Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy.

Many chemotherapies, which are still the main clinical treatment for primary tumors, will induce persistent DNA damage in non-tumor stromal cells, especially cancer-associated fibroblasts (CAFs), and activate them to secrete senescence-associated secretory phenotype (SASP). The transition could further result in the formation of tumor immunosuppressive microenvironment and cause drug resistance of neighboring tumor cells. To solve this dilemma, a multi-functional biomimetic drug delivery system (named mPtP@Lipo) was rationally developed by combining CAFs reshaper ginsenoside 20(S)-protopanaxadiol (PPD) and cisplatin prodrug (PtLA) to inhibit tumor progression and the formation of SASP. To achieve effective delivery of these molecules deep into the desmoplastic tumor, fibroblast membrane was fused with liposomes as a targeting carrier. In vitro and in vivo results showed that mPtP@Lipo could penetrate deep into the tumor, reverse CAFs phenotype and inhibit SASP formation, which then blocked the immunosuppressive progress and thus reinforced anti-tumor immune response. The combination of chemotherapeutics and CAFs regulator could achieve both tumor inhibition and tumor immune microenvironment remodeling. In conclusion, mPtP@Lipo provides a promising strategy for the comprehensive stromal-desmoplastic tumor treatment.

A longitudinal network analysis of interaction factors among Chinese women at high risk for perinatal depression.

OBJECTIVE: Few studies have applied a health ecological model to understand perinatal depression among high-risk women, and existing research remains primarily cross-sectional in nature. This study aimed to explore the interplay among family function, perceived stress, insomnia symptoms, cognitive reactivity subscales (such as hopelessness/suicidality, aggression, control/perfectionism, avoidant coping, and acceptance/coping), mindfulness subscales (including attention, present focus, awareness, and acceptance), physiological indicators (e.g., hgb, 25-hydroxyvitamin D, and HbA1C), and depressive symptoms in Chinese high-risk women during the perinatal period. DESIGN: This was a longitudinal population-based cohort study. SETTING: This two-wave prospective study was conducted in Fujian Province, China, from December 2021 to January 2023. PARTICIPANTS: We used convenience sampling to enroll 368 pregnant patients from obstetrical clinics and inpatient departments of three tertiary hospitals (level 3) in Fuzhou and Quanzhou City, Fujian Province, China. MEASUREMENTS AND FINDINGS: In the statistical analysis, cross-sectional data were analyzed via the contemporaneous network method, and longitudinal data were analyzed via the cross-lagged panel network method. The core symptoms in the depression-related symptom network during the third trimester and three months postpartum were identified as attention (ATT) (strength = 1.02) and acceptance/coping (ACC) (strength = 1.19). All bridge symptoms were shown as depression (EPDS) (bridging strength = 0.07 and 0.09). A comparison between the first and second survey networks showed a reduced edge weight for the association between depressive symptoms and insomnia symptoms (to 0 in the second survey network, diff = -0.18, P < 0.001). Conversely, the association between depressive symptoms and control/perfectionism increased to 0.252 (diff = 0.25, P < 0.001). Through cross-lagged panel network analysis, the EPDS (out strength = 3.68, OEI =3.60) was identified as the most influential symptom and the most predictable symptom (R² = 0.76). Perceived stress (PSS) (in strength = 2.49) and hopelessness/suicidality (HOP) (IEI = 1.96) were identified as the most susceptible symptoms. KEY CONCLUSIONS: Cross-sectional network analysis combined with longitudinal network analysis revealed the mechanism of action between symptoms. Attention (ATT) and acceptance/coping (ACC) were identified as the core symptoms in the network of depression-related symptoms during the third trimester and three months postpartum, and the bridge symptoms were both depression (EPDS). In the dynamic network, depression (EPDS) was identified as the most influential and predictable symptom, and perceived stress (PSS) and hopelessness/suicidality (HOP) were identified as the most susceptible symptoms. IMPLICATIONS FOR PRACTICE: Targeted interventions focused on attention and coping can reduce stress during pregnancy and enhance postpartum well-being. Strengthening family support and routine screening for symptoms such as stress and depression (EPDS) are crucial for improving maternal mental health globally, particularly in resource-limited settings.

Research on the comprehensive child life intervention program (CCLIP) for adjusting medical fear in children with central nervous system (CNS) cancers: a randomized controlled trial study protocol.

BACKGROUND: Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children's quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. METHODS: This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. DISCUSSION: This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Pathological complete response to neoadjuvant lorlatinib in a patient with stage IIIA ALK-positive non-small cell lung cancer: a case report.

Background: Given the promising efficacy of targeted therapies in patients with advanced non-small cell lung cancer (NSCLC) harboring oncogenic drivers, its use in adjuvant and even neoadjuvant therapy is increasing. Lorlatinib is a potent brain-penetrating third-generation anaplastic lymphoma kinase (ALK) and c-ros oncogene 1, receptor tyrosine kinase (ROS1) tyrosine kinase inhibitors (TKIs) with broad ALK mutation coverage. Currently, there is a limited evidence regarding the efficacy of lorlatinib as neoadjuvant therapy in locally advanced NSCLC in the presence of ALK rearrangements. The aim of this case report is to describe a rare case of pathological complete response (pCR) to neoadjuvant lorlatinib in a patient with stage IIIA ALK-positive NSCLC, providing evidence for neoadjuvant targeted therapy. Case Description: A 35-year-old male was pathologically diagnosed with locally advanced stage IIIA (cT2bN2M0) ALK-positive NSCLC. Clinically, the patient had pulmonary nodules in the left inferior lobe, which were enlarged progressively with follow-up, with the largest measuring approximately 4.6 cm × 2.8 cm by computed tomography (CT) scan and we found that the lymph nodes (stations 4L, 7, and 8) were invaded by metastasis. Following a 3-month neoadjuvant treatment with lorlatinib at 100 mg daily, his CT scan demonstrated a partial response (PR). This patient then underwent a left inferior lobectomy with mediastinal lymph node dissection (MLD) and mediastinal cyst resection via video-assisted thoracoscopic surgery (VATS). Postoperative pathology revealed a pCR. This patient continued to receive lorlatinib and remained disease free at his 10-month follow-up. Conclusions: Herein we reported the case of a pCR in stage IIIA ALK-positive NSCLC patient treated with neoadjuvant lorlatinib. Our findings underscore the potential of lorlatinib as a neoadjuvant treatment for resectable ALK-positive NSCLC.

Enhanced Recognition of a Herbal Compound Epiberberine by a DNA Quadruplex-Duplex Structure.

The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.

High-Density Genetic Map Construction and Quantitative Trait Locus Analysis of Fruit- and Oil-Related Traits in Camellia oleifera Based on Double Digest Restriction Site-Associated DNA Sequencing.

Camellia oleifera, an important tree species and source of edible oil in China, has received significant attention owing to the oil's high unsaturated fatty acid content, which has benefits for human health. However, the mechanisms underlying C. oleifera yield and oil quality are largely unknown. In this study, 180 F1 progenies were obtained from two parents with obvious differences in fruit- and oil-related traits. We constructed a high-density genetic map using a double digest restriction site-associated DNA sequencing (ddRAD-Seq) strategy in C. oleifera. This map spanned 3327 cM and anchored 2780 markers in 15 linkage groups (LGs), with an average marker interval of 1.20 cM. A total of 221 quantitative trait loci (QTLs) associated with fruit- and oil-related traits were identified across three years' worth of phenotypic data. Nine QTLs were detected simultaneously in at least two different years, located on LG02, LG04, LG05, LG06, and LG11, and explained 8.5-16.6% of the phenotypic variation in the corresponding traits, respectively. Seventeen major QTLs were obtained that explained 13.0-16.6% of the phenotypic variance. Eleven and five flanking SNPs of major QTLs for fruit- and oil-related traits were detected which could be used for marker-assisted selection in C. oleifera breeding programs. Furthermore, 202 potential candidate genes in QTL regions were identified based on the collinearity of the genetic map and the C. oleifera "CON" genome. A potential regulatory network controlling fruit development and oil biosynthesis was constructed to dissect the complex mechanism of oil accumulation. The dissection of these QTLs will facilitate the gene cloning underlying lipid synthesis and increase our understanding in order to enhance C. oleifera oil yield and quality.

Analysis of the Tensile Properties and Probabilistic Characteristics of Large-Tow Carbon Fiber-Reinforced Polymer Composites.

Large-tow carbon fiber-reinforced polymer composites (CFRP) have great application potential in civil engineering due to their low price, but their basic mechanical properties are still unclear. The tensile properties of large-tow CFRP rods and plates were investigated in this study. First, the tensile properties of unidirectional CFRP rods and plates were studied, and the test results of the relevant mechanical properties were statistically analyzed. The tensile strength of the CFRP rod and plate are 2005.97 MPa and 2069.48 MPa. Second, the surface of the test specimens after failure was observed using a scanning electron microscope to analyze the type of failure and damage evolution process. Finally, the probabilistic characteristics of the mechanical properties were analyzed using normal, lognormal, and Weibull distributions for parameter fitting. Quasi-optimality tests were performed, and a probability distribution model was proposed for the mechanical properties of large-tow CFRP rods and plates.

High-Temperature Resistance of Anchorage System for Carbon Fiber-Reinforced Polymer Composite Cable-A Review.

Unidirectional carbon fiber-reinforced polymer (CFRP) may exhibit significant mechanical softening in the transverse direction at an elevated temperature. While significant transverse compressive stress exists on CFRP due to the clamping force from anchorage, a CFRP cable may exhibit anchorage failure when suffering an accidental fire disaster. The high-temperature resistance of a CFRP cable anchorage is critical, and clarifying the performance deterioration and failure mechanism of a CFRP cable anchorage system at elevated temperature is fundamental for clarifying its fire resistance. This paper reviews the current research status of the high-temperature resistance of CFRP cable anchorage systems from two aspects, including the high-temperature resistance of the comprising materials and the anchorage system. The reviews on the high-temperature properties of the comprising materials are summarized from two aspects. Firstly, the mechanical performance degradation of bonding epoxy resin at elevated temperatures and the effect of a filler on its mechanical-thermal properties are analyzed. Secondly, the mechanical performances of CFRP composites at elevated temperatures are summarized, with consideration of the stress state of the CFRP cable under the constraint of an anchorage device. The reviews on the high-temperature resistance of the anchorage system also include two aspects. Firstly, the temperature field solution method for the anchorage system is summarized and discussed. Secondly, the current research status of the anchorage performance at elevated temperatures is also summarized and discussed. Based on these reviews, the research shortage of the high-temperature resistance of CFRP cable anchorage systems is summarized, and further research is recommended.

Adsorption behavior and mechanism of Cu(II) by sodium alginate/carboxymethylcellulose/magnesium hydroxide (SC-MH) hydrogel.

In the present work, an environmentally-friendly, reusable hydrogel ball characterized by its great adsorption capacity to Cu(II) was synthesized. The preparation of this hydrogel drew on sodium alginate (SA) and carboxymethyl cellulose (CMC) as primary composition elements. The endeavor brought novelty by ingeniously infusing it with slurry magnesium hydroxide (MH). The factors (pH, SC-MH amount, initial concentration, adsorption time) that are critical to adsorption were also investigated. FTIR, SEM-EDS and XPS were used to reveal the adsorption mechanism of Cu on SC-MH. The results show that the surface of SC-MH is rough, and there are a large number of gully-like structures conducive to adsorption, which are rich in hydroxyl and carboxyl groups. Under the optimum conditions, the maximum adsorption capacity reached 215.68 mg/g. Based on its high R2 value (0.999), the Langmuir model is determined to be the most appropriate for describing the adsorption behavior, indicating monolayer homogeneous adsorption. The kinetic data align well with the pseudo-second-order kinetic model. Furthermore, thermodynamic analysis reveals the adsorption process to be spontaneous and endothermic, as demonstrated by a negative ΔG and positive ΔH (38.8859 KJ/mol). The mechanism involves electrostatic attraction, chelation, Mg(OH)2 adsorption and ion exchange.

Validation of the Maslach Burnout Inventory-General Survey 9-item short version: psychometric properties and measurement invariance across age, gender, and continent.

Background: The Maslach Burnout Inventory-General Survey (MBI-GS) stands as the preeminent tool for assessing burnout across various professions. Although the MBI-GS9 emerged as a derivative of the MBI-GS and has seen extensive use over several years, a comprehensive examination of its psychometric properties has yet to be undertaken. Methods: This study followed the Standards for Educational and Psychological Testing guidelines to validate the MBI-GS9. Employing a combined approach of classical test theory and item response theory, particularly Rasch analysis, within an integrated framework, the study analyzed data from 16,132 participants gathered between 2005 and 2015 by the Centre for Organizational Research at Acadia University. Results: The findings revealed that the MBI-GS9 exhibited satisfactory reliability and validity akin to its predecessor, the MBI-GS. Across its three dimensions, Cronbach's α and omega coefficients ranged from 0.84 to 0.91. Notably, the MBI-GS9 displayed no floor/ceiling effects and demonstrated good item fit, ordered threshold, acceptable person and item separation and reliability, clear item difficulty hierarchy, and a well-distributed item threshold. However, the results suggested a recommended minimum sample size of 350 to mitigate potential information loss when employing the MBI-GS9. Beyond this threshold, the observed mean difference between the MBI-GS and MBI-GS9 held minimal practical significance. Furthermore, measurement equivalence tests indicated that the MBI-GS9 maintained an equivalent three-factor structure and factor loadings across various gender, age, and continent groups, albeit with inequivalent latent values across continents. Conclusion: In sum, the MBI-GS9 emerges as a reliable and valid alternative to the MBI-GS, particularly when utilized within large, diverse samples across different age and gender demographics. However, to address potential information loss, a substantial sample size is recommended when employing the MBI-GS9. In addition, for cross-cultural comparisons, it is imperative to initially assess equivalence across different language versions at both the item and scale levels.

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

An 8-week community-based resilience group intervention for Chinese parents who lost their only child: A two-armed pragmatic waitlist-control trial.

OBJECTIVE: This study developed and evaluated a structured, 8-week community-based resilience group intervention for Chinese parents who have lost their only child and exhibit extended bereavement and suboptimal levels of resilience. METHOD: Eighty parents were recruited from two communities and allocated to the intervention group (n = 42) or the waitlist-control group (n = 38). The 8-week community-based resilience group intervention was developed based on Kumpfer's resilience theory and previous studies. The primary outcomes were resilience and depression, and the secondary outcomes were posttraumatic growth (PTG), subjective well-being (SWB), social avoidance (SAD), sleep quality, and serum dehydroepiandrosterone (DHEA) levels. Outcomes were assessed at four time points: before (T0), immediately after (T1), 3 months after (T2), and 12 months after (T3) the intervention. The data were analyzed following the intention-to-treat principle. RESULTS: The general linear model results indicated a significant Group × Time interaction effect on resilience, depression, PTG, SWB, and SAD, with medium and large effect sizes (Cohen's d: 0.58-1.41). Those in the intervention group experienced better resilience from T1 to T2 and better depression, PTG, SWB, and SAD from T1 to T3 compared to the waitlist-control group. No significant differences were found between groups over time for sleep quality and DHEA levels. CONCLUSIONS: This intervention effectively increased resilience by T2 and improved PTG, SWB, depression, and SAD by T3 compared with control group, which can be implemented in the local community setting and collaborated with social workers to assist bereaved parents in the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Experimental Study on Water-Plugging Performance of Grouted Concrete Crack.

In this paper, ordinary Portland cement, ultrafine cement, polyurethane, and epoxy resin were selected as typical grouting materials. Grouting simulation tests were first conducted to prepare the grouted concrete crack sample. The effect of concrete crack parameters (i.e., crack aperture and roughness), grout water-cement ratio, and grouting pressure on the water-plugging performance of different grouting materials was explored through the impermeability test. The microstructure of grouted concrete cracks was analyzed by means of scanning electron microscopy (SEM) and computed tomography (CT), and the difference in water-plugging performance of different grouting materials was explained at the micro level. The results show that the impermeability of the four grouting materials was ranked as follows: Epoxy resin > polyurethane > ultra-fine cement > ordinary Portland cement. The concrete cracks grouted by epoxy resin have the highest plugging failure water pressure and the lowest permeability, which is the optimal grouting material. The effectiveness of crack grouting in water-plugging was directly proportional to the grouting pressure, provided the pressure did not exceed a certain value. When the pressure surpassed the threshold, the increase in pressure did not have a significant impact on the water plugging performance. For the two cement-based materials, the threshold pressure was 1 MPa, while for the other two chemical grouts, it was 2 MPa. The two cement-based grouts with a water-cement ratio of 0.8 showed optimal water-plugging performance. The water-plugging performance of ordinary Portland cement paste, ultra-fine cement pastes, and polyurethane grout was negatively correlated with crack aperture and positively correlated with crack roughness. However, the water-plugging performance of epoxy resin grout was not affected by crack aperture or roughness.

Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy.

Background: Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer. Methods: Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors. Results: Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®. Conclusion: Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.

Inorganic nanoparticles for photothermal treatment of cancer.

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.

Gold nanoparticles decorated on MOF derived Cu5Zn8 hollow porous carbon nanocubes for magnetic resonance imaging guided tumor microenvironment-mediated synergistic chemodynamic and photothermal therapy.

Combining chemodynamic therapy (CDT) with photothermal therapy (PTT) has developed as a promising approach for cancer treatment, as it enhances therapeutic efficiency through redox reactions and external laser induction. In this study, we designed metal organic framework (MOF) -derived Cu5Zn8/HPCNC through a carbonization process and decorated them with gold nanoparticles (Au@Cu5Zn8/HPCNC). The resulting nanoparticles were employed as a photothermal agent and Fenton catalyst. The Fenton reaction facilitated the conversation of Cu2+ to Cu+ through reaction with local H2O2, generating reactive hydroxyl radicals (·OH) with potent cytotoxic effects. To enhance the Fenton-like reaction and achieve combined therapy, laser irradiation of the Au@Cu5Zn8/HPCNC induced efficient photothermal therapy by generating localized heat. With a significantly increased absorption of Au@Cu5Zn8/HPCNC at 808 nm, the photothermal efficiency was determined to be 57.45 %. Additionally, Au@Cu5Zn8/HPCNC demonstrated potential as a contrast agent for magnetic resonance imaging (MRI) of cancers. Furthermore, the synergistic combination of PTT and CDT significantly inhibited tumor growth. This integrated approach of PTT and CDT holds great promise for cancer therapy, offering enhanced CDT and modulation of the tumor microenvironment (TME), and opening new avenues in the fight against cancer.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.