Multifunctional Porous Bilayer Artificial Skin for Enhanced Wound Healing.

Meeting the exacting demands of wound healing encompasses rapid coagulation, superior exudate absorption, high antibacterial efficacy, and imperative support for cell growth. In this study, by emulating the intricate structure of natural skin, we prepare a multifunctional porous bilayer artificial skin to address these critical requirements. The bottom layer, mimicking the dermis, is crafted through freeze-drying a gel network comprising carboxymethyl chitosan (CMCs) and gelatin (GL), while the top layer, emulating the epidermis, is prepared via electrospinning poly(l-lactic acid) (PLLA) nanofibers. With protocatechuic aldehyde and gallium ion complexation (PA@Ga) as cross-linking agents, the bottom PA@Ga-CMCs/GL layer featured an adjustable pore size (78-138 µm), high hemostatic performance (67s), and excellent bacterial inhibition rate (99.9%), complemented by an impressive liquid-absorbing capacity (2000% swelling rate). The top PLLA layer, with dense micronanostructure and hydrophobic properties, worked as a shield to effectively thwarted liquid or bacterial penetration. Furthermore, accelerated wound closure, reduced inflammatory responses, and enhanced formation of hair follicles and blood vessels are achieved by the porous artificial skin covered on the surface of wound. Bilayer artificial skin integrates the advantages of nanofibers and freeze-drying porous materials to effectively replicate the protective properties of the epidermal layer of the skin, as well as the cell migration and tissue regeneration of the dermis. This bioabsorbable artificial skin demonstrates structural and functional comparability to real skin, which would advance the field of wound care through its multifaceted capabilities.

Brain metastasis magnetic resonance imaging-based deep learning for predicting epidermal growth factor receptor (EGFR) mutation and subtypes in metastatic non-small cell lung cancer.

Background: The preoperative identification of epidermal growth factor receptor (EGFR) mutations and subtypes based on magnetic resonance imaging (MRI) of brain metastases (BM) is necessary to facilitate individualized therapy. This study aimed to develop a deep learning model to preoperatively detect EGFR mutations and identify the location of EGFR mutations in patients with non-small cell lung cancer (NSCLC) and BM. Methods: We included 160 and 72 patients who underwent contrast-enhanced T1-weighted (T1w-CE) and T2-weighted (T2W) MRI at Liaoning Cancer Hospital and Institute (center 1) and Shengjing Hospital of China Medical University (center 2) to form a training cohort and an external validation cohort, respectively. A multiscale feature fusion network (MSF-Net) was developed by adaptively integrating features based on different stages of residual network (ResNet) 50 and by introducing channel and spatial attention modules. The external validation set from center 2 was used to assess the performance of MSF-Net and to compare it with that of handcrafted radiomics features. Receiver operating characteristic (ROC) curves, accuracy, precision, recall, and F1-score were used to evaluate the effectiveness of the models. Gradient-weighted class activation mapping (Grad-CAM) was used to demonstrate the attention of the MSF-Net model. Results: The developed MSF-Net generated a better diagnostic performance than did the handcrafted radiomics in terms of the microaveraged area under the curve (AUC) (MSF-Net: 0.91; radiomics: 0.80) and macroaveraged AUC (MSF-Net: 0.90; radiomics: 0.81) for predicting EGFR mutations and subtypes. Conclusions: This study provides an end-to-end and noninvasive imaging tool for the preoperative prediction of EGFR mutation status and subtypes based on BM, which may be helpful for facilitating individualized clinical treatment plans.

Adaptive interference suppression based on an invariant subspace of matrices matching for a horizontal array in underwater acoustics.

Passive detection of target-of-interest (TOI) within strong interferences poses a challenge. This paper introduces an adaptive interference suppression based on an invariant subspace of matrix matching. Assume that the TOI-bearing intervals are known. We define a correlation ratio for each eigenvector to obtain the highest one. Then, we use invariant subspace of matrix matching to measure the distance between two invariant projection matrices of this eigenvector. This identifies and removes the eigenvectors associated with TOI. Finally, the remaining eigenvectors are subtracted from the sample covariance matrix to suppress interference and noise. The viability of the proposed method is demonstrated experimentally.

Degree of disorder-regulated ion transport through amorphous monolayer carbon.

Nanopore technology, re-fueled by two-dimensional (2D) materials such as graphene and MoS2, controls mass transport by allowing certain species while denying others at the nanoscale and has a wide application range in DNA sequencing, nano-power generation, and others. With their low transmembrane transport resistance and high permeability stemming from their ultrathin nature, crystalline 2D materials do not possess nanoscale holes naturally, thus requiring additional fabrication to create nanopores. Herein, we demonstrate that nanopores exist in amorphous monolayer carbon (AMC) grown at low temperatures. The size and density of nanopores can be tuned by the growth temperature, which was experimentally verified by atomic images and further corroborated by kinetic Monte Carlo simulation. Furthermore, AMC films with varied degrees of disorder (DOD) exhibit tunable transmembrane ionic conductance over two orders of magnitude when serving as nanopore membranes. This work demonstrates the DOD-tuned property in amorphous monolayer carbon and provides a new candidate for modern membrane science and technology.

Structural and functional reorganization of inhibitory synapses by activity-dependent cleavage of neuroligin-2.

Recent evidence has demonstrated that the transsynaptic nanoscale organization of synaptic proteins plays a crucial role in regulating synaptic strength in excitatory synapses. However, the molecular mechanism underlying this transsynaptic nanostructure in inhibitory synapses still remains unclear and its impact on synapse function in physiological or pathological contexts has not been demonstrated. In this study, we utilized an engineered proteolysis technique to investigate the effects of acute cleavage of neuroligin-2 (NL2) on synaptic transmission. Our results show that the rapid cleavage of NL2 led to impaired synaptic transmission by reducing both neurotransmitter release probability and quantum size. These changes were attributed to the dispersion of RIM1/2 and GABAA receptors and a weakened spatial alignment between them at the subsynaptic scale, as observed through superresolution imaging and model simulations. Importantly, we found that endogenous NL2 undergoes rapid MMP9-dependent cleavage during epileptic activities, which further exacerbates the decrease in inhibitory transmission. Overall, our study demonstrates the significant impact of nanoscale structural reorganization on inhibitory transmission and unveils ongoing modulation of mature GABAergic synapses through active cleavage of NL2 in response to hyperactivity.

Electrospun organic/inorganic hybrid nanofibers for accelerating wound healing: a review.

Electrospun nanofiber membranes hold great promise as scaffolds for tissue reconstruction, mirroring the natural extracellular matrix (ECM) in their structure. However, their limited bioactive functions have hindered their effectiveness in fostering wound healing. Inorganic nanoparticles possess commendable biocompatibility, which can expedite wound healing; nevertheless, deploying them in the particle form presents challenges associated with removal or collection. To capitalize on the strengths of both components, electrospun organic/inorganic hybrid nanofibers (HNFs) have emerged as a groundbreaking solution for accelerating wound healing and maintaining stability throughout the healing process. In this review, we provide an overview of recent advancements in the utilization of HNFs for wound treatment. The review begins by elucidating various fabrication methods for hybrid nanofibers, encompassing direct electrospinning, coaxial electrospinning, and electrospinning with subsequent loading. These techniques facilitate the construction of micro-nano structures and the controlled release of inorganic ions. Subsequently, we delve into the manifold applications of HNFs in promoting the wound regeneration process. These applications encompass hemostasis, antibacterial properties, anti-inflammatory effects, stimulation of cell proliferation, and facilitation of angiogenesis. Finally, we offer insights into the prospective trends in the utilization of hybrid nanofiber-based wound dressings, charting the path forward in this dynamic field of research.

A Skin-Inspired Self-Adaptive System for Temperature Control During Dynamic Wound Healing.

The thermoregulating function of skin that is capable of maintaining body temperature within a thermostatic state is critical. However, patients suffering from skin damage are struggling with the surrounding scene and situational awareness. Here, we report an interactive self-regulation electronic system by mimicking the human thermos-reception system. The skin-inspired self-adaptive system is composed of two highly sensitive thermistors (thermal-response composite materials), and a low-power temperature control unit (Laser-induced graphene array). The biomimetic skin can realize self-adjusting in the range of 35-42 °C, which is around physiological temperature. This thermoregulation system also contributed to skin barrier formation and wound healing. Across wound models, the treatment group healed ~ 10% more rapidly compared with the control group, and showed reduced inflammation, thus enhancing skin tissue regeneration. The skin-inspired self-adaptive system holds substantial promise for next-generation robotic and medical devices.

Right ventricular-pulmonary artery coupling is an independent risk factor for coronary artery lesions in children with Kawasaki disease.

BACKGROUND: The recognition ability of right ventricular-pulmonary artery (RV-PA) coupling for coronary artery lesions (CAL) in children with Kawasaki disease (KD) has not been well characterized. This study aimed to determine whether RV-PA coupling is an independent the risk factors for CAL in children with KD. METHODS: Between October 2021 and August 2023, RV-PA coupling was assessed in 59 KD children using the ratio between echocardiographic tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (PASP). Multivariable logistic regression analysis was used to identify the independent risk factors for CAL among the demographic, clinical, laboratory and echocardiographic data. RESULTS: Twenty-nine of 59 KD children had CAL according to the diagnostic criteria of echocardiography. There were significantly different white blood cell count, C-reactive protein, erythrocyte sedimentation rate, left ventricular ejection fraction, PASP and RV-PA coupling at admission, and significantly different acute/subacute phase ratio of RV-PA coupling between KD children with and without CAL ( P  < 0.05). Multivariate logistic regression analysis identified that acute/subacute phase ratio of RV-PA coupling (OR = 26.800; 95% CI, 1.276-562.668; P  = 0.034) was an independent risk factor for CAL in children with KD. The area under receiver operating characteristic curve for the acute/subacute phase ratio of RV-PA coupling was 0.715 (95%CI: 0.624 - 0.825) to predict CAL in KD children ( P  < 0.05), with a sensitivity of 81.25% and a specificity of 62.57% at the optimal cutoff value of 0.839. CONCLUSION: The acute/subacute phase ratio of RV-PA coupling was an independent risk factor for CAL in KD children.

S-100ß level is closely associated with myocardial work in patients with acute ischemic stroke.

BACKGROUND: The more severe the acute stroke is, the more serious myocardial damage is. This study aimed to determine the relationship between myocardial work and S100ß, a quantitative biomarker of active cerebral lesions, in patients with acute ischemic stroke (AIS). METHODS: A total of 63 patients with AIS were examined by myocardial work echocardiography, 4D echocardiography with the measurement of left ventricular (LV) myocardial work, volume and function within 24-48 h of symptom onset, respectively. Their plasma S100ß was measured from a peripheral blood sample within 2-6 h of symptom onset. RESULTS: Patients with elevated S-100ß level had significantly increased ratios of peak early diastolic transmitral filling velocity to peak early diastolic lateral mitral annulus tissue velocity(E/e') and global longitudinal strain (GLS), and significantly reduced global work index(GWI) and global constructive work (GCW) compared with those with normal S-100ß level (p < 0.05). S-100ß positively correlated with E/e'(r = 0.878, p < 0.0001) and GLS (r = 0.511, p = 0.002) but negatively correlated with GWI(r = -0.409, p = 0.034) and GCW(r = -0.353, p = 0.041). S-100ß showed an excellent ability to differentiate if a reduced GWI [cut-off value, 120.79 pg/mL; area under receiver operating characteristic curve (AUC), 1.000; sensitivity, 100%; specificity, 100%], GCW (cut-off value, 120.79 pg/mL;AUC,1.000; sensitivity,100%; specificity, 100%) and an increased E/e' (cut-off value, 91.1 pg/mL;AUC,0.913; sensitivity,80%; specificity, 100%) or not, but poor ability to differentiate if an increased GLS(cut-off value, 91.1 pg/mL; AUC,0.576; sensitivity,63.64%; specificity, 83.33%) or not. CONCLUSION: S-100ß level is closely associated with LV function. It is highly competent in determining an impaired myocardial work in patients with AIS.

Feasibility of Two-Screw Anterior Fixation for Odontoid Fractures in a Chinese Population: A Morphometric Study Based on Computed Tomography.

Background: To evaluate the feasibility of treating odontoid fractures in the Chinese population with two cortical screws based on computed tomography (CT) scans and describe a new measurement strategy to guide screw insertion in treating these fractures. Methods: A retrospective review of cervical computed tomographic scans of 128 patients (aged 18-76 years; men, 55 [43.0%]) was performed. The minimum external transverse diameter (METD), minimum external anteroposterior diameter (MEAD), maximum screw length (MSL), and screw projection back angle (SPBA) of the odontoid process were measured on coronal and sagittal CT images. Results: The mean values of METD and MEAD were 10.0 ± 1.1 mm and 12.0 ± 1.0 mm, respectively, in men and 9.2 ± 1.0 mm and 11.0 ± 1.0 mm, respectively, in women. Both measurements were significantly higher in men (p < 0.001). In total, 87 individuals (68%) had METD > 9.0 mm that could accommodate two 3.5-mm cortical screws. The mean MSL value and SPBA range were 34.4 ± 2.9 mm and 13.5°-24.2°, respectively, with no statistically significant difference between men and women. Conclusions: The insertion of two 3.5-mm cortical screws was possible for anterior fixation of odontoid fractures in 87 patients (68%) in our study, and there was a statistically significant difference between men and women.

Effects of Inherent Minerals on Pyrolysis Behavior and Kinetics of Jimsar Oil Shale.

In order to reveal the influences of different inherent minerals on the pyrolysis behavior and kinetics of oil shale, decarburization, and desilication, samples were obtained by pickling and demineralization. The influence of inherent minerals on the activation energy of oil shale at different conversion rates and the pyrolysis kinetic model were researched by the equal conversion method and principal curve method. The results demonstrated that the average and maximum weight loss rates and volatile release characteristic index of JM-C were lower than that of JM-R; however, JM-S appeared with the opposite trend. At the initial stage (α = 0.2-0.6), the pyrolysis activation energy of JM-C was basically the same as that of JM-R, while the pyrolysis activation energy of JM-S decreased. At the later stage (α = 0.6-0.8), the pyrolysis activation energy of JM-C was higher than that of JM-R, while the activation energy of JM-S was between JM-C and JM-R. The existence of inherent carbonates reduced the pyrolysis activation energy of oil shale, but only at the later stage of pyrolysis. In addition, the existence of inherent carbonates changed the pyrolysis kinetic model of oil shale from an order model to a one-dimensional diffusion model, encompassing f(α) = (1 - α)2.5 and f(α) = 0.5α-1. However, the existence of inherent silicates increased the activation energy of oil shale pyrolysis. Moreover, its mechanism was consistent with the original model, namely, an order model, f(α) = 1 - α.

Exudate Absorbing and Antimicrobial Hydrogel Integrated with Multifunctional Curcumin-Loaded Magnesium Polyphenol Network for Facilitating Burn Wound Healing.

Burns are among the most common causes of trauma worldwide. Reducing the healing time of deep burn wounds has always been a major challenge. Traditional dressings not only require a lengthy medical procedure but also cause unbearable pain and secondary damage to patients. In this study, we developed an exudate-absorbing and antimicrobial hydrogel with a curcumin-loaded magnesium polyphenol network (Cur-Mg@PP) to promote burn wound healing. That hydrogel was composed of an ε-poly-l-lysine (ε-PLL)/polymer poly(γ-glutamic acid) (γ-PGA) hydrogel (PP) and curcumin-loaded magnesium polyphenol network (Cur-Mg). Because of the strong water absorption property of ε-PLL and γ-PGA, Cur-Mg@PP powder can quickly absorb the wound exudate and transform into a moist and viscous hydrogel, thus releasing payloads such as magnesium ion (Mg2+) and curcumin (Cur). The released Mg2+ and Cur demonstrated good therapeutic efficacy on analgesic, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration. Our findings provide a strategy for accelerating burn wound healing.

Using Radiomics to Differentiate Brain Metastases From Lung Cancer Versus Breast Cancer, Including Predicting Epidermal Growth Factor Receptor and human Epidermal Growth Factor Receptor 2 Status.

OBJECTIVE: We evaluated the feasibility of using multiregional radiomics to identify brain metastasis (BM) originating from lung adenocarcinoma (LA) and breast cancer (BC) and assess the epidermal growth factor receptor (EGFR) mutation and human epidermal growth factor receptor 2 (HER2) status. METHODS: Our experiment included 160 patients with BM originating from LA (n = 70), BC (n = 67), and other tumor types (n = 23), between November 2017 and December 2021. All patients underwent contrast-enhanced T1- and T2-weighted magnetic resonance imaging (MRI) scans. A total of 1967 quantitative MRI features were calculated from the tumoral active area and peritumoral edema area and selected using least absolute shrinkage and selection operator regression with 5-fold cross-validation. We constructed radiomic signatures (RSs) based on the most predictive features for preoperative assessment of the metastatic origins, EGFR mutation, and HER2 status. Prediction performance of the constructed RSs was evaluated based on the receiver operating characteristic curve analysis. RESULTS: The developed multiregion RSs generated good area under the receiver operating characteristic curve (AUC) for identifying the LA and BC origin in the training (AUCs, RS-LA vs RS-BC, 0.767 vs 0.898) and validation (AUCs, RS-LA vs RS-BC, 0.778 and 0.843) cohort and for predicting the EGFR and HER2 status in the training (AUCs, RS-EGFR vs RS-HER2, 0.837 vs 0.894) and validation (AUCs, RS-EGFR vs RS-HER2, 0.729 vs 0.784) cohorts. CONCLUSIONS: Our results revealed associations between brain MRI-based radiomics and their metastatic origins, EGFR mutations, and HER2 status. The developed multiregion combined RSs may be considered noninvasive predictive markers for planning early treatment for BM patients.

Advances in Stimuli-Responsive Chitosan Hydrogels for Drug Delivery Systems.

Sustainable and controllable drug transport is one of the most efficient ways of disease treatment. Due to high biocompatibility, good biodegradability, and low costs, chitosan and its derivatives are widely used in biomedical fields. Specifically, chitosan hydrogel enables drugs to pass through biological barriers because of their abundant amino and hydroxyl groups that can interact with human tissues. Moreover, the multi-responsive nature (pH, temperature, ions strength, and magnetic field, etc.) of chitosan hydrogels makes precise drug release a possibility. Here, the synthesis methods, modification strategies, stimuli-responsive mechanisms of chitosan-based hydrogels, and their recent progress in drug delivery are summarized. Chitosan hydrogels that carry and release drugs through subcutaneous (dealing with wound dressing), oral (dealing with gastrointestinal tract), and facial (dealing with ophthalmic, ear, and brain) are reviewed. Finally, challenges toward clinic application and the future prospects of stimuli-responsive chitosan-based hydrogels are indicated.

The role of ROS-pyroptosis in PM2.5 induced air-blood barrier destruction.

Fine particulate matter (PM2.5) has attracted increasing attention due to its health-threatening effects. Although numerous studies have investigated the impact of PM2.5 on lung injuries, the specific mechanisms underlying the damage to the air-blood barrier after exposure to PM2.5 remain unclear. In this study, we established an in vitro co-culture system using lung epithelial cells and capillary endothelial cells. Our findings indicated that the tight junction (TJ) proteins were up-regulated in the co-cultured system compared to the monolayer-cultured cells, suggesting the establishment of a more closely connected in vitro system. Following exposure to PM2.5, we observed damage to the air-blood barrier in vitro. Concurrently, PM2.5 exposure induced significant oxidative stress and activated the NLRP3 inflammasome-mediated pyroptosis pathway. When oxidative stress was inhibited, we observed a decrease in pyroptosis and an increase in TJ protein levels. Additionally, disulfiram reversed the adverse effects of PM2.5, effectively suppressing pyroptosis and ameliorating air-blood barrier dysfunction. Our results indicate that the oxidative stress-pyroptosis pathway plays a critical role in the disruption of the air-blood barrier induced by PM2.5 exposure. Disulfiram may represent a promising therapeutic option for mitigating PM2.5-related lung damage.

Angiogenesis, hemocompatibility and bactericidal effect of bioactive natural polymer-based bilayer adhesive skin substitute for infected burned wound healing.

Thermal wounds are complex and lethal with irregular shapes, risk of infection, slow healing, and large surface area. The mortality rate in patients with infected burns is twice that of non-infected burns. Developing multifunctional skin substitutes to augment the healing rate of infected burns is vital. Herein, we 3D printed a hydrogel scaffold comprising carboxymethyl chitosan (CMCs) and oxidized alginate grafted catechol (O-AlgCat) on a hydrophobic electrospun layer, forming a bilayer skin substitute (BSS). The functional layer (FL) was fabricated by physiochemical crosslinking to ensure favorable biodegradability. The gallium-containing hydrophobic electrospun layer or backing layer (BL) could mimic the epidermis of skin, avoiding fluid penetration and offering antibacterial activity. 3D printed FL contains catechol, gallium, and biologically active platelet rich fibrin (PRF) to adhere to both tissue and BL, show antibacterial activity, encourage angiogenesis, cell growth, and migration. The fabricated bioactive BSS exhibited noticeable adhesive properties (P ≤ 0.05), significant antibacterial activity (P ≤ 0.05), faster clot formation, and the potential to promote proliferation (P ≤ 0.05) and migration (P ≤ 0.05) of L929 cells. Furthermore, the angiogenesis was significantly higher (P ≤ 0.05) when evaluated in vivo and in ovo. The BSS-covered wounds healed faster due to low inflammation and high collagen density. Based on the obtained results, the fabricated bioactive BSS could be an effective treatment for infected burn wounds.

Nucleolus assembly impairment leads to two-cell transcriptional repression via NPM1-mediated PRC2 recruitment.

The nucleolus is a compartmentalized organelle in eukaryotic cells known to form during embryogenesis, yet how its layered architecture is transformed from homogenous precursor bodies is unclear, and any impacts of this formation on embryonic cell fate determination remain unknown. Here, we demonstrate that lncRNA LoNA tethers granular-component-enriched NPM1 to dense-fibrillar-component-enriched FBL and drives the formation of compartmentalized nucleolus via facilitating liquid-liquid phase separation of those two nucleolar proteins. Phenotypically, LoNA-deficient embryos show developmental arrest at the two-cell (2C) stage. Mechanistically, we demonstrate that LoNA deficiency leads to nucleolar formation failure, resulting in mislocalization and acetylation of NPM1 in the nucleoplasm. Acetylated NPM1 recruits and guides PRC2 complex to 2C genes, where PRC2 complex trimethylates H3K27, leading to transcriptional repression of these genes. Collectively, our findings reveal that lncRNA is required for the establishment of nucleolar structure, and this process has an impact on two-cell embryonic development via 2C transcriptional activation.

Comprehensive analysis of prediction of the EGFR mutation and subtypes based on the spinal metastasis from primary lung adenocarcinoma.

Purpose: To investigate the use of multiparameter MRI-based radiomics in the in-depth prediction of epidermal growth factor receptor (EGFR) mutation and subtypes based on the spinal metastasis in patients with primary lung adenocarcinoma. Methods: A primary cohort was conducted with 257 patients who pathologically confirmed spinal bone metastasis from the first center between Feb. 2016 and Oct. 2020. An external cohort was developed with 42 patients from the second center between Apr. 2017 and Jun. 2021. All patients underwent sagittal T1-weighted imaging (T1W) and sagittal fat-suppressed T2-weight imaging (T2FS) MRI imaging. Radiomics features were extracted and selected to build radiomics signatures (RSs). Machine learning classify with 5-fold cross-validation were used to establish radiomics models for predicting the EGFR mutation and subtypes. Clinical characteristics were analyzed with Mann-Whitney U and Chi-Square tests to identify the most important factors. Nomogram models were developed integrating the RSs and important clinical factors. Results: The RSs derived from T1W showed better performance for predicting the EGFR mutation and subtypes compared with those from T2FS in terms of AUC, accuracy and specificity. The nomogram models integrating RSs from combination of the two MRI sequences and important clinical factors achieved the best prediction capabilities in the training (AUCs, EGFR vs. Exon 19 vs. Exon 21, 0.829 vs. 0.885 vs.0.919), internal validation (AUCs, EGFR vs. Exon 19 vs. Exon 21, 0.760 vs. 0.777 vs.0.811), external validation (AUCs, EGFR vs. Exon 19 vs. Exon 21, 0.780 vs. 0.846 vs.0.818). DCA curves indicated potential clinical values of the radiomics models. Conclusions: This study indicated potentials of multi-parametric MRI-based radiomics to assess the EGFR mutation and subtypes. The proposed clinical-radiomics nomogram models can be considered as non-invasive tools to assist clinicians in making individual treatment plans.

PM2.5 induce myocardial injury in hyperlipidemic mice through ROS-pyroptosis signaling pathway.

Exposure to particulate matters with diameters below 2.5 µm (PM2.5) is considered a major risk factor for cardiovascular diseases (CVDs). The closest associations between PM2.5 and CVDs have been observed in hyperbetalipoproteinemia cases, although the detailed underpinning mechanism remains undefined. In this work, hyperlipidemic mice and H9C2 cells were used to examine the effects of PM2.5 on myocardial injury and their underlying mechanisms. The results revealed that PM2.5 exposure caused severe myocardial damage in the high-fat mouse model. Oxidative stress and pyroptosis were also observed along with myocardial injury. After inhibiting pyroptosis with disulfiram (DSF), the level of pyroptosis was effectively reduced as well as myocardial injury, suggesting that PM2.5 induced the pyroptosis pathway and further caused myocardial injury and cell death. Afterwards, by suppressing PM2.5-induced oxidative stress with N-acetyl-L-cysteine (NAC), myocardial injury was markedly ameliorated, and the upregulation of pyroptosis markers was reversed, which indicated that PM2.5-pyroptosis was also improved. Taken together, this study revealed that PM2.5 induce myocardial injury through the ROS-pyroptosis signaling pathway in hyperlipidemia mice models, providing a potential approach for clinical interventions.

Development of "smart" drug delivery systems for chemo/PDT synergistic treatment.

Although chemotherapy and photodynamic therapy (PDT) have been developed for fighting cancer, the complex and heterogeneous nature of tumors makes it difficult for a single therapy to completely inhibit tumor growth. In order to reduce multidrug resistance of cancer cells to chemotherapeutic drugs and overcome low PDT efficiency in the hypoxic tumor microenvironment (TME), chemo/PDT synergistic treatment has received much attention in recent years. Depending on the characteristic signals of TME, various drug delivery systems can be constructed to target tumors and improve the therapeutic efficacy and the pharmacokinetic profile of anticancer drugs. This review highlights the synergistic strategies, treatment protocols, and design of chemo/PDT co-therapy in recent years to explore its scope and limitations. Taking advantage of stimuli-responsive materials and active cancer-targeting agents, cancer-targeting synergistic therapy is presented and discussed, providing ideas and suggestions for the construction of chemo/PDT co-therapy "smart" nanocarriers.