Bacterial outer membrane vesicle-cancer cell hybrid membrane-coated nanoparticles for sonodynamic therapy in the treatment of breast cancer bone metastasis.

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.

The relationship of social isolation and sleep in older adults: evidence from cross-sectional and longitudinal studies.

OBJECTIVES: This study aimed to explore the relationship between social isolation and sleep in later life and the role of loneliness in this relationship. METHODS: In Study 1, we conducted a cross-sectional analysis of the correlation between social isolation and sleep in community-dwelling older adults (N = 108). This relationship was assessed using subjective and objective measures. Moreover, we examined the mediating role of loneliness cross-sectionally (Study 1) and longitudinally (Study 2). Longitudinal study was based on three waves of data from the National Scale Life, Health, and Aging Project (N = 1, 554). RESULTS: The results showed that social isolation was robustly associated with sleep in the general population of older adults. Specifically, subjective social isolation was associated with subjective sleep, and objective social isolation was associated with objective sleep. The results of the longitudinal study showed that loneliness mediated the reciprocal link between social isolation and sleep across time after controlling for autoregressive effects and basic demographics. CONCLUSIONS: These findings address the gap in the literature on the link between social isolation and sleep in older adults, extending the understanding of improvement in older adults' social networks, sleep quality, and psychological well-being.

The clinical application of ultrasonography with superb microvascular imaging-a review.

Superb microvascular imaging (SMI) is among the latest doppler ultrasound methods. It uses an advanced clutter filter to eliminate artifacts caused by breathing, movement and retains the low-speed blood signals in microvessels. The great advantage of SMI is that it can intuitively detect very slow blood signals in microvessels, providing clinicians with more significant information about flow distribution in the target area. Therefore, it is speculated that SMI has important application value. The purpose of this article is to outline the application of SMI in different parts of the body.

Mummified Thyroid Nodules: Conventional and Contrast-Enhanced Ultrasound Features.

OBJECTIVES: The purpose of our study was to highlight the conventional and contrast-enhanced ultrasound (US) features of mummified thyroid nodules, which should help differentiate them from histologically proven papillary thyroid carcinomas (PTCs). METHODS: Thirty-one patients with 33 mummified thyroid nodules, which showed suspicious US findings that were suggestive of malignancy, as well as 33 patients with 38 surgically confirmed PTCs were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of shadowing and halo, presence of punctate echogenic foci, vascularity, and contrast enhancement parameters for each nodule. The final diagnosis of mummified thyroid nodules was confirmed via fine-needle aspiration (FNA) or surgery. RESULTS: Of the 33 mummified thyroid nodules, 9 (27.3%) were confirmed by surgery to be benign, and 24 (72.7%) were proven by FNA to be benign. A univariate analysis indicated that the mummified thyroid nodules more frequently showed wider-than-tall shapes, marked hypoechogenicity, the presence of posterior shadowing, the absence of nodular vascularity, hypoenhancement or no enhancement, and peak index and area under the curve indices of less than 1 in the findings of preoperative US and contrast-enhanced US compared to PTCs. A multivariate analysis showed that marked hypoechogenicity and an area under the curve index of less than 1 were independent characteristics related to mummified nodules for discriminating from PTCs (all P < .05). CONCLUSIONS: Benign thyroid nodules may display shrinkage over time and may reveal malignant US features. Awareness of these findings and their connection with initial and follow-up US examinations should help identify mummified thyroid nodules and to avoid surgical excision or unnecessary FNA.

Analysis of left ventricular fluid dynamics in dilated cardiomyopathy by echocardiographic particle image velocimetry.

OBJECTIVE: The aim was to analyze left ventricular (LV) fluid dynamics in dilated cardiomyopathy (DCM) by using echocardiographic particle image velocimetry (E-PIV). METHODS: Twenty patients with DCM and twenty healthy volunteers were examined. LV ultrasound contrast was administered by intravenous bolus injection. At least three dynamic contrast-enhanced echocardiographic images of cardiac cycles from apical three-chamber view and four-chamber view were obtained. The acquired echocardiographic image loops were processed off line by HyperFlow. RESULTS: In healthy hearts, the filling flow in the left ventricle finally comes to be a single large clockwise vortex, which smoothly redirects the blood to the outflow tract. Meanwhile, aberrant flow patterns are observed in the patients with DCM. In the DCM group, the vortex area (0.237 ± 0.063 vs 0.196 ± 0.129, P = .029), vortex depth (0.396 ± 0.134 vs 0.293 ± 0.143, P = .025), and vortex length (0.534 ± 0.089 vs 0.435 ± 0.176, P = .004) are significantly higher. The flow force angle (29.979 ± 8.208 vs 35.896 ± 6.044, P = .013) is significantly lower, and energy dissipation (0.975 ± 0.552 vs 0.578 ± 0.295, P = .006) is significantly higher. A negative linear relation is indicated between the following pairs of parameters: vortex depth and LV ejection fraction (EF) (r = -.350, P = .027); vortex length and LV EF (r = -.321, P = .044); energy dissipation and LV EF (r = -.523, P = .001). A positive linear relation is indicated between flow force angle and LV EF (r = .365, P = .021). CONCLUSION: E-PIV can effectively and quantitatively evaluate LV fluid dynamics in patients with DCM. LV fluid dynamics and LV systolic function interact with and affect each other.

Contrast-enhanced ultrasound of small cell carcinoma in urinary bladder: a case report and review of literature.

BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is a relatively rare malignant bladder tumor, and few reports have investigated the microvasculature of SCCB imaged using contrast-enhanced ultrasound (CEUS). CASE PRESENTATION: A 63-year-old female was admitted to our hospital after experiencing painless gross hematuria for one week. The gray-scale ultrasound (US) demonstrated a 4.8 × 3.4 × 3.6-cm3 hypoechoic mass in the apex of the urinary bladder with a wide base and an irregular surface; the mass did not move with changes in body position. Color Doppler flow imaging (CDFI) showed rich blood flow in the mass. CEUS with low mechanical index (MI) of 0.06 confirmed a highly enhanced 5.0 × 3.3 × 3.8 cm3 mass within the bladder at the apex wall. The time-intensity curves (TICs) showed a wash-in time of 10 s, a time to peak (TTP) of 33 s, a signal intensity (SI) of 62.7% and a wash-out time > 60 s. Finally, the transurethral resection of the bladder tumor (TURBT) was performed, and the pathological examination proved the diagnosis of SCCB. CONCLUSION: CEUS can provide valuable information related to the rich microvasculature of SCCB, which may be helpful in its diagnosis.

Expression of IL-17A and IL-17F in lipopolysaccharide-induced acute lung injury and the counteraction of anisodamine or methylprednisolone.

Th17 cytokines IL-17A and IL-17F as pro-inflammatory cytokines played an important role in triggering inflammatory responses. However, little was known about the expression of IL-17A and IL-17F in acute lung injury (ALI). Therefore, the present study investigated the expression of IL-17A and IL-17F in lipopolysaccharide (LPS)-induced ALI in rats and rat pulmonary microvascular endothelial cells (PMVEC) by enzyme-linked immunosorbant assay or reverse transcription-polymerase chains reaction. Anisodamine and methylprednisolone were also investigated as anti-inflammatory strategy in the process of LPS-induced ALI. Lung injury was evaluated by histological changes, right lung wet weight:body weight (LW/BW) ratios, and protein education and total leukocyte count of bronchoalveolar lavage fluid (BALF). Our findings showed that LPS exposure elevated the levels of leukocyte number, protein education in BALF and the ratios of LW/BW, increased the expression of IL-17A and IL-17F in the lung tissues homogenate, BALF and serum of ALI rats. Up-regulation of IL-17F expression was also observed after LPS challenge in rat PMVEC. Treatment with anisodamine or methylprednisolone significantly inhibited the increases of parameters of ALI induced by LPS, and markedly reduced the expression of IL-17A and IL-17F in rats and the IL-17F expression in PMVEC. These data suggested that IL-17A and IL-17F maybe play an important role in LPS-induced ALI via autocrine and paracrine mechanisms, and anisodamine is similar in extent to methylprednisolone that contributes to relieve LPS-induced ALI.

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.

Macrophage-derived biomimetic nanoparticles enhanced SDT combined with immunotherapy inhibited tumor growth and metastasis.

Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy.

Temperature-Sensitive Nanocarbon Hydrogel for Photothermal Therapy of Tumors.

Background: Intelligent hydrogels continue to encounter formidable obstacles in the field of cancer treatment. A wide variety of hydrogel materials have been designed for diverse purposes, but materials with satisfactory therapeutic effects are still urgently needed. Methods: Here, we prepared an injectable hydrogel by means of physical crosslinking. Carbon nanoparticle suspension injection (CNSI), a sentinel lymph node imaging agent that has been widely used in the clinic, with sodium ß-glycerophosphate (ß-GP) were added to a temperature-sensitive chitosan (CS) hydrogel (CS/GP@CN) as an agent for photothermal therapy (PTT). After evaluating the rheological, morphological, and structural properties of the hydrogel, we used 4T1 mouse breast cancer cells and B16 melanoma cells to assess its in vitro properties. Then, we intratumorally injected the hydrogel into BALB/c tumor-bearing mice to assess the in vivo PTT effect, antitumor immune response and the number of lung metastases. Results: Surprisingly, this nanocarbon hydrogel called CS/GP@CN hydrogel not only had good biocompatibility and a great PTT effect under 808nm laser irradiation but also facilitated the maturation of dendritic cells to stimulate the antitumor immune response and had an extraordinary antimetastatic effect in the lungs. Discussion: Overall, this innovative temperature-sensitive nanocarbon hydrogel, which exists in a liquid state at room temperature and transforms to a gel at 37 °C, is an outstanding local delivery platform with tremendous PTT potential and broad clinical application prospects.

Multimodal predictive factors of metastasis in lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

Objective: The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is a crucial component of the central lymph nodes (LNs). We aimed to evaluate multimodal predictive factors of LN-prRLN metastasis in patients with papillary thyroid carcinomas (PTCs), including the clinical data, pathologic data, and preoperative sonographic characteristics of PTCs. Methods: A total of 403 diagnosed PTC patients who underwent unilateral, sub-total, or total thyroidectomy with central neck dissection were enrolled in this retrospective study. The clinical data, pathologic data, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of PTCs were collected and evaluated for predicting LN-prRLN metastasis. Results: In this study, 96 PTC patients with LN-prRLN metastasis and 307 PTC patients without LN-prRLN metastasis were included. Univariate analysis demonstrated that PTC patients with LN-prRLN metastasis more often had younger age, larger size, multifocal cancers, A/T < 1, well-margins, microcalcification, petal-like calcification, internal vascularity, centripetal perfusion pattern and surrounding ring enhancement. Multivariate logistic regression analysis revealed that the CEUS centripetal perfusion pattern, central LN detected by ultrasound and LN-arRLN metastasis were independent characteristics for predicting LN-prRLN metastasis in PTC patients. Conclusion: According to our research, it is essential for clinicians to thoroughly dissect central LNs, particularly LN-prRLNs.

Correction: Indocyanine-green-loaded microbubbles for localization of sentinel lymph node using near-infrared fluorescence/ultrasound imaging: a feasibility study.

[This corrects the article DOI: 10.1039/C5RA26814A.].

Role of CD47-SIRPα Checkpoint in Nanomedicine-Based Anti-Cancer Treatment.

Many cancers have evolved various mechanisms to evade immunological surveillance, such as the inhibitory immune checkpoint of the CD47-SIRPα signaling pathway. By targeting this signaling pathway, researchers have developed diverse nanovehicles with different loaded drugs and modifications in anticancer treatment. In this review, we present a brief overview of CD47-SIRPα interaction and nanomedicine. Then, we delve into recent applications of the CD47-SIRPα interaction as a target for nanomedicine-based antitumor treatment and its combination with other targeting pathway drugs and/or therapeutic approaches.

The Effect of Nighttime Snacking on Cognitive Function in Older Adults: Evidence from Observational and Experimental Studies.

Evidence shows that supplementary snacking could provide older adults with nutrients that cannot be obtained through three meals a day. However, whether and how supplementary snacking, especially nighttime snacking, affects older adults' cognitive function remain unclear. The present study examined the effect of nighttime snacking on cognitive function for older adults. In study 1, we investigated the association between nighttime snacking and cognitive function based on data from 2618 community-dwelling older adults from the China health and nutrition survey (CHNS). In study 2, we conducted an experiment (n = 50) to explore how nighttime acute energy intake influences older adults' performance on cognitive tasks (immediate recall, short-term delayed recall, and long-term delayed recall). Both the observational and experimental studies suggested that nighttime snacking facilitated older adults' cognitive abilities, such as memory and mathematical ability, as indicated by subjective measures (study 1) and objective measures (studies 1 and 2). Moreover, this beneficial effect was moderated by cognitive load. These findings bridge the gap in the literature on the relationships between older adults' nighttime snacking and cognitive function, providing insight into how to improve older adults' dietary behaviors and cognitive function.

Resilience and Prosocial Behavior Among Chinese University Students During COVID-19 Mitigation: Testing Mediation and Moderation Models of Social Support.

Purpose: Suffering during events such as the COVID-19 pandemic threatens university students' physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation. Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior. Results: Pearson's correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students' prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts. Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students' prosocial behavior.

IR780 Based Sonotherapeutic Nanoparticles to Combat Multidrug-Resistant Bacterial Infections.

Multidrug-resistant (MDR) bacterial strains have emerged and weakened the therapeutic effects of antibacterial drugs. Sonodynamic therapy (SDT) takes advantage of noninvasiveness and deep tissue-penetrating features and has been rejuvenated to combat MDR bacteria and their biofilm-associated infections. To improve the efficacy of antibacterial SDT, we first developed IR780-based PLGA nanoparticles as sonosensitizers for high-frequency ultrasound (US)-monitored antibacterial SDT of MRSA myositis by therapeutic low-frequency US. In this study, the developed shell-core-structured IR780@PLGA nanoparticles were designed with a polymer shell PLGA with the sonosensitizer IR780 loaded on. High-frequency diagnostic US was introduced to monitor the sonotherapeutic progression of bacterial myositis by therapeutic low-frequency US. Importantly, the in vitro and in vivo results confirmed that IR780@PLGA nanoparticles combined with US irradiation possess high efficiency for antibacterial therapy. This approach provides a simple and efficient strategy to monitor and combat MDR bacterial infection.

Platelet Membrane Biomimetic Nanoparticles Combined With UTMD to Improve the Stability of Atherosclerotic Plaques.

Although research on the treatment of atherosclerosis has progressed recently, challenges remain in developing more effective, safer and transformative strategies for the treatment of atherosclerosis. Nanomaterials have recently played a unique role in many fields, including atherosclerosis treatment. Platelets are common component in the blood. Due to their inherent properties, platelets can target and adhere to atherosclerotic plaques. Ultrasound-targeted microbubble destruction (UTMD) shows great prospects in promoting the efficiency of drug delivery in treating solid tumors. In this study, we explored the possibility that UTMD assists platelet biomimetic rapamycin (RAP)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (RAP@PLT NPs) in the treatment of atherosclerosis. The biomimetic nano-formulations exhibit better targeting ability to plaques when administered in vivo. Targeted destruction of Sonovue™ in the aortic area further improved the efficiency of targeting plaques. Moreover, the progression of atherosclerotic plaques was inhibited, and the stability of plaques was improved. Together, our study established a novel strategy for targeted delivery of nanoparticles in atherosclerotic plaques, by combining the advantages of the ultrasonic cavitation effect and biomimicking nanoparticles in drug delivery.

MnO2 coated multi-layer nanoplatform for enhanced sonodynamic therapy and MR imaging of breast cancer.

Sonodynamic therapy (SDT) is a promising new anti-tumor therapy that inhibits tumor growth by ultrasound activation of sonosensitizers to produce reactive oxygen species (ROS). However, the problems of hypoxia in the microenvironment within solid tumors and the effectiveness of SDT will decrease due to the little accumulation of sonosensitizers at the tumor site, as well as tumor cell tolerance, have limited the development of SDT. To overcome these problems, a core-shell structured nanoparticle (IR780/PLGA@MnO2 NPs) loaded with IR780 and manganese dioxide (MnO2) was developed as a nanocarrier to transport the sonosensitizer IR780 and the generated oxygen into the tumor tissue. The MnO2 shell layer of IR780/PLGA@MnO2 NPs can prevent the premature release of IR780 in the blood and also it can react with acidic and high H2O2, the generated oxygen can relieve tumor tissue hypoxia, and the generated Mn can enhance magnetic resonance imaging (MRI) signal intensity by acting as a contrast agent for MRI. More importantly, the released IR780 can produce ROS to kill tumor cells under ultrasound excitation. This PH-responsive and H2O2-triggered SDT based on the IR780/PLGA@MnO2NPs is an effective platform to inhibit tumor growth with negligible systemic toxicity. This work develops a multifunctional therapeutic integrated nanoplatform for breast cancer treatment, which is expected to be used in the clinic.

Multi-Modal Imaging Monitored M2 Macrophage Targeting Sono-Responsive Nanoparticles to Combat MRSA Deep Infections.

Background: MRSA with high morbidity and mortality is prone to cause serious infection, SDT has become a new antibiotic-free modality for bacterial infection treatment. Switching from proinflammatory M1 macrophages to anti-inflammatory M2 macrophages dominant could activate the immune system to generate an anti-infection immune response. Methods: Herein, we developed M2 macrophages derived cell membranes coated PLGA nanoparticles with IR780 encapsulation (M2/IR780@PLGA) for antibacterial SDT and subsequent M2 macrophage polarization to enhance the therapeutic efficacy of MRSA myositis. For in situ visualization of antibacterial SDT, both diagnostic high-frequency US and magnetic resonance imaging (MRI) were introduced to monitor the sono-therapeutic progression of M2/IR780@PLGA nanoparticles in mice with bacterial myositis. Results: Our developed M2/IR780@PLGA nanoparticles exhibited excellent antibacterial effects due to the IR780 under low-frequency US irradiation in vitro. In an MRSA-infected mice model, a great deal of M2/IR780@PLGA nanoparticles accumulated at the site of inflammation due to M2 macrophage coating. The infected legs in the M2/IR780@PLGA nanoparticles-based SDT group were significantly smaller, fewer blood flow signals, a slight muscular edema without obvious intermuscular abscesses under high-frequency US and MR images guidance. Histopathology proved the infected legs in the M2/IR780@PLGA nanoparticles-mediated SDT group had less clumped bacteria infiltration, more M2 macrophage expression and less M1 macrophage expression. The percentage of mature dendritic cells in spleens was much higher in the group of mice with M2/IR780@PLGA nanoparticles-based SDT. Conclusion: This study provides a promising nanoparticles-based SDT anti-bacterial strategy, which could effectively enhance the antibacterial SDT and subsequent promote M2 macrophage polarization to boost the therapeutic efficacy of MRSA myositis.