Heavy metals immobilization and bioavailability in multi-metal contaminated soil under ryegrass cultivation as affected by ZnO and MnO2 nanoparticle-modified biochar.

Pollution by heavy metals (HMs) has become a global problem for agriculture and the environment. In this study, the effects of pristine biochar and biochar modified with manganese dioxide (BC@MnO2) and zinc oxide (BC@ZnO) nanoparticles on the immobilization and bioavailability of Pb, Cd, Zn, and Ni in soil under ryegrass (Lolium perenne L.) cultivation were investigated. The results of SEM-EDX, FTIR, and XRD showed that ZnO and MnO2 nanoparticles were successfully loaded onto biochar. The results showed that BC, BC@MnO2 and BC@ZnO treatments significantly increased shoots and roots dry weight of ryegrass compared to the control. The maximum dry weight of root and shoot (1.365 g pot-1 and 4.163 g pot-1, respectively) was reached at 1% BC@MnO2. The HMs uptake by ryegrass roots and shoots decreased significantly after addition of amendments. The lowest Pb, Cd, Zn and Ni uptake in the plant shoot (13.176, 24.92, 32.407, and 53.88 µg pot-1, respectively) was obtained in the 1% BC@MnO2 treatment. Modified biochar was more successful in reducing HMs uptake by ryegrass and improving plant growth than pristine biochar and can therefore be used as an efficient and cost effective amendment for the remediation of HMs contaminated soils. The lowest HMs translocation (TF) and bioconcentration factors were related to the 1% BC@MnO2 treatment. Therefore, BC@MnO2 was the most successful treatment for HMs immobilization in soil. Also, a comparison of the TF values of plant showed that ryegrass had a good ability to accumulate all studied HMs in its roots, and it is a suitable plant for HMs phytostabilization.

[Transcriptional analysis of the molecular response of Arabidopsis to manganese stress and recovery].

Manganese (Mn) is an essential element for plants and plays a role in various metabolic processes. However, excess manganese can be toxic to plants. This study aimed to analyze the changes in various physiological activities and the transcriptome of Arabidopsis under different treatments: 1 mmol/L MnCl2 treatment for 1 day or 3 days, and 1 day of recovery on MS medium after 3 days of MnCl2 treatment. During the recovery phase, minor yellowing symptoms appeared on the leaves of Arabidopsis, and the content of chlorophyll and carotenoid decreased significantly, but the content of malondialdehyde and soluble sugar increased rapidly. Transcriptome sequencing data shows that the expression patterns of differentially expressed genes exhibit three major models: initial response model, later response model, recovery response model. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis identified several affected metabolic pathways, including plant hormone signal transduction mitosolysis activates protein kinase (MAPK) phytohormone signaling, phenylpropanoid biosynthesis, ATP binding cassette transporters (ABC transporter), and glycosphingolipid biosynthesis. Differential expressed genes (DEGs) involved in phenylpropanoid biosynthesis, ABC transporter, and glycosphingolipid biosynthesis, were identified. Sixteen randomly selected DEGs were validated through qRT-PCR and showed consistent results with RNA-seq data. Our findings suggest that the phenylpropanoid metabolic pathway is activated to scavenge reactive oxygen species, the regulation of ABC transporter improves Mn transport, and the adjustment of cell membrane lipid composition occurs through glycerophospholipid metabolism to adapt to Mn stress in plants. This study provides new insights into the molecular response of plants to Mn stress and recovery, as well as theoretical cues for cultivating Mn-resistant plant varieties.

Characteristic and mechanism of biological nitrogen and phosphorus removal facilitated by biogenic manganese oxides (BioMnOx) at various concentrations of Mn(II).

Biogenic manganese oxides (BioMnOx) have attracted considerable attention as active oxidants, adsorbents, and catalysts. However, characteristics and mechanisms of nitrification-denitrification in biological redox reactions mediated by different concentrations of BioMnOx are still unclear. Fate of nutrients (e.g., NH4+-N, TP, NO3--N) and COD were investigated through different concentrations of BioMnOx produced by Mn(II) in the moving bed biofilm reactor (MBBR). 34% and 89.2%, 37.8% and 89.8%, 57.3% and 88.9%, and 62.1% and 90.4% of TN and COD by MBBR were synchronously removed in four phases, respectively. The result suggested that Mn(II) significantly improved the performance of simultaneous nitrification and denitrification (SND) and TP removal based on manganese (Mn) redox cycling. Characteristics of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and electron transfer system activity (ETSA) were discussed, demonstrating that ROS accumulation reduced the ETSA and GSH-Px activities when Mn(II) concentration increased. Extracellular polymeric substance (EPS) function and metabolic pathway of Mn(II) were explored. Furthermore, effect of cellular components on denitrification was evaluated including BioMnOx performances, indicating that Mn(II) promoted the non-enzymatic action of cell fragments. Finally, mechanism of nitrification and denitrification, denitrifying phosphorus and Mn removal was further elucidated through X-ray photoelectron spectroscopy (XPS), high throughput sequencing, and fourier transform infrared reflection (FTIR). This results can bringing new vision for controlling nutrient pollution in redox process of Mn(II).

Can xenobiotics support the growth of Mn(II)-oxidizing bacteria (MnOB)? A case of phenol-utilizing bacteria Pseudomonas sp. AN-1.

Biogenic manganese oxides (BioMnOx) produced by Mn(II)-oxidizing bacteria (MnOB) have garnered considerable attention for their exceptional adsorption and oxidation capabilities. However, previous studies have predominantly focused on the role of BioMnOx, neglecting substantial investigation into MnOB themselves. Meanwhile, whether the xenobiotics could support the growth of MnOB as the sole carbon source remains uncertain. In this study, we isolated a strain termed Pseudomonas sp. AN-1, capable of utilizing phenol as the sole carbon source. The degradation of phenol took precedence over the accumulation of BioMnOx. In the presence of 100 mg L-1 phenol and 100 µM Mn(II), phenol was entirely degraded within 20 h, while Mn(II) was completely oxidized within 30 h. However, at the higher phenol concentration (500 mg L-1), phenol degradation reduced to 32% and Mn(II) oxidation did not appear to occur. TOC determination confirmed the ability of strain AN-1 to mineralize phenol. Based on the genomic and proteomics studies, the Mn(II) oxidation and phenol mineralization mechanism of strain AN-1 was further confirmed. Proteome analysis revealed down-regulation of proteins associated with Mn(II) oxidation, including MnxG and McoA, with increasing phenol concentration. Notably, this study observed for the first time that the expression of Mn(II) oxidation proteins is modulated by the concentration of carbon sources. This work provides new insight into the interaction between xenobiotics and MnOB, thus revealing the complexity of biogeochemical cycles of Mn and C.

MnO2 nanoparticles trigger hepatic lipotoxicity and mitophagy via mtROS-dependent Hsf1Ser326 phosphorylation.

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO2 NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism. Here, we investigated whether and how dietary MnO2 NPs affect hepatic lipid metabolism in vertebrates. We found that, excessive MnO2 NPs intake increased hepatic and mitochondrial Mn content, promoted hepatic lipotoxic disease and lipogenesis, and inhibited hepatic lipolysis and fatty acid ß-oxidation. Moreover, excessive MnO2 NPs intake induced hepatic mitochondrial oxidative stress, damaged mitochondrial function, disrupted mitochondrial dynamics and activated mitophagy. Importantly, we uncovered that mtROS-activated phosphorylation of heat shock factor 1 (Hsf1) at Ser326 residue mediated MnO2 NPs-induced hepatic lipotoxic disease and mitophagy. Mechanistically, MnO2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced phosphorylation and nucleus translocation of Hsf1 and its DNA binding capacity to plin2/dgat1 and bnip3 promoters, respectively. Overall, our findings uncover novel mechanisms by which mtROS-mediated mitochondrial dysfunction and phosphorylation of Hsf1S326 contribute to MnO2 NPs-induced hepatic lipotoxicity and mitophagy, which provide new insights into the effects of metal oxides nanoparticles on hepatotoxicity in vertebrates.

Simultaneous antibiotic removal and mitigation of resistance induction by manganese bio-oxidation process.

Microbial degradation to remove residual antibiotics in wastewater is of growing interest. However, biological treatment of antibiotics may cause resistance dissemination by mutations and horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). In this study, a Mn(Ⅱ)-oxidizing bacterium (MnOB), Pseudomonas aeruginosa MQ2, simultaneously degraded antibiotics, decreased HGT, and mitigated antibiotic resistance mutation. Intracellular Mn(II) levels increased during manganese oxidation, and biogenic manganese oxides (BioMnOx, including Mn(II), Mn(III) and Mn(IV)) tightly coated the cell surface. Mn(II) bio-oxidation mitigated antibiotic resistance acquisition from an E. coli ARG donor and mitigated antibiotic resistance inducement by decreasing conjugative transfer and mutation, respectively. BioMnOx also oxidized ciprofloxacin (1 mg/L) and tetracycline (5 mg/L), respectively removing 93% and 96% within 24 h. Transcriptomic analysis revealed that two new multicopper oxidase and one peroxidase genes are involved in Mn(II) oxidation. Downregulation of SOS response, multidrug resistance and type Ⅳ secretion system related genes explained that Mn(II) and BioMnOx decreased HGT and mitigated resistance mutation by alleviating oxidative stress, which makes recipient cells more vulnerable to ARG acquisition and mutation. A manganese bio-oxidation based reactor was constructed and completely removed tetracycline with environmental concentration within 4-hour hydraulic retention time. Overall, this study suggests that Mn (II) bio-oxidation process could be exploited to control antibiotic contamination and mitigate resistance propagation during water treatment.

Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics.

Manganese (Mn), a nutrient inorganic trace element, is necessary for a variety of physiological processes of animal body due to their important roles in oxidative regulation effects and other aspects of activities. Moreover, manganese ion (Mn2+) has widely reported to be crucial for the regulations of different immunological responses, thus showing promising application as potential adjuvants and immunotherapeutics. Taking the advantages of Mn-based biological and immunological activities, Manganese dioxide nanoparticles (MnO2 NPs) are a new type of inorganic nanomaterials with numerous advantages, including simple preparation, low cost, environmental friendliness, low toxicity, biodegradable metabolism and high bioavailability. MnO2 NPs, as a kind of drug carrier, have also shown the ability to catalyze hydrogen peroxide (H2O2) to produce oxygen (O2) under acidic conditions, which can enhance the efficacy of radiotherapy, chemotherapy and other therapeutics for tumor treatment by remodeling the tumor microenvironment. More importantly, MnO2 NPs also play important roles in immune regulations both in innate and adaptive immunity. In this review, we summarize the biological activities of Manganese, followed by the introduction for the biological and medical functions and mechanisms of MnO2 NPs. What's more, we emphatically discussed the immunological regulation effects and mechanisms of MnO2 NPs, as well as their potentials to serve as adjuvants and immunomodulators, which might benefit the development of novel vaccines and immunotherapies for more effective disease control.

Detoxification and metabolism of glyphosate by a Pseudomonas sp. via biogenic manganese oxidation.

Biogenic manganese oxides (BMO) are widely distributed in groundwater and provides promise for adsorbing and oxidizing a wide range of micropollutants, however, the continuous biodegradation and bioavailability of micropollutants via cycle biogenic Mn(II) oxidation remains to be elucidated. In this study, glyphosate was degraded and to serve as the nutrient source by a Pseudomonas sp. QJX-1. The addition of glyphosate will not affect the Mn(II) oxidation function of the strain but will affect its Mn(II) oxidation process and effect. The glyphosate degradation products could further be used as the C, N and P sources for bacterium growth. Analysis of the RNA-seq data suggested that Mn(II) oxidation driven by oxidoreductases for glyphosate degradation. The long-term column experiments using biological Mn(II) cycling to realize continuous detoxification and metabolism of glyphosate, and thus revealed the synergism effects of biological and chemical conversion on toxic micropollutants and continuous metabolism in an aquatic ecosystem.

Electrochemical Nanosensors for Sensitization of Sweat Metabolites: From Concept Mapping to Personalized Health Monitoring.

Sweat contains a broad range of important biomarkers, which may be beneficial for acquiring non-invasive biochemical information on human health status. Therefore, highly selective and sensitive electrochemical nanosensors for the non-invasive detection of sweat metabolites have turned into a flourishing contender in the frontier of disease diagnosis. A large surface area, excellent electrocatalytic behavior and conductive properties make nanomaterials promising sensor materials for target-specific detection. Carbon-based nanomaterials (e.g., CNT, carbon quantum dots, and graphene), noble metals (e.g., Au and Pt), and metal oxide nanomaterials (e.g., ZnO, MnO2, and NiO) are widely used for modifying the working electrodes of electrochemical sensors, which may then be further functionalized with requisite enzymes for targeted detection. In the present review, recent developments (2018-2022) of electrochemical nanosensors by both enzymatic as well as non-enzymatic sensors for the effectual detection of sweat metabolites (e.g., glucose, ascorbic acid, lactate, urea/uric acid, ethanol and drug metabolites) have been comprehensively reviewed. Along with this, electrochemical sensing principles, including potentiometry, amperometry, CV, DPV, SWV and EIS have been briefly presented in the present review for a conceptual understanding of the sensing mechanisms. The detection thresholds (in the range of mM-nM), sensitivities, linear dynamic ranges and sensing modalities have also been properly addressed for a systematic understanding of the judicious design of more effective sensors. One step ahead, in the present review, current trends of flexible wearable electrochemical sensors in the form of eyeglasses, tattoos, gloves, patches, headbands, wrist bands, etc., have also been briefly summarized, which are beneficial for on-body in situ measurement of the targeted sweat metabolites. On-body monitoring of sweat metabolites via wireless data transmission has also been addressed. Finally, the gaps in the ongoing research endeavors, unmet challenges, outlooks and future prospects have also been discussed for the development of advanced non-invasive self-health-care-monitoring devices in the near future.

Light-independent anaerobic microbial oxidation of manganese driven by an electrosyntrophic coculture.

Anaerobic microbial manganese oxidation (AMMO) has been considered an ancient biological metabolism for Mn element cycling on Archaean Earth before the presence of oxygen. A light-dependent AMMO was recently observed under strictly anoxic conditions, providing a new proxy for the interpretation of the evolution of oxygenic photosynthesis. However, the feasibility of biotic Mn(II) oxidation in dark geological habitats that must have been abundant remains unknown. Therefore, we discovered that it would be possible to achieve AMMO in a light-independent electrosyntrophic coculture between Rhodopseudomonas palustris and Geobacter metallireducens. Transmission electron microscopy analysis revealed insoluble particle formation in the coculture with Mn(II) addition. X-ray diffraction and X-ray photoelectron spectroscopy analysis verified that these particles were a mixture of MnO2 and Mn3O4. The absence of Mn oxides in either of the monocultures indicated that the Mn(II)-oxidizing activity was induced via electrosyntrophic interactions. Radical quenching and isotopic experiments demonstrated that hydroxyl radicals (•OH) produced from H2O dissociation by R. palustris in the coculture contributed to Mn(II) oxidation. All these findings suggest a new, symbiosis-dependent and light-independent AMMO route, with potential importance to the evolution of oxygenic photosynthesis and the biogeochemical cycling of manganese on Archaean and modern Earth.

Role of intracellular energy metabolism in Mn(â ¡) removal by the novel bacterium Stenotrophomonas sp. MNB17.

Microorganism-mediated Mn(Ⅱ) removal has gained increasing attention as a valuble bioremediation approach. In this study, a novel strain Stenotrophomonas sp. MNB17 - obtained from marine sediments - was found to show Mn(Ⅱ) removal efficiencies of 98.51-99.38% within 7 days and 92.24% within 20 days at Mn(Ⅱ) concentrations of 10-40 mM and 50 mM, respectively. On day 7, 80.44% of 50 mM Mn(Ⅱ) was oxidized to Mn(Ⅲ/Ⅳ), whereas only 2.11-2.86% of 10-40 mM Mn(Ⅱ) was oxidized. This difference in the proportion of Mn-oxides suggested that the strain MNB17 could remove soluble Mn(Ⅱ) via distinct mechanisms under different Mn(Ⅱ) concentrations. At 10 mM Mn(Ⅱ), indirect mechanisms were employed by strain MNB17 to remove Mn(Ⅱ). The sufficient energy generated by increased cellular respiration led to enhanced ammonification, and MnCO3 was the main component of the Mn-precipitates (97.27%). Meanwhile, intracellular fatty acids were degraded and served as an important carbon source for respiration. At 50 mM Mn(Ⅱ), most of the soluble Mn(Ⅱ) was oxidized, and Mn-oxides dominated the Mn-precipitates (80.44%). Mn(Ⅱ) oxidation likely contributed to electrons for energy production, as the down-regulation of respiratory pathways resulted in a deficit of electron supply, which warrants futher study. The exogenous addition of tricarboxylic acid cycle substrates (malate, α-ketoglutarate, oxaloacetate, succinate, and fumarate) was found to accelerate Mn(Ⅱ) removal as MnCO3 at a concentration of 50 mM. Overall, this study reports a novel strain MNB17 with the biotechnological potential of Mn(Ⅱ) removal and elucidates the function of cellular energy metabolism during the Mn(Ⅱ) removal process. In addition, it demonstrates the potential of aerobic respiration-related substrates in accelerating the removal of high concentrations of Mn(Ⅱ) for the first time.

Mitochondria-Targeted Degradable Nanocomposite Combined with Laser and Ultrasound for Synergistic Tumor Therapies.

Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA-MnO2-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA-MnO2-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO2, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA-MnO2-IR780 was delivered to the tumor site, MnO2 was decomposed by hydrogen peroxide, producing Mn2+ and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA-MnO2-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA-MnO2-IR780 for safe and highly-efficiency synergistic therapy for cancer.

MnO2 nanoparticles as a minimalist multimode vaccine adjuvant/delivery system to regulate antigen presenting cells for tumor immunotherapy.

In the field of tumor immunotherapy, tumor vaccines have unique advantages including fewer side effects, tumor-specificity and immune memory, and hence attract more and more attention. In the development of tumor vaccines, a critical challenge lies in the exploitation of appropriate vaccine adjuvants/delivery systems that need to meet multiple requirements to achieve potent cellular immunity while simultaneously requiring single composition to simplify the clinical translation process. Among numerous materials, only manganese dioxide (MnO2) nanoparticles with rare physicochemical properties seem to meet the demanding criteria of simplicity and multifunctionality. However, the potential of MnO2 nanoparticles as vaccine adjuvants/delivery systems has not been well exploited, despite their widespread applications in the biomedical field. In this study, the mechanism and efficacy of single MnO2 nanoparticles as a minimalist multi-mode tumor vaccine adjuvant/delivery system were fully investigated by using a model antigen ovalbumin (OVA) to construct tumor vaccines OVA/MnO2. The obtained results show that MnO2 nanoparticles act as an ideal delivery system by multiple modes to deliver the antigen to the cytoplasm of dendritic cells to induce cellular immune response. Moreover, MnO2 nanoparticles also act as a superior adjuvant depot to sustainably release Mn2+ to enhance the immune response through a STING pathway in dendritic cells. Both the delivery function and the adjuvant effect of MnO2 nanoparticles contribute to improved cellular immunity and anti-tumor efficacy of tumor vaccines OVA/MnO2. From the results, MnO2 nanoparticles are found to be a promising minimalist multi-mode vaccine adjuvant/delivery system for the development of practical tumor vaccines.

Biodegradable Nanocatalyst with Self-Supplying Fenton-like Ions and H2O2 for Catalytic Cascade-Amplified Tumor Therapy.

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by in situ conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H2O2) in tumor cells severely limit their efficacy. Herein, a new strategy has been developed by loading the chemotherapy prodrug disulfiram (DSF) and coating glucose oxidase (GOD) on the surface of Cu/ZIF-8 nanospheres and finally encapsulating manganese dioxide (MnO2) nanoshells to achieve efficient DSF-based cancer chemotherapy and dual-enhanced chemodynamic therapy (CDT). In an acidic TME, the nanocatalyst can biodegrade rapidly and accelerate the release of internal active substances. The outer layer of MnO2 depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H2O2. Benefiting from the chelation reaction between the released Cu2+ and DSF, a large amount of cytotoxic CuET products is generated, and the Cu+ are concurrently released, thereby achieving efficient chemotherapy and satisfactory CDT efficacy. Furthermore, the release of Mn2+ can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.

Site 2 of the Yersinia pestis substrate-binding protein YfeA is a dynamic surface metal-binding site.

The substrate-binding protein YfeA (also known as YPO2439 or y1897) is a polyspecific metal-binding protein that is crucial for nutrient acquisition and virulence in Yersinia pestis, the causative microbe of plague. YfeA folds into a monomeric c-clamp like other substrate-binding proteins and has two metal-binding sites (sites 1 and 2). Site 2 is a bidentate surface site capable of binding Zn and Mn atoms and is a unique feature of YfeA. Occasionally, the site 2 residues of two YfeA molecules will cooperate with the histidine tag of a third YfeA molecule in coordinating the same metal and lead to metal-dependent crystallographic packing. Here, three crystal structures of YfeA are presented at 1.85, 2.05 and 2.25 Šresolution. A comparison of the structures reveals that the metal can be displaced at five different locations ranging from ∼4 to ∼16 Šaway from the canonical site 2. These observations reveal different configurations of site 2 that enable cooperative metal binding and demonstrate how site 2 is dynamic and freely available for inter-protein metal coordination.

Smart Manganese Dioxide-Based Lanthanide Nanoprobes for Triple-Negative Breast Cancer Precise Gene Synergistic Chemodynamic Therapy.

Small interfering RNA (siRNA)-based gene therapy has been widely studied as a promising treatment for malignant triple-negative breast cancer (TNBC), but efficient delivery of siRNA still remains a challenge. In this study, a smart manganese dioxide (MnO2)-based lanthanide nanoprobe therapeutic nanoplatform (ErNPs@MnO2-siS100A4-RGD) was developed for tumor imaging and precise stimuli-responsive S100A4 siRNA (siS100A4)-mediated gene therapy in synergism with chemodynamic therapy (CDT) of TNBC. ErNPs@MnO2-siS100A4-RGD has a tumor microenvironment-responsive capability attributed to the presence of MnO2, which can be degraded by glutathione (GSH) in the tumor region while releasing siRNA and generating Mn2+ to achieve precise gene therapy and a Fenton-like reaction-mediated CDT effect on TNBC. Subsequently, the lanthanide nanoprobes (ErNPs) are exposed to the second near-infrared region (NIR-II) fluorescence emission to realize the precise tumor location. Both the in vitro and in vivo results demonstrated that the smart nanoplatform possessed high siRNA delivery efficiency and GSH-responsive precise siRNA releasing ability, and compared with individual gene therapy, the GSH-depletion-enhanced CDT effect further reinforced TNBC inhibition, demonstrating excellent GSH-responsive-enhanced NIR-II precise tumor imaging therapy. These results indicate that the nanoplatform provides a crucial foundation for further research on theranostic systems of TNBC.

Manganese (II) chloride leads to dopaminergic neurotoxicity by promoting mitophagy through BNIP3-mediated oxidative stress in SH-SY5Y cells.

BACKGROUND: Manganese overexposure can induce neurotoxicity, lead to manganism and result in clinical manifestations similar to those of parkinsonism. However, the underlying molecular mechanism is still unclear. This study demonstrated that MnCl2 induces mitophagy and leads to neurotoxicity by promoting BNIP3-mediated reactive oxygen species (ROS) generation. METHODS: Human neuroblastoma SH-SY5Y cells were used throughout our experiments. Cell viability was detected by cell proliferation/toxicity test kits. Mitochondrial membrane potential was measured by flow cytometry. ROS generation was detected using a microplate reader. Protein levels were evaluated by Western blot. Transmission electron microscopy was used to evaluate mitochondrial morphology. Co-immunoprecipitation was used to verify the interaction between BNIP3 and LC3. RESULTS: MnCl2 led to loss of mitochondrial membrane potential and apoptosis of SH-SY5Y cells by enhancing expression of BNIP3 and conversion of LC3-I to LC3-II. Moreover, MnCl2 reduced expression of the mitochondrial marker protein TOMM20 and promoted interaction between BNIP3 and LC3. The results also indicated that a decrease in BNIP3 expression reduced the mitochondrial membrane potential loss, attenuated apoptosis and reduced mitochondrial autophagosome formation in SH-SY5Y cells after MnCl2 treatment. Finally, we found that manganese-induced ROS generation could be reversed by the antioxidant N-acetyl cysteine (NAC) or silencing BNIP3 expression. CONCLUSIONS: BNIP3 mediates MnCl2-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.

Fractionation of Heavy Metals in Multi-Contaminated Soil Treated with Biochar Using the Sequential Extraction Procedure.

Heavy metals (HMs) toxicity represents a global problem depending on the soil environment's geochemical forms. Biochar addition safely reduces HMs mobile forms, thus, reducing their toxicity to plants. While several studies have shown that biochar could significantly stabilize HMs in contaminated soils, the study of the relationship of soil properties to potential mechanisms still needs further clarification; hence the importance of assessing a naturally contaminated soil amended, in this case with Paulownia biochar (PB) and Bamboo biochar (BB) to fractionate Pb, Cd, Zn, and Cu using short sequential fractionation plans. The relationship of soil pH and organic matter and its effect on the redistribution of these metals were estimated. The results indicated that the acid-soluble metals decreased while the fraction bound to organic matter increased compared to untreated pots. The increase in the organic matter metal-bound was mostly at the expense of the decrease in the acid extractable and Fe/Mn bound ones. The highest application of PB increased the organically bound fraction of Pb, Cd, Zn, and Cu (62, 61, 34, and 61%, respectively), while the BB increased them (61, 49, 42, and 22%, respectively) over the control. Meanwhile, Fe/Mn oxides bound represents the large portion associated with zinc and copper. Concerning soil organic matter (SOM) and soil pH, as potential tools to reduce the risk of the target metals, a significant positive correlation was observed with acid-soluble extractable metal, while a negative correlation was obtained with organic matter-bound metal. The principal component analysis (PCA) shows that the total variance represents 89.7% for the TCPL-extractable and HMs forms and their relation to pH and SOM, which confirms the positive effect of the pH and SOM under PB and BB treatments on reducing the risk of the studied metals. The mobility and bioavailability of these metals and their geochemical forms widely varied according to pH, soil organic matter, biochar types, and application rates. As an environmentally friendly and economical material, biochar emphasizes its importance as a tool that makes the soil more suitable for safe cultivation in the short term and its long-term sustainability. This study proves that it reduces the mobility of HMs, their environmental risks and contributes to food safety. It also confirms that performing more controlled experiments, such as a pot, is a disciplined and effective way to assess the suitability of different types of biochar as soil modifications to restore HMs contaminated soil via controlling the mobilization of these minerals.

Biodegradable flower-like manganese for synergistic photothermal and photodynamic therapy applications.

A flower-like nanostructured MnO2 with near-infrared (NIR) light-triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed. Different from the reported MnO2 nanomaterials those were used in the nanomedicine field for only relieving tumor hypoxia and/or imaging, the flower-like MnO2 inherently acts as a competent agent for simultaneously enhanced photothermal and photodynamic therapy. A flower-like nanostructured MnO2 with near-infrared (NIR) light triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed.

Probing Dynamic Features of Phagosome Maturation in Macrophage using Au@MnOx @SiO2 Nanoparticles as pH-Sensitive Plasmonic Nanoprobes.

Phagosome maturation in macrophage is essential to the clearance of pathogenic materials in host defence but the dynamic features remain difficult to be measured in real time. Herein, we reported the multilayered Au@MnOx @SiO2 nanoparticle as a robust pH-sensitive plasmonic nanosensor for monitoring the dynamic acidification features over the phagosome maturation process in macrophage under darkfield microscopy. For this multilayered nanosensor, the gold nanoparticle core plays a role of signal reporter, the MnOx shell and the outmost SiO2 act as the sensing layer and the protecting layer, respectively. After subject to the acidic buffer solution, the MnOx layer in the multilayered nanoprobe could be decomposed rapidly, resulting in a remarkable spectral shift and color change under darkfield microscopy. We demonstrated this nanosensor for the investigation of single phagosome acidification dynamics by monitoring the color changes of nanoprobes after phagocytosis over time. The nanoprobes after phagocytosized in macrophage displayed a slight color change within the first hour and then cost several minutes to change from red to green in the next stage, indicating the phagosome undergoes a slow first and then fast acidification feature as well as a slow-to-fast acidification translation over the phagosome maturation process. Moreover, we validated that the slow-to-fast acidification translation was dependent on the activation of V-ATPase from the ATP depletion assay. We believed that this nanosensor is promising for studying the dynamic acidification features as well as disorders in phagosome maturation in phagocytic cells, which might provide valuable information for understanding the disease pathogenesis related to phagosome dysfunctions.