Abiotic stresses, such as drought, salinity, temperature fluctuations, waterlogging, and heavy metal contamination, have a detrimental impact on plants, leading to reduced global agricultural productivity. The accumulation of cadmium (Cd) and arsenic (As) in agricultural soil, resulting from both natural and anthropogenic activities, poses significant threats to crop production and food safety. Dehydrins, also known as Group II Late Embryogenesis Abundant (LEA) proteins, are intrinsically disordered proteins that play crucial roles in protecting cellular structures during abiotic stress conditions. These proteins are considered promising candidates for enhancing plant tolerance to environmental stresses through their membrane-stabilizing and protective functions.

Breast cancer remains the most common malignancy among women worldwide. Current systemic treatment strategies include chemotherapy, immunotherapy, bone-stabilizing agents, endocrine therapy for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA mutation cases. However, effectively overcoming drug resistance and reducing recurrence and metastasis rates remain major therapeutic challenges.

Vitamin B12 (B12) is a strong antioxidant and a cofactor for methionine synthase supporting DNA/RNA/protein methylation. We previously demonstrated that oral high-dose B12 supplement mitigates diabetic cardiomyopathy in Akita diabetic mice expressing twice the normal levels of Elmo1 (Engulfment and cell motility 1). To assess how B12 prevents early kidney damage, we treated Elmo1HH mice and diabetic Elmo1HH Ins2Akita/+ mice with or without B12 in drinking water starting at 8 weeks of age. At 16 weeks, markedly reduced mesangial expansion was detected in the B12-treated diabetic kidneys (22% of glomeruli affected vs. 70% in the untreated diabetic kidneys). RNAseq analysis of the kidneys revealed that B12 suppressed expression of genes for adaptive immune response, while it upregulated those for solute carrier transporters and antioxidant genes. Strikingly, B12 treatment suppressed activators of circadian rhythm, Clock and Bmal1, and upregulated repressors like Cry1/2, Per1-3 and Dbp, suggesting a shift in their rhythmicity. B12 also upregulated linker histone H1 variants, and enhanced chromatin stability and cell cycle regulation. In BU.MPT proximal tubular cells in culture, B12 shifted forward the circadian expression phase of Bmal1 and Per1. Taken together, B12 supplement effectively mitigates early development of diabetic nephropathy in diabetic mice, potentially involving regulation of circadian rhythm.

Tuber mustard (Brassica juncea var. tumida) is an economically important vegetable crop, with its tumorous stem serving as the primary raw material for Fuling mustard production. However, multiple abiotic stress during growth often leads to significant yield losses. As a vital hormone for plant stress adaptation, abscisic acid (ABA) plays essential roles in stress responses. However, despite the agricultural importance of tuber mustard, no studies have yet reported on ABA related functions in this crop. In this study, we identified the F-box protein gene BjuFIP as a key regulator in ABA signaling. BjuFIP was ubiquitously expressed across all tissues and significantly upregulated by ABA treatment. Histochemical analysis of ProBjuFIP::GUS transgenic Arabidopsis seedlings further confirmed ABA-induced BjuFIP expression. Functional characterization revealed that Arabidopsis overexpressing BjuFIP exhibited an ABA-insensitive phenotype, suggesting that BjuFIP negatively regulates ABA signaling in tuber mustard. Furthermore, protein-protein interaction assays, including yeast two-hybrid and bimolecular fluorescence complementation, demonstrated that BjuFIP physically interacts with BjuASK1, a core component of the SCF ubiquitin ligase complex, and BjuPYL3, an ABA receptor. These findings suggest that BjuFIP might modulate the ABA signaling pathway through regulation of BjuPYL3. These findings not only advance our understanding of ABA signaling in tuber mustard but also offer valuable genetic targets for breeding stress-tolerant varieties with stable yields.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used to treat type 2 diabetes, exhibit cardioprotective effects by improving myocardial energy metabolism, reducing oxidative stress, and modulating inflammation and fibrosis, which are critical in the context of acute myocardial infarction (AMI). Our research aims to explore the molecular mechanisms of SGLT2 inhibitors, with a focus on their influence on non-coding RNAs through sirtuins pathways, to identify novel biomarkers and therapeutic strategies for preventing heart failure following AMI.

Single-cell proteomics by mass spectrometry (SCP) is an emerging technology in which hundreds or thousands of proteins can be directly quantified in typical human cells. As the proteins detected and quantified by SCP are heavily biased toward proteins of highest abundance, chromatin proteins are an attractive target for analysis. To this end, I applied SCP to the analysis of cancer cells treated with mocetinostat, a class specific histone deacetylase inhibitor. I find that 16 PTMs can be confidently identified and localized with high site specificity in single cells. Drug treatment reveals apparent heterogeneity in the abundance and distribution of the accumulated acetylation sites in histone tails. While other techniques exist to measure histone modifications in single human cells, the approach presented here allows simultaneous quantification of hundreds of proteins, allowing phenotypic insight as well as epigenetic inferences in each individual cell. All raw and processed data described in this study has been made publicly available through the ProteomeXchange/MASSIVE repository system as MSV000093434.

Fusarium graminearum is the predominant pathogenic fungus causing Fusarium head blight, posing significant threats to food security and agricultural development. In this study, gene knockout technology was employed to construct FgNR (nitrate reductase gene) knockout and complemented mutants of F. graminearum to investigate the biological functions of FgNR. The results demonstrated that deletion of FgNR significantly reduced the growth rate and conidial germination rate of F. graminearum. The knockout mutants were unable to grow on basic medium containing only nitrate, while the wild type and complementation grew normally. The growth rate of ΔFgNR was enhanced under NaCl and KCl stress. Furthermore, ΔFgNR exhibited compromised cell membrane and cell wall integrity, as well as reduced tolerance to external oxidants. Additionally, the pathogenicity of ΔFgNR was significantly attenuated, accompanied by decreased deoxynivalenol (DON) production. The expression levels of Tri5 and Tri6 genes were downregulated, whereas the expression level of Tri10 was upregulated in the mutant strain. Compared to the wild-type strain, the knockout mutant exhibited decreased sensitivity to prothioconazole, accompanied by a marked increase in FgCYP51A gene expression. These findings indicate that FgNR plays critical roles in asexual reproduction, pathogenicity, nitrogen source utilization, and responses to abiotic stress and fungicide sensitivity in F. graminearum.

Harmful cyanobacterial blooms (HCBs), driven by eutrophication, pose critical threats to aquatic ecosystems and public health. Current studies focused on inhibitory effect of single-component allelochemical on HCBs, yet cyanobacteria in natural environments are simultaneously exposed to multiple allelochemicals. Thus, it is more meaningful to study composite allelochemicals formulation for HCBs control. Our previous study found that the composite allelochemicals agent of 4-tert-butylcatechol and l-lysine (CAA-TL) can synergistically inhibit the growth of Microcystis aeruginosa. In this study, we investigated the inhibitory mechanism of CAA-TL against M. aeruginosa, integrating physiological, transcriptomic, and metabolomic approaches. CAA-TL reduced the cell density of M. aeruginosa by more than 90 % within four days, and significantly decreased the Chl-a content and chlorophyll fluorescence parameters. The integrated transcriptomic and metabolomic results showed that: (1) 471 upregulated and 312 downregulated differential expressed genes (DEGs) and 433 upregulated and 215 downregulated differential metabolites (DMs) were identified; (2) CAA-TL markedly impacted the expression of photosynthesis related genes (e.g., PsbA, PsbL, PsaB and PsaK) indicating the inhibition of photosynthetic activity; (3) CAA-TL impacted DNA and protein synthesis through downregulation of nucleotide metabolism; (4) CAA-TL disrupted energy supply via the dysregulation of energy metabolism pathways. These findings reveal the inhibitory mechanism of CAA-TL via an integrated omics approach and provide theoretical support for their eco-friendly application in HCBs control.

Fusarium graminearum is responsible for Fusarium head blight in wheat, resulting in considerable economic losses in grain production. Controlling F. graminearum requires elucidating the biological functions of key genes associated with growth and mycotoxin biosynthesis. In this study, the alternative oxidase inhibitor propyl gallate (PG) was found to markedly reduce the tolerance of F. graminearum PH-1 to azoxystrobin (AZ), indicating that alternative oxidase (AOX) is essential for AZ resistance in F. graminearum. The biological functions of FgAOX were further investigated by comparing biochemical and transcriptomic changes between the FgAOX deletion mutant and wild-type F. graminearum PH-1. Compared to the PH-1, the FgAOX deletion mutant showed reduced conidial production, thickened septa, and increased deoxynivalenol accumulation, and enhanced the sensitivity to AZ. Transcriptomic analysis revealed that FgAOX is involved in regulating energy metabolism, oxidative stress response, and secondary metabolite biosynthesis. Deletion of FgAOX triggered a reprogramming of energy metabolism, affecting the TCA cycle, glycolysis/gluconeogenesis, and lipid metabolism, ultimately leading to enhanced ATP synthesis. Consequently, reactive oxygen species levels increased, and the expression of genes related to antioxidant enzymes and redox processes was significantly altered, disrupting cellular redox homeostasis. These findings highlight the important role of FgAOX in the AZ resistance as well as vegetative growth, toxin production, oxidative stress response, and energy metabolism of F. graminearum, providing insights for potential disease management strategies.

Fusarium graminearum, the major causal agent of Fusarium head blight (FHB) in cereals, threatens global wheat production and food safety through yield losses and contamination with the mycotoxin deoxynivalenol (DON). Here, we evaluated aminopyrifen, a novel 2-aminonicotinate fungicide, for its efficacy and mechanism of action against F. graminearum. Sensitivity assays of 103 field isolates revealed potent inhibition of mycelial growth (mean EC₅₀ = 0.0547 μg/mL) with no resistant strains detected. Aminopyrifen disrupted hyphal and conidial morphology, suppressed toxisome formation, and markedly reduced DON biosynthesis by downregulating TRI gene expression. Functional analyses showed that the acyltransferase FgGWT1 is essential for fungal growth, conidiation, virulence, and toxisome formation, and its inhibition by aminopyrifen phenocopied gene deletion. These findings establish aminopyrifen as a promising candidate fungicide with a novel target, offering potential for effective FHB management and reduced DON contamination in wheat.

Pathological mitochondrial hyperfission and ectopic lipid deposition in renal tubules are critical contributors to the progression of diabetic kidney disease (DKD), with SUMO1-mediated modification of DRP1 functioning as a key driving mechanism. The traditional Chinese medicine formula Suoquan Yishen Formula (SQYSF) has demonstrated clinical efficacy in ameliorating DKD; however, it remains unclear whether it improves the mitochondrial-lipid metabolism network by modulating this post-translational modification.

Drug resistance is a major obstacle in the clinical management of small cell lung cancer (SCLC), we have proved the promising anticancer effect of recombinant human arginase (rhArg, BCT-100) in SCLC in vitro and in vivo. In order to promote the clinical application of recombinant human arginase, it is necessary to explore the underlying resistant mechanisms of BCT-100 in SCLC. Here, we cultured and obtained the acquired drug-resistant SCLC cell line (H446-BR), which displayed different cellular phenotypes (enhanced migration ability) compared with the parental cell line (H446). sestrin3 (SESN3) was confirmed with high expression in resistant cell line. Knockdown SESN3 could re-sensitize resistant cells to BCT-100 treatment and reverse the aggressive feature of H446-BR. The Akt-mTOR signal pathway and ASS1, which were highly expressed in resistant cells, were down-regulated after silencing SESN3. MK-2206 and rapamycin suppressed the expression of ASS1 in H446-BR cell. In xenograft model, BCT-100 has little anti-tumor effect on H446-BR compared with H446 as well as H446-BR silenced sestrin3. Collectively, these results elucidate SESN3 plays an essential role in resistant mechanism, which will provide a valuable source of information for translational research.

This study aimed to investigate the role of DNMT1 in CRC progression and its regulatory relationship with TRAF6 and EZH2.

Hepatocellular carcinoma (HCC), a predominant cause of cancer-related mortality, is commonly linked to constitutive activation of oncogenic pathways such as STAT3. Continuous STAT3 activation drives tumor progression by enhancing proliferation, survival, and metastatic capability, thus presenting a rational therapeutic target. JI017, an herbal product-based formulation containing Angelica gigas, Aconitum carmichaelii, and Zingiber officinale Roscoe, is rich in bioactive compounds with anti-inflammatory and antioxidant activities. While JI017 has shown anticancer effects in various malignancies, its mechanisms in HCC have not been well characterized.

In recent years, the role of novel protein acylation modifications in neuroinflammation has gradually become a hot research topic. In this paper, we reviewed the molecular mechanisms of five types of acylation modifications, namely lactylation (Kla), succinylation (Ksucc), crotonylation (Kcr), β-hydroxybutyrylation (Kbhb) and palmitoylation, and their association with neuroinflammation. To clarify the roles of these acylation modifications in neuroinflammation, we summarized the acyl donors, key regulatory enzymes (acyltransferases and deacylases), and dynamic regulatory networks for each modification type. On the one hand, they are directly involved in the inflammatory response by regulating microglial activation and pro-inflammatory factor release; on the other hand, they can indirectly affect the neurodegenerative disease process through metabolic reprogramming. This article also discusses drug development for novel acylases, including strategies based on enzyme activity inhibition or metabolic intervention, and points out the limitations of current studies. Future studies need to explore the spatial and temporal dynamics of acylation modifications, cross-regulatory networks and their functions in the neuroimmune microenvironment to provide new targets for the development of precise anti-neuroinflammatory therapies. The discovery of novel acylation modifications not only expands the theoretical framework of protein post-translational modification (PTM), but also opens up a multi-dimensional intervention pathway for the treatment of neuroinflammation-related diseases.

Breast cancer remains a major clinical challenge due to its high recurrence and metastatic potential. Here, we develop a multifunctional photothermal nanocomposite, GS@AM@M, integrating gold nanorods and mesoporous silica for synergistic photothermal-epigenetic immunotherapy. GS@AM@M exhibits excellent photothermal conversion efficiency under NIR-II (808 nm) irradiation, while its mesoporous framework enables efficient coloading of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and the histone deacetylase inhibitor mocetinostat (MGCD). To enhance tumor targeting and immune evasion, the nanocomposite is camouflaged with macrophage-derived cell membranes. Upon NIR-II irradiation, GS@AM@M accumulates within tumors and enables controlled drug release. The combined therapy induces immunogenic cell death (ICD), promotes dendritic cell maturation, and activates cytotoxic CD8+ T cells. Meanwhile, epigenetic reprogramming of the MYC/Type I IFN signaling axis enhances CCL5 secretion, thereby recruiting and amplifying CD8+ T-cell responses. This synergistic mechanism effectively eradicates both primary and metastatic tumors while establishing durable immune memory to prevent recurrence. By integrating photothermal therapy, immunotherapy, and epigenetic modulation, GS@AM@M provides a potent and precise platform for comprehensive breast cancer treatment.

Allergic disease is a common and symptomatically heterogeneous group of inflammatory disorders marked by overactive Th2 and mast cell (MC) responses along with eosinophil infiltration. Treatment options require continual assessment due to breakthrough symptoms on standard regimens. One approach to improved therapy is drug repurposing. Our lab previously showed that cholesterol-lowering statin drugs can suppress IgE-mediated mast cell function by inhibiting protein isoprenylation, a pathway using cholesterol biosynthesis intermediates. Additionally, mast cells are activated by the alarmin IL-33, released by epithelial cells after contact with cellular stressors. We hypothesized that IL-33-mediated mast cell function can be inhibited by disrupting isoprenylation via statins or the dual farnesyltransferase (FT) geranylgeranyltransferase-1 inhibitor, FGTI-2734.

Escherichia coli is considered a major extended-spectrum β-lactamases producer, of which CTX-M is the most common member. However, the different variants of this primary resistance-determinant make it challenging to detect by conventional PCR-based techniques. Therefore, in this study, we investigated the transcriptional response of 2 secondary resistance genes, repB and mtgA, under sub-inhibitory concentrations of oxy-imino cephalosporins in resistant isolates of E. coli harboring blaCTX-M. The STRING database and Cytoscape software were used to identify the secondary resistance genes by gene network analysis. The cephalosporin-resistant isolate of E. coli co-harboring repB and mtgA, along with blaCTX-M, was employed for the current study. The blaCTX-M-carrying plasmid was successfully eliminated from the native-type isolate using 6% and 8% SDS treatment for 7 days. The plasmid was also transformed into a recipient strain, E. coli DH5α, by the heat-shock method. All three models were grown under sub-inhibitory stress of cephalosporins, and the transcriptional response of repB and mtgA was determined by quantitative real-time PCR. The study revealed that the transcriptional responses of both repB and mtgA were antibiotic-specific, which potentially can serve as a secondary resistance reporter for cephalosporin resistance in E. coli.

Nitrogen (N) availability is a key determinant of plant growth and development. Here, we investigate how different N sources shape Arabidopsis thaliana root system architecture, metabolism and hormone dynamics. L-glutamine (L-GLN) significantly enhances root biomass compared to nitrate (KNO3) without compromising shoot growth. This effect emerges after 2 weeks and is independent of L-GLN's role as a carbon or ammonium source or of potential L-GLN-induced pH changes due to ammonium release, indicating a specific function of L-GLN as a N source and signaling molecule. A reverse genetic screen identified AMINO ACID PERMEASE 1 (AAP1)-mediated uptake and GLUTAMINE SYNTHETASE (GS)-dependent assimilation as essential for L-GLN-induced root biomass. In contrast, the N-sensing regulators NITRATE TRANSPORTER 1.1 (NRT1.1) and AMMONIUM TRANSPORTER (AMT) family members contribute to the differential root responses between KNO3 and L-GLN. Metabolic profiling revealed distinct amino acid signatures under these N sources, irrespective of genotype. Hormonal analyses showed that L-GLN modulates auxin homeostasis, with auxin supplementation restoring primary root growth and lateral root symmetry under L-GLN conditions. L-GLN also reconfigures cytokinin balance by elevating cZ while reducing tZ, collectively shaping root system architecture through hormone-dependent regulation. Together, these findings establish L-GLN as an integrator of N metabolism and hormone signaling in root development, highlighting its signaling capacity beyond nutrient supply and offering new perspectives for improving N use efficiency.

Carbon monoxide (CO), a gaseous secondary messenger, plays a crucial role in regulating growth and stress responses in plants. MicroRNAs (miRNAs), which are small noncoding RNAs comprising 21-24 nucleotides, modulate gene expression by directing messenger RNA cleavage or inhibiting translation. However, the impact of CO on miRNAs is rarely investigated in plants. In this study, we examined the regulatory interactions between CO and miRNAs in sweet potato (Ipomoea batatas 'Tainung 57'). A small RNA library prepared from CO-treated sweet potato leaves was constructed and analyzed using next-generation sequencing technology. A CO-induced novel 22-nucleotide-long miRNA, designated tag202, was identified. The expression of tag202 was increased in response to CO treatment. Overexpression and knockdown studies of tag202 in transgenic sweet potato revealed an inverse relationship between tag202 expression and its predicted target gene, which encodes a Malectin-like domain-containing receptor-like kinase (IbMLD-RLK) localized to the plasma membrane. The IbMLD-RLK mRNAs were predominantly cleaved at the canonical cleavage position within the tag202 binding region, which was mediated by tag202. The IbMLD-RLK protein was indicated to interact with IbMEK1, a component of the mitogen-activated protein kinase (MAPK) signaling cascade. In response to wounding, the expression of pri-tag202 and IbMLD-RLK was decreased and increased, respectively. Exogenous CO supplementation disrupted this response. In conclusion, CO-induced tag202 acts as a regulatory switch, targeting IbMLD-RLK to modulate the MAPK signaling pathway. This study offers new insights into the molecular mechanisms of CO-responsive miRNAs and their roles in regulating responses to wounding.