Carbene-Stabilized Phosphagermylenylidene: A Heavier Analog of Isonitrile.

Phosphagermylenylidenes (R-P═Ge), as heavier analogs of isonitriles, whether in their free state or as complexes with a Lewis base, have not been previously identified as isolable entities. In this study, we report the synthesis of a stable monomeric phosphagermylenylidene within the coordination sphere of a Lewis base under ambient conditions. This species was synthesized by Lewis base-induced dedimerization of a cyclic phosphagermylenylidene dimer or via Me3SiCl elimination from a phosphinochlorogermylene framework. The deliberate integration of a bulky, electropositive N-heterocyclic boryl group at the phosphorus site, combined with coordination stabilization by a cyclic (alkyl)(amino)carbene at the low-valent germanium site, effectively mitigated its natural tendency toward oligomerization. Structural analyses and theoretical calculations have demonstrated that this unprecedented species features a P═Ge double bond, characterized by conventional electron-sharing π and σ bonds, complemented by lone pairs at both the phosphorus and germanium atoms. Preliminary reactivity studies show that this base-stabilized phosphagermylenylidene demonstrates facile release of ligands at the Ge atom, coordination to silver through the lone pair on P, and versatile reactivity including both (cyclo)addition and cleavage of the P═Ge double bond.

A systematic review on reporting quality of economic evaluations for negotiated glucose-lowering drugs in China national reimbursement drug list.

BACKGROUND: This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). METHODS: We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal-Wallis test and Mann-Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. RESULTS: We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal-Wallis test and Mann-Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. CONCLUSIONS: There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Polarization-insensitive and high-efficiency edge coupler for thin-film lithium niobate.

In this Letter, we propose and demonstrate a fiber-to-chip edge coupler (EC) on an x-cut thin film lithium niobate (TFLN) for polarization-insensitive (PI) coupling. The EC consists of three width-tapered full-etched waveguides with silica cladding and matches well with a single-mode fiber (SMF). The measured results show that the minimum coupling losses for TE0/TM0 modes remain to be 0.9 dB/1.1 dB per facet, and the polarization dependent loss (PDL) is <0.5 dB over the wavelength range from 1260 to 1340 nm. Moreover, the EC features large misalignment tolerance of ±2 µm in the Z direction and ±1.5 µm in the X direction for both polarizations for a 1 dB penalty. To the best of our knowledge, this is the first realized O-band edge coupler on TFLN with SMF. The proposed device shows promising potential for integration into TFLN polarization diversity devices.

Impact of the diseased lung microenvironment on the in vivo fate of inhaled particles.

Inhalation drug delivery is superior for local lung disease therapy. However, there are several unique absorption barriers for inhaled drugs to overcome, including limited drug deposition at the target site, mucociliary clearance, pulmonary macrophage phagocytosis, and systemic exposure. Moreover, the respiratory disease state can affect or even destroy the physiology of the lung, thus influencing the in vivo fate of inhaled particles compared with that in healthy lungs. Nevertheless, limited information is available on this effect. Thus, in this review, we present pathological changes of the lung microenvironment under varied respiratory diseases and their influence on the in vivo fate of inhaled particles; such insights could provide a basis for rational inhalation particle design based on specific disease states.

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.

AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.

Genome-wide characterization and expression analysis of the HD-Zip II gene family in response to drought and GA3 stresses in Nicotiana tabacum.

BACKGROUND: Homeodomain-leucine ZIPper (HD-ZIP) transcription factors play crucial roles in plant growth, development, and stress responses. The HD-ZIP family is categorised into four groups (HD-ZIP I-IV). While extensive genome-wide studies have been conducted on the HD-ZIP I, III, and IV subfamily in Nicotiana tabacum (tobacco), comprehensive reports on the HD-ZIP II subfamily genes are limited. METHODS: Bioinformatics resources and tools were utilised to analyse molecular characteristics, phylogenetic homology, and protein interactions. Expression pattern analyses in various tissues and the relative expression of NtHD-ZIP II genes under drought and GA3 treatment were assessed by qRT-PCR. RESULTS: In this study, 24 HD-ZIP II members were systematically identified and categorised into seven independent clades through phylogenetic analysis involving tobacco and other plant species. We found that 19 NtHD-ZIP II genes exhibited tissue-specific expression. The transcripts of NtHD-ZIPII3, 4, 14, 23, 24 were notably induced under the drought treatments, while those of NtHD-ZIPII7, 11, 12, 20 were suppressed. Furthermore, NtHD-ZIPII15 transcripts decreased following GA3 treatment, whereas the transcripts of NtHD-ZIPII7, 8, 11, 12 were induced after GA3 treatment. Notably, an increase in trichomes was observed in tobacco leaves treated with GA3 and subjected to drought. CONCLUSIONS: The expression levels of some HD-ZIP II genes were altered, and an increase in glandular trichomes was induced under GA3 and drought treatments in tobacco. Overall, our findings provide insights into the expression patterns of NtHD-ZIP II genes and will facilitate their functional characterisation in future studies.

Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics.

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells_6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells_6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM.

Association between CBL gene polymorphism and susceptibility of microscopic polyangiitis in a Chinese population: A case-control analysis.

OBJECTIVE: To assess whether Casitas B-lineage lymphoma (CBL) gene polymorphism influences the risk of microscopic polyangiitis (MPA) in Chinese populations. METHODS: In total, 266 MPA patients and 297 healthy controls were recruited for a case-control study. Five CBL SNPs were genotyped using multiplex polymerase chain reaction and high-throughput sequencing. The relationship between SNPs and the risk of MPA under different genetic models was evaluated by SNPstats. SNP-SNP interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Finally, the association between CBL SNPs and treatment effects were assessed. RESULTS: The results showed that CBL rs2276083 was associated with decreasing MPA risk under dominant (OR: 0.53; p = 0.014) and recessive models (OR: 0.52; p = 0.0034). Stratification analysis indicated that rs2276083 and rs2509671 in age < 60 years, rs2276083 in female or in Han population were protective factors for MPA. The CBL haplotype (A-A-G-C-T) was associated with an increased risk of MPA. GMDR suggested that CBL rs2276083, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) rs1607237, and autophagy-related gene 7 (ATG7) rs7549008 might interact with each other in MPA development (p = 0.0107). CBL rs1047417 with AG genotype and rs11217234 with AG genotype had better clinical treatment effects than other two genotypes (p = 0.048 and p = 0.025, respectively). CONCLUSION: The genetic polymorphism of CBL had a potential association with the risk of MPA and clinical treatment effects in Guangxi population in China.

Correction: A label-free and immobilization-free approach for constructing photoelectrochemical nucleic acid sensors utilizing DNA-silver nanoparticle affinity interactions.

Correction for 'A label-free and immobilization-free approach for constructing photoelectrochemical nucleic acid sensors utilizing DNA-silver nanoparticle affinity interactions' by Jing Yi et al., Analyst, 2024, https://doi.org/10.1039/D4AN00098F.

MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models.

Mucin 16 (MUC16) participates in the process of embryo implantation, but few studies have examined the association between MUC16 and pregnancy loss. To investigate this association, the expression of MUC16 in serum and decidua was compared between women with pregnancy loss and ongoing pregnancies. In vitro experiments and animal models were used to explore the role and underlying mechanisms of MUC16 in pregnancy loss. In human study, the expression of MUC16 in serum and decidua was both consistently lower in the women with pregnancy loss compared with those in women with ongoing pregnancies. In vitro experiments revealed the interaction of MUC16 with peripheral blood natural killer (pNK) cells. MUC16 changed the phenotype and reduced the pro-inflammation ability of pNK cells. MUC16 also inhibited the cytotoxicity of pNK cells through the Src homology region 2 domain-containing phosphatase-1/extracellular signal-regulated kinase (SHP-ERK) pathway. Furthermore, MUC16 promoted the migration, invasion and tube formation of trophoblast cells by co-culturing together with pNK cells. In vivo experiments, the mouse model of abortion was used to further confirm that intraperitoneal administration of MUC16 could rescue the pregnancy loss. This study reveals the still-unknown connection between MUC16 and pNK cells and indicates that MUC16 provides a novel method for future prediction and treatment of unfavorable pregnancy outcomes.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

Sharp bend and large FSR ring resonator based on the free-form curves on a thin-film lithium niobate platform.

Sharp bends are crucial for large-scale and high-density photonics integration on thin-film lithium niobate platform. In this study, we demonstrate low-loss (<0.05 dB) and sharp bends (Reff = 30 µm) using free-form curves with a 200-nm-thick slab and a rib height of 200 nm on x-cut lithium niobate. Employing the same design method, we successfully realize a compact fully-etched ring resonator with a remarkably large free spectral range of 10.36 nm experimentally. Notably, the equivalent radius of the ring resonator is a mere 15 µm, with a loaded Q factor reaching 2.2 × 104.

The Performance Analysis of Grouting Repair Effect on the Accuracy of Disturbance Stress Test in Damaged Surrounding Rock Mass.

Disturbance stress assessment is crucial for ensuring the safety of deep engineering projects. Currently, the primary technique for continuously monitoring three-dimensional disturbance stress is the stress relief method, but its accuracy can be compromised by rock damage that occurs after excavation. To mitigate this issue, grouting is employed to repair damaged rock masses and enhance their mechanical properties. However, the impact of grouting techniques on improving the accuracy of disturbance stress testing is challenging to evaluate through laboratory and in situ experiments. To address this problem, numerical simulation technology is employed to investigate disturbance stress testing after the repair of damaged surrounding rock through grouting. The simulation results indicate that grouting repair significantly enhances the accuracy of stress testing. As the depth of damaged rock mass repair increases, the error in stress testing decreases. Achieving complete repair of the initial damage zone during grouting is essential to eliminate errors in stress testing. Expanding on the positive effects of grouting repair on stress testing, a segmented testing method for disturbance stress is proposed. The method involves separately testing the initial stress and stress changes, thereby reducing the stress level within the rock, minimizing rock failure, and enhancing the accuracy of disturbance stress testing. This study provides valuable reference methods, and the outcomes of this research will serve as a foundation for enhancing the accuracy of disturbance stress testing in deep hard rock engineering.

Insights into the antibacterial effectiveness of linalool against Shigella flexneri on pork surface: Changes in bacterial growth and pork quality.

Shigella flexneri has the ability to contaminate pork and cause foodborne diseases. This study aimed to examine the effectiveness of linalool (a natural preservative) against S. flexneri and explore its potential application in contaminated pork. The results showed that linalool was capable of damaging the cell membrane and binding to the DNA of S. flexneri, and inhibiting biofilm formation and disrupting mature biofilms. The antibacterial effectiveness of linalool on the surface of pork was further demonstrated by analyzing the physicochemical properties of the pork (i.e., weight loss rate, pH value, color index, and TVB-N value) and its protein profiles. Linalool did not completely kill S. flexneri in pork at minimum bactericidal concentration (MBC) concentration and its antibacterial effect of linalool was stronger during the initial stage of storage. During storage, linalool influenced the abundance of specific proteins in the pork, particularly those involved in pathways related to fat metabolism. These findings offer novel insights into the antibacterial efficacy of linalool and its underlying mechanism in pork.

Spatio-temporal variations of methane fluxes in sediments of a deep stratified temperate lake.

Spatio-temporal variability of sediment-mediated methane (CH4) production in freshwater lakes causes large uncertainties in predicting global lake CH4 emissions under different climate change and eutrophication scenarios. We conducted extensive sediment incubation experiments to investigate CH4 fluxes in Lake Stechlin, a deep, stratified temperate lake. Our results show contrasting spatial patterns in CH4 fluxes between littoral and profundal sites. The littoral sediments, ∼33% of the total sediment surface area, contributed ∼86.9% of the annual CH4 flux at the sediment-water interface. Together with sediment organic carbon quality, seasonal stratification is responsible for the striking spatial difference in sediment CH4 production between littoral and profundal zones owing to more sensitive CH4 production than oxidation to warming. While profundal sediments produce a relatively small amount of CH4, its production increases markedly as anoxia spreads in late summer. Our measurements indicate that future lake CH4 emissions will increase due to climate warming and concomitant hypoxia/anoxia.

CsRAXs negatively regulate leaf size and fruiting ability through auxin glycosylation in cucumber.

Leaves are the main photosynthesis organ that directly determines crop yield and biomass. Dissecting the regulatory mechanism of leaf development is crucial for food security and ecosystem turn-over. Here, we identified the novel function of R2R3-MYB transcription factors CsRAXs in regulating cucumber leaf size and fruiting ability. Csrax5 single mutant exhibited enlarged leaf size and stem diameter, and Csrax1/2/5 triple mutant displayed further enlargement phenotype. Overexpression of CsRAX1 or CsRAX5 gave rise to smaller leaf and thinner stem. The fruiting ability of Csrax1/2/5 plants was significantly enhanced, while that of CsRAX5 overexpression lines was greatly weakened. Similarly, cell number and free auxin level were elevated in mutant plants while decreased in overexpression lines. Biochemical data indicated that CsRAX1/5 directly promoted the expression of auxin glucosyltransferase gene CsUGT74E2. Therefore, our data suggested that CsRAXs function as repressors for leaf size development by promoting auxin glycosylation to decrease free auxin level and cell division in cucumber. Our findings provide new gene targets for cucumber breeding with increased leaf size and crop yield.

Innovative applications of artificial intelligence during the COVID-19 pandemic.

The COVID-19 pandemic has created unprecedented challenges worldwide. Artificial intelligence (AI) technologies hold tremendous potential for tackling key aspects of pandemic management and response. In the present review, we discuss the tremendous possibilities of AI technology in addressing the global challenges posed by the COVID-19 pandemic. First, we outline the multiple impacts of the current pandemic on public health, the economy, and society. Next, we focus on the innovative applications of advanced AI technologies in key areas such as COVID-19 prediction, detection, control, and drug discovery for treatment. Specifically, AI-based predictive analytics models can use clinical, epidemiological, and omics data to forecast disease spread and patient outcomes. Additionally, deep neural networks enable rapid diagnosis through medical imaging. Intelligent systems can support risk assessment, decision-making, and social sensing, thereby improving epidemic control and public health policies. Furthermore, high-throughput virtual screening enables AI to accelerate the identification of therapeutic drug candidates and opportunities for drug repurposing. Finally, we discuss future research directions for AI technology in combating COVID-19, emphasizing the importance of interdisciplinary collaboration. Though promising, barriers related to model generalization, data quality, infrastructure readiness, and ethical risks must be addressed to fully translate these innovations into real-world impacts. Multidisciplinary collaboration engaging diverse expertise and stakeholders is imperative for developing robust, responsible, and human-centered AI solutions against COVID-19 and future public health emergencies.

Betamethasone transdermal administration combined with fractional Er:YAG lasers or microplasma radiofrequency technology improved hypertrophic scars: A retrospective study.

OBJECTIVE: This retrospective study aims to compare the efficacy rates in treating hypertrophic scars among four distinct groups of patients who either underwent fractional Erbium: yttrium-aluminum-garnet (Er:YAG) laser or microplasma radiofrequency technology as standalone treatments or in combination with compound betamethasone transdermal administration. METHOD: The study retrospectively examined 208 patients treated at our institution from April 2011 to December 2022 for hypertrophic scars, receiving no less than three treatments (with an interval of 8 weeks between each). The patients were categorized into four groups: the F group (treated with fractional Er:YAG laser), the F + B group (treated with fractional Er:YAG laser combined with compound betamethasone transdermal administration), the P group (treated with microplasma radiofrequency technology), and the P + B group (treated with microplasma radiofrequency technology combined with compound betamethasone transdermal administration). The therapeutic effects were evaluated based on the changes in the Vancouver Scar Scale (VSS) scores before and after treatment in these groups. RESULTS: There was no statistically significant difference in the VSS scores among the four groups before treatment. After undergoing three sessions of the aforementioned four types of treatment, all groups showed a decrease in VSS scores, with average posttreatment VSS scores for the F group scored 5.15 ± 2.084, F + B group scored 3.7 ± 1.781, P group scored 4.41 ± 1.933, and P + B group scored 3.16 ± 1.775, respectively. With an increasing number of treatments, the total effective rate gradually increased in all four groups, and the combination treatment using compound betamethasone transdermal administration proved more effective than the standalone treatment. CONCLUSION: All four treatments yielded favorable outcomes, with the combined therapy involving compound betamethasone transdermal administration proving more effective than the standalone treatments, meriting further clinical attention.

14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.