Generation and characterization of an iPS cell line (PUMCi006-A) from skin fibroblasts of a patient with an M239T mutation in PSEN2 gene.

Presenilin-2 (PSEN2) mutation is one of the pathogenic factors of autosomal dominant early-onset Alzheimer's disease (EOAD). We generated a human induced pluripotent stem cell (iPSC) line from fibroblasts of an EOAD patient carrying PSEN2 mutation (c.716 T > C) utilizing Sendai reprogramming kit. The resulting iPSC line carried patient-specific point mutation, exhibited typical iPSC morphology, retained a normal karyotype, expressed pluripotency markers, and could form embryoid bodies. Established iPSC line serve as valuable resource for EOAD disease pathogenesis modelling and drug screening.

Anti-SFT2D2 autoantibodies alter dendrite spine and cause psychotic behavior in mice.

BACKGROUND: Autoimmunity plays an important role in schizophrenia (SCZ). Autoantibodies against SFT2D2 have been reported in patients with SCZ; however, the specific mechanism remains unclear. This study aimed to describe an autoimmune model, namely, mice immunized against SFT2D2-peptides. METHODS: ApoE-/- and WT mice (C57BL/6) were immunized four times (day 0, day 14, day 21, day 35) with SFT2D2 peptide or KLH via subcutaneous injection. Behavioral tests were conducted after the third immunization, and immunochemistry of brain tissue were performed after the sacrifice of the mice. RESULTS: Active immunization with KLH-coupled SFT2D2-derived peptides in both WT and ApoE-/- (compromised blood-brain barrier) mice led to high circulating levels of anti-SFT2D2 IgG. While there was no detectable deficit in WT mice, impaired pre-pulse inhibition, motor impairments, and reduced cognition in ApoE-/- mice, without signs of anxiety and depression were observed. In addition, immunohistochemical assays demonstrated that activated microglia and astrocytes were increased but neuronal dendritic spine densities were decreased, accompanied by increased expression of complement molecule C4 across brain regions in ApoE-/- mice. CONCLUSIONS: In model mice with compromised blood-brain barrier, endogenous anti-SFT2D2 IgG can activate glial cells and modulate synaptic plasticity, and induce a series of psychosis-like changes. These antibodies may reveal valuable therapeutic targets, which may improve the treatment strategies for a subgroup of SCZ patients.

MADS8 is indispensable for female reproductive development at high ambient temperatures in cereal crops.

Temperature is a major factor that regulates plant growth and phenotypic diversity. To ensure reproductive success at a range of temperatures, plants must maintain developmental stability of their sexual organs when exposed to temperature fluctuations. However, the mechanisms integrating plant floral organ development and temperature responses are largely unknown. Here, we generated barley and rice loss-of-function mutants in the SEPALLATA-like MADS-box gene MADS8. The mutants in both species form multiple carpels that lack ovules at high ambient temperatures. Tissue-specific markers revealed that HvMADS8 is required to maintain floral meristem determinacy and ovule initiation at high temperatures, and transcriptome analyses confirmed that temperature-dependent differentially expressed genes in Hvmads8 mutants predominantly associate with floral organ and meristem regulation. HvMADS8 temperature-responsive activity relies on increased binding to promoters of downstream targets, as revealed by a cleavage under targets and tagmentation (CUT&Tag) analysis. We also demonstrate that HvMADS8 directly binds to 2 orthologs of D-class floral homeotic genes to activate their expression. Overall, our findings revealed a new, conserved role for MADS8 in maintaining pistil number and ovule initiation in cereal crops, extending the known function of plant MADS-box proteins in floral organ regulation.

LHPP-mediated inorganic pyrophosphate hydrolysis-driven lysosomal acidification in astrocytes regulates adult neurogenesis.

In bacteria, archaea, protists, and plants, the hydrolysis of pyrophosphate (PPi) by inorganic pyrophosphatase (PPase) can, under stress conditions, substitute for ATP-driven proton flux to generate a proton gradient and induce luminal acidification. However, this strategy is considered to be lost in eukaryotes. Here, we report that LHPP, a poorly understood PPase that exhibits activity at acidic pH, is primarily expressed in astrocytes and partly localized on lysosomal membranes. Under stress conditions, LHPP is recruited to vacuolar ATPase (V-ATPase) and facilitates V-ATPase-dependent proton transport and lysosomal acidification by hydrolyzing PPi. LHPP knockout (KO) mice have no discernable phenotype but are resilient to chronic-stress-induced depression-like behaviors. Mechanistically, LHPP deficiency prevents lysosome-dependent degradation of C/EBPß and induces the expression of a group of chemokines that promote adult neurogenesis. Together, these findings suggest that LHPP is likely to be a therapeutic target for stress-related brain disease.

SMURF2 facilitates ubiquitin-mediated degradation of ID2 to attenuate lung cancer cell proliferation.

SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) functions as either a tumor promoter or tumor suppressor in several tumors. However, the detailed effect of SMURF2 on non-small cell lung cancer has not been fully understood. In this study, SMURF2 expression and its diagnostic value were analyzed. Co-Immunoprecipitation (Co-IP), proximity ligation assay (PLA), chromatin immunoprecipitation (ChIP) and nude mice tumor-bearing model were applied to further clarify the role of SMURF2 in lung cancer. SMURF2 expression was reduced in the tumor tissues of patients with NSCLC and high SMURF2 expression was significantly correlated with favorable outcomes. Furthermore, the overexpression of SMURF2 significantly inhibited lung cancer cell progression. Mechanistically, SMURF2 interacted with inhibitor of DNA binding 2 (ID2), subsequently promoting the poly-ubiquitination and degradation of ID2 through the ubiquitin-proteasome pathway. Downregulated ID2 in lung cells dissociates endogenous transcription factor E2A, a positive regulator of the cyclin-dependent kinase inhibitor p21, and finally induces G1/S arrest in lung cancer cells. This study revealed that the manipulation of ID2 via SMURF2 may control tumor progression and contribute to the development of novel targeted antitumor drugs.

Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice.

Objective: An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS. Methods: After 14-day acclimation, the grouped ApoE-/- mice were immunized four times (day 0, day 7, day 14, day 28) with different spike-protein-derived peptides (coupled with KLH) or KLH via subcutaneous injection. Antibody level, state of glial cells, gene expression, prepulse inhibition, locomotor activity, and spatial working memory were assessed from day 21. Results: An increased level of anti-S1-111 IgG was measured in their sera and brain homogenate after the immunization. Crucially, anti-S1-111 IgG increased the density of microglia, activated microglia, and astrocytes in the hippocampus, and we observed a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among S1-111-immunized mice. Transcriptome profiling showed that up-regulated genes in S1-111-immunized mice were mainly associated with synaptic plasticity and mental disorders. Discussion: Our results show that the non-neutralizing antibody anti-S1-111 IgG induced by the spike protein caused a series of psychotic-like changes in model mice by activating glial cells and modulating synaptic plasticity. Preventing the production of anti-S1-111 IgG (or other non-neutralizing antibodies) may be a potential strategy to reduce CNS manifestations in COVID-19 patients and vaccinated individuals.

Regulatory Mechanisms and Reversal of CD8+T Cell Exhaustion: A Literature Review.

CD8+T cell exhaustion is a state of T cell dysfunction during chronic infection and tumor progression. Exhausted CD8+T cells are characterized by low effector function, high expression of inhibitory receptors, unique metabolic patterns, and altered transcriptional profiles. Recently, advances in understanding and interfering with the regulatory mechanisms associated with T cell exhaustion in tumor immunotherapy have brought greater attention to the field. Therefore, we emphasize the typical features and related mechanisms of CD8+T cell exhaustion and particularly the potential for its reversal, which has clinical implications for immunotherapy.

THERMOSENSITIVE BARREN PANICLE (TAP) is required for rice panicle and spikelet development at high ambient temperature.

In cereal plants, the size of the panicle (inflorescence) is a critical factor for yield. Panicle size is determined by a complex interplay of genetic and environmental factors, but the mechanisms underlying adaptations to temperature stress during panicle development remain largely unknown. We identify the rice THERMOSENSITIVE BARREN PANICLE (TAP) gene, which encodes a transposase-derived FAR1-RELATED SEQUENCE (FRS) protein and is responsible for regulating panicle and spikelet development at high ambient temperature. The tap mutants display high temperature-dependent reproductive abnormalities, including compromised secondary branch and spikelet initiation and pleiotropic floral organ defects. Consistent with its thermosensitive phenotype, TAP expression is induced by high temperature. TAP directly promotes the expression of OsYABBY3 (OsYAB3), OsYAB4, and OsYAB5, which encode key transcriptional regulators in panicle and spikelet development. In addition, TAP physically interacts with OsYAB4 and OsYAB5 proteins; phenotypic analysis of osyab4 tap-1 and osyab5 tap-1 double mutants indicates that TAP-OsYAB4/OsYAB5 complexes act to maintain normal panicle and spikelet development. Taken together, our study reveals the novel role of a TE-derived transcription factor in controlling rice panicle development under high ambient temperatures, shedding light on the molecular mechanism underlying the adaptation of cereal crops to increasing environmental temperatures.

Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.

Lymphocyte-specific protein tyrosine kinase (LCK) is common in a variety of hematologic malignancies but comparatively less common in solid tumors. This study aimed to explore the potential diagnostic and prognostic value of LCK across tumors through integrative and comprehensive pan-cancer analysis, as well as experimental validation. Multiple databases were used to explore the expression, alteration, prognostic value, association with immune infiltration, and potential functional pathways of LCK in pan-cancers. The results were further validated by western blotting and qPCR of patient samples as well as tumor cell lines. High LCK expression typically represents a better prognosis. Notably, drug sensitivity prediction of LCK identified P-529 as a candidate for drug development. Gene Annotations (GO) and KEGG analyses showed significant enrichment of PD-L1 and the T-cell receptor pathway. The results from patient samples and tumor cell lines confirmed these conclusions in LIHC. In conclusion, LCK is differentially expressed in multiple tumors and normal tissues. Further analysis highlighted its association with prognostic implications, pan-cancer genetic alterations, and immune signatures. Our data provide evidence for a diagnostic marker of LCK and the possible use of LCK as a target for the treatment of tumors.

Case report: Eosinophilic pneumonia associated with vedolizumab therapy in a patient with ulcerative colitis.

Extraintestinal manifestations are common in patients with inflammatory bowel disease, while respiratory involvement is less common. Vedolizumab is a new class of anti-integrin biological agents approved for treating inflammatory bowel disease. In this report, we present the case of a 38-year-old patient with ulcerative colitis for 7 years who developed cough, fever, and pulmonary infiltrates after taking vedolizumab. There was a spontaneous improvement in clinical symptoms and radiological abnormalities after discontinuing vedolizumab and introducing steroids. Despite the rarity of vedolizumab-induced eosinophilic pneumonia, the case reports indicate that patients with unexplained respiratory symptoms that are taking vedolizumab should be fully contemplated.

Induction of A Disintegrin and Metalloproteinase with Thrombospondin motifs 1 by a rare variant or cognitive activities reduces hippocampal amyloid-ß and consequent Alzheimer's disease risk.

Amyloid-ß (Aß) derived from amyloid precursor protein (APP) hydrolysis is acknowledged as the predominant hallmark of Alzheimer's disease (AD) that especially correlates to genetics and daily activities. In 2019, meta-analysis of AD has discovered five new risk loci among which A Disintegrin and Metalloproteinase with Thrombospondin motifs 1 (ADAMTS1) has been further suggested in 2021 and 2022. To verify the association, we re-sequenced ADAMTS1 of clinical AD samples and subsequently identified a novel rare variant c.-2067A > C with watchable relevance (whereas the P-value was not significant after adjustment). Dual-luciferase assay showed that the variant sharply stimulated ADAMTS1 expression. In addition, ADAMTS1 was also clearly induced by pentylenetetrazol-ignited neuronal activity and enriched environment (EE). Inspired by the above findings, we investigated ADAMTS1's role in APP metabolism in vitro and in vivo. Results showed that ADAMTS1 participated in APP hydrolysis and consequently decreased Aß generation through inhibiting ß-secretase-mediated cleavage. In addition, we also verified that the hippocampal amyloid load of AD mouse model was alleviated by the introduction of ADAMTS1, and thus spatial cognition was restored as well. This study revealed the contribution of ADAMTS1 to the connection of genetic and acquired factors with APP metabolism, and its potential in reducing hippocampal amyloid and consequent risk of AD.

Pharmacological induction of AMFR increases functional EAAT2 oligomer levels and reduces epileptic seizures in mice.

Dysregulation of excitatory amino acid transporter 2 (EAAT2) contributes to the development of temporal lobe epilepsy (TLE). Several strategies for increasing total EAAT2 levels have been proposed. However, the mechanism underlying the oligomeric assembly of EAAT2, impairment of which inhibits the formation of functional oligomers by EAAT2 monomers, is still poorly understood. In the present study, we identified E3 ubiquitin ligase AMFR as an EAAT2-interacting protein. AMFR specifically increased the level of EAAT2 oligomers rather than inducing protein degradation through K542-specific ubiquitination. By using tissues from humans with TLE and epilepsy model mice, we observed that AMFR and EAAT2 oligomer levels were simultaneously decreased in the hippocampus. Screening of 2386 FDA-approved drugs revealed that the most common analgesic/antipyretic medicine, acetaminophen (APAP), can induce AMFR transcriptional activation via transcription factor SP1. Administration of APAP protected against pentylenetetrazol-induced epileptogenesis. In mice with chronic epilepsy, APAP treatment partially reduced the occurrence of spontaneous seizures and greatly enhanced the antiepileptic effects of 17AAG, an Hsp90 inhibitor that upregulates total EAAT2 levels, when the 2 compounds were administered together. In summary, our studies reveal an essential role for AMFR in regulating the oligomeric state of EAAT2 and suggest that APAP can improve the efficacy of EAAT2-targeted antiepileptic treatments.

Ethylene inhibits rice root elongation in compacted soil via ABA- and auxin-mediated mechanisms.

Soil compaction represents a major agronomic challenge, inhibiting root elongation and impacting crop yields. Roots use ethylene to sense soil compaction as the restricted air space causes this gaseous signal to accumulate around root tips. Ethylene inhibits root elongation and promotes radial expansion in compacted soil, but its mechanistic basis remains unclear. Here, we report that ethylene promotes abscisic acid (ABA) biosynthesis and cortical cell radial expansion. Rice mutants of ABA biosynthetic genes had attenuated cortical cell radial expansion in compacted soil, leading to better penetration. Soil compaction-induced ethylene also up-regulates the auxin biosynthesis gene OsYUC8. Mutants lacking OsYUC8 are better able to penetrate compacted soil. The auxin influx transporter OsAUX1 is also required to mobilize auxin from the root tip to the elongation zone during a root compaction response. Moreover, osaux1 mutants penetrate compacted soil better than the wild-type roots and do not exhibit cortical cell radial expansion. We conclude that ethylene uses auxin and ABA as downstream signals to modify rice root cell elongation and radial expansion, causing root tips to swell and reducing their ability to penetrate compacted soil.

Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice.

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (n = 80) and RNA expression microarray data (n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size (n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 (n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.

Sensitive detection of electrophysiology and dopamine vesicular exocytosis of hESC-derived dopaminergic neurons using multifunctional microelectrode array.

Clinical transplantation of human embryonic stem cells derived dopaminergic neurons (hESC-DDNs) is expected to be a potential therapy for treating neurodegenerative diseases. However, the assessment of the physiological functions, including electrophysiology and dopamine (DA) vesicular exocytosis of hESC-DDNs are not impeccable currently, which deeply limits the clinical application of hESC-DDNs. To overcome this challenge, we developed a multifunctional microelectrode array (MEA) which can detect both electrophysiological signals and DA vesicular exocytosis. The reduced oxidation graphene, poly(3,4-ethylenedioxythiophene) and poly (sodium-4-styrenesultanate) nanocomposites (rGO/PEDOT:PSS) were electrochemically deposited on the MEAs to improve their electrical characterizations with low impedance and small phase delay, and electrochemical characterizations with low oxidation potential, low detection limit, high sensitivity, wide linear range and high sensitivity. In the hESC-DDNs experiment, the modified MEA could detect electrophysiological signals with low noise (25 µV) and high signal-to-noise ratio (>5.4), and the weak current signals generated by DA vesicular exocytosis with high sensitivity (∼pA), high time resolution (sub-millisecond) and low noise (3 pA). Moreover, due to increased accuracy, the MEA could clearly distinguish two typical kinds of exocytosis spike events ("Spikes with foot" and "Spikes without foot") and found that the slow and low release through the fusion pore was an important mode of DA vesicular exocytosis in hESC-DDNs. Our work proved that the hESC-DDNs had the basic physiological functions as human dopaminergic neurons, which would be beneficial to the clinical application of the hESC-DDNs.

Generation of a human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient carrying an E363Q mutation in PSEN1 gene.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive decline even leading to incapacity, which prevalence estimates that about 5% of AD cases are caused by mutations in genes such as Presenilin-1 (PSEN1). Here we report the generation and characterization of an iPSC line derived from a patient carrying an E363Q mutation in PSEN1 gene. The iPSC line we generated presented a typical morphology, normal karyotype, free from Sendai viral vectors and exogenous factors, expressed endogenous pluripotency marker genes and proteins, which could form embryoid bodies in vitro and form teratoma in vivo as well, demonstrating its pluripotency.

Rice SIAH E3 Ligases Interact with RMD Formin and Affect Plant Morphology.

Formins are actin-binding proteins that are key to maintaining the actin cytoskeleton in cells. However, molecular mechanisms controlling the stability of formin proteins in plants remain unknown. Here, we have identified six rice SIAH-type E3 ligases, named RIP1-6 (RMD Interacting Protein 1-6) respectively, with ubiquitination enzyme activity in vitro. All six proteins can form homo- and hetero-dimers with themselves, and hetero-dimers with type II formin RMD/OsFH5. In vivo assays showed that RIP1-6 proteins localize in the cytoplasm with a punctate distribution, and all of them interact with RMD to change its native diffuse cytoplasmic localization to match that of RIP1-6. To our surprise, degradation experiments revealed that RIP1, RIP5, and RIP6 decrease rather than increase the degradation rate of RMD. Genetic analyses revealed redundancy between these six genes; either single or double mutants did not show any obvious phenotypes. However, the sextuple rip1-6 mutant displayed dwarf height, wrinkled seeds and wider leaves that were similar to the previously reported rmd mutant, and defective microfilaments and increased flag leaf angles that were not reported in rmd mutant. Collectively, our study provides insights into the mechanisms determining formin protein stability in plants.

The SFT2D2 gene is associated with the autoimmune pathology of schizophrenia in a Chinese population.

Background: The relative risk of GWAS-confirmed loci strongly associated with schizophrenia may be underestimated due to the decay of linkage disequilibrium between index SNPs and causal variants. This study is aimed to investigate schizophrenia-associated signals detected in the 1q24-25 region in order to identify a causal variant in LD with GWAS index SNPs, and the potential biological functions of the risk gene. Methods: Re-genotyping analysis was performed in the 1q24-25 region that harbors three GWAS index SNPs associated with schizophrenia (rs10489202, rs11586522, and rs6670165) in total of 9801 case-control subjects of Chinese Han origin. Circulating autoantibody levels were assessed using an in-house ELISA against a protein derived fragment encoded by SFT2D2 in total of 682 plasma samples. Results: A rare variant (rs532193193) in the SFT2D2 locus was identified to be strongly associated with schizophrenia. Compared with control subjects, patients with schizophrenia showed increased anti-SFT2D2 IgG levels. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.803 with sensitivity of 28.57% against specificity of 95% for the anti-SFT2D2 IgG assay. Discussion: Our findings indicate that SFT2D2 is a novel gene for risk of schizophrenia, while endogenous anti-SFT2D2 IgG may underlie the pathophysiology of the immunological aspects of schizophrenia.

Rice SEPALLATA genes OsMADS5 and OsMADS34 cooperate to limit inflorescence branching by repressing the TERMINAL FLOWER1-like gene RCN4.

The spatiotemporal control of meristem identity is critical for determining inflorescence architecture, and thus yield, of cereal plants. However, the precise mechanisms underlying inflorescence and spikelet meristem determinacy in cereals are still largely unclear. We have generated loss-of-function and overexpression mutants of the paralogous OsMADS5 and OsMADS34 genes in rice (Oryza sativa), and analysed their panicle phenotypes. Using chromatin immunoprecipitation, electrophoretic mobility-shift and dual-luciferase assays, we have also identified RICE CENTRORADIALIS 4 (RCN4), a TFL1-like gene, as a direct downstream target of both OsMADS proteins, and have analysed RCN4 mutants. The osmads5 osmads34 mutant lines had significantly enhanced panicle branching with increased secondary, and even tertiary and quaternary, branches, compared to wild-type (WT) and osmads34 plants. The osmads34 mutant phenotype could largely be rescued by also knocking out RCN4. Moreover, transgenic panicles overexpressing RCN4 had significantly increased branching, and initiated development of c. 7× more spikelets than WT. Our results reveal a role for OsMADS5 in panicle development, and show that OsMADS5 and OsMADS34 play similar functions in limiting branching and promoting the transition to spikelet meristem identity, in part by repressing RCN4 expression. These findings provide new insights to better understand the molecular regulation of rice inflorescence architecture.

SMALL REPRODUCTIVE ORGANS, a SUPERMAN-like transcription factor, regulates stamen and pistil growth in rice.

Organ size is determined mainly by cell division and cell expansion. Several genetic factors regulating development of plant lateral organs have been characterized, but those involved in determining reproductive organ size and separation in rice (Oryza sativa) remain unknown. We have isolated the rice gene SMALL REPRODUCTIVE ORGANS (SRO) encoding a nucleus-localized Cys2His2 (C2 H2 ) zinc finger protein orthologous to Arabidopsis transcription factor (TF) SUPERMAN (SUP). Combined developmental, genetic, histological and transcriptomic analyses were used to determine the function of SRO in regulating reproductive organ size. SRO affects genes involved in cell division, cell expansion and phytohormone signalling in the rice flower. SRO is specifically expressed in the first stages of stamen filament development to regulate their correct formation and separation. In addition, SRO noncell-autonomously regulates the size and functionality of male and female reproductive organs. The B-class MADS-box gene OsMADS16/SPW1 is epistatic to SRO, whereas SRO regulates reproductive organ specification and floral meristem determinacy synergistically with C-class genes OsMADS3 and OsMADS58. These findings provide insights into how an evolutionarily conserved TF has a pivotal role in reproductive organ development in core eudicots and monocots, through partially conserved expression, function and regulatory network.