Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.

BACKGROUND: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.

BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma.

BACKGROUND: Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. RESULTS: In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. CONCLUSIONS: Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Video Abstract.

Engineering a triple-functional magnetic gel driving mutually-synergistic mild hyperthermia-starvation therapy for osteosarcoma treatment and augmented bone regeneration.

Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe3O4/GOx/MgCO3@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Biodegradable Hollow-Structured Nanozymes Modulate Phenotypic Polarization of Macrophages and Relieve Hypoxia for Treatment of Osteoarthritis.

Nanozymes are widely applied for treating various major diseases, including neurological diseases and tumors. However, the biodegradability of nanozymes remains a great challenge, which hinders their further clinical translation. Based on the microenvironment of osteoarthritis (OA), a representative pH-responsive biodegradable hollow-structured manganese Prussian blue nanozyme (HMPBzyme) is designed and applied for treatment of OA. HMPBzyme with good pH-responsive biodegradability, biocompatibility, and multi-enzyme activities is constructed by bovine serum albumin bubbles as a template-mediated biomineralization strategy. HMPBzyme suppresses hypoxia-inducible factor-1α (HIF-1α) expression and decreases reactive oxygen species (ROS) level in the in vitro experiment. Furthermore, HMPBzyme markedly suppresses the expression of ROS and alleviates the degeneration of cartilage in OA rat models. The results indicate that the biodegradable HMPBzyme inhibits oxidative damage and relieves hypoxia synergistically to suppress inflammation and promote the anabolism of cartilage extracellular matrix by protecting mitochondrial function and down-regulating the expression of HIF-1α, which modulates the phenotypic conversion of macrophages from pro-inflammatory M1 subtype to anti-inflammatory M2 subtype for OA treatment. This research lays a solid foundation for the design, construction, and biomedical application of biodegradable nanozymes and promotes the application of nanozymes in biomedicine.

Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis.

Magnetic micro-/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA-Fe3 O4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA-Fe3 O4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration-free NPs can assemble into micro-/milli-scale swarms capable of robust maneuver and reconfigurable transformation for on-demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs' inherent enzymatic effect and swarming-triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming-enhanced ultrasound signals aid in imaging-guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.

Failure mode effect and criticality analysis of ultrasound device by classification tracking.

BACKGROUND: Medical ultrasound device has been more and more widely used in the hospital and Its safety risk is significantly increased when failures occur. However, there is a lack of quantitative risk assessments of different types of failure modes for medical ultrasound device. This study utilizes a failure mode, effect and criticality analysis (FMECA) approach for quantitative risk evaluation of different failure modes for ultrasound devices. METHODS: The 4216 medical ultrasound device failure records at various hospitals were investigated. A failure mode and effect analysis method was developed for the quantitative evaluation of the risks of different failure modes. Visual correlation analysis was conducted for all categories to identify the causes of various failure modes. Based on the severity, occurrence and detectability of the failure causes determined, the risk priority number (RPN) for each failure mode was back-calculated through the obtained tracking diagram. RESULTS: The failure modes of unclear images, unable to power on and dark shadows on an image had the highest RPNs. One failure mode could be caused by various factors, and the failure location was not necessarily related to the cause of the failure. CONCLUSIONS: This quantitative approach more accurately evaluated the risks of different failure modes, and the results of the corresponding analysis of failure modes and causes could support the rapid determination of the causes of failures in clinical practice.

A Three-in-One Strategy: Injectable Biomimetic Porous Hydrogels for Accelerating Bone Regeneration via Shape-Adaptable Scaffolds, Controllable Magnesium Ion Release, and Enhanced Osteogenic Differentiation.

The repair of bone defects with irregular shapes, particularly in a minimally invasive manner, remains a major challenge. For synthetic bone grafts, injectable hydrogels are superior to conventional scaffolds because they can adapt satisfactorily to the defect margins and can be injected into deeper areas of injury via a minimally invasive procedure. Based on the poly(lactide-co-glycolide)(PLGA)/1-methyl-2-pyrrolidinone solution reported in our previous study, we successfully synthesized injectable MgO/MgCO3@PLGA (PMM) hydrogels, namely, injectable biomimetic porous hydrogels (IBPHs), to accelerate bone regeneration. In addition to exhibiting excellent injectability, PMM hydrogels could transform into porous scaffolds in situ through a liquid-to-solid phase transition and completely fill irregular bone defects via their superb shape adaptability. Moreover, sustainable and steady release of Mg2+ was achieved by regulating the weight ratio of the incorporated MgO and MgCO3 particles. Via controlled release of Mg2+, PMM hydrogels significantly promoted proliferation, osteogenic differentiation, migration, and biomineral deposition of immortalized mouse embryonic fibroblasts. More importantly, micro-CT imaging and histological analysis indicated that concomitant with their gradual degradation, PMM hydrogels effectively stimulated in situ bone regeneration in rat calvarial defects with an increase in the bone volume fraction of almost 2-fold compared with that in the control group. These findings suggest that injectable PMM hydrogels can satisfactorily match bone defects and form porous scaffolds in situ and can significantly promote bone regeneration via controllable Mg2+ release. The remarkable features of IPBHs may open a new avenue for the exploration of in situ repair systems for irregular bone defects to accelerate bone regeneration and have great potential for clinical translation.

Ultrasound lymphatic imaging for the diagnosis of metastatic central lymph nodes in papillary thyroid cancer.

OBJECTIVES: Up to 40% of papillary thyroid cancer (PTC) patients have lymph node metastasis, a condition that implies persistent, recurrent, or progressive disease. However, the American Joint Committee on Cancer Manual states that there is no reliable examination for adequate lymph node staging. Therefore, our aim is to develop a lymphatic imaging technique using ultrasonography to address this challenge. METHODS: We consecutively enrolled PTC patients who underwent ultrasound (US) lymphatic imaging via the peritumoral injection of contrast media. Identification of the sentinel lymph nodes and the targeted sentinel lymph nodes was separately based on the lymphatic drainage pathway and the enhancement patterns. Every identified targeted node was assigned a score, according to the features on conventional US and enhancement patterns, and was referred for ultrasound-guided fine-needle aspiration. Cytological and histopathologic results represented the statuses of the targeted lymph nodes and overall central lymph nodes, respectively, which were applied to evaluate the diagnostic performance of US lymphatic imaging. RESULTS: In total, 100 PTC patients were included. On the basis of the cytological results, the sensitivity (97.1%, 95% confidence interval [CI]: 84.7-99.9%) of detecting positive targeted nodes by US lymphatic imaging significantly increased by 45.5% at a threshold of 4 or higher (p = 0.0001), without loss of specificity (p = 1.0000). The surgical results showed that the metastatic degree was positively correlated with an increase in the score (τ: 0.671, p < 0.001). CONCLUSION: Ultrasound lymphatic imaging has a high diagnostic performance, and its corresponding scoring system facilitates grading of the nodal burden in the central compartment. KEY POINTS: • Ultrasound neck lymphatic imaging is an effective contrast-enhanced ultrasound (CEUS) technique (applied after the peritumoral injection of contrast media) for identifying sentinel lymph nodes in the central compartment by tracing the imaged afferent lymphatic vessel. • Lack of enhancement or perfusion defects is the typical enhancement pattern for recognizing the involved central lymph nodes. • Ultrasound lymphatic imaging for identification of positive central lymph nodes before surgery may effectively avoid complications associated with the surgical sentinel node procedure.

Self-synergistic effect of Prussian blue nanoparticles for cancer therapy: driving photothermal therapy and reducing hyperthermia-induced side effects.

BACKGROUND: Photothermal therapy (PTT), involving application of localized hyperthermia to kill cancer cells, has attracted wide attention in cancer therapy. The production of reactive oxygen species (ROS) during PTT may cause irreversible damage to healthy tissues around the tumor. Simultaneously, hyperthermia can stimulate inflammatory response, thus promoting tumor recurrence and metastasis. Therefore, it is of paramount importance to reduce the undesired side effects for further development of PTT. RESULTS: Using a hydrothermal method, spherical Prussian blue nanoparticles (PBs) with uniform size were prepared. The PBs exhibited good dispersion and stability in saline with an average hydrodynamic size of 110 nm. The prepared PBs had a high photothermal conversion efficiency and photothermal stability. The PBs showed intrinsic ROS scavenging properties in vitro. Antioxidant and anti-inflammatory effects of PBs were also observed in vivo. Assessment of toxicity and endoplasmic reticulum stress-inducing ability showed that PBs did not induce an inflammatory response. Tissues of major organs of mice stained with hematoxylin-eosin showed no significant damage, indicating good biocompatibility and safety of PBs. CONCLUSION: The designed single-component PBs with intrinsic ROS scavenging and anti-inflammatory properties could avoid inflammatory response and heat stress-induced ROS during PTT. Thus, further research on PBs is worthwhile to achieve their clinical translation and promote the development of PTT.

Biodegradable reduce expenditure bioreactor for augmented sonodynamic therapy via regulating tumor hypoxia and inducing pro-death autophagy.

BACKGROUNDS: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor strategy is challenged by the rapid depletion of oxygen, as well as the hypoxic tumor microenvironment. Instead of the presently available coping strategies that amplify the endogenous O2 level, we have proposed a biodegradable O2 economizer to reduce expenditure for augmenting SDT efficacy in the present study. RESULTS: We successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) via conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (hematoporphyrin monomethyl ether; HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia conditions. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induced excessive activation of autophagy for promoting the therapeutic efficacy. As a result, when accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP could achieve the remarkable antitumor activity, which was systematically validated both in vivo and in vitro assays. CONCLUSIONS: This work not only provides a reduce expenditure means for enduring SDT, but also represents an inquisitive strategy for tumor treatments by inducing pro-death autophagy.

Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation.

BACKGROUND: The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake. RESULTS: Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy. CONCLUSIONS: This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies.

Hollow Prussian Blue Nanozymes Drive Neuroprotection against Ischemic Stroke via Attenuating Oxidative Stress, Counteracting Inflammation, and Suppressing Cell Apoptosis.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi3+-assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Facile Synthesis of Yolk-Shell-Structured Triple-Hybridized Periodic Mesoporous Organosilica Nanoparticles for Biomedicine.

The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk-shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery.

Shear Wave Elastography of the Spleen for Monitoring Transjugular Intrahepatic Portosystemic Shunt Function: A Pilot Study.

OBJECTIVES: To assess the feasibility of splenic shear wave elastography in monitoring transjugular intrahepatic portosystemic shunt (TIPS) function. METHODS: We measured splenic shear wave velocity (SWV), main portal vein velocity (PVV), and splenic vein velocity (SVV) in 33 patients 1 day before and 3 days to 12 months after TIPS placement. We also measured PVV, SVV, and SWV in 10 of 33 patients with TIPS dysfunction 1 day before and 3 to 6 days after TIPS revision. Analyses included differences in portosystemic pressure gradient (PPG), PVV, SVV, and mean SWV before and after TIPS procedures; comparison of median SWV before and after TIPS procedures; differences in PVV, SVV, and SWV before and at different times up to 12 months after TIPS placement; accuracy of PVV, SVV, and SWV in determining TIPS dysfunction; and correlation between PPG and SWV. RESULTS: During 12 months of follow-up, 23 of 33 patients had functioning TIPS, and 10 had TIPS dysfunction. The median SWV was significantly different before and after primary TIPS placement (3.60 versus 3.05 m/s; P = .005), as well as before and after revision (3.73 versus 3.06 m/s; P = .003). The PPG, PVV, and SVV were also significantly different before and after TIPS placement and revision (P < .001). The PPG and SWV decreased, whereas PVV and SVV increased, after successful TIPS procedures. A positive correlation was observed between PPG and SWV (r = 0.70; P < .001), and a negative correlation was observed between PPG and PVV and SVV (r = -0.65; P < .001). The areas under the receiver operating characteristic curve for PVV, SVV, and SWV in determining TIPS dysfunction were 0.82, 0.84, and 0.81, respectively. CONCLUSIONS: Splenic SWV is compatible with splenoportal venous velocity in quantitatively monitoring TIPS function and determining TIPS dysfunction.

A Facile Multi-interface Transformation Approach to Monodisperse Multiple-Shelled Periodic Mesoporous Organosilica Hollow Spheres.

The synthesis of well-defined and complex hollow structures via a simple method is still a major challenge. In this work, a facile and controllable "multi-interface transformation" approach for preparation of monodisperse multi-shelled periodic mesoporous organosilica (PMO) hollow spheres has been established by a one-step hydrothermal treatment of successively grown organosilica particles. The multi-shelled PMO hollow spheres have inorganic-organic hybrid frameworks, controllable number (1-4) of shells, high surface area (∼805 m(2)/g), accessible ordered mesochannels (∼3.2 nm), large pore volume (1.0 cm(3)/g), and uniform and tunable diameter (300-550 nm), chamber size (4-54 nm), and shell thickness (10-30 nm). In addition, various organic groups (alkyl, aromatic, and heteroelement fragments) are successfully incorporated into the multi-shelled PMO hollow spheres by successively adding different bridged organosilica precursors. Notably, the distribution of different kinds of organic groups in the multi-shelled PMO hollow spheres can be precisely controlled, showing great potential for future applications. We propose that the formation of the multi-shelled PMO hollow structures is ascribed to the creation of multiple highly cross-linked organosilica interfaces, providing a new and interesting fundamental principle for PMO materials. Due to their unique structure and frameworks, triple-shelled ethane-bridged PMO hollow spheres were successfully loaded with an anti-cancer drug doxorubicin and perfluoropentane gas, which present excellent effects in the killing of cancer cells and ultrasound imaging. It is expected that the multi-interface transformation strategy provides a simple, controllable, versatile, and template-free method for preparation of various multifunctional PMOs for different applications.

Evaluation of superparamagnetic iron oxide-polymer composite microcapsules for magnetic resonance-guided high-intensity focused ultrasound cancer surgery.

BACKGROUND: Superparamagnetic poly (lactic-co-glycolic acid) (PLGA)-coated Fe3O4 microcapsules are receiving increased attention as potential diagnostic and therapeutic modalities in the field of oncology. In this study, PLGA-coated Fe3O4 microcapsules were combined with a magnetic resonance imaging-guided high-intensity focused ultrasound (MR-guided HIFU) platform, with the objective of investigating the effects of these composite microcapsules regarding MR-guided HIFU liver cancer surgery in vivo. METHODS: PLGA-coated Fe3O4 microcapsules consisting of a liquid core and a PLGA-Fe3O4 shell were fabricated using a modified double emulsion evaporation method. Their acute biosafety was confirmed in vitro using MDA cells and in vivo using rabbits. To perform MR-guided HIFU surgery, the microcapsules were intravenously injected into a rabbit liver tumor model before MR-guided HIFU. T2-weighted images and MR signal intensity in normal liver parenchyma and tumor tissue were acquired before and after injection, to assess the MR imaging ability of the microcapsules. After MR-guided HIFU ablation tissue temperature mapping, the coagulative volume and histopathology of the tumor tissue were analyzed to investigate the ablation effects of MR-guided HIFUs. RESULTS: Scanning and transmission electron microscopy showed that the microcapsules displayed a spherical morphology and a shell-core structure (mean diameter, 587 nm). The hysteresis curve displayed the typical superparamagnetic properties of the microcapsules, which are critical to their application in MR-guided HIFU surgery. In MR-guided HIFU surgery, these microcapsules functioned as an MRI contrast agent, induced significant hyperthermal enhancement (P < 0.05) and significantly enhanced the volume of coagulative necrosis (P < 0.05). CONCLUSIONS: The administration of PLGA-coated Fe3O4 microcapsules is a potentially synergistic technique regarding the enhancement of MR-guided HIFU cancer surgery.

Adaptive Multi-Dimensional Weighted Network With Category-Aware Contrastive Learning for Fine-Grained Hand Bone Segmentation.

Accurately delineating and categorizing individual hand bones in 3D ultrasound (US) is a promising technology for precise digital diagnostic analysis. However, this is a challenging task due to the inherent imaging limitations of the US and the insignificant feature differences among numerous bones. In this study, we have proposed a novel deep learning-based solution for pediatric hand bone segmentation in the US. Our method is unique in that it allows for effective detailed feature mining through an adaptive multi-dimensional weighting attention mechanism. It innovatively implements a category-aware contrastive learning method to highlight inter-class semantic feature differences, thereby enhancing the category discrimination performance of the model. Extensive experiments on the challenging pediatric clinical hand 3D US datasets show the outstanding performance of the proposed method in segmenting thirty-eight bone structures, with the average Dice coefficient of 90.0%. The results outperform other state-of-the-art methods, demonstrating its effectiveness in fine-grained hand bone segmentation. Our method will be globally released as a plugin in the 3D Slicer, providing an innovative and reliable tool for relevant clinical applications.