Biomed Environ Sci. 2025 Jun 20;38(6):773-778. doi: 10.3967/bes2025.067.

NO ABSTRACT

PMID:40616494 | DOI:10.3967/bes2025.067

BMC Plant Biol. 2025 Jul 4;25(1):879. doi: 10.1186/s12870-025-06907-x.

NO ABSTRACT

PMID:40615974 | DOI:10.1186/s12870-025-06907-x

Sci Rep. 2025 Jul 4;15(1):23921. doi: 10.1038/s41598-025-09075-y.

ABSTRACT

Traditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better survival in bladder cancer for luminal and basal squamous subtypes, as well as in melanoma for RAS-hotspot subtypes. Our detailed deconvolution and mutational correlation analyses uncover 35 therapeutic target and candidate response biomarkers hypotheses (including CASP8 and RAS pathway genes).

PMID:40615649 | DOI:10.1038/s41598-025-09075-y

EMBO Rep. 2025 Jul 4. doi: 10.1038/s44319-025-00517-2. Online ahead of print.

ABSTRACT

Co-infections generally cause exacerbated pathologies in patients, yet a knowledge gap between clinical data and the underlying molecular mechanisms remains. Clinical studies focus on patient outcome, but much less is known about molecular mechanisms and convergence points that define the interaction between different pathogens. In this review, we will summarize the current standing of the literature at the various scales of magnitude that co-infections impact: epidemiology, clinical observations, tissue- and organ-specificity, the single-cell level, and molecular mechanisms. Given the scarcity of systematic research across systems, we will focus on molecular interaction points that have been identified, comment on their generalizability and, where required, extrapolate from single-pathogen studies. More research of the host-pathogen-pathogen interface is direly warranted, and we hope to inspire advances addressing the intricate network between two co-occurring pathogens and their host. In addition to direct implications for co-infections, acquiring a better understanding of how microorganisms interact in this complex environment will enable us to better understand single-pathogen infections as well, which can lead to the development of novel treatment approaches.

PMID:40615578 | DOI:10.1038/s44319-025-00517-2

Nat Commun. 2025 Jul 4;16(1):6187. doi: 10.1038/s41467-025-61303-1.

ABSTRACT

The formation of complex tissues during embryonic development requires an intricate spatiotemporal coordination of local mechanical processes regulating global tissue morphogenesis. Here, we uncover a novel mechanism that mechanically regulates the shape of the anterior neural plate (ANP), a vital forebrain precursor, during zebrafish gastrulation. Combining in vivo and in silico approaches we reveal that the ANP is shaped by global tissue flows regulated by distinct force-generating processes. We show that mesendoderm migration and E-cadherin-dependent differential tissue interactions control distinct flow regimes in the neuroectoderm. Initial opposing flows lead to neuroectoderm cell internalisation and progressive multilayer tissue folding which in turn provide forces driving ANP tissue reshaping. We find that convergent extension is dispensable for internalisation but required for ANP tissue extension. Our results highlight how spatiotemporal regulation and coupling of different mechanical processes between tissues in the embryo control the first internalisation and folding events of the developing brain.

PMID:40615398 | DOI:10.1038/s41467-025-61303-1

Nat Commun. 2025 Jul 4;16(1):6119. doi: 10.1038/s41467-025-60873-4.

ABSTRACT

mRNA modifications are vital in regulating cellular processes. Beyond N6-methyladenosine (m6A), most other internal mRNA modifications lack dedicated catalytic machinery and are typically introduced by tRNA-modifying enzymes. The distribution and stoichiometry of these modifications on mRNAs remain debated and require further validation. Furthermore, their precise function remains controversial due to the challenges of excluding the intricate combinational effects of tRNA modifications. Here, we biochemically validate that NSUN6, a tRNA structure-dependent methyltransferase, independently catalyzes 5-methylcytidine (m5C) formation with robust activity on mRNA by recognizing the CUCCA motif in a certain stem-loop structure. NSUN6 employs different strategies to recognize tRNA and mRNA substrates. By introducing mutations, we further separate its catalytic capabilities toward mRNA and tRNA revealing that NSUN6 promotes breast cancer cell migration depending on mRNA m5C modification. Mechanistically, a cohort of mRNAs involved in cell migration carries high levels of NSUN6-mediated site-specific m5C modification, thus being stabilized by the preferential binding of m5C readers YBX1 and YBX3. Moreover, introducing a single-site high-level m5C can significantly increase the stability of therapeutic mRNAs in cells. Our findings underscore the pivotal role of m5C-modified mRNAs in promoting breast cancer cell migration and their potential for therapeutic applications.

PMID:40615396 | DOI:10.1038/s41467-025-60873-4

Nat Commun. 2025 Jul 4;16(1):6170. doi: 10.1038/s41467-025-61125-1.

ABSTRACT

Hematopoietic stem cells (HSC) with multilineage potential are critical for T cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). The Kitlo HSC subset is enriched for multipotential precursors, but their T cell potential remains poorly characterized. Using a preclinical allo-HCT mouse model, we demonstrate that Kitlo HSCs provide superior thymic recovery and T cell reconstitution, resulting in improved immune responses to post-transplant infection. Kitlo HSCs with augmented bone marrow (BM) lymphopoiesis mitigate age-associated thymic alterations and enhance T cell recovery in middle-aged mice. Mechanistically, chromatin profiling reveals Kitlo HSCs exhibiting higher activity of lymphoid-specifying transcription factors, such as, ZBTB1. Zbtb1 deletion diminishes HSC engraftment and T cell potential; by contrast, reinstating Zbtb1 in megakaryocytic-biased Kithi HSCs rescues hematopoietic engraftment and T cell potential in vitro and in vivo. Furthermore, age-associated decline in Kitlo HSCs is associated with diminished T lymphopoietic potential in aged BM precursors; meanwhile, Kitlo HSCs in aged mice maintain enhanced lymphoid potential, but their per-cell capacity is diminished. Lastly, we observe an analogous human BM KITlo HSC subset with enhanced lymphoid potential. Our results thus uncover an age-related epigenetic regulation of lymphoid-competent Kitlo HSCs for T cell reconstitution.

PMID:40615375 | DOI:10.1038/s41467-025-61125-1

Mol Cell Endocrinol. 2025 Jul 2:112609. doi: 10.1016/j.mce.2025.112609. Online ahead of print.

ABSTRACT

Indiscriminate exposure to chemical substances has emerged as a critical global health concern. Human exposure to emerging contaminants, including pharmaceutical residues, pesticides, food additives, and chemicals employed in packaging and bottle production, is associated with an increased incidence of diseases, including thyroid disorders. Several chemicals potentially dysregulate thyroid embryonic development and the adult hypothalamic‒pituitary‒thyroid (HPT) axis. In this study, we applied systems biology approaches to identify biological processes associated with the most highly upregulated and downregulated genes in human thyroid transcriptome data from both the embryonic and adult stages. As a result, new gene/protein‒chemical interactions linked to recognized toxicities in the thyroid gland and the HPT axis were identified. This analysis identified 195 distinct chemical substances that may interact with these highly expressed proteins and exhibit thyroid toxicity. Our findings underscore the developmental period as a critical window of vulnerability to chemical exposure, with potential adverse effects on thyroid development and programming. Finally, our data suggest new targets for emerging chemicals in the thyroids of adult individuals, potentially compromising thyroid function.

PMID:40615107 | DOI:10.1016/j.mce.2025.112609

Biosystems. 2025 Jul 2:105527. doi: 10.1016/j.biosystems.2025.105527. Online ahead of print.

ABSTRACT

The synthesis of adenosine triphosphate (ATP), the universal biological currency, by oxidative phosphorylation and photophosphorylation catalyzed by the FOF1-ATP synthase is the fundamental means of cellular energy generation in animals, plants, and microorganisms. Since the ocean area and the amount of biomass is very large, the formation of ATP and its utilization by the myriad energy-consuming processes in the cell is the principal net chemical reaction taking place on the surface of the earth. This is indeed a most important reaction. How exactly does it occur? Since the development of the famous colorimetric assay for measurement of inorganic phosphate (Pi) in 1925, followed by the discovery of ATP in 1929, an enormous amount of research has been done to understand these intracellular energy-linked processes. I present an account of the major developments on ATP synthesis and hydrolysis in a century of research, and summarize the current state of knowledge. My account focuses on the fields of bioenergetics, muscle contraction, and motility in cell life, and covers key aspects of metabolic disease, mitochondrial apoptosis, and cell death in relation to ATP and the ATP synthase, and the permeability transition pore. It includes developments at molecular, cellular, and macroscopic levels-ascending into ecology-thanks to the conservative nature of metabolic pathways, with ATP as the universal intermediate in the coupled reactions of biological energy transduction. New, emerging sub-fields on ATP and the Warburg Effect, purinergic signaling, condensates and the role of ATP as a biological hydrotope are discussed briefly, and possible applications in aging and precision medicine are foreseen. I have divided the subject matter into the following five eras to cover the vast ground. (i)-the beginning era of the 1920s (Section 2), (ii)-an era of trials and trails of the 1930s ‒ 1940s (Sections 3.1 ‒ 3.5), (iii)-an era of population-based biochemistry and enzymology in the 1950s ‒ 1980s (Sections 4.1 ‒ 4.9), (iv)-a high-tech era of the 1990s ‒ 2020s of high-resolution structural and single-molecule studies, but also an interdisciplinary era of systems biology that integrates approaches from physics, chemistry, biology, mathematics, and engineering (Sections 5.1 ‒ 5.15), (v)-future prospects (Section 6). The article works out new explanations-with quantitative equations or physical criteria developed for the first time-that may help resolve longstanding issues in muscle contraction, bioenergetics, and transport. My tryst with ATP during 35-years of research is also described, and the search for a theory with greater numerical accuracy is emphasized. Errors of previous theories are identified and corrected, and apparent contradictions are resolved. The aim is to explain and correctly interpret the cumulative experimental record, check for consistency of theory with experiment, remove the inconsistencies in previous theories, and arrive at a unified molecular theory of energy coupling, transduction, ATP synthesis, and ATP hydrolysis. To conclude, a number of recommendations for the progress of scientific research in interdisciplinary and multidisciplinary areas have been made.

PMID:40615069 | DOI:10.1016/j.biosystems.2025.105527

Appetite. 2025 Jul 2:108215. doi: 10.1016/j.appet.2025.108215. Online ahead of print.

ABSTRACT

Diet-induced obesity resulting from excessive calorie consumption has been associated with taste disorders in both mice and humans. While this relationship is well-established, there is still limited knowledge on how calorie-restricted diets affect the sense of taste in normal-weight individuals. We hypothesized that differences in body composition of mice subjected to caloric restriction (CR) or intermittent fasting (IF) compared to ad libitum chow are associated with changes in bitter and sweet taste signaling. Male C57BL/6NRj mice were fed either ad libitum (control), 75% of the weight of the ad libitum chow (CR), or were submitted to IF (cycles of 24 h fasting and 24 h refeeding) for two weeks. Gene expression analysis of taste bud cell types of the circumvallate papillae (CV) was performed using qPCR and microarray analysis, and the chemosensory surface of the fungiform papillae (FP) was analyzed at the tongue tip. Taste preferences for sweet (sucralose) and bitter (caffeine) were analyzed with a two-bottle preference test. The FP number was higher in fasting groups compared to controls by up to 35% ± 9.8% (p < 0.001) in the CR group, accompanied by increased Tas1r2 and Tas1r3 expression. Taste responses showed higher sensitivity and preference towards sweet taste in the CR group and reduced aversion towards bitter taste compared to control animals. In conclusion, this study demonstrates an association between body composition, FP, and changes in sweet taste sensitivity and preference in mice subjected to restrictive diets.

PMID:40614780 | DOI:10.1016/j.appet.2025.108215

Semin Liver Dis. 2025 Jul 4. doi: 10.1055/a-2649-1560. Online ahead of print.

ABSTRACT

A new paradigm for drug development and patient therapeutic strategies is required, especially for complex, heterogeneous diseases including metabolic dysfunction-associated steatotic liver disease (MASLD). Heterogeneity in MASLD patients is driven by genetics, various co-morbidities, gut microbiota composition, lifestyle, environment and demographics that produce multiple patient disease presentations and outcomes. Existing drug development methods have had limited success for complex, heterogeneous diseases like MASLD where only a fraction of patients respond to specific treatments, prediction of a therapeutic response is not presently possible and the cost of the new classes of drugs are high. However, it is now possible to generate patient digital twins (PDTs) that are computational models of patients using clinomics and other "omics" data collected from patients to make various predictions including responses to therapeutics. PDTs are then integrated with patient biomimetic twins (PBTs) that are patient-derived organoids or induced pluripotent stem cells that are then differentiated into the optimal number of organ-specific cells to produce organ experimental models. The PBTs mimic key aspects of the patient's pathophysiology, enabling predictions to be tested. In conclusion: integration of patient digital twins and patient biomimetic twins has the potential to create a powerful precision medicine platform, yet there are challenges.

PMID:40614771 | DOI:10.1055/a-2649-1560

Childs Nerv Syst. 2025 Jul 4;41(1):225. doi: 10.1007/s00381-025-06884-4.

ABSTRACT

BACKGROUND: Neural tube defects (NTDs) are severe congenital malformations with complex and multifactorial etiologies involving genetic, environmental, and metabolic factors. Despite folic acid fortification efforts, a considerable proportion of cases remains unexplained at the molecular level.

OBJECTIVE: This study aimed to identify rare pathogenic variants in patients with NTDs using whole exome sequencing (WES) and to evaluate their functional significance through systems biology approaches.

METHODS: WES was performed on nine unrelated patients with clinically diagnosed NTDs. Variants were filtered using ACMG-AMP criteria and curated via the Franklin by Genoox platform. Genes carrying pathogenic or likely pathogenic variants were analyzed using STRING for protein-protein interactions and Metascape for functional enrichment.

RESULTS: Seven genes (PAH, ADGRG6, MPDZ, NARS1, ITGB2, PIGV, and STIL) harbored rare, clinically significant variants. Mutation types included missense, stop-gain, and frameshift, with both heterozygous and homozygous inheritance patterns. STRING analysis revealed a subnetwork involving MPDZ and ITGB2, related to tight junction integrity. Metascape analysis identified enrichment in biological processes such as catecholamine metabolism, floor plate development, and immune regulation.

CONCLUSION: This study supports a polygenic and mechanistically diverse model of NTD pathogenesis, wherein rare variants affect developmental pathways including metabolism, cell adhesion, and neurogenesis. Integrating high-throughput sequencing with systems biology enhances variant interpretation and may inform future diagnostics and prevention strategies.

PMID:40613906 | DOI:10.1007/s00381-025-06884-4

Biochem Soc Trans. 2025 Jul 4:BST20253039. doi: 10.1042/BST20253039. Online ahead of print.

ABSTRACT

Decades of research into the molecular signalling determinants of B cell fates, and recent progress in characterising the genetic drivers of lymphoma, has led to a detailed understanding of B cell malignancies but also revealed daunting heterogeneity. While current therapies for diffuse large B-cell lymphoma are effective for some patients, they are largely agnostic to the biology of each individual's disease, and approximately one third of patients experience relapsed/refractory disease. Consequently, the challenge is to understand how each patient's mutational burden and tumour microenvironment combine to determine their response to treatment; overcoming this challenge will improve outcomes in lymphoma. This mini review highlights how data-driven modelling, statistical approaches and machine learning are being used to unravel the heterogeneity of lymphoma. We review how mechanistic computational models provide a framework to embed patient data within knowledge of signalling. Focusing on recurrently dysregulated signalling networks in lymphoma (including NF-κB, apoptosis and the cell cycle), we discuss the application of state-of-the-art mechanistic models to lymphoma. We review recent advances in which computational models have demonstrated the power to predict prognosis, identify promising combination therapies and develop digital twins that can recapitulate clinical trial results. With the future of treatment for lymphoma poised to transition from one-size-fits-all towards personalised therapies, computational models are well-placed to identify the right treatments to the right patients, improving outcomes for all lymphoma patients.

PMID:40613779 | DOI:10.1042/BST20253039

Nucleic Acids Res. 2025 Jun 20;53(12):gkaf611. doi: 10.1093/nar/gkaf611.

ABSTRACT

Precise control of gene activity within a host cell is crucial in bioengineering applications. Despite significant advancements in cis-regulatory sequence activity prediction and reverse engineering, the context-dependent effects of host cellular environment have long been neglected, leading to ongoing challenges in accurately modeling regulatory processes. Here, we introduce an insulated design strategy to purify and model host-independent transcriptional activity. By integrating heterologous paired cis- and trans-regulatory modules into an orthogonal host cell, we established a controllable transcriptional regulatory system. Using a deep learning-based algorithm combined with an experimental data purification process, we achieved the de novo design full-length transcriptional promoter sequences driven by a host-independent activity landscape. Notably, this landscape accurately captured the transcriptional activity of the insulated system, enabling the generation of cis-regulatory sequences with desirable sequence and functional diversity for two distinct trans-RNA polymerases. Importantly, their activities are precisely predictable in both bacterial (Escherichia coli) and mammalian (Chinese hamster ovary) cell lines. We anticipated that de novo design strategy can be expanded to other complex cis-regulatory elements by integrating the deep learning-based algorithm with the construction of paired cis- and trans-regulatory modules in orthogonal host systems.

PMID:40613715 | DOI:10.1093/nar/gkaf611

Nucleic Acids Res. 2025 Jun 20;53(12):gkaf570. doi: 10.1093/nar/gkaf570.

ABSTRACT

Ligation is a common treatment for the resulting DNA nanostructures to gain extra stability. In this study, we aim to utilize ligation as an active process in self-assembly instead of post-assembly stabilization. Our investigation focuses on constructs with transiently paired segments. Transient base pairing fails to hold up the assembled complex, but ligation treatment turns the transient base pairing into permanent ones and thus induces the desired self-assembly. We apply the method to a number of assembly tasks, leading to the successful construction of discrete and extended DNA nanostructures. Furthermore, we apply the ligation-based method in the hierarchical assembly of preformed DNA nanostructure units into higher-order superstructures.

PMID:40613704 | DOI:10.1093/nar/gkaf570

Front Immunol. 2025 Jun 19;16:1615914. doi: 10.3389/fimmu.2025.1615914. eCollection 2025.

ABSTRACT

Gouty arthritis (GA) is a sterile inflammatory disease driven by monosodium urate (MSU) crystal deposition, which activates innate and adaptive immune responses. Key mechanisms involve NLRP3 inflammasome activation, cytokine release (IL-1β, TNF-α, IL-6), and dysregulated autophagy, positioning GA at the intersection of metabolic and autoimmune disorders. While conventional therapies (colchicine, NSAIDs) remain first-line, their limitations in refractory cases have spurred the development of biologic agents targeting pro-inflammatory pathways. Clinical studies demonstrate that TNF-α inhibitors (etanercept, infliximab), IL-6 blockade (tocilizumab), and autophagy modulators effectively reduce flares and inflammation in treatment-resistant GA. Emerging strategies, including combination therapies and biomarker-guided approaches, highlight the shift toward precision medicine in GA management. This review summarizes current insights into GA's immunopathogenesis and evaluates the therapeutic potential of immunomodulatory biologics.

PMID:40612947 | PMC:PMC12221926 | DOI:10.3389/fimmu.2025.1615914

Front Immunol. 2025 Jun 19;16:1591860. doi: 10.3389/fimmu.2025.1591860. eCollection 2025.

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health emergency since its emergence in late 2019. Endothelial dysfunction is a hallmark of COVID-19, leading to severe illness, i.e. coagulopathy, multi-organ failure. FX06, a fibrin-derived peptide naturally occurring in the human body, formerly known as Bβ15-42, is a promising therapeutic candidate for endothelial complications like capillary leakage in COVID-19 and other forms of acute respiratory disorders. The aim of this project is to investigate whether FX06 can attenuate COVID-19 cytokine-triggered inflammatory processes in vitro.

METHODS: To mimic the inflammatory status of COVID-19, a human pulmonary microvascular endothelial cell line (ECs) - HULEC-5a, was treated with a cytokine cocktail comprised of ten different cytokines or chemokines at concentrations found in serum profiles of COVID-19 patients with severe illness, further referred to as the severe cytokine cocktail. ECs were treated with the severe cytokine cocktail for 24 h, in the absence or presence of FX06 for 2 h.

RESULTS: The severe cytokine cocktail enhanced peripheral blood mononuclear cell (PBMC)-endothelial adhesion and monolayer transmigration. This deleterious effect was significantly reduced by FX06. FX06 was also shown to mitigate the cytotoxic activity of allogeneic CD8+ T cells, which increased upon cytokine treatment. FX06 restored continuous vascular endothelial (VE)-cadherin/CD144 distribution on the EC surface and reversed morphological changes mediated by the severe cytokine cocktail, such as the elongation of F-actin stress fibers. FX06 reduced capillary-like structure formation of the severe cytokine cocktail treated-ECs, indicating FX06 down-regulated the pro-inflammatory angiogenic activity caused by the severe cytokine cocktail. Additionally, FX06 might assist in maintaining the normal barrier function of ECs by altering the surface expression of Syndecan-1 (SDC1/CD138). Proteomics and phosphoproteomics analyses demonstrated that FX06 in the presence of the severe cytokine cocktail inactivated RhoGTPase, which was confirmed by western blotting that FX06 attenuated RhoA, a member of RhoGTPase, enhanced by the severe cytokine cocktail and down-regulated the expression of the phosphorylated downstream protein, ROCK1.

CONCLUSION: Overall, FX06 shows promising potential in normalizing ECs and reducing vascular leakage to protect the endothelium against the proinflammatory effect of COVID-19-triggered cytokines.

PMID:40612940 | PMC:PMC12225545 | DOI:10.3389/fimmu.2025.1591860

Front Plant Sci. 2025 Jun 19;16:1601956. doi: 10.3389/fpls.2025.1601956. eCollection 2025.

ABSTRACT

Lygodium japonicum is a valuable medicinal plant with increasing demand in China, yet large-scale cultivation remains limited, relying heavily on wild populations. As climate change accelerates, its potential distribution is expected to shift, affecting suitable growth areas. Despite its medicinal importance, research on its adaptability and future habitat changes is limited. This study used an optimized MaxEnt ecological niche model and Geographic Information System (GIS) to predict the potential suitable habitats of L. japonicum under current and future climate conditions (2041-2060 and 2061-2080) across three greenhouse gas emission scenarios (SSP126, SSP245, SSP585). Results show that under current climatic conditions, the potential habitat of L. japonicum spans approximately 216.31 × 104 km², with high suitability areas concentrated in southern and eastern China. In future climate scenarios, While the total suitable habitat area remains stable, the area of high suitability is significantly reduced. Specifically, under the SSP126 scenario, high suitability areas are projected to decrease by 44.1% during 2041-2060. The centroid of high suitability areas is expected to shift northward, though a localized southward shift is observed under the SSP126 scenario. Key environmental factors influencing the species' distribution include temperature seasonality (bio4), May precipitation (prec5), and mean diurnal temperature range (bio2). These findings highlight the potential impacts of climate change on L. japonicum's distribution and are crucial for the conservation and sustainable utilization of the species in China, particularly under changing climatic conditions.

PMID:40612605 | PMC:PMC12223322 | DOI:10.3389/fpls.2025.1601956

BMC Plant Biol. 2025 Jul 3;25(1):868. doi: 10.1186/s12870-025-06861-8.

ABSTRACT

BACKGROUND: Lychee (Litchi chinensis Sonn.), longan (Dimocarpus longan Lour.), and rambutan (Nephelium lappaceum L.) are popular tropical fruits in the family Sapindaceae, known for their succulent arils-specialized seed appendage with significant biological and commercial value. Despite their agricultural relevance, the molecular mechanisms underlying aril development in these species remain poorly understood.

RESULTS: We conducted RNA-sequencing to profile transcriptomes during aril development, complemented by in-situ hybridization to validate the spatial expression of LcLBD1. OrthoFinder identified species-specific and shared differentially expressed genes (DEGs), while functional enrichment analyses (GO, KEGG) and transcriptional network modeling elucidated regulatory pathways. After detailed analyses of transcriptomes, species-specific and shared DEGs were identified across lychee, longan, and rambutan using OrthoFinder. Members of the bHLH and MYB gene families were implicated in early aril development. Species-specific DEGs were primarily enriched in metabolic pathways. From shared DEGs, we identified ten transcription factors (AGL8, AP3, SHP1, WOX13, LBD1, LBD3, OBP1, SPL2, SPL3, and SPL9) and three genes (IAA8, CSLD5, and CYCD3;2) as key regulators. Interestingly, in-situ hybridization localized LcLBD1 expression to funicle and small aril cells, suggesting roles in cell differentiation and division.

CONCLUSION: We have identified ten transcription factors and three genes affecting aril development in lychee, longan, and rambutan, and validated the expression of LcLBD1 in funicle and aril cells. These results offer a new perspective on the molecular mechanism of aril development and lay the groundwork for future research into the functions and regulatory mechanisms of candidate genes.

PMID:40610859 | DOI:10.1186/s12870-025-06861-8

Nat Chem Biol. 2025 Jul 3. doi: 10.1038/s41589-025-01951-y. Online ahead of print.

ABSTRACT

The stimulator of interferon genes (STING) innate immune pathway can exacerbate inflammatory diseases when aberrantly activated, emphasizing an unmet need for STING antagonists. However, no inhibitors have advanced to the clinic because it remains unclear which mechanistic step(s) of human STING activation are crucial for inhibition of downstream signaling. Here we report that C91 palmitoylation is not universally necessary for human STING signaling. Instead, evolutionarily-conserved C64 is basally palmitoylated and is crucial for preventing unproductive STING oligomerization. The effects of palmitoylation at C64 and C91 converge on the control of intradimer disulfide bond formation at C148. Together, dynamic equilibria of these cysteine post-translational modifications allow proper STING ligand-binding domain self-assembly and scaffolding function. Given this complex landscape, we took inspiration from STING's natural autoinhibitory mechanism and identified an eight-amino-acid peptide that binds a defined pocket at the oligomerization interface, setting the stage for future therapeutic development.

PMID:40610719 | DOI:10.1038/s41589-025-01951-y