Search Results (473)

Rootstocks are widely used in viticulture as an agronomic measure to cope with biotic and abiotic stresses. In winegrapes, the aroma is one of the major factors defining the quality of grape berries and wines. In the present work, the grape aroma and wine aroma of Cabernet Sauvignon (CS) grafted on three rootstocks were investigated to inform the selection of rootstocks to utilize. 1103P, 5A, and SO₄ altered the composition of aromatic volatiles in CS grapes and wines. Among them, 5A and SO₄ had less effect on green leaf volatiles in the berries and wines, while 1103P increased green leaf volatile concentrations, up-regulating VvADH2 expression in both vintages. VvLOXA, VvLOXC, VvHPL1, VvADH1, VvADH2, and VvAAT were co-regulated by vintage and rootstock. Orthogonal partial least squares regression analysis (OPLS-DA) showed that the differential compounds in CS/1103P and CS berries were dominated by green leaf volatiles. Furthermore, the concentrations of 1-hexanol in the CS/1103P wines were significantly higher than in the other treatments in the two vintages. 1103P altered the expression of genes in the LOX-HPL pathway and increased the concentration of grape green leaf volatiles such as 1-hexanol and 1-hexanal, while vine vigor also affected green leaf volatile concentrations, the combination of which altered the aromatic composition of the wine and gave it more green flavors. Full article

Biomass-derived growth stimulants are widely recognized as green and economical solutions that can significantly enhance microalgae culture efficiency and optimize the biomanufacturing process of target products. In this paper, we investigated the effect of ethanol synergized with guaiacol (GA) on biomass and β-1,3 glucan accumulation in edible microalgae, namely Euglena gracilis. The ethanol-induced mixotrophic mode significantly increased biomass and paramylon production by 12.68 and 6.43 times, respectively, compared to the autotrophic control group. GA further exerted toxic excitatory effects (hormesis) on top of ethanol mixotrophic nutrition. At the optimal concentration of 10 mg·L⁻¹ GA, chlorophyll a, carotenoids, and paramylon production increased by 8.96%, 11.75%, and 16.67%, respectively, compared to the ethanol-treated group. However, at higher concentrations, the biomass and paramylon yield decreased significantly. This study not only establishes an effective combinatorial strategy for enhancing paramylon biosynthesis but also provides novel insights into the hormesis mechanism of phenolic compounds in microalgae cultivation. The developed approach demonstrates promising potential for sustainable production of high-value algal metabolites while reducing cultivation costs, which could significantly advance the commercialization of microalgae-based biorefineries in food and pharmaceutical industries. Full article

Background: Treatment of metastatic cancer remains a challenge, because cancer cells acquire resistance even to the most contemporary therapies. This study analyzed the role of the phosphoprotein Stathmin 1 (STMN1) in regulating cancer cell growth and metastatic potential. Methods: Public datasets with metastatic castration-resistant prostate cancer (mCRPC) and breast cancer (BC) were analyzed to determine the interrelationship between STMN1, hepatocyte growth factor (HGF) and MET proto-oncogene (MET) expression, overall survival, and response to chemotherapy. Site-directed mutagenesis, cell cycle analysis, proliferation, and migration and invasion assays determined the impact of STMN1 phosphorylation on proliferation and metastatic potential. Results: Increased STMN1 associates with HGF and MET gene expression in mCRPC, and taxane chemotherapy further increases HGF expression. STMN1 and HGF are highest, and overall survival is poorest in mCRPC in the liver compared to other sites, implying the metastatic site influences their expression levels and potentially the pattern of metastatic spread. Increased STMN1 and MET also predict taxane responsiveness in BC patients. Analysis of STMN1 serine (S)16, 25, 38, and 63 determined that total (t) STMN1 and STMN1 S16 phosphorylation (pSTMN1^S16) are co-regulated by HGF/MET during cell cycle progression, pSTMN1^S16 alone can promote cell proliferation, and pSTMN1^S16 shortens the cell cycle similar to HGF treatment, while STMN1^S16 dephosphorylation lengthens the cell cycle to arrest cell growth in G2/M, similar to HGF plus the MET inhibitor AMG337. Importantly, STMN1^S16 does not promote metastasis. Conclusions: Selectively inhibiting STMN1^S16 phosphorylation may provide an alternative strategy for inhibiting MET-mediated cell growth to eliminate metastatic cancer cells and inhibit further metastasis. Full article

This study examined the regulatory mechanism of calcium (Ca) amendment on the dynamics of soil organic carbon (SOC) fractions and extracellular enzyme activities, elucidating the role of Ca in soil carbon cycling processes. A field experiment with maize was conducted, comparing treatments of low calcium (T1), high calcium (T2), and a calcium-free control (CK). Measurements included inter-root SOC fractions—soluble organic carbon (DOC), microbial biomass carbon (MBC), and readily oxidizable organic carbon (ROC)—and the activities of the following extracellular enzymes: β-xylanase, β-glucosidase (β-glu), phenol oxidase (Phox), peroxidase (Pero), phosphatase (Phos), acetylaminoglucosidase (NAG), and urease. The main findings indicated the following: (1) Calcium addition significantly increased SOC content (115.04% and 99.22% higher in T1 and T2, respectively, than CK during the entire reproductive period) and enhanced microbial activity (elevated DOC and MBC). However, SOC decreased by 8.44% (T1) and 16.38% (T2) relative to CK in the late reproductive stage (irrigation–ripening), potentially reflecting microbial utilization (supported by the inverse correlation between SOC and MBC/DOC), and maize carbon reallocation during grain filling. (2) Calcium activated β-glu, Phox, Phos, NAG, and urease (p < 0.05), with pronounced increases in Phox (241.13 IU·L⁻¹) and Phos (1126.65 U·L⁻¹), indicating enhanced organic matter mineralization and phosphorus availability. (3) Calcium-driven MBC and ROC accumulation was associated with the positive regulation of Phox (path coefficient > 0.8) and the negative regulation of Phos. SOC was co-regulated by β-glu and Phos (R² = 0.753). (4) Calcium dynamically optimized the short-term carbon distribution through enzyme activity while promoting long-term sequestration. Our study provides new evidence supporting multi-pathway interactions through which calcium mediates enzyme networks to influence the soil carbon cycle. The findings provide a theoretical foundation for calcium fertilizer management and soil carbon sequestration strategies in agriculture, advancing academic and practical goals for sustainable development and carbon neutrality. Full article

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts. Full article

Intrinsically disordered regions (IDRs), defined as protein segments lacking stable tertiary structures, are ubiquitously present in the human proteome and enriched with disease-associated mutations. IDRs harbor molecular recognition features (MoRFs) and post-translational modification sites (e.g., phosphorylation), enabling dynamic intermolecular interactions through conformational plasticity. Furthermore, IDRs drive liquid–liquid phase separation (LLPS) of biomacromolecules via multivalent interactions such as electrostatic attraction and pi–pi interactions, generating biomolecular condensates that are essential throughout the cellular lifecycle. These condensates separate intracellular space, forming a physical barrier to avoid interference between other molecules, thereby improving reaction specificity and efficiency. As a dynamically equilibrated process, LLPS formation and maintenance are regulated by multiple factors, endowing the condensates with rapid responsiveness to environmental cues and functional versatility in modulating diverse signaling cascades. Consequently, disruption of LLPS homeostasis can derail its associated biological processes, ultimately contributing to disease pathogenesis. Moreover, precisely because liquid–liquid phase separation (LLPS) is co-regulated by multiple factors, it may provide novel insights into the pathogenic mechanisms of disorders such as autism spectrum disorder (ASD), which result from the cumulative effects of multiple etiological factors. Full article

The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells. Full article

Background: Membranous nephropathy (MN), a prevalent glomerular disorder, remains poorly understood in terms of its association with mitochondrial dynamics (MD). This study investigated the mechanistic involvement of mitochondrial dynamics-related genes (MDGs) in the pathogenesis of MN. Methods: Comprehensive bioinformatics analyses—encompassing Mendelian randomization, machine-learning algorithms, and single-cell RNA sequencing (scRNA-seq)—were employed to interrogate transcriptomic datasets (GSE200828, GSE73953, and GSE241302). Core MDGs were further validated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Results: Four key MDGs—RTTN, MYO9A, USP40, and NFKBIZ—emerged as critical determinants, predominantly enriched in olfactory transduction pathways. A nomogram model exhibited exceptional diagnostic performance (area under the curve [AUC] = 1). Seventeen immune cell subsets, including regulatory T cells and activated dendritic cells, demonstrated significant differential infiltration in MN. Regulatory network analyses revealed ATF2 co-regulation mediated by RTTN and MYO9A, along with RTTN-driven modulation of ELOA-AS1 via hsa-mir-431-5p. scRNA-seq analysis identified mesenchymal–epithelial transitioning cells as key contributors, with pseudotime trajectory mapping indicating distinct temporal expression profiles: NFKBIZ (initial upregulation followed by decline), USP40 (gradual fluctuation), and RTTN (persistently low expression). RT-qPCR results corroborated a significant downregulation of all four genes in MN samples compared to controls (p < 0.05). Conclusions: These findings elucidate the molecular underpinnings of MDG-mediated mechanisms in MN, revealing novel diagnostic biomarkers and therapeutic targets. The data underscore the interplay between mitochondrial dynamics and immune dysregulation in MN progression, providing a foundation for precision medicine strategies. Full article

Emotional attunement, or emotional co-regulation in a relationship, can manifest as interpersonal neural synchrony, where partners exhibit similar anti-phase or phase-shifted brain activity. In adult romantic relationships, emotional attunement may differ according to relationship satisfaction. No study has examined how relationship satisfaction difference influences interpersonal neural synchrony. This exploratory pilot study on 17 couples (unmarried Chinese undergraduate couples in a Southeast Asian university) investigated whether relationship satisfaction difference influenced interpersonal neural synchrony during a shared emotive experience. Each couple wore an fNIRS cap to measure brain activity in their prefrontal cortex (PFC) while co-viewing seven videos intended to evoke positive, negative or neutral emotions. We found preliminary evidence that relationship satisfaction difference modulated interpersonal neural synchrony in the right ventral PFC regions, including the right ventromedial PFC (involved in the encoding of emotional values to stimuli and emotional regulation), right ventrolateral PFC (involved in voluntary emotional regulation) and the right orbitofrontal cortex (involved in processing of emotional experiences and regulation of emotions). This suggested that couples with mismatched relationship satisfaction displayed greater interpersonal neural synchrony, possibly due to mutual social cognitive processes when viewing emotive videos together. Further studies can replicate the findings with larger, diverse samples. Full article

Multi-agent reinforcement learning (MARL) has demonstrated significant application potential in addressing cooperative control, policy optimization, and task allocation problems in complex systems. This paper focuses on its applications and development in water environmental systems, providing a systematic review of the theoretical foundations of multi-agent systems and reinforcement learning and summarizing three representative categories of mainstream MARL algorithms. Typical control scenarios in water systems are also examined. From the perspective of cooperative control, this paper investigates the modeling mechanisms and policy coordination strategies of MARL in key tasks such as water supply scheduling, hydro-energy co-regulation, and autonomous monitoring. It further analyzes the challenges and solutions for improving global cooperative efficiency under practical constraints such as limited resources, system heterogeneity, and unstable communication. Additionally, recent progress in cross-domain generalization, integrated communication–perception frameworks, and system-level robustness enhancement is summarized. This work aims to provide a theoretical foundation and key insights for advancing research and practical applications of MARL-based intelligent control in water infrastructure systems. Full article

The chloroplast signal recognition particle (cpSRP) components cpSRP43 and cpSRP54 not only form a complex with light-harvesting chlorophyll (Chl)-binding proteins to direct them to the thylakoid membrane, but also serve other functions. cpSRP43 independently acts as a chaperone for some tetrapyrrole biosynthesis (TBS) enzymes, while cpSRP54 participates in the co-translational targeting of plastid-encoded proteins. However, it remains unclear to what extent the two cpSRP components are coregulated—despite their distinct functions—and whether both participate in genomes-uncoupled (GUN)-mediated retrograde signaling. Here, we demonstrate that cpSRP43 and cpSRP54 accumulation is strongly interdependently controlled: overexpression of one protein increases the level of the other, while a deficiency in one of the two proteins leads to a simultaneous decrease in the other component. Disruption of this balance, e.g., by combining the overexpression of one component with a knockout of the other, results in severe chlorosis, stunted growth, and reduced levels of Chl and tetrapyrrole intermediates. Moreover, cpSRP43 deficiency exacerbates the pale-green phenotype of gun4 and gun5 mutants, highlighting a synergistic impact on TBS; however, cpSRP43 overexpression fails to rescue these defects. Remarkably, loss of cpSRP43 does not affect the expression of nuclear-encoded photosynthetic genes under intrinsic plastid stress, clearly demonstrating that cpSRP43 is not involved in plastid-to-nucleus retrograde signaling. Overall, our findings underscore that the fine-tuned expression of cpSRP43 and cpSRP54 is crucial for proper chloroplast function and pigment biosynthesis, while cpSRP43 alone does not participate in the retrograde signaling pathway. Full article

Cancer treatment remains a formidable challenge globally. Natural products, particularly natural alkaloids, have emerged as significant resources for the development of novel anti-tumor drugs due to their structural diversity and unique biological activities. Our team previously isolated an alkaloid, 6-hydroxymethyldihydrochelerythrine (6-HMDN), from Zanthoxylum ailanthoides. Subsequent in vitro and in vivo activity screenings, utilizing cell-based assays and a zebrafish xenograft model, revealed that 6-HMDN significantly inhibited the proliferation of HepG2 and MCF7 cells and effectively suppressed HepG2 cell migration. Mechanistic studies indicated that 6-HMDN induced tumor cell apoptosis by modulating the Bcl-2/Bax protein balance and activating the caspase cascade. Furthermore, 6-HMDN augmented intracellular reactive oxygen species (ROS) levels, thereby promoting ferroptosis, as evidenced by lipid ROS accumulation and glutathione (GSH) depletion. Additionally, 6-HMDN attenuated focal adhesion kinase (FAK) phosphorylation, leading to the inhibition of tumor cell migration. In vivo experiments further substantiated the capacity of 6-HMDN to effectively suppress tumor proliferation and metastasis. These findings demonstrate that 6-HMDN exhibits potent anti-tumor activity, exerting its effects through multiple mechanisms involving the regulation of apoptosis, ferroptosis, and the FAK signaling pathway. Therefore, 6-HMDN may be considered a promising candidate for anti-tumor drug development. Full article

Testicular orphan receptors TR2 and TR4 serve as central regulators of erythropoiesis, orchestrating the entire continuum of erythroid progenitor cell proliferation, differentiation, and maturation. As core components of the direct repeat erythroid determinant (DRED) complex, they activate erythroid-specific transcriptional programs to dynamically control the spatiotemporal expression of globin genes. These nuclear receptors not only engage in functional interactions with key erythroid transcription factors GATA1 and KLF1 to coregulate erythroid differentiation and maturation but also recruit epigenetic modifier complexes such as DNMT1 and LSD1 to modulate chromatin states dynamically. Research has established that dysfunctions in TR2/TR4 are implicated in β-thalassemia and sickle cell disease (SCD): β-thalassemia is associated with the defective silencing of γ-globin genes, while in SCD, TR2/TR4 antagonizes BCL11A to reactivate fetal hemoglobin (HbF) expression. This review systematically dissects the molecular regulatory networks of TR2/TR4 in erythroid cells, interprets their dual regulatory properties across different stages of erythroid differentiation, and explores the therapeutic potential of targeting TR2/TR4 for treating erythroid-related disorders such as β-thalassemia and SCD, thereby providing novel directions for hematological disorder therapy. Full article

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment. Full article

Rice tillering is an important trait that is genetically and environmentally co-regulated. Nitorgen is one of the key nutrients affecting tillering, and straw return further affects tiller development by altering soil heterogeneity. In order to analyze the genetic regulation mechanism of rice tillering and its interactions with the environment, 124 recombinant inbred line (RIL) populations derived from two superior Peijiu lines, 9311 and PA64s, were used as materials in this study, and the dynamic tillering phenotypes were measured under three treatments (no nitrogen application, nitrogen application, and nitrogen + straw return) for two consecutive years. Using an existing genetic map, we conducted single-environment, multi-environment, and meta-QTL analyses to systematically identify tiller-related genetic loci and their environmental interactions. The main findings were as follows: (1) A total of 57 QTLs were identified in the single-environment QTL analysis, of which 44 were unreported new QTLs. Four QTLs showed temporal pleiotropy, ten QTLs contributed more than 10% to the phenotypes under the no-N treatment, and five QTLs contributed more than 10% under the straw return treatment. Among them, the phenotypic contribution of mks1-355 (qD1tn1-3) and mks1-352 (qD2TN1-2) both exceeded 40%. (2) Multi-environmental QTL analysis detected 15 QTLs. Of these, qmD1TN1 (mks1-356) showed no environmental interaction effect, while qmD1TN12 (mks12-267), qmD2TN1 (mks1-334), qmD2TN3-1 (mks3-105), and qmD5TN6 (mks6-71) exhibited antagonistic pleiotropy, suggesting that these QTL need to be considered for environmental specificity in breeding. (3) Meta-QTL analysis localized 52 MQTLs, of which MQTL3.1 and MQTL6.8 contained 82 and 59 candidate genes, respectively, and no reported tiller-related genes were found. (4) mks1-355 (qD1tn1-3), mks1-352 (qD2TN1-2), and mks1-356 (qmD1TN1) may be located in the same genetic locus, and their phenotypic contributions were more than 40%. These QTLs were detected stably for two consecutive years, and they may be the main effector QTLs in tillering that are less affected by the environment. Further analysis revealed that these QTLs corresponded to MQTL1.6, which contains 56 candidate genes. Of these, the expression level of OsSPL2 gene in the parental line 9311 was significantly higher than that of PA64s, and there were polymorphic differences in the coding region. It was hypothesized that OsSPL2 was the main effector gene of this QTL. This study provides important genetic resources for mining candidate genes related to tillering and nitrogen efficiency in rice and lays a theoretical foundation for directional breeding and molecular marker development in specific environments. Full article