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.

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.

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.].

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.

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.

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.

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.

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.

M1 Macrophage-Derived Sonoresponsive Nanoparticles for Sonodynamic Anticancer Therapy.

Background: Many nanocarriers currently developed have potential in tumor targeting, but there are still several limitations to their applications in clinical treatment. It is crucial to explore novel nanocarriers with higher biocompatibility and targeting efficiency to overcome the barriers of the tumor microenvironment to penetrate deeply into the tumor. Methods: In this work, we designed multilayer sonoresponsive M1/IR780@PLGA nanoparticles, which can actively target tumor tissues, and repolarize M2 macrophages in the tumor microenvironment into M1 macrophages to stimulate antitumor immune effects. When the nanoparticles reach the tumor site, ultrasound (US) irradiation is applied to the tumor site, and the sonosensitizer consumes oxygen and generates ROS, thereby triggering local tumor cell death. Results: The M1/IR780@PLGA nanoparticle-based antitumor sonodynamic therapy (SDT) significantly inhibited tumor growth, triggered a great number of M2 tumor-associated macrophages to convert into M1 macrophages in the tumor microenvironment and promoted dendritic cell maturation to activate the antitumor immune response. Conclusion: M1/IR780@PLGA nanoparticles potentiate antitumoral efficacy through SDT and antitumor immune responses by activating dendritic cells maturation and M1 macrophage repolarization in the tumor microenvironment.

Case report: Large follicular thyroid carcinoma with multiple cervical lymph node metastases.

Introduction: Follicular thyroid carcinoma (FTC) rarely metastasizes to regional lymph nodes, as they mainly metastasize through hematogenous route; in particular, a large FTC with only lateral lymph node metastasis and without distant metastasis has rarely been reported. Case report: We present a 66-year-old male patient with a progressively growing thyroid for more than 20 years, causing tracheal compression and narrowing. Neck ultrasonography, computed tomography (CT), magnetic resonance (MR) imaging and positron emission tomography-computed tomography (PET/CT) were carried out to obtain images of the thyroid and surrounding tissues. Total thyroidectomy and cervical lateral and central lymph node dissection were undertaken, and histopathological, and immunohistochemical evaluations and molecular pathology confirmed the diagnosis of FTC with multiple cervical lymph node metastases. Conclusion: We have reported a rare case of large FTC with diffuse nodal involvement but no distant metastases. We present the thyroid ultrasound, neck CT, MR and whole body PET/CT.

Contrast-enhanced ultrasound characteristics of preoperative central cervical lymph node metastasis in papillary thyroid carcinoma.

This study evaluated the preoperative diagnostic value of lymph node ultrasonography in distinguishing between benign and malignant central cervical lymph nodes (CCLNs) in patients with papillary thyroid carcinoma (PTC). A total of 176 patients who had PTC with 216 CCLNs (49 benign and 155 malignant) were enrolled in this study and preoperatively imaged by ultrasonography, including conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). We evaluated the ultrasonography parameters for each lymph node. Binary logistic regression analysis indicated that multifocality of PTC and the absence of Hashimoto's thyroiditis are independent clinical features related to patients with PTC who also have malignant CCLNs. For preoperative ultrasonography features, heterogeneous enhancement and centripetal perfusion are independent ultrasonographic features to identify malignant and benign CCLNs. This study demonstrated that preoperative CEUS characteristics help to distinguish malignant CCLNs from benign CCLNs.

Papillary thyroid microcarcinoma with contralateral large humerus metastasis and cervical lymph node metastasis: A case report.

Introduction: Papillary thyroid microcarcinoma (PTMC) that metastasizes to bone, especially metastasizes to contralateral humerus with so large mass, is rarely reported before. Case report: We presented a 50-year-old female patient with a large painful mass in the right humerus for 5 years, presenting with swelling of the right shoulder with limited mobility. Positron emission tomography-computed tomography (PET/CT) showed a large mass in the right humerus, bilateral lung lesions, and enlarged lymph nodes in the right supraclavicular fossa. Right humerus lesion biopsy and immunohistochemical evaluations confirmed that the lesion originated from the thyroid tissue. Then, the thyroid ultrasonography showed a hypo-echoic solid nodule with an irregular taller-than-wide shape in the upper of left thyroid lobe and enlarged lymph nodes with the absence of fatty hilum in the contralateral right IV compartment. The total thyroidectomy and cervical lymph node dissection were undertaken; the histopathology confirmed the diagnosis of PTMC with contralateral cervical lymph node metastasis. Conclusion: We reported a case of PTMC with contralateral large humerus and cervical lymph node metastasis and demonstrated the PET/CT images of the metastatic large humerus and thyroid ultrasonographic appearances of the PTMC and enlarged cervical lymph node.

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.

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.

Value of Contrast-Enhanced Ultrasound in Mummified Thyroid Nodules.

Mummified thyroid nodules (MTNs) are rarely reported and are usually misdiagnosed as malignant nodules. This article first reviewed the contrast-enhanced ultrasound (CEUS) enhancement features of 218 MTNs and classified them into three (A, B, C) patterns. The A pattern MTNs show linear hypo-enhancement, the B pattern MTNs show heterogeneous hypo-enhancement, and the C pattern MTNs show no enhancement in thyroid nodules. The A and C pattern enhancements of MTNs demonstrated a high specificity compared with the enhancement of previously reported typical papillary thyroid carcinomas (PTCs). To further study the B pattern MTNs, 24 B pattern MTNs and 42 PTCs were enrolled in this study, and CEUS parameters for each nodule were evaluated. Univariate analysis indicated that compared with PTCs, the B pattern MTNs more frequently exhibited heterogeneous hypo-enhancement and clear margins after clearance (p <0.05). A multivariate analysis revealed that heterogeneous hypo-enhancement and clear margins after clearance were independent characteristics related to the B pattern MTNs for differentiating them from PTCs (p <0.05). Thus, preoperative CEUS may provide more important information for distinguishing MTNs from malignant thyroid nodules to avoid surgical excisions or unnecessary fine-needle aspiration (FNA).

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.

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.

Value of Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). Two hundred and one cervical LNs (157 metastatic from PTC and 44 benign) were evaluated using conventional ultrasonography (US) and CEUS before biopsy or surgery. Histopathology was used as the gold standard. We evaluated the size, long axis/short axis ratio (L/S), fatty hilum, hyper-echogenicity, calcification, cystic change, peripheral vascularity and CEUS parameters for each lymph nodule. The CEUS parameters included enhancement type, homogeneity, perfusion type, ring enhancement, peak intensity (PI) index and area under the curve (AUC) index. Univariate analysis demonstrated that compared with benign LNs, malignant LNs more frequently had L/S < 2, absence of a fatty hilum, presence of hyper-echogenicity, presence of calcification, peripheral vascularity, hyper-enhancement, heterogeneous enhancement, centripetal perfusion, ring enhancement, PI index > 1 and AUC index > 1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that hyper-enhancement, centripetal perfusion, and ring enhancement are independent CEUS characteristics related to malignant LNs for their differentiation from benign LNs (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to identify malignant cervical LNs from benign cervical LNs.