Immunosenescence, a process with a dysfunctional immune response that may favor infection is associated with an increase in inflammatory responses mediated by proinflammatory cytokines, characteristic of inflammaging. Aging and immunosenescence have a relationship relating to oxidative stress and inflammaging. Therefore, natural antioxidant compounds could be candidates for the control of the oxidative process. Our purpose was to evaluate the effect of resveratrol (Resv) on the antioxidant, antiviral, and anti-inflammatory responses induced by toll-like receptors (TLRs) 3, 4, and 7/8 agonists stimulation on peripheral blood mononuclear cells (PBMCs) of elderly and healthy female individuals (63-82 years old) and young and healthy female individuals (21-31 years old). Our data show that Resv may upregulate antioxidant factor expression, such as catalase (CAT) and SIRT1, in response to TLR4 and TLR7/8 agonists, similarly in both young and aged groups. Moreover, the Resv anti-inflammatory effect was detected by inhibiting IL-1β, TNF-α, and IL-10 secretion levels, as well as by the chemokines CCL2 and CCL5, induced by TLR4 and TLR7/8 stimulation. Curiously, Resv decreased antiviral genes, such as MxA, STING, and IRF7 expression, possibly by reducing the inflammatory effects of interferon-induced genes. Taken together, our results demonstrate the ability of Resv to stimulate antioxidant factors, leading to a downmodulation of the inflammatory response induced by innate immune stimulation. These findings point out Resv as a strategy to control the upregulation of inflammatory response, even in elderly individuals.

Sainfoin (Onobrychis viciifolia) is a type of leguminous plant with high feeding value. It contains a high concentration of tannins at all growth stages, which can precipitate soluble proteins and form a large number of persistent foams in the rumen, so that ruminant livestock will not develop dilatation disease during green feeding and grazing. The germination rate of O. viciifolia seeds is very low under natural conditions. The preliminary experiment showed that 600 mg/L GA3 treatment significantly improved the germination rate and seed vitality of sainfoin seeds. In comparison to CK, GA3 significantly decreased the relative content of endogenous inhibitors, with the most notable reduction observed in 4-nitroso-N-phenyl-benzenamine. Therefore, we selected the dry seed stage (GZ), imbibition stage (XZ), split stage (LK), and radicle emergence stage (MF) of four different germination stages treated with GA3 for transcriptome analysis. RNA-seq identified 1392, 2534 and 4284 differentially expressed genes (DEGs) in GZ vs. XZ, XZ vs. LK, and LK vs. MF, respectively. During seed germination, DEGs are mainly enriched in hormone signaling and phenylalanine biosynthesis pathways, and up-down-regulation of these DEGs may alter hormone and secondary metabolite levels to promote germination. The results of weighted gene co-expression network construction (WGCNA) also indicate that plant hormone signal transduction and phenylpropanoid biosynthesis play a dominant role in GA3-induced seed germination. In conclusion, the combined analysis of transcriptomic and physiological indicators provided new insights into seed germination and a theoretical basis for further study of candidate genes.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is characterized by a poor prognosis. Although Kinsenoside (KIN) possesses a wide range of pharmacological activities, its effect and mechanism in TNBC remain unclear. The objective of this research was to explore the therapeutic effectiveness and the molecular mechanisms of KIN on TNBC. Xenograft experiment was carried out to assess the impact of KIN on TNBC in vivo. The effect of KIN on TNBC in vitro was evaluated through the analysis of cell cytotoxicity and colony formation assays. Oil Red O staining and BODIPY 493/503 fluorescence staining were employed to detect the effect of KIN on lipid droplet (LD) formation. Transcriptomics and inhibitor-rescue experiments were conducted to investigate the role of KIN on TNBC. Mechanistic experiments, including quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, diacylglycerol acyltransferase 1 (DGAT1) overexpression assay, and flow cytometric assay, were employed to uncover the regulatory mechanisms of KIN on TNBC. KIN inhibited tumor growth without causing obvious toxicity to the liver and kidneys. In vitro experiments demonstrated that KIN significantly inhibited the viability and proliferation of TNBC cells, accompanied by decreased LD formation and lipid content. Polyunsaturated fatty acids (PUFAs) levels were significantly increased by KIN. Furthermore, transcriptomics and inhibitor-rescue experiments revealed that KIN induced ferroptosis in TNBC cells. KIN could significantly regulate ferroptosis-related proteins. Lipid peroxidation, iron accumulation, and GSH depletion also confirmed this. The LD inducer mitigated the KIN-induced ferroptosis in TNBC. The overexpression of DGAT1 attenuated the effects of KIN on cell viability and proliferation. Furthermore, the overexpression of DGAT1 inhibited the effect of KIN to trigger ferroptosis in TNBC cells. Our findings confirmed that KIN could trigger ferroptosis by suppressing DGAT1-mediated LD formation, thereby demonstrating a promising therapeutic effect of KIN in TNBC.

The liver is the most lethal metastatic site in castration-resistant prostate cancer (CRPC). Overexpression of MET protein has been reported in CRPC, and MET is an important driver gene in androgen-independent CRPC cells. Mouse CRPC cell line CRTC2 was established by subcutaneous injection of hormone-sensitive PC cells (TRAMP-C2) in castrated nude mice. CRCT2/luc2 cells were injected into the spleen of castrated nude mice, and liver metastasis was confirmed at 2 weeks post-injection. We administered MET inhibitor (MET-I) and HGF activator inhibitor (HGFA-I) to this liver metastasis model and assessed the therapeutic effect. After intrasplenic injection, CRTC2 showed a higher incidence of liver metastasis whereas no metastasis was observed in TRAMP-C2. Microarray analysis revealed increased expression of HGF, MET, and HPN, HGFAC (encoding HGF activating proteases) in liver metastasis. Proliferation of CRCT2 was significantly inhibited by co-administration of MET-I and HGFA-I by in vitro analysis with HGF-enriched condition. In an analysis of the mouse model, the combination-therapy group showed the strongest reduction for liver metastasis. Immunohistochemical staining also revealed the strongest decrease in phosphorylation of MET in the combination-therapy group. Co-culture with HGF-expressed mouse fibroblasts showed attenuation of the inhibitory effect of MET-I; however, additional HGFA-I overcame the resistance. We established an androgen-independent CRPC cell line, CRTC2, and liver metastasis model in mice. Significant effect was confirmed by combined treatment of MET-I and HGFA-I by in vitro and in vivo analysis. The results suggested the importance of combined treatment with both MET- and HGF-targeting agents in the treatment of HGF-enriched conditions including liver metastasis.

Estrogen receptor β (ERβ) is the most highly expressed subtype in the colon epithelium and mediates the protective effect of estrogen against the development of colon cancer. Indeed, the expression of this receptor is inversely related to colorectal cancer progression. Structurally estrogen-like compounds, including vitamin E components, affect cell growth by binding to ERs. In the present study, cell proliferation was measured by cell counting in a Bürker hemocytometer, and ERβ expression was measured by Real-Time qPCR and immunoenzymatic methods. The results obtained show that natural δ-tocopherol (δ-Toc) and two of its semi-synthetic derivatives, bis-δ-tocopheryl sulfide (δ-Toc)2S and bis-δ-tocopheryl disulfide (δ-Toc)2S2, play an antiproliferative role and upregulate ERβ expression, similar to 17-β-estradiol (17β-E2), in human colon adenocarcinoma HCT8 cells engineered to overexpress ERβ protein (HCT8-β8). These events are not present in HCT8-pSV2neo and in HCT8-β8 pretreated with ICI 182,780, suggesting that they are mediated by the binding of compounds to ERβ, as also boosted by an in silico assay. The antiproliferative effect is independent of the intracellular redox state and (δ-Toc)2S and (δ-Toc)2S2 reduce cell proliferation at concentrations lower than that of δ-Toc and all tested compounds are also able to upregulate ERβ expression. Taken together, the data indicate that, through the involvement of ERβ activity and expression, δ-Toc, (δ-Toc)2S, and (δ-Toc)2S2 may provide potential therapeutic support against colorectal cancer.

Feedstock plants for biofuel production can be cultivated on polluted sites that are unsuitable for edible crop production. This approach combines environmental restoration and renewable energy production, therefore enhancing the economic viability of plant-derived biofuels. Previous studies have indicated that exposure to environmental pollutants may elevate lignin levels in exposed plants, potentially impacting the biomass digestibility and the efficiency of bioethanol conversion. In this study, we investigated the impact of the antimicrobial agent chlortetracycline on lignin biosynthesis in the reference organism Arabidopsis thaliana. Toxicity testing showed that exposure to chlortetracycline significantly reduced plant growth at concentrations above 2.5 mg L-1. Using Fourier-transform infrared spectroscopy (FTIR) analysis, we observed a significant increase in the lignin signature, ranging from 16 to 40%, in plants exposed to chlortetracycline as compared to non-exposed control plants. Transcriptomic analysis (RNA sequencing) was conducted to determine the molecular basis of plant response to chlortetracycline, revealing significant enrichment of several genes involved in lignin biosynthesis and the phenylpropanoid pathway, including cinnamyl alcohol dehydrogenase and peroxidases. Exposure to chlortetracycline also resulted in the overexpression of genes involved in the metabolism of xenobiotic compounds, including cytochrome P450 monooxygenases, glutathione S-transferases, and glycosyltransferases. Chlortetracycline also induced several genes involved in plant response to stress and defense mechanisms, including transcription factors (e.g., WRKY, MYB, AP2/ERF families), pathogenesis-related proteins, and genes involved in stress signaling. These results suggest that the antibiotic chlortetracycline triggers multiple stress responses in A. thaliana, which may cause changes in lignin biosynthesis, reductions in plant growth, increases in the lignin content, and induction of defense metabolic pathways.

Tumor-associated macrophages (TAMs) significantly influence tumor progression and patient responses to conventional chemotherapy. However, the interplay between anti-cancer drugs, immune responses in the tumor microenvironment, and their implications for cancer treatment remains poorly understood. This study investigates the effects of vinorelbine on M2 macrophages in lung cancer and its capacity to modulate TAMs toward an M1 phenotype. Peripheral blood mononuclear cells (PBMCs) were polarized into M2 macrophages, and subsequent phenotype alterations upon vinorelbine treatment were assessed. Additionally, we evaluated vinorelbine's impact on gene and protein expression associated with cancer progression and cell invasion in non-small-cell lung cancer (NSCLC) cells indirectly co-cultured with M2 macrophages. Notably, vinorelbine, particularly at low concentrations, reprogrammed M2 macrophages to exhibit M1-like characteristics. While M2 macrophages enhanced cancer cell invasion, vinorelbine significantly mitigated this effect. M2 macrophages led to the overexpression of numerous genes linked to tumor growth, angiogenesis, invasion, and immune suppression in NSCLC cells, increasing the BCL2/BAX ratio and promoting cellular resistance to apoptosis. The anti-tumor efficacy of vinorelbine appears to be partly attributed to the reprogramming of M2 macrophages to the M1 phenotype, suggesting that low-dose vinorelbine may optimize therapeutic outcomes while minimizing toxicity in cancer patients.

Dalbergia odorifera is widely used to treat cardiovascular diseases. Our research group found that Dalbergia odorifera volatile oil has a good anti-myocardial ischemic effect, and its main pharmacodynamic components are trans-nerolol and its oxides. However, the exact mechanisms underlying this effect have not yet been elucidated. This study aimed to explore the potential myocardial protective effects of trans-nerolol and its underlying molecular mechanisms. Molecular docking was used to predict and visualize the possible mechanism of the anti-apoptotic myocardial protection by trans-nerolol. The myocardial protective effect of trans-nerolol was evaluated by observing pathological injury, myocardial enzyme levels, oxidation, antioxidant levels, and the expression of related proteins. Molecular docking results showed that trans-nerolol binds closely to cytochrome C (Cytc) and apoptosis-related proteins, suggesting that it may play a role in interacting with these target proteins. The results showed that pre-treatment with dose-dependent trans-nerolol significantly mitigated the myocardial histological damage; decreased lactate dehydrogenase (LDH), creatinine kinase (CK), alanine transaminase (ALT), and aspartate transaminase (AST) levels; reduced nitric oxide (NO) production, hydrogen peroxide (H2O2), and lipid peroxide (LPO); and increased the total antioxidant content (T-AOC), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities compared with the model group. In addition, dose-dependent trans-nerolol significantly increased the Na+-K+-ATPase and Ca2+-Mg2+-ATPase levels. Moreover, trans-nerolol markedly reduced the endogenous and external apoptotic pathways; downregulated the protein expression of Cytc, apoptotic protease activating factor-1 (Apaf1), Fibroblast-associated (Fas), Cysteine-aspartate protease 3 (Caspase3), Cysteine-aspartate protease 8 (Caspase8), and Cysteine-aspartate protease 9 (Caspase9); and upregulated the expression of Heat shock protein 70 (Hsp70) and B-cell lymphoma-2 (Bcl-2). These data indicate that trans-nerolol exerts protective effects against myocardial ischemia (MI), and its mechanism is associated with the suppression of the Cytc- and caspase-signaling pathways. Trans-nerolol has a therapeutic effect on MI, and its mechanism of action is related to its anti-apoptotic effect. These results suggest that Dalbergia odorifera has a potential role to be developed as an MI-promoting therapeutic agent.

Glucose is the preferred carbon source for most cells. However, cells may encounter other carbon sources that can be utilized. How cells match their metabolic gene expression to their carbon source, beyond a general glucose repressive system (catabolite repression), remains little understood. By studying the effect of up to seven different carbon sources on Snf1 phosphorylation and on the expression of downstream regulated genes, we searched for the mechanism that identifies carbon sources. We found that the glycolysis metabolites glucose-6-phosphate (G6P) and glucose-1-phosphate (G1P) play a central role in the adaptation of gene expression to different carbon sources. The ratio of G1P and G6P activates analogue calcium signaling via the proton-exporter Pma1 to regulate downstream genes. The signaling pathway bifurcates with calcineurin-reducing ADH2 (alcohol dehydrogenase) expression and with Cmk1-increasing ZWF1 (glucose-6-phosphate dehydrogenase) expression. Furthermore, calcium signaling is not only regulated by the present carbon source; it is also regulated by past carbon sources. We were able to manipulate this ionic memory mechanism to obtain high expression of ZWF1 in media containing galactose. Our findings provide a universal mechanism by which cells respond to all carbon sources.

Dinaciclib, a potent cyclin-dependent kinase (CDK) inhibitor, has demonstrated considerable antitumor effects in various malignancies. However, its impact on oral squamous cell carcinoma (OSCC), a predominant and highly aggressive form of head and neck squamous cell carcinoma (HNSC) with limited treatment options, remains underexplored. We conducted gene set enrichment analyses in HNSC patients that reinforced the relevance of these cell cycle-related genes to OSCC pathogenesis. Given the known dysregulation of cell cycle-related genes in HNSC patients, we hypothesized that Dinaciclib may inhibit OSCC growth by targeting overexpressed cyclins and CDKs, thereby disrupting cell cycle progression and inducing apoptosis. This study investigated Dinaciclib's effects on cell proliferation, cell cycle progression, and apoptosis in the OSCC cell lines Ca9-22, OECM-1, and HSC-3. Our results demonstrated that Dinaciclib significantly reduces OSCC cell proliferation in a dose-dependent manner. Flow cytometry and Western blot analyses showed that Dinaciclib induces cell cycle arrest at the G1/S and G2/M transitions by downregulating Cyclins A, B, D, and E, along with CDKs 1 and 2-key regulators of these checkpoints. Furthermore, Dinaciclib treatment upregulated apoptotic markers, such as cleaved-caspase-3 and cleaved-PARP, confirming its pro-apoptotic effects. In conclusion, these findings highlight Dinaciclib's therapeutic promise in OSCC by simultaneously disrupting cell cycle progression and inducing apoptosis. These results support further exploration of Dinaciclib as a viable monotherapy or combination treatment in OSCC and other HNSC subtypes to improve patient outcomes.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, arises from skeletal muscle cells that fail to differentiate terminally. Two subgroups of RMS, fusion-positive and fusion-negative RMS (FPRMS and FNRMS, respectively), are characterized by the presence or absence of the PAX3/7-FOXO1 fusion gene. RMSs frequently exhibit increased expression of human epidermal growth factor receptor-2 (HER2). Trastuzumab is a humanized monoclonal antibody targeting HER2, and its potential role in RMS treatment remains to be elucidated. Syndecan-4 (SDC4) is a heparan sulfate proteoglycan (HSPG) affecting myogenesis via Rac1-mediated actin remodeling. Previously, we demonstrated that the SDC4 gene is amplified in 28% of human FNRMS samples, associated with high mRNA expression, suggesting a tumor driver role. In this study, after analyzing the copy numbers and mRNA expressions of other HSPGs in human RMS samples, we found that in addition to SDC4, syndecan-1, syndecan-2, and glypican-1 were also amplified and highly expressed in FNRMS. In RD (human FNRMS) cells, elevated SDC4 expression was accompanied by low levels of phospho-Ser179 of SDC4, leading to high Rac1-GTP activity. Notably, this high SDC4 expression in RD cells decreased following trastuzumab treatment. Trastuzumab decreased the levels of G1/S checkpoint regulators cyclin E and cyclin D1 and reduced the cell number; however, it also downregulated the cyclin-dependent kinase inhibitor p21. The level of MyoD, a transcription factor essential for RMS cell survival, also decreased following trastuzumab administration. Our findings contribute to the understanding of the role of SDC4 in FNRMS. Since HER2 is expressed in about half of RMSs, the trastuzumab-mediated changes observed here may have therapeutic implications.

Long non-coding RNAs (lncRNAs) are involved in plant biotic and abiotic stress responses, in which Ca2+ also plays a significant role. There is diversity in the regulation of different gene expressions by cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc). However, no studies have yet explored the interrelationship between lncRNAs and calcium signaling, nor how calcium signaling regulates the expression of lncRNAs. Here, we use transgenic materials PV-NES and NLS-PV, which simulate [Ca2+]cyt- and [Ca2+]nuc-deficient mutants, respectively, and wild type (WT) materials in response to hyperosmolarity (250 mM sorbitol) or salt stresses (125 mM NaCl) at different time points to obtain RNA-seq data, respectively. Then, we proceed with the screening of lncRNAs, adding 688 new lncRNAs to the known Arabidopsis lncRNA database. Subsequently, through the analysis of differentially expressed lncRNA genes, it was found that cytosolic or nucleosolic calcium signals have distinct regulatory effects on differentially expressed lncRNAs (DElncRNAs) and differentially expressed protein-coding genes (DEPCGs) treated with high-concentration NaCl and sorbitol at different times. Furthermore, through weighted correlation network analysis (WGCNA), it is discovered that under hyperosmolarity and salt stresses, lncRNA-associated PCGs are related to the cell wall structure, the plasma membrane component, and osmotic substances through trans-regulation. In addition, by screening for cis-regulatory target PCGs of Ca2+-regulated lncRNAs related to osmotic stress, we obtain a series of lncRNA-PCG pairs related to water transport, cell wall components, and lateral root formation. Therefore, we expand the existing Arabidopsis lncRNA database and obtain a series of lncRNAs and PCGs regulated by [Ca2+]cyt or [Ca2+]nuc in response to salt and hyperosmolarity stress, providing a new perspective for subsequent research on lncRNAs. We also explore the trans- and cis-regulated target PCGs of lncRNAs regulated by calcium signaling, providing new insights for further studying salt stress and osmotic stress.

Gastrointestinal (GI) cancers, which mainly include malignancies of the esophagus, stomach, intestine, pancreas, liver, gallbladder, and bile duct, pose a significant global health burden. Unfortunately, the prognosis for most GI cancers remains poor, particularly in advanced stages. Current treatment options, including targeted and immunotherapies, are less effective compared to those for other cancer types, highlighting an urgent need for novel molecular targets. NEK (NIMA related kinase) kinases are a group of serine/threonine kinases (NEK1-NEK11) that play a role in regulating cell cycle, mitosis, and various physiological processes. Recent studies suggest that several NEK members are overexpressed in human cancers, including gastrointestinal (GI) cancers, which can contribute to tumor progression and drug resistance. Among these, NEK2 stands out for its consistent overexpression in all types of GI cancer. Targeting NEK2 with specific inhibitors has shown promising results in preclinical studies, particularly for gastric and pancreatic cancers. The development and clinical evaluation of NEK2 inhibitors in human cancers have emerged as a promising therapeutic strategy. Specifically, an NEK2 inhibitor, T-1101 tosylate, is currently undergoing clinical trials. This review will focus on the gene expression and functional roles of NEKs in GI cancers, as well as the progress in developing NEK inhibitors.

As key enzymes in the gibberellin (GA) biosynthesis pathway, GAoxs function as regulators of bioactive GA levels and plant architecture, yet little is understood about GAoxs in Gossypium. In this study, 78 GAox genes identified in four cotton species were divided into three subgroups: GA2ox, GA3ox, and GA20ox. Syntenic relationships of GAoxs in Gossypium suggested that divergencies in gene function may be attributed to whole-genome duplication during evolution. Cis-acting element analysis suggested that the GbGAox genes might participate in plant growth, development, and hormone responses. Moreover, transcriptome analysis was performed to characterize the molecular response of the exogenous GA3 application. It was found that DEGs (differentially expressed genes) are widely involved in cell division and cell wall modification, in which the most XTH (xyloglucan endotransglucosylase/hydrolase) and GAox genes responded actively to the exogenous GA3 treatment. Some transcription factors and protein kinases cooperated with those GbGAoxs in response to GA3. These findings underlie the biological function of GAox genes and their responses to GA3 in regulating plant growth in Gossypium barbadense.

MiRNAs regulate follicle development and atresia, steroid production, granulosa cell (GC) proliferation, and apoptosis. However, the target genes and the functioning of novel miRNAs remain unexplored. We reveal the targeting relationship between novel-m0297-5p and WNT5A and the specific regulatory mechanism of GC proliferation in small-tailed Han sheep using whole transcriptomic sequencing. We performed whole transcriptomic sequencing on small-tailed Han sheep ovarian GCs supplemented with 10 ng/mL of transforming growth factor-β1 (TGF-β1) during the early stages. This led to identifying the differential expression of novel-m0297-5p and Wnt family member 5A (WNT5A) and predicting their targeting relationship. Based on this, we hypothesized that TGF-β1 could mediate novel-m0297-5p targeting WNT5A to participate in the proliferation process of GCs in small-tailed sheep. We confirmed the relationship between TGF-β1 and both novel-m0297-5p and WNT5A. The mimicry of novel-m0297-5p inhibited GC activity and proliferation. However, the inhibition of novel-m0297-5p yielded the opposite effect. We validated the binding site for novel m0297-5p within the 3'UTR of WNT5A using dual-luciferase reporter gene. TGF-β1 alleviated the impact induced by the mimicry of novel-m0297-5p on cell viability. Inhibitor co-transfection for both novel-m0297-5p and si-WNT5A suppressed the granulocyte proliferation induced by novel-m0297-5p inhibition. These findings suggest that TGF-β1 can mediate the inhibitory effect of novel-m0297-5p targeting WNT5A on GC proliferation and activity in small-tailed Han sheep. This study provides an experimental basis for research on the biological function of GCs and their impact on follicle development.

Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. Prunella vulgaris L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of Prunella vulgaris are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of Prunella vulgaris significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of Ptp1b, Pi3k, Akt and mtor and upregulate the mRNA and protein expression levels of Il-24 in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.

Apyrases (APYs) directly regulate intra- and extra-cellular ATP homeostasis and play a key role in the process of plants adapting to various stresses. In this study, we identified and characterized soybean APY (GmAPY) family members at the genomic level. The results identified a total of 18 APYRASE homologous genes with conserved ACR domains. We conducted a bioinformatics analysis of GmAPYs, including sequence alignment, phylogenetic relationships, and conserved motifs. According to the phylogenetic and structural characteristics, GmAPYs in soybeans are mainly divided into three groups. The characteristics of these GmAPYs were systematically evaluated, including their collinearity, gene structure, protein motifs, cis-regulatory elements, tissue expression patterns, and responses to aluminum stress. A preliminary analysis of the function of GmAPY1-4 was also conducted. The results showed that GmAPY1-4 was localized in the nucleus, presenting relatively high levels in roots and root nodules and demonstrating high sensitivity and positive responses under aluminum stress circumstances. Further functional characterization revealed that the overexpression of GmAPY1-4 in hairy roots not only induced root growth under normal growth conditions but also significantly prevented root growth inhibition under aluminum stress conditions and contributed to maintaining a relatively higher fresh root weight. By contrast, RNAi interference with the expression of GmAPY1-4 in hairy roots inhibited root growth under both normal and aluminum stress conditions, but it exerted no significant influence on the dry or fresh root weight. To sum up, these findings support the significant functional role of GmAPY1-4 in root growth and the aluminum stress response. These findings not only enhance our comprehension of the aluminum stress response mechanism by identifying and characterizing the APY gene family in the soybean genome but also provide a potential candidate gene for improving aluminum tolerance in soybeans in the future.

Serine acetyltransferase (SAT) is a critical enzyme in the sulfur-assimilation pathway of cysteine, playing an essential role in numerous physiological functions in plants, particularly in their response to environmental stresses. However, the structural characteristics of the soybean SAT gene family remain poorly understood. Members of the soybean SAT gene family were identified using the Hidden Markov Model approach. Bioinformatics tools, such as ExPASy, PlantCARE, MEME, and TBtools-II, were employed to examine the physicochemical properties, cis-regulatory elements, conserved motifs, gene structures, and chromosomal positions of the GmSAT genes. RT-qPCR was conducted to evaluate the expression profiles of GmSAT genes under NaCl-induced stress, identifying genes likely involved in the salt-stress response. A total of ten GmSAT genes were identified in the soybean genome and grouped into three subfamilies. Genes within each subfamily shared notable structural similarities and conserved motifs. Analysis of cis-regulatory elements revealed that the promoters of these genes contain several elements linked to plant growth and stress-related responses. Expression patterns of GmSAT genes varied across different soybean tissues, with GmSAT10 showing higher expression in roots, while GmSAT1 and GmSAT2 had lower expression in the same tissue. Following NaCl treatment, expression levels of seven GmSAT genes were significantly increased in the roots, indicating their potential involvement in the plant's adaptation to salt stress. GmSAT genes appear to play crucial roles in soybean's response to salt stress, offering insights that could aid in the development of salt-tolerant soybean varieties.

Afatinib-induced tumor and microenvironment modifications in head and neck squamous cell carcinoma were evaluated by spatial transcriptomics in surgical specimens and RNA-sequencing in tumor biopsies of patients included in the EORTC-90111-24111 window-of-opportunity study. The aim was to explore tumor evolution and composition under anti-HER therapy. Based on our previous investigations by RNA-seq on tumor biopsies, surgical slides of ID08 and ID15 from the epithelial-to-mesenchymal (EMT) cluster and ID30 from the non-EMT cluster were investigated with spatial transcriptomics. Dimension reduction in ID30 revealed 14 clusters, with clusters overlapping three tumor nodules and the stroma. Differential expression analysis between tumor nodules showed enrichment of the hallmark EMT genelist, with 123 genes in common between the analyses. These genes were involved in PDGF and MET signaling pathways. By comparing gene expression in paired tumor biopsies and the 123 genes from differential analyses obtained in ID30, a list of 13 genes involved in cancer pathways and EMT emerged, which were also highly expressed in ID08 and ID15. These results show a progressive apparition of genes implicated in EMT, MET, and PDGF pathways in tumors after afatinib. Notably, a list of 13 genes emerged which may contain targets to prevent tumor evolution after anti-HER therapy.

To successfully metastasize, cancer cells must evade detachment induced cell death, known as anoikis. Unraveling the mechanisms that gastric cancer (GC) circumvent anoikis and achieve peritoneal metastasis especially during unanchored growth, could significantly improve patient outcomes. Our study reveals that GC cells exhibit increased lipid peroxidation, MDA production, and cell death during suspension culture, which can be mitigated by the intervention with liproxstatin-1 and ferrostatin-1. We discovered that oleic acid (OA) or adipocytes stimulate lipid accumulation in GC cells, thereby inhibiting lipid peroxidation and cell death. Lipid mass spectrometry confirmed an upregulation of triglyceride synthesis, indicating that the accumulation of lipid droplet may confer resistance to ferroptosis during suspension growth. In vitro assays demonstrated that OA not only induces lipid droplet accumulation but also upregulates the expression of ferroptosis suppressor protein 1 (FSP1), a process that can be abrogated by the double knockout of GPD1/1L genes. Additionally, we have demonstrated that a decrease in the ubiquitination of FSP1 in GC cells upon lipid droplet accumulation, as well as silencing or pharmacological targeting FSP1, promotes ferroptosis and disrupts the peritoneal metastatic potential of GC cells. Collectively, our findings highlight the potential of FSP1 as a promising therapeutic target for metastatic gastric cancer.