Aerobic Se(IV) reducing bacteria and their reducing characteristics in estuarine sediment.

Microorganisms play a critical role in the biogeochemical cycling of selenium in natural ecosystems, particularly in reducing selenite (Se(IV)) to element selenium (Se(0)) which reduces its mobility and bioavailability. However, Se(IV)-reducing bacteria and their reducing characteristics in estuarine sediments remain inadequately understood. In this study, the reduction of Se(IV) was confirmed to be microbially driven through the cultivation of a mixture of estuarine sediment and Se(IV) under aerobic conditions. Community analysis indicates that Bacillus was primarily involved in the reduction of Se(IV). A strain with high salt tolerance (7.5 % NaCl) and Se(IV) resistance (up to 200 mM), Bacillus cereus SD1, was isolated from an estuarine sediment. The reduction of Se(IV) occurred concomitantly with the onset of microbial growth, and reduction capacity increased approximately 5-fold by adjusting the pH. In addition, Se(IV) reduction in Bacillus cereus SD1 was significantly inhibited by sulfite, and the key enzyme activity tests revealed the possible presence of a sulfite reductase-mediated Se(IV) reduction pathway. These research findings provide new insights into the bioreducing characteristics and the biogeochemical cycling of selenium in estuarine environments.

Effects of denitrification on speciation and redistribution of arsenic in estuarine sediments.

Microbially-mediated redox processes involving arsenic (As) and its host minerals significantly contribute to the mobilization of As in estuarine sediments. Despite its significance, the coupling between As dynamics and denitrification processes in these sediments is not well understood. This study employed sequential sediment extractions and simultaneous monitoring of dissolved iron (Fe), nitrogen (N), and sulfur (S) to investigate the impact of nitrate (NO3-) on the speciation and redistribution of As, alongside changes in microbial community composition. Our results indicated that NO3- additions significantly enhance anaerobic arsenite (As(III)) oxidation, facilitating its immobilization by increased adsorption onto sediment matrices in As-contaminated estuarine settings. Furthermore, NO3- promoted the conversion of As bound to troilite (FeS) and pyrite (FeS2) into forms associated with Fe oxides, challenging the previously assumed stability of FeS/FeS2-bound As in such environments. Continuous NO3- additions ensured As and Fe oxidation, thereby preventing their reductive dissolution and stabilizing the process that reduces As mobility. Changes in the abundance of bacterial communities and correlation analyses revealed that uncultured Anaerolineaceae and Thioalkalispira may be the main genus involved in these transformations. This study underscores the critical role of NO3- availability in modulating the biogeochemical cycle of As in estuarine sediments, offering profound insights for enhancing As immobilization techniques and informing environmental management and remediation strategies in As-contaminated coastal regions.

Metals and polycyclic aromatic hydrocarbons pollutants in industrial parks under valley landforms in Tibetan Plateau: Spatial pattern, ecological risk and interaction with soil microorganisms.

The spatial patterns of pollutants produced by industrial parks are affected by many factors, but the interactions among polycyclic aromatic hydrocarbons (PAHs), metals, and soil microorganisms in the valley landforms of the Tibetan Plateau are poorly understood. Thus, this study systematically investigated the distribution and pollution of metals and PAHs in soil around an industrial park in the typical valley landform of the Tibetan Plateau and analyzed and clarified the interaction among metals, PAHs, and microorganisms. The results were as follows: metal and PAH concentrations were affected by wind direction, especially WN-ES and S-N winds; Cd (2.86-54.64 mg·kg-1) had the highest soil concentrations of the metals screened, followed by variable concentrations of Cu, Pb, and Zn; the pollution levels of metals and PAHs in the S-N wind direction were lower than those in the WN-ES wind direction; the Cd content of Avena sativa in the agricultural soil around the factory exceeded its enrichment ability and food safety standards; the closer to the center of the park, the higher the ecological risk of PAHs; and the TEQ and MEQ values of the PAHs were consistent with their concentration distributions. The results of the soil microbial diversity and co-occurrence network in the dominant wind direction showed that metal and PAH pollution weakened the robustness of soil microbial communities. Additionally, the diversity and robustness of soil microbial communities at the S wind site were higher than those at the ES wind site, which might be attributed to the lower metal content of the former than the latter, which plays a negative role in the biodegradation of PAHs. The results of this study provide insights into the site selection, pollutant supervision, and environmental remediation of industrial parks in typical landforms.

Molecular composition and characteristics of Sediment-adsorbed Dissolved Organic Matter (SDOM) along the coast of China.

Sediment-adsorbed Dissolved Organic Matter (SDOM) in coast plays a crucial role in the terrestrial and marine carbon cycle processes of the global environment. However, understanding the transport dynamics of SDOM along the coast of China, particularly its interactions with sediments, remains elusive. In this study, we analyzed the δ13C and δ15N stable isotopic compositions, as well as the molecular characteristics of SDOM collected from coastal areas spanning the Bohai Sea (BS), Yellow Sea (YS), East China Sea (ECS), and South China Sea (SCS), by using isotope ratio mass spectrometry and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS). We identified the predominant sources of carbon and nitrogen in coastal sediments, revealing terrigenous origins for most C and N, while anthropogenic sources dominated in the SCS. Spatial variations in SDOM chemodiversity were observed, with diverse molecular components influenced by distinct environmental factors and sediment sources. Notably, lignins and saturated compounds (such as proteins/amino sugars) were the predominant molecular compounds detected in coastal SDOM. Through Mantel tests and Spearman's correlation analysis, we elucidated the significant influence of spatial environmental factors (temperature, DO, salinity, and depth) and sediment sources on SDOM molecular chemodiversity. These findings contribute to a more comprehensive understanding of the carbon cycle dynamics along the Chinese coast.

Simultaneous stabilization of particulate and bioavailable arsenic in soils from the realgar mining area by polyacrylamide, nano-SiO2, and ferrihydrite composite materials.

Arsenic (As) contamination in realgar mining areas poses a severe environmental and health risk, highlighting the critical need for effective strategies to manage As migration, particularly in its particulate and bioavailable states. Soil erosion and water leaching serve as significant pathways for spreading As, emphasizing the imperative to curtail its mobility. In the present study, we proposed an effective strategy that combines the utilization of polyacrylamide (PAM), nano-SiO2 (NS), and ferrihydrite (Fh) to elevate the stability of As in soils from a realgar mining area. The results show that this composite material demonstrates the capability to concurrently regulate soil erosion and mitigate the leaching of bioavailable As. The combination of the three materials in the proportion of 0.5 % PAM +0.1 % NS + 1.0 % Fh can reduce the soil particulate and bioavailable As content by 99.11 % and 93.98 %, respectively. The unconfined compressive strength of the soil can be increased by about 30 % under this condition. The SEM analyses show that the addition of PAM and NS can significantly enhance the aggregation of soil particles and then reduce the soil erosion rate. These findings highlight the significant potential of the proposed approach in mitigating As contamination in soil within mining environments. The approach offers a sustainable and comprehensive solution to address the transport of heavy metal contaminants in both particulate and bioavailable states in mining areas.

Bacterial community in the metal(loid)-contaminated marine vertical sediments of Jinzhou Bay: Impacts and adaptations.

Metal(loid) discharge has led to severe coastal contamination; however, there remains a significant knowledge gap regarding its impact on sediment profiles and depth-resolved bacterial communities. In this study, geochemical measurements (pH, nutrient elements, total and bioavailable metal(loid) content) consistently revealed decreasing nitrogen, phosphorus, and metal(loid) levels with sediment depth, accompanied by reduced alpha diversity. Principal coordinate analysis indicated distinct community compositions with varying sediment depths, suggesting a geochemical influence on diversity. Ecological niche width expanded with depth, favoring specialists over generalists, but both groups decreased in abundance. Taxonomic shifts emerged, particularly in phyla and families, correlated with sediment depth. Microbe-microbe interactions displayed intricate dynamics, with keystone taxa varying by sediment layer. Zinc and arsenic emerged as key factors impacting community diversity and composition using random forest, network analysis, and Mantel tests. Functional predictions revealed shifts in potential phenotypes related to mobile elements, biofilm formation, pathogenicity, N/P/S cycles, and metal(loid) resistance along sediment profiles. Neutral and null models demonstrated a transition from deterministic to stochastic processes with sediment layers. This study provides insights into the interplay between sediment geochemistry and bacterial communities across sediment depths, illuminating the factors shaping these ecosystems.

Iodide and sulfite synergistically accelerate the photo-reduction and recovery of As(V) and As(III) in sulfite/iodide/UV process: Efficiency and mechanism.

Photo-reduction of arsenic (As) by hydrated electron (eaq-) and recovery of elemental arsenic (As(0)) is a promising pathway to treat As-bearing wastewater. However, previously reported sulfite/UV system needs large amounts of sulfite as the source of eaq-. This work suggests a sulfite/iodide/UV approach that is more efficient and consumes much less chemical reagents to remove As(III) and As(V) and recover valuable As(0) from wastewater, hence preventing the production of large amounts of As-containing hazardous wastes. Our results showed that more than 99.9% of As in the aqueous phase was reduced to highly pure solid As(0) (>99.5 wt%) by sulfite/iodide/UV process under alkaline conditions. Sulfite and iodide worked synergistically to enhance reductive removal of As. Compared with sulfite/UV, the addition of iodide had a substantially greater effect on As(III) (over 200 times) and As(V) (approximately 30 times) removals because of its higher absorptivity and quantum yield of eaq-. Furthermore, more than 90% of the sulfite consumption was decreased by adding a small amount of iodide while maintaining similar reduction efficiency. Hydrated electron (eaq-) was mainly responsible for As(III) and As(V) reductions and removals under alkaline conditions, while both SO3•- and reactive iodine species (e.g., I•, I2, I2•-, and I3-) may oxidize As(0) to As(III) or As(V). Acidic circumstances caused sulfite protonation and the scavenging of eaq- by competing processes. Dissolved oxygen (O2) and CO32- prevented As reduction by light blocking or eaq- scavenging actions, but Cl-, Ca2+, and Mg2+ showed negligible impacts. This study presented an efficient method for removing and recovering As from wastewater.

Divergent adaptation strategies of abundant and rare bacteria to salinity stress and metal stress in polluted Jinzhou Bay.

Understanding how abundant (AT) and rare (RT) taxa adapt to diverse environmental stresses is vital for assessing ecological processes, yet remains understudied. We collected sediment samples from Liaoning Province, China, representing rivers (upstream of wastewater outlet), estuaries (wastewater outlets), and Jinzhou Bay (downstream of wastewater outlets), to comprehensively evaluate AT and RT adaptation strategies to both natural stressors (salinity stress) and anthropogenic stressors (metal stress). Generally, RT displayed higher α- and ß-diversities and taxonomic groups compared to AT. Metal and salinity stresses induced distinct α-diversity responses in AT and RT, while ß-diversity remained consistent. Both subcommunities were dominated by Woeseia genus. Metal stress emerged as the primary driver of diversity and compositional discrepancies in AT and RT. Notably, AT responded more sensitively to salinity stress than RT. Stress increased topological parameters in the biotic network of AT subcommunities while decreasing values in RT subcommunities, concurrently loosening interactions of AT with other taxa and strengthening interactions of RT with others in biotic networks. RT generally exhibited greater diversity of metal resistance genes compared to AT. Greater numbers of genes related to salinity tolerance was observed for the RT than for AT. Compared to AT, RT demonstrated higher diversity of metal resistance genes and a greater abundance of genes associated with salinity tolerance. Additionally, deterministic processes governed AT community assembly, reinforced by salinity stress. However, the opposite trend was observed in the RT, where the importance of stochastic process gradually increased with metal stresses. The study is centered on exploring the adaptation strategies of both AT and RT to environmental stress. It underscores the importance of future research incorporating diverse ecosystems and a range of environmental stressors to draw broader and more reliable conclusions. This comprehensive approach is essential for gaining a thorough understanding of the adaptive mechanisms employed by these microorganisms.

Direct immobilization of Se(IV) from acidic Se(IV)-rich wastewater via ferric selenite Co-precipitation.

The attenuation of acidic Se(IV)-rich wastewater, including those associated with acid mine drainage (AMD) and nonferrous metallurgical wastewater (NMW), presents a serious environmental challenge. This study investigates the effects of diverse factors from pH values to Se(IV)/Fe(III) molar ratios, initial Se(IV) concentrations, and alkali neutralization agents on the direct co-precipitation of ferric selenites in AMD and NMW systems involving different orders of Fe(III) and alkali addition. Our results show that amorphous sulfate-substituted ferric (hydrogen) selenite and Se(IV)-bearing ferrihydrite-schwertmannite are the major Se(IV)-attenuation solids except that gypsum is an additional phase in the NMW system with Ca(OH)2 neutralization. Produced ferric selenites achieve 98-99.8% of Se(IV) immobilization under optimal conditions of pH 4.5, Se(IV)/Fe(III) molar ratios of 0.0625-0.5, and initial Se(IV) concentrations of 0.15-1.3 mmol·L-1. Moreover, completing FeSO4+ and FeHSeO32+/FeSeO3+ complexes as well as different ferric selenite co-precipitates are shown to collectively control aqueous Se(IV) remaining. Specifically, three distinct trends of aqueous Se(IV) concentrations separately correspond to changes in the four factors. The co-precipitation in the NMW system via pH adjustment followed by Fe(III) addition is more efficient for Se(IV) fixation than that in the AMD system because of minimal complexation, concurrent Fe(III) hydrolysis, and enhanced ferric selenite co-precipitation in the former.

AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Synergistic anti-tumour activity of ginsenoside Rg3 and doxorubicin on proliferation, metastasis and angiogenesis in osteosarcoma by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways.

OBJECTIVES: The most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism. METHODS: The potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated. KEY FINDINGS: Our study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice. CONCLUSIONS: Consequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.

Enhancement of arsenic uptake and accumulation in green microalga Chlamydomonas reinhardtii through heterologous expression of the phosphate transporter DsPht1.

Arsenate (AsV) is a predominant arsenic contaminant in aerobic water. Microalgae have been recently used in the phytoremediation of arsenic-contaminated water. However, the amount of AsV uptake in microalgae is limited, which hinders the application of microalgae in arsenic-contaminated water treatment. Here, we found that the expression of a novel phosphate transporter DsPht1 in Dunaliella salina was highly upregulated after AsV exposure. Fluorescent protein-tagging analysis showed the plasma membrane location of DsPht1. Furthermore, DsPht1 was overexpressed in a model microalga Chlamydomonas reinhardtii. The DsPht1 transgenetic lines accumulated up to 6.4-fold higher total arsenic than the untransformed line, and the AsV amount in total arsenic increased by 8.3-fold. Moreover, the organoarsenic content was also higher in the transgenetic lines. Overall, the DsPht1 transformants generated in this study increased arsenate uptake and transformation, which are promising for the effective phytoremediation of arsenic-contaminated water.

Diversity, functional potential, and assembly of bacterial communities in metal(loid)-contaminated sediments from a coastal industrial basin.

A comprehensive understanding of ecological processes related to bacterial communities in these ecosystems is critical for improving the sustainability of estuarine-coastal ecosystem functions. However, the community composition, functional potential, and assembly mechanisms of bacterial community in metal(loid)-contaminated estuarine-coastal habitats remain poorly understood, especially along lotic systems extending from rivers to estuaries and to bays. Here, we collected sediment samples associated with sewage outlets from rivers (upstream/midstream of sewage outlet), estuaries (sewage outlets), and Jinzhou Bay (downstream of sewage outlets) within Liaoning Province, China in order to evaluate the relationships between microbiome and metal(loid) contamination. Sewage discharge markedly increased the concentrations of metal(loid)s in sediments, including of As, Fe, Co, Pb, Cd, and Zn. Significant discrepancies in alpha diversity and community composition were observed among the sampling sites. The above dynamics were primarily caused by salinity and metal(loid) concentrations (i.e., of As, Zn, Cd, and Pb). Furthermore, metal(loid) stress significantly increased abundances of metal(loid)-resistant genes, but decreased abundances of denitrification genes. Dechloromonas, Hydrogenophaga, Thiobacillus, and Leptothrix were denitrifying bacteria present within sediments of this estuarine-coastal ecosystem. Moreover, the stochastic processes dominated the community assembly in estuary offshore sites, while deterministic processes dominated river community assembly mechanisms. Salinity and total nitrogen concentration, rather than metal(loid) concentrations, governed the assembly processes in these sites. Overall, these elucidate mechanisms involved in constructing community diversities, functional potential, and assembly.

Rare earth elements in oysters and mussels collected from the Chinese coast: Bioaccumulation and human health risks.

Rare earth elements (REEs) are increasingly used in various industries worldwide, resulting in their release into aquatic ecosystems. We evaluated the distribution and bioaccumulation of 14 REEs in marine sediments and biotas along the Chinese coasts. The total concentration of REEs (ΣREEs) in sediments was 41.65-170.94 mg/kg. The concentrations of ΣREEs were 1.97-4.77 and 0.62-4.96 mg/kg dry mass (DM) for oysters and mussels. The concentration of total light REEs (ΣLREEs) was higher than the concentration of total heavy REEs (ΣHREEs) at all samples. The bioaccumulation factor (BAF) of ΣLREEs was higher than ΣHREEs and BAF of ΣREE was 0.34-1.49 and 0.25-1.10 for oysters and mussels. The positive correlation between sediments and biotas was higher in mussels than oysters, showing a good potential for being environmental indicators for REEs. The risk of REEs to humans via oysters and mussels consumption could be negligible based on the estimated daily intake.

Influence of DOM and its subfractions on the mobilization of heavy metals in rhizosphere soil solution.

Long-term industrial pollution, wastewater irrigation, and fertilizer application are known factors that can contribute to the contamination of heavy metals (HMs) in agricultural soil. In addition, dissolved organic matter (DOM) plays key roles in the migration and fate of HMs in soil. This study investigated the effects of amending exogenous DOM extracted from chicken manure (DOMc), humus soil (DOMs), rice husk (DOMr), and its sub-fractions on the mobilization and bio-uptake of Cd, Zn, and Pb. The results suggested that the exogenous DOM facilitate the dissolution of HMs in rhizosphere soil, and the maximum solubility of Zn, Cd, and Pb were 1264.5, 121.3, and 215.7 µg L-1, respectively. Moreover, the proportion of Zn-DOM and Cd-DOM increased as the DOM concentration increased, and the highest proportions were 97.5% and 86.9%. However, the proportion of Pb-DOM was stable at > 99% in all treatments. In addition, the proportion of hydrophilic acid (Hy) and Pb/Cd in the rhizosphere soil solution were 17.5% and 8.3%, respectively. This finding suggested that the Hy-metals complex has a vital influence on the mobilization of metals, besides its complexation with fulvic acid and humic acid. Furthermore, the elevated DOM addition contributed to an increment of HMs uptake by Sedum alfredii, in the following order, DOMc > DOMs > DOMr. This study can provide valuable insights to enhance the development of phytoremediation technologies and farmland manipulation. Since the risk that exogenous DOM would increase the uptake of HMs by crops, it is also needed to evaluate this case from an agricultural management perspective.

Oxidation and incorporation of adsorbed antimonite during iron(II)-catalyzed recrystallization of ferrihydrite.

The toxicity and mobility of antimony (Sb) are strongly influenced by the redox transformation of widely spread 2-line ferrihydrite (Fh) in natural soils and sediments. This study investigated the transformation and redistribution of adsorbed antimonite (Sb(III)) during Fe(II)-catalyzed recrystallization of Fh under anaerobic conditions. X-ray diffraction (XRD), transmission electron microscopy (TEM), and synchrotron based X-ray absorption spectroscopy (XAS) were utilized to characterize the mineralogy and morphology of generated minerals as well as the speciation of Sb and Fe. Chemical analysis and Sb LIII-edge XANES spectra demonstrated that a great part of Sb(III) (80%-90%) was oxidized to Sb(V) by reactive oxygen species (ROS) during the Fe(II)-catalyzed transformation of Fh. Chemical extraction results showed that the mobility of Sb was significantly reduced with 50%-70% of initially adsorbed Sb(III) transformed to phosphate-unextractable phase. Antimony K-edge EXAFS analysis showed the SbO6 octahedra were incorporated into secondary minerals by substituting the Fe atoms. Our findings shed new light on the understanding of the geochemical behavior of Sb(III) under anoxic conditions.

Contamination of pyrethroids in agricultural soils from the Yangtze River Delta, China.

This study focused on contamination levels and spatial distributions of four common pyrethroids found in agricultural soils of the Yangtze River Delta (YRD), China. Pyrethroids were detected in 241 soil samples (88.8% detection rate) with total concentrations ranging from  cypermethrin (1.10 ng/g) > deltamethrin (0.89 ng/g) > cyhalothrin (0.20 ng/g). The highest concentration of fenpropathrin was recorded as 37.6 ng/g. The highest detection rate of 63.9% was found for cyhalothrin. A distinct pattern of spatial distribution was observed where high concentrations of pyrethroids were detected in sites around Taihu Lake. Potential sources of pyrethroids in agricultural soils from the YRD region include pyrethroids used for pest control and wastewater irrigation in the region. Redundancy and correlation analyses show that the soil TOC values have played a significant role in the behavior of pyrethroids in agricultural soils of the YRD region. Potential ecological risks of pyrethroids in agricultural soils of the YRD region are low. Cypermethrin and cyhalothrin showed potential toxic effects on the ecological conditions of agricultural soils in 4.6% and 2.9% of the sampling sites, respectively. Further studies should pay more attention to the potential human health risks posed by pyrethroids in agricultural soils for the protection of soil quality and food safety.

Identification of cofilin-1 as a novel mediator for the metastatic potentials and chemoresistance of the prostate cancer cells.

Prostate cancer (PCa) is the most common malignancy among men. Tumor metastasis and chemoresistance contribute to the major cause of the mortality. In this study, we compared the protein profiles of two prostate cancer cell lines with different metastatic potentials, and identified cofilin-1 (CFL1) was one of the most differentially expressed proteins between two cell lines. Further results suggested that cofilin-1 promoted the remodeling of F-actin cytoskeleton, and enhanced the proliferation, migration and invasion of the prostate cancer cells via activation of P38 MAPK signaling pathway. In addition, cofilin-1 elevated the expression and drug efflux activity of multidrug resistance protein 1 (MDR1) by P38 MAPK signaling pathway, resulting in decrease of the adriamycin-induced apoptosis as well as the lytic cell death, and the subsequent resistance against adriamycin. Collectively, cofilin-1 might serve as a novel target candidate for both inhibiting the metastasis and reversing the chemoresistance of PCa.

FGF9 inhibition by a novel binding peptide has efficacy in gastric and bladder cancer per se and reverses resistance to cisplatin.

Aberrant over-expressions of FGF9 in gastric cancer (GC) and its high-affinity receptor FGFR3c in bladder cancer (BC) provide possibilities for the treatment of GC and BC via targeting FGF9. In this study, we isolated a novel FGF9-binding peptide (P4) by screening a phage display random heptapeptide library. Sequence comparison showed that P4 shared high homology with the conserved motif in the immunoglobulin-like (Ig-like) domain II∼III (D2-D3) linker of the FGF9 high-affinity receptor (FGFR3c). The interaction between P4 and FGF9 was confirmed by the surface plasmon resonance (SPR) assay. Functional analysis indicated that P4 counteracted FGF9-induced aggressive phenotype, including cell proliferation, migration, and invasion in vitro, as well as suppressed tumor growth in vivovia down-regulation of the MAPKs and Akt cascades. More importantly, we found that FGF9 served as an underlying mechanism of the chemoresistance in GC and BC cells, and P4 could increase the sensitivity to the chemical agent via antagonizing the suppression effects of FGF9 on cell apoptosis. Taken together, our study identified a novel binding peptide for FGF9, which may serve as a potential therapeutic agent for malignant tumors featured by abnormally up-regulation of FGF9.