Prognostic value of left ventricular global longitudinal strain on speckle echocardiography for predicting chemotherapy-induced cardiotoxicity in breast cancer patients: A systematic review and meta-analysis.

BACKGROUND: Literature suggests that left ventricular global longitudinal strain (LV-GLS) on speckle echocardiography has the potential to predict cardiotoxicity amongst breast cancer patients receiving chemotherapy such as anthracycline, taxane, cyclophosphamide, and trastuzumab. Our study aimed to collect evidence for the prognostic value of LV-GLS for predicting chemotherapy-induced cardiotoxicity in breast cancer patients. METHODS: A detailed search of the PubMed, Google Scholar, Cochrane Library, and Scopus databases was conducted for published articles up to August 31, 2022. In our meta-analysis, we looked at 13 studies with a total of 1007 breast cancer patients getting chemotherapy that looked at the predictive value of GLS. RESULTS: Absolute GLS change during treatment showed a pooled sensitivity of 84% (95% CI 74% to 91%) and a pooled specificity of 77% (95% CI 68% to 84%).  For a relative change in GLS, we observed a pooled sensitivity of 76% (95% CI 56% to 89%) and a pooled specificity of 83% (95% CI 73% to 90%).  For an absolute change in GLS, we observed a positive likelihood ratio (LR), and the negative LR was 4 and .21. Summary receiver operating characteristics curve with prediction and confidence intervals represents a promising summary area under the curve (sAUC) of .88, 95% CI ranges from .85 to .91 for absolute change in GLS, as well as for relative change (sAUC, .87, 95% CI .84 to .90). CONCLUSION: Our results demonstrated an estimation of LV-GLS after the beginning of required chemotherapy, including anthracyclines and trastuzumab, had a promising prognostic value for predicting the likelihood of cancer therapeutics-related cardiac dysfunction. To confirm our findings, well-designed prospective adequately powered diagnostic randomised trials are necessary.

Engineering active heterojunction architecture with oxygenated-Co, Mo bimetallic sulfide heteronanosheet and graphene oxide for peroxymonosulfate activation.

Bimetallic sulfides have distinctive catalytic property in activating peroxymonosulfate (PMS) for water remediation. Polyoxometalates as potential precursors have rarely been reported for the catalytic degradation of refractory organic pollutants. Herein, a composite catalyst of Co-Mo bimetallic sulfides supported onto graphene oxide (O-CoMoS/GO) with a heterojunction architecture was synthesized through a hydrothermal strategy with polyoxometalates ((NH4)4[CoIIMo6O24H6]·6H2O) as the precursor and applied in the PMS activation. This material showed a superior performance for the catalytic degradation of the model organic pollutant, 4-chlorophenol (rapidly removed within 10 min with an apparent reaction rate constant of 0.5458 min-1). O-CoMoS/GO outperformed most of the reported catalysts in terms of activity and had a strong tolerance towards common organic and inorganic compounds in water, and could perform well in different real water systems. Experimental and theoretical results indicated that the introduction of GO could achieve the enrichment of electrons on the metals and reduce the d band center (εd) of Co close to the Fermi level (εF), thereby facilitating the interfacial electron transfer process. The activation mechanism was due to the as-prepared bimetallic sulfides and the formation of heterojunction structure with GO, where Co(II) as the active center could be regenerated by the adjacent Mo element (as co-catalyst) and by gathering electrons from GO through the Co/Mo-O-C coupling. This work provides insights into the design of bimetallic sulfide catalysts in activating PMS for water remediation.

Doped Graphene To Mimic the Bacterial NADH Oxidase for One-Step NAD+ Supplementation in Mammals.

Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD+, are closely associated with numerous diseases. While supplementing cells with precursors needed for NAD+ synthesis has shown poor efficacy in combatting NAD+ decline, an alternative strategy is the development of synthetic materials that catalyze the oxidation of NADH into NAD+, thereby taking over the natural role of the NADH oxidase (NOX) present in bacteria. Herein, we discovered that metal-nitrogen-doped graphene (MNGR) materials can catalyze the oxidation of NADH into NAD+. Among MNGR materials with different transition metals, Fe-, Co-, and Cu-NGR displayed strong catalytic activity combined with >80% conversion of NADH into NAD+, similar specificity to NOX for abstracting hydrogen from the pyridine ring of nicotinamide, and higher selectivity than 51 other nanomaterials. The NOX-like activity of FeNGR functioned well in diverse cell lines. As a proof of concept of the in vivo application, we showed that FeNGR could specifically target the liver and remedy the metabolic flux anomaly in obesity mice with NAD+-deficient cells. Overall, our study provides a distinct insight for exploration of drug candidates by design of synthetic materials to mimic the functions of unique enzymes (e.g., NOX) in bacteria.

Inhibition of transcription of VP2 by mutations in the DNA binding domains of mink enteritis virus NS1 protein.

The NS1 protein of mink enteritis virus (MEV) is a multidomain and multifunctional protein that plays a critical role in viral replication, with predicted nuclease, helicase and transactivation activities. The nuclease and helicase domains of NS1 protein are involved in interaction with viral DNA. Herein, potential amino acids critical for DNA binding in the MEV NS1 were mutated, all of which resulted in a termination of viral production from an infectious MEV clone. Although E121, H129/131, Y212 and K470/472 mutants retained their P38 and 5'UTR transactivation activity, K196/197 and K406 mutations eliminated this. Interestingly, VP2 protein was produced following transfection of F81 cells with pMEV-NS1-196K2G (K196G and K197G) and pMEV-NS1-K406G when pNS1 was co-transfected in trans, indicating that the substitutions did not affect the integrity of the DNA sequence that bound to NS1 protein but inhibited the biological properties of NS1 protein itself. The ability of NS1 protein to interact with SP1 was inhibited by both 196K2G and K406G substitutions, while 196K2G resulted in failure to bind to the DNA-binding sites in the P38 promoter, and the oligomerization of K406G was inhibited. All of these could explain the transcriptional repression.

Structure and function of the parvoviral NS1 protein: a review.

Parvoviruses possess a single-stranded DNA genome of about 5 kb, which contains two open reading frames (ORFs), one encoding nonstructural (NS) proteins, the other capsid proteins. The NS1 protein contains an N-terminal origin-binding domain, a helicase domain, and a C-terminal transactive domain, and is essential for effective viral replication and production of infectious virus. We first summarize the developments in the structure of NS1 protein, including the original binding domain and the helicase domain. We discuss the role of different DNA substrates in the oligomerization of these two domains of NS1. During the parvovirus life cycle, the NS1 protein is closely related to the viral gene expression, viral replication, and infection. We provide the current understanding of the impact of parvovirus NS1 protein mutations on its biological properties. Overall, in this review, we focus on the structure and function of the parvoviral NS1 protein.

Transcriptional activation of Mink enteritis virus VP2 by the C-terminal of its NS1 protein.

Mink enteritis virus (MEV) NS1 is a multidomain and multifunctional protein containing origin binding, helicase, and transactivation domains. In particular, parvoviral NS1 proteins are transactivators of the viral capsid protein promoter although the manner by which they exert these transactivation effects remained unclear. In this study, the region of the transactivation domain of the NS1 C-terminal was found located at aa 557 ~ 668 and any deletion within this region reduced the transactivation activity. A dominant negative mutation of the 63 aa deletion in the C-terminal of NS1 protein resulted in loss of ability to activate P38 and VP2-5'UTR in a dual-luciferase reporter assay system, a VP2 protein expression system, and within the whole MEV genome, independent of downstream genes. Additionally, a full-length MEV clone deficient in its NS1 C-terminal failed to rescue the virus, possibly due to the loss of integrity of DNA sequences interacting with NS1 protein, and expression of VP2 was also inhibited even when normal NS1 protein was supplied in trans.

Kynurenic acid ameliorates NLRP3 inflammasome activation by blocking calcium mobilization via GPR35.

The inflammasome has been linked to diverse inflammatory and metabolic diseases, and tight control of inflammasome activation is necessary to avoid excessive inflammation. Kynurenic acid (KA) is a tryptophan metabolite in the kynurenine pathway. However, the roles and mechanisms of the regulation of inflammasome activation by KA have not yet been fully elucidated. Here, we found that KA suppressed caspase-1 activation and IL-1ß production in macrophages by specifically inhibiting canonical and noncanonical activation of the NLRP3 inflammasome. Mechanistically, KA reduced calcium mobilization through G-protein receptor 35 (GPR35), resulting in reduced mitochondrial damage and decreased mtROS production, thus blocking NLRP3 inflammasome assembly and activation. Importantly, KA prevented lipopolysaccharide-induced systemic inflammation, monosodium urate-induced peritoneal inflammation, and high-fat diet-induced metabolic disorder. Thus, KA ameliorated inflammation and metabolic disorders by blocking calcium mobilization-mediated NLRP3 inflammasome activation via GPR35. Our data reveal a novel mechanism for KA in the modulation of inflammasome activation and suggest that GPR35 might be a promising target for improving NLRP3 inflammasome-associated diseases by regulating calcium mobilization.

Acute and Subchronic Oral Toxicity of Anthraquinone in Sprague Dawley Rats.

OBJECTIVE: This study was conducted to evaluate the acute and subchronic toxicity of anthraquinone. An acute toxicity test was performed in female Sprague Dawley (SD) rats, and the oral median lethal dose (LD50) of anthraquinone was estimated to be >5000 mg/kg body weight (BW). In the subchronic study, groups of 10 male and 10 female rats were dosed with anthraquinone by gavage at 0, 1.36, 5.44, 21.76, and 174.08 mg/kg BW, 7 days/week for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 1.36 mg/kg BW group. When the animals received 5.44 mg/kg BW or more of anthraquinone, hyaline droplet accumulation in the renal tubules was observed in both the male and female rats, and anemia was observed in the females. When the anthraquinone dose reached 174.08 mg/kg BW, mild hepatocellular hypertrophy around the central vein of the hepatic lobule and hypothyroidism were observed in the female rats. During the recovery period, changes in clinical symptoms and parameters were considerably alleviated. Based on the results of this study, the no observed adverse effect level (NOAEL) for anthraquinone in rats was set at 1.36 mg/kg BW, and the lowest observed adverse effect level (LOAEL) was 5.44 mg/kg BW.

Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments.

While hypoxia promotes carcinogenesis, tumour aggressiveness, metastasis, and resistance to oncological treatments, the impacts of hyperoxia on tumours are rarely explored because providing a long-lasting oxygen supply in vivo is a major challenge. Herein, we construct micro oxygen factories, namely, photosynthesis microcapsules (PMCs), by encapsulation of acquired cyanobacteria and upconversion nanoparticles in alginate microcapsules. This system enables a long-lasting oxygen supply through the conversion of external radiation into red-wavelength emissions for photosynthesis in cyanobacteria. PMC treatment suppresses the NF-kB pathway, HIF-1α production and cancer cell proliferation. Hyperoxic microenvironment created by an in vivo PMC implant inhibits hepatocarcinoma growth and metastasis and has synergistic effects together with anti-PD-1 in breast cancer. The engineering oxygen factories offer potential for tumour biology studies in hyperoxic microenvironments and inspire the exploration of oncological treatments.

Antibiotic-Like Activity of Atomic Layer Boron Nitride for Combating Resistant Bacteria.

The global rise of antimicrobial resistance (AMR) that increasingly invalidates conventional antibiotics has become a huge threat to human health. Although nanosized antibacterial agents have been extensively explored, they cannot sufficiently discriminate between microbes and mammals, which necessitates the exploration of other antibiotic-like candidates for clinical uses. Herein, two-dimensional boron nitride (BN) nanosheets are reported to exhibit antibiotic-like activity to AMR bacteria. Interestingly, BN nanosheets had AMR-independent antibacterial activity without triggering secondary resistance in long-term use and displayed excellent biocompatibility in mammals. They could target key surface proteins (e.g., FtsP, EnvC, TolB) in cell division, resulting in impairment of Z-ring constriction for inhibition of bacteria growth. Notably, BN nanosheets had potent antibacterial effects in a lung infection model by P. aeruginosa (AMR), displaying a 2-fold increment of survival rate. Overall, these results suggested that BN nanosheets could be a promising nano-antibiotic to combat resistant bacteria and prevent AMR evolution.

Nano-enabled photosynthesis in tumours to activate lipid peroxidation for overcoming cancer resistances.

Apoptosis dysregulation is an important mechanism responsible for the intrinsic and acquired resistance of melanoma, which necessitates the exploration of oncological treatments to activate nonapoptotic cell death. Herein, we developed nano-enabled photosynthesis in tumours to activate lipid peroxidation and ferroptosis to overcome melanoma resistance. Controlled photosynthesis was conducted in tumours to construct a hyperoxic microenvironment with photosynthetic microcapsules (PMCs), which were prepared by encapsulating cyanobacteria and upconversion nanoparticles in alginate microcapsules and driven by external near infrared photons. The combination of PMCs and X-rays evoked lipid peroxidation, Fe2+ release, glutathione peroxidase 4 suppression, glutathione reduction and ferroptosis in melanoma cells and xenografts. Consequently, the intrinsic and acquired resistance in melanoma could be overcome by the combined treatment, which further inhibited tumour metastases and improved the survival rate of melanoma-bearing mice. Overall, the development of nano-enabled photosynthesis in tumours will inspire the exploration of oncological treatments.

Seasonal variation of transport pathways and potential source areas at high inorganic nitrogen wet deposition sites in southern China.

This study attempts to identify the dominant transport pathways, potential source areas, and their seasonal variation at sites with high inorganic nitrogen (IN) wet deposition flux in southern China. This is a long-term study (2010-2017) based on continuous deposition measurements at the Guangzhou urban site (GZ) and the Dinghushan Natural Reserve site (DHS) located in the Pearl River Delta (PRD) region. A dataset on monthly IN concentration in precipitation and wet deposition flux were provided. The average annual fluxes measured at both sites (GZ: 33.04±9.52, DHS: 20.52±10.22 kg N/(ha∙year)) were higher, while the ratios of reduced to oxidized N (GZ: 1.19±0.77, DHS: 1.25±0.84) were lower compared with the national mean level and the previous reported level throughout the PRD region. The dominant pathways were not always consistent with the highest proportional trajectory clusters. The transport pathways contributing most of deposition were identified in the north and north-northeast in the dry season and in the east-southeast, east, and south-southwest in the wet season. A weighted potential source contribution function (WPSCF) value >0.3 was determined reasonably to define the potential source area. Emission within the PRD region contributed the majority (≥95% at both sites) of the IN deposition in the wet season, while the contribution outside the region increased significantly in the dry season (GZ: 27.86%, DHS: 95.26%). Our results could help create more effective policy to control precursor emissions for IN fluxes, enabling reduction of the ecological risks due to excessive nitrogen.

Induction of COX-2 by feline calicivirus via activation of the MEK1-ERK1/2 pathway, and attenuation of feline lung inflammation and injury by MEK1 inhibitor AZD6244 (selumetinib).

Feline calicivirus (FCV) is an important and highly prevalent pathogen of cats that causes acute infectious respiratory disease. Here it is shown in vitro that FCV induces the production of cyclooxygenase-2 (COX-2) through the MEK1-ERK1/2 signaling pathway. Screening of FCV proteins revealed that FCV non-structural protein VPg enhanced COX-2 mRNA expression and protein production in CRFK cells in a concentration-dependent manner. Regions 24-54aa and 84-111aa in FCV VPg were essential for up-regulation. In vivo, COX-2 and IL-6 production caused by FCV infection of kittens was significantly suppressed by the MEK1 inhibitor AZD6244 (selumetinib) and lung inflammation and injury were practically eliminated, with body temperature being returned to normal. AZD6244 may therefore find application as an effective therapeutic agent for the treatment of FCV infection.

Characterization of the key aroma compounds in aged Chinese Xiaoqu Baijiu by means of the sensomics approach.

The aromatic characteristics of Xiaoqu Baijiu differ noticeably and were investigated using the sensomics approach. Aroma extract dilution analysis revealed more aroma-active compounds in aged Xiaoqu Baijiu than fresh Xiaoqu Baijiu, with 55 compounds identified with flavor dilution (FD) factors of ≥8. Using sensomics, 51 odorants were identified as important aroma compounds in aged Xiaoqu Baijiu. Omission models suggested that 3-hydroxy-4,5-dimethyl-2(5H)-furanone (sotolon), vanillin, and 3-(methylthio)propionaldehyde (methional) played critical roles in the overall aroma characteristics of aged Xiaoqu Baijiu. Furthermore, 1,1-dimethoxyethane, 3-methylbutanal, dimethyl trisulfide, ethyl acetate, and ethyl isovalerate also exhibited significant roles in the aroma characteristics of aged Xiaoqu Baijiu. This work may provide a better understanding on Chinese Xiaoqu Baijiu and the changes of aroma compounds during the aging process of liquor.

A comparative study on the physicochemical properties, reactivity and long-term performance of sulfidized nanoscale zerovalent iron synthesized with different kinds of sulfur precursors and procedures in simulated groundwater.

There are plentiful ways to synthesize sulfidized nanoscale zerovalent iron (S-nZVI), and this study investigated the influence of sulfur reagents (Na2S, Na2S2O3, Na2S2O4) and sulfidation sequence (co-sulfidation and post-sulfidation method) on the physicochemical properties, reactivity, and long-term performance of S-nZVI in simulated groundwater. The results suggested that the co-sulfidized nZVI (S-nZVIco) has higher reactivity (∼2-fold) than S-nZVIpost due to the stronger electron transfer capacity, deriving from the higher content of Fe0 and reductive sulfur species. However, during aging, the reactivity of S-nZVIco would be lost more rapidly than S-nZVIpost, due to the faster corrosion of Fe0 and more oxidation of reductive sulfur species. S-nZVIpost has the superior long-term performance with the degradation rate of trichloroethylene (TCE) remained at 30%∼60% even after 90 d of aging. Sulfur precursors can control the selectivity of S-nZVI by affecting the sulfur speciation on the particle surface. The proportion of reductive sulfur species on S-nZVIpost synthesized by Na2S was higher than S-nZVIpost synthesized by Na2S2O3 or Na2S2O4, resulting in a higher selectivity of the former S-nZVIpost than the latter S-nZVIpost. In addition, sulfidation procedures and sulfur precursors did not affect the degradation pathway of TCE. Nevertheless, the degradation product distribution can be affected by the different physicochemical transformation of various types of S-nZVI with the aging time. These results indicated that sulfur reagents and sulfidation procedures have crucial effects on the reactivity and long-term performance of S-nZVI, which can be designed for the specific application scenarios.

Mesoporous ferrihydrite-supported Pd nanoparticles for enhanced catalytic dehalogenation of chlorinated environmental pollutant.

Organic chlorides are a group of ubiquitous environmental pollutants that have attracted wide attention because of their carcinogenetic effect on human. Catalytic hydrodechlorination represents one of the most promising methods for the removal of these contaminants, but it suffers from drawbacks such as catalytic inefficiency and/or instability, and the danger of using H2 as hydrogen source. The relationship between the catalyst structure and its dehalogenation activity has not been completely understood. By combining the advantages of Pd nanocatalyst and mesoporous ferrihydrite (Fh) with its distinctive structure, here we present a new composite material with Pd nanoparticles (NPs) supported onto the Fh (Pd/Fh), which has excellent catalytic dehalogenation performance with a rapid, complete dechlorination of chlorophenol (turnover frequency 25.2 min-1) and the ability to perform well over a wide range of pH and temperature. The superior catalytic property of Pd/Fh can be attributed to the three unique functions of Fh, including: 1) having abundant hydroxyl groups that provide interaction sites with metals for incorporating highly dispersed small Pd NPs; 2) facilitating the fast adsorption of chlorophenol onto the catalyst surface via hydrogen bonding and importantly, 3) working as an electron mediator to greatly enhance the electron transfer from iron or chemicals (e.g., NaBH4) to the catalyst, thereby achieving a synergistic effect between Pd catalyst and support, and an enhanced dechlorination activity. In essence, this work presents a promising catalyst for the efficient dehalogenation of chlorinated environmental pollutants and provides an insight into the relationship between catalyst structure and dehalogenation activity.

Lower uric acid level may be associated with hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND: Previous studies have shown that uric acid (UA) is a powerful water-soluble antioxidant and free radical scavenger for humans. However, the relationship between serum uric acid (SUA) and hemorrhagic transformation (HT) is still controversial. To address this challenge, we aimed to explore the association between serum UA and HT in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: A retrospective analysis was conducted in patients with anterior circulation AIS who underwent IVT at Affiliated Hospital of Qingdao University from 2016 to 2021. HT was evaluated by CT or MRI within 7 days after admission. Baseline demographic, clinical, and laboratory data were compared between the HT and non-HT groups, and between different types of HT groups which were documented according to the European Cooperative Acute Stroke Study III Classification (ECASS III). RESULTS: A total of 727 AIS patients were enrolled, including 112 patients who experienced HT (HT group) and 615 patients who did not experience HT (non-HT group). Patients with HT had significantly lower UA levels compared to those without HT (253.65 ± 97.75 vs 315.97 ± 96.42, p < 0.001); however, there was no significant difference for UA levels in different types of HT (p = 0.907). After adjusting confounders, patients in the fourth UA quartile showed a significant decrease in HT compared with those in the first quartile (OR 0.266, 95% CI 0.107-0.661, p = 0.006). The best cutoff value was identified as 218.5 µmol/L after analysis. CONCLUSIONS: These findings suggest that low levels of UA may be associated with HT after IVT.

Influence of several crucial groundwater components on the toxicity of nanoscale zero-valent iron towards Escherichia coli under aerobic and anaerobic conditions.

In this paper, the effects of several groundwater components (heavy metals, inorganic anions, and organics) on the cytotoxicity of nanoscale zero-valent iron (NZVI) towards Escherichia coli (E. coli) under aerobic/anaerobic conditions were studied. The results showed that NZVI exhibited much higher toxicity in anaerobic conditions than aerobic conditions. Under the state of air-saturation, corrosion of NZVI occurred rapidly, at the same time, it could stably and continuously generate Fe (Ⅱ) and trigger reactive oxygen species (ROS), which led to oxidative stress in E. coli. While in the deareated state, the TEM images showed that the integrity of the cell membrane was destroyed, which validated that the main mechanism of NZVI cytotoxicity was the rapid membrane damage of E. coli. The presence of Cr (Ⅵ) reduced the toxicity of NZVI through oxidation-reduction with NZVI, especially under anaerobic conditions. In contrast, the presence of Cd (Ⅱ) could be adsorbed onto NZVI to increase the cytotoxicity of NZVI. The presence of phosphate and humic acid greatly improved the survival rate of E. coli through the complex reaction with Fe (Ⅱ), especially under aerobic conditions. On the one hand, the formed Fe (II)-phosphate/humic acid complex could reduce the production of ROS. On the other hand, the complex accumulated on the outer surface of E. coli cells could provide steric hindrance to impede the contact between NZVI and cell. These findings were crucial for practical significance to evaluate environmental risk during the groundwater remediation process by using NZVI.

Biotransformation of rare earth oxide nanoparticles eliciting microbiota imbalance.

BACKGROUND: Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. RESULTS: This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G-) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G- and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G- cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G-/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G-/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. CONCLUSIONS: This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G- and G+ bacteria and disclosed that La2O3-induced membrane damages of G- cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.

Nanoparticle-induced ferroptosis: detection methods, mechanisms and applications.

Although ferroptosis is an iron-dependent cell death mechanism involved in the development of some severe diseases (e.g., Parkinsonian syndrome, stroke and tumours), the combination of nanotechnology with ferroptosis for the treatment of these diseases has attracted substantial research interest. However, it is challenging to differentiate nanoparticle-induced ferroptosis from other types of cell deaths (e.g., apoptosis, pyroptosis, and necrosis), elucidate the detailed mechanisms and identify the key property of nanoparticles responsible for ferroptotic cell deaths. Therefore, a summary of these aspects from current research on nano-ferroptosis is important and timely. In this review, we endeavour to summarize some convincing techniques that can be employed to specifically examine ferroptotic cell deaths. Then, we discuss the molecular initiating events of nanosized ferroptosis inducers and the cascade signals in cells, and therefore elaborate the ferroptosis mechanisms. Besides, the key physicochemical properties of nano-inducers are also discussed to acquire a fundamental understanding of nano-structure-activity relationships (nano-SARs) involved in ferroptosis, which may facilitate the design of nanomaterials to deliberately tune ferroptosis. Finally, future perspectives on the fundamental understanding of nanoparticle-induced ferroptosis and its applications are provided.