Effect of CO2-H2O Interaction with High-Rank Coal on Mechanical Properties and Acoustic Emission Characteristics under Confining Pressure.

The adsorption of CO2 by coal leads to changes in its mechanical properties, particularly when considering supercritical CO2 and water with supercritical CO2 adsorption. This is strongly linked to the efficiency of CO2-enhanced coalbed methane (CO2-ECBM) extraction and the safety of CO2 geological storage. This study focuses on 3# coal from the Datong Mine in Gaoping City, Shanxi Province. The high-rank coal's mechanical properties, including the triaxial compressive strength and elastic modulus, were examined under the combined effects of CO2 injection pressure, CO2 injection time, and moisture content. The triaxial compressive strength and elastic modulus of the coal showed a decrease following CO2 injection. Increasing the CO2 injection pressure, prolonging the CO2 injection time, and increasing the moisture content were favorable for coal softening. In particular, the triaxial compressive strength and elastic modulus of the coal sample after 144 h of water and supercritical CO2 softening decreased by 67.67 and 64.15%, respectively. Injecting CO2 into coal changed its failure mode. The dry raw coal sample exhibited a brittle shear failure mode, while the coal samples showed transitional shear failure after injecting 6 MPa CO2 and 8 MPa CO2 and ductile nondilatant barreling failure after injecting water and 8 MPa CO2 (with a moisture content of 3.02%). Moreover, the cumulative acoustic emission energy of the coal samples followed a similar trend to the decrease in mechanical properties under different conditions. The physical and chemical interactions among coal, CO2, and water caused the softening of coal; these included the generation of the swelling stress, the dissolution of minerals by carbonate solutions, the reduction in surface energy of coal owing to CO2 adsorption, and the extraction and plasticization reactions of organic matter in coal. The research results are of great significance for further understanding CO2-ECBM and CO2 geological sequestration.

Estimating helmet wearing rates via a scalable, low-cost algorithm: a novel integration of deep learning and google street view.

INTRODUCTION: Wearing a helmet reduces the risk of head injuries substantially in the event of a motorcycle crash. Countries around the world are committed to promoting helmet use, but the progress has been slow and uneven. There is an urgent need for large-scale data collection for situation assessment and intervention evaluation. METHODS: This study proposes a scalable, low-cost algorithm to estimate helmet-wearing rates. Applying the state-of-the-art deep learning technique for object detection to images acquired from Google Street View, the algorithm has the potential to provide accurate estimates at the global level. RESULTS: Trained on a sample of 3995 images, the algorithm achieved high accuracy. The out-of-sample prediction results for all three object classes (helmets, drivers, and passengers) reveal a precision of 0.927, a recall value of 0.922, and a mean average precision at 50 (mAP50) of 0.956. DISCUSSION: The remarkable model performance suggests the algorithm's capacity to generate accurate estimates of helmet-wearing rates from an image source with global coverage. The significant enhancement in the availability of helmet usage data resulting from this approach could bolster progress tracking and facilitate evidence-based policymaking for helmet wearing globally.

Clinical study on the influence of phacoemulsification on retinal structure of senile cataract based on data mining.

BACKGROUND: With the improvement of the level of science and technology, diagnosis and treatment technology of ophthalmology has continuously improved, especially with the rise of optical coherence tomography. Alternative methods have enabled clinicians to obtain more information and make greater breakthroughs in the occurrence and development of many ophthalmic diseases. OBJECTIVE: To investigate changes in retinal structure in the macular area of senile diabetic cataract patients undergoing cataract phacoemulsification. METHODS: This was a prospective cohort study. A total of 68 cataract patients (78 eyes) who voluntarily received phacoemulsification combined with intraocular lens implantation in the Department of Ophthalmology of our hospital from December 2018 to December 2021 were selected. They were divided into A (diabetic) and B (non-diabetic) according to whether they were complicated with diabetes. There were 24 cases (28 eyes) in A and 44 cases (50 eyes) in B. Cataract patients were collected before and after surgery. Day, 1 week, and 1 month, data on the average thickness of the fovea retina and thickness of the retinal nerve fiber layer around the optic disc (average thickness, nasal thickness, topic side thickness, upper thickness, and lower thickness) were statistically analyzed analyze. RESULTS: The average retinal thickness of the macular fovea in Group A was found to be greater than that of Group B, however, there was no statistically significant difference between the two groups. At week one and week thirty, Group A's layer of retinal nerve fibers surrounding the optic disc thickened; there was no discernible difference between the two groups. One week and one month following surgery, however, showed a one-week difference in upper thickness compared to preoperative days. There was no discernible change between the preoperative and 1-day times. CONCLUSION: Both diabetic cataract patients and simple age-related cataract patients will have different degrees of increased foveal retinal thickness after surgery. However, the foveal retinal thickness of patients with diabetes increases more.

AFE-GAN: Synthesizing Electrocardiograms with Atrial Fibrillation Characteristics Using Generative Adversarial Networks.

Labeled ECG data in diseased state are, however, relatively scarce due to various concerns including patient privacy and low prevalence. We propose the first study in its kind that synthesizes atrial fibrillation (AF)-like ECG signals from normal ECG signals using the AFE-GAN, a generative adversarial network. Our AFE-GAN adjusts both beat morphology and rhythm variability when generating the atrial fibrillation-like ECG signals. Two publicly available arrhythmia detectors classified 72.4% and 77.2% of our generated signals as AF in a four-class (normal, AF, other abnormal, noisy) classification. This work shows the feasibility to synthesize abnormal ECG signals from normal ECG signals.Clinical significance - The AF ECG signal generated with our AFE-GAN has the potential to be used as training materials for health practitioners or be used as class-balance supplements for training automatic AF detectors.

The High-Efficiency Design Method for Capacitive MEMS Accelerometer.

In this research, a high-efficiency design method of the capacitive MEMS accelerometer is proposed. As the MEMS accelerometer has high precision and a compact structure, much research has been carried out, which mainly focused on the structural design and materials selection. To overcome the inconvenience and inaccuracy of the traditional design method, an orthogonal design and the particle swarm optimization (PSO) algorithm are introduced to improve the design efficiency. The whole process includes a finite element method (FEM) simulation, high-efficiency design, and verification. Through the theoretical analysis, the working mechanism of capacitive MEMS accelerometer is clear. Based on the comparison among the sweep calculation results of these parameters in the FEM software, four representative structural parameters are selected for further study, and they are le, nf, lf and wPM, respectively. le and lf are the length of the sensing electrode and fixed electrode on the right. nf is the number of electrode pairs, and wPM is the width of the mass block. Then, in order to reduce computation, an orthogonal design is adopted and finally, 81 experimental groups are produced. Sensitivity SV and mass Ma are defined as evaluation parameters, and structural parameters of experimental groups are imported into the FEM software to obtain the corresponding calculation results. These simulation data are imported into neural networks with the PSO algorithm. For a comprehensively accurate examination, three cases are used to verify our design method, and every case endows the performance parameters with different weights and expected values. The corresponding structural parameters of each case are given out after 24 iterations. Finally, the maximum calculation errors of SV and Ma are 1.2941% and 0.1335%, respectively, proving the feasibility of the high-efficiency design method.

Efficient Thermal-Stress Coupling Design of Chiplet-Based System with Coaxial TSV Array.

In this research, an efficient thermal-stress coupling design method for a Chiplet-based system with a coaxial through silicon via (CTSV) array is developed by combining the support vector machine (SVM) model and particle swarm optimization algorithm with linear decreasing inertia weight (PSO-LDIW). The complex and irregular relationship between the structural parameters and critical indexes is analyzed by finite element simulation. According to the simulation data, the SVM model is adopted to characterize the relationship between structural parameters and critical indexes of the CTSV array. Based on the desired critical indexes of the CTSV array, the multi-objective evaluation function is established. Afterwards, the structural parameters of the CTSV array are optimized through the PSO-LDIW algorithm. Finally, the effectiveness of the developed method is verified by the finite element simulation. The simulated peak temperature, peak stress of the Chiplet-based system, and peak stress of the copper column (306.16 K, 28.48 MPa, and 25.76 MPa) well agree with the desired targets (310 K, 30 MPa, and 25 MPa). Therefore, the developed thermal-stress coupling design method can effectively design CTSV arrays for manufacturing high-performance interconnect structures applied in Chiplet-based systems.

The overgeneralization of pain-related fear in individuals with higher pain sensitivity: A behavioral and event-related potential study.

Fear generalization contributes to the development and maintenance of pain. Pain sensitivity has been proposed to predict the strength of fear responses to aversive stimuli. However, whether individual variation in pain sensitivity affects pain-related fear generalization and its underlying cognitive processing remains unclear. To address this gap, we recorded behavioral and event-related potential (ERP) data among 22 high pain sensitivity (HPS) and 22 low pain sensitivity (LPS) healthy adults when exposed to a fear generalization paradigm. The behavioral results indicate that the HPS group displayed higher unconditioned stimulus expectancy and greater fear, arousal, and anxiety ratings to conditioned stimulus and generalization stimulus than the LPS group (all p values < 0.05). The ERP results showed that the HPS group exhibited a larger late positive potential evoked by GS2, GS3 and CS- (all p < 0.005) but a smaller N1 evoked by all CS and GSs (all p values < 0.05) relative to the LPS group. These findings suggest that individuals with a high level of pain sensitivity allocate more attention resources to pain-related threatening stimuli, which contributes to an overgeneralization of pain-related fear.

The excessive generalization of fear affected by perceptual bias in experimental pain individuals: Evidence from an event-related potential study.

INTRODUCTION: Excessiv generalization of fear contributes to the development and maintenance of pain. Prior research has demonstrated the importance of perception in fear generalization and found that individuals in painful conditions exhibited perceptual bias. However, the extent to which perceptual bias in pain affects the generalization of pain-related fear and its underlying neural activity remains unclear. METHODS: Here, we tested whether perceptual bias in experimental pain individuals led to the overgeneralization of pain-related fear by recording behavioral and neural responses. To this end, we established an experimental pain model by spraying capsaicin on the surface of the seventh cervical vertebra of the participant. A total of 23 experimental pain participants and 23 matched nonpain controls learned fear conditioning and then completed the fear generalization paradigm combined with the perceptual categorization task. RESULTS: We found that the novel and safety cues were more likely to be identified as threat cues in the experimental group, resulting in higher US expectancy ratings compared to the control group. The event-related potential results showed that the experimental group exhibited earlier N1 latency and smaller P1 and late positive potential amplitudes than those in the control group. CONCLUSION: Our findings suggest that the experimental pain individuals exhibited an excessive generalization of fear affected by perceptual bias and reduced their attentional allocation to pain-related fear stimuli.

Fabrication of Ti3Al-Based Intermetallic Alloy by Laser Powder Bed Fusion Using a Powder Mixture.

Due to their light weight and outstanding mechanical properties at high temperatures, Ti3Al-based intermetallic alloys have driven increasing interest from both academia and industry; however, when additive manufacturing (AM) is applied to them, the outcome is hardly satisfying. In this work, we report a crack-free Ti3Al-based alloy fabrication by laser powder bed fusion (LPBF) using a mixture of a commercial Ti-48Al-2Cr-2Nb powder and a pure Ti powder. With the aid of a high cooling rate during LPBF, the as-built sample shows a ductile ß phase with some partially-melted particles. After the heat treatment, partially-melted particles were dissolved, and the sample showed equiaxed α2 precipitates in the ß matrix. The hardness was 515 ± 38 HV in the as-built sample and 475 ± 37 HV in the heat-treated sample. This study shows a novel strategy to fabricate crack-free Ti3Al-based alloy using LPBF from powder blends.

Synthesis of Triblock Polycarboxylate Superplasticizers with Well-Defined Structure and Its Dispersing Performance in ß-Hemihydrate Gypsum.

In this work, a novel AaBAb-type triblock polycarboxylate superplasticizers (PCEs) with well defined molecular structures were designed and synthesized, firstly, by reversible addition-fragmentation chain transfer (RAFT) polymerization, to explore the structure-property relationship PCEs in the ß-hemihydrate gypsum (ß-HH) system. Three PCEs with the same molecular weight and different structure were obtained by changing the feed ratio of the RAFT agent, initiator, and monomer. The effect of the chemical structure of PCEs on their dispersing property and water reduction capacity were assessed in gypsum by measuring the flowability of pastes and the adsorption ability of PCEs on gypsum. Results showed that among three PCEs, when the monomer ratio is 5:1 and a:b = 1:1, PCE-1 exhibited a higher working efficiency, verifying the contribution of regulating structural parameters to the improvement in performances of gypsum paste, because PCE-1 showed the strongest binding capacity with calcium ions due to the relatively equal amount of carboxyl groups at both ends. The AaBAb-type PCEs provide a special advantage over the conventional comb polymer to understand the relation between the structure and property of PCEs, and a direction for further development of PCEs of high performance.

Exosomal circFBLIM1 Promotes Hepatocellular Carcinoma Progression and Glycolysis by Regulating the miR-338/LRP6 Axis.

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Circular RNAs (circRNAs) play a vital role in cancer development and progression. This study investigated the role and potential mechanism of circRNA filamin binding LIM protein 1 (circFBLIM1) in HCC. Methods: Exosomes were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot assay. The levels of circFBLIM1, miR-338, and low-density lipoprotein receptor-related protein 6 (LRP6) were measured by quantitative real-time polymerase chain reaction or Western blot. Glycolysis was analyzed by detecting glucose consumption, lactate production, ATP level, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was detected by flow cytometry. Xenograft assay was performed to analyze tumor growth in vivo. The interaction among circFBLIM1, miR-338, and LRP6 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Results: CircFBLIM1 was highly expressed in HCC serum exosomes and HCC cells. Inhibition of circFBLIM1 confined HCC glycolysis and progression. CircFBLIM1 knockdown blocked tumorigenesis in vivo. CircFBLIM1 was a sponge of miR-338 and promoted HCC progression and glycolysis by regulating miR-338. Moreover, miR-338 suppressed HCC progression and glycolysis via targeting LRP6. Mechanistically, circFBLIM1 functioned as an miR-338 sponge to upregulate LRP6. Conclusion: CircFBLIM1 facilitated HCC progression and glycolysis via modulating the miR-338/LRP6 axis, which may provide promising therapeutic targets for HCC.

Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study.

Objective: The purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function. Methods: Thirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations. Result: Compared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = -2.175, p = 0.034), gamma (t = -2.332, p = 0.023), and local efficiency (t = -2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = -3.581, p = 0.0007), and the network efficiency values (t = -2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores. Conclusion: Our study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP.

SNHG5/miR-299-5p/ATF2 Axis as a Biomarker in Immune Microenvironment of Intervertebral Disc Degeneration.

Methods: The data sets of GSE56081 and GSE63492 in the Gene Expression Omnibus (GEO) database were used for screening and analysis, and the key gene markers were verified by GSE34095 and GSE126883. Finally, the infiltration of immune cells in the data were analyzed by MCPcounter analysis package. Results: In this study, a ceRNA containing 15 lncRNAs, 9 miRNAs, and 103 mRNAs was constructed. After multimodel screening and verification, key gene marker was found, namely, ATF2. The lncRNA/miRNA/mRNA axis closely related to ATF2 have also been found, namely, SNHG5/miR-299-5p/ATF2. In the analysis of immune infiltration, ATF2 was negatively correlated with T cells but positively correlated with neutrophils and endothelial cells. Conclusion: The SNHG5/miR-299-5p/ATF2 can be used as biomarker of IDD, and infiltration of immune cells plays an important role in the pathological development of IDD. In addition, as a marker of IDD, the involvement of the above-mentioned axis in the pathological development of IDD remains to be further explored.

Effect of transcranial direct-current stimulation on executive function and resting EEG after stroke: A pilot randomized controlled study.

BACKGROUND: The effects of transcranial direct current stimulation (tDCS) on post-stroke executive impairment (PSEI) remain controversial. Resting stateelectroencephalogram (EEG) can assist in the diagnosis and assessment of executive dysfunction. OBJECTIVES: We aimed to use EEG to explore the effect of tDCS on executive function among stroke patients. METHODS: Twenty-four patients with PSEI were randomly divided into experimental and control groups, which received real and sham stimulation, respectively. Anodal electrical stimulation was applied to the left dorsolateral prefrontal lobe (F3). The stimulation intensity was 2 mA for 20 min once daily for 7 days. Executive function was monitored using neuropsychological scales. RESULTS: The experimental group outperformed the control group in clinical scale results, with significant differences in the following scores: symbol digital modalities test, TMT-A, TMT-B, and digital span test. In the left central zone, theta band power was significantly higher after anodal electrical stimulation than before. Analysis of the correlation between EEG power and psychometric scores revealed that the power change was positively correlated with the scores on the symbol digital modality test (r = 0.435, p < 0.05). CONCLUSION: Anodal tDCS can enhance executive function in patients with PSEI, and tDCS-related improvements are related to the enhancement of theta power in the affected region.

Visually Perceived Negative Emotion Enhances Mismatch Negativity but Fails to Compensate for Age-Related Impairments.

Objective: Automatic detection of auditory stimuli, represented by the mismatch negativity (MMN), facilitates rapid processing of salient stimuli in the environment. The amplitude of MMN declines with ageing. However, whether automatic detection of auditory stimuli is affected by visually perceived negative emotions with normal ageing remains unclear. We aimed to evaluate how fearful facial expressions affect the MMN amplitude under ageing. Methods: We used a modified oddball paradigm to analyze the amplitude of N100 (N1) and MMN in 22 young adults and 21 middle-aged adults. Results: We found that the amplitude of N1 elicited by standard tones was smaller under fearful facial expressions than neutral facial expressions and was more negative for young adults than middle-aged adults. The MMN amplitude under fearful facial expressions was greater than neutral facial expressions, but the amplitude in middle-aged adults was smaller than in young adults. Conclusion: Visually perceived negative emotion promotes the extraction of auditory features. Additionally, it enhances the effect of auditory change detection in middle-aged adults but fails to compensate for this decline with normal ageing. Significance: The study may help to understand how visually perceived emotion affects the early stage of auditory information processing from an event process perspective.

Conservation and Diversity of miR166 Family Members From Highbush Blueberry (Vaccinium corymbosum) and Their Potential Functions in Abiotic Stress.

MicroRNA166 (miR166) is highly conserved and has diverse functions across plant species. The highbush blueberry (Vaccinium corymbosum) genome is thought to harbor 10 miRNA166 loci (Vco-miR166), but the extent of their evolutionary conservation or functional diversification remains unknown. In this study, we identified six additional Vco-miR166 loci based on conserved features of the miR166 family. Phylogenetic analyses showed that mature Vco-miR166s and their precursor cluster in several clades are evolutionary conserved with diverse species. The cis-regulatory elements in the Vco-miR166 promoters indicated functions related to different phytohormones and defense responses. We also identified putative targets of vco-miR166s, which targeted the same gene families, suggesting the functional conservation and diversification of Vco-miR166 family members. Furthermore, we examined the accumulation patterns of six mature Vco-miR166s in response to abiotic stresses by stem-loop reverse RT-qPCR, which revealed their upregulation under freezing, cold, and heat stress, while they were downregulated by drought compared to control growth conditions. However, Vco-miR166 members showed different expression patterns when exposed to salt stress. These results showed that conserved Vco-miR166 family members display functional diversification but also coordinately influence plant responses to abiotic stress.

Characteristics of Coal Porosity Changes before and after Triaxial Compression Shear Deformation under Different Confining Pressures.

It is important to explore the changes in coal pores in response to triaxial compression and shear deformation for coal mine gas drainage and efficient coalbed methane mining. To study the variation in coal pores depending on stress, first, a mechanical analysis was carried out, and then the characteristics of coal samples before and after triaxial compression were quantitatively analyzed combined with low-temperature nitrogen adsorption experiments. The compressive strength of the coal samples with a high elastic modulus is significantly greater than that of coal samples with a low elastic modulus. Sihe coal samples with a larger elastic modulus experienced higher peak stress and strain during compression than those from the Chengzhuang Mine with a smaller elastic modulus. With the exception of the coal sample from the Chengzhuang Mine with a confining pressure of 15 MPa, the peak strength and axial strain of the coal samples gradually increased with an increase in confining pressure. The larger the elastic modulus, the greater the axial strain. After triaxial compression, pores with diameters ranging from 2 to 5 nm exhibited a significant change. After the compression of coal with a high elastic modulus, the pore volume and pore specific surface area decreased with the increase in confining pressure, by 60.7 and 59.7%, respectively (compared with raw coal). The complex pore structure consisting of mesopores and macropores (>11 nm) became simpler. The volume and specific surface area of the pores of the coal samples with a low elastic modulus first increased, then decreased, and then increased again with the increase in confining pressure, and after compression, the roughness and complexity of macropores of coal samples are greater than those of micropores. The changes induced in the coal samples of the two mining areas in response to compression differ, which are related to the mechanical properties of the coal bodies.

LANCL1 as the Key Immune Marker in Neuropathic Pain.

Objective: This study is to explore key immune markers and changes of immune microenvironment in neuropathic pain (NeuP). Method: The data sets of GSE145199 and GSE145226 in Gene Expression Omnibus (GEO) database was used to analyze, and the key immune markers were verified by GSE70006 and GSE91396, and the infiltration degree of immune cells in different samples were analyzed by CIBERSORT analysis package. Results: In this study, we found a key immune marker, namely, LANCL1. Regulatory axis closely related to LANCL1 has also been found, namely, miR-6325/LANCL1 axis. In the immune infiltration analysis, we also found that the LANCL1 is positively correlated with T cells CD4 naïve (r = 0.880, p < 0.05). Conclusion: In this study, we found that LANCL1 may be a protective factor for NeuP, and the miR-6325/LANCL1 axis may be involved in the occurrence and development of NeuP. Cascade reactions including mast cells, macrophages, and T cells may be an important reason for the aggravation of nerve damage.

Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity.

Breast cancer is prevalent and diverse with significantly high incidence and mortality rates. Curcumin (Cur), a polyphenol component of turmeric, has been widely recognized as having strong anti-breast cancer activity. However, its anti-cancer efficiency is largely impaired by some of its concomitant negative properties, including its poor solubility, low cellular uptake, and severe reported side effects. Hence, the necessity arises to develop a novel low-toxic and high-efficiency targeting drug delivery system (DDS). In this study, we developed a pH-sensitive tumor self-targeting DDS (Cur@HFn) based on self-assembled HFn loaded with Cur, in which Cur was encapsulated into HFn cavity by using a disassembly/reassembly strategy, and the Cur@HFn was characterized by ultraviolet-visible (UV-vis), dynamic light scattering (DLS), and transmission electron microscope (TEM). A variety of breast cancer cell models were built to evaluate cytotoxicity, apoptosis, targeting properties, and uptake mechanism of the Cur@HFn. The pharmacodynamics was also evaluated in tumor (4T1) bearing mice after intravenous injection. In vitro release experiments showed that Cur@HFn is pH sensitive and shows sustained drug release under slightly acidic conditions. Compared with Cur, Cur@HFn has stronger cytotoxicity, cellular uptake, and targeting performance. Our study supported that Cur@HFn has a higher in vivo therapeutic effect and lower systemic toxicity. The safety evaluation results indicated that Cur@HFn has no hematotoxicity, hepatotoxicity, and nephrotoxicity. The findings of the present study showed that the Cur@HFn has been successfully prepared and has potential application value in the treatment of breast cancer.

Amplification of ferroptosis with a liposomal nanoreactor cooperates with low-toxicity doxorubicin apoptosis for enhanced tumor chemotherapy.

Despite the remarkable tumor inhibition effect of doxorubicin (DOX), its cardiotoxicity severely limits the clinical dosage and further impairs the chemotherapy efficacy. To improve the biosafety and effectiveness of conventional chemotherapy, we propose a strategy to co-deliver DOX and ART to supplement apoptosis with ferroptosis. To this end, ART and DOX were incorporated into ferrous LiMOFs to develop a nanoreactor, utilizing ferrous ions as a catalyst to decompose ART into radicals and thus to induce efficient ferroptosis. Further, DOX can induce another form of death, apoptosis, which in combination enhances tumor inhibition. The synthesized nanoreactor (DOX/ART@LiMOFs) possesses a size of ∼100 nm and maintains a regular crystal structure. The pH-responsive disassociation endows it with acid-sensitive drug-releasing kinetics, and the liposomal bilayers bring about a sustained release feature (up to 12 h). The cellular ROS assay indicated that the supply of ferrous ions dramatically increased the ROS mediated by ART and led to markedly enhanced tumor inhibition in animal tests accompanied by the apoptosis of DOX. Consequently, this work presents an innovative strategy to synchronously induce potent ferroptosis and apoptosis, promoting conventional cancer chemotherapy.