N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Distinct effects of canopy vs understory and organic vs inorganic N deposition on root resource acquisition strategies of subtropical Moso bamboo plants.

Atmospheric nitrogen (N) deposition inevitably alters soil nutrient status, subsequently prompting plants to modify their root morphology (i.e., adopting a do-it-yourself strategy), mycorrhizal symbioses (i.e., outsourcing strategy), and root exudation (i.e., nutrient-mining strategy) linking with resource acquisition. However, how N deposition influences the integrated pattern of these resource-acquisition strategies remains unclear. Furthermore, most studies in forest ecosystems have focused on understory N and inorganic N deposition, neglecting canopy-associated processes (e.g., N interception and assimilation) and the impacts of organic N on root functional traits. In this study, we compared the effects of canopy vs understory, organic vs inorganic N deposition on eight root functional traits of Moso bamboo plants. Our results showed that N deposition significantly decreased arbuscular mycorrhizal fungi (AMF) colonization, altered root exudation rate and root foraging traits (branching intensity, specific root area, and length), but did not influence root tissue density and N concentration. Moreover, the impacts of N deposition on root functional traits varied significantly with deposition approach (canopy vs. understory), form (organic vs. inorganic), and their interaction, showing variations in both intensity and direction (positive/negative). Furthermore, specific root area and length were positively correlated with AMF colonization under canopy N deposition and root exudation rate in understory N deposition. Root trait variation under understory N deposition, but not under canopy N deposition, was classified into the collaboration gradient and the conservation gradient. These findings imply that coordination of nutrient-acquisition strategies dependent on N deposition approach. Overall, this study provides a holistic understanding of the impacts of N deposition on root resource-acquisition strategies. Our results indicate that the evaluation of N deposition on fine roots in forest ecosystems might be biased if N is added understory.

Effects of arsenic on the transport and attachment of microplastics in porous media.

Understanding the impact of arsenic (As(III), inorganic pollutant widely present in natural environments) on microplastics (MPs, one type of emerging contaminants) mobility is essential to predict MPs fate and distribution in soil-groundwater systems, yet relevant research is lacking. This study explored the effects of As(III) copresent in suspensions (0.05, 0.5, and 5 mg/L) on MPs transport/attachment behaviors in porous media containing varied water contents (θ = 100 %, 90 %, and 60 %) under different ionic strengths (5, 10, and 50 mM NaCl) and flow rates (2, 4, and 8 m/day). Despite solution ionic strengths, flow rates, porous media water contents, sizes, and surface charges of MPs, with coexisting humic acid, and in actual water samples, As(III) of three concentrations increased MPs transport in quartz sand and natural sandy soil. The increased electrostatic repulsion between MPs and sand caused by the altered MPs surface charge via the adsorption of As(III) together with steric repulsion from As(III) in solution contributed to the promoted MPs mobility in porous media. The occupying attachment sites by As(III) partially contributed to the increased mobility of MPs with negative surface charge in porous media. Clearly, As(III) coexisting in suspensions would enhance MPs transport in porous media, increasing MPs environment risks.

Soil Geobacteraceae are the key predictors of neurotoxic methylmercury bioaccumulation in rice.

Contamination of rice by the potent neurotoxin methylmercury (MeHg) originates from microbe-mediated Hg methylation in soils. However, the high diversity of Hg methylating microorganisms in soils hinders the prediction of MeHg formation and challenges the mitigation of MeHg bioaccumulation via regulating soil microbiomes. Here we explored the roles of various cropland microbial communities in MeHg formation in the potentials leading to MeHg accumulation in rice and reveal that Geobacteraceae are the key predictors of MeHg bioaccumulation in paddy soil systems. We characterized Hg methylating microorganisms from 67 cropland ecosystems across 3,600 latitudinal kilometres. The simulations of a rice-paddy biogeochemical model show that MeHg accumulation in rice is 1.3-1.7-fold more sensitive to changes in the relative abundance of Geobacteraceae compared to Hg input, which is recognized as the primary parameter in controlling MeHg exposure. These findings open up a window to predict MeHg formation and accumulation in human food webs, enabling more efficient mitigation of risks to human health through regulations of key soil microbiomes.

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

Background: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Results: Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-ß (PDGFR-ß) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-ß (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-ß expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions: The high expression of α-SMA, PDPN, PDGFR-ß in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Community assembly and microbial interactions in an alkaline vanadium tailing pond.

Intensive development of vanadium-titanium mines leads to an increasing discharge of vanadium (V) into the environment, imposing potential risks to both environmental system and public health. Microorganisms play a key role in the biogeochemical cycling of V, influencing its transformation and distribution. In addition, the characterization of microbial community patterns serves to assess potential threats imposed by elevated V exposure. However, the impact of V on microbial community remains largely unknown in alkaline V tailing areas with a substantial amounts of V accumulation and nutrient-poor conditions. This study aims to explore the characteristics of microbial community in a wet tailing pond nearby a large-scale V mine. The results reveal V contamination in both water (0.60 mg/L) and sediment tailings (340 mg/kg) in the tailing pond. Microbial community diversity shows distinctive pattern between environmental metrices. Genera with the functional potential of metal reduction\resistance, nitrogen metabolism, and carbon fixation have been identified. In this alkaline V tailing pond, V and pH are major drivers to induce community variation, particularly for functional bacteria. Stochastic processes primarily govern the assemblies of microbial community in the water samples, while deterministic process regulate the community assemblies of sediment tailings. Moreover, the co-occurrence network pattern unveils strong selective pattern for sediment tailings communities, where genera form a complex network structure exhibiting strong competition for limited resource. These findings reveal the patterns of microbial adaptions in wet vanadium tailing ponds, providing insightful guidelines to mitigate the negative impact of V tailing and develop sustainable management for mine-waste reservoir.

Pyrrhotite-dependent microbial reduction and magnetic separation for efficient vanadium detoxification and recovery in contaminated aquifer.

Microbial reduction under anaerobic condition is a promising method for remediating vanadate [V(V)] contamination in aquifers, while V(V) may be re-generated with redox fluctuations. The inability to remove vanadium after remediation has become a key issue limiting bioremediation. In this study, we proposed the use of pyrrhotite, a natural mineral with magnetic properties, to immobilize V(V) to insoluble V(IV) under microbial action and remove vanadium from the aquifer using a magnetic field, which could avoid the problem of V(V) recontamination under redox fluctuating conditions. Up to 49.0 ± 4.7 % of vanadium could be removed from the aquifer by the applied magnetic field, and the vanadium in the aquifer after the reaction was mainly in the acid-extractable and reducible states. pH had a strong effect on the magnetic recovery of V(V), while the influence of initial V(V) concentration was weak. Microbial community structure analysis showed that Thiobacillus, Proteiniphilum, Fermentimonas, and Desulfurivibrio played key roles for V(V) reduction and pyrrhotite oxidation. Structural equation model indicated the positive correlation between these genera with the magnetic recovery of vanadium. Real time-qPCR confirmed the roles of functional genes of V(V) reduction (napA and nirK) and SO42- reduction (dsrA) in such biological processes. This study provides a novel route to sustainable V(V) remediation in aquifers, with synchronous recovery of vanadium resources without rebound.

Deciphering Vanadium Speciation in Smelting Ash and Adaptive Responses of Soil Microorganisms.

Abundant smelting ash is discharged during pyrometallurgical vanadium (V) production. However, its associated V speciation and resultant ecological impact have remained elusive. In this study, V speciation in smelting ash and its influence on the metabolism of soil microorganisms were investigated. Smelting ashes from V smelters contained abundant V (19.6-115.9 mg/g). V(V) was the dominant species for soluble V, while solid V primarily existed in bioavailable forms. Previously unrevealed V nanoparticles (V-NPs) were prevalently detected, with a peak concentration of 1.3 × 1013 particles/g, a minimal size of 136.0 ± 0.6 nm, and primary constituents comprising FeVO4, VO2, and V2O5. Incubation experiments implied that smelting ash reshaped the soil microbial community. Metagenomic binning, gene transcription, and component quantification revealed that Microbacterium sp. and Tabrizicola sp. secreted extracellular polymeric substances through epsB and yhxB gene regulation for V-NPs aggregation to alleviate toxicity under aerobic operations. The V K-edge X-ray absorption near-edge structure (XANES) spectra suggested that VO2 NPs were oxidized to V2O5 NPs. In the anaerobic case, Comamonas sp. and Achromobacter sp. reduced V(V) to V(IV) for detoxification regulated by the napA gene. This study provides a deep understanding of the V speciation in smelting ash and microbial responses, inspiring promising bioremediation strategies to reduce its negative environmental impacts.

Therapeutic strategies targeting the NLRP3­mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review).

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Enhanced Thermal Conductivity of High-Density Polyethylene Composites with Hybrid Fillers of Flaky and Spherical Boron Nitride Particles.

The synergistic effect between different fillers plays a crucial role in determining the performance of composites. In this work, spherical boron nitride (BN) and flaky BN are used as hybrid fillers to improve the thermal conductivity (TC) of high-density polyethylene (HDPE) composites. A series of HDPE composites were prepared by adjusting the mass ratio (1:0, 4:1, 2:1, 1:1, 1:2, 1:4, and 0:1) of spherical BN and flaky BN. The SEM results indicate that the spherical BN (with a particle size of 3 µm) effectively filled the gaps between the flaky BN (with a particle size of 30 µm), leading to the formation of more continuous heat conduction paths with the composite. Remarkably, when the mass ratio of spherical BN to flaky BN was set to 1:4 (with a total BN filling amount of 30 wt%), the TC of the composite could reach up to 1.648 Wm-1K-1, which is obviously higher than that of the composite containing a single filler, realizing the synergistic effect of the hybrid fillers. In addition, the synergistic effect of fillers also affects the thermal stability and crystallization behavior of composites. This work is of great significance for optimizing the application of hybrid BN fillers in the field of thermal management.

Construction of Fluorescent G-Quadruplex Nanowires for Label-Free and Accurate Monitoring of Circular RNAs in Breast Cancer Cells and Tissues with Low Background.

Circular RNAs (circRNAs) represent an emerging category of endogenous transcripts characterized by long half-life time, covalently closed structures, and cell-/tissue-specific expression patterns, making them potential disease biomarkers. Herein, we demonstrate the construction of fluorescent G-quadruplex nanowires for label-free and accurate monitoring of circular RNAs in breast cancer cells and tissues by integrating proximity ligation-rolling circle amplification cascade with lighting up G-quadruplex. The presence of target circRNA facilitates the SplintR ligase-mediated ligation of the padlock probe. Upon the addition of primers, the ligated padlock probe can serve as a template to initiate subsequent rolling circle amplification (RCA), generating numerous long G-quadruplex nanowires that can incorporate with thioflavin T (ThT) to generate a remarkably improved fluorescence signal. Benefiting from good specificity of SplintR ligase-mediated ligation reaction and exponential amplification efficiency of RCA, this strategy can sensitively detect target circRNA with a limit of detection of 4.65 × 10-18 M. Furthermore, this method can accurately measure cellular circRNA expression with single-cell sensitivity and discriminate the circRNA expression between healthy para-carcinoma tissues and breast cancer tissues, holding great potential in studying the pathological roles of circRNA and clinic diagnostics.

Elucidating Multiple Electron-Transfer Pathways for Metavanadate Bioreduction by Actinomycetic Streptomyces microflavus.

While microbial reduction has gained widespread recognition for efficiently remediating environments polluted by toxic metavanadate [V(V)], the pool of identified V(V)-reducing strains remains rather limited, with the vast majority belonging to bacteria and fungi. This study is among the first to confirm the V(V) reduction capability of Streptomyces microflavus, a representative member of ubiquitous actinomycetes in environment. A V(V) removal efficiency of 91.0 ± 4.35% was achieved during 12 days of operation, with a maximum specific growth rate of 0.073 d-1. V(V) was bioreduced to insoluble V(IV) precipitates. V(V) reduction took place both intracellularly and extracellularly. Electron transfer was enhanced during V(V) bioreduction with increased electron transporters. The electron-transfer pathways were revealed through transcriptomic, proteomic, and metabolomic analyses. Electrons might flow either through the respiratory chain to reduce intracellular V(V) or to cytochrome c on the outer membrane for extracellular V(V) reduction. Soluble riboflavin and quinone also possibly mediated extracellular V(V) reduction. Glutathione might deliver electrons for intracellular V(V) reduction. Bioaugmentation of the aquifer sediment with S. microflavus accelerated V(V) reduction. The strain could successfully colonize the sediment and foster positive correlations with indigenous microorganisms. This study offers new microbial resources for V(V) bioremediation and improve the understanding of the involved molecular mechanisms.

RNA methylation-driven assembly of fluorescence-encoded nanostructures for sensitive detection of m6A modification writer METTL3/14 complex in human breast tissues.

N6-methyladenosine (m6A) is an ubiquitous post-transcriptional modification catalyzed by METTL3/14 complex in eukaryotic mRNAs. The abnormal METTL3/14 complex activity affects multiple steps of RNA metabolism and may induce various diseases. Herein, we demonstrate the RNA methylation-driven assembly of fluorescence-encoded nanostructures for sensitive detection of m6A modification writer METTL3/14 complex in human breast tissues. METTL3/14 complex can catalyze the methylation of RNA probe to prevent it from being cleaved by MazF. The intact RNA probe is recognized by the magnetic bead (MB)-capture probe conjugates to induce duplex-specific nuclease (DSN)-assisted cyclic digestion, exposing numerous shorter ssDNAs with 3'-OH end. The shorter ssDNAs on the MB surface can act as the primers to initiate terminal deoxynucleotidyl transferase (TdT)-enhanced tyramide signal amplification (TSA), forming the Cy5 fluorescence-encoded nanostructures. After magnetic separation, the Cy5 fluorescence-encoded nanostructures are digested by DNase I to release abundant Cy5 fluorophores that can be simply quantified by fluorescence measurement. This assay achieves good specificity and high sensitivity with a detection limit of 58.8 aM, and it can screen METTL3/14 complex inhibitors and quantify METTL3/14 complex activity at the single-cell level. Furthermore, this assay can differentiate the METTL3/14 complex level in breast cancer patient tissues and healthy volunteer tissues.

Vanadium in the Environment: Biogeochemistry and Bioremediation.

Vanadium(V) is a highly toxic multivalent, redox-sensitive element. It is widely distributed in the environment and employed in various industrial applications. Interactions between V and (micro)organisms have recently garnered considerable attention. This Review discusses the biogeochemical cycling of V and its corresponding bioremediation strategies. Anthropogenic activities have resulted in elevated environmental V concentrations compared to natural emissions. The global distributions of V in the atmosphere, soils, water bodies, and sediments are outlined here, with notable prevalence in Europe. Soluble V(V) predominantly exists in the environment and exhibits high mobility and chemical reactivity. The transport of V within environmental media and across food chains is also discussed. Microbially mediated V transformation is evaluated to shed light on the primary mechanisms underlying microbial V(V) reduction, namely electron transfer and enzymatic catalysis. Additionally, this Review highlights bioremediation strategies by exploring their geochemical influences and technical implementation methods. The identified knowledge gaps include the particulate speciation of V and its associated environmental behaviors as well as the biogeochemical processes of V in marine environments. Finally, challenges for future research are reported, including the screening of V hyperaccumulators and V(V)-reducing microbes and field tests for bioremediation approaches.

Integration of a copper-based metal-organic framework with an ionic liquid for electrochemically discriminating cysteine enantiomers.

The identification of cysteine enantiomers is of great significance in the biopharmaceutical industry and medical diagnostics. Herein, we develop an electrochemical sensor to discriminate cysteine (Cys) enantiomers based on the integration of a copper metal-organic framework (Cu-MOF) with an ionic liquid. Because the combine energy of D-cysteine (D-Cys) with Cu-MOF (-9.905 eV) is lower than that of L-cysteine (L-Cys) with Cu-MOF (-9.694 eV), the decrease in the peak current of the Cu-MOF/GCE induced by D-Cys is slightly higher than that induced by L-Cys in the absence of an ionic liquid. In contrast, the combine energy of L-Cys with an ionic liquid (-1.084 eV) is lower than that of D-Cys with an ionic liquid (-1.052 eV), and the ionic liquid is easier to cross-link with L-Cys than with D-Cys. When an ionic liquid is present, the decrease in the peak current of the Cu-MOF/GCE induced by D-Cys is much higher than that induced by L-Cys. Consequently, this electrochemical sensor can efficiently discriminate D-Cys from L-Cys, and it can sensitively detect D-Cys with a detection limit of 0.38 nM. Moreover, this electrochemical sensor exhibits good selectivity, and it can accurately measure the spiked D-Cys in human serum with a recovery ratio of 100.2-102.6%, with wide applications in biomedical research and drug discovery.

Development of a chiral electrochemical sensor based on copper-amino acid mercaptide nanorods for enantioselective discrimination of tryptophan enantiomers.

Chirality is an important property of nature and it regulates fundamental phenomena in nature and organisms. Here, we develop a chiral electrochemical sensor based on copper-amino acid mercaptide nanorods (L-CuCys NRs) to discriminate tryptophan (Trp) isomers. The chiral L-CuCys NRs are prepared in alkaline solution based on the facile coordination reaction between the sulfhydryl groups of L-Cys and copper ions. Since the stability constant (K) of L-CuCys NRs with L-Trp (752) are much higher than that of L-CuCys NRs with D-Trp (242), the cross-linking bonds between L-CuCys NRs and L-Trp are more stable than those between L-CuCys NRs and D-Trp. Consequently, this electrochemical sensor can selectively recognize the Trp isomers with an enantiomeric electrochemical difference ratio (IL-Trp/ID-Trp) of 3.22, and it exhibits a detection limit of 0.26 µM for L-Trp. Moreover, this electrochemical sensor can quantitatively measure Trp isomers in complex samples. Importantly, this electrochemical sensor has the characteristics of high stability, good repeatability, easy fabrication, low cost, and efficient discrimination of tryptophan (Trp) isomers.

Tumor-derived exosomal miR-148b-3p mediates M2 macrophage polarization via TSC2/mTORC1 to promote breast cancer migration and invasion.

BACKGROUND: Emerging evidence has revealed that tumor-associated macrophages (TAMs) and exosomes play a crucial role in the microenvironment for tumor growth. However, the mechanisms through which exosomal miRNAs modulate TAMs and tumor development in breast cancer are not fully understood. METHODS: We constructed a macrophage model and an indirect coculture system consist of breast cancer cells and macrophages. Exosomes were isolated from BC cells culture supernatant and identified by transmission electron microscopy, Western blot and Nanosight LM10 system. The expression of miR-148b-3p in exosomes was determined by qRT-PCR and the effect of exosomal miR-148b-3p on macrophage polarization was measured using qRT-PCR and ELISA. The proliferation, migration and invasion of BC cells were estimated by EdU, wound healing assay and transwell assay. We employed bioinformatics, luciferase reporter assay and Western blot to identify the target gene of miR-148b-3p. Western blot was used to clarify the mechanism of exosomal miR-148b-3p mediated the crosstalk between BC cells and M2 macrophages. RESULTS: Cancer-derived exosomes could induce M2 polarization of macrophages, which promoted the migration and invasion of breast cancer cells. We found that exosomal miR-148b-3p was overexpressed in breast cancer cell-derived exosomes and correlated with lymph node metastasis, late tumor stage and worse prognosis. Upregulated miR-148b-3p expression in exosomes modulated macrophage polarization by targeting TSC2, which promoted the proliferation and might affect migration and invasion of breast cancer cells. Interestingly, we found that exosomal miR-148b-3p could induce M2 macrophage polarization via the TSC2/mTORC1 signaling pathway in breast cancer. CONCLUSION: Overall, our study elucidated that miR-148b-3p could be transported by exosomes from breast cancer cells to surrounding macrophages and induced M2 polarization by targeting TSC2, providing novel insights for breast cancer therapy.

Coupling of selenate reduction and pyrrhotite oxidation by indigenous microbial consortium in natural aquifer.

Pyrrhotite is ubiquitously found in natural environment and involved in diverse (bio)processes. However, the pyrrhotite-driven bioreduction of toxic selenate [Se(VI)] remains largely unknown. This study demonstrates that Se(VI) is successfully bioreduced under anaerobic condition with the participation of pyrrhotite for the first time. Completely removal of Se(VI) was achieved at initial concentration of 10 mg/L Se(VI) and 0.56 mL/min flow rate in continuous column experiment with indigenous microbial consortium and pyrrhotite. Variation in hydrochemistry and hydrodynamics affected Se(VI) removal performance. Se(VI) was reduced to insoluble Se(0) while elements in pyrrhotite were oxidized to Fe(III) and SO42-. Breakthrough study indicated that biotic activity contributed 81.4 ± 1.07% to Se(VI) transformation. Microbial community analysis suggested that chemoautotrophic genera (e.g., Thiobacillus) could realize pyrrhotite oxidation and Se(VI) reduction independently, while heterotrophic genera (e.g., Bacillus, Pseudomonas) contributed to Se(VI) detoxification by utilizing metabolic intermediates generated through Fe(II) and S(-II) oxidation, which were further verified by pure culture tests. Metagenomic and qPCR analyses indicated genes encoding enzymes for Se(VI) reduction (e.g., serA, napA and srdBAC), S oxidation (e.g., soxB) and Fe oxidation (e.g., mtrA) were upregulated. The elevated electron transporters (e.g., nicotinamide adenine dinucleotide, cytochrome c) promoted electron transfer from pyrrhotite to Se(VI). This study gains insights into Se biogeochemistry under the effect of Fe(II)-bearing minerals and provides a sustainable strategy for Se(VI) bioremediation in natural aquifer.

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin-Induced Resistance and Stemness in Human Lung Cancer A549 Cells.

The survival rate of lung cancer patients remains low largely due to chemotherapy resistance during treatment, and cancer stem cells (CSCs) may hold the key to targeting this resistance. Cisplatin is a chemotherapy drug commonly used in cancer treatment, yet the mechanisms of intrinsic cisplatin resistance have not yet been determined because lung CSCs are hard to identify. In this paper, we proposed a mechanism relating to the function of ursolic acid (UA), a new drug, in reversing the cisplatin resistance of lung cancer cells regulated by CSCs. Human lung cancer cell line A549 was selected as the model cell and treated to become a cisplatin-resistant lung cancer cell line (A549-CisR), which was less sensitive to cisplatin and showed an enhanced capability of tumor sphere formation. Furthermore, in the A549-CisR cell line expression, levels of pluripotent stem cell transcription factors Oct-4, Sox-2, and c-Myc were increased, and activation of the Jak2/Stat3 signaling pathway was promoted. When UA was applied to the cisplatin-resistant cells, levels of the pluripotent stem cell transcription factors were restrained by the inhibition of the Jak2/Stat3 signaling pathway, which reduced the enrichment of tumor stem cells, and in turn, reversed cisplatin resistance in lung cancer cells. Hence, as a potential antitumor drug, UA may be able to inhibit the enrichment of the lung CSC population by inhibiting the activation of the Jak2-Stat3 pathway and preventing the resistance of lung cancer cells to cisplatin.