Differentiation route determines the functional outputs of adult megakaryopoiesis.

Emerging evidence has revealed a direct differentiation route from hematopoietic stem cells to megakaryocytes (direct route), in addition to the classical differentiation route through a series of restricted hematopoietic progenitors (stepwise route). This raises the question of the importance of two alternative routes for megakaryopoiesis. Here, we developed fate-mapping systems to distinguish the two routes, comparing their quantitative and functional outputs. We found that megakaryocytes were produced through the two routes with comparable kinetics and quantity under homeostasis. Single-cell RNA sequencing of the fate-mapped megakaryocytes revealed that the direct and stepwise routes contributed to the niche-supporting and immune megakaryocytes, respectively, but contributed to the platelet-producing megakaryocytes together. Megakaryocytes derived from the two routes displayed different activities and were differentially regulated by chemotherapy and inflammation. Our work links differentiation route to the heterogeneity of megakaryocytes. Alternative differentiation routes result in variable combinations of functionally distinct megakaryocyte subpopulations poised for different physiological demands.

ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aß Secretion.

Human apolipoprotein E (ApoE) apolipoprotein is primarily expressed in three isoforms (ApoE2, ApoE3, and ApoE4) that differ only by two residues. ApoE4 constitutes the most important genetic risk factor for Alzheimer's disease (AD), ApoE3 is neutral, and ApoE2 is protective. How ApoE isoforms influence AD pathogenesis, however, remains unclear. Using ES-cell-derived human neurons, we show that ApoE secreted by glia stimulates neuronal Aß production with an ApoE4 > ApoE3 > ApoE2 potency rank order. We demonstrate that ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases. Activated ERK1/2 induces cFos phosphorylation, stimulating the transcription factor AP-1, which in turn enhances transcription of amyloid-ß precursor protein (APP) and thereby increases amyloid-ß levels. This molecular mechanism also regulates APP transcription in mice in vivo. Our data describe a novel signal transduction pathway in neurons whereby ApoE activates a non-canonical MAP kinase cascade that enhances APP transcription and amyloid-ß synthesis.

Micropeptide PACMP inhibition elicits synthetic lethal effects by decreasing CtIP and poly(ADP-ribosyl)ation.

Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.

The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in the regulation of cognition and behavior as well as in the neuropathology of neurological and mental disorders. The angiotensin II type 1 receptor (AT1R) mediates most functional and neuropathology-relevant actions associated with the central RAS. However, an overarching comprehension to guide translation and utilize the therapeutic potential of the central RAS in humans is currently lacking. We conducted a comprehensive characterization of the RAS using an innovative combination of transcriptomic gene expression mapping, image-based behavioral decoding, and pre-registered randomized controlled discovery-replication pharmacological resting-state functional magnetic resonance imaging (fMRI) trials (N = 132) with a selective AT1R antagonist. The AT1R exhibited a particular dense expression in a subcortical network encompassing the thalamus, striatum, and amygdalo-hippocampal formation. Behavioral decoding of the AT1R gene expression brain map showed an association with memory, stress, reward, and motivational processes. Transient pharmacological blockade of the AT1R further decreased neural activity in subcortical systems characterized by a high AT1R expression, while increasing functional connectivity in the cortico-basal ganglia-thalamo-cortical circuitry. Effects of AT1R blockade on the network level were specifically associated with the transcriptomic signatures of the dopaminergic, opioid, acetylcholine, and corticotropin-releasing hormone signaling systems. The robustness of the results was supported in an independent pharmacological fMRI trial. These findings present a biologically informed comprehensive characterization of the central AT1R pathways and their functional relevance on the neural and behavioral level in humans.

Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1.

Generation of defined neuronal subtypes from human pluripotent stem cells remains a challenge. The proneural factor NGN2 has been shown to overcome experimental variability observed by morphogen-guided differentiation and directly converts pluripotent stem cells into neurons, but their cellular heterogeneity has not been investigated yet. Here, we found that NGN2 reproducibly produces three different kinds of excitatory neurons characterized by partial coactivation of other neurotransmitter programs. We explored two principle approaches to achieve more precise specification: prepatterning the chromatin landscape that NGN2 is exposed to and combining NGN2 with region-specific transcription factors. Unexpectedly, the chromatin context of regionalized neural progenitors only mildly altered genomic NGN2 binding and its transcriptional response and did not affect neurotransmitter specification. In contrast, coexpression of region-specific homeobox factors such as EMX1 resulted in drastic redistribution of NGN2 including recruitment to homeobox targets and resulted in glutamatergic neurons with silenced nonglutamatergic programs. These results provide the molecular basis for a blueprint for improved strategies for generating a plethora of defined neuronal subpopulations from pluripotent stem cells for therapeutic or disease-modeling purposes.

Sertoli cells are the source of stem cell factor for spermatogenesis.

Several cell types have been proposed to create the required microenvironment for spermatogenesis. However, expression patterns of the key growth factors produced by these somatic cells have not been systematically studied and no such factor has been conditionally deleted from its primary source(s), raising the question of which cell type(s) are the physiological sources of these growth factors. Here, using single-cell RNA sequencing and a series of fluorescent reporter mice, we found that stem cell factor (Scf), one of the essential growth factors for spermatogenesis, was broadly expressed in testicular stromal cells, including Sertoli, endothelial, Leydig, smooth muscle and Tcf21-CreER+ stromal cells. Both undifferentiated and differentiating spermatogonia were associated with Scf-expressing Sertoli cells in the seminiferous tubule. Conditional deletion of Scf from Sertoli cells, but not any other Scf-expressing cells, blocked the differentiation of spermatogonia, leading to complete male infertility. Conditional overexpression of Scf in Sertoli cells, but not endothelial cells, significantly increased spermatogenesis. Our data reveal the importance of anatomical localization for Sertoli cells in regulating spermatogenesis and that SCF produced specifically by Sertoli cells is essential for spermatogenesis.

TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells.

The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4(+)CD8(+) double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells and redirected CD4(+) T cells to a CD8(+) T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8(+) lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4(+) T cell fate and establish CD8(+) T cell identity.

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton.

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1f/fmice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

Promoted hydrogen and acetaldehyde production from alcohol dehydrogenation enabled by electrochemical hydrogen pumps.

The dehydrogenation reaction of bioderived ethanol is of particular interest for the synthesis of fuels and value-added chemicals. However, this reaction historically suffered from high energy consumption (>260 °C or >0.8 V) and low efficiency. Herein, the efficient conversion of alcohol to hydrogen and aldehyde is achieved by integrating the thermal dehydrogenation reaction with electrochemical hydrogen transfer at low temperature (120 °C) and low voltage (0.06 V), utilizing a bifunctional catalyst (Ru/C) with both thermal-catalytic and electrocatalytic activities. Specifically, the coupled electrochemical hydrogen separation procedure can serve as electrochemical hydrogen pumps, which effectively promote the equilibrium of ethanol dehydrogenation toward hydrogen and acetaldehyde production and simultaneously purifies hydrogen at the cathode. By utilizing this strategy, we achieved boosted hydrogen and acetaldehyde yields of 1,020 mmol g-1 h-1 and 1,185 mmol g-1 h-1, respectively, which are threefold higher than the exclusive ethanol thermal dehydrogenation. This work opens up a prospective route for the high-efficiency production of hydrogen and acetaldehyde via coupled thermal-electrocatalysis.

Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.

The mixed-lineage leukemia (MLL)-AF10 fusion oncoprotein recruits DOT1L to the homeobox A (HOXA) gene cluster through its octapeptide motif leucine zipper (OM-LZ), thereby inducing and maintaining the MLL-AF10-associated leukemogenesis. However, the recognition mechanism between DOT1L and MLL-AF10 is unclear. Here, we present the crystal structures of both apo AF10OM-LZ and its complex with the coiled-coil domain of DOT1L. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. We further show that zinc stabilizes the DOT1L-AF10 complex and may be involved in the regulation of the HOXA gene expression. Our studies may also pave the way for the rational design of therapeutic drugs against MLL-rearranged leukemia.

CodonBERT: a BERT-based architecture tailored for codon optimization using the cross-attention mechanism.

MOTIVATION: Due to the varying delivery methods of messenger RNA (mRNA) vaccines, codon optimization plays a critical role in vaccine design to improve the stability and expression of proteins in specific tissues. Considering the many-to-one relationship between synonymous codons and amino acids, the number of mRNA sequences encoding the same amino acid sequence could be enormous. Finding stable and highly expressed mRNA sequences from the vast sequence space using in silico methods can generally be viewed as a path-search problem or a machine translation problem. However, current deep learning-based methods inspired by machine translation may have some limitations, such as recurrent neural networks (RNNs), which have a weak ability to capture the long-term dependencies of codon preferences. RESULTS: We develop a BERT-based architecture that uses the cross-attention mechanism for codon optimization. In CodonBERT, the codon sequence is randomly masked with each codon serving as a key and a value. In the meantime, the amino acid sequence is used as the query. CodonBERT was trained on high-expression transcripts from Human Protein Atlas mixed with different proportions of high codon adaptation index (CAI) codon sequences. The result showed that CodonBERT can effectively capture the long-term dependencies between codons and amino acids, suggesting that it can be used as a customized training framework for specific optimization targets. AVAILABILITY: CodonBERT is freely available on https://github.com/FPPGroup/CodonBERT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1.

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

CRISPR-based genome editing of a diurnal rodent, Nile grass rat (Arvicanthis niloticus).

BACKGROUND: Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. The present study aims to address this major limitation by developing experimental procedures necessary for genome editing in a well-established diurnal rodent model, the Nile grass rat (Arvicanthis niloticus). RESULTS: A superovulation protocol was established, which yielded nearly 30 eggs per female grass rat. Fertilized eggs were cultured in a modified rat 1-cell embryo culture medium (mR1ECM), in which grass rat embryos developed from the 1-cell stage into blastocysts. A CRISPR-based approach was then used for gene editing in vivo and in vitro, targeting Retinoic acid-induced 1 (Rai1), the causal gene for Smith-Magenis Syndrome, a neurodevelopmental disorder. The CRISPR reagents were delivered in vivo by electroporation using an improved Genome-editing via Oviductal Nucleic Acids Delivery (i-GONAD) method. The in vivo approach produced several edited founder grass rats with Rai1 null mutations, which showed stable transmission of the targeted allele to the next generation. CRISPR reagents were also microinjected into 2-cell embryos in vitro. Large deletion of the Rai1 gene was confirmed in 70% of the embryos injected, demonstrating high-efficiency genome editing in vitro. CONCLUSION: We have established a set of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats. The methods developed will guide future genome editing of this and other diurnal rodent species, which will promote greater utility of these models in basic and translational research.

Amplifying Photon Upconversion in Alloyed Nanoparticles for a Near-Infrared Photodetector.

Photon upconverison has attracted a substantial amount of interest in diverse fields due to its characteristic anti-Stokes emissions. However, obtaining intense emission under low-power laser irradiation has remained a challenge. Here we report a mechanistic design of activator-sensitizer alloyed nanoparticles to achieve bright upconversion under weak infrared irradiation. This design allows a nearest sensitizer-activator separation to facilitate efficient energy transfer that results in remarkably enhanced upconversion (>2 orders of magnitude) under 0.26 W cm-2 irradiation compared to that of the Er sublattice, and the upconversion quantum yield also shows a 20-fold increase. Interestingly, the alloyed nanoparticles exhibit a gradual change in emission color with an increase in Yb3+ content, and moreover, their emission colors can be dynamically controlled by simply modulating the excitation laser power and pulse widths. Such alloyed nanoparticles show great promise for application in a near-infrared photodetector.

Jellyfish-Inspired Self-Healing Luminescent Elastomers Based on Borate Nanoassemblies for Dual-Model Encryption.

Responsive luminescent materials that reversibly react to external stimuli have emerged as prospective platforms for information encryption applications. Despite brilliant achievements, the existing fluorescent materials usually have low information density and experience inevitable information loss when subjected to mechanical damage. Here, inspired by the hierarchical nanostructure of fluorescent proteins in jellyfish, we propose a self-healable, photoresponsive luminescent elastomer based on dynamic interface-anchored borate nanoassemblies for smart dual-model encryption. The rigid cyclodextrin molecule restricts the movement of the guest fluorescent molecules, enabling long room-temperature phosphorescence (0.37 s) and excitation wavelength-responsive fluorescence. The building of reversible interfacial bonding between nanoassemblies and polymer matrix together with their nanoconfinement effect endows the nanocomposites with excellent mechanical performances (tensile strength of 15.8 MPa) and superior mechanical and functional recovery capacities after damage. Such supramolecular nanoassemblies with dynamic nanoconfinement and interfaces enable simultaneous material functionalization and self-healing, paving the way for the development of advanced functional materials.

Pregranulosa cell-derived FGF23 protects oocytes from premature apoptosis during primordial follicle formation by inhibiting p38 MAPK in mice.

A large number of oocytes in the perinatal ovary in rodents get lost for unknown reasons. The granulosa cell-oocyte mutual communication is pivotal for directing formation of the primordial follicle; however, little is known if paracrine factors participate in modulating programmed oocyte death perinatally. We report here that pregranulosa cell-derived fibroblast growth factor 23 (FGF23) functioned in preventing oocyte apoptosis in the perinatal mouse ovary. Our results showed that FGF23 was exclusively expressed in pregranulosa cells, while fibroblast growth factor receptors (FGFRs) were specifically expressed in the oocytes in perinatal ovaries. FGFR1 was one of the representative receptors in mediating FGF23 signaling during the formation of the primordial follicle. In cultured ovaries, the number of live oocytes declines significantly, accompanied by the activation of the p38 mitogen-activated protein kinase signaling pathway, under the condition of FGFR1 disruption by specific inhibitors of FGFR1 or silencing of Fgf23. As a result, oocyte apoptosis increased and eventually led to a decrease in the number of germ cells in perinatal ovaries following the treatments. In the perinatal mouse ovary, pregranulosa cell-derived FGF23 binds to FGFR1 and activates at least the p38 mitogen-activated protein kinase signaling pathway, thereby regulating the level of apoptosis during primordial follicle formation. This study reemphasizes the importance of granulosa cell-oocyte mutual communication in modulating primordial follicle formation and supporting oocyte survival under physiological conditions.

ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on m6A modification.

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.

Single-cell RNA sequencing reveals the altered innate immunity in immune checkpoint inhibitor-related myocarditis.

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group). Subcluster determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Bulk-RNA sequencing was performed for further validation. Our results revealed the diversity of cellular populations in ICI-related myocarditis, marked by their distinct transcriptional profiles and biological functions. Monocytes, NKs as well as B cells contribute to the regulation of innate immunity and inflammation in ICI-related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICI-related myocarditis. Our study has created a cell atlas of PBMC during ICI-related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI-related myocarditis in continuous exploration.

Self-Trapped Exciton Emission in Highly Polar 0D Hybrid Ammonium/Hydronium-Based Perovskites Triggered by Antimony Doping.

Various monovalent cations are employed to construct metal halide perovskites with various structures and functionalities. However, perovskites based on highly polar A-site cations have seldom been reported. Here, a novel hybrid 0D (NH4)x(OH3)3-xInCl6 perovskite with highly polar hydronium OH3+ cations is introduced in this study. Upon doping with Sb3+, hybrid 0D (NH4)x(OH3)3-xInCl6 single crystals exhibited highly efficient broadband yellowish-green (550 nm) and red (630 nm) dual emissions with a PLQY of 86%. The dual emission arises due to Sb3+ occupying two sites within the crystal lattice that possess different polarization environments, leading to distinct Stokes shift energies. The study revealed that lattice polarity plays a significant role in the self-trapped exciton emission of Sb3+-doped perovskites, contributing up to 25% of the Stokes shift energy for hybrid 0D (NH4)x(OH3)3-xInCl6:Sb3+ as a secondary source, in addition to the Jahn-Teller deformation. These findings highlight the potential of Sb3+-doped perovskites for achieving tunable broadband emission and underscore the importance of lattice polarity in determining the emission properties of perovskite materials.