Differentiation and immunosuppressive function of CD19+CD24hiCD27+ regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway.

BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

Expandable-RCNN: toward high-efficiency incremental few-shot object detection.

This study aims at addressing the challenging incremental few-shot object detection (iFSOD) problem toward online adaptive detection. iFSOD targets to learn novel categories in a sequential manner, and eventually, the detection is performed on all learned categories. Moreover, only a few training samples are available for all sequential novel classes in these situations. In this study, we propose an efficient yet suitably simple framework, Expandable-RCNN, as a solution for the iFSOD problem, which allows online sequentially adding new classes with zero retraining of the base network. We achieve this by adapting the Faster R-CNN to the few-shot learning scenario with two elegant components to effectively address the overfitting and category bias. First, an IOU-aware weight imprinting strategy is proposed to directly determine the classifier weights for incremental novel classes and the background class, which is with zero training to avoid the notorious overfitting issue in few-shot learning. Second, since the above zero-retraining imprinting approach may lead to undesired category bias in the classifier, we develop a bias correction module for iFSOD, named the group soft-max layer (GSL), that efficiently calibrates the biased prediction of the imprinted classifier to organically improve classification performance for the few-shot classes, preventing catastrophic forgetting. Extensive experiments on MS-COCO show that our method can significantly outperform the state-of-the-art method ONCE by 5.9 points in commonly encountered few-shot classes.

Comprehensive bioinformatics analysis unveils THEMIS2 as a carcinogenic indicator related to immune infiltration and prognosis of thyroid cancer.

The aim of this study was to identify biomarkers associated with the initiation and prognosis of thyroid cancer and elucidate the underlying pathogenic mechanisms. We obtained expression profiles and clinical information from the Cancer Genome Atlas (TCGA)-THCA and three datasets (GSE53157, GSE82208, and GSE76039). The three microarray datasets were combined using Perl and the sva package in R and termed 'merged dataset'. Weighted gene co-expression network analysis (WGCNA) identified 15 gene co-expression modules in the merged dataset and 235 hub genes. Venn diagram analysis revealed 232 overlapping genes between the merged and THCA datasets. Overlapping genes were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The least absolute shrinkage and selection operator (LASSO) regression identified THEMIS2 as a candidate hub gene. Cox, Kaplan-Meier (K-M) survival and gene set enrichment analysis (GSEA) confirmed the correlation of THEMIS2 with overall survival, its enrichment in immunologic processes, and its association with the p53 and JAK-STAT signaling pathways. Its expression was positively correlated with those of immune checkpoints and the infiltration level of immune cells. Receiver operating characteristic curve (ROC) analysis confirmed that THEMIS2, a diagnostic biomarker, could distinguish between tumor and normal specimens. The nomogram (ROC or DCA) model containing THEMIS2, age, and stage predicted favourable prognoses. Thus, THEMIS2 was a biomarker of immune infiltration and prognosis in thyroid cancer.

Inhibition of NF-κB and ERK signaling pathways in osteoclasts and M1 macrophage polarization: Mechanistic insights into the anti-osteoporotic effects of Pseudolaric acid B.

Osteoporosis, characterized by bone metabolism disruption leading to gradual bone loss and increased fracture susceptibility, is linked to the excessive activation of osteoclasts. Pseudolaric acid B (PAB), identified as an NF-κB signaling inhibitor crucial for osteoclastogenesis, is explored here for its protective effects in osteoporosis. Noncytotoxic PAB's impact on osteoclast differentiation was assessed through cell viability and osteoclast formation assays, with subsequent testing of osteoclast function via bone resorption assays. Quantitative real-time polymerase chain reaction evaluated PAB's genetic-level impact on osteoclastogenesis. Network pharmacology, western blot, and luciferase reporter gene assays were employed to elucidate PAB's regulatory mechanism. In an in vivo model of osteoporosis induced by ovariectomy (OVX) in mice, micro-CT, H&E staining, and TRAP staining facilitated histomorphometry analysis, while flow cytometry verified macrophage polarization. PAB demonstrated inhibitory effects on osteoclast formation and bone resorption in BMM and RAW264.7 cells, suppressing osteoclast-specific genes. Bioinformatic analysis, western blot, and luciferase assay results indicated PAB's inhibition of IκBα phosphorylation in the NF-κB signaling pathway and ERK in MAPKs, elucidating its mechanism. In vivo experiments confirmed PAB's attenuation of osteoporosis by reducing osteoclast formation in OVX mice. PAB further facilitated macrophage conversion from M1 to M2 and suppressed IL-1ß, TNF-α, and IL-6 synthesis. In conclusion, PAB prevents osteoporosis by inhibiting RANKL-induced osteoclastogenesis through NF-κB and ERK signaling pathway suppression, coupled with macrophage polarization. These findings indicate the potential therapeutic role of PAB in osteoporosis.

Root-derived long-distance signals trigger ABA synthesis and enhance drought resistance in Arabidopsis.

Vascular plants have evolved intricate long-distance signaling mechanisms to cope with environmental stress, with reactive oxygen species (ROS) emerging as pivotal systemic signals in plant stress responses. However, the exact role of ROS as root-to-shoot signals in the drought response has not been determined. In this study, we reveal that compared with wild-type plants, ferric reductase defective 3 (frd3) mutants exhibit enhanced drought resistance concomitant with elevated NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) transcript levels and abscisic acid (ABA) contents in leaves as well as increased hydrogen peroxide (H2O2) levels in roots and leaves. Grafting experiments distinctly illustrate that drought resistance can be conferred by the frd3 rootstock regardless of the scion genotype, indicating that long-distance signals originating from frd3 roots promote an increase in ABA levels in leaves. Intriguingly, the drought resistance conferred by the frd3 mutant rootstock is weakened by the CAT2-overexpressing scion, suggesting that H2O2 may be involved in long-distance signaling. Moreover, the results of comparative transcriptome and proteome analyses support the drought resistance phenotype of the frd3 mutant. Taken together, our findings substantiate the notion that frd3 root-derived long-distance signals trigger ABA synthesis in leaves and enhance drought resistance, providing new evidence for root-to-shoot long-distance signaling in the drought response of plants.

GDF10 and IDO1 as a thyroid cancer prognostic biomarker associated with immune infiltration.

Objection: The aim of this work is to screen the immune-related genes to predict the prognosis and provide a new direction of treatment for patients with thyroid cancer (THCA). Methods: The mRNA and clinical features of THCA patients were collected from the Cancer Genome Atlas (TCGA) databases. The immune-related genes were obtained from the ImmPort databases. The bio-information methods were performed to screen the differential expression genes (DEGs) and genes related to immunity between the THCA patients and normal individuals. On this basis, the hub prognosis immunity genes were screened by Veen. The related genes were obtained by constructing the protein-protein interaction network. The enrichment analyses were performed based on the protein and protein interaction (PPI) related genes. The hub immune checkpoint was screened by correlation analysis. Finally, the hub gene and the immunity checkpoint-miRNA (or transcription factor, drug) interaction network were constructed. A drug-sensitive analysis also was performed. Results: The GDF10 was screened. The PPI genes were enriched in the TGF-beta signaling pathway, signaling pathways regulating, the pluripotency of stem cells, Cytokine-cytokine receptor interaction, and so on. The hub immunity checkpoint IDO1 was obtained. The joint indicator of two hub genes was positively related to the thyroid differentiation score. Three interaction factors were found to be related to the two hub genes, and 7 kinds of drugs screened act on the two hub genes at the same time. Conclusion: This work indicated that immune-related gene GDF10 and immune checkpoint IDO1 are important for the prognosis prediction of THCA patients, and immunity is involved in the proliferation, and differentiation of tumor cells.

Sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than moderate.

We collected thyroid-related hormone index levels, sleep duration, and other basic characteristics of the population with depression from the NHANES 2009-2012 cycles and evaluated the association of Thyroid-Stimulating Hormone Index (TSHI) with sleep duration in the euthyroid population with depression via different analysis methods. We found that the association between TSHI and sleep duration was only found in patients with depression degree < Moderate (score: 1-14) rather than > Moderate group. Among the populations with degree < Moderate (N = 1918), only 4 indexes (parametric Thyroid Feedback Quantile Index, PTFQI, Thyrotroph Thyroxine Resistance Index, TT4RI, Thyroid-Stimulating Hormone TSH, and TSHI) reflecting the sensitivity to thyroid hormones were related to the sleep duration, with a significant non-linear relationship after adjusting for potential confounders (all P < 0.05). Trend analysis indicated that with the level increase of these 4 indexes, the sleep duration increased (all P for trend < 0.001). Further, we found that TSHI was relatively more important among the 4 indexes. Sum up, sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than Moderate. Poor sensitivity referred to a longer sleep duration.

Therapeutic potential of CB1R activation by Qingyangshen glycoside M1 for seizure relief.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum otophyllum C.K.Schneid.PI.Wilson, commonly referred as ''Qingyangshen'' (QYS), is a traditional folk medicine from Yunnan, renowned for its efficacy in neurological and psychiatric disorders. Glycosides isolated from QYS have shown promise in alleviating epilepsy, however, mechanisms of action and specific molecular targets remain to be elucidated. AIM OF THE STUDY: The study aimed to evaluate the anticonvulsant effects of Qingyangshen glycosides M1 (M1), a C21 steroidal glycoside from QYS, on pentylenetetrazol (PTZ)-induced convulsions in zebrafish (Danio rerio), and its neuroprotective effect on Glutamate (Glu)-induced damage to PC12 cells, and importantly to identify its potential molecular targets. MATERIALS AND METHODS: To evaluate anticonvulsant activity of M1, 7 days-post-fertilization (7-dpf) animals were pretreated (by immersion) and then exposed to PTZ (10 mM) solution. Furthermore, Glu-induced PC12 cell damage was employed to investigate the neuroprotective and anti-apoptotic capacity. Cells were pretreated with various concentrations of M1 (0-10 µM) for 12 h and then co-treated with Glu (15 mM) for an additional 24 h. The cell viability, apoptosis rate and apoptosis-related proteins (p-PI3K, PI3K, Akt, p-Akt, CREB, p-CREB, BDNF, Bax and Bcl-2) were measured using CCK-8, annexin V/PI and Western blot assays. To model the expected interaction between M1 and candidate cannabinoid receptor type 1 (CB1R), ERK phosphorylation, molecular docking, and drug affinity responsive target stability (DARTS) techniques were employed. Finally, CB1R antagonist Rimonabant (Rim) was validated by co-administration in both zebrafish and cells to confirm the requirement of CB1R for M1 efficacy. RESULTS: At a concentration of 400 µM, M1 dramatically reversed PTZ-induced convulsive-like behaviors in zebrafish, as evidenced by a significant reduction in locomotor activity. In the context of Glu-induced cytotoxicity, M1 (10 µM) demonstrated a notable increase in cell viability and suppressed apoptosis through modulation of the Bax/Bcl-2 ratio and activation of the PI3K/Akt/CREB/BDNF signaling axis. These effects were facilitated through CB1R activation. In contrast, Rim dampened the beneficial activities of M1 as a cannabinoid agonist. CONCLUSIONS: These results demonstrated that M1 as a potential CB1R activator, exhibiting anticonvulsive effects in a PTZ-induced zebrafish model and neuroprotective properties via the PI3K/Akt/CREB/BDNF signaling axis in a Glu-induced PC12 cell injury model. Notably, the observed seizure relief attenuated by CB1R chemical antagonism.

Life-stage specificity and temporal variations in transcriptomes and DNA methylomes of the reef coral Pocillopora damicornis in response to thermal acclimation.

Understanding the acclimation capacity of reef corals across generations to thermal stress and its underlying molecular underpinnings could provide insights into their resilience and adaptive responses to future climate change. Here, we acclimated adult brooding coral Pocillopora damicornis to high temperature (32 °C vs. 29 °C) for three weeks and analyzed the changes in phenotypes, transcriptomes and DNA methylomes of adult corals and their brooded larvae. Results showed that although adult corals did not show noticeable bleaching after thermal exposure, they released fewer but larger larvae. Interestingly, larval cohorts from two consecutive lunar days exhibited contrasting physiological resistance to thermal stress, as evidenced by the divergent responses of area-normalized symbiont densities and photochemical efficiency to thermal stress. RNA-seq and whole-genome bisulfite sequencing revealed that adult and larval corals mounted distinct transcriptional and DNA methylation changes in response to thermal stress. Remarkably, larval transcriptomes and DNA methylomes also varied greatly among lunar days and thermal treatments, aligning well with their physiological metrics. Overall, our study shows that changes in transcriptomes and DNA methylomes in response to thermal acclimation can be highly life stage-specific. More importantly, thermally-acclimated adult corals could produce larval offspring with temporally contrasting photochemical performance and thermal resilience, and such variations in larval phenotypes are associated with differential transcriptomes and DNA methylomes, and are likely to increase the likelihood of reproductive success and plasticity of larval propagules under thermal stress.

Expression and prognosis analysis of integrin subunit α3 (ITGA3) in papillary thyroid cancer.

Integrin subunit α3 (ITGA3) is a member of the integrin family and interacts with extracellular matrix proteins. However, there have been few reports regarding the role of ITGA3 in papillary thyroid cancer. The expression levels of ITGA3 were firstly analyzed by bioinformatics tools and in vitro experiments, followed by evaluating its prognostic significance in papillary thyroid cancer patients using Kaplan-Meier, receiver operating characteristic, and Cox regression analyses. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted and the upstream miRNAs of ITGA3 were determined. The results showed that the ITGA3 mRNA and protein levels were higher in the papillary thyroid cancer group than those in the normal group (all P < 0.05). Moreover, ITGA3 performed well in distinguishing the recurrence-free survival (RFS) status and served as an independent prognostic factor of papillary thyroid cancer patients (P < 0.01). Besides, significant relations between ITGA3 and genetic alterations were observed (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction and cell adhesion molecules were the shared regulatory pathways. Moreover, ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b. Of note, the ITGA3 mRNA level was reduced after has-miR-199b-3p/5p was overexpressed. In conclusion, ITGA3 could be a reliable biomarker and have potential value in predicting the RFS status of papillary thyroid cancer patients.

TET1 is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Papillary Thyroid Cancer.

To investigate the function of ten-eleven translocation 1 (TET1) and its underlying mechanism in papillary thyroid cancer (PTC). Using the RNA-Seq data based on GDC TCGA, we analyzed the gene expression pattern of TET1 in PTC. Immunohistochemistry was carried out to assess the TET1 protein level. Then, its diagnostic and prognostic functions were determined by various bioinformatics approaches. Enrichment analysis was performed to explore the potential pathways in which TET1 is mainly involved. Finally, the immune cell infiltration analysis was conducted and the association of TET1 mRNA expression with the expression levels of immune checkpoints, tumor mutation burden (TMB) score, microsatellite instability (MSI) score, and cancer stem cells (CSC) score was examined. TET1 expression was lower in PTC tissues compared with that in normal tissues (P < 0.01). Besides, TET1 had a certain value in diagnosing PTC, and low-TET1 mRNA expression led to favorable disease-specific survival (DSS) (P < 0.01). The enrichment analysis revealed autoimmune thyroid disease and cytokine-cytokine receptor interaction were the consistent pathways in which TET1 participated. TET1 was negatively correlated with the Stromal score and Immune score. The different proportions of immune cell subtypes were observed between high- and low-TET1 expression groups. Interestingly, TET1 mRNA expression was inversely related to the expression levels of immune checkpoints, and TMB, MSI, and CSC scores. TET1 might be a robust diagnostic and prognostic biomarker for PTC. TET1 affected the DSS of PTC patients possibly through the regulation of immune-related pathways and tumor immunity.

Knockout of OsSPL10 confers enhanced glufosinate resistance in rice.

This study shows that OsSPL10 is a novel genetic locus of glufosinate resistance in rice. OsSPL10 negatively regulates the expression of OsGS genes and thereby decreases GS activity. Knockout of OsSLP10 thus enhances glufosinate resistance, making it a candidate gene for improvement of crop glufosinate and stress resistance.

Apolipoprotein A-1 Accelerated Liver Regeneration Through Regulating Autophagy Via AMPK-ULK1 Pathway.

BACKGROUND & AIMS: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. METHODS: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. RESULTS: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. CONCLUSIONS: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

Construction of novel 7 integrin-related gene signatures in thyroid cancer construction of model based on integrin genes.

Advanced and metastatic THCA patients usually have a poor prognosis. Thus, this study aimed to establish a risk model to discriminate the high risk population. The expression and clinical data were obtained from TCGA database. The cluster analysis, lasso, univariate and multivariate cox analyses were used to construct risk model. K-M, ROC and DCA were applied to validate the efficiency and stability of the model. GO, KEGG, and ssGSEA analysis were performed to identify the potential mechanism of signatures. The 7-gene prognosis model was constructed, including FAM27E3, FIGN, GSTM4, BEX5, RBPMS2, PHF13, and DCSTAMP. ROC and DCA results showed our model had a better prognosis prediction performance than other risk models. The high risk score was associated with the poor prognosis of THCA patients with different clinical characteristics. The risk score was closely related to cell cycle. Further, we found that the expressions of signatures were significantly dysregulated in THCA and associated with prognosis. These gene expressions were affected by some clinical characteristics, methylation and CNV. Some signatures played a role in drug sensitivity and pathway activation. We constructed a 7-gene signature model based on the integrin-related genes, which showed a great prognostic value in THCA.

The impact of drug shortages on drug prices: evidence from China.

Introduction: Drug shortages pose a serious global public health challenge, affecting China and other countries. Evidence from USA shows that short-supplied drugs demonstrated a very high price growth during and after a shortage. However, the effect of shortages on drug prices in China remains unknown. This paper aims to understand the impact of drug shortages on prices and explore implications for shortage prevention policy. Methods: We collected the purchase prices and delivery rates of 120 drugs from April 2019 to December 2021 across whole China. We examined price progression of affected drugs using linear mixed-effects models and performed subgroup analyses based on the number of manufacturers and the severity of shortage. Results: Non-shortage cohort had an annual price growth of 11.62% (95% confidence interval [CI] 8.34 to 14.98). Shortage cohort demonstrated an annual price growth of 8.08% (95%CI 0.12 to 16.77) in the period preceding a shortage, 27.57% (95%CI 6.17 to 52.87) during a shortage, and 9.38% (95%CI -12.64 to 36.39) in the post-shortage period. Drug shortages' impact on prices varied across subgroups. Compared with that of drug markets supplied by a single manufacturer, the price growth rate of markets supplied by more than one manufacture declined more after the shortage resolution. Conclusion: Shortages resulted in significant price increases of study markets, especially the low-priced markets, while the shortage resolution slowed the growth. The primary shortage driver has shifted from the low price to others drivers, such as unavailability of active pharmaceutical ingredients. For currently sole-supplied drugs, the expedited review of applications from other manufacturers should be considered.

New animal model of chronic gout reproduces pathological features of the disease in humans.

OBJECTIVES: Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans. METHODS: A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed. RESULTS: After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice. CONCLUSIONS: Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.

A DNA barcode library for woody plants in tropical and subtropical China.

The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests.

The OsNLP3/4-OsRFL module regulates nitrogen-promoted panicle architecture in rice.

Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.