Doping-Engineered Piezoelectric Ultrathin Nanosheets for Synergistically Piezo-Chemocatalytic Antitumor and Antibacterial Therapies Against Cutaneous Melanoma.

The post-surgical melanoma recurrence and wound infections have persistently troubled clinical management. Piezocatalytic therapy features high efficiency in generating reactive oxygen species (ROS) for tumor therapy, but it faces limitations in piezoelectricity and redox-active site availability. Herein, Fe-doped ultrathin Bi4Ti3O12 nanosheets (designated as Fe-UBTO NSs) with synergistically piezo-chemocatalytic activity are engineered for antitumor and antibacterial treatment against cutaneous melanoma. The doping-engineered strategy induces oxygen vacancies and lattice distortions in Fe-UBTO NSs, which narrows bandgap to enhance piezocatalytic 1O2 and H2O2 generation by improving the electron-hole pairs separation, hindering their recombination, and increasing oxygen adsorption. Moreover, Fe doping establishes a piezo-chemocatalytic system, in which the piezocatalysis enables the self-supply of H2O2 and expedites electron transfer in Fenton reactions, inducing increased ·OH production. Besides, the atomic-level thickness and expanded surface area enhance the sensitivity to ultrasound stimuli and expose more redox-active sites, augmenting the piezo-chemocatalytic efficiency, and ultimately leading to abundant ROS generation. The Fe-UBTO-mediated piezo-chemocatalytic therapy causes intracellular oxidative stress, triggering apoptosis and excessive autophagy of tumor cells. Moreover, this strategy accelerates wound healing by facilitating sterilization, angiogenesis, and collagen deposition. This work provides distinct options to develop doping-engineered ultrathin nanosheets with augmented piezo-chemocatalytic activity for postoperative management of cutaneous melanoma.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Automated Breast Volume Scanner Is More Valuable Than Hand-Held Ultrasound in Diagnosis of Small Breast cancer: An Analysis of 725 Patients With 912 Lesions Evaluations.

ABSTRACT: This study aimed to evaluate the clinical value of automated breast volume scanner (ABVS) compared with hand-held ultrasound (HHUS). From January 2015 to May 2019, a total of 912 breast lesions in 725 consecutive patients were included in this study. κ statistics were calculated to identify interobserver agreement of ABVS and HHUS. The diagnostic performance for ABVS and HHUS was expressed as the area under the receiver operating characteristic curve, as well as the corresponding 95% confidence interval, sensitivity, and specificity. The sensitivities of ABVS and HHUS were 95.95% and 93.69%, and the specificities were 85.47% and 81.20%, respectively. A difference that nearly reached statistical significance was observed in sensitivities between ABVS and HHUS (P = 0.0525). The specificity of ABVS was significantly higher than that of HHUS (P = 0.006). When lesions were classified according to their maximum diameter, the sensitivity and specificity of ABVS were significantly higher than HHUS for lesions ≤20 mm, while they made no statistical significance between ABVS and HHUS for lesions >20 mm. The interobserver agreement for ABVS was better than that of HHUS. Automated breast volume scanner was more valuable than HHUS in diagnosing breast cancer, especially for lesions ≤20 mm, and it could be a valuable diagnostic tool for breast cancer.

A conditional inference tree model for predicting cancer risk of non-mass lesions detected on breast ultrasound.

OBJECTIVES: To generate and validate a prediction model based on imaging features for cancer risk of non-mass lesions (NMLs) detected on breast ultrasound (US). METHODS: In this single-center study, consecutive women with 503 NMLs detected on breast US between 2012 and 2019 were retrospectively identified. The lesions were randomly assigned to the training or testing dataset with a 70/30 split. Age, symptoms, lesion size, and US features were collected. Multivariate analyses were employed to identify risk factors associated with malignancy. The predictive model was developed by using conditional inference trees (CTREE). RESULTS: There were 498 patients (50.9 ± 13.29 years; range, 22-88 years) with 503 NMLs with histopathologic results or > 2-year follow-up, including 224 (44.5%) benign and 279 (55.5%) malignant lesions. At multivariate analysis, age (odds ratio (OR) = 1.08, 95% confidence interval (CI), 1.06-1.11, p < 0.001), NMLs with focal mass effect (OR = 3.03, 95% CI, 1.59-5.81, p = 0.001), indistinct glandular-fat interface (GFI) (OR = 4.23, 95% CI, 2.31-7.73, p < 0.001), geographic (OR = 3.47, 95% CI, 1.20-10.8, p = 0.022) and mottled (OR = 3.67, 95% CI, 1.32-10.21, p = 0.013) patterns, and calcifications (OR = 2.15, 95% CI, 1.16-4.01, p = 0.016) were associated with malignancy. The GFI status, architectural patterns, general morphology, and calcifications were consistently identified as the strongest US predictors of malignancy using CTREE analysis. Based on these factors, individuals were stratified into six risk groups. The predictive model showed an area under the curve of 0.797 in the testing dataset. CONCLUSION: The CTREE model efficiently aids in interpreting and managing ultrasound-detected breast NMLs, overcoming BI-RADS limitations by refining cancer risk stratification. CLINICAL RELEVANCE STATEMENT: The CTREE model allows for the reclassification of BI-RADS categories into subgroups with varying malignancy probabilities, thus providing a valuable enhancement to the BI-RADS assessment for the diagnosis of ultrasound-detected NMLs, with the potential to minimize unnecessary biopsies. KEY POINTS: • The indistinct glandular-fat interface (GFI) status, NML with focal mass effect, geographic or mottled patterns, and calcifications are the strongest imaging predictors of malignant non-mass lesions (NMLs) detected on breast US. • A practical system has been created to categorize NMLs found in breast US; each classification is associated with a degree of diagnostic certainty. • The model may contribute to patient stratification by determining the relative likelihood of malignancy and thus support clinical decision-making and evidence-based management.

Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization.

The infiltration of inflammatory cells, especially macrophages, integrated with the production of reactive oxygen and nitrogen species (RONS) and the release of inflammatory cytokines play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Synergistic combination of RONS scavenging and macrophage repolarization from pro-inflammatory M1 phenotype towards anti-inflammatory M2 phenotype, provides a promising strategy for efficient RA treatment. Herein, this study reported a unique self-assembly strategy to construct distinct rosmarinic acid nanoparticles (RNPs) for efficient RA treatment using the naturally occurring polyphenol-based compound, rosmarinic acid (RosA). The designed RNPs exhibited favorable capability in scavenging RONS and pro-inflammatory cytokines produced by macrophages. Attributing to the widened vascular endothelial-cell gap at inflammation sites, RNPs could target and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats for guaranteeing therapeutic effect. In vivo investigation demonstrated that RNPs alleviated the symptoms of RA, including joint swelling, synovial hyperplasia, cartilage degradation, and bone erosion in CIA rats. Additionally, the designed RNPs promoted macrophage polarization from M1 phenotype towards M2 phenotype, resulting in the suppressed progression of RA. Therefore, this research represents the representative paradigm for RA therapy using antioxidative nanomedicine deriving from the natural polyphenol-based compound.

Quantitative Indicators of Retraction Phenomenon on an Automated Breast Volume Scanner: Initial Study in the Diagnosis and Prognostic Prediction of Breast Tumors.

Retraction phenomenon is a unique sign on an automated breast volume scanner coronal plane image and has high specificity in differentiating benign lesions from malignant breast cancer. The purpose of this study was to quantify the retraction phenomenon by setting different rules to describe connected regions from different dimensions. In total, six quantitative indicators (FΩ1,FΓ,FS,FΩ2,FΩ3and FL) were obtained. FΩ1, FΩ2 and FΩ3 represent the relative areas of the connected region under different rules. FΓandFS represent the number ratio and absolute area of the connected region, respectively. FL represents the ratio of edge numbers. Two hundred fourteen patients with 214 lesions (90 benign and 124 malignant) were enrolled in this study. All quantitative indicators in the malignant group were significantly higher than those in the benign group (all p values <0.001). The indicator FΓ achieved the highest area under the receiver operating characteristic curve (AUC) (0.701, 95% confidence interval: 0.631-0.771). Both FΓ and FS had significant associations with axillary lymph node metastasis (p = 0.023 and 0.049). Compared with the classic texture feature gray-level co-occurrence matrix, retraction phenomenon quantization improved the AUC by 8.3%. The results indicate that retraction phenomenon quantitative indicators have certain value in distinguishing benign and malignant breast lesions and seem to be associated with axillary lymph node metastasis.