Segregation of morphogenetic regulatory function of Shox2 from its cell fate guardian role in sinoatrial node development.

Shox2 plays a vital role in the morphogenesis and physiological function of the sinoatrial node (SAN), the primary cardiac pacemaker, manifested by the formation of a hypoplastic SAN and failed differentiation of pacemaker cells in Shox2 mutants. Shox2 and Nkx2-5 are co-expressed in the developing SAN and regulate the fate of the pacemaker cells through a Shox2-Nkx2-5 antagonistic mechanism. Here we show that simultaneous inactivation of Nkx2-5 in the SAN of Shox2 mutants (dKO) rescued the pacemaking cell fate but not the hypoplastic defects, indicating uncoupling of SAN cell fate determination and morphogenesis. Single-cell RNA-seq revealed that the presumptive SAN cells of Shox2-/- mutants failed to activate pacemaking program but remained in a progenitor state preceding working myocardium, while both wildtype and dKO SAN cells displayed normal pacemaking cell fate with similar cellular state. Shox2 thus acts as a safeguard but not a determinant to ensure the pacemaking cell fate through the Shox2-Nkx2-5 antagonistic mechanism, which is segregated from its morphogenetic regulatory function in SAN development.

Breaking the trade-off between capacity and stability in vanadium-based zinc-ion batteries.

Water in electrolytes is a double-edged sword in zinc-ion batteries (ZIBs). While it allows for proton insertion in the cathode, resulting in a significant increase in capacity compared to that of organic ZIBs, it also causes damage to electrodes, leading to performance degradation. To overcome the capacity-stability trade-off, organic solvents containing a small amount of water are proposed to mitigate the harmful effects of water while ensuring sufficient proton insertion. Remarkably, in a Zn(OTf)2 electrolyte using 8% H2O in acetonitrile as the solvent, Zn‖(NH4)0.5V2O5·0.5H2O exhibited a capacity as high as 490 mA h g-1 at a low current (0.3 A g-1), with a capacity retention of 80% even after 9000 cycles at high current (6 A g-1), simultaneously achieving the high capacity as in pure aqueous electrolytes and excellent stability as in organic electrolytes. We also found that the water content strongly impacts the kinetics and reversibility of ion insertion/extraction and zinc stripping/plating. Furthermore, compared to electrolytes with pure acetonitrile or H2O solvents, electrolytes with only 8% H2O in acetonitrile provide higher capacities at temperatures ranging from 0 to -50 °C. These discoveries enhance our understanding of the mechanisms involved in ZIBs and present a promising path toward enhancing electrolyte solutions for the creation of high-performance ZIBs.

Agaricus bisporus-Derived Glucosamine Hydrochloride Regulates VEGF through BMP Signaling to Promote Zebrafish Vascular Development and Impairment Repair.

Glucosamine hydrochloride (GAH) is a natural component of glycoproteins present in almost all human tissues and participates in the construction of human tissues and cell membranes. GAH has a wide range of biological activities, particularly in anti-inflammatory and osteogenic damage repair. At present, little is known about how GAH functions in angiogenesis. To determine the role of GAH on vascular development and impairment repair, we used the inhibitors VRI, DMH1, and dorsomorphin (DM) to construct vascular-impaired models in Tg(kdrl: mCherry) transgenic zebrafish. We then treated with GAH and measured its repair effects on vascular impairment through fluorescence intensity, mRNA, and protein expression levels of vascular-specific markers. Our results indicate that GAH promotes vascular development and repairs impairment by regulating the vascular endothelial growth factor (VEGF) signaling pathway through modulation of bone morphogenetic protein (BMP) signaling. This study provides an experimental basis for the development of GAH as a drug to repair vascular diseases.

Enhancing Energy Conversion Efficiency and Durability of Alkaline Nickel-Zinc Batteries with Air-Breathing Cathode.

Despite their high output voltage and safety advantages, rechargeable alkaline nickel-zinc batteries face significant challenges associated with the cathodic side reaction of oxygen evolution, which results in low energy efficiency (EE) and poor stability. Herein, we propose to leverage the side oxygen evolution reaction (OER) in nickel-zinc batteries by coupling electrocatalysts for oxygen reduction reactions (ORR) in the cathode, thus constructing an air breathing cathode. Such a novel battery (Ni-ZnAB), designed in a pouch-type cell with a lean electrolyte, exhibits an outstanding EE of 85 % and a long cycle life of 100 cycles at 2 mA cm-2 , which are significantly superior to those of traditional Ni-Zn batteries (54 %, 50 cycles). Compared to Ni-Zn, the enhanced EE of Ni-ZnAB is attributed to the contribution from ORR, while the improved cycling stability is because the stability of the anode, cathode and electrolyte are also enhanced in Ni-ZnAB. Furthermore, an ultrahigh stability of 500 cycles with an average EE of 84 % at 2 mA cm-2 was achieved using a mold cell with rich electrolyte, demonstrating the strong application potential of Ni-ZnAB.

Hewettite ZnV6 O16 ⋠8H2 O with Remarkably Stable Layers and Ultralarge Interlayer Spacing for High-Performance Aqueous Zn-Ion Batteries.

Aqueous Zn-ion batteries (ZIBs) are promising candidates for grid-scale energy storage because of their intrinsic safety, low-cost and high energy-intensity. Vanadium-based materials are widely used as the cathode of ZIBs, especially A2 V6 O16 ⋅ nH2 O (AVO, A=NH4 + , Na, K). However, AVO suffers from serious dissolution, phase transformation and narrow gallery spacing (∼3 Å), leading to poor cycling stability and rate capability. Herein, we unveiled the root cause of the performance degradation in the AVO cathode and therefore developed a new high-performance cathode of ZnV6 O16 ⋅ 8H2 O (ZVO) for ZIB. Through a method of ion exchange induced phase transformation, AVO was converted to hewettite ZVO with larger gallery spacing (∼6 Å) and more stable V6 O16 layers. ZVO cathode thus constructed delivers a high capacity of 365 and 170 mAh g-1 at 0.5 and 15 A g-1 , while 86 % and 70 % of its capacity are retained at 0.5 A g-1 after 300 cycles and at 15 A g-1 after 10000 cycles, substantially better than conventional AVO.

Overexpression of Fgf8 in the epidermis inhibits hair follicle development.

The hair follicle is a classical model for studying epithelial-mesenchymal interactions. Given the critical role of fibroblast growth factor 8 (Fgf8) in embryonic development, we generated a mouse model that overexpresses Fgf8 specifically in the epidermis. Interestingly, these mutant mice exhibited stunted, smaller bodies and severe hypotrichosis. Histological analysis showed that the hair follicles in the mutants were arrested at stage 2 of hair development. The density of hair follicles in the mutant mice was also lower compared to that in the control mice. Overexpression of Fgf8 inhibited the proliferation of epidermal cells and simultaneously promoted apoptosis, leading to the arrest of hair follicle development. Further analysis showed that sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) were downregulated and upregulated, respectively. To summarize, our study demonstrates that FGF signalling plays an important role in the regulation of hair follicle development.

Conditional deletion of Bmp2 in cranial neural crest cells recapitulates Pierre Robin sequence in mice.

Bone morphogenetic protein (BMP) signaling plays a crucial role in the development of craniofacial organs. Mutations in numerous members of the BMP signaling pathway lead to several severe human syndromes, including Pierre Robin sequence (PRS) caused by heterozygous loss of BMP2. In this study, we generate mice carrying Bmp2-specific deletion in cranial neural crest cells using floxed Bmp2 and Wnt1-Cre alleles to mimic PRS in humans. Mutant mice exhibit severe PRS with a significantly reduced size of craniofacial bones, cleft palate, malformed tongue and micrognathia. Palate clefting is caused by the undescended tongue that prevents palatal shelf elevation. However, the tongue in Wnt1-Cre;Bmp2f/f mice does not exhibit altered rates of cell proliferation and apoptosis, suggesting contribution of extrinsic defects to the failure of tongue descent. Further studies revealed obvious reduction in cell proliferation and differentiation of osteogenic progenitors in the mandible of the mutants, attributing to the micrognathia phenotype. Our study illustrates the pathogenesis of PRS caused by Bmp2 mutation, highlights the crucial role of BMP2 in the development of craniofacial bones and emphasizes precise coordination in the morphogenesis of palate, tongue and mandible during embryonic development.