-DVSe) and further repaired by halogen atoms (F, Cl, Br and I). For the MoSe2 with Se vacancies, Cl, Br and I atoms can occupy the Se vacancies and form three bonds with the neighboring Mo atoms, but F atom only can form two F-Mo bonds with the lowest adsorption energies due to its smaller atomic radius. Halogen atoms possess one more electron than Se atom, which results in a local magnetic moment of 1µB for single vacancy and 2µB for double vacancies. The MoSe2 with Se vacancies exhibits n-type doping semiconductor, which agrees well with the experimental observations. After halogen atoms doping in the defective site, the defective levels shift from electron donor levels to the electron acceptor levels, and finally reduces the n-type doping from the defective structure through a p-doping process. Compared to the defective MoSe2, absorption enhancement around low energy area of 0∼3 eV is observed in the halogen-repaired MoSe2 structures. Our results provide new insights in structural repairing of the transition metal dichalcogenides and promote their remarkable properties for applications in optoelectronics.

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