Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology.

Environmental pollutants have been recognized for their ability to induce various adverse outcomes in both the environment and human health, including inflammation, apoptosis, necrosis, pyroptosis, and autophagy. Understanding these biological mechanisms has played a crucial role in risk assessment and management efforts. However, the recent identification of ferroptosis as a form of programmed cell death has emerged as a critical mechanism underlying pollutant-induced toxicity. Numerous studies have demonstrated that fine particulates, heavy metals, and organic substances can trigger ferroptosis, which is closely intertwined with lipid, iron, and amino acid metabolism. Given the growing evidence linking ferroptosis to severe diseases such as heart failure, chronic obstructive pulmonary disease, liver injury, Parkinson's disease, Alzheimer's disease, and cancer, it is imperative to investigate the role of pollutant-induced ferroptosis. In this review, we comprehensively analyze various pollutant-induced ferroptosis pathways and intricate signaling molecules and elucidate their integration into the driving and braking axes. Furthermore, we discuss the potential hazards associated with pollutant-induced ferroptosis in various organs and four representative animal models. Finally, we provide an outlook on future research directions and strategies aimed at preventing pollutant-induced ferroptosis. By enhancing our understanding of this novel form of cell death and developing effective preventive measures, we can mitigate the adverse effects of environmental pollutants and safeguard human and environmental health.

Nano-microflora Interaction Inducing Pulmonary Inflammation by Pyroptosis.

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.

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.

Using Chicken Embryos to Identify the Key Determinants of Nanoparticles for the Crossing of Air-Blood Barriers.

Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air-blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air-blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air-blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.

d-Band Center of Rare Earth Oxides Determines Biotransformation-Induced Cell Membrane Damage.

Biotransformation of rare earth oxide (REO) nanoparticles on biological membranes may trigger a series of adverse health effects in biosystems. However, the physicochemical mechanism of the complicated biotransformation behavior remains elusive. By investigating the distinctly different biotransformation behavior of two typical REOs (Gd2O3 and CeO2) on erythrocyte membranes, we demonstrate that dephosphorylation by stripping phosphate from phospholipids correlates highly with the membrane destructive effects of REOs. Density functional theory calculations decode the decisive role of the d-band center in dephosphorylation. Furthermore, using the d-band center as an electronic descriptor, we unravel a universal structure-activity relationship of the membrane-damaging capability of 13 REOs (R2 = 0.82). The effect of ion release on dephosphorylation and physical damage to cell membranes by Gd2O3 are largely excluded. Our findings depict a clear physicochemical microscopic picture of the biotransformation of REOs on the nano-bio interface, providing a theoretical basis for safe application of REOs.

Nanoscale Zinc-Based Metal-Organic Frameworks Induce Neurotoxicity by Disturbing the Metabolism of Catecholamine Neurotransmitters.

As a group of new nanomaterials, nanoscale metal-organic frameworks (MOFs) are widely applied in the biomedical field, exerting unknown risks to the human body, especially the central nervous system. Herein, the impacts of MOF-74-Zn nanoparticles on neurological behaviors and neurotransmitter metabolism are explored in both in vivo and in vitro assays modeled by C57BL/6 mice and PC12 cells, respectively. The mice exhibit increased negative-like behaviors, as demonstrated by the observed decrease in exploring behaviors and increase in despair-like behaviors in the open field test and forced swimming test after exposure to low doses of MOF-74-Zn nanoparticles. Disorders in the catecholamine neurotransmitter metabolism may be responsible for the MOF-74-Zn-induced abnormal behaviors. Part of the reason for this is the inhibition of neurotransmitter synthesis caused by restrained neurite extension. In addition, MOF-74-Zn promotes the translocation of more calcium into the cytoplasm, accelerating the release and uptake and finally resulting in an imbalance between synthesis and catabolism. Taken together, the results from this study indicate the human toxicity risks of nanoscale low-toxicity metal-based MOFs and provide valuable insight into the rational and safe use of MOF nanomaterials.

Lead I R-wave indexes: A novel electrocardiographic criterion for distinguishing the origin of idiopathic premature ventricular contractions from the three subregions of the aortic sinus cusps.

PURPOSE: The current study was conducted to investigate the electrocardiographic (ECG) characteristics of idiopathic premature ventricular contractions (PVCs) originating from the aortic sinus cusp (ASC) and establish a novel ECG criterion to discriminate PVCs originating from the right coronary cusp (RCC), left coronary cusp (LCC), and the left and right coronary cusp junction (LRJ). METHODS: A retrospective analysis was performed on a total of 133 patients with idiopathic PVCs who underwent successful mapping and ablation. The sites of origin (SOO) were confirmed using fluoroscopy and a three-dimensional mapping system during radiofrequency catheter ablation (RFCA). Among the patients, 69 had PVCs originating from the LCC, 39 from the RCC, and 25 from the LRJ. Characteristics of surface 12­lead electrocardiograms (ECGs) recorded during PVCs were analyzed. Q-, R-, S, and R'-wave amplitudes were measured in lead I, and the lead I R-wave indexes (IRa, IRb, IRc, IRd, and IRe) were derived by employing multiplication, subtraction, sum, and division operations on these ECG measurements. Notably, IRb and IRe demonstrated usefulness as ECG indexes for discriminating PVCs originating from RCC, LCC, and LRJ in the ASC. RESULTS: The R- and S-wave amplitudes in lead I exhibited statistically significant differences among the three groups (P < 0.001 and P < 0.001, respectively). In discriminating PVCs originating from the RCC from the other two groups, IRb showed the largest area under the curve (AUC) of 0.813, as assessed by receiver operating characteristic (ROC) analysis, with a cutoff value of ≤0.5 indicating PVCs of RCC origin. The sensitivity and specificity were 80.3% and 78.7%, respectively. For discriminating PVCs arising from the LCC from those in the LRJ group, IRe exhibited the largest AUC of 0.801, with an optimal cutoff value of 0. An IRe value >0 indicated PVCs originating from the LRJ, while an IRe value ≤0 indicated PVCs originating from the LCC. The sensitivity and specificity of the IRe index were 84.0% and 70.7%, respectively. CONCLUSION: Lead I R-wave indexes provided simple and useful ECG criteria for discriminating PVCs originating from the LCC, RCC, and LRJ in the left ventricular outflow tract (LVOT).

Fluoroplast Doped by Ag2O Nanoparticles as New Repairing Non-Cytotoxic Antibacterial Coating for Meat Industry.

Foodborne infections are an important global health problem due to their high prevalence and potential for severe complications. Bacterial contamination of meat during processing at the enterprise can be a source of foodborne infections. Polymeric coatings with antibacterial properties can be applied to prevent bacterial contamination. A composite coating based on fluoroplast and Ag2O NPs can serve as such a coating. In present study, we, for the first time, created a composite coating based on fluoroplast and Ag2O NPs. Using laser ablation in water, we obtained spherical Ag2O NPs with an average size of 45 nm and a ζ-potential of -32 mV. The resulting Ag2O NPs at concentrations of 0.001-0.1% were transferred into acetone and mixed with a fluoroplast-based varnish. The developed coating made it possible to completely eliminate damage to a Teflon cutting board. The fluoroplast/Ag2O NP coating was free of defects and inhomogeneities at the nano level. The fluoroplast/Ag2O NP composite increased the production of ROS (H2O2, OH radical), 8-oxogualnine in DNA in vitro, and long-lived active forms of proteins. The effect depended on the mass fraction of the added Ag2O NPs. The 0.01-0.1% fluoroplast/NP Ag2O coating exhibited excellent bacteriostatic and bactericidal properties against both Gram-positive and Gram-negative bacteria but did not affect the viability of eukaryotic cells. The developed PTFE/NP Ag2O 0.01-0.1% coating can be used to protect cutting boards from bacterial contamination in the meat processing industry.

Antibacterial Nanomaterials: Mechanisms, Impacts on Antimicrobial Resistance and Design Principles.

Antimicrobial resistance (AMR) is one of the biggest threats to the environment and health. AMR rapidly invalidates conventional antibiotics, and antimicrobial nanomaterials have been increasingly explored as alternatives. Interestingly, several antimicrobial nanomaterials show AMR-independent antimicrobial effects without detectable new resistance and have therefore been suggested to prevent AMR evolution. In contrast, some are found to trigger the evolution of AMR. Given these seemingly conflicting findings, a timely discussion of the two faces of antimicrobial nanomaterials is urgently needed. This review systematically compares the killing mechanisms and structure-activity relationships of antibiotics and antimicrobial nanomaterials. We then focus on nano-microbe interactions to elucidate the impacts of molecular initiating events on AMR evolution. Finally, we provide an outlook on future antimicrobial nanomaterials and propose design principles for the prevention of AMR evolution.

Nano-enabled Quenching of Bacterial Communications for the Prevention of Biofilm Formation.

Biofilm formation is a major threat to industry, the environment and human health. While killing of embedded microbes in biofilms may inevitably lead to the evolution of antimicrobial resistance (AMR), catalytic quenching of bacterial communications by lactonase is a promising antifouling approach. Given the shortcomings of protein enzymes, it is attractive to engineer synthetic materials to mimic the activity of lactonase. Herein, an efficient lactonase-like Zn-Nx -C nanomaterial was synthesized by tuning the coordination environment around zinc atoms to mimic the active domain of lactonase for catalytical interception of bacterial communications in biofilm formation. The Zn-Nx -C material could selectively catalyze 77.5 % hydrolysis of N-acylated-L-homoserine lactone (AHL), a critical bacterial quorum sensing (QS) signal in biofilm construction. Consequently, AHL degradation downregulated the expression of QS-related genes in antibiotic resistant bacteria and significantly prevented biofilm formation. As a proof of concept, Zn-Nx -C-coated iron plates prevented 80.3 % biofouling after a month exposure in river. Overall, our study provides a nano-enabled contactless antifouling insight to avoid AMR evolution by engineering nanomaterials for mimicking the key bacterial enzymes (e.g., lactonase) functioning in biofilm construction.

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer.

In this study, we explored the pyroptosis-related biomarkers and signatures of colorectal cancer (CRC). Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA)-COADREAD and were analyzed for differentially expressed genes (DEGs). DEGs in CRC‒pyroptosis-related genes (CRC‒PRGs) were obtained by intersecting DEGs associated with CRC and PRGs. The CRC‒PRGs were verified; functional enrichment analysis was performed with Gene Ontology (GO) followed by cluster analysis. Cox analyses and LASSO regression were used in TCGA dataset to construct a prognostic model for patients with CRC. A prognostic risk assessment model was constructed and efficacy was evaluated. Decision curve analysis was utilized to assess the role of the Lasso-Cox regression prognostic model for clinical utility at 1, 3, and 5 years. Twelve CRC‒PRGs were identified as prognostic pyroptosis-related DEGs. CXCL8, IL13RA2, MELK, and POP1 were selected as prognostic genes to construct features with a good prognostic performance in GEO and TCGA. Functional enrichment indicated that the 4-gene signature might be involved in CRC tumorigenesis and development through various pathways by playing a prognostic role in CRC. Furthermore, the results of the immune landscape analysis showed that the expression of CXCL8 and IL13RA2 in TCGA-COADREAD dataset was positively correlated with significant differential enrichment of most immune cells. A novel prognostic model consisting of four key genes, CXCL8, IL13RA2, MELK, and POP1, can accurately predict the survival of patients with CRC. This finding may provide a new perspective for the treatment of pyroptosis-related CRC.

Lighting Nanoscale Insulators by Steric Restriction-Induced Emissions.

Luminescence detection is a sensitive approach for high-resolution visualization of nano-/macrosized objects, but it is challenging to light invisible insulators owing to their inert surfaces. Herein, we discovered a steric restriction-induced emission (SRIE) effect on nanoscale insulators to light them by fluorogenic probes. The SRIE effect enabled us to specifically differentiate a representative nanoscale insulator, boron nitride (BN) nanosheets, from 18 tested nanomaterials with 420-fold increments of photoluminescence intensity and displayed 3 orders of magnitude linearity for quantitative analysis as well as single-particle level detection. Molecular dynamics simulations indicated that the hydrophobic and electron-resistant surfaces of BN nanosheets restricted intramolecular motions of fluorogenic molecules for blockage of the nonradiative path of excited electrons and activation of the radiative electron transition. Moreover, the lighted BN nanosheets could be successfully visualized in complex cellular and tissue biocontexts. Overall, the SRIE effect will inspire more analytical techniques for inert materials.

Pixelated volume holographic optical element for augmented reality 3D display.

Augmented reality (AR) three-dimensional (3D) display is the hardware entrance of metaverse and attracts great interest. The fusion of physical world with 3D virtual images is non-trivial. In this paper, we proposed an AR 3D display based on a pixelated volume holographic optical element (P-VHOE). The see-through combiner is prepared by spatial multiplexing. A prototype of AR 3D display with high diffraction efficiency (78.59%), high transmission (>80%) and non-repeating views is realized. Virtual 3D objects with high fidelity in depth is reconstructed by P-VHOE, with a complex wavelet structural similarity (CW-SSIM) value of 0.9882. The proposed prototype provides an efficient solution for a compact glasses-free AR 3D display. Potential applications include window display, exhibition, education, teleconference.

The interfacial interactions of nanomaterials with human serum albumin.

The fates of nanomaterials (NMs) in vivo are greatly dependent on their interactions with human serum proteins. However, the interfacial molecular details of NMs-serum proteins are still difficult to be probed. Herein, the molecular interaction details of human serum albumin (HSA) with Au and SiO2 nanoparticles have been systematically interrogated and compared by using lysine reactivity profiling mass spectrometry (LRP-MS). We demonstrated the biocompatibility of Au is better than SiO2 nanoparticles and the NMs surface charge state played a more important role than particle size in the combination of NMs-HSA at least in the range of 15-40 nm. Our results will contribute to the fundamental mechanism understanding of NMs-serum protein interactions as well as the NMs rational design.

Coronas of micro/nano plastics: a key determinant in their risk assessments.

As an emerging pollutant in the life cycle of plastic products, micro/nanoplastics (M/NPs) are increasingly being released into the natural environment. Substantial concerns have been raised regarding the environmental and health impacts of M/NPs. Although diverse M/NPs have been detected in natural environment, most of them display two similar features, i.e.,high surface area and strong binding affinity, which enable extensive interactions between M/NPs and surrounding substances. This results in the formation of coronas, including eco-coronas and bio-coronas, on the plastic surface in different media. In real exposure scenarios, corona formation on M/NPs is inevitable and often displays variable and complex structures. The surface coronas have been found to impact the transportation, uptake, distribution, biotransformation and toxicity of particulates. Different from conventional toxins, packages on M/NPs rather than bare particles are more dangerous. We, therefore, recommend seriously consideration of the role of surface coronas in safety assessments. This review summarizes recent progress on the eco-coronas and bio-coronas of M/NPs, and further discusses the analytical methods to interpret corona structures, highlights the impacts of the corona on toxicity and provides future perspectives.

Clinical Characteristics of Patients with Arrhythmias of the Idiopathic Outflow Tract Ventricular: Age, Gender, Comorbidities, Laboratory Test Results, and Echocardiographic Parameters.

Context: Idiopathic ventricular arrhythmias (IVAs) are a spectrum of ventricular arrhythmia (VA) without structural heart disease (SHD), that includes premature ventricular contractions (PVCs) and ventricular tachycardia (VT). The clinical characteristics of patients with PVCs or VT remain unclear, including distribution of the origin of arrhythmias, age and gender differences, comorbidities, laboratory tests, and electrocardiographic parameters. Objective: The study intended to compare the clinical characteristics of the right ventricular outflow tract (RVOT)- and left ventricular outflow tract (LVOT)-VT of a large group of consecutive patients, to investigate the distribution of the origin of the arrhythmias, age and gender differences, comorbidities, laboratory-examination results, and echocardiographic parameters. Methods: The research team designed a retrospective study to collect data on the above-mentioned variables. Setting: The study occurred at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 774 patients with symptomatic ventricular arrhythmias, 328 males and 446 females with the mean age of 48.6 ± 15.7 years, who underwent catheter ablation between January 2015 and January 2019. Participants were divided into the right ventricular outflow tract (RVOT) group and left ventricular outflow tract (LVOT) group, according to the different origins of their arrhythmias, with 428 participants in the RVOT group and 180 in the LVOT group. Outcome Measures: The research team collected and analyzed the data for the original sites of the IVAs; ages; genders; comorbidities; laboratory examinations, including routine blood tests, liver function, kidney function, blood lipid and potassium; and echocardiographic parameters. Results: Among the 774 participants, 76 had experienced VTs and 698 PVCs. The original site of IVAs was 2.38 times more likely to be in the RVOT than the LVOT, with the ratio for RVOT/LVOT = 2.38. IVAs usually occurred in participants between 50 and 70 years old and exhibited a decreasing incidence after 70 years of age. IVAs derived from the His bundle were more common in older participants, with a mean age of 60.4 ± 10.4 years, while IVAs derived from the fascicular were more common in younger patients, with a mean age of 36.08 ± 16.01 years. Compared with the LVOT group, the RVOT group was younger, 51.91 ± 14.65 years vs 46.95 ± 14.95 years, respectively (P < .001). PVCs in the RVOT group were more common in women, with the ratio of females/males = 2.10, and no gender difference existed in the overall incidence of IVAs in the LVOT group (P > .05). The most common cardiovascular comorbidities of outflow tract ventricular arrhythmias (OTVAs) were hypertension, coronary heart disease, and hyperlipidemia, while the most common noncardiovascular comorbidities were diabetes, ischemic stroke, and thyroid disease. The red-blood-cell counts, hemoglobin, creatinine, and gamma-glutamyl transpeptidase (GGT) of the LVOT group were higher than those from the RVOT, with P = .008, P = .009, P = .001, and P < .001, respectively. The left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVS), and left ventricular posterior wall thickness (LVPWT) in the LVOT group were larger than those in the RVOT group (P <.001), while the LVOT group's left ventricular ejection fraction (LVEF%) was lower than that of the RVOT group. Conclusions: The outflow tract served as the major original site of IVAs, and significant differences existed between participants in the LVOT and RVOT groups in age; gender; comorbidities; results of laboratory examinations, including red-blood-cell counts, hemoglobin, creatinine, and GGT; and echocardiographic parameters, including LVEF%, LAD, LVEDD, IVS, and LVPWT.

S-R index in V1/V3 serves as a novel criterion to discriminate idiopathic premature ventricular contractions originating from posteroseptal right ventricular outflow tract versus right coronary cusp.

AIM: The current study aimed to establish a novel electrocardiographic (ECG) criterion for discrimination of idiopathic premature ventricular contractions (PVCs) originating from posteroseptal right ventricular outflow tract (sRVOT-p) versus right coronary cusp (RCC). METHODS: A total of 76 patients with idiopathic PVCs who underwent mapping and successful ablation were retrospectively included. Among them, 37 patients had PVCs from sRVOT-p origin and 39 patients from RCC origin. The surface ECGs during PVCs were recorded. S-R different index in V1/V3 was calculated with the following formula of 0.134*V3R-0.133*V1S. RESULTS: ECG characteristics showed wider total QRS duration, smaller R-wave amplitude on lead V2-V5, and larger S-wave amplitude on lead V1-V3 in sRVOT-p origin than RCC origin. Lead V3 was the most common transitional lead in two groups. Receiver operating characteristic (ROC) curve analysis showed that S-wave amplitude on lead V1 exhibited the largest AUC of 0.772, followed by the AUC of R-wave amplitude on lead V3 of 0.771. Subsequently, 0.134*V3R-0.133*V1S index was obtained by multiplication, subtraction, sum, and division of these ECG measurements, which exhibited the largest AUC of 0.808. The optimal cut-off value was -0.26 for differentiating RCC from sRVOT-p origin, with the sensitivity of 78.4% and specificity of 77.8%. Moreover, 0.134*V3R-0.133*V1S index was superior to previous criteria in analysis of PVCs originating from sRVOT-p and RCC. CONCLUSIONS: 0.134*V3R-0.133*V1S is a novel ECG criterion to discriminate sRVOT-p from RCC origin in patients with idiopathic PVCs, which may provide guidance for approach of radiofrequency catheter ablation.

SnSe Nanosheets Mimic Lactate Dehydrogenase to Reverse Tumor Acid Microenvironment Metabolism for Enhancement of Tumor Therapy.

The acidic tumor microenvironment (TME) is unfriendly to the activity and function of immune cells in the TME. Here, we report inorganic nanozymes (i.e., SnSe NSs) that mimic the catalytic activity of lactate dehydrogenase to degrade lactate to pyruvate, contributing to the metabolic treatment of tumors. As found in this study, SnSe NSs successfully decreased lactate levels in cells and tumors, as well as reduced tumor acidity. This is associated with activation of the immune response of T cells, thus alleviating the immunosuppressive environment of the TME. More importantly, the nanozyme successfully inhibited tumor growth in mutilate mouse tumor models. Thus, SnSe NSs show a promising result in lactate depletion and tumor suppression, which exemplifies its potential strategy in targeting lactate for metabolic therapy.

Stromal cell-derived factor-1 promotes osteoblastic differentiation of human bone marrow mesenchymal stem cells via the lncRNA-H19/miR-214-5p/BMP2 axis.

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) plays an important role in the osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs), but the specific mechanism remains unclear. Our study aimed to clarify the role of the lncRNA-H19/miR-214-5p/BMP2 axis in the osteoblastic differentiation of hBMMSCs induced by SDF-1. METHODS: We used reverse-transcriptase polymerase chain reaction, western blotting, alkaline phosphatase activity test, and Alizarin red staining to evaluate the osteoblastic differentiation of primary hBMMSCs and the luciferase reporter assay to determine if lncRNA-H19 binds with miR-214-5p. RESULTS: Our results indicated that SDF-1 (50 ng/mL) promotes the osteoblastic differentiation of hBMMSCs, significantly upregulates osteoblastogenic genes (OCN, OSX, RUNX2, and ALP), and increases Alizarin red staining, alkaline phosphatase activity, and lncRNA-H19 expression. Luciferase reporter assay verified that lncRNA-H19 binds with and represses miR-214-5p, thereby upregulating BMP2 expression. Use of miR-214-5p inhibitor or overexpression of lncRNA-H19 can promote the osteoblastic differentiation of hBMMSCs, but miR-214-5p or shH19 inhibits the osteoblastic differentiation of hBMMSCs. Treatment with an miR-214-5p inhibitor could rescue the inhibitory effect of shH19 on the osteoblastic differentiation of hBMMSCs. CONCLUSIONS: Taken together, SDF-1 promotes the osteoblastic differentiation of hBMMSCs through the lncRNA-H19/miR-214-5p/BMP2 axis. Increased osteoblastic differentiation by an miR-214-5p inhibitor reveals a new possible strategy for the treatment of bone defect and osteoporosis.

Effectiveness of P-wave ECG index and left atrial appendage volume in predicting atrial fibrillation recurrence after first radiofrequency catheter ablation.

BACKGROUND: The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation. METHODS: A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm. RESULTS: According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan-Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan-Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001). CONCLUSION: PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.