Sonodynamic therapy (SDT), as a novel non-invasive strategy for eliminating tumor, has the advantages of deeper tissue penetration, fewer side effects, and better patient compliance, compared with ...photodynamic therapy (PDT). In SDT, ultrasound was used to activate sonosensitizer to produce cytotoxic reactive oxygen species (ROS), induce the collapse of vacuoles in solution, and bring about irreversible damage to cancer cells. In recent years, much effort has been devoted to developing highly efficient sonosensitizers which can efficiently generate ROS. However, the traditional organic sonosensitizers, such as porphyrins, hypericin, and curcumins, suffer from complex synthesis, poor water solubility, and low tumor targeting efficacy which limit the benefits of SDT. In contrast, inorganic sonosensitizers show good
in vivo
stability, controllable physicochemical properties, ease of achieving multifunctionality, and high tumor targeting, which greatly expanded their application in SDT. In this review, we systematically summarize the nanomaterials which act as the carrier of molecular sonosensitizers, and directly produce ROS under ultrasound. Moreover, the prospects of inorganic nanomaterials for SDT application are also discussed.
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As phototheranostic agents, carbon dots (CDs), have recently drawn considerable attention due to their excellent physicochemical properties. However, the complex synthetic route and ...high-cost of CDs greatly limit their practical application. To address this issue, given their nearly infinite supply from nature, Hypocrella bambusae is used as the precursor for the preparation of CDs in this study. The obtained Hypocrella bambusae CDs (HBCDs) possess good water solubility, broad absorption (350–800 nm), red-light emission (maximum peak at 610 nm), and low biotoxicity. Moreover, HBCDs can highly generate 1O2 (0.38) and heat (27.6%) under 635 nm laser irradiation. These excellent properties of HBCDs capacitate them to be utilized for bimodal fluorescence/photoacoustic imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT). This work provides a new candidate for tumor treatment with the combination of PDT and PTT, and explores a novel approach for the preparation of CD-based phototheranostic agents with natural biomass as raw carbon sources.
A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization ...and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.
This study demonstrates a strategy to fabricate stimuli‐responsive branched polymeric prodrug‐based theranostic nanomedicine. The anticancer mechanism is studied well and the in vitro and vivo behaviors including biodistribution, retention, and anticancer efficacy can be monitored well by imaging. This stimuli‐responsive polymeric demonstrates great potential of a platform for cancer nanotheranostics.
Few studies have explored the association between organizational justice and mental health, particularly in collectivist countries. Hence, the aim of the present study was to evaluate the impact of ...organizational justice on psychological distress and to discuss the findings in collectivist culture. A cross-sectional survey was conducted among nurses from public hospitals in western of China, July 2022, which followed the STROBE guidelines. This study used Chinese versions of the Organizational Justice Scale and Kesseler Psychological Distress Scale to assess the perceptions of organizational justice and mental health levels, respectively. A total of 663 nurses completed the questionnaires. The psychological distress of university-educated and low-income nurses was poor. There was a moderately positive relationship between organizational justice and psychological distress (R = 0.508, P < .01), indicating that the greater level of organizational injustice, the poorer mental health. Hierarchical regression analysis showed that organizational justice was an strong predictor of psychological distress, accounting for approximately 20.5% of the psychological distress. The findings of this study highlight the importance of interpersonal injustice and distributive injustice on psychological distress specific in Chinese culture, suggesting that nursing management or leaders should notice that the most being taken seriously by nurses is their recognition and respect for subordinate, meanwhile, alerting nurses, in some sense, a negative relationship with leaders as a kind of workplace bullying could harm their mental health. The promulgation of organizational justice policy to protect employees from the government and the real role of employee labor union organizations are urgently needed.
Traditional mode conversion ultrasonic motors are typically composed of the superposition of multiple vibration modes, making them more complex than single-mode ultrasonic motors. This complexity ...makes it difficult to miniaturize. A micro radial-torsional vibration mode ultrasonic motor is proposed and tested in this work. It is excited by a single-phase excitation signal. The proposed motor utilizes the radial in-plane vibration mode of the stator to convert the torsional vibration mode of the inner ring through the beams. The torsional vibration of the inner ring causes the rotor to rotate due to the friction force between the inner ring and the rotor. Based on the designed structure and verified using the finite element method, a prototype motor with a mass of 2.6 g and overall dimensions of Ô20 mm in diameter and 15 mm in height is fabricated and characterized. During the mechanical output performance test, the prototype achieved a maximum no-load speed of 3300 r/min and a stall torque of 0.2 mN<inline-formula> <tex-math notation="LaTeX">\cdot </tex-math></inline-formula>m at the driving voltage of 100 V<inline-formula> <tex-math notation="LaTeX">_{\mathrm {p-p}} </tex-math></inline-formula>.
As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In ...this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor–acceptor–donor (D–A–D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-β-cyclodextrin (M-β-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes.
Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled ...release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.
•A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared.•Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment.•Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites.•The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy.
Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites. Display omitted
Purpose
The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the ...selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs.
Methods
The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up.
Results
A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996,
p
= 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571,
p
= 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443,
p
= 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940,
p
< 0.001) were independent prognostic factors in multivariable analyses.
Conclusions
When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.
Supramolecular self‐assemblies of dendritic peptides with well‐organized nanostructures have great potential as multifunctional biomaterials, yet the complex self‐assembly mechanism hampers their ...wide exploration. Herein, a self‐stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG‐dendritic peptide‐pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self‐assembly process of PDPP is concentration‐dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self‐assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi‐aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8‐fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight‐fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA‐seq demonstrates that these effects of SSAs are related to the inhibition of MET‐PI3K‐Akt pathway. Overall, the supramolecular self‐assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.
A self‐stabilized supramolecular assembly (SSA) from the PEGylated dendritic peptide conjugate is presented, which builds on the concentration‐dependent supramolecular self‐assembly that demonstrates ultrahigh colloidal stability and enhanced tumor retention to boost its photodynamic therapeutic efficiency. This study reveals the supramolecular self‐assembly mechanism of SSAs and further expands the advanced functions of dendritic peptides in the field of cancer therapy.
The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after ...in vitro fertilization and embryo transfer (IVF-ET).
This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools.
A total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up- and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo.
These data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.
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