Direct cell reprogramming: approaches, mechanisms and progress.

The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional views on cell identity and cell fate determination. Direct reprogramming (also known as transdifferentiation) refers to cell fate conversion without transitioning through an intermediary pluripotent state. Given that the number of cell types that can be generated by direct reprogramming is rapidly increasing, it has become a promising strategy to produce functional cells for therapeutic purposes. This Review discusses the evolution of direct reprogramming from a transcription factor-based method to a small-molecule-driven approach, the recent progress in enhancing reprogrammed cell maturation, and the challenges associated with in vivo direct reprogramming for translational applications. It also describes our current understanding of the molecular mechanisms underlying direct reprogramming, including the role of transcription factors, epigenetic modifications, non-coding RNAs, and the function of metabolic reprogramming, and highlights novel insights gained from single-cell omics studies.

Epigenetic Regulation of Cardiomyocyte Maturation by Arginine Methyltransferase CARM1.

BACKGROUND: During the neonatal stage, the cardiomyocyte undergoes a constellation of molecular, cytoarchitectural, and functional changes known collectively as cardiomyocyte maturation to increase myocardial contractility and cardiac output. Despite the importance of cardiomyocyte maturation, the molecular mechanisms governing this critical process remain largely unexplored. METHODS: We leveraged an in vivo mosaic knockout system to characterize the role of Carm1, the founding member of protein arginine methyltransferase, in cardiomyocyte maturation. Using a battery of assays, including immunohistochemistry, immuno-electron microscopy imaging, and action potential recording, we assessed the effect of loss of Carm1 function on cardiomyocyte cell growth, myofibril expansion, T-tubule formation, and electrophysiological maturation. Genome-wide transcriptome profiling, H3R17me2a chromatin immunoprecipitation followed by sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing were used to investigate the mechanisms by which CARM1 (coactivator-associated arginine methyltransferase 1) regulates cardiomyocyte maturation. Finally, we interrogated the human syntenic region to the H3R17me2a chromatin immunoprecipitation followed by sequencing peaks for single-nucleotide polymorphisms associated with human heart diseases. RESULTS: We report that mosaic ablation of Carm1 disrupts multiple aspects of cardiomyocyte maturation cell autonomously, leading to reduced cardiomyocyte size and sarcomere thickness, severe loss and disorganization of T tubules, and compromised electrophysiological maturation. Genomics study demonstrates that CARM1 directly activates genes that underlie cardiomyocyte cytoarchitectural and electrophysiological maturation. Moreover, our study reveals significant enrichment of human heart disease-associated single-nucleotide polymorphisms in the human genomic region syntenic to the H3R17me2a chromatin immunoprecipitation followed by sequencing peaks. CONCLUSIONS: This study establishes a critical and multifaceted role for CARM1 in regulating cardiomyocyte maturation and demonstrates that deregulation of CARM1-dependent cardiomyocyte maturation gene expression may contribute to human heart diseases.

Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor.

VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.

Direct cardiac reprogramming comes of age: Recent advance and remaining challenges.

The adult human heart has limited regenerative capacity. As such, the massive cardiomyocyte loss due to myocardial infarction leads to scar formation and adverse cardiac remodeling, which ultimately results in chronic heart failure. Direct cardiac reprogramming that converts cardiac fibroblast into functional cardiomyocyte-like cells (also called iCMs) holds great promise for heart regeneration. Cardiac reprogramming has been achieved both in vitro and in vivo by using a variety of cocktails that comprise transcription factors, microRNAs, or small molecules. During the past several years, great progress has been made in improving reprogramming efficiency and understanding the underlying molecular mechanisms. Here, we summarize the direct cardiac reprogramming methods, review the current advances in understanding the molecular mechanisms of cardiac reprogramming, and highlight the novel insights gained from single-cell omics studies. Finally, we discuss the remaining challenges and future directions for the field.

Metabolomic reveals the responses of sludge properties and microbial communities to high nitrite stress in denitrifying phosphorus removal systems.

Nitrite, as an electron acceptor, plays a good role in denitrifying phosphorus removal (DPR); however, high nitrite concentration has adverse affects on sludge performance. We investigated the precise mechanisms of responses of sludge to high nitrite stress, including surface characteristics, intracellular and extracellular components, microbial and metabolic responses. When the nitrite stress reached 90 mg/L, the sludge settling performance was improved, but the activated sludge was aging. FTIR and XPS analysis revealed a significant increase in the hydrophobicity of the sludge, resulting in improve settling performance. However, the intracellular carbon sources synthesis was inhibited. In addition, the components in the tightly bound extracellular polymeric substances (TB-EPS) of sludge were significantly reduced and indicated the disturb of metabolism. Notably, Exiguobacterium emerged as a new genus when face high nitrite stress that could maintaining survival in hostile environments. Moreover, metabolomic analysis demonstrated strong biological response to nitrite stress further supported above results that include the inhibited of carbohydrate and amino acid metabolism. More importantly, some lipids (PS, PA, LysoPA, LysoPC and LysoPE) were significantly upregulated that related enhanced membrane lipid remodeling. The comprehensive analyses provide novel insights into the high nitrite stress responses mechanisms in activated sludge systems.

Molecular and cellular basis of embryonic cardiac chamber maturation.

Heart malformation is the leading cause of human birth defects, and many of the congenital heart diseases (CHDs) originate from genetic defects that impact cardiac development and maturation. During development, the vertebrate heart undergoes a series of complex morphogenetic processes that increase its ability to pump blood. One of these processes leads to the formation of the sheet-like muscular projections called trabeculae. Trabeculae increase cardiac output and permit nutrition and oxygen uptake in the embryonic myocardium prior to coronary vascularization without increasing heart size. Cardiac trabeculation is also crucial for the development of the intraventricular fast conduction system. Alterations in cardiac trabecular development can manifest as a variety of congenital defects such as left ventricular noncompaction. In this review, we discuss the latest advances in understanding the molecular and cellular mechanisms underlying cardiac trabecular development.

In Situ Formed Gradient Composite Solid Electrolyte Interphase Layer for Stable Lithium Metal Anodes.

Lithium (Li) metal anode (LMA) is highly considered as a desirable anode material for next-generation rechargeable batteries because of its high specific capacity and the lowest reduction potential. However, uncontrollable growth of Li dendrites, large volume change, and unstable interfaces between LMA and electrolyte hinder its practical application. Herein, a novel in situ formed artificial gradient composite solid electrolyte interphase (GCSEI) layer for highly stable LMAs is proposed. The inner rigid inorganics (Li2 S and LiF) with high Li+ ion affinity and high electron tunneling barrier are beneficial to achieve homogeneous Li plating, while the flexible polymers (poly(ethylene oxide) and poly(vinylidene fluoride)) on the surface of GCSEI layer can accommodate the volume change. Furthermore, the GCSEI layer demonstrates fast Li+ ion transport capability and increased Li+ ion diffusion kinetics. Accordingly, the modified LMA enables excellent cycling stability (over 1000 h at 3 mA cm-2 ) in the symmetric cell using carbonate electrolyte, and the corresponding Li-GCSEI||LiNi0.8 Co0.1 Mn0.1 O2 full cell demonstrates 83.4% capacity retention after 500 cycles. This work offers a new strategy for the design of dendrite-free LMAs for practical applications.

iSMNN: batch effect correction for single-cell RNA-seq data via iterative supervised mutual nearest neighbor refinement.

Batch effect correction is an essential step in the integrative analysis of multiple single-cell RNA-sequencing (scRNA-seq) data. One state-of-the-art strategy for batch effect correction is via unsupervised or supervised detection of mutual nearest neighbors (MNNs). However, both types of methods only detect MNNs across batches of uncorrected data, where the large batch effects may affect the MNN search. To address this issue, we presented a batch effect correction approach via iterative supervised MNN (iSMNN) refinement across data after correction. Our benchmarking on both simulation and real datasets showed the advantages of the iterative refinement of MNNs on the performance of correction. Compared to popular alternative methods, our iSMNN is able to better mix the cells of the same cell type across batches. In addition, iSMNN can also facilitate the identification of differentially expressed genes (DEGs) that are relevant to the biological function of certain cell types. These results indicated that iSMNN will be a valuable method for integrating multiple scRNA-seq datasets that can facilitate biological and medical studies at single-cell level.

Comparison of the immunogenicity of nasal-spray rVSV vector, adenovirus vector, and inactivated COVID-19-based vaccines in rodent models.

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.

LncPSCA in the 8q24.3 risk locus drives gastric cancer through destabilizing DDX5.

Genome-wide association studies (GWAS) have identified multiple gastric cancer risk loci and several protein-coding susceptibility genes. However, the role of long-noncoding RNAs (lncRNAs) transcribed from these risk loci in gastric cancer development and progression remains to be explored. Here, we functionally characterize a lncRNA, lncPSCA, as a novel tumor suppressor whose expression is fine-regulated by a gastric cancer risk-associated genetic variant. The rs2978980 T > G change in an intronic enhancer of lncPSCA interrupts binding of transcription factor RORA, which down-regulates lncPSCA expression in an allele-specific manner. LncPSCA interacts with DDX5 and promotes DDX5 degradation through ubiquitination. Increased expression of lncPSCA results in low levels of DDX5, less RNA polymerase II (Pol II) binding with DDX5 in the nucleus, thus activating transcription of multiple p53 signaling genes by Pol II. These findings highlight the importance of functionally annotating lncRNAs in GWAS risk loci and the great potential of modulating lncRNAs as innovative cancer therapy.

Functional coordination of non-myocytes plays a key role in adult zebrafish heart regeneration.

Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, but also involves complex interactions between distinct cardiac cell types including non-cardiomyocytes (non-CMs). However, the subpopulations, distinguishing molecular features, cellular functions, and intercellular interactions of non-CMs in heart regeneration remain largely unexplored. Using the LIGER algorithm, we assemble an atlas of cell states from 61,977 individual non-CM scRNA-seq profiles isolated at multiple time points during regeneration. This analysis reveals extensive non-CM cell diversity, including multiple macrophage (MC), fibroblast (FB), and endothelial cell (EC) subpopulations with unique spatiotemporal distributions, and suggests an important role for MC in inducing the activated FB and EC subpopulations. Indeed, pharmacological perturbation of MC function compromises the induction of the unique FB and EC subpopulations. Furthermore, we developed computational algorithm Topologizer to map the topological relationships and dynamic transitions between functional states. We uncover dynamic transitions between MC functional states and identify factors involved in mRNA processing and transcriptional regulation associated with the transition. Together, our single-cell transcriptomic analysis of non-CMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of this process.

BODIPY Based OFF-ON Fluorescent Probe for Endogenous Carbon Monoxide Imaging in Living Cells.

Carbon monoxide (CO) is one of the signaling molecules that are ubiquitous in humans, which involves in the regulation of human physiology and pathology. In this work, the probe PEC was designed and synthesized based on BODIPY fluorophore that can selectively detect CO through reducing the nitro group to amino group, resulting in a "turn-on" fluorescence response with a simultaneous increase in the concentration of CO. The response is selective over a variety of relevant reactive free radicals, ions, and amino acid species. PEC has the advantages of good stability, good water solubility, and obvious changes in fluorescence signals. In addition, PEC can be used to detect and track endogenous CO in living cells.

Single-cell transcriptomics reconstructs fate conversion from fibroblast to cardiomyocyte.

Direct lineage conversion offers a new strategy for tissue regeneration and disease modelling. Despite recent success in directly reprogramming fibroblasts into various cell types, the precise changes that occur as fibroblasts progressively convert to the target cell fates remain unclear. The inherent heterogeneity and asynchronous nature of the reprogramming process renders it difficult to study this process using bulk genomic techniques. Here we used single-cell RNA sequencing to overcome this limitation and analysed global transcriptome changes at early stages during the reprogramming of mouse fibroblasts into induced cardiomyocytes (iCMs). Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells during reprogramming. We also constructed routes of iCM formation, and delineated the relationship between cell proliferation and iCM induction. Further analysis of global gene expression changes during reprogramming revealed unexpected downregulation of factors involved in mRNA processing and splicing. Detailed functional analysis of the top candidate splicing factor, Ptbp1, revealed that it is a critical barrier for the acquisition of cardiomyocyte-specific splicing patterns in fibroblasts. Concomitantly, Ptbp1 depletion promoted cardiac transcriptome acquisition and increased iCM reprogramming efficiency. Additional quantitative analysis of our dataset revealed a strong correlation between the expression of each reprogramming factor and the progress of individual cells through the reprogramming process, and led to the discovery of new surface markers for the enrichment of iCMs. In summary, our single-cell transcriptomics approaches enabled us to reconstruct the reprogramming trajectory and to uncover intermediate cell populations, gene pathways and regulators involved in iCM induction.

Delineating chromatin accessibility re-patterning at single cell level during early stage of direct cardiac reprogramming.

Direct conversion of cardiac fibroblast into induced cardiomyocytes (iCMs) by forced expression of cardiac transcription factors, such as Mef2c, Gata4, and Tbx5 (MGT), holds great promise for regenerative medicine. The process of cardiac reprogramming consists of waves of transcriptome remodelling events. However, how this transcriptome remodelling is driven by the upstream chromatin landscape alteration is still unclear. In this study, we performed single-cell ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) on early reprogramming iCMs given the known epigenetic changes as early as day 3. This approach unveiled networks of transcription factors (TFs) involved in the early shift of chromatin accessibility during cardiac reprogramming. Combining our analysis with functional assays, we identified Smad3 to be a bimodal TF in cardiac reprogramming, a barrier in the initiation of reprogramming and a facilitator during the intermediate stage of reprogramming. Moreover, integrative analysis of scATAC-seq with scRNA-seq data led to the identification of active TFs important for iCM conversion. Finally, we discovered a global rewiring of cis-regulatory interactions of cardiac genes along the reprogramming trajectory. Collectively, our scATAC-seq study and the integrative analysis with scRNA-seq data provided valuable resources to understand the epigenomic heterogeneity and its alteration in relation to transcription changes during early stage of cardiac reprogramming.

Effect of Surface Heterogeneities on Interactions between Air Bubbles and Heterogeneous Surfaces.

The effects of surface heterogeneities on bubble-particle interactions have received little attention although heterogeneities are common for varieties of substance surfaces. In this work, heterogeneous surfaces consisting of discrete hydrophilic dots on a hydrophobic background were fabricated. The interactions between air bubbles and heterogeneous surfaces with different hydrophilic area fractions were investigated using a high-sensitivity microbalance coupled with a high-speed video camera. It was found that the snap-in, maximum adhesion, and pull-off forces increased as the hydrophilic area fraction decreased. These experimental results were compared with the calculated interaction forces. The comparison between experimental results and the calculated interaction forces showed that the normalized contact line length (δ) should be considered in the calculation of the snap-in force, and its value was between 1 and the δ value corresponding to the maximum pinning strength. In contrast, δ = 1 is more appropriate for the calculation of maximum adhesion force, indicating that the corrugations in the three-phase contact line could be neglected. These findings demonstrate that discrete hydrophilic defects make bubble-surface attachment difficult but have nearly no effect on bubble-surface detachment. Better understanding of the interactions between air bubbles and heterogeneous surfaces potential offers a new thought to control the bubble-particle interactions using appropriately design of particle surfaces.

Value of prediction model in distinguishing gallbladder adenoma from cholesterol polyp.

BACKGROUND AND AIM: Gallbladder adenomatous polyp is a pre-cancerous neoplasm, and it is difficult to classify from cholesterol polyps before cholecystectomy. The study aimed to clarify the risk characteristics of gallbladder adenomas and establish a prediction model to differentiate gallbladder adenomas from cholesterol polyp lesions. METHODS: From May 2019 to December 2021, the patients underwent cholecystectomy in the Shanghai Eastern Hepatobiliary Surgery Hospital were retrospectively reviewed. According to the permanent pathology test, the patients were divided into adenomas and cholesterol polyps groups. All the included cases received ultrasound equipment examinations before cholecystectomy and their clinical information were completely recorded. Then the patients' baseline characteristics and ultrasound imaging variables were analyzed by logistic regression. Finally, a predictive model for gallbladder adenomas will be established and assessed based on the independent risk factors. RESULTS: A total of 423 cases including 296 cholesterol polyps and 127 gallbladder adenomas were analyzed in detail. Multivariate logistic regression analysis revealed that solitary polyp lesion (OR = 2.954, 95% CI 1.759-4.960, P < 0.001), the maximal diameter of lesions (OR = 1.244, 95% CI 1.169-1.324, P < 0.001), and irregular shape of polyp lesions (OR = 5.549, 95% CI 1.979-15.560, P = 0.001) were the independent predictive factors of gallbladder adenomas. According to the results, regression equation of logit(P) = -3.828 + 1.083*number of gallbladder polyps lesions (GPLs) + 0.218*diameter of GPLs + 1.714*shape of GPLs was established. Area under the curve (AUC) was 0.828 (95% CI 0.782-0.874, P < 0.001). When logit P > 0.204, the sensitivity of estimating adenoma was 79.5%, the specificity of recognizing adenoma was 70.6%, and the whole correct ratio was 73.3%. While the AUC of diameter (10 mm) being a predictive factor in this study was only 0.790 (95% CI 0.741-0.839, P < 0.001). And the sensitivity and specificity of 10 mm as the optimal diagnostic cutoff value to diagnose adenomas were 74.8% and 65.9%, respectively. CONCLUSIONS: The risk factors of solitary polyp lesion, larger diameter, and irregular morphology feature of polyp lesions were significantly related to gallbladder adenomas. And the predictive model established in the study can effectively identify adenomas from cholesterol polyps and help patients to select the optimal treatment protocol.

Degradation of acid red 73 wastewater by hydrodynamic cavitation combined with ozone and its mechanism.

Many azo dyes are consumed in the textile and dyeing industry, which makes the wastewater recalcitrant and toxic to the aquatic environment. Dye degradation by the combination of hydrodynamic cavitation and ozone (HC + O3) has caused extensive interest. The degradation mechanism of the hybrid system needs further investigation. This study investigated the degradation of acid red 73 (AR73) by HC + O3. Meanwhile, the degradation pathways and mechanisms were present. The optimal operation parameters were: inlet pressure of 0.15 MPa, O3 dosage of 45 mg/min, initial dye concentration of 10 mg/L, and initial pH at 7.5. As a result, the decolorization rate, removal of UV254 and NH3-N were 100%, 71.28%, and 87.36% in 30 min, respectively. Humic acid and most of the co-existing anions (HCO3-, SO42-, Cl-, PO43-, NO3-) played a positive role in the degradation of AR73, while NO2- restrained. The reactive species of singlet oxygen (1O2), hydroxyl radicals (·OH) and super oxygen radicals (·O2-) showed synergism in the hybrid system, and the decolorization was attributed to the fracture of azo bonds by 1O2. Meanwhile, aromatic amines were generated and further degraded into small molecule compounds. The research certificated that the HC + O3 can be an effective technology for azo dye degradation.

LncRNA CCAT1 Upregulates ATG5 to Enhance Autophagy and Promote Gastric Cancer Development by Absorbing miR-140-3p.

BACKGROUND: Long noncoding RNA colon cancer-associated transcript 1 (LncRNA CCAT1) is highly expressed in gastric cancer tissues and plays a role in autophagy. However, the underlying mechanism still needs to be further clarified. OBJECTIVE: To study the role of LncRNA CCAT1 in regulating autophagy of gastric cancer cells, analyze its downstream targets, and elucidate the mechanism. METHODS: qPCR detected the expression of LncRNA CCAT1 in gastric cancer cells. The proliferation, migration, and invasion ability of LncRNA CCAT1 and the expression level of autophagy-related proteins in gastric cancer cells were detected. Bioinformatics method predicted the downstream targets of LncRNA CCAT1, and they were verified by dual-luciferase assay. The relationship between LncRNA CCAT1, miR-140, and ATG5 was verified by co-transfection, and the expression levels of ATG5 and ATG5-ATG12 complex proteins were detected. Finally, the role of LncRNA CCAT1 in vivo was confirmed by gastric cancer transplantation model. RESULTS: LncRNA CCAT1 was highly expressed in gastric cancer cells. LncRNA CCAT1 can promote the proliferation, migration, invasion, and autophagy activity of gastric cancer cells. LncRNA CCAT1 can bind to miR-140-3p and regulate its expression, while miR-140-3p further regulates the expression of ATG5. Overexpression of LncRNA CCAT1 can promote tumor growth in nude mice. After LncRNA CCAT1 silencing, the positive expression rate of ATG5 in nude mice was low. CONCLUSION: LncRNA CCAT1 may inhibit the expression of miR-140-3p by sponge adsorption, thus weakening its inhibitory effect on ATG5. Eventually, gastric cancer cells were more prone to autophagy under the pressure of stress.

Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region.

The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-ß, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.

Formation of NaF-Rich Solid Electrolyte Interphase on Na Anode through Additive-Induced Anion-Enriched Structure of Na+ Solvation.

High-capacity sodium (Na) anodes suffer from dendrite growth due to the high reactivity, which can be overcome through inducing a stable NaF-rich solid electrolyte interphase (SEI). Herein, we propose an additive strategy for realizing the anion-enriched structure of Na+ solvation to obtain a NaF-rich SEI. The electron-withdrawing acetyl group in 4-acetylpyridine (4-APD) increases the coordination number of PF6 - in the Na+ solvation sheath to facilitate PF6 - to decompose into NaF. Thus, the NaF-rich SEI with high mechanical stability and interfacial energy is formed to repress the growth of Na dendrites. With the 4-APD-contained electrolyte, the symmetric Na||Na cells show excellent cycling performance over 360 h at 1.0 mA cm-2 . Meanwhile, excellent stability is also achieved for Na||Na3 V2 (PO4 )2 O2 F full cells with high Coulombic efficiency (97 %) and capacity retention (91 %) after 200 cycles.