STIM1 promotes acquired resistance to sorafenib by attenuating ferroptosis in hepatocellular carcinoma.

Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.

OBJECTIVE AND DESIGN: Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD. METHODS: The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes. RESULTS: Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo. CONCLUSION: Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.

B. subtilis CNBG-PGPR-1 induces methionine to regulate ethylene pathway and ROS scavenging for improving salt tolerance of tomato.

Soil salinity severely threatens plant growth and crop yields. The utilization of PGPR is an effective strategy for enhancing plant salt tolerance, but the mechanisms involved in this process have rarely been reported. In this study, we investigated the effects of Bacillus subtilis CNBG-PGPR-1 on improving plant salt tolerance and elucidated the molecular pathways involved. The results showed that CNBG-PGPR-1 significantly improved the cellular homeostasis and photosynthetic efficiency of leaves and reduced ion toxicity and osmotic stress caused by salt in tomato. Transcriptome analysis uncovered that CNBG-PGPR-1 enhanced plant salt tolerance through the activation of complex molecular pathways, with plant hormone signal transduction playing an important role. Comparative analysis and pharmacological experiments confirmed that the ethylene pathway was closely related to the beneficial effect of CNBG-PGPR-1 on improving plant salt tolerance. Furthermore, we found that methionine, a precursor of ethylene synthesis, significantly accumulated in response to CNBG-PGPR-1 in tomato. Exogenous L-methionine largely mimicked the beneficial effects of CNBG-PGPR-1 and activated the expression of ethylene pathway-related genes, indicating CNBG-PGPR-1 induces methionine accumulation to regulate the ethylene pathway in tomato. Finally, CNBG-PGPR-1 reduced salt-induced ROS by activating ROS scavenger-encoding genes, mainly involved in GSH metabolism and POD-related genes, which were also closely linked to methionine metabolism. Overall, our studies demonstrate that CNBG-PGPR-1-induced methionine is a key regulator in enhancing plant salt tolerance through the ethylene pathway and ROS scavenging, providing a novel understanding of the mechanism by which beneficial microbes improve plant salt tolerance.

Gut microbiota and tumor-associated macrophages: potential in tumor diagnosis and treatment.

Avoiding immune destruction and polymorphic microbiomes are two key hallmarks of cancer. The tumor microenvironment (TME) is essential for the development of solid tumors, and the function of tumor-associated macrophages (TAMs) in the TME is closely linked to tumor prognosis. Therefore, research on TAMs could improve the progression and control of certain tumor patients. Additionally, the intestinal flora plays a crucial role in metabolizing substances and maintaining a symbiotic relationship with the host through a complex network of interactions. Recent experimental and clinical studies have suggested a potential link between gut microbiome and TME, particularly in regulating TAMs. Understanding this association could improve the efficacy of tumor immunotherapy. This review highlights the regulatory role of intestinal flora on TAMs, with a focus on gut microbiota and their metabolites. The implications of this association for tumor diagnosis and treatment are also discussed, providing a promising avenue for future clinical treatment strategies.

A plant growth-promoting bacteria Priestia megaterium JR48 induces plant resistance to the crucifer black rot via a salicylic acid-dependent signaling pathway.

Xanthomonas campestris pv. campestris (Xcc)-induced black rot is one of the most serious diseases in cruciferous plants. Using beneficial microbes to control this disease is promising. In our preliminary work, we isolated a bacterial strain (JR48) from a vegetable field. Here, we confirmed the plant-growth-promoting (PGP) effects of JR48 in planta, and identified JR48 as a Priestia megaterium strain. We found that JR48 was able to induce plant resistance to Xcc and prime plant defense responses including hydrogen peroxide (H2O2) accumulation and callose deposition with elevated expression of defense-related genes. Further, JR48 promoted lignin biosynthesis and raised accumulation of frees salicylic acid (SA) as well as expression of pathogenesis-related (PR) genes. Finally, we confirmed that JR48-induced plant resistance and defense responses requires SA signaling pathway. Together, our results revealed that JR48 promotes plant growth and induces plant resistance to the crucifer black rot probably through reinforcing SA accumulation and response, highlighting its potential as a novel biocontrol agent in the future.

Crucial role of Ca2+ /CN signalling pathway in the antifungal activity of disenecioyl-cis-khellactone against Botrytis cinerea.

BACKGROUND: Botrytis cinerea causes grey mould and is one of the most destructive fungal pathogens affecting important fruit and vegetable crops. In preliminary studies, we found that disenecioyl-cis-khellactone (DK) had strong antifungal activity against several fungi species including B. cinerea [half maximal effective concentration (EC50 ) = 11.0 µg mL-1 ]. In this study, we aimed to further evaluate the antifungal activity of DK against B. cinerea and determine the role of calcium ion/calcineurin (Ca2+ /CN) signalling pathway on its antifungal effect. RESULTS: DK was effective against B. cinerea in both in vitro and in vivo assays. Exogenous Ca2+ reduced the antifungal activity of DK. The combination of DK and cyclosporine A (CsA) did not exhibit an additive effect against B. cinerea. In contrast to CsA, DK reduced the intracellular Ca2+ concentration in B. cinerea. DK bound to calcineurin A (cnA) and up-regulated the expression of PMC1 and PMR1 genes. Moreover, DK sensitivity of △bccnA significantly decreased compared with that of Bc05.10 strain. CONCLUSION: DK is a promising lead compound for developing fungicides against B. cinerea. The Ca2+ /CN signalling pathway plays a crucial role in the DK antifungal activity, and cnA is one of the targets of DK against B. cinerea. DK directly reacts with cnA, which up-regulates the transcription of Ca2+ /CN-dependent target genes PMC1 and PMR1, decreasing the intracellular Ca2+ concentration and disturbing the intracellular Ca2+ balance, leading to cell death. © 2022 Society of Chemical Industry.

Antifungal Activity and Possible Mechanism of Bacillus amyloliquefaciens FX2 Against the Postharvest Apple Ring Rot Pathogen.

Botryosphaeria dothidea-induced apple ring rot is one of the most serious postharvest diseases in apple production. In our preliminary work, we isolated a bacterial strain (FX2) from an infested apple orchard. Here, we confirmed the strong antifungal activity of FX2 on B. dothidea. Through phylogenetic analysis and morphological observations, we identified FX2 as a Bacillus amyloliquefaciens strain. We also found that 10% cell-free supernatant (CFS) of FX2 significantly affected mycelial growth and morphology and almost completely inhibited spore germination and germ tube elongation in B. dothidea. Furthermore, 10% CFS damaged the cell ultrastructure, resulting in a remarkable increase in cellular leakage in B. dothidea mycelia. Thus, CFS has the potential to effectively reduce in vivo B. dothidea infection, reduced lesion diameters to 64.7% compared with the control group, and reduced disease incidence by 15%. Finally, ultrafiltration, desalting chromatography, and anion exchange chromatography showed that the antifungal constituents in CFS are composed mainly of antifungal proteins. We further characterized these potential antifungal proteins via liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Herein, we provide novel insights into the antifungal mechanisms of B. amyloliquefaciens FX2, and we highlight its potential as a novel biocontrol agent for controlling postharvest apple ring rot.

The complete chloroplast genome sequence of Michelia compressa.

Michelia compressa is an evergreen ornamental tree species. The high-throughput sequencing technology was used to sequence and assemble the chloroplast genome of Michelia compressa. Results showed that the chloroplast genome is 160,061 bp in length, of which the inverted repeats sequence (IRs) is 26,581 bp, the large single-copy region (LSC) and the small single copy region (SSC) are 88,097 bp and 18,802 bp, respectively. The GC content of the plastome was 39.2%, with 43.2%, 37.9% and 34.2% in IRs, LSC and SSC, respectively. A total of 132 genes are annotated, 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. This study enriched the Michelia compressa genomic information which provides the basis for rational exploitation and utilization of germplasm resources.

[Quantitative relationships between leaf total nitrogen concentration and canopy reflectance spectra of rice].

By the method of statistics, this paper approached the quantitative relationships between leaf total nitrogen concentration (LNC) and canopy reflectance spectra of rice, based on the data from 5-year field experiments involving different varieties and nitrogen fertilization rates. The results showed that the LNC had higher correlations with the key spectral parameters of two bands than of single band. The relative, differential, and normalized difference vegetation indices (RVI, DVI, NDVI) of the bands in near infrared (760-1,220 nm) and visible light 510 nm, 560 nm, 680 nm and 710 nm all showed significantly positive correlations to LNC, and NDVI showed the best. All the parameters having significant correlations with LNC were selected to compare the R2 and SE in the regression equations with LNC, which confirmed that the NDVI of R1220 and R710 was the best parameter for predicting the LNC. The quantitative equation LNC = 3.2708 x NDVI (1220, 710) + 0.8654 was tested by the data from other three field experiments with different rice cultivars, water conditions and nitrogen fertilization rates, and the estimated R2, slope, and RMSE were ranged in 0.674-0.862, 0.908-1.010 and 11.315%-19.491%, respectively, indicating a good fit between the predicted and observed values of LNCs, which suggested that this model was feasible for predicting the LNC of rice under different cultivation conditions.

[Biosorptive-flotation and desorption operation of heavy metals from wastewater effluents by Gordona amarae].

The process of adsorptive-flotation and desorption to remove and recovery heavy metals from aqueous solution was studied using Gordona amarae as sorbent, and the mechanisms of biosorption and flotation were analyzed. Experimental results showed that the selectivity of Gordona amarae for various heavy metal cations was Pb > Hg > Cu, and the restrain oneself of Cu2+ was the highest. the present of NH4+ ion on loaded Pb2+ cells was remarkably improved, however, K+, Na+, Ca2+, Mg2+ of co-existing ions slightly restrained influence. The flotation recoveries respectively of Pb2+ and biomass more than 93% and 96% for with DA dosage of 17.5 mmol/L in the pH of 9.5, and that was almost quantitative remaining around 94% and 97% being desorbed when desorption frequence of Na2CO3 was up to three times. The measure of Zeta potential and infrared spectroscopy analysis showed that the ioselectric point of Gordona amarae in water was 3.50, up to 4.02 when loaded Pb2+, down to 3.02 when DA doseage added in the loaded biomass. Experiments indicated the lead bosorpting process was likely to involving in the group of -NHCOCH3 and COO- on the cell wall, while the biosorptive flotation was concerned cooperatively to be basing on electrostatic attraction, hydrogen bond, ion exchange and chemical complexation. SEM observation showed that Gordona amarae biomass loaded Hg2+ changed into flocculent matter.

[Flotation mechanism on Mycobacterium phlei and adsorption of Pb2+ by collectors].

The possibility of removal of heavy metals from waste water by adsorption flotation using Mycobacterium phlei as adsorbent was investigated, and the collection mechanism of collectors on adsorbent was analyzed. From the single flotation tests, it shows that cationic collectors have a stronger collecting ability for Mycobacterium phlei than anionic collectors. The adsorptive flotation experiment shows that floatability process occurred within 10 minutes, the recovery of Mycobacterium phlei and the removing rate of Pb2+ are high by using cationic collectors during pH value from 4 to 7. At 45mmol/L of Di-buty lamine as collector, and 4.75 of pH, the recovery of Mycobacterium phlei and the removing rate of Pb2+ are 92 % and 98%. The isoelectric point of Mycobacterium phlei is 3.09 at pH of the solution, which increased when Pb2+ or Di-buty lamine is adsorption by Mycobacterium phlei. The good floatability of Mycobacterium phlei with cationic collectors results from the intense zeta potential on the surface of cell, Adsorptive flotation may have practical applications for the removal of hazardous metals from contaminated water supplies.